STERRORETEKTIVE METATHESIS

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0011 This invention was made with government support tinder NIK Grant No.

GM031332. The U.S. Government has certain rights in the invention.

RELATED APPLICATIONS

[002] This application claims the benefit of U.S. Provisional Patent Application No.

62/671,891 filed May 15, 2018, and of U.S. Provisional Patent Application No. 62/803,603 filed February 1 1 , 2039, the contents of which are incorporated herein by reference.

TECHNICAL FIELD

[003] Prostaglandins are an important class of naturally occurring molecules that are found in mammalian tissues and exhibit a broad range of biological functions and widespread medical applications. [Marks F. and FUrstenberger G. P ostaglandins . Laukotrienes and Other Eicosamids·, Wifey-Biackwel!, 1999. Funk, C. D. Prostaglandins and Leukotricnes: Advances in Eicosanoid Biology. Science 2001, 294, 1871— T 875.]

[004] Efforts directed toward the synthesis of various prostaglandins has had a profound effect on the development of new strategies and tactics employed in the field of synthetic chemistry', emanating from the seminal studies of Corey beginning in the 1960’s. [Corey, E. J.; Weinshenker, N. M.; Schaaf, T. K2; Huber W Stereo-Controlled Synthesis of Dl- Prostaglandins F2. alpha, and E2. J Am.Chem. Soc 1969, 91, 5675-5677. Das, S.;

Chandrasekhar, S.; Yadav, I. S ; Gree, R. Recent Developments in the Synthesis of

Prostaglandins and Analogues. Chem. Rev. 2097, 107 3286-3337. Peng, H.; Chen, F.-E. Recent Advances in Asymmetric Total Synthesis of Prostaglandins. Org. Biomol. Chem. 2617, IS, 6281-6303.]

BACKGROUND

[005] The recently discovered A ⁱ² ~prostaglandin J family (I), (2), (3) and (4) as shown in Figure 1, features a unique cross-conjugated dienone motif and appealing anticancer activity. _A

[Straus D. S.; Glass C. K. Cyclopentenone Prostaglandins: New Insights on Biological Activities and Cellular Targets, Med. Res. Rev. 2001, 21, 185-210.]

[006] A ^I2 -PGJ3 (3), for example, was isolated as a secondary metabolite and was shown to selectively induce apoptosis of leukemia stem ceils over normal hematopoietic stems ceils with high potency. [Hegde, S,; Kaushal, N,; Ravindra, K, C.; Chiaro, C.; Hater, K, T,; Gandhi,

U. H.; Thompson, J. T.; van den Heuvel, J. P.; Kennet, M. J,; Hankey, P.; Paulson R, F.; Frabhu K. S. A ^!2 ~Prostag!andin h, an Omega-3 Fatty Acid-Derived Metabolite, Selectively Ablates Leukemia Stem Cells in Mice. Blood 011, 118, 6909-6919.]

1007] Studies of its stability, bioavailability, and hypersensitivity make A ^{f 2} -PG.H an intriguing drug candidate for leukemia treatment. [Kudva, A. K.; Kaushal, N.; Mohinta, S.: Kennett, M. J.; August, A.; Paulson, R. F.; Prabhu, K. S. Evaluation of the Stability,

Bioavailability, and Hypersensitivity of the Omega-3 Derived Anti-Leukemic Prostaglandin:

A ^!2 -Pros†aglandin J ₃ FLOS ONE 2013, 8, e80622,]

[008] Synthetic efforts toward A ^’2 -prostaglandin J compounds began in 2003, with a number of syntheses of A ^; APGi2 (1) and 15d-PGJ ₂ (2) reported through various approaches, [ Biekley, J. F,; Jadhav, V.; Roberts, S. M,; Santoro, M. G.; Steiner, A.; Sutton, P. W. Synthesis of Optically Active Prostaglandin j ₂ and 15- Deoxy-A ⁱ² _’ ⁱ⁴ Prostaglandin j ₂ . Synleii 2003, 1 170- 1174. Brummond, K. M.; Sill, P. C.; Chen, FI. The First Total Synthesis of IS-Deoxy-A ⁵² _’’ ⁴ - Prostaglandin J ₂ and the Unambiguous Assignment of the C14 Stereochemistry. Org. Lett. 2004, 6, 149-352. Aeharya, H. P.; Kobayashi, Y. Total Synthesis of A ¹² -PGJ ₂ , 15-Deoxy-A ^{12 ! 4} -PGJ ₂ , and Related Compounds. Tetrahedron Lett. 2004, 45, 1 199-1202. Aeharya, H, P.; Kobayashi,

Y. Highly Efficient Total Synthesis ofA ^{f 2} -PGJ ₂ , 15-Deoxy-A ^{!2 ,4} ~ PGJ ₂ , and Their Analogues. Tetrahedron 2006, 62, 3329-3343. Kira, N.-.T.; Moon, H.; Park, T.: Yun, H,; Jung, J.-W.; Chang, D.-J.; Kim, D.-D.; Sub, Y.-G, Concise and Enantioselective Total Synthesis of 15-Deoxy-A ^12»14 - Proslaglandin h. J. Org. Chem. 201Q, 75, 7458-7460. Egget, J.; Fischer, S.; Bretscher, P.;

Freigang, S.i Kopf, M; Carreira, E. M. Total Synthesis of Prostaglandin 15d~PGJ ₂ and

Investigation of Its Effect on the Secretion of IL-6 and 1L-12, Org Lett 2015, 17, 4340-4343.] [009] Elegant contributions to the total synthesis of A ^;2 -FGJ3 (3) were reported by

Nicolaou and co-workers and more recently by the Aggarwal group. [Nicolaou, K. C.; Heretsch, P.; El Marrouni, A.: Hale, C. R. H.; Pulukuri, K K.; Kudva, A. K.; Malayan, V.; Prabhu, K. S. Total Synthesis of A ^!2 ~Prostaglandin !¾, a Highly Potent and Selective Antileukemic Agent, Angew Chem. Ini. Ed. 2014, 53, 10443-10447, Nicolaou, K. C.: Pulukuri, K. K,; Yu, R.; Rigol, S.; Heretsch, P,; Grove, C. L; Hale, C. R, H,; El Marrouni, A, Total Synthesis of D ¹² - Prostaglandin J3: Evolution of Synthetic Strategies to a Streamlined Process, Chem. - Ear. J. 2016, 22, 8559-8570. Pelss, A.: Gandhamsetty, N.; Smith, J. R.i Mailhoi, D.: Sllvi, M.; Watson, A. J, A.; Perez-Powell, L; Prevost, S,; Schutzenmeister, N,; Moore, P, R.; Aggarwal V. K.

Reoptimization of the Organoeatalyzed Double Aklol Domino Process to a Key Ena!

Intermediate and Its Application to the Total Synthesis of A ¹² -Prostaglandin J ₃ Chem.-Eur. ,/ 2018, 24 , 9542-9545.]

|010] A number ofA^-PGJs analogues were also accessible via a streamlined synthesis developed by Nicolaou and co-workers to enable a comprehensive structural-activity relationship (SAR) study of their anti-cancer activities. [Nicolaou, K. C.: Pulukuri, K. K,; Rigol, S,; Heretsch, P„; Yu, R.; Grove, C. Li Hale, C. R, H.; ElMarrouni, A.; Fetz, V„; Bronstrup, M ; Aiijay M.; Sandoval J.; Gavrilyuk J, Synthesis and Biological Investigation of A ⁱ² - Prostaglandin J ₃ (A ⁱ² -PGJ3) Analogues and Related Compounds. J. Am. Chem. Soc. 2016, 138, 6550-6560,]

[811] Unless otherwise indicated, the invention is not limited to specific reactants, reaction conditions, or the like, as such may vary. It is also to be understood that the

terminology used herein is for the purpose of describing particular embodiments and is not to be interpreted as being limiting.

[012] As used in the pecification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, tor example, reference to "a substituent" encompasses a single substituent as well as two or more substituents, and the like

[013] As used in the specification and the appended claims, the terms "for example", "for instance", "such as" or "including" are meant to introduce examples that further clarify more general subject matter. Unless otherwise specified, these examples are provided only as an aid for understanding the invention and are not meant to be limiting in any fashion

[014] in this specification and in the claims that follow, reference will be made to a number of terms, which shall be defined to have the meanings as described herein

[015] The term "alkyl" as used herein, refers to a linear, branched, or cyclic saturated hydrocarbon group typically although not necessarily containing 1 to 24 carbon atoms, preferably 1 to 12 carbon atoms, such as methyl (Me), ethyl (Et), n -propyl (Pr or n-Pr), isopropyl (i-Pr), n-butyl (Bu or n-Bu), isobutyl (i-Bu), t- butyl (t-Bu), octyl (Oct), decyl, and the like, as well as eycloalkyl groups such as cyclopentyl (Cp), cyclohexyl (Cy) and the like.

Generally, although again not necessarily, alkyl groups herein contain 1 to about 8 carbon atoms. The term "lower alkyl" refers to an alkyl group of 1 to 6 carbon atoms, and the specific term "eycloalkyl" refers to a cyclic alkyl group typically having 3 to 8, preferably 5 to 7, carbon atoms. The term "substituted alkyl" refers to alky! substituted with one or more substituent groups and the terms "heteroatom-containing alkyl" and "heteroalkyl" refer to alkyl in which at least one carbon atom is replaced with a heteroatom. If not otherwise indicated, the terms "alkyl" and "lower alkyl" include linear, branched, cyclic, unsuhstituted, substituted, and/or heteroatom- containing alkyl and lower alkyl, respectively

[016] The term "alkylene" as used herein refers to a difunetional linear, branched, or cyclic alkyl group, where "alkyl” is as defined above

[017] The term "alkenyl" as used herein refers to a linear, branched, or cyclic hydrocarbon group of 2 to 24 carbon atoms containing at least one double bond, such as ethenyi, mpropenyi, iso-propenyl, n-butenyl, iso-butenyl, octenyl, decenyi, tetradecenyl, bexadecenyl, and the like. Preferred alkenyl groups herein contain 2 to 12 carbon atoms The term "lower alkenyl" refers to an alkenyl group of 2 to 6 carbon atoms, and the specific term "cycloaikenyl" refers to a cyclic alkenyl group, preferably having 3 to 8 carbon atoms. The term "substituted alkenyl" refers to alkenyl substituted with one or more substituent groups, and the terms "heteroatom -containing alkenyl" and "heteroalkenyl" refer to alkenyl in which at least one carbon atom is replaced with a heteroatom. If not otherwise indicated, the terms "alkenyl" and "lower alkenyl" Include linear, branched cyclic, unsubstituted, .substituted, and/or heteroatom-containing alkenyl and lower alkenyl, respectively.

[018] The term "alkenylene" as used herein refers to a difunctional linear, branched, or cyclic alkenyl group, where "alkenyl" is as defined above.

[019] The term "alkyny!" as used herein refers to a linear or branched hydrocarbon group of 2 to 24 carbon atoms containing at least one triple bond, such as ethynyl, n-propynyi, and the like. Preferred alkynyi groups herein contain 2 to 12 carbon atoms. The term "lower alkynyl" refers to an alkynyi group of 2 to 6 carbon atoms. The term "substituted alkynyl" refers to alkynyl substituted with one or more substituent groups, and tbs terms "heteroatom-containing alkynyi" and "heteroa!kynyf ' refer to alkynyl in which at least one carbon atom is replaced with a heteroatom. If not otherwise indicated, the terms "alkynyi" and "lower alkynyl" include linear, branched, unsubstituted, substituted, and/or heteroatom-containing alkynyl and lower alkynyl, respectively.

[Q2Q] The term "alkynylene" as used herein refers to a difunctionai alkynyi group where "alkynyl" is as defined above

[02 i ] The term "aikoxy" as used herein refers to an alkyl group bound through a single, terminal ether linkage: that is, an "alkoxy" group may be represented as -O-alkyl where alkyl is as defined above. A "lower alkoxy” group refers to an alkoxy group containing 1 to 6 carbon atoms. Analogously, "aikenyioxy" and "lower aikenyloxy" respectively refer to an alkenyl and iower alkenyl group bound through a single, terminal ether linkage, and "alkynyloxy" and "lower alkynyloxy" respectively refer to an alkynyl and lower alkynyl group bound through a single, terminal ether linkage

[922] The term "aryl" as used herein, and unless otherwise specified, refers to an aromatic substituent containing a single aromatic ring or multiple aromatic rings that are fused together, directly linked, or indirectly linked (such that the different aromatic rings are bound to a common group such as a methylene or ethylene moiety). Preferred aryl groups contain 5 to 24 carbon atoms, and particularly preferred aryl groups contain 6 to 10 carbon atoms. Exemplary aryl groups contain one aromatic ring or two fused or linked aromatic rings, e.g., phenyl (Ph), naphthyl, biphenyl, diphenylether, diphenyiamine, benzophenone, phenanihryl and the like. "Substituted aryl" refers to an aryl moiety substituted with one or more substituent groups, and the terms "heteroatom containing aryl" and "heieroaryf ' refer to aryl substituents in which at least one carbon atom is replaced with a heteroatom, as will be described in further detail herein. [023] The term "aryloxy" as used herein refers to an aryl group bound through a single, terminal ether linkage, wherein "aryl" is as defined above. An "aryloxy" group may be represented as -Q-aryl where aryl Is as defined above. Preferred aryloxy groups contain 5 to 24 carbon atoms, and particularly preferred aryloxy groups contain 6 to 10 carbon atoms. Examples of aryloxy groups include, without limitation, phenoxy, o-halo-phenoxy, rn-halo-phersoxy, p- halo-phenoxy, o-methoxy-phenoxy, m-methoxy-phenoxy, p-methoxy~phenoxy, 2,4-dimethoxy- phenoxy, 3,4,5-trimethoxy-phenoxy, and the like.

[024] The term "aikaryl" refers to an aryl group with an alkyl substituent and the term "aralkyl" refers to an alkyl group with an aryl substituent, wherein "ary!" and "alkyl" are as defined above. Preferred aikaryl and aralkyl groups contain 6 to 24 carbon atoms, and particularly preferred aikaryl and aralkyl groups contain 6 to 16 carbon atoms Aikaryl groups include, without limitation, p-methylphenyl, 2,4-dimethylphenyl, p-cyclohexylphenyl, 2,7- dimethylnaphthy!, 7-cydooctylnaphthyi, 3-ethyi-cyclopenta- 1 ,4-diene, and the like. Examples of aralkyl groups include, without limitation, benzyl, 2~phenyl~ethyi, 3 -phenyl-propyl, s - phenyl - butyl 5-phenyI-pentyJ, 4-phenylcyclohexyl, 4-benzylcyclohexyl, 4~phenylcyelohexyknethyl, 4- benzylcyelohexylmethyl, and the like. The terms "alkaryloxy" and "aralkyloxy" refer to

substituents of the formula -OR wherein R is aikaryl or aralkyl, respectively, as just defined.

[025] The term "acyl" refers to substituents having the formula -(CO)-alkyl, -(CQ)-aryl, - (CO)-aralkyL -(CO)-alkaryi -(CO)-alkenyl, or -(CO)-aikynyl, and the term "aeyioxy" refers to substituents having the formula -0(C0)-a!kyl, -0(CO)-aryl, -0(CO)-ara3kyl, ~0(C0)-aikaryl, - 0(CO)-aikenyl, or ---(CO)-alkynyl wherein "alkyl," "aryl”, "aralkyl",“aikaryl”,“alkenyl”, and “alkynyl” are as defined above. The acetoxy group (-0(CO)CH ₃ , often abbreviated as -OAc) is a common example of an aeyioxy group.

[026] The terms ''cyclic" and "ring" refer to aiicyclie or aromatic groups that may or may not be substituted and/or heteroatom containing, and that may be monocyclic, bicyclic, or polycyclic The term "a!icyclic" is used in the conventional sense to refer to an aliphatic cyclic moiety, as opposed to an aromatic cyclic moiety, and may be monocyclic, bicyclic or polycyclic.

[027] The term "polycyclic ring" refers to aiicyclie or aromatic groups that may or may not be substituted and/or heteroatom containing, and that have at least two closed rings tethered, fused, linked via a single bond or bridged. Polycyclic rings include without limitation naphthyl, biphenyl, phenanihryl and the like. [028] The term "spiro compound" refers to a chemical compound, that presents a twisted structure of two or more rings (a ring system) in which 2 or 3 rings are linked together by one common atom,

[029] The terms "halo" and "halogen" and "halide" are used in the conventional sense to refer to a fluorine (F), chlorine (Cl), bromine (Br), or iodine (I) substituent.

[030] The terms "cis"/"Z" and "trans'V'i?" as used herein, are used interchangeably and refer to the geometry of the double bonds.

[031 j "Hydrocarhyl" refers to univalent hydroearbyl radicals containing 1 to 24 carbon atoms, most preferably 1 to 12 carbon atoms, including linear, branched, cyclic., saturated and unsaturated species, such as alkyl groups, alkenyl groups, alkynyl groups, aryl groups, and the like. The term "lower hydroearbyl" refers to a hydroearbyl group of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, and the term "hydrocarbyiene" refers to a divalent hydroearbyl moiety containing 1 to 24 carbon atoms, preferably 1 to 12 carbon atoms, including linear, branched, cyclic, saturated and unsaturated species. The term "lower hydrocarbyiene" refers to a hydrocarbyiene group of i to 6 carbon atoms. "Substituted hydroearbyl" refers to hydroearbyl substituted with one or more substituent groups, and the terms "heteroatom-containing hydroearbyl" and "heterohydrocarbyl" refer to hydroearbyl in which at least one carbon atom is replaced with a heteroatom. Similarly, "substituted hydrocarbyiene" refers to hydrocarbyiene substituted with one or more substituent groups, and the terms "heteroatom-containing hydrocarbyiene" and heterohydrocarbylene" refer to hydrocarbyiene in which at least one carbon atom is replaced with a heteroatom. Unless otherwise indicated, the term "hydroearbyl" and "hydrocarbyiene" are to be interpreted as including substituted and/or heteroatom-containing hydroearbyl and hydrocarbyiene moieties, respectively.

[032] The term "heteroatom-containing" as in a "heteroatom-containing hydroearbyl group" refers to a hydrocarbon molecule or a hydroearbyl molecular fragment in which one or more carbon atoms is replaced with an atom other than carbon, e.g., nitrogen, oxygen, sulfur, phosphorus or silicon typically nitrogen, oxygen or sulfur. Similarly, the term "heteroaikyi" refers to an alkyl substituent that is heteroatom-containing, the term "heterocyclic" refers to a cyclic substituent that is heteroatom-containing, the terms "heteroaryi" and "heteroaromatic" respectively refer to "aryl" and "aromatic” substituents that are heteroatom-containing, and the like. It should be noted that a "heterocyclic” group or compound may or may not be aromatic, and further that "heterocycies" may be monocyclic, bicyclic, or polycyclic as described above with respect to the term "aryl." Examples of heteroalkyl groups include without limitation alkoxyaryl, aikylsulfany!-substituted alkyl, N-alkylated amino alkyl, and the like. Examples of heteroaryl substituents include without limitation pyrrolyl, pynroiidinyl, pyridinyl, quinolinyl, indolyi, pyrimidinyl, imidazolyi, 1 ,2,4-triazolyl, tetrazolyl, etc., and examples of heteroatom- containing alicydie groups include without limitation pyrrolidines, morpholine, piperazine, piperidines, etc.

[033] By "substituted" as in "substituted hydroearbyi", "substituted alkyl", "substituted aryl", and the like, as alluded to in some of the aforementioned definitions, is meant that in the hydroearbyi, alkyl, aryl, or other moiety, at least one hydrogen atom bound to a carbon (or other) atom is replaced with one or more non-hydrogen substituents. Examples of such substituents include, without limitation groups such as halo, hydroxyl, sulihydryl, C C ₂₄ alkoxy, C2-C24 alkenyloxy, C¾~C?.4 alkynyloxy, CS-CM aryloxy, C ₆ -C ₄ aralkyioxy, C ₆ -C ₂₄ alkaryloxy, acyl (including C2-C24 aikylcarbonyl (-CO-alkyl) and C ₆ -C ₂ arylcarbonyl (-CO- aryi)), acyloxy (-O-acyl, including C2-C ₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C ₆ -C ₂ arylcarbonyloxy (-O-CO-aryl)), C2-C24 alkoxycarbonyl (-(COVO-alkyl), C6~C¾ aryloxycarbonyl (-(CO)-O-aryl), halocarbonyl (-CO)-X where X is halo), C ₂ -C ₂₄ alkylcarbonato (-O(CO)-O- alkyl), C6-C24 arylcarbonato (-G-(CO)-Oaryl), carboxy (-CC)OH), carbamoyl (-(CO)-NH ₂ ), mono-(Ci-C24 alky])-substituted carbamoyl (-(CO)-NH (C 1 -C24 alkyl)), di-(Ci-C24 alkyl)- substituted carbamoyl (~(CO)~N(CI -C24 alkyl}?}, mono~(Ci-C’ ₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C j -C24 haloalkyl)), di-(C?-C24 haloalkyl)-substituted carbamoyl (-(CO)-N(Cj-C24 haloalkyl)2), mono-(Cs-C24 aiyl)-substituted carbamoyl (~(CO)~NH-ary3), di-(Cs-C24 aryl)- substituted carbamoyl (-(CO)-N(Cs-C24 aryl)?.)- dt-N-(Ci-C24 alkyl), N-(Cs-C24 aryl)-substituted carbamoyl (-(CO)-N(CI-C24 a3kyf)(Cs-C24 aryl), thiocarbamoyl (-(CS)- -b), mono-(C;-C ₂₄ aikyl)-substituted thiocarbamoyl (-(CS)-NB(C;-C24 alkyl)), di-(C-.-C24 alkyl)-substituted thiocarbamoyl (-(CS)-N(Ci~C24 alkyl) ₂ ), mono~(Cs~C2 ₄ aryl)-substiiuted thiocarbamoyl (~(CS)~ NH-aryl), di-(Cs-C ₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C5-C24 aryik), di-N-(Ci-C ₂₄ alkyl), N-(CS-C24 aryl)-substituted thiocarbamoyl (-(CS)-N(CI -€2 ₄ alkyI)(Cs-C24 aryl), earbamido (-NH-(C0)-NH2), cyano(-ON), cyanato (-0-CºN), thiocyanato (-S~CºN), isocyanate (-NCO), thioisocyanate (-NCS), formyl (-(CO)-H), thioformyl (-(CS)-H), amino (-NH ₂ ), mono-(Cs-C ₂₄ alkyl)-suhstituted amino (-NH(Ct-C24 alkyl), di-(Ci-C24 alkyi)-substituted amino ((-N(C]-C ₂₄ alkyl)2), mono-(Cs"C24 aryl)-substi luted amino (-NH(Cs-C24 aryl), di-(C5-C24 ary!)-substituted amino (-N(Cs-C24 aryl)2), C2-C24 aikyiamido (-NH-(CO)-alkyl), C6-C2-1 arylamido (-NH-(CO)- aryi), iraino (-CRNH where, R includes without limitation I-I, C ₁ -C ₂₄ alkyl, C5-C ₂₄ aryl, C ₆ -C ₂₄ alkaryl, C ₆ -C ₂₄ aralkyl, etc.), C ₂ -C ₂ alky! iraino (-CRN(a!kyi), where R includes without limitation H, Ci-C-24 alkyl, C5-C24 aryl, Ce-C ₂₄ alkaryl, C6-C24 aralkyl, etc.), arylimino (- CRN(aryi), where R includes without limitation H, Ci-Cjo alkyl, C ₅ -C ₂₄ aryl, C6-C ₂₄ alkaryl, C ₆ - C24 aralkyl, etc,), nitro (-NO2), nitroso (-MO), sulfo (-SO2-OM), Ci-C24 alkylsulfanyl (-S-alkyl; also termed "a!kyithio"), C5-C24 arylsulfanyl (-S-aryl; also termed "aryllhio"), C1-C ₂₄

alkylsulfinyl (-(SO)-alkyl), C5-C24 arylsulfinyl {-(SO)-aryl), Ci-C ₂₄ alkylsulfonyl (-SCh-alkyi), C!-C ^' 24 monoalkylaminosulfonyl (-SC>2-N(H) alkyl), C.-C24 dialkylaminosulibnyl (-SO2- Nialkyl)?), C5-C24 arylsulfonyl (-SCfe-aryl), boryl (-BH ₂ ), borono (-B(OH) ₂ ), boronato (-B(OR)?. where R includes without limitation alkyl or other hydrocarbyl), phosphono (~P(0)(QH) ₂ ), phospho (-PO2), phosphine (-PH _? .), silyl (-SiR _? wherein R is H or hydrocarbyl), and silyloxy (- O-silyl); and the hydrocarbyl moieties Ci-C ₂₄ alkyl (preferably Ci-Cj ₂ alkyl, more preferably Ci- Cft alkyl), C ₂ -C ₂₄ alkenyl (preferably C ₂ -C ₁₂ alkenyl, more preferably C - , alkenyl), C _? .-C ₂₄ alkynyl (preferably C2-C12 alkynyl, more preferably C2-C6 alkynyl), C ₅ -C ₂₄ aryl (preferably Cs- C14 aryl), C C ₂₄ alkaryl (preferably Ce~C _\ e alkaryl), and C6-C ₂₄ aralkyl (preferably C ₀ -C ₁₆ aralkyl),

[034] By "functionalized" as in "functionalized hydrocarbyl", "functionalized alkyl", "functionalized olefin", "functionalized cyclic olefin", and the like, is meant that in the hydrocarbyl, alkyl, olefin, cyclic olefin, or other moiety', at least one H atom bound to a carbon (or other) atom is replaced with one or more functional groups such as those described hereinabove. The term "functional group" is meant to include any functional species that is suitable for the uses described herein. In particular, as used herein, a functional group would necessarily possess the ability to react with or bond to corresponding functional groups on a substrate surface.

[035] In addition, the aforementioned functional groups may, if a particular group permits, be further substituted with one or more additional functional groups or with one or more hydrocarbyl moieties such as those specifically enumerated above. Analogously, the above mentioned hydrocarbyl moieties may be further substituted with one or more functional groups or additional hydrocarbyl moieties such as those specifically mentioned above. Analogously, the above-mentioned hydrocarbyl moieties may be further substituted with one or more functional groups or additional hydrocarbyl moieties as noted above.

[036] 'Optional’ or "optionally" means that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not. For example, the phrase "optionally substituted" means that a nonhydrogen substituent may or may not be present on a given atom, and, thus, the description includes structures wherein a non-hydrogen substituent is present and structures wherein a non- hydrogen substituent is not present,

[037] The term "terminal olefin" as used herein means an olefin wherein one of the olefinie carbons (i,e., the carbons of the carbon-carbon double bond) is substituted by at least one non hydrogen substituent and the other olefinie carbon is unsubstituted,

[038] The term "nil", as used herein, means absent or nonexistent.

[039] The term "suifhydryl" as used herein, represents a group of formula

[040] The term "hydroxy!" as used herein, represents a group of formula "-OH".

[0411 The term "carbonyl" as used herein, represents a group of formula "~C(0)~ ",

[042 [ The term "ketone" as used herein, represents an organic compound having a carbonyl group linked to a carbon atom such as ~C(0)R ^x , wherein R ^x can be alkyl, aryl, eycloalkyi, eyeioalkenyl, heterocyeie as defined above.

[043] The term "ester" as used herein, represents an organic compound having a carbonyl group linked to a carbon atom such as -€(0)OR* wherein R can be alkyl, aryl, eycloalkyi, eyeioalkenyl, heterocycle as defined above

[044] The term "amine" as used herein, represents a group of formula "-NR ^x R ^y ", wherein R ^x and R ^y can be the same or independently H, alkyl, ary], eycloalkyi, eyeioalkenyl, heterocyeie as defined above.

The term "carboxyl" as used herein, represents a group of formula "~C(0)0~".

The term "sulfonyl" as used herein, represents a group of formula "-SO _? ;".

The term "sulfate" as used herein, represents a group of formula "-0~S(0) ₂ -0-". The term "sulfonate" as used herein, represents a group of the formula "-S(0) ₂ -0-

The term "carboxylic acid" as used herein, represents a group of formula

C(0)0H ^:

The term "nitro" as used herein, represents a group of formula "-NO2".

The term "cyano" as used herein, represents a group of formula "-CN".

The term "amide" as used herein, represents a group of formula”-C(i))NR ^: R ^y ", wherein R ^x and R ^y can be the same or independently H, alkyl, aryl, eycloalkyi, eyeioalkenyl, heterocyeie as defined above.

[053] The term "sulfonamide" as used herein, represents a group of formula

S(0) ₂ NR ^X R>·" wherein R ^x and R ^y can be the same or independently H, alkyl, aryl, eycloalkyi, eyeioalkenyl, heterocyeie as defined above. [054] The term "sulfoxide" as used herein, represents a group of formula "-S(Q)~ "

[OSS] The term "phosphonic acid” as used herein, represents a group of formula

P(0)(0I-i) ₂ ".

[OSS] The terra "phosphoric acid" as used herein, represents a group of formula

0P(0)(0H) ₂ ".

]057| The term "sulphonic acid" as used herein, represents a group of formula

S(0) ₂ OH".

[OSS] The formula "H", as used herein, represents a hydrogen atom.

[059] The formula Ό", as used herein, represents an oxygen atom.

[069] The formula "NT as used herein, represents a nitrogen atom.

[061] The formula "5" as used herein represents a sulfur atom.

[062] Functional groups may be protected in cases where the functional group interferes with the metathesis catalyst, and any of the protecting groups commonly used in the art may be employed. Acceptable protecting groups may be found, for example, in Greene et ah. Protective Groups in Organic Synthesis, 5th Ed. (New York: Wiley, 2014). Examples of protecting groups include acetals, cyclic acetals, horonate esters (boronates), cyclic boronate esters (cyclic boronates), carbonates, or the like. Examples of protecting groups inc lude cyclic acetals or cyclic boronate esters.

[063] Olefin cross-metathesis is a convergent method for building C-C double bonds in natural product syntheses. [Cheng-Sanehez, 1.: Sarabia, F. Recent Advances in Total Synthesis via Metathesis Reactions. Synthesis 2018, 50, 3749-3786. Furstner, A. Metathesis in Total Synthesis. Chem. Commun. 2011, 47, 6505. Nieo!aou, K. C.; Bulger, P. G,; Sarlah, D,

Metathesis Reactions in Total Synthesis. Angew Chem. hit Ed. 2905, 44, 4490-4527.]

However, it has seldom been applied in the previous syntheses of A ^{I 3} -PGJ family. Most importantly, conventional metathesis catalysts typically gave imperfect control of alkene geometry,

[064] Previous syntheses relied on the semi-hydrogenation of alkynes or Wittig reactions, requiring multi-step functional group manipulation with concomitant waste generation. From a strategic perspective, chemoseiectivity among multiple a!kenes has also been another concern, especially in the later stages. Stereoselective and a!kene-chemoselective metathesis catalysts are in demand to realize a convergent synthesis from simple alkene building blocks. [065] A series of cydometal Sated ruthenium-based catalysis fe.g, R«-l, Ra-2) as shown in Figure 2, were recently developed by Grubbs and eo-workers.

Figure 2, Z-seleciive metathesis catalysts

|066] The ruthenium catalysts of Figure 2 enabled Z-selective metathesis through a favored syn -meiallacyelobuiane intermediate (Scheme I, Path A).

Scheme 1

[Endo, K.; Grubbs, R, H. Chelated Ruthenium Catalysts for Z-Selective Olefin Metathesis. J Am. Chem Soc. 2011, 133, 8525-8527. Keitz, B. K.; Endo, K.; Patel, P, R.; Herbert, M. B,; Grubbs, R. H. Improved Ruthenium Catalysts for Z-Selective Olefin Metathesis. J. Am. Chem. Soc. 2012, 134, 693-699.] [067] More recently, cateehodithiolate-based catalyst Ru~3 and its dithiolate variants were developed by Hoveyda group and showed high Z-selecfcivity in ring opening metathesis polymerizations, ring-opening cross-metathesis, and cross-metathesis with Z-olefins.

Figure 3. Slereoreteniive metathesis catalysts

[068] In fact, high kinetic ^ ^' -selectivity in cross-metathesis with ^-starting materials was also observed with Ru~3, the s-lPr analogue Ra-4, and other less bulky fast-initiating analogues developed by Materia Inc. arid the Grubbs group, that defined these catalysts as stereoretentive. [Johns, A. M,; Ahmed, T, S.: Jackson, B. W.; Grubbs, R. H.: Pederson, R, L. High Trans Kinetic Selectivity in Ruthenium-Based Olefin Cross-Metathesis through

Stereoretention. Org. Lett . 21)16, 18, 772-775. Ahmed,. T. S,; Grubbs, R. H. Fast-Initiating, Ruthenium-Based Catalysts for improved Activity in Highly ^-Selective Cross Metathesis J. Am. Chem. Soc , 2017, 139, 1532-1537. Khan, R. K M.: Torker, S,; Hoveyda, A. H. Readily Accessible and Easily Modifiable Ru-Rased Catalysts for Efficient and Z-Seieetive Ring- Opening Metathesis Polymerization and Ring-Opening/Cross- Metathesis. J Am. Che . Soc. 2013, 135, 10258-10261. Hoveyda, A. H. Evolution of Catalytic Stereoselective Olefin Metathesis: From Ancillary Transformation to Purveyor of Stereochemical Identity. J Org. Chem. 2014, 79, 4763-4792. Koh, M. J.; Khan, R. K. M,; Torker, S.; Hoveyda, A, H. Broadly .Applicable Z- and Diastereoselective Ring-Opening/Cross-Metathesis Catalyzed by a Dithiolate Ru Complex. Angew. Chem. Int. Ed 2014, 53, 1968- 1972.]

[069] The origin of the stereoretention was attributed to the formation of a side-bound metal !acyeiobutane intermediate, of which the a-substituents are forced down to minimize steric interactions with the bulky M-aryl groups of the NHC. As a result, when starting with Z-alkene.s, the b-substituent points down to generate Z-alkene products (Scheme 1, Path B). When starting with ii-aikenes, however, the b-substituent has to point up into the open space between two N- aryl groups, leading to the generation of C-alkene products, albeit with slower rates (Scheme 1, Path C). [870] Cross-metathesis between two terminal aikenes is not possible with

stereoretentive metathesis catalysts however, because the intermediate methylidene species are unstable and lead to catalyst decomposition. [ Koh, M. I.; Khan, R. K. M.; Torker, S.; Yu, M; Mikus, M. S.; Hoveyda, A. H. High-Value Alcohols and Higher-Oxidation- State Compounds by Catalytic Z-Selective Cross-Metathesis. Nature 201S, 517, 181-186.]

[071] A methylene capping strategy was recently reported as a remedy to this problem enabling the cross-metathesis of two terminal aikenes, [ Xu, C.; Shen, X.; Hoveyda, A. H. In Situ Methylene Capping: A General Strategy for Efficient Stereoretentive Catalytic Olefin Metathesis. The Concept, Methodological Implications, and Applications to Synthesis of

Biologically Active Compounds. ,/ Am. ( hern Soc. 2817, 139, 10919-10928.] Despite the unique properties of these stereoretentive catalysts, to date limited synthetic evaluation of these catalysts has been conducted [Stereoretentive metathesis using Ru: Montgomery, T. Ahmed, T S ; Grubbs, R. H Stereoretentive Olefin Metathesis: An Avenue to Kinetic Selectivity.

Angew. Chem. Ini. Ed. 2017, 56, 1 1024-1 1036. Ahmed, T . S.; Grubbs, R. H A Highly Efficient Synthesis of Z-Macrocycles P.; Grubbs, R. H Using Stereoretention for the Synthesis ofE- Macroeyc!es with Ruthenium-Based Olefin Metathesis Catalysts. Chem. Sci. 2018, 9, 35 BO- 3583. Jung, K.; Kim, K.; Sung, Ahmed, T S.; Hong S. H.; Grubbs, R. H.; Choi, T.-L. ^’ Toward Perfect Regiocontrol for b-Seleeiive Cyelopoiymerization Using a Ru-Based Olefin Metathesis Catalyst. Macromolecules 2818 51, 4564-4571. Stereoretentive metathesis using Mo, W: Couturier J.-L.; Pail!et, C.: Leconte, M.; Basset, J.-M.; Weiss, K. A Cyc!ometalated Aryloxy(Chloro) Neopenlylidene-tungsten Complex: A Highly Active and Stereoselective

Catalyst for the Metathesis of Cis- and Trans-2-Pentene, Norbornene, 1 -Methy 1-Norbomene, and Ethyl Oleate. Angew. Chem. . Ed. 1992, 31, 628-631. 1, am, 1. K.; Zhu, C ; Bukhryakov, V.: MOller, P.; Hoveyda, A.; Schrock, R. R Synthesis and Evaluation of Molybdenum and Tungsten Monoaryloxide Halide Alkylidene Complexes for Z-Selective Cross-Metathesis of Cyclooctene and Z- 1 ,2-Dichioroethylene. J. Am. Chem. Soc. 2816, 138, 15774-15783 Nguyen, T. T ; Koh, M. J.; Shen, X ; Romiti, F.; Schrock, R. K ; Hoveyda, A. H. Kinetically Controlled ϋ-Selective Catalytic Olefin Metathesis. Science 2816, 352, 569-575 Shen, X.; Nguyen, T. T.; Koh, M j.: Xu, D.; Speed, A. W. H.; Schrock, R. R ; Hoveyda, A H. Kinetically E ^' -Seleetive Macrocydic Ring-Closing Metathesis. Nature 2817, 541, 380-385. Koh, M. J.: Nguyen, T. T.; Lam, J. K.; Torker, S.; Hyvl, J ; Schrock, R. R.; Hoveyda, A. H. Molybdenum Chloride

Catalysts for Z-Seieetive Olefin Metathesis Reactions. Nature 2817, 542, 80-85.] [072 \ Herein, we present a total synthesis of the olefin-enriched A ⁱ² -prostaglandin j natural products (1)— (4) of Figure 1, by implementing a concise stereoretentive metathesis approach. This also sets a perfect test ground to evaluate the reactivity, ehemoselectivity, and functional group compatibility of these newly developed metathesis catalysts,

[073] Retrosynthetically, A ¹² -PGi3 (3) for example, can be simplified into a truncated prostaglandin structure 22 by use of stereoretentive metathesis (Scheme 2).

Scheme 2, Reirosynthet Analysis of A ^{S ?} -PGJ3 (3)

[074] A three-component coupling strategy can be applied toward the synthesis of 22, using a relatively simple and commercially available ally! Grignard reagent, co-chain aldehyde 21, and a chiral cyciopentenone The O-Boe group of (i?)-6 can be used as a traceless slereoinduetive group to set the C8 stereocenter. [Noyori, R,; Suzuki, M Prostaglandin

Syntheses by Three-Component Coupling. Angew. Chem. Ini. Ed. 1984, 23, 847-876. Arisetti, N.; Reiser, O. Traceless Stereoinduction for the Enantiopure Synthesis of Substituted-2- Cyclopentenones, Org. Lett 2015, 17, 94-97.]

[075] Following the retrosynthctic analysis of A^-PGIs (3) we aimed to synthesize A ¹² -

PGJ2 (1). Therefore, chiral cyciopentenone (j?)~6 was prepared from furfuryl alcohol in a three- step process including a kinetic resolution method developed by Reiser and coworkers (Scheme 3). [Ulbrich, K,; Kreitmeier, P.; Vilaivan, T.; Reiser, O. Enantioselective Synthesis of 4- Heterosubstituted Cyclopentenones. J. Org . Chem. 2013, 78, 4202-4206.]

Scheme 3, Preparation of Chiral Cyciopentenone (i?)-6

The o)~chain aldehyde 10 was prepared from hexana! 7 through asymmetric Keck allylation, [Yadav, J. S.; Suresh, B,; Srihari, P, Stereoselective Total Synthesis of the Marine Maeroiide Sanctolide A: Total Synthesis of the Marine Macrolide SanetoHde A. Ear. J. Org Chem. 2015, 201, 5856-5863.] The TBS protection, and ozonolysis are also shown in (Scheme

(79% y el ) @ (93% yield) 10

[077] With all the starting materials for the three-component coupling in hand,

CuBr*Me ₂ S and LiCl facilitated the diastereoseiective conjugate addition of the allyl magnesium bromide. The enolate formed was trapped by the subsequently added enchain aldehyde electrophile, and the O-Boc group was eliminated in the course of the aldol reaction to form the desired cyelopentenone. [078] Elimination with MsC! and DMAP favored E-product 11 as the major product in reasonable yield (45% over 2 steps. Scheme 5).

THF, -78 °C, 1 b

2. MsCi, DMAP, CH ₂ C! ₂

(45% yield over 2 steps)

[079] Stereoretentive metathesis was then evaluated on 11 Since 11 cannot react with another terminal alkene using stereoretentive metathesis catalysts, we considered a symmetric Z- aikene 13 as the coupling partner which could also be made by homodimerizaiion of readily available 12 through stereoretentive metathesis. With 1 moi% loading of Ru-4 as the catalyst, 98% conversion could be achieved by applying dynamic vacuum to remove the by-product, cis - 3- hexene (bp 66-68 °C) from the reaction mixture. Next, 11 with an additional 5 mol% catalyst Mu -4 were added into the reaction mixture, and the alcohol product 14 could be isolated in 95% yield in high Z-selectivity (>99% 2). This result established the efficacy of an efficient one-pot stereoretentive homodimerization/cross-metathesis strategy to build the C5 Z-alkene.

Scheme 6, Preparation of Alcohol 14

(95% yield, >@S:1 2/E) [080] In contrast, synthesis of PGE2 and PGF2a required a large excess of gaseous butene and more complicated operations in the previously reported methylene capping strategy. [Xu, C.; Shen, X.; Hoveyda, A H In Situ Methylene Capping: A General Strategy for Efficient Stereoretentive Catalytic Olefin Metathesis. The Concept, Methodological Implications, and Applications to Synthesis of Biologically Active Compounds. J. Am. Chem Soc. 2017, 139, 10919- 10928.] Ley oxidation and deprotection of the TBS group of 14 in aqueous HF furnished the natural product A ¹⁷ - -prostaglandin i? (1) in 89% yield over the last two steps.

[081] The same three-component coupling sequence was performed to obtain 16, and the enal functionality of aldehyde 15 was well tolerated in the aldol step, as shown in Scheme 8.

2. MsC!. OMAR, CH ₂ C¾

THF, -78 %, 1 h

(41 % yield over 2 steps, 88% es

[082] 16 was then subjected to the standard one-pot stereoretentive homodimerization/ cross-metathesis conditions, and alcohol 17 was obtained in excellent yield (93% yield, Scheme 9) with high Z-selectivity (>99% Z). The 04 E-alkene tolerated the reaction, consistent with the much slower reaction of £~alkenes with Ra-4 as seen previously. [Johns, A. M; Ahmed, T S„; Jackson, B. W.; Grubbs, R. R; Pederson, R, L. High Trans Kinetic Selectivity in Ruthenium- Based Olefin Cross-Metathesis through Stereoretention. Org. Lett. 2016, 18, 772-775. Ahmed, T. S.; Grubbs, R. H Fast-Initiating, Ruthenium-Based Catalysts for Improved Activity in Highly ^-Selective Cross Metathesis J. Am. Chem. Sac. 2017, 139, 1532-1537.] We also assessed the enantiopurity of intermediates 16 and 17. Three-component coupling product 16 proceeded with a small loss in enantiopurity (88% ee) from (R)~6 (>99% ee); but the metathesis product 17 was obtained without significant erosion of enantiopurity (87% ee).

, ,

one-pot homocoupling/stereoretentive metathesis

This result demonstrates that stereoretentive metathesis with catalyst Ru-4 also retained the stereochemistry of the C8 stereocenter. Ley oxidation of 17 again gave 15-deoxy- A ¹² ' ^;4 -prostag!andin Js (2) in 68% yield.

Scheme 10, Synthesis of A ^i2,34 -Prostaglandin ,h (2) 15-deoxy-A _' -prcistagiaridin J ₂ 2

Synthesis of A ^{! i} -prostaglandin J ₃ (3) began with the preparation of the co-chain aldehyde 21. We envisioned the Z-alkene in 21 could also be generated from stereoretentive metathesis. First, we obtained chiral alcohol 18 through a reported chiral pool strategy with (R)- epichlorohydrin as the starting material (Scheme 11), [Bai, Y.; Shen, X.; Li, Y,; Dai, M. Total Synthesis of (-)~Spinosyn A via Carhonyiative Maerolaetonization. J Am. Chem.

138 , 10838-10841.]

vinyimagnesiijm bromide, THF

(95% yield)

(58% yield)

ois-3 -hexene [085] TBS protection of the alcohol 18 and subsequent removal of the 1,3-dithiol gave aldehyde 20 Stereoretentive metathesis of 20 with an excess amount of els- 3-hexene using catalyst Ru-4 (4 mol%) afforded co-chain aldehyde 21 in good yield (88%) with high Z- selectivity (>99% Z). The short synthesis of aldehyde 21 proved that a broad range of functional groups, including aldehydes, can be tolerated without protecting group manipulations using stereoretentive catalysis. Then, product 22 was synthesized through the standard three- component coupling sequence from (J?)-6 (Scheme 12).

(40% yield over 2 steps)

[0§6] Surprisingly, fast ring closing metathesis ( CM) with Ru-4 yielded 24 as a byproduct (31% yield) bearing an unusual 9~membered ring and the desired alcohol product 23 was obtained in only 44% yield.

[087] Alternatively, we chose to use eyelometallaied catalyst Ru-2 to circumvent the crossover ofalkene reactivity. Because tri -substituted meta!lacyclobutane intermediates arc highly unfavorable with this cyeiometailated catalyst, this pathway can be easily avoided Figure 4,

Figure 4; Trisuhstitisted Metaliacydobutaue Intermediate with Ru~2 o 3

22 23 28

52 yield) · '·:.·'¾ yield)

[088] [ Herbert, M. B.; Grubbs, R. H. Z-Selective Cross Metathesis with Ruthenium

Catalysts: Synthetic Applications and Mechanistic Implications Angew. Chem. Ini . Ed. 2015, 54, 5018-5024.] Chemoseiective cross-metathesis of 5-hexen-I-ol (25) with the allyl group of furnished the desired product 23 in good yield (52%) with a trace amount of by-product 26 (less than 2%, Scheme 14). The RCM product 24 was not observed under these conditions.

i8S91 The side-reaction of 07 internal Z-alkene could be attributed to ethylene produced or the residual ruthenium ethylldene species in the solution. Then, Ley oxidation of 23 and deprotection of the TBS group with aqueous HF provided A ^l2 ~prostaglandin is (3) in 8 linear steps.

(52% yield)

Finally, in the synthesis of ISd-PGJs (4) (Scheme 16), crossover of metathesis reactivity between the ally! group and the Cl 7 Z-alkene of 28 could also be expected. Standard stereoretcniive metathesis conditions with Ru~4 provided desired product 29 in 36% yield and by-products 30 and 31.

Scheme 16, Synthesis of 15d~PG,h (4)

[0911 28 as well as by-products 29 and 30 were obtained using Ra-2 and no improvement of chemoselectivity was observed. Compared to A ^!2 ~PGJ (3) synthesis, where the steric bulk of the QTBS group may be beneficial to achieving good chemoselectivity 28 has no such steric hindrance. However, no RCM of 28 was observed, possibly due to the ring strain of the RCM product. Though 30 could not be separated from 29, the mixture was subjected to pyridinium chloroehromate (PCC) oxidation and Pirmick oxidation conditions allowing us to isolate 15-deoxy- D ^{ϊ2 !4} ~ prostaglandin h (4) (12% yield from 28). Ley oxidation of a mixture of 29 and 39 was also performed but resulted in a significant amount of decomposition products

[092] In conclusion, we were able to achieve a concise and convergent synthesis of four

A ⁵² -prostagiandin J natural products in shorter sequences (7-8 steps in the longest linear sequences) empowered by stereoretentive and stereoselective metathesis. Furthermore, the reactivity, chemoselectivity, and functional group compatibility of stereoretentive metathesis was evaluated. This study should inspire further practical applications of stereoselective metathesis, such as a facile one-pot stereoretentive homodimcrization/cross-meiathesis strategy to introduce Z-alkenes with excellent geometric control. The modularity and expediency of this chemistry opens the synthesis of other prostaglandins and analogues to enable SAR studies in cancer treatment. With the well-defined kinetiealiy Z/E-seiective catalysts that have been developed to overcome the inherent thermodynamic preference of alkene product geometry, olefin metathesis can play a pivotal role in the synthesis design

O!efrn Metathesis Catalysts

[ 93] In one embodiment the invention provides a stereoretentive ruthenium olefin metathesis catalyst represented by the structure of Formula (I),

wherein:

X is O or S:

Y is O or S:

Z is N or CR ³² ;

W is O, halogen, NR ³³ or S;

R ¹ is H, optionally substituted C.. ₂₄ alkyl, halogen, - C(0)R ^2S , - OR ²⁶ , CN, - NR ²⁷ R ^2S , NC¾, - CF3, -S(0) _X R ^2S , -P(0)(0H)2, -0F(0)(0H) ₂ , -SR ^3! , optionally substituted heterocyde, optionally substituted C;;-s eycloalkyl, optionally substituted C _5-24 aryl, optionally substituted C3-8 eycloalkenyl, or together with R ² can form a spiro compound or together with R ³ or together with R ⁴ can form a polycyclic ring;

R ² is H, optionally substituted C _1-24 alkyl, halogen, - C(0)R ^2s , - OR ²⁶ , CN, - NR ²⁷ R ³⁸ , NO ₂ , - CF _3J --S(0) _X R ⁷ · ⁹ , -P(0)(0H) ₂ , 0P(0)(0H) _2, -SR ³¹ , optionally substituted heterocyde, optionally substituted C3.8 eycloalkyl, optionally substituted C5.24 aryl, optionally substituted C3-8 eycloalkenyl or together with R ^! can form a spiro compound or together with R ³ or together with R ⁴ can for: n a polycyclic ring;

R ³ is H, optionally substituted Cj- ₂₄ alkyl, halogen, - C(Q)R ^2S , - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO ₂ , - CF¾, -S(0)xR ²⁹ , -P(Q)(OH) _¾ -OP(0)(OH) ₂ , -SR ⁱ , optionally substituted heterocyde, optionally substituted C?-a eycloalkyl, optionally substituted€ _5-24 aryl or optionally substituted€ _3.3 eycloalkenyl or together with R ² or together with R ¹ can form a polycyclic ring or together with R ⁴ can form a spiro compound;

R ⁴ is H, optionally substituted C1-24 alkyl, halogen, - C(())R ^2S , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , N0 ₂ , - CF:„ -S(0) _x R ^2S , -P(0)(0H) ₂ , -0P(0)(0H)2 _, -SR ³⁵ , optionally substituted heterocyde, optionally substituted Cs-s eycloalkyl, optionally substituted C _5-24 aryl, optionally substituted C _3-8 cycloalkenyl, or together with R ³ can form a spiro compound or together with R ² or together with R ^! can term a polycyclic ring;

R ⁵ is H, optionally substituted 0,- ₂₄ alkyl, halogen, - CCOJR ²³ , - OR ⁷ · ⁶ , CN, - NR ²⁷ R ⁷⁸ , NO2, - CFs, -S(0)xR ²⁹ , -P(0)(0H) ₂ , -OP(0)(OH)2, -SR ³ⁱ , optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C5- ₂₄ aryl, optionally substituted C3.8 cycloalkenyl, or together with R ⁶ can form an optionally substituted polycyclic ring;

R ⁶ is H, optionally substituted Ci _-24 alkyl, halogen, -€(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO ₂ , - CFj, -S(Q) _X R ²⁹ , -F(0)(0H) ₂ , -OP(())(OH) _J., -SR ³¹ , optionally substituted heterocycle, optionally substituted C3-8 cycloaikyl, optionally substituted C5-24 aryl, optionally substituted C _{3. g} cycloalkenyl, or together with R ⁵ or together with R ⁷ can form an optionally substituted polycyclic ring;

R ⁷ is H, optionally substituted C _1-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO ₂ , - CF3, -S(0) _x R ²⁹ , -P(0)(OH) ₂ , -OP(0)(OH) _2> -SR ³¹ , optionally substituted heterocycle, optionally substituted C ₃ -s cycloalkyl, optionally substituted€5-24 ar 3 optionally substituted C3-8 cycloalkenyl. or together with R ⁶ or together with R ⁸ can form an optionally substituted polycyclic ring;

R ⁸ is H, optionally substituted C1 -24 alkyl, halogen, - C(0)R ²⁵ , - OR ⁷ · ⁶ , CN, - NR ²⁷ R ⁷ · ⁸ , NO ₂ , - CF3, -S(G) _X R ²⁹ , -P(0)(OH}2, -0P(0)(0H)2 -SR ³¹ , optionally substituted heterocyeie, optionally substituted€3-8 cycloalkyl, optionally substituted Cs-24 aryl, optionally substituted C3-8 cycloalkenyl, or together with R ⁷ or together with R ⁹ can form an optionally substituted polycyclic ring;

R ^s is H, optionally substituted C _!-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO _¾ - CF3, ~S(0)xR ⁷ · ⁹ , -P(0)(0H) ₂ , -OP(0)(OH)2 _, -SR ^3; , optionally substituted heterocyeie, optionally substituted C3-8 cycloalkyl, optionally substituted Cs-24 aryl, optionally substituted C3-8 cycloalkenyl, or together with R ⁸ can form an optionally substituted polycyclic ring;

R ⁱ⁰ is H, optionally substituted Cj-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO _¾ - CF3, -S(Q) _X R ²⁹ , ~P(0)(QH)2, -0P(0)(0H)2 _, -SR ³¹ , optionally substituted heterocyeie, optionally substituted C3-8 cycloaikyl, optionally substituted Cs- ₂₄ aryl, optionally substituted C _3-8 cycloalkenyl, or together with R ⁿ can form an optionally substituted polycyclic ring;

R ⁿ is H, optionally substituted Cs . ₂₄ alkyl, halogen, - C(0)R ^2S , - OR ²⁶ , CN, - NR ²⁷ R ⁷ · ⁸ , N<¾, - CF3, -S(0)xR ^2S , P(0)(0H)2, -OP(0)(OH) ₂ -SR ³ⁱ , optionally substituted heterocyeie, optionally substituted C3-8 cycloaikyl, optionally substituted C5-24 aryl, optionally substituted C3-8 cycloalkenyl or together with R ^,G or together with R ¹² can form an optionally substituted polycyclic ring;

R ^,2 is H, optionally substituted Cj.24 alkyl halogen, - C(0)R ² \ - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO?, - CP3, -S(0) _x R ²⁹ , -P(0)(0H) ₂ , -0P(0)(0H)? _, -SR ³¹ , optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C _5.24 aryl, optionally substituted C _3-8 cycloalkenyl, or together with R ^u or together with R ¹³ can fonrs an optionally substituted polycyclic ring;

R ¹³ is H, optionally substituted Ci-24 alkyl, halogen, - C(G)R ² \ - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO _? . - CF3, -S(0) _x R ²⁹ , -P(0)(0H) ₂ , -OP(0)(OH)2, -SR ³ⁱ , optionally substituted heterocycle, optionally substituted C ₃ -3 cycloalkyl, optionally substituted C5-24 ar l, optionally substituted C _3-8 cycioalkenyl, or together with R ⁱ⁴ or together with R ¹² can form an optionally substituted polycyclic ring;

R ^u is H, optionally substituted Cj. ₂ 4 alkyl, halogen, - C(0)R ² °, - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO?, ~ CF3, -S(0)xR ²⁹ , -P(0)(0H)2, -0P(0)(0H)2, -SR ³¹ , optionally substituted heterocycle, optionally substituted C ₃ -8 cycloalkyl, optionally substituted Cs- ₂₄ aryl, optionally substituted C3- ₈ cycioalkenyl, or together with R ¹³ can form a polycyclic ring;

R ¹⁵ is H, optionally substituted C _f -24 alkyl, halogen, - C(Q)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , N(¾, - CFj, -S(0) _x R ²⁹ , -P(0)(0H) ₂ , -0P(0)(0H) _2, -SR ³¹ , optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C5.24 aryl or optionally substituted C -8 cycioalkenyl, or together with R ^!<> can form an optionally substituted polycyclic ring;

R ¹⁶ is H, optionally substituted Cj- ₂₄ alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CS¾, -S(()) _X R ²⁹ , -P(0)(0H} _? , ~0P(0)(0H) _2, -SR ³ⁱ , optionally substituted heterocycle, optionally substituted C ₃ -8 eycloalkyf, optionally substituted C _5-24 aryl or optionally substituted C _3-8 cycioalkenyl, or together with R ^{i 5} or together with R ^{: 7} can form an optionally substituted polycyclic ring;

R ¹⁷ is H, optionally substituted C1-24 alkyl, halogen, - C(())R ^2S , - OR ^¾ , CN, - NR ²⁷ R ^2S , N0 ₂ , - CFj, -S(0) _x R ²⁹ , -P(0){OH) ₂ , -0P(0)(0H) _2, -SR ³¹ , optionally substituted heterocycle, optionally substituted C3-8 cyeloaikyl, optionally substituted C5-24 aryl or optionally substituted C3-8 cycioalkenyl, or together with R ¹⁸ or together with R ^lfl can form an optionally substituted polycyclic ring;

R ¹ * is H, optionally substituted Cj- ₂₄ alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO ₂ , - CF3, -S(0) R ^2S , ~P(0)(0H)?, -0P(0)(0H) _2> -SR ^3t , optionally substituted heterocycle, optionally substituted Cs-g cycloalkyl, optionally substituted Cs-24 aryl or optionally substituted C _3.8 cycloalkenyl, or together with R ^{i 7} can form an optionally substituted polycyclic ring:

R ⁱ⁹ is H, optionally substituted C TA alkyl, -C(R ³⁴ )(R ^3S )COOR: ^¾ , -C(R ^M XR ³⁵ )C(0)H, -

C(R ³⁴ )(R ³⁵ )C(t))NR ^4f OR ⁴⁰ , - C(0)R ^2S , optionally substituted heterocycle, optionally substituted C3-8 cycioalkyl, optionally substituted C _5-24 aryl, optionally substituted C3- ₈ cycloalkenyl, or together with R ³³ can form an optionally substituted heterocyclic ring or is nil when W is halogen;

R ²⁰ is H, optionally substituted C1-24 alkyl, halogen, - C(0)R ^2s , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, -S(0) _x R ²⁹ , ~P(0)(OH) ₂ , -0R(0)(0H) _2, -SR ³¹ , optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted Cs-24 aryl, optionally substituted C3-8 cycloalkenyl or together with R ^{2 :} can form a polycyclic ring;

R ²¹ is H, optionally substituted CUM alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO _? ., - CF3, -S(0)XR ²⁹ , -P(Q)(GH)2, - ^Q P(())(()H)2 _, -SR ³¹ , optionally substituted heterocyele, optionally substituted C3-8 cycloalkyl, optionally substituted C5-24 aryl, optionally substituted C ₃ -s cycloaikenyi or together with R ²⁰ or together with R ²² can form a polycyclic ring;

R ²² is H, optionally substituted C5..24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, -S(0)xR ²⁹ , -P(0)(0H)2, -0P(0)(0H) _2, -SR ^3’1 , optionally substituted heterocycle, optionally substituted C _3- a cycloalkyl, optionally substituted C _5-24 aryl, optionally substituted C _3-8 cycloalkenyl or together with R ^J or together with R ²³ can form a polycyclic ring;

R ²³ is H, optionally substituted C1 - ₂₄ alkyl, halogen, - C(0)R ² \ - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO?, - CF3, -S(0) _X R ²⁹ , -P(0)(0H)?, -0F(0)(0H) _2, -SR ³ⁱ , optionally substituted heterocyele, optionally substituted C ₃ -s cycioalkyl, optionally substituted C _5-24 aryl, optionally substituted C _3- s cycloaikenyi or together with R ²² can form a polycyclic ring;

R ²⁴ is H, optionally substituted Ch- ₂₄ alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ^S , NO2, - CFj, -S(0)xR ²⁹ , -P(0)(0H)?., -OP(0)(OH) _2, -SR ^{j !} , optionally substituted heterocyele, optionally substituted C _3-8 cycioalkyl, optionally substituted Cs-2 ₄ aryl or optionally substituted C _3-8 cycloaikenyi;

R ²⁵ is OH, OR ^3lJ , NR ²⁷ R ² *, optionally substituted C _1.24 alkyl, optionally substituted C _3-8 cycioalkyl, optionally substituted heterocyele, optionally substituted C _5-24 aryl or optionally substituted C _3-8 cycloaikenyi, R ²⁶ is H, optionally substituted C;- ₂₄ alkyl, optionally substituted C _3- s cycloalkyl, optionally substituted heterocycle, optionally substituted C _5-24 aryl or optionally substituted C _3- s cyeioaikenyi;

R ²⁷ is H, optionally substituted C _{1 24} alkyl, optionally substituted C _3-8 cyeioaikyl, optionally substituted heterocycle, optionally substituted Cs- ₂₄ aryl or optionally substituted C3-» eycloalkenyl;

R ²⁸ is H, optionally substituted C _1-24 alkyl, optionally substituted C _3- 8 cyeioaikyl, optionally substituted heterocycie, optionally substituted ί ·? ₄ aryl or optionally substituted C _3- s cycloalkenyl;

R ²⁹ is H, optionally substituted C _1-24 alkyl OR ²⁶ , - NR ²⁷ R ²⁸ , optionally substituted heterocycie, optionally substituted C _3-8 cycloalkyl, optionally substituted€ _5-24 ary! or optionally substituted C3-3 eycloalkenyl;

R ³⁹ is optionally substituted C _{1 -24} alkyl, optionally substituted C _3-8 cyeioaikyl, optionally substituted heterocycie, optionally substituted C5-2 ₄ aryl or optionally substituted C g eycloalkenyl;

R ⁱ is H, optionally substituted Ct-24 alkyl, optionally substituted C _3-8 cyeioaikyl, optionally substituted heterocycie, optionally substituted C5-24 aryl or optionally substituted C ₃ -s eycloalkenyl;

R ³² Is H, optionally substituted C1-24 alkyl, optionally substituted C _3- s cyeioaikyl, optionally substituted heterocycie, optionally substituted Cs- ₂₄ aryl or optionally substituted C ₃ ..g

eycloalkenyl:

R ^JJ is H, optionally substituted Cj- ₂₄ alkyl, optionally substituted Cs-g cyeioaikyl, optionally substituted heterocycie, optionally substituted Cs-24 aryl, optionally substituted C _3-8 cyeioaikenyi, or together with R ^{i 9} can form an optionally substituted heterocyclic ring;

R ³⁴ is H, optionally substituted C-.- ₂₄ alkyl, optionally substituted C _3-8 cyeioaikyl, optionally substituted heterocycie, optionally substituted€5-24 aryl or optionally substituted C3-8 eycloalkenyl;

R ³⁵ is H, optionally substituted Ct- ₂₄ alkyl, optionally substituted€ _3-?, cyeioaikyl, optionally substituted heterocycie, optionally substituted C5- ₂₄ aryl or optionally substituted C _3-8

eycloalkenyl:

R ^j6 is H, optionally substituted C1.24 alkyl, optionally substituted C3-8 cyeioaikyl, optionally substituted heterocycie, optionally substituted€ _5-24 aryl or optionally substituted€ _3-8 cyeioaikenyi; R ³⁷ is optionally substituted C[ . ₂₄ alkyl, optionally substituted C3-8 cyeloalkyi, optionally substituted heterocycle, optionally substituted C5-2.4 aryl or optionally substituted C3 .8 cycloalkenyl;

R ^j8 is H, optionally substituted C _{l -2} 4 alkyl, optionally substituted C3-8 cyeloalkyi, optionally substituted hetcrocycle, optionally substituted C _5-24 aryl or optionally substituted C _3.8 cycloalkenyf;

R ³⁹ is H, optionally substituted C _1-24 alkyl, optionally substituted C _3-8 cyeloalkyi, optionally substituted heterocycle, optionally substituted C _5-24 aryl or optionally substituted C _3-8

cycloalkenyl;

R ⁴⁰ is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted C _3.8 cycloalkyl, optionally substituted heterocycle, optionally substituted C _5-24 aryl or optionally substituted C _3-8

cycloalkenyl:

R ⁴ⁱ is H, optionally substituted C _{1 -24} alkyl, optionally substituted C _3.8 cyeloalkyi, optionally substituted heterocycle, optionally substituted C5. ₂₄ aryl or optionally substituted C3-8 cycloalkenyl;

R ⁴² is K, optionally substituted Ci- ₂₄ alkyl, optionally substituted C3-8 cyeloalkyi, optionally substituted heterocycle, optionally substituted C _5-24 aryl or optionally substituted C _3-8

cycloalkenyl; and

x is 1 or 2.

(694) When certain groups, such as: Ci- ₂₄ alkyl, C3-8 cycloalkyl, heterocycle, C5-24 aryl,

C _3-8 cycloalkenyl groups or the polycyclic rings, are optionally substituted, the substituents are selected from: halogen, -OH, -SH, Ci-C ₂₄ alkoxy, C ₂ -C24 alkenyloxy, C2-C24 alkynyloxy, C5-C24 aryloxy, C6-C2 aralkyloxy, Cs-C-24 alkaryioxy. -CO-(Ci-C24 alkyl), -CO- (Ce-C ₂₄ aryl), -O-CO- (C1-C24 alkyl), -0-C0-(C ₆ -C aryl), -(C0)-0-(Ci-C24 alkyl), ~iCO)~0-(C6-C ₂₄ aryl), (-O-(CO)- O- (C1-C24 alkyl), -0-(C0)-0-(C6-C ₂₄ aryl), (-COOH), (-(CO)-NH ₂ ), (-(CO)-NH(C -C ₂₄ alkyl)), (-(CO)-N(CI-C ₂₄ alkyl);), -(C0)-NH-(Cs-C2 ₄ aryl), (-(CQ)-N(Cs-C ₂₄ atyl) ₂ ), (-(CO)-N(Ci-C ₂ 4 alkyl)(C-5-C24 aryl), (-(CS)-NH ₂ ), (-(CS)-NH(Ci-C ₂₄ alkyl)), (-(CS)-N(CI-C ₂₄ alkyl) ₂ ), -(CS)- NH-( C ₆ -C ₂₄ aryl), (-(CS)-N{C ₅ -C ₂₄ aryl) ₂ ), di-N-(Ci-C ₂₄ alkyl), (-(CS)-N(Ci-C ₂₄ alkyl)(C ₅ -C ₂₄ aryl), (- 1 !-(CO)- ! s _{:; )} , (-C-N). (-0~CºN), (-S-CºN), (-NCO), (-NCS), (-(CO)-H), (-(CS)-H), (-NH ₂ ), (-NH(Ci-C ₂₄ alkyl), ((-N(CI-C ₂₄ aikyl) ₂ ), (-NH(Cs-C ₂₄ aryl), (-N(Cs-C ₂₄ aryl);), -NH- (CO)-(Ci-Ce alkyl), -NH-(CO)-( C ₆ -C ₂₄ aryl), -C(C-C.u alkyl)(NH), (-CHN(Ci-C ₂₄ alkyl), (- CHN(C6-C ₂₄ aryl), (-NO2), (-NO), (-SO2-OH), -S-(Ci-C ₂₄ alkyl), (-S-(C ₅ -C ₂₄ aryl), {-(SO)-(C _f - C24 alkyl), (-(SO)-(C ₅ -C ₂₄ and), S02.-(Ci-C ₂₄ alkyl), (-S ^Q ₂ -N(H)( Cj-C ₂₄ alkyl), (-S0 _2~ N(Ci-C ₂₄ alky 1)2), (- OHOC aryl). (-BH _? ), B(QH) ₂ ) _S (-B(0)(Ci-C _M aikyl) ₂ , (-R(0)(0H) ₂ ), (-PO2), (- PH ₂ ), -SJHS, (-O-silyi), CVC24 alkyl C1-C12 alkyl C;~C ₆ alkyl, C2-C24 alkenyl, C2-C12 alkenyl, C2-G5 alkenyl, C2-C24 alkynyl, C2-C12 alkynyl, Cz-Ce alkynyl, C5-C24 aryl, C5-C14 asyl, C6-C24 alkaryl, Ce-Ci* a!karyl, C.6-C24 aralkyl and Cs~C; 6 aralkyl which are as defined herein.

[095] In another embodiment, the invention provides a catalyst represented by

Formula (1) wherein: X is S; Y is 8: Z is N or CR ³² ; W is O, N ³ or S: R ¹ is H, optionally substituted Cm ₂ alkyl, halogen: R ² is H, optionally substituted Ci _-l2 alkyl halogen; R ³ is H, optionally substituted Cm _?, alkyl, halogen; R' ^? is H, optionally substituted Cm ₂ alkyl, halogen; R ^s is H, optionally substituted Cm ₂ alkyl halogen; R ⁶ is H, optionally substituted Cm ₂ alkyl, halogen; R ^? is H, optionally substituted Cm ₂ alkyl, halogen; R ⁸ is H, optionally substituted Cm ₂ alkyl halogen; R is H, optionally substituted Cm ₂ alkyl, halogen; R ^;o is H, optionally substituted Cm2 alkyl, halogen; R ^{i f} is H, optionally substituted Cm 2 ally!, halogen; R ¹² is H. optionally substituted Cm ₂ alkyl, halogen; R ^:3 is H, optionally substituted Cm ₂ alkyl, halogen: R ^:4 is H, optionally substituted Cm _? alkyl, halogen; R ¹⁵ is H, optionally substituted Cm _? alkyl, halogen, optionally substituted heterocyeie, optionally substituted C ₃ -* cyeloalkyl, optionally substituted Cs-io aryl or optionally substituted C _3-8 cyeloalkenyl; R ¹⁶ is H, optionally substituted Cm2 alkyl, halogen, optionally substituted heterocyeie, optionally substituted C?-s cycloalkyl, optionally substituted Ce-io aryl or optionally substituted C _3-S cyeloalkenyl R ¹⁷ is H, optionally substituted Cm ₂ alkyl, halogen, - optionally substituted heterocyeie, optionally substituted Ca-g cyeloalkyl optionally substituted Ce-io aryl or optionally substituted Ci-e cyeloalkenyl. or together with R ¹⁸ can form a polycyclic ring; R ^s8 is H, optionally substituted Cm _? alkyl, halogen, optionally substituted heterocycle, optionally substituted C _3-8 cyeloalkyl optionally substituted Cg-io aryl or optionally substituted C3-8 cyeloalkenyl or together with R ^{1 7} can form a polycyclic ring; R ^!9 is H, optionally substituted Cm _? alkyl, -C(R ³⁴ )(R ^3s )-CGOR ³⁶ , -C(R ⁴ )(R ³⁵ )-C{0)H, - C(R ³⁴ )(R ³⁵ )-C(0)R ³⁷ , -C(R ³⁴ )(R ³⁵ )-CR ³⁸ (OR ³⁹ )(OR ⁴⁰ ), -C(R ³⁴ )(R ^3S )-C(0)-NR ^4, R ⁴² , - C(R ³⁴ )(R ³⁵ )-C(0)-MR ^4! 0R ⁴ °, - C(0)R ²⁵ , optionally substituted heterocyeie, optionally substituted C¾.« cyeloalkyl, optionally substituted Ce-io aryl, optionally substituted C _3-S cyeloalkenyl, or together with R- ^e can form an optionally substituted heterocyclic ring; R ²⁰ is H, optionally substituted Cm2 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO?, -CF3, - S(Q)„;R ²⁹ , -P(())(0H) _2, -0P(0)(0H) _?, -SR ³ 1 optionally substituted heterocyeie, optionally substituted Cm cyeloalkyl, optionally substituted Ce-io aryl, optionally substituted C _3-8 cyeloalkenyl or together with R ²ⁱ can form a polycyclic ring; R ^{2 :} is H, optionally substituted Ci- ₁₂ alkyl, halogen, - NR ^2? R ²⁸ , optionally substituted heterocyeie, optionally substituted C _3.8 cycloalkyl, optionally substituted Ce-so aryl, optionally substituted C _3-8 cycloalkenyl or together with R ²⁰ or together with R ²² can form a polycyclic ring: R ²² is H, optionally substituted Ci-u alkyl, halogen, - C(0)R ^2S , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO ₂ , -CF _¾ --S(0) _x R ²⁹ , -P(0)(0H) ₂ , - 0P(0)(0H) _2, -SR ^{3 i} , optionally substituted heterocycle, optionally substituted C _3-8 cycloalkyl, optionally substituted€ _0-10 aryl, optionally substituted C _3- s cycioalkenyi or together with R ²ⁱ or together with R ²³ can form a polycyclic ring; R ²³ is H, optionally substituted C>.n alkyl, halogen, optionally substituted heterocyde, optionally substituted C _3-8 cycloalkyl, optionally substituted Cg-io aryl or optionally substituted C3-8 cycloalkenyl or together with R ²² can form a polycyclic ring; R ²⁴ is H; R ²⁵ is OH, OR ³⁹ , NR ²⁷ R ²⁸ , optionally substituted C _1-12 alkyl, optionally substituted C3-8 cycloalkyi, optionally substituted heterocyde, optionally substituted€5-10 aryl or optionally substituted C _3.8 cycioalkenyi; R ²⁶ is H, optionally substituted C _1-12 alkyl optionally substituted C3-8 cycloalkyi, optionally substituted heterocyde, optionally substituted C _o. so aryl or optionally substituted C _3-8 cycioalkenyi; R ²⁷ is H, optionally substituted C _{M 2} alkyl, optionally substituted C _3- s cycloalkyi, optionally substituted heterocyde, optionally substituted Ce-;o aryl or optionally substituted€ _3-8 cycioalkenyi; R ^2S is H, optionally substituted CV ₁₂ alkyl, optionally substituted C ₃ -s cycloalkyi, optionally substituted heterocyde, optionally substituted C _6- :o aryl or optionally substituted C _3-8 cycioalkenyi; R ²⁹ is H, optionally substituted Ci- ₁₂ alkyl, OR ²⁶ , - MR ²⁷ R ²⁸ , optionally substituted heterocyde, optionally substituted C ₃ -* cycloalkyi, optionally substituted Ceno aryl or optionally substituted C ₃ -s cycioalkenyi; R ³⁰ is optionally substituted Cy !2 alkyl, optionally substituted C _3-g cycloalkyi. optionally substituted heterocyde, optionally substituted Ce-io aryl or optionally substituted C _3-8 cycioalkenyi; R. ³¹ is H, optionally substituted Ci-i2 alkyl, optionally substituted C _3- s cycloalkyi, optionally substituted heterocyde, optionally substituted CCMO aryl or optionally substituted C _3-8 cycioalkenyi; R ³² is H, optionally substituted Ci-; ₂ alkyl, optionally substituted C _3-8 cycloalkyi, optionally substituted heterocyde, optionally substituted Ck-to aryl or optionally substituted C _3- a cycioalkenyi; R ³³ is H, optionally substituted Ci-n alkyl, optionally substituted€ _3-8 cycloalkyi, optionally substituted heterocyde, optionally substituted Ce-io ary! or optionally substituted C _3-8 cycioalkenyi, or together with R ^iS can form an optionally substituted heterocyclic ring; R ³¹ is H, optionally substituted C _1.12 alkyl, optionally substituted C3-8 cycloalkyi, optionally substituted heterocyde, optional!y substituted Cs-io aryl or optionally substituted C _{3 g} cycioalkenyi; R ^3S is H, optionally substituted C 2 alkyl, optionally substituted C3-8 cycloalkyi, optionally substituted heterocyde, optionally substituted Cg-;o ary! or optionally substituted C - _S cycioalkenyi; R ³⁶ is H, optionally substituted C _M2 alkyl, optionally substituted C?-g eycioalkyl, optionally substituted heterocyde, optionally substituted CCM O aryl or optionally substituted C ₃ -s cycloalkenyl; R ³⁷ Is optionally substituted C; ₀₂ alkyl, optionally substituted C ₃ -s cycloalkyl, optionally substituted heterocycle, optionally substituted Cs-io aryl or optionally substituted C3 8 cycloalkenyl; R ³³ is H, optionally substituted C - ₁₂ alkyl, optionally substituted C _3- s cyeloa!kyi, optionally substituted heterocyele, optionally substituted Cs-io aryl or optionally substituted C _3.8 cycloalkenyl; R ³⁹ is H, optionally substituted Cj.12 alkyl optionally substituted Cs-s eycioa!kyl, optionally substituted heterocyele, optionally substituted Ce-io aryl or optionally substituted C _3-g cycloalkenyl; R' ^?0 is H, optionally substituted€1-12 alkyl, optionally substituted C _3-8 cycloalkyl, optionally substituted heterocyele, optionally substituted Cs-io aryl or optionally substituted C3. ₃ cycloaikenyl; R ⁴⁵ is H, optionally substituted C _1-12 alkyl, optionally substituted C ₃ -s cycloalkyl, optionally substituted heterocyele, optionally substituted Ce-io aryl or optionally substituted C _3- s cycloaikenyl; R ⁴² is H, optionally substituted C _M? alkyl, optionally substituted C _3- s cyeloaikyl, optionally substituted heterocyele, optionally substituted C _O -JO aryl or optionally substituted C _3-8 cycloaikenyl; and x is 1 or 2.

[096] In another embodiment, the invention provides a catalyst represented by

Formula (I) wherein: X is S; Y is S; Z is N or CR ³² ; W Is O or NR ³³ ; R ¹ is H, linear or branched Ci - alkyl, or halogen; R ² is H linear or branched C ~ ₆ alkyl, or halogen; R ³ is H, linear or branched C -s alkyl, or halogen; R ⁴ Is H, linear or branched Ci-s alkyl or halogen; R ⁵ is H, linear or branched C; - ₆ alkyl; R ⁶ is H, linear or branched C _1-0 alkyl; R ⁷ is H, linear or branched Ci-s alkyl; R ⁵ is H or C1-0 alkyl; R ⁹ is H, linear or branched C-- ₆ alkyl; R ^{1 0} is H, linear or branched C· -6 alkyl; R ^{1 1} is H, linear or branched C1-6 alkyl; R ^{J 2} is H, linear or branched C1 -6 alkyl: R ¹³ is H, linear or branched Ct-6 alkyl or together with R ¹⁴ forms a naphthyl ring; R ¹⁴ is H, linear or branched Ch-a alkyl or together with R ¹³ forms a naphthyl ring; R ^is is I f phenyl, linear or branched Ci-¾ alkyl, halogen or together with R ⁵⁶ forms a naphthyl ring; R ¹⁶ is H, phenyl, linear or branched Cj -6 alkyl, halogen or together with R ^{1 5} or together with R ^{j 7} forms a naphthyl ring; R ^{1 7} is H, phenyl, linear or branched Ci-s alkyl, halogen or together with R ^{! 6} or together with R ^;s forms a naphthyl ring; R ^{i 8} is H, phenyl, linear or branched Cj-r, alkyl, halogen or together with R ¹⁶ or together with R ^!e forms a naphthyl ring; R ¹⁹ is H, phenyl, C _1-6 alkyl, ~C(R ³⁴ )(R ³⁵ )

C(R ³⁴ )(R ^3S )€(G) NR ^4, R ⁴² , -C(R ^M )(R ³⁵ ) C(O) NR ⁴ⁱ OR ⁴⁰ or together with R ³³ forms a five, six or seven memhered heterocyclic ring; R ²⁰ is H, linear or branched Cue alkyl, - C(0)R ²⁵ , - OR ²⁵ , CN, - NR ²⁷ R ^2S , NO2, -CF ₃ , ~S(0) _X R ²⁹ , -P(0)(0H)2, -OP(0)(OH) _2, SR ³ⁱ , pyridine, piperidine, imidazole, indolizine, Indazole, optionally substituted C _3- s cydoaikyl, phenyl, naphthalene, cyclohexene or together with R ²¹ can form a polycyele; R ²¹ is H, phenyl, -NR ²⁷ R ² *, linear or branched Ci- ₆ alkyl, halogen or together with R ²⁰ or together with R ²² can form a poiycyele; R ²² is H, linear or branched Cue alkyl, halogen, - C(0)R ^2S , - OR ²⁶ , CN, - NR ²⁷ R ^2S , N(¼, -CF¼ - S(0)sR ² , -P(0)(0H) ₂ , -0R(0)(0H) _2, -SR ³¹ , pyridine, piperidine, imidazole, indolizine, indazole, optionally substituted Cfog cydoaikyl, phenyl, naphthalene, cyclohexene or together with R ²⁵ or together with R ²³ can form a polycyde; R ²ⁱ is H, phenyl, linear or branched Ci- ₆ alkyl or together with R ²² can form a polycyde; R ²⁴ is H, linear or branched Ci -g alkyl; R ²⁵ is OIL OR ³⁰ , NR ²⁷ R ² *, linear or branched Cos alkyl; R ²⁶ is H, linear or branched Cw alkyl; R ²⁷ is H, linear or branched Cog alkyl; R ^2¾ is H, linear or branched CL-g alkyl; R ²⁹ is H, linear or branched Ci-g alkyl, -NR ²⁷ R ²⁸ ; R ³⁰ is optionally substituted Cfog alkyl, optionally substituted€3-8 cydoaikyl, optionally substituted heterocycle, optionally substituted phenyl or optionally substituted cycioalkenyl; R ³¹ is H, linear or branched Ci - , alkyl; R ³² is H, linear or branched Cos alkyl; R ³³ Is H, linear or branched Ci- ₆ alkyl, or together with R ⁱ⁹ forms a five, six or seven membered heterocyclic ring; R ³⁴ is H, or linear or branched Ci- ₆ alkyl; R ³⁵ is H, or linear or branched Ci- ₆ alkyl; R ³⁶ is H, linear or branched Ci -6 alkyl; R ^3/ is linear or branched Cos alkyl; R ^3S is H or linear or branched Cos alkyl; R ³⁹ is II, linear or branched Cue alkyl; R ⁴⁰ is H, linear or branched Ci .?, alkyl; R ⁴¹ is H, linear or branched Cos alkyl; R ⁴² is H, linear or branched Cs- ₆ alkyl; and x is 1 or 2,

Q 7) In one embodiment, the invention provides a catalyst represented by Formula (1) wherein; X is S; Y Is S; Z is N or CR ³² ; W is O, NR ³³ or S; R ^; is Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu or H; R ² is Me, Et, ΐ-Pr, n-Pr, n-Bu, t-Bu, s-Bu or H; R ³ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁴ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁵ is H, F, Ci, Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁶ is H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁷ Is H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³ is H, F, Cl, Br, i, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁹ is H, F, Ci, Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu: R ¹⁰ is FI, F, CL Br, I, Me, Et, i-Pr, n-Pr, n-Ru, t-Bu, or s-Bu; K ^{1 :} is H, Me, F, CL Br, I, Et, i-Pr, n-Pr, n-Bu t-Bu, or s-Bu: R ¹² is H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ¹³ is H, Me, F, CI, Br, I, Et, n-Pr, i-Pr, n-Bu, t-Bu or s-Bu; R ¹⁴ is F, Cl, Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu or H; R ^{', s} is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, F, Br, I, Cl, or together with R ⁱ⁶ forms a naphthyl or a phenanthryl ring; R ¹⁹ is H, F, Cl Br, I, or together with R ^{i ¾} forms a naphthyl or a phenanthryl ring; R ⁵⁷ is H, F, CL Br, I, or together with R ^{1 S} forms a naphthyl, or a phenanthryl ring; R ^{! ¾} is FI, CI, F, Br, L 3,5-dichioro-phenyl, phenyl, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu or together with R ¹⁷ forms a naphthyl, or a phenanthryl; R ¹⁹ Is H, phenyl, C _f -g alkyl, -C(R ³⁴ )(R ³⁵ ) COOR ³⁶ , -C(R ³⁴ )(R ^3S ) C(0)H, ~C(R ³⁴ )(R ³⁵ ) C(0)R ³⁷ , -C(R ⁴ )(R ^JS ) CR ^3S (OR ³⁹ )(OR ⁴⁰ ), -C(R ³⁴ )(R ³⁵ ) C(O) NR ⁴ⁱ R ⁴² , - C(R ³⁴ )(R ^3S ) C(O) NR ^{4 l} OR'°; R ²⁰ is H, F, CL Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, - C(0)R ^2S - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , N0 ₂ , -CF ₃ , -S(0) _x R ^2S , -P(0)(0H) ₂ , _t 0R(0)(0H) _2, -SR ³ⁱ , pyridine, piperidine, Imidazole, indohzine. indazoie, optionally substituted C ₃ -s eyeloalkyl, phenyl naphthalene, or eyclohexene; R ^2J is H, phenyl, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s~Bu, - NR ²⁷ R ²⁸ F, Cl, Br, or I; R ²² is H, Me, Et, i-Pr, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NQ _¾ - CFj, -S(0) _x R ²⁹ , -P(0)(OH) ₂ , -OP(0)(OH)?. ~SR ^{3 i} , pyridine, piperidine, imidazole, indolizine, indazoie, cyclohexyl, phenyl, naphthalene, cyclohexene F, Cl, Br, or I; R ²² is H, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , N0 ₂ , -CF ₃ , -S(C3) _>; R ² , -P(0)(0H) ₂ , -0P(0)(0H) _? „ or -SR ³¹ ; R ²³ is H, F, Cl, Br, I, phenyl, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ²⁴ is H; R ²⁴ is II, or Me; R ²³ is OH, OR ³⁰ , NR ²⁷ R ²⁸ , Me, Et or i-Pr; R ^¾ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s.-Bu; R ²⁷ is H, Me,

n-Bu, t-Bu, or s-Bu; R ³² is Me, Et. n-Pr or H; R ³³ is H, Me, Et, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s- Bu, or together with R ¹⁹ forms a morpholine, a thio-niorphoiino, a pyrroiidino, a piperidino, or a piperazino ring; R ³⁴ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³⁵ is H, or Me, Et, i-Pr. n-Pr, n-Bu, t-Bu, or s-Bu: R ³⁶ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³⁷ is Me, Et, i-Pr, n-Pr, n-

Bu, t-Bu, or s-Bu; R ³⁸ is H or Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³⁹ is I I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁴⁰ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁴¹ is H, Me, Fit, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁴² is FI, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; and x is 1 or 2.

[09S| In one embodiment, the invention provides a catalyst represented by Formula (!) wherein: X is S; Y is S; Z is N;. W is O; R ^! is Me or H; R ² is Me or H; R ³ is H; R ⁴ is H; R ⁵ is H, F, Me, t-Bu or i-Pr: R ^® is H or t-Bu: R ⁷ is El, F or Me; R ⁸ is H, F or t-Bu; R ⁹ is H, F, Me, t-Bu or i-Pr; R ¹⁰ Is FI, F, Me, t-Bu or i-Pr; R ^{5 1} is H or t-Bu; R ¹² is H, F or Me; R ¹³ is H, F or t-Bu; R ¹⁴ is F, Me, i-Pr, t-Bu or H; R ^{: S} Is H, Me, F, Br, 1, Cl, or together with R ¹⁶ forms a naphthyl; R ¹⁶ is H, or together with R ¹⁵ forms a naphthyl; R ¹⁷ is H or together with R ¹⁸ forms a naphthyl, or a phenanthryi ring; R ^{i S} is Cl, F, Br, I, 3,5-dichloro-phenyL phenyl, t-Bu or together with R ¹⁷ forms a naphthyl, or a phenanthryi ring; R ¹⁹ is i-Pr; R ²⁰ is FI or phenyl; R ²¹ is FI; R ²² Is H, - C(0)R ²⁵ , -

R ²⁹ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, -NR^R ²⁸ ; R ³⁰ is Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu: and R ¹ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu. [Q99] in one embodiment, the invention provides a catalyst represented by Formula (I) wherein: X is S; Y is S; Z is N; W is O; R ^! is Me; R ² is Me; R ³ is H; R ⁴ is H; R ⁵ is F; R ⁶ is H; R ⁷ is FI or F; R ⁸ is H; R ⁹ is F; R ¹⁰ is F: R ^{! l} is H; R ⁱ² Is H; R ¹³ is H; R ^!4 is F; R ^iS is Cl; R ^{i 6} is H; R ⁱ⁷ is H; R ^{! 8} is Ch R ¹⁹ is i-Fr; R ² " is phenyl; R ²ⁱ is H; R ²² is H; R ²³ is H; and R ²⁴ is H.

[100] In one embodiment the invention provides a catalyst represented by Formula (1) wherein: X is S; Y is S; Z is N; W is O; R ¹ is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ Is Me; R ⁶ is H; R ⁷ is Me; R ⁸ is H; R ⁹ Is Me; R ^!0 is Me; R ⁿ is H; R ⁱ² is Me; R ⁱ³ is H; R ¹⁴ Is Me; R ¹⁵ is Cl; R' ⁶ is H; R ^!7 is H; R ^!8 is Ci; R ¹⁹ is I-Fr; R ²⁰ is phenyl; R ^2! is H; R ²² is H; R ²³ Is H; and R ²⁴ is FI.

[101] In one embodiment, the invention provides a catalyst represented by Formal» (1) wherein: X is S; Y Is S; Z Is N; W is O; R ¹ is H; R ² is H; R ³ is H; R ⁴ is H; II ^s is i-Fr; R ⁶ is H; R ⁷ Is H; R ⁸ is H; R ⁹ is I-Pr; R ^!0 is i-Fr; R ⁿ Is H; R ^;2 is FI; R ¹³ is H; R ^’:4 is i-Fr; R ^:5 is Cl; R ^,s Is H; K ^':7 is H; R ^'1 * is Cl; R ⁱ⁹ is i-Pr; R ²⁰ is phenyl; R ^2f is H; R ²² is H; R ²³ is H; and R ²⁴ is H.

[102] In one embodiment, the invention provides a catalyst represented by Formula (I) wherein:

Is H or F;

H; R ⁵⁸ is Cl; R ¹⁹ is i-Pr; R ²⁰ is H; R ^2t is H; R ²² is H; R ²³ Is H; and R ²⁴ is Fi.

[193] In one embodiment, the invention provides a catalyst represented by Formula (I) wherein: X is S; Y is S; Z is N; W is O; R ¹ is H; R ² is H; R ³ is H; R ⁴ is FI; R ^s is Me; K ⁶ is H; R ⁷ Is Me; R ⁸ is H; R ⁹ is Me; R ^!0 is Me; R» is H; R' ² is Me; R ⁵³ is H; R ¹⁴ Is Me; R ^iS is Cl; R ¹⁶ is H;

R ^{! 7} is H; R ^!S is Cl; R ¹⁹ is i-Pr; Rr' ^u is H; R ^2! is H; R ²² is H; R ²³ is H; and R ²⁴ is H.

In one embodiment, the invention provides a catalyst represented by wherein: X is S; Y is S; Z is N; W Is O; ⁵ is H; R ² Is K; R ³ Is H; R ⁴ is H; R ⁵ is i-Pr; R ⁶ is H; R ⁷ is FI; R ⁸ is id; R ⁹ is i-Pr; R ¹⁰ is i-Fr; R ^{i ¾} is H; R ⁵² is H; R ¹³ is H; R ⁱ⁴ Is i-Pr; R ⁵⁵ Is Cl; R ⁱ⁶ is H; R ⁱ⁷ is H; R ^{f 8} is Cl; R ¹⁹ is i-Pr; R ²⁰ is H; R ²¹ is H; R ²² is H; R ²³ is H; and R ²⁴ is PL

In one embodiment, the Invention provides a compound wherein the moiety

3q

substituted G _UM alkyl, halogen, - C(0)R ^:!5 , - OR ²⁶ , CN, - NR ^2? R ²⁸ , N0 ₂ , -Cl¾ -S(0) _x R ²⁹ , - P(())(0H) ₂ , -OPiOXOPf^ -SR ³¹ , optionally substituted heteroeycle, optionally substituted C _3~ s cycloalkyl, optionally substituted Cs- ₂₄ aryl or optionally substituted CM cycloaikcnyl, and "f ^! is 0. 1, 2, 3, or 4 [106] In one embodiment, the invention provides a compound wherein the moiety

, , , , .

[107] In one embodiment, the invention provides a compound wherein the moiety

In one embodiment the invention a compound of Formnia (I) is selected from

41

[109] in one embodiment, the invention provides a Z-se!ective ruthenium olefin metathesis catalyst represented by the structure of Form ala (V),

wherein,

W is Q, halogen, NR ³³ or S;

X ⁵ is hydrogen, halide, nitrate, optionally substituted C ₁ -C2 ₀ alkyl, optionally substituted C -C 4 aryl, optionally substituted C.-Chc alkoxy, optionally substituted C ₁ -C ₂₀ alkylcarboxylate, optionally substituted C5-C ₂₄ aryloxy, optionally substituted C ₂ -C ₂₀ alkoxycarbonyl, optionally substituted C6-C ₂ aryioxyearbonyl, optionally substituted C6-C24 arylcarboxylate, optionally substituted C2-C24 acyl, optionally substituted C ₂ -C ₂₄ acyloxy, optionally substituted C ₄ -C20 alkylsuifonato optionally substituted C ₅ -C ₂₄ arylsulfonato, optionally substituted C1-C20 alkyisulfanyl, optionally substituted C ₅ -C ₂₄ arylsulfanyl, optionally substituted C- _; - C ₂₀

alkylsulfinyl, or optionally substituted C5-C24 arylsulflnyl;

R ^! is H, optionally substituted Ci-2 ₄ alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , N(¾, - CF3, S(Q)xR ²⁹ , -P(0)(0H)2, -OP(0)(OH) ₂ , -SR ³¹ , optionally substituted heterocycle, optionally substituted C -s cycloalkyL optionally substituted€ _5-24 aryl, optionally substituted C _3-8 cycloaikenyi, or together with R ² can form a spiro compound or together with / or together w'ith R ⁴ can form a polycyclic ring;

R ² is H, optionally substituted Ci-24 alkyl, halogen, - C{G)R ²⁵ , - OR ²⁶ , CN, - NR ^2? R ²⁸ , N0 ₂ , - CF3, -S(0) _x R ²⁹ , -P(0)(0H) _3> ·OR(0)(OH)2, -SR ^j! , optionally substituted heterocycle, optionally substituted C _3-8 cycloaikyl, optionally substituted C _5-24 aryl, optionally substituted C ₃ -s cycloalkenyl or together with R ¹ can form a spiro compound or together with R ³ or together with R ⁴ can form a polycyclic ring;

R ³ is H, optionally substituted C 1-2-1 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO ₂ , - CF3, -~S(0) _x R ²⁹ , -P(0)(0H)2, -0P(0)(0H) ₂ , -SR ³¹ , optionally substituted heterocycle, optionally substituted C _3-8 cycloaikyl, optionally substituted C5-2 ₄ aryl or optionally substituted C ₃ -s cycloaikenyi or together with R ² or together with R ¹ can form a polycyclic ring or together with R ⁴ can form a spiro compound:

R ⁴ is H, optionally substituted C _1-24 alkyl, halogen, - C(Q)R ²⁵ , - OR ²⁶ , CN, - R ²⁷ R ²⁸ , N(¾, - CF , -S(0) _x R ²⁹ , ~P(0)(0H)2, -OP(0)(OH) _2, -SR ¹ , optionally substituted heterocycie, optionally substituted C _3- * cycloaikyl, optionall substituted C5-24 aryl, optionally substituted C3-S cycloaikenyi, or together with R ³ can form a spiro compound or together with R ² or together with R ¹ can form a polycyclic ring;

R ⁵ is H, optionally substituted Ci-2 ₄ alkyl, halogen, - C(0)R ^2S , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, -S(0) _x R ²⁹ , -P(0)(0H) ₂ , -OP(0)(OH) _2, -SR ³ⁱ , optionally substituted heterocycie, optionally substituted C ₃ -s cycloaikyl, optionally substituted C5- ₂₄ aryl, optionally substituted C ₃ -s cycloaikenyi, or together with R ⁶ can form an optionally substituted polycyclic ring;

R ⁶ is H, optionally substituted Ci-2 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ^2S , N0 ₂ , - CF3, -S(0) _x R ²⁹ , -P(0)(0PI) ₂ , -0F(0)(0H) _2, -SR ³¹ , optionally substituted heterocycie, optionally substituted C ₃ .* cycloaikyl, optionally substituted C5-24 aryl, optionally substituted C _3-8 cycloalkenyl, or together with R ⁵ or together with R ⁷ can form an optionally substituted polycyclic ring;

R ⁷ is H, optionally substituted Cj-24 alkyl, halogen, - C(0)R ²ⁱ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, -S(0) _x R ²⁹ , -P(Q)(OH) _? ., ~QP(Q)(GH) ₂ -SR ^{J !} , optionally substituted heterocycle, optionally substituted C ₃ -g cycioalkyl, optionally substituted€ _5-24 aryl optionally substituted C _3.g cycloalkenyl, or together with R or together with R ^s can form an optionally substituted polycyclic ring;

R ⁸ is H, optionally substituted Cj. ₂ 4 alkyl, halogen, - C(0)R ² \ - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO?, - CF3, ~S(0)xR ²⁹ , -P(0)(0H)2, -OPiOXOH^, -SR ^i! , optionally substituted heterocycle, optionally substituted C _3- s cycioalkyl, optionally substituted C _5-24 aryl, optionally substituted C _3-8 cycloalkeny], or together with R ⁷ or together with R ⁹ can form an optionally substituted polycyclic ring;

R ⁹ is H, optionally substituted C1-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO ₂ , - CF3, -S(0) _x R ²⁹ , -P(0)(0H) ₂ „ ~OP(Q)(QH) ₂ -SR ³¹ , optionally substituted heterocycle, optionally substituted C _3- s cycioalkyl, optionally substituted C5-24 aryl, optionally substituted C3-8 cycloaikenyi, or together with R ^s cars form an optionally substituted polycyclic ring;

R ^;9 is H, optionally substituted Cs- ₂₄ alkyl, -C(R ³⁴ )(R ³⁵ )COGR ³⁶ , -C(R’ ⁴ )(R ^:,5 )C(0)H, - C(R ³⁴ )(R ³⁵ )C(0)R ³⁷ , -C(R ³⁴ )(R ³⁵ )CR ³⁸ (OR ³⁹ )(OR ⁴⁰ ), -C(R ³⁴ )(R ^3S )C(0)NR ⁴ 'R ⁴² , - C(R ³⁴ )(R ³⁵ )C(0)NR ⁴ⁱ OR ⁴ °, - C(0)R ²³ , optionally substituted heterocycle, optionally substituted C3-8 cycioalkyl, optionally substituted Cs- ₂₄ aryl, optionally substituted C3-8 cycloaikenyi, or together with R ³³ can form an optionally substituted heterocyclic ring or is nil when W is halogen;

R ²⁰ is H, optionally substituted Ci- ₂₄ alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO ₂ , - CP ₃ , -S(G) _X R ²⁹ , -P(0)(OH) ₂ , ~QP(0)(0H) _2, -SR ³¹ , optionally substituted heterocycle, optionally substituted C -s cycioalkyl, optionally substituted C _>?4 aryl, optionally substituted C ₃ s cycloaikenyi or together with R ^2! can form a polycyclic ring;

R ²¹ is H, optionally substituted Ci- ₂₄ alkyl, halogen, - C(())R ^2S , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NΌ ₂ , - CF ₃ , -S(0) _X R ²⁹ , -P(0)(OH) ₂ , -C)P(0)(0H) _{2, "} SR ^j1 , optionally substituted heteroeycle, optionally substituted C3-8 cycioalkyl, optionally substituted C _5-24 aryi, optionally substituted C _3- s cycloaikenyi or together with R ²⁰ or together with R ²² can form a polycyclic ring;

R ²² is H, optionally substituted C _1.24 alkyl, halogen, - C(0)R ^¾ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO _2» - CF ₃ , ---S(0) R ²⁹ , -P(0)(0H)2, -OP(0)(OH) _2, -SR ³ⁱ , optionally substituted heteroeycle, optionally substituted C3-8 cycloaikyl, optionally substituted€5-34 aryl, optionally substituted C3-8 eycloalkenyl or together with R ²¹ or together with R ²³ can form a polycyclic ring;

R ²³ is H, optionally substituted Ci-w alkyl, halogen, - C(0)R ^2S , - OR ²⁶ , CN, - NR ²⁷ R ^2s , O2, - CF3, -S(0) _X R ²⁹ , ~P(0)(0H} ₂ , -QP(0)(GH) _2, -SR ^{J i} , optionally substituted heteroeycle optionally substituted C _3-8 cycloalkyl, optionally substituted C _5-24 aryl, optionally substituted C _3-8 cycloalkenyl or together with R ²² can form a polycyclic ring;

R ²⁴ is H, optionally substituted C1-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , N(¼, - CFi, -S(0) _x R ²⁹ , -F(0)(0H)2 _{} “} OP(0)(OH) _{2; ~} SR ³ⁱ , optionally substituted heteroeycle, optionally substituted C3-8 cycloalkyl, optionally substituted C5-24 aryl or optionally substituted C _3-8 eycloalkenyl;

R ²⁵ is OH, OR ³⁰ , NR ²⁷ R ²⁸ , optionally substituted C1-24 alkyl, optionally substituted C3-8 cycloaikyl, optionally substituted heteroeycle, optionally substituted C5-24 aryl or optionally substituted C3-8 eycloalkenyl,

R ^2tJ is H, optionally substituted C1-24 alkyl, optionally substituted ( ,- _« cycloaikyl, optionally substituted heteroeycle, optionally substituted Cs-24 aryl or optionally substituted C3.8 eycloalkenyl;

R ²⁷ is H, optionally substituted Ci -24 alkyl, optionally substituted C3-8 cycloaikyl, optionally substituted heteroeycle, optionally substituted C5-24 aryl or optionally substituted C3-8 eycloalkenyl;

R ²⁸ is H, optionally substituted Cj -7.4 alkyl, optionally substituted C3-8 cycloaikyl, optionally substituted heteroeycle, optionally substituted Cs-2 aryl or optionally substituted C3-8 eycloalkenyl;

R ²⁹ is H, optionally substituted C1-24 alkyl, OR ²⁶ , - NR ²⁷ R ²⁸ , optionally substituted heteroeycle, optionally substituted C3-8 cycloaikyl, optionally substituted Cs-24 aryl or optionally substituted C3-8 eycloalkenyl;

R ³⁰ is optionally substituted C1 -24 alkyl optionally substituted Cs-s cycloaikyl, optionally substituted heteroeycle, optionally substituted Cs-24 aryl or optionally substituted C3-8 eycloalkenyl;

R ³¹ is H, optionally substituted C1-24 alkyl, optionally substituted C3-8 cycloaikyl, optionally substituted heteroeycle, optionally substituted C5-24 aryl or optionally substituted C _3-8

eycloalkenyl; R ³² is H, optionally substituted C1-24 alkyl, optionally substituted C3-8 eycloalkyl, optionally substituted heterocycle, optionally substituted C ₂₄ aryl or optionally substituted C _3-g cycloalkenyl;

R ³³ is H, optionally substituted C - ₂₄ alkyl, optionally substituted C _3.g eycloalkyl, optionally substituted heterocycle, optionally substituted C _5-24 aryl, optionally substituted C _3-8 cydoalkenyi, or together with R ¹⁹ can form an optionally substituted heterocyclic ring;

R ³⁴ is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted Cs-s eycloalkyl, optionally substituted heterocycle, optionally substituted C5-24 aryl or optionally substituted Cs-s cydoalkenyi;

R ³⁵ is H, optionally substituted CT . ₂₄ alkyl, optionally substituted C3-3 eycloalkyl. optionally substituted heterocycle, optionally substituted Cs-24 aryl or optionally substituted C _3-8 cydoalkenyi:

R ^j6 is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted€ _3-? , eycloalkyl, optionally substituted heterocycle. optionally substituted Cs-24 aryl or optionally substituted C _3-8 cyeloaikenyl;

R ³⁷ is optionally substituted C;- ₄ alkyl, optionally substituted C3-8 eycloalkyl, optionally substituted heterocycle, optionally substituted C5-24 aryl or optionally substituted Cs-s cyeloaikenyl;

R ³⁸ is H, optionally substituted Cs- ₂₄ alky!, optionally substituted C _3-8 eycloalkyl, optionally substituted heterocycle, optionally substituted C5-2 ₄ aryl or optionally substituted C3-8 cyeloaikenyl;

R ³⁹ is H, optionally substituted Ci -24 alkyl, optionally substituted Cs-g eycloalkyl, optionally substituted heterocycie, optionally substituted Cs-24 aryl or optionally substituted€3-8 cyeloaikenyl ;

R ^_1 ° is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted C3-8 eycloalkyl, optionally substituted heterocycie, optionally substituted Cs-24 aryl or optionally substituted Cs-s cyeloaikenyl;

R ⁴ⁱ is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted€ _3-8 eycloalkyl, optionally substituted heterocycie, optionally substituted Cs-2 ₄ ary! or optionally substituted C _3-8 cydoalkenyi;

R ⁴² is 11, optionall substituted Ci -24 alkyl, optionally substituted C _3-8 eycloalkyl, optionally substituted heterocycie, optionally substituted C5-24 aryl or optionally substituted€ _3-8 cydoalkenyi; x is 1 or 2; and wherein the ad a manly: can be optionally substituted by one or more C; -a alkyl groups.

[110] In one embodiment, the invention provides a stereoretentive ruthenium olefin metathesis catalyst represented by the structure of Formula (V), wherein: W is O; X‘ is benzoate, pivalate, Cj-Cs acyl, Cz-Cs alkoxycarbonyl, Cs-Ce alkyl, phenoxy, C _f -C ₆ alkoxy, Ci-C- ₆ alkylsulfanyl, aryl, or Ci-C- ₆ alkylsulfonyl; R' is I-{, optionally substituted CM ₂ alkyl, halogen; R ² is H, optionally substituted Cm2 alkyl, halogen; R ³ is H, optionally substituted C1. 12 alkyl, halogen;

R ⁴ is H, optionally substituted CM2 alkyl, halogen: R ⁵ is H, optionally substituted Cm _? alkyl, halogen; R ^f ' is H, optionally substituted Cm _? alkyl, halogen; R ⁷ is H, optionally substituted Cm _? alkyl, halogen; R ⁸ is H, optionally substituted Cm? alkyl, halogen; R ⁹ is H, optionally substituted Cm? alkyl, halogen; R ^{, 9} is H, optionally substituted Cm2 alkyl, -C(R ³⁴ )(R ³⁵ )-COOR ³⁶ , - C(R ^M )(R ³⁵ )-C(0)H, -C(R ³⁴ )(R ³³ )-C(0)R ³⁷ , R:(R ^j4 )(R ⁵ )-CR ³⁸ (OR ³⁹ )(OR ^4Q ), -C(R ³⁴ )(R ^3S )-C(0)- NR ^4I R ⁴² , C(R ³⁴ )(R ³⁵ )“C(0)“NR ^4’ OR ⁴⁰ , - C(0)R ²⁵ , optionally substituted heteroeycle, optionally substituted C _3- s cycloaikyl, optionally substituted Ce-io aryl, optionally substituted C3-8 eycloalkenyL or together with R ³³ can form an optionall substituted heterocyclic ring; R ² ds H, optionally substituted Cm2 alkyl, halogen, - C(0)R ^2s , - OR ^2¾ , CN, - NR ²⁷ R ^2¾ , NO2, -CF3, - S(G) _X R ²⁹ , -P(0)(0H)¾ -0P(Q)(QH) _2, -SR ^{3 f} , optionally substituted heteroeycle, optionally substituted C _3- s cycloaikyl, optionally substituted Ck io aryl, optionally substituted C?-s cyeSoaikenyl or together with R ²¹ can form a polycyclic ring; R ^2; is H, optionally substituted Cn 12 alkyl, halogen, - NR ²⁷ R ²⁸ , optionally substituted heteroeycle, optionally substituted Cs s cycloaikyl, optionally substituted C _f t-io aryl, optionally substituted Co s cycloalkenyl or together with R ²⁰ or together with R ²² can form a polycyclic ring; R ²² is H, optionally substituted Cm2 alkyl, halogen, - C(G)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ² l N(¾, -CF ₃ , -S(G) _X R ²⁹ , -P(0)(0H} ₂ , - OP(())(OH) _?, ~SR ^{3 ;} , optionally substituted heteroeycle, optionally substituted C _3-8 cycloaikyl optionally substituted Ce-io aryl, optionally substituted C _3.g cydoalkenyl or together with R ²ⁱ or together with R ²³ can form a polycyclic ring; R ²³ is H, optionally substituted Cm _? alkyl, halogen, optionally substituted heteroeycle, optionally substituted C3-8 cycloaikyl, optionally substituted Ce-io aryl or optionally substituted C _3-8 cydoalkenyl or together with R ²² can form a polycyclic ring; R ²⁴ is H; R ^2¾ is OH, OR ³⁰ , NR ²⁷ R ^2S , optionally substituted Cm? alkyl, optionally substituted Cs-g cycloaikyl, optionally substituted heteroeycle. optionally substituted C&.10 ary] or optionally substituted C _3-8 cydoalkenyl; ^2i> is H, optionally substituted Cm ₂ alkyl, optionally substituted C3-8 cycloaikyl, optionally substituted heteroeycle, optionally substituted Ce-io aryl or optionally substituted€ _? -s cydoalkenyl; R ²⁷ is H, optionally substituted Cm _? alkyl, optionally substituted Css eycioalkyl, optionally substituted heterocycle, optionally substituted Ccmo aryl or optionally substituted C _3-8 cycloalkehyl; R ²⁸ is H, optionally substituted Cm ₂ alkyl, optionally substituted C _3-S eycioalkyl, optionally substituted heteroeycie, optionally substituted Csuo aryl or optionally substituted C _3.8 cyeloalkenyl; R ²⁹ is H, optionally substituted Cm ₂ alkyl, OR ²⁶ , - NR ^2V R ^2S , optionally substituted heteroeycie, optionally substituted C _3-8 eycioalkyl, optionally substituted Cwo aryl or optionally substituted Cs-s cycloalkenyl; R ³⁰ is optionally substituted Ci - n alkyl, optionally substituted C3-3 eycioalkyl, optionally substituted heteroeycie, optionally substituted Ceuo aryl or optionally substituted C _3-8 cycloalkenyl: R ^{3 1} is H, optionally substituted CM2 alkyl, optionally substituted C _3-8 eycioalkyl, optionally substituted heteroeycie, optionally substituted Qwo aryl or optionally substituted Cs-8 cyeloalkenyl; R- ² is H, optionally substituted Cm2 alkyl, optionally substituted C3-8 eycioalkyl, optionally substituted heteroeycie, optionally substituted Qmc aryl or optionally substituted€ _3-8 cyeloalkenyl; R ³³ is FI, optionally substituted Cm alkyl, optionally substituted C _3.8 eycioalkyl, optionally substituted heterocycle, optionally substituted Ce-io aryl or optionally substituted C _3-8 cyeloalkenyl, or together with R ^l9 can form an optionally substituted heterocyclic ring; R ³⁴ is H, optionally substituted Cm ₂ alkyl, optionally substituted Cm* eycioalkyl, optionally substituted heteroeycie, optionally substituted C ₆ -io aryl or optionally substituted C _3-8 cyeloalkenyl; R ³⁵ is H, optionally substituted C _1-12 alkyl, optionall substituted C3-8 eycioalkyl, optionally substituted heteroeycie, optionally substituted Ce-so aryl or optionally substituted C _3-8 cyeloalkenyl; R ³⁶ is H, optionally substituted€ _1-12 alkyl, optionally substituted C3- ₈ eycioalkyl optionally substituted heteroeycie, optionally substituted Cg-io aryl or optionally substituted C¾-s cyeloalkenyl; R ³⁷ is optionally substituted C ₁ - ₂ alkyl, optionally substituted C _3-8 eycioalkyl, optionally substituted heteroeycie, optionally substituted Cs-io aryl or optionally substituted C _?. s cyeloalkenyl; R ^3S is H, optionally substituted CM _?, alkyl, optionally substituted C _3-8 eycioalkyl, optionally substituted heteroeycie, optionally substituted C _? mo aryl or optionally substituted Cs-s cyeloalkenyl; R ³⁹ is H, optionally substituted Cm ₂ alkyl, optionally substituted€ _3-8 eycioalkyl, optionally substituted heteroeycie, optionally substituted Ce-io aryl or optionally substituted C _{3 -8} cyeloalkenyl; R ⁴⁰ is H, optionally substituted Cm ₂ alkyl, optionally substituted C _3-8 cycloalkyl, optionally substituted heterocycle, optionally substituted Cmo aryl or optionally substituted C _3-8 cyeloalkenyl; R ⁴ⁱ is H, optionally substituted Cm ₂ alkyl, optionally substituted C _3-8 cycloalkyl, optionally substituted heterocycle, optionally substituted CYmo aryl or optionally substituted C _3-8 cyeloalkenyl; R ⁴² is H, optionally substituted Cm ₂ alkyl, optionally substituted C _3-8 eycioalkyl, optionally substituted heteroeycie, optionally substituted C _{SM O} aryl or optionally substituted C _3-8 cycloalkenyl; x is i or 2; and wherein the adamanty! can be optionally substituted by one or more Cos alkyl groups.

[Ill] In another embodiment, the invention provides a catalyst represented by

Formula (V) wherein: W is ⁽⁾ ; X ^; is CF3CO2, CH3CO2, CH3CH2CO2 CFH2CO2, (CH ₃ ) ₃ C02, (CS-ishCHCOz , (CF ₃ )2(CH ₃ )C0 ₂ , (CI ^; :)(Cf hyCO:·, benzoate, naphthylatc, tosyiate, mesylate, or trifluorometbane-sulfonate; R ¹ is H, linear or branched Ci-e alkyl, or halogen; R ² is H linear or branched C1 -0 alkyl, or halogen; R ³ is H, linear or branched Ci- alkyl, or halogen; R ⁴ is H, linear or branched Ci-e alkyl or halogen; R ^s is H, linear or branched Ci-g alkyl: R ⁶ is H, linear or branched Ci-s alkyl; R ⁷ is H, linear or branched C _1-6 alkyl; R ⁸ is H or Ci~ ₆ alkyl; R ⁹ is H, linear or branched Ci-e alkyl; R ^l9 is H, phenyl, Ci-e alkyl, -C(R ³⁴ )(R ^3S ) COO.R ³⁶ , ~C(R ³⁴ )(R ³⁵ ) C(0)H, - C(R ³⁴ )(R ³⁵ ) C(G)R ³⁷ , -C(R ³⁴ )(R ³⁵ ) CR ³⁸ (OR ³⁹ )(OR ⁴⁰ ), ~C(R ³⁴ )(R ³⁵ ) C(O) NR ⁴¹ R ⁴² , -C(R ³⁴ )(R ³⁵ ) C(O) NR ⁴¹ OR ⁴⁰ or together with R ³³ forms a five, six or seven mcmbered heterocyclic ring; R ²⁰ is H, linear or branched C|. _{; 6} alkyl, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO ₂ , -CF ₃ , -S(0)*R ²⁹ - P(0)(0H)2, -OP(0)(OH) _2, -SR ³¹ , pyridine, piperidine, imidazole, indolizine, indazo!e, optionally substituted C _3.g eyeloalkyl, phenyl, naphthalene, cyciohexene or together with R ^{2 !} can form a polycyele; R ²¹ is H, phenyl, -NR ²⁷ R ²⁸ , linear or branched Cj-s alkyl, halogen or together with R ²⁰ or together with R ²² can form a polycycle; R ²² is H, linear or branched Ci- ₆ alkyl, halogen, - C(G)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO ₂ , -CF ₃ , -SfOj.R ²⁹ , -P(0)(0H) ₂ , -OP(O)(OH) _2: -SR ³ⁱ , pyridine, piperidine, imidazole, indolizine, indazoie, optionally substituted C ₃ -s cycloalkyl, phenyl, naphthalene, cyciohexene or together with R ²¹ or together with R ²³ can form a polycycle; R ²³ is H, phenyl, linear or branched Cj- ₆ alkyl or together with R ²² can form a polycycie; R ²⁴ is H, linear or branched C _5-& alkyl; R ²⁵ is OH, OR ³⁰ , NR ²⁷ R ^2S , linear or branched C-.- ₆ alkyl; R ²⁶ is H, linear or branched C _t -e alkyl; R ²⁷ is H, linear or branched Ci-s alkyl; R ²⁸ is H, linear or branched Ci- _d alkyl; R ²⁹ is H, linear or branched C -s alkyl, -NR ²⁷ R ^2S ; R ³⁰ is optionally substituted Cue alkyl, optionally substituted C ₃ -* cycloalkyl, optionally substituted heterocycle, optionally substituted phenyl or optionally substituted Cj-s cycloalkenyl; R ³¹ is H, linear or branched C5-6 alkyl; R ³² is H, linear or branched Cj-e alkyl; R ³³ is H, linear or branched Ci. ₆ alkyl, or together with R ¹⁹ forms a five, si or seven menibered heterocyclic ring; R ³⁴ is H, or linear or branched Ci- ₆ alkyl; R ³⁵ is H, or linear or branched Ci- _¾ alkyl; is H, linear or branched Ci- ₆ alkyl; R ³ · ⁷ is linear or branched Ci- ₆ alkyl; R ³⁸ is H or linear or branched Cos alkyl; R ³⁹ is H, linear or branched Cj- ₆ alkyl; R ⁴⁹ is H, linear or branched Ci _-6 alkyl; R ^4! is H, linear or branched Ci- ₆ alkyl; R ⁴² is H, linear or branched Ci- ₆ alkyl; x is 1 or 2; and wherein the adamanty! can be optionally substituted by one or more Ci _-6 alkyl groups. 1112] in one embodiment, the invention provides a catalyst represented by Formula

(V) wherein: W is O; X ¹ is CF3CO2, CH3CO2, CH3CH2CO2.CFHaCOi, (CHsfeCQs.

(CH ₃ )2CHCi ⁾ ₂ , (CF ₃ )2(CH ₃ )C0 ₂ , ί( ΐ· ^' 0(P = 0?CO:, benzoate, naphthylate, tosylate, mesylate, or trifluoromethane-sulfbnate; R ^f is Me, Et i-Pr, n-Pr, n-Bu, t-Bu, s-Bu or H; R ² is Me, El, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu or H; R ³ is H, Me, Et. i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁴ is H, Me, Et, i~

Pr, n-Pr, n-Bu, t-Bu, or s-Bu: R ⁵ is H, F, Cl, Br, f, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁶ is

H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr, n-Bu. t-Bu, or s-Bu; R ⁷ is H, F, CL Br, I, Me, Et, ί-Pr, n-Pr, n- Bu, 1-Bu, or s-Bu; R ⁸ is H, F, Cl, Br, I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁹ is H, F, Cl, Br,

I, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R’ ⁹ is H, phenyl, Ci -s alkyl, -C(R ³⁴ )(R ³⁵ ) COGR ³⁶ , -

pyridine, piperidine, imidazole, mdolizine, indazole, optionally substituted C _3-8 cydoalkyl, phenyl, naphthalene, or cyelohexene: R ²¹ is H, phenyl, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, - NR ²⁷ R ²⁸ F, Cl, Br, or I: R ²² is H, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, -CF ₃ , -S(0) _x R ²⁹ , - P(0)(OH) ₂ , -0P(0)(0H) ₂ , or -SR ^3f ; R ²³ is H, F, Cl, Br, I, phenyl, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ²⁴ is H; R ²⁴ is H, or Me; R ²⁵ is OH, OR ³⁰ , NR ²⁷ R ²⁸ , Me, Et, or i-Pr; R ²⁶ is H, Me, Et, i- Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ²⁷ is H, Me, Et, or i-Pr; R ²⁸ is H, Me, Et, i-Pr, n-Pr, u-Bu, t-Bu, or s-Bu; R ^2S is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, or ~NR ²⁷ R ²⁸ ; R ³⁰ is Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ^{3 i} is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³² is Me, Et, n-Pr or H; R ³³ is H, Me, Et, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, or together with R ^l9 forms a morpholino, a thio- morpholino, a pyrrolidino, a piperidine, or a piperazine ring; R ³⁴ is II, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³³ is H, or Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³⁶ is H, Me, Et, i-Pr, n-Pr, n- Bu, t-Bu, or s-Bu; R ³⁷ is Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³⁸ is H or Me, Et, i-Pr, n-Pr, n- Ru, t-Bu, or s-Bu; R ³⁹ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ⁴⁰ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ^4' is H, Me, Et, i-Pr, n-Pr, n-Bu, t~Bu, or s-Bu; R ⁴² is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; x is I or 2; and wherein the adamantyl can be optionally substituted by one or more Me groups.

[113] In one embodiment, the invention provides a catalyst represented by Formula

(V) wherein: W is O; X ¹ is nitrate; R. ^f is H; R ² is H; R ³ is H; R ⁴ is H; R ³ is H, F, Me, Et, or i-Pr;

R ⁶ is H, F, Me, Et, or i-Pr; R ⁷ is H, F, Me, Et, or ί-Pr; R ⁸ is H, F, Me, Et, or i-Pr; R ⁹ is H, F, Me,

Et, or i-Pr; R ¹⁹ is H, phenyl, Cj-s alkyl, -C(R ³⁴ )(R ^3S ) COOR ³⁶ , -C(R ³⁴ )(R ³⁵ ) C(C ⁾ )H, -C(R ³⁴ )(R ^3S ) ^ C(Q)R ³⁷ , -C(R ³⁴ )(R ^3S ) CR ³⁸ (OR ³⁹ )(OR ⁴⁰ ), -C(R ³⁴ )(R ^3S ) C(O) NR ⁴¹ R ⁴² , -C(R ³⁴ )(R ³⁵ } C(O)

Bu, or s-Bu; R ²⁷ Is H, Me, Et, or I-Pr; R ²⁸ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ²⁹ Is H, Ms, Et, i-Pr, n-Pr, n-Bu, t-Bu, s-Bu, or -NR ²⁷ R ²⁸ ; R ³⁰ is Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³ⁱ is H, Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³² is Me, Et, n-Pr or H; R ³⁴ is H, F. Me, Et, or i-Pr; R ³⁵ Is H, F, Me, Et, or i-Pr; R ³⁶ is H, F, Me, Et, or I-Pr; R ³⁷ Is Me, Et, i-Pr, n-Pr, n-Bu, t-Bu, or s-Bu; R ³⁸ is K, F, Me, Et, or I-Pr; R ³⁹ Is is H, F, Me, Et, or i-Pr; R ⁴⁰ Is is H, F, Me, Et, or i-Pr; R ⁴¹ is is H, F, Me, Et, or i-Pr; and R ⁴² is Is H, F, Me, Et, or i-Pr.

[114] In one embodiment, the invention provides a catalyst represented by Formula

(V) wherein: W is O; X ^! is nitrate; R ¹ Is H; R ² Is H; R ³ Is H; R ⁴ is H; R ⁵ is Me; R ⁶ is H; R ⁷ is Me; R ^s is H; R ⁹ is Me; R' ⁹ is i-Pr; R ²⁰ is H; R ^2! is H; R ²² Is H; R ²³ Is H; R ²⁴ is H.

1115] In one embodiment, the invention provides a catalyst represented by Formula

(V) wherein: W Is O; X ^s is nitrate; R* is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is i-Pr; R ⁶ Is H; R ⁷ Is H; R ⁸ is H; R ⁹ is i-Pr; R ^!9 is i-Pr; R ²⁰ is H; R ²¹ is H; R ²² Is H; R ²³ is H; R ²⁴ Is H.

|I16j In one embodiment, the Invention provides a compound of Formula (V) is selected from:

|117] It will he appreciated that the amount of catalyst that Is used (i.e., the“catalyst loading ^'5 ) In the reaction is dependent upon a variety of factors such as the identity of the reactants and the reaction conditions that are employed. It is therefore understood that catalyst loading may be optimally and independently chosen for each reaction. In general, however, the catalyst will be present in an amount that ranges from a low of about 0,1 ppm, 1 ppm, or 5 ppm, to a high of about 10 ppm, 15 ppm, 25 ppm, 50 ppm, 100 ppm, 200 ppm, 500 ppm, or 1000 ppm relative to the amount of an olefmie substrate,

[118] The catalyst will generally he present in an amount that ranges from a low of about 0.00001 mol%, 0.0001 mol%, or 0.0005 mol%, to a high of about 0.001 mol%, 0.0015 rnol%, 0.0025 mol%, 0.005 mol%, 0.01 mol%, 0,02 moi%, 0.05 mol%, or 0.1 moi% relative to the olefmie substrate.

[119] When expressed as the molar ratio of olefin to catalyst, the catalyst (the '‘olefin to catalyst ratio”), loading will generally he present in an amount that ranges from a low of about 10,000,000:1. 1,000,000: 1, 500,000: 1 or 200,00: 1, to a high of about 100,000:1 60,000: 1, 50,000: 1, 45,000;] , 40,000: 1, 30,000:1, 20,000:1, 10,000:1 , 5,000: 1, or 1,000: 1.

[120] These and other aspects of the Invention will be apparent to the skilled artisan in light of the following detailed description and examples.

1121 f The invention provides a method that produces a compound (i.e., a product, olefin product; e.g., cross-metathesis product) having at least one carbon-carbon double bond (e.g., a product internal olefin) in a Z/E selectivity ratio of 95/5, or 96/4, or 97/3, or 98/2, or 99/1. In some eases, 100% of the at least one carbon-carbon double bond produced in the cross- metathesis reaction has a Z-conflguration

In one embodiment, the invention provides a method for producing at least one A ¹² -Prostagiandin J product represented by F«

OH and ^ si ^N¾ -''' = ^{A '} ' - _aiK | wherein at least one carbon-carbon double bond has a Z/E-selectivIty of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l;

comprising submitting an alcohol product of Formula i

to oxidation in the presence of tetrapropylamrnonium perruthenate and 4~methylmorpholine N~ oxide monohydrate or to oxidation In the presence of pyridinium chioroehromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

Formula (II)

and cis-ocfen-l-ol in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I) or in the presence of a Z-sclective ruthenium olefin metathesis catalyst represented by Formula (V); wherein R ^v is selected from wherein the stereoretentive ruthenium olefin metathesis catalyst represented by IS

X is O or S;

Y is O or S;

Z is N or CR ³² ;

W is O, halogen, NR ³³ or S;

R ¹ is H, optionally substituted Ci-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CM, - NR ²⁷ R ^2S , NO _¾ - CFs, S(0) _x R ²⁹ „ -R(0)(0H) ₂ , -0P(0}(0H) ₂ , -SR ³¹ , optionally substituted heterocyele, optionally substituted ( _H cycloalkyl, optionally substituted C _. s _~ 24 aryl, optionally substituted Cj.g cyeloalkenyi, or together with R ² can form a spiro compound or together with R ³ or together w'ith R ⁴ can form a polycyclic ring;

R ² is H, optionally substituted CY24 alkyl, halogen, -€(G)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ NO2, - CF3, ~-S(0)xR ²⁹ , -P(0)(0H) ₂ , -0P(0)(0H)y -SR ³¹ , optionally substituted heterocycle, optionally substituted C3 cycloalkyl, optionally substituted C5-24 aryl, optionally substituted C3-8 cycloalkenyl or together with R ¹ can form a spiro compound or together with R ³ or together with R ⁴ can form a polycyclic ring;

R ³ is H, optionally substituted C1.24 alkyl, halogen, - C(())R ²⁵ , - OR ² ”, CM, - NR ²⁷ R ²⁸ , N<¾, - CF , -S(0)xR ²⁹ , -P(0)(0H) ₂ , -0P(0)(0H) ₂ , -SR ^{3 :} , optionally substituted heterocyele, optionally substituted C.vs cycloalkyl, optionally substituted C5-24 aryl or optionally substituted Cs-s cyeloalkenyi or together with R ² or together with R* can form a polycyclic ring or together with R ⁴ can form a spiro compound; R ⁴ is H, optionally substituted Cj-a* alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, -S(0) _Z R ²⁹ , -F(0)(0H) ₂ , -QP(0)(0H) _2, -SR·’ ¹ , optionally substituted heterocycle, optionally substituted C ₃ -8 cycioaikyi, optionally substituted C _5-24 aryl, optionally substituted C ₃₄ eyeloalkenyl, or together with R ³ can form a spiro compound or together with R ² or together with R ^: can form a polycyclic ring;

R ⁵ is H, optionally substituted C1 -24 alkyl halogen, - C(0)R ² \ - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, -S(Q) _t R ²⁹ , F(0)(0H) ₂ , -OP(Q)(OH) _{2 ~} SR ^{3 ;} , optionally substituted heteroeycle, optionally substituted C ₃ cycloalkyl, optionally substituted C _5-24 and, optionally substituted C¾.s eyeloalkenyl, or together with R ⁶ can form an optionally substituted polycyclic ring;

R ⁶ is H, optionally substituted C _1-24 alkyl, halogen, - C(Q)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO2, - CF¾, -S(0) _x R ²⁹ , -P(0)(0H) ₂ , -0P(0)(0H) _{2. ~} SR ³¹ , optionally substituted heterocycle, optionally substituted C ₃ -8 cycioaikyi, optionally substituted C _5-24 aryl, optionally substituted C3 eyeloalkenyl, or together with R ⁵ or together with R ⁷ can form an optionally substituted polycyclic ring;

R ⁷ is H, optionally substituted C _1-24 alkyl, halogen, - C(0)R ²³ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF ₃ , S(0) _x R ²⁹ , ~F(0)(0H) ₂ , -0P(0)(0H) ₂ -SR ^: , optionally substituted heterocycle, optionally substituted C34 cycioaikyi, optionally substituted€5-24 aryl optionally substituted C3 eyeloalkenyl, or together with R ⁶ or together with R ⁸ can form an optionally substituted polycyclic ring;

R ⁸ is H, optionally substituted Ci _-24 alkyl, halogen, - C(Q)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, -S(0) _x R ²⁹ , -F(0)(0H) ₂ , -0P(0)(0H) _{2. ~} SR ³¹ , optionally substituted heteroeycle, optionally substituted C ₃₄ cycioaikyi, optionally substituted C _5.2 aryl, optionally substituted C ₃₄ eyeloalkenyl, or together with R ⁷ or together with R ⁹ can form an optionally substituted polycyclic ring;

R ⁹ Is H, optionally substituted Ci-24 alkyl, halogen, - C(Q)R ⁱ³ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO?, - CF ₃ , -S(0) _x R ²⁹ , -P(0)(0H) ₂ , -OP(0)(OH) _2, -SR ³ h optionally substituted heteroeycle, optionally substituted C _3-8 cycioaikyi, optionally substituted Cs- ₂₄ aryl, optionally substituted C _3-S eyeloalkenyl, or together with R ⁸ can form an optionally substituted polycyclic ring;

R ^K ’ is H, optionally substituted€ _1-24 alkyl halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, ~ NR ²⁷ R ²⁸ , N0 ₂ , - CF ₃ , S(0) _x R ²⁹ , -P(0)(0H) ₂ , ~OP(Q)(OH)?. -SR ³¹ , optionally substituted heteroeycle, optionally substituted C ₃ -8 cycioaikyi, optionally substituted C _5-2 aryl, optionally substituted C _3-8 eyeloalkenyl, or together with R ⁿ can form an optionally substituted polycyclic ring; R ⁿ is H, optionally substituted Ci-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO _? , - CF ₃ , ^~ S(0) _X R ²⁹ , -P(0)(0H) ₂ , -0P(0)(0H}? _. -SR ³¹ , optionally substituted heterocycle, optional iy substituted Cua cycloaikyl, optionally substituted C _5.24 aryl, optionally substituted C _3.g

cycloalkenyl or together with R ⁱ⁰ or together with R ¹² can form an optionally substituted polycyclic ring;

R ¹² is H, optionally substituted Ci-24 alkyl, halogen, - C(Q)R ²ⁱ , - OR ²⁶ , CN, - NR ^2? R ²⁸ , NO2, - CF ₃ , -S(0) _X R ²⁹ , -P(0)(0H) ₂ , -0P(0)(0H)2, -SR ^{3 i} , optionally substituted heterocycle, optionally substituted C3.8 cycloaikyl, optionally substituted C _5-24 aryl, optionally substituted C _3-8 cycloalkenyl, or together with R ^{1 1} or together with R ¹³ can form an optionally substituted polycyclic ring;

II ^s3 is H, optionally substituted Ci-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ^2S , NO?, - CFj, -S(0)XR ²⁹ , -P(0)(0H)2, -0P(0)(QH) ₂ , -SR ³¹ , optionally substituted heterocycie, optionally substituted C _3-g cycloaikyl, optionally substituted C _5.24 aryl, optionally substituted C _3.8 cycloalkenyl, or together with R ¹⁴ or together with R ^;2 can form an optionally substituted polycyclic ring;

R is H, optionally substituted C;-?4 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ² *, NO2, - CF3, -S(0)XR ²⁹ , -P(0)(0H)2, -0P(0)(0H) ₂ -SR ³¹ , optionally substituted heterocycie, optionally- substituted C3-8 cycloaikyl, optionally substituted C _5-24 aryl, optionally substituted C _3-8 cycloalkenyl, or together with R ¹³ can form a polycyclic ring;

R ^{, s} is H, optionally substituted C1-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , N<¾, - CFj, -S(0) _x R ²⁹ , -P(0)(0H) ₂ , -0P(0)(0H)2, -SR ^i! , optionally substituted heterocycie, optionally substituted C3-8 cycloaikyl, optionally substituted C5-24 aryl or optionally substituted C ₃ -* cyeloaikenyi, or together with R ¹⁶ can form an optionaily substituted polycyclic ring;

R ^l5 is H, optionally substituted C1. ₂₄ alkyl, halogen, - C(0)R ² \ - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO _? , - CF3, -8(0) _C K ²⁹ -P(0)(0H) _2S -0P{0}( l t} _? -SR ³ⁱ , optionally substituted heterocycie, optionally substituted C ₃ -s cycloaikyl, optionally substituted C5-24 aryl or optionally substituted Cus cyeloaikenyi, or together with R ^:S or together with R' ⁷ can form an optionally substituted polycyclic ring;

R ^{: 7} is H, optionally substituted Ci-24 alkyl, halogen, - C(0)R ^2¾ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF?, -S(0) _x R ²⁹ , -P(0)(0H) ₂ , -OP(Q)(QH) _2, -SR ³¹ , optionally substituted heterocycie, optionally substituted C3-8 cycloaikyl, optionally substituted Cs-24 aryl or optionally substituted C3-8 cyeloaikenyi, or together with R ¹⁸ or together with R ¹⁶ can form an optionally substituted polycyclic ring; R ¹⁸ is H, optionally substituted Ci-24 alkyl, halogen, - C(Q)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF ₃ , -S(0) _x R ²⁹ , -P(0)(OH) ₂ , -0P(0)(0H) ₂ -SR ³¹ , optionally substituted heterocycle, optionally substituted C s eycloalkyi, optionally substituted C5 ₂₄ aryl or optionally substituted€ ₃ -8 eycloa!keny!, or together with R ¹⁷ can form an optionally substituted polycyclic ring;

R ^ls is H, optionally substituted C1-24 alkyl, -C(R ³⁴ )(R ³⁵ )CQOR ³⁶ , -C(R ³⁴ )(R ³⁵ )C(Q)H, - C(R ³⁴ )(R ³⁵ )C(0)R ³⁷ , -C(R ³⁴ )(R ³⁵ )CR ³⁸ (OR ³⁹ )(OR ⁴⁰ ), -C(R ³⁴ )(R ³⁵ )C(0)NR ⁴¹ R ⁴² , - C(R ³⁴ )(R ³⁵ )C(O)NR ⁴¹ OR' ^:0 , - C(Q)R ²⁵ , optionally substituted heterocycle, optionally substituted C _3-8 eycloalkyi, optionally substituted C5-24 aryl, optionally substituted C3-8 cycloalkeny!, or together with R ³³ can form an optionally substituted heterocyclic ring or is nil when W is halogen;

R ^2u is H, optionally substituted C _1.24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ² *, NO2, - CF3, --S(0)xR ²⁹ , -P(0)(()H)2, -0R(0){0H) ₂ , -SR ³¹ , optionally substituted heterocycle, optionally- substituted Cj-s eycloalkyi, optionally substituted C _5-24 aryl, optionally substituted C ₃ -s cycloaikenyl or together with R ²¹ can form a polycyclic ring;

R ²¹ is H, optionally substituted Ci-2 alkyl, halogen, -€(Q)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, -S(0)xR ²⁹ , -P(())(OK)2, -OP(0)(OH) _2, -SR ³¹ , optionally substituted heterocycle, optionally substituted tb s cycloalkyl, optionally substituted Cs- ₂₄ aryl, optionally substituted C _3-S cycloaikenyl or together with R ²⁰ or together with R ²² can form a polycyclic ring:

R ²² is H, optionally substituted Ci-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, ~S(0)xR ²⁹ , -P(0)(0H)2, -OP(0)(OH) ₂ , -SR ³¹ , optionally substituted heterocycle, optionally substituted C _3-8 eycloalkyi, optionally substituted Cs- ₂₄ aryl, optionally substituted C ₃ -g cycloaikenyl or together with R ²ⁱ or together with R ²ⁱ cars form a polycyclic ring;

R ²³ is H, optionally substituted Ci-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , N0 ₂ , - CF3, -S(0)xR ²⁹ , -P(0)(0H)2, -OP(0)(OH) _2, -SR ³¹ , optionally substituted heterocycle, optionally- substituted C _3.3 eycloalkyi, optionally substituted€ _5-24 aryl, optionally substituted Ca-g cycloaikenyl or together with R ²² can form a polycyclic ring:

R ²⁴ is H, optionally substituted C ₁ .. ₂₄ alkyl, halogen, - C(0)R ²⁵ , - OR ^¾ , CN, - NR ²⁷ R ²⁸ , NO ₂ , - CFj, -S(0) _x R ²⁹ , -P(0)(OH)2,“0R(0)(0I·G) _2, -SR ⁴¹ , optionally substituted heterocycle, optionally substituted C3-8 eycloalkyi, optionally substituted C5-24 aryl or optionally substituted C _3-8 cycloaikenyl;

R ²⁵ is OH, OR ³⁰ , NR ^2? R ²⁸ , optionally substituted€1-2 ₄ alkyl, optionally substituted C _3-8 cycloalkyl, optionally substituted heterocycle, optionally substituted C _5-24 aryl or optionally substituted C3- ₈ cycloaikenyl, R ²⁶ is H, optionally substituted Ci- ₂₄ a!kyi, optionally substituted C _3-S cycloalkyl, optionally substituted heterocycle, optionally substituted C _5-24 aryl or optionally substituted€ _3-8 cycloaikenyi;

R ²⁷ is H, optionally substituted C _1-24 alkyl, optionally substituted C _3.8 cycloalkyl, optionally substituted heterocycle, optionally substituted C _5.24 aryl or optionally substituted Cj-s

cycloaikenyi;

R ^2S is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted C _3-8 cycloalkyl optionally substituted heterocyele, optionally substituted C _5-24 aryl or optionally substituted C _3-8

cycloaikenyi;

R ²⁹ is H, optionally substituted Ci- ₂₄ alkyl, OR ²⁶ , - KR ²⁷ R ²⁸ , optionally substituted heterocyele, optionally substituted C3-8 cycloalkyl, optionally substituted C _5-24 aryl or optionally substituted C _3-8 cycloalkenyl;

R ^u is optionally substituted C _t-24 alkyl, optionally substituted C _3-8 cycloalkyl, optionally substituted heterocyele, optionally substituted C _5-24 aryl or optionally substituted€ _3-8 cycloaikenyi;

R ^3! is H, optionally substituted Ci. ₂₄ alkyl, optionally substituted Ca-a cycloalkyl, optionally substituted heterocyele, optionally substituted€ _5-24 aryl or optionally substituted C3-8 cycloaikenyi;

R ³² is H, optionally substituted Ci-24 alkyl, optionally substituted Cs-s cycloalkyl, optionally substituted heterocyele, optionally substituted C5-24 aryl or optionally substituted C3-8 cycloaikenyi;

R ³³ is H, optionally substituted Ci _-24 alkyl, optionally substituted Cs-s cycloalkyl, optionally substituted heterocyele, optionally substituted Cs- ₂₄ aryl, optionally substituted C _3-8

cycloaikenyi, or together with R ^{! 9} can form an optionally substituted heterocyclic ring;

R ^j4 is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted Cs-s cycloalkyl, optionally substituted heterocyele, optionally substituted Cs-24 aryl or optionally substituted C3-8 cycloaikenyi;

R ³ -’ is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted C _3-8 cycloalkyl, optionally substituted heterocyele, optionally substituted C _5-24 aryl or optionally substituted C _3-8 cycloaikenyi;

R ³⁶ is H, optionally substituted Ci _-24 alkyl, optionally substituted Cs-s cycloalkyl, optionally substituted heterocyele, optionally substituted Cs-24 aryl or optionally substituted C _3-8

cycloaikenyi; R ³⁷ is optionally substituted C _{1 -24} alkyl, optionally substituted C ₃ -s cycloaikyl, optionally substituted heterocycie, optionally substituted C _5-24 an or optionally substituted C ₃ -s cycloalkenyl;

R ^JS is H, optionally substituted C _{1 -24} alkyl, optionally substituted C _3- 8 cycloaikyl, optionally substituted heterocycie, optionally substituted€ _5-24 aryl or optionally substituted C _3-8

cycloalkenyl;

R ³⁹ is H, optionally substituted C _1-2 alkyl, optionally substituted C _3- s cycloaikyl, optionally substituted heterocycie, optionally substituted Cs- ₂₄ aryl or optionally substituted C _3- * cycloalkenyl;

R ^‘ ° is H, optionally substituted C _{1 .24} alkyl, optionally substituted C _3-8 cycloaikyl, optionally substituted heterocycie, optionally substituted Cs- ₂₄ aryl or optionally substituted C _3-8 cycloalkenyl:

R ^4t is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted C _3-8 cycloaikyl, optionally substituted heterocycie, optionally substituted C _5-24 aryl or optionally substituted C ₃ -s

cycloalkenyl;

R ⁴² is H, optionally substituted C _1-24 alkyl, optionally substituted C _3.. s cycloaikyl, optionally substituted heterocycie, optionally substituted Cs- ₂₄ aryl or optionally substituted C _3-8 cycloalkenyl;

x is 1 or 2; and wherein the Z-selective ruthenium olefin metathesis catalyst represented by Formula {¥) is

wherein:

W is O, halogen, NR ³³ or S;

X ^: is hydrogen, halide, nitrate, optionally substituted Ci-Cbc alkyl, optionally substituted C ₅ -C ₂₄ aryl, optionally substituted C1-C20 alkoxy, optionally substituted Ci-Cdo aikylcarboxylate, optionally substituted C ₅ -C ₂₄ aryloxy, optionally substituted C ₂ -C ₂₀ alkoxyearbonyl, optionally substituted C ₆ -C ₂ aryloxycarbonyl, optionally substituted C ₆ -C ₂₄ atylcarboxylate, optionally substituted C ₂ -C ₂₄ acyl, optionally substituted C ₂ -C ₂₄ acyloxy, optionally substituted Ci-C ₂ o alkylsulfonato, optionally substituted C5-C24 aryisulfonato, optionally substituted C Cnc alkylsuifanyl, optionally substituted C5-C ₂₄ arylsulfanyj, optionally substituted C]~C ₂ o aSkyisulfmyl, or optionally substituted C5-C ₆₄ arytsulfmyi;

R ¹ is H, optionally substituted C1- ₂₄ alkyl, halogen, - C(Q)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, -S(0) _x R ²⁹ , ~P(0)(0H)2, -OP(0)(OH)2, -SR ³¹ , optionally substituted heterocycle, optionally substituted C3-8 cycloa!kyl, optionally substituted Cs- ₂₄ aryl, optionally substituted C3.8 cyeioalkenyl, or together with R ² can form a spiro compound or together with R ³ or together with R ⁴ can form a polycyclic ring;

R ² is H, optionally substituted C5-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , N(¾, - CF3, ~S(0) _x R ²⁹ , -P( ⁽⁾ )(OH)?., -OP(0)(OH)?„ -SR ³ⁱ , optionally substituted heterocycie, optionally substituted€ ₃ -8 cycloalkyl, optionally substituted C _5-24 aryl, optionally substituted C _. cs cyeioalkenyl or together with R ^! can form a spiro compound or together with R ³ or together with R ⁴ can form a polycyclic ring;

R ³ is H, optionally substituted CUM alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NOs, - CF ₃ , -S(0) _X R ²⁹ , -P(G)(0H)2, -0P(0)(0H)2, -SR ³¹ , optionally substituted heterocycie, optionally substituted C3.8 cycioalkyl, optionally substituted Cs- ₂₄ aryl or optionally substituted C3-8 cycloalkenyl or together with R ⁷ · or together with R ^! can form a polycyclic ring or together with R ⁴ can form a spiro compound;

R. ⁴ is H, optionally substituted C; .2 ₄ alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NC¾, -

CF3, -S(0)xR ²⁹ , P(0)(OH)2, -0P(0)(0H)2 _, -SR- k optionally substituted heterocycie, optionally substituted C ₃ -8 cycioalkyl, optionally substituted C _5.24 aryl _, optionally substituted C _3-S cyeioalkenyl, or together with R ³ can fonn a spiro compound or together with R ² or together with R ^! can form a polycyclic ring;

R ⁵ is H, optionally substituted C _1-24 alkyl, halogen, - C(0)R ²³ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO _? ., - CF3, -S(0) _x R ²⁹ , -P(0)(0H)2, -OP(O)(OH)2 -SR ³¹ , optionally substituted heterocycie, optionally substituted C¾-s cycioalkyl, optionally substituted€ _5-24 ary!, optionally substituted€3-8 cycloalkenyl, or together with R ⁶ can form an optionally substituted polycyclic ring;

R ⁶ is H, optionally substituted Ci- 4 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO2, - CF3, -S(Q)xR ²⁹ , -P(0)(()H)2, -0P(0)(0H)2 _{, ~} SR ³¹ , optionally substituted heterocycie, optionally substituted (>,-s cycioalkyl, optionally substituted C _5-24 aryl, optionally substituted C _3-8 cycloalkenyl, or together with R ^s or together with R ⁷ can form an optionally substituted polycyclic ring;

R ⁷ is H, optionally substituted C _{1 -2-1} alkyl, halogen, - C(Q)R ^2S , - OR ²⁶ , CN, - NR ²⁷ R ^2¾ , NO ₂ , - CF3, ~S(0)xR ²⁹ -P(0)(()H) ₂ , 0P(0)(0H) ₂ -SR ^3f , optionally substituted heteroeycle, optionally substituted C _3- s cycloalkyl, optionally substituted C _5-24 aryl optionally substituted Cs s cycloalkenyl, or together with R ⁶ or together with R ^s can form an optionally substituted polycyclic ring;

R ⁸ is H, optionally substituted Ci- ₂₄ alkyl, halogen, -€(0)R ²⁵ , - OR ²⁶ , CN, ~ N’R ²⁷ R ²⁸ , NQ ₂ , - CF3, -S(0) _¾ R ²⁹ , -P(0)(0H) ₂ , -0P(0)(0H) _2, -SR ³¹ , optionally substituted heteroeycle, optionally substituted C3-8 cycloalkyl, optionally substituted C _5-24 aryl, optionally substituted C _3- s cycloalkenyl, or together with R ⁷ or together with R ⁷ can form an optionally substituted polycyclic ring;

R ⁹ is H, optionally substituted€; .21 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - R ²⁷ R ²⁸ , NO·?, - CF ₃ , ~S(Q)XR ²⁹ , P(0)(0H)2, -OP(0)(OH)2 _, -SR ³ⁱ , optionally substituted heteroeycle, optionally substituted C _3- s cycloalkyl, optionally substituted€5-24 aryl, optionally substituted C3-8 cycloalkenyl, or together with R ⁸ can form an optionally substituted polycyclic ring;

R ^t9 is H, optionally substituted C _{1 -24} alkyl, -C(R ³⁴ )(R ³⁵ )COOR ^M , -C(R ³⁴ )(R ³⁵ )C(0)H, -

C(R ³⁴ )(R ³⁵ }C(0)NR ^{4 f} R ⁴⁰ , - C(0)R ^2s , optionally substituted heteroeycle, optionally substituted C3-s cycloalkyl, optionally substituted C5- ₂₄ aryl, optionally substituted C ₃ -* cycloalkenyl, or together with R ³³ can form an optionally substituted heterocyclic ring or is nil when W is halogen;

R ^A ’is H, optionally substituted Cj- ₂₄ alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO ₂ , - CF3, -S(0)xR ²⁹ , -P(0)(0K}2, -0P(0)(0H) _2, -SR ^3, ₃ optionally substituted heteroeycle, optionally substituted C _3-s cycloalkyl, optionally substituted C _5-2-1 aryi, optionally substituted C _3-8 cycloalkenyl or together with R ²¹ can form a polycyclic ring;

R ²¹ is H, optionally substituted Ci- ₂₄ alkyl, halogen, - C(0)R ^2s , - OR ²⁶ , CN, - NR ²⁷ R ^2S , N<¾, - CF ₃ , -S(0) _X R ² , -P(0)(0H)2, -OP(0)(OH)2 _, -SR ^3! , optionally substituted heteroeycle, optionally substituted C3-8 cycloalkyl, optionally substituted C _5-24 aryl, optionally substituted C _3-8 cycloalkenyl or together with R ²⁰ or together with R ²² can form a polycyclic ring;

R ²² is FI, optionally substituted Ci-24 alkyl, halogen, - C(0)R ²⁵ , - OR ²⁶ , CN, - NR ²⁷ R ²⁸ , NO?, - CF;j, -S(0)xR ²⁹ , -P(0)(OH)?„ -OP(0)(OH)2 _, -SR ³¹ , optionally substituted heteroeycle, optionally substituted C>,-s eyc!oalkyi, optionally substituted C$.24 aryl, optionally substituted C3-8 cyeioaikenyi or together with R ^2! or together with R ⁷³ can form a polycyclic ring;

R ²³ is Si, optionally substituted C -24 alkyl, halogen, - C(0)R ²⁵ , - OR ⁷⁶ , CN, - NR ²⁷ R ^2S , NCb, - CF3, -S(0) _x R ²⁹ , -P(0)(0H) _? „ -OP(0)(OH) _2, -SR ³⁵ , optionally substituted heterocycie, optionally substituted€ _3. * cycloalkyl, optionally substituted C _5-24 aryl, optionally substituted C _3-8 cyeioaikenyi or together with R ⁷² can form a polycyclic ring;

R ²⁴ is H, optionally substituted Ci- _?.4 alkyl, halogen, - C(G)R ^2S , - OR ²⁶ , CM, - MR ²⁷ R ^2s , NO ₂ , - CF3, -S(0)xR ²⁹ , ~P(0)(0H)2, -OR(0)(OH) _2, -SR ^3f , optionally substituted heterocycie, optionally substituted C _3-8 cycloalkyl, optionally substituted C _5-24 aryl or optionally substituted C _3-8 cyeioaikenyi;

R ²⁵ is OH, OR ³⁰ , NR ²⁷ R ²⁸ , optionally substituted C _1-24 alkyl, optionally substituted Ci-g eydoaikyl, optionally substituted heterocycie, optionally substituted C _5-24 aryl or optionally substituted C _3.8 cyeioaikenyi,

R ⁷⁶ is H, optionally substituted C _1-2 alkyl, optionally substituted C _3-8 cycloalkyl, optionally substituted heterocycie, optionally substituted C _5.24 aryl or optionally substituted C _3-S

cyeioaikenyi;

R ²⁷ is H, optionally substituted Ci- ₂₄ alkyl optionally substituted€ _{3 3} cycloalkyl, optionally substituted heterocycie, optionally substituted€ _5-2 aryl or optionally substituted C _3-8

R ^2S is H, optionally substituted Ci- ₄ alkyl, optionally substituted C _3-8 eydoaikyl, optionally substituted heterocycie, optionally substituted C _5-24 aryl or optionally substituted Cg-g cyeioaikenyi;

R ²⁹ is H, optionally substituted Co- ₂₄ alkyl, OR ^2b , ~ NR ²⁷ R ² *, optionally substituted heterocycie, optionally substituted€ _3-8 eydoaikyl, optionally substituted C _5.24 aryl or optionally substituted €3-8 cyeioaikenyi:

R ³⁰ is optionally substituted Cj- ₂₄ alkyl, optionally substituted Cj-g eydoaikyl, optionally substituted heterocycie, optionally substituted C _5-24 aryl or optionally substituted C _3-8 cyeioaikenyi;

R ³⁵ is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted C _3-8 eydoaikyl, optionally- substituted heterocycie, optionally substituted€ _5-24 aryl or optionally substituted C _3-8 cyeioaikenyi; R ⁱ² is H, optionally substituted Ct- ₂₄ alkyl, optionally substituted C _. vs eydoaikyl, optionally substituted heterocycle, optionally substituted C _5-24 aiyi or optionally substituted C _3.8 cydoalkenyl;

R ³³ is H, optionally substituted C s . ₃₄ alkyl, optionally substituted C _3-8 eycloalkyl, optionally substituted heterocyde, optionally substituted€5-24 aryl, optionally substituted C3. S cydoalkenyl, or together with R ¹⁹ ean form an optionally substituted heterocyclic ring;

R ³⁴ is H, optionally substituted C;- ₂ alkyl, optionally substituted C _3-8 eycloalkyl, optionally substituted heteroeycle, optionally substituted C _5-24 aryl or optionally substituted Cs-s cycloalkenyl;

R ^3S is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted C _3-8 eycloalkyl, optionally substituted heterocycle, optionally substituted€ _5-24 aryl or optionally substituted€ _3-8 cy oalkenyl;

R ³⁶ is H, optionally substituted C _1-24 alkyl, optionally substituted C _3.8 eycloalkyl, optionally substituted heterocyde, optionally substituted C _5-24 aryl or optionally substituted C _3-8 cydoalkenyl;

R ³⁷ is optionally substituted Ci _-2 4 alkyl, optionally substituted C _3-8 eycloalkyl, optionally substituted heterocyde, optionally substituted C _5-24 aryl or optionally substituted C _3-8 eycloalkeiiyl;

R ³⁸ is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted C _3-8 eycloalkyl, optionally substituted heterocyde, optionally substituted C5-24 aryl or optionally substituted C _3-8 cydoalkenyl;

R ³⁹ is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted C _3.g eycloalkyl, optionally substituted heterocyde, optionally substituted€5-24 aryl or optionally substituted C _3-8 cydoalkenyl;

R ° is H, optionally substituted Ci- ₂₄ alkyl, optionally substituted€ _3-8 eycloalkyl, optionally substituted heterocyde, optionally substituted C _5-24 aryl or optionally substituted C _3-8 cydoalkenyl;

R ⁴¹ is H, optionally substituted€ ₀₂₄ alkyl, optionally substituted C ₃ -. ₃ eycloalkyl, optionally substituted heteroeycle, optionally substituted C5-24 aryl or optionally substituted C _3-8 cydoalkenyl;

R ⁴² is H, optionally substituted Ct- alkyl, optionally substituted€3-8 eycloalkyl, optionally substituted heterocyde, optionally substituted C5-24 aryl or optionally substituted Cs-s cydoalkenyl; and x is I or 2

[123] in one embodiment, the invention provides a method for producing at least one alcohol represented by For and a (III)

wherein at least one carbon-carbon double bond has a Z/E-seieetivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1 or >99/<l; comprising: subjecting a substrate represented by Formula (II)

together with cis-octen-l-ol in the presence of a siereoretentive ruthenium olefin metathesis catalyst represented by Formula (I) as defined herein or in the presence of a Z-selective ruthenium olefin metathesis catalyst represented by Formula (V) as defined herein; and wherein:

R ^v is selected from

mbodiment, the invention provides a method for producing at least one alcohol product represented by

wherein at least one carbon -carbon double bond has a Z/E-seieetivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<ί ; comprising subjecting a substrate represented by Formula (II)

wherein: R ^v is with cis-5-octen-l-ol to a cross-metathesis reaction in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I) as defined herein

[125] In one embodiment the invention provides a method for producing at least one alcohol product represented by Formula (HI)

wherein at least one carbon-carbon double bond has a 27£~se!ectivity of 95/5, or 96/4, or 97/3, or

98/2, or 99/1, or >99/<l; comprising, subjecting a substrate

wherein: R ^v is - s Bb ; with cis-S-oeten-!-ol to a cross-metathesis reaction in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I) as defined herein.

[126] In one embodiment, the invention provides a method for producing at least one

A ¹² -Prostaglandin I product represented

wherein at least one carbon-carbon double bond has a Z/E-selectivity of 95/5, or 96/4, or 97/3 or 98/2, or 99/1 , or >99/<l ; comprising, subjecting a substrate represented by Formula (II)

Formula (II)

wherein: R ^v is _^ with cis-5~ocien-l-oi to a cross-metathesis reaction in the presence of a stereoreientive ruthenium olefin metathesis catalyst represented by Formula (I) as defined herein.

[127] In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z'Έ-seleetivity of 95/5, or 96/4, or 97/3 or 98/2, or 99/1, or >99/<l ; comprising, subjecting a substrate represented by Formula (II)

wherein: R ^v is OTBS with eis-5-octen- 1 -ol to a cross-metathesis reaction in the presence of a stereoreientive ruthenium olefin metathesis catalyst represented by Formula (!) as defined herein.

[128] In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/fi-seleetivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising, subjecting a substrate represented by Formula (H)

wherein: R ^v - is , with cis~5~octen-l-ol to a cross-metathes s reaction in the presence of a Z-selective ruthenium olefin metathesis catalyst represented by Formula (V) as defined herein

[129] In one embodiment, the invention provides a method for producing at least one alcohol product represented by F

wherein at least one carbon-carbon double bond has a ZZK-sefeciivity of 95/5, or 96/4 or 97/3, or 98/2, or 99/1 , or >99/<i ; comprising, subjecting a substrate represented by Fe

wherein: R ^v is OTBS ; with cis-5-octen-l -ol to a cross-metathesis reaction in the presence of a Z-selective ruthenium olefin metathesis catalyst represented by Formula (V) as defined herein.

[130] In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-se!ectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l; comprising, subjecting a substrate represented by Form ala (II)

wherein: R ^v is _w ¾h cis-5-octen-l-ol to a cross-metathesis reaction in the presence of a Z-selective ruthenium olefin metathesis catalyst represented by Formula (V) as defined herein.

[131] In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/Z-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1 , or >99/<i; comprising subjecting a substrate represented by Formula (II)

wherein: R ^v is GTBS , with cis-5-octen-l-ol to a cross-metathesis reaction in the presence of a Z-selective ruthenium olefin metathesis catalyst represented by Formula (V) as defined herein.

IΪΪ one embodiment, the invention provides a method for producing at least one A ^!2 ~Prostaglandin j product represented by Formula (IV),

wherein: I is \/ and wherein at least one carbon-carbon double bond has a

ZhF-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l; comprising submitting an alcohol product

to oxidation in the presence of ietrapropylaromonium permthenate and 4-methyimorphoiine N- oxide monohydrate or to oxidation in the presence of pyridinium ebloroehromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

Formula (II) and ds-octen-l-oi in the presence of a stereoreientive ruthenium olefin metathesis catalyst represented by Formula (1) as defined herein; and wherein R ^v is

[133] In one embodiment, the invention provides a method for producing at least one

A ⁱ² -Prostaglandin i product represented by Formula (IV),

wherein: R ² is ; and wherein at least one carbon-carbon double bond has a

Z/fb-se [activity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising submitting an alcohol product

to oxidation in the presence of tetrapropylammorsiura perruthenate and 4-methyimorphoiine N- oxide monohydrate or to oxidation in the presence of pyridinium chlorochromate and sodium chlorite; wherein the alcohol product of Formula (ill) is formed during the cross-metathesis reaction between a substrate represented by Formula (IX)

and cis-oeten~l ~ol in the presence of a Z-selective ruthenium olefin metathesis catalyst represented by Formula (V) as defined herein; and wherein R ^v is * **

[134] In one embodiment, the invention provides a method for producing at least one

A ^':2 ~Prostagiandin J product represented

wherein: R ^x is OH ; and wherein at feast one carbon-carbon double bond has a

Z/E-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1 , or >99/<1 ; by submitting an alcohol product of f

to oxidation in the presence of tetrapropyl ammonium perrulhenate and 4-methyfmorpholine N- oxide monohydrate or to oxidation in the presence of pyridinium chloroehromate and sodiu chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and cis-octen-l-ol in the presence of a stereoretentive ruthenium olefin metathesis catalyst

represented by Formula (I) as defined herein; and wherein R ^v is OTBS

1351 In one embodiment, the invention provides a method for producing at least one

A ⁱ² ~Prostaglandin J product represented by Formula (IV),

Formula (IV)

wherein: R ^z is OH ; and wherein at least one carbon-carbon double bond has a

Z/ifselectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising submitting an alcohol product of Formula (Ill)

to oxidation in the presence of tetrapropyl am onium perruthenate and 4~methylmorpholine N- oxide monohydrate or to oxidation in the presence of pyridlnium ehloroehromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and ci.s-oeten-l -ol in the presence of a Z-seleetive ruthenium olefin metathesis catalyst represented by Formula (V) as defined herein; and wherein K ^v is selected from

mbodiment, the invention provides a method for producing at least one D ^-Prostaglandin i product represented by

Formula (IV)

wherein: R ^; is ; and wherein at least one carboii-carbon double bond has a Z/E selectivity of 95/5 or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1 ; comprising, submitting an alcohol product of Formula

to oxidation in the presence of tetrapropylammonium permthenate and 4-methyimorpholine N- oxide monohydrate or to oxidation in the presence of pyridmiura chlorochromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and cis-octen - i -ol in the presence of a slereoreten ive ruthenium olefin metathesis catalyst

represented by Formula (i) as defined herein; and wherein R ^v is

(137] In one embodiment, the invention provides a method for producing at least one

A ^{: 7} --Prostagl ndin J product represented by Formula (IV),

wherein: R is OH ; and wherein at least one carbon-carbon double bond has a Z/E-se!ectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1 , or >99/<i ; by submitting an alcohol product of Formula (III)

to oxidation in the presence of ietrapropylammonium perruthenate and 4-methyimorpholine N- oxide monohydrate or to oxidation in the presence of pyridinium chlorochromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented

and cis-oefen-l -ol in the presence of a Z-seleetive ruthenium olefin metathesis catalyst represented by Formula (V) as defined herein; and wherein R ^v is selected from

mbodiment, the invention provides a method for producing at feast one A ^’2 -Prostagfandin j product represented by

wherein: R is ^ ^S ^ ^ ; and wherein at least one carbon-carbon double bond has a 7JE- selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l; comprising, submitting an alcohol product of Formula (III)

to oxidation in the presence of tetrapropylammomum perruthenate and 4~methylmorpholine N- oxide monohydrate or to oxidation in the presence of pyridinium ehioroehromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and cis-octen-l-ol in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I) as defined herein; and wherein R ^v is

[139| In one embodiment, the invention provides a method for producing at least one

A ^!2 -Frostaglandin J product represented by Formula (IV),

wherein: R is and wherein at least one carbon-carbon double bond has a Z/E-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising, submitting an alcohol product of Formula

to oxidation in the presence of tetrapropylammomum perruthenate and 4-meihyImorpholine K~ oxide monohydrate or to oxidation in the presence of pyridinium ehioroehromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and cis-octen-l -ol in the presence of a Z-se!eetive ruthenium olefin metathesis catalyst

represented Formula (V) as defined herein; and wherein R ^v is ^: r ^ ^sssss·

In one embodiment, the invention provides a method for producing at least one alcohol product represented by Fe

wherein at least one carbon-carbon double bond has a Z/E-selectivxty of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l; comprising, subjecting a substrate represented by Fori

cross-metathesis reaction in the presence of a stereoretentive ruthenium olefin metathesis eataiyst represented by Formula (I), wherein: X is S; Y is S; Z is X; W is O; R ^! is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is i-

141] In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (ill)

wherein at least one earbon-earbon double bond has a Z/F-sdeetivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising, subjecting a substrate represented by Formula (II)

wherein: R s selected from dx--' with cis-5-octen-l -ol to a cross-metathesis reaction in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I), wherein: X is S; Y is S; Z is N; W is O; R ¹ is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is Me; R ⁶ is H; R ⁷ is Me; R ^s is H; R ⁹ is Me; R*° is Me; R ^{! 1} is H; R ¹² is Me; R ¹³ is H; R ⁱ⁴ is Me; R ^{f 5} is Cl; R ¹⁶ is H: R ^{i 7} is H; R ¹⁸ is Ci; R ^iy is i-Pr; R ²⁰ is H; R ²¹ is H; R ²² is H; R ²³ is H; and R ²⁴ is H, [142] In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/fi'-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising, subjecting a substrate represented by Formula (II)

wherein: R ^v is selected from

; with eis-5-octen-l-oi to a cross-metathesis reaction in the presence of a 2-seiective ruthenium olefin metathesis catalyst represented by Formula (V), wherein W is O; X ^! is nitrate; R ^; is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is i-Pr; R ⁶ is H; R ⁷ is H; R ⁸ is H; R ⁹ is i-Pr; R ⁵⁹ is i-Pr; R ²⁰ is H; R ²⁵ is H; R ²² is H; R ²³ is H; R ²⁴ is H.

In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of 95/5, or 96/4, or 97/3, or

98/2, or 99/1, or >99/<l; comprising, subjecting a substrate represented by Formula (P)

wherein: R ^v is selected from

: with cis-5-octen-l-oi to a cross-metathesis reaction in the presence of a 2-seieetive ruthenium olefin metathesis catalyst represented by Formula {¥), wherein W is O; X ^’: is nitrate; R ^: is H; R ⁷ is H; R ³ is H: R ⁴ is H: R ⁵ is Me; R ⁶ is H; R ⁷ is Me; R ⁸ is H; R ⁵ is Me; R ^!v is i-Fr; R ²⁰ is H; R ²¹ is H; R ²² is H; R ²³ is H; R ² is H.

[146] In one embodiment, the invention provides a method for producing at least one

A ⁱ² -Prostagfandin J product represented by

Formula wherein: R ^‘ is selected from

and wherein at least one earbon-earbon double bond has a Z/E-seleet vlty of 95/5, or 96/4, or 97/3, or 98/2, or 99/1 , or >99/<I ; by submitting an alcohol product of Formula (III),

wherein R ^v is selected from

to oxidation in the presence of tetrapropylammonium perruthenate and 4-methylmorpholine N- oxide monohydrate or to oxidation in the presence of pyridinium chiorochromate and sodium chlorite; wherein the aieohoi product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

Formula (II)

and cis-octen-l-ol in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I); wherein X is S; Y is S; Z is N; W is O; R ^! is H: R ² is H: R ³ is H; R ⁴

[147] In one embodiment, the invention provides a method for producing at least one

D ^; --Prostaglandin J product represented by Fo mula <w\

wherein: R* Is selected from

_a ; and wherein at least one carbon-carbon double bond has a Z/E~se3eetivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; by submiting an alcohol product of] wherein R ^v is selected from

to oxidation in the presence of tetrapropyianimonium perruthenate and 4-methylmorpholine N- oxide monohydrate or to oxidation in the presence of pyridinlum chlorochromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and e s-oeten l Ol in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I); wherein X is S; Y is S; Z is N; W is O; R ^: is H; R ² is H: R ³ is H: R ⁴

[148] In one embodiment, the invention provides a method for producing at least one

A ¹² ~Prosiaglandin I product represented

wherein: ^z is selected from < OH

; nd wherein at least one carbon-carbon double bond has a Z/E-selectivliy of 95/5, or 96/4, or 97/3 or 98/2, or 99/1 , or >99/<l ; by submitting an alcohol product of Fc

to oxidation in the presence of tetrapropylammonium permthenate and 4-methy!morpholine N- oxide monohydrate or to oxidation in the presence of pyridinium chlorochromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented

and cis-octen-l-ol in the presence of a /.-selective ruthenium olefin metathesis catalyst represented by Formula (V); wherein W is G: X ^J is nitrate; R ¹ is H: R ² is H; R ³ is H; R' ¹ is H;

[149] In one embodiment, the invention provides a method for producing at least one

A ⁱ² -Prostag!andin I product r

wherein: R ^K is selected from

and wherein at least one carbon-carbon double bond has a Z/£ ^’ -seieetivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l; by submitting an alcohol product of/

to oxidation in the presence of tetrapropyl ammonium perruthenate and 4-methylmorphoiine N- oxide monohydraie or to oxidation in the presence of pyridinium chloroehromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and cis-octen-l ol in the presence of a Z-se!ective rutheniu olefin metathesis catalyst represented by Formula (¥); wherein W is O; X ¹ is nitrate; R’ is H; R ² is H; R ³ is H; R ⁴ is H; R ^s is i-Pr; R ⁶ is H; R ⁷ is H; R ⁸ is H: R ⁹ is i-Pr; R ¹⁹ is i-Pr; R ²⁰ is H; R ²¹ is H; R ²² is H: R ²³ is H; R ²⁴ is H.

| ISO] In one embodiment, the invention provides a method for producing at least one alcohoi product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<1 : comprising, subjecting a substrate represented by F

wherein: cross-metathesis reaction in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I), wherein: X is S; Y is S; Z is N; W is O; R ¹ is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is Me; R ⁶ is H; R ⁷

1 S 1 j In one embodiment, the invention provides a method for producing at least one alcohol product represented by Ft

wherein at least one carbon-carbon double bond has a Z7E~seieetiviiy of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising, subjecting a substrate represented by Forr

Formula

wherein: R ^v is OTBS ; with cis-5-octen-l-ol to a cross-metathesis reaction in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I), wherein: X is S; Y is S; Z is N; W is O; R ¹ is H; R ² is H; R ³ is H; R ⁴ is H; R ^s is f-Pr; R ⁶ is H; R ⁷ is P: R ⁸ is H; R ⁹ is i-Pr; R ^iC is i-Fr; R ^{1 1} is FI; R ¹² is H; R ^!3 is H; R ⁱ⁴ is i-Pr; R ^is is Cl; R ^':6 is H; R ⁱ⁷ is H; R ^{! B} is Ci; R ¹⁹ is i-Pr; R ²⁰ is H; R ^2S is H; R ²² is H; R ²³ is H; and R ²⁴ is H.

In one embodiment, the invention provides a method for producing at least one aicoho! product represented by Formula (HI)

wherein at least one carbon-carbon double bond has a ZTs-seleetivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising, subjecting a substrate represented by Formula (II)

Formula (II) wherein: R ^v is : with cis-5-octen-l-oi to a cross-metathesis reaction in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by

(I), wherein: X is S; Y is S; Z is N; W is O; R ¹ is H; R ² is H; R ³ is H: R ⁴ is H; R ⁵ is Me: R ⁶ is Fi; R ⁷ is Me; R ^s is H; R ⁹ is Me; R ¹⁰ is Me; R ^{1 1} is FI; R ¹² is Me; R° is II; R ¹⁴ is Me: R ¹⁵ is Cl; R ^’:6 is H; R ¹⁷ is H; ¹⁸ is Cl; R ¹⁹ is i-Pr; R ²⁰ is H; R ²ⁱ is H; R ²² is H; R ²³ is H; and R ²⁴ is H.

[1S3| In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (Hi)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising: subjecting a substrate represented by Formula (II)

wherein: R ^v is ; with cis-5-oetcn-l-ol to a cross-metathesis reaction in the presence of a stcreoretentive ruthenium olefin metathesis catalyst represented by Formula (I), wherein: X is S; Y is S; Z is N; W is O; R ⁵ is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is i-Fr; R ⁶ is H: R ^? is H; R ^s is H; R'- is i~Pr; R ^!0 is i~Pr; R ^{1 1} is H; R ^!2 is H: R ^l is H; R ^J4 is i-Pr; R ^;S is Cl; R ¹⁶ is H; R ^{1 7} is H; R ¹⁸ is Cl; R ^s9 is i-Pr; R ²⁰ is H; R ²ⁱ is H; R ²² is H; R ²³ is H; and R ²⁴ is H.

[1S4J In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z/E-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l comprising, subjecting a substrate represented by Formula (II)

wherein: R ^v is OTBS ; with cis-5-octen-l -ol to a cross-metathesis reaction in the presence of a Z-se!ective ruthenium olefin metathesis catalyst represented by Formula (V), wherein W is O; X ^f is nitrate; ^J is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is Me; R ⁶ is H; R ⁷ is Me; R ^s is H; R ⁹ is Me; R ¹⁹ is i-Pr; R ²⁰ is H; R ²¹ is H; R ²² is H; R ²³ is H; R ²⁴ is f-L

II 55; In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Z'is-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising, subjecting a substrate represented by Formula (II)

wherein; R ^v is OTBS ; with cis-5-octen-l -ol to a cross-metathesis reaction In the presence of a Z-selective ruthenium olefin metathesis catalyst represented by Formula (V), wherein W is O; X ^; is nitrate; R ¹ is H; R ² is H; R ³ is H; R ⁴ is H; R ³ is i-Pr; R ⁶ is H; R ⁷ is H; R ⁸ is H; R ⁹ is i-Pr; R ⁵⁹ is i-Pr; R ²⁰ is H; R ²ⁱ is H; R ²² is H; R ²³ is H; R ²⁴ is H.

In one embodiment, the invention provides a method for producing at least one alcohol product represented

wherein at least one carbon-carbon double bond has a Twselectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising, subjecting a substrate represented by Formula (II)

wherein: R ^v is · with eis-S-oeten-l-ol to a cross-metathesis reaction in the presence of a Z-seiective ruthenium olefin metathesis catalyst represented by Formula (V), wherein W is O; X ^! is nitrate; R ^f is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is i-Pr; R ⁶ is H; R ⁷ is H; R ⁸ is H; R ⁹ is ί-Pr; R ^{! 9} is i-Pr; R ³⁰ is H; R ²¹ is H; R ²² is H; R ²³ is H: R ²⁴ is H.

[157] In one embodiment, the invention provides a method for producing at least one alcohol product represented by For ula (III)

wherein at least one carbon-carbon double bond has a ZcF-seleciivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising: subjecting a substrate represented by Formula (II)

wherein: R ^v is with cis S-ocien-l~oi to a cross-metathesis reaction in the presence of a Z-selective ruthenium olefin metathesis catalyst represented by Formula (V), wherein W is O; X ¹ is nitrate; R ¹ is H; R ² is H; R ³ is H; R ⁴ is H; R ³ is Me; R ⁶ is H; R ⁷ is Me; R ⁸ is H; R ⁹ is Me; R ¹⁹ is I-Pr; R ²⁰ is H; R ²¹ is H; R ²² Is H: R ²³ is H; R ²⁴ is IP

[158] In one embodiment, the invention provides a method for producing at least one alcohol product represented by Formula (III)

wherein at least one carbon-carbon double bond has a Zdf-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising, subjecting a substrate represented by

wherein: R ^v is ; _w |th cis-5-octen-l-ol to a cross-metathesis reaction in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented Formula (I), wherein: X is S; Y is S; Z is N; W is O; R ¹ is H; R ² is H; R ³ is H; R ⁴ is H: R ^s is Me; R ⁶ is H; R ⁷ is Me; R ^s is H; R ⁹ is Me; R ⁱ⁰ is Me; R‘ ¹ is H; R ¹² is Me; R ¹³ is H; R ¹⁴ is Me; R ⁱ⁵ is Ci; R ¹⁶ is H; R ¹⁷ is H; R ^{i 8} is Cl; R ¹⁹ is i-Pr; R ²⁰ is H; R ²ⁱ is H; R ²² is H; R ²³ is H; and R ²⁴ is H

[159] in one embodiment, the invention provides a method for producing at ieast one alcohol product represented by Formula (III)

For ula (Hi)

wherein at least one carbon-carbon double bond has a ZZE-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l; comprising: subjecting a substrate represented by Formula (II)

Formula (II) 93

wherein: R ^v is ; with eis-5-octen~l~ol to a cross-metathesis reaction in the presence of a stereoretendve ruthenium olefin metathesis catalyst represented by Formula (I), wherein X is S; Y is S; Z is Nr W is O; R ^l is H; R ² is I I; R ³ is H; R ⁴ is H; R ^s is ί-Pr; R ⁶ is H; R ⁷ is H; R ³ is H; R ⁹ is i-Pr; R ^!0 is i-Pr; R” is H; R ¹² is H; R ¹³ is H; R ^:4 is i-Pr; R ⁱ⁵ is Cl: R ¹⁶ is H; R ^i? is H; R ^!S is Cl; R ¹⁹ is i-Pr; R ²⁰ is H; R ^2! is H; R ²² is H: R ²³ is H; and R ²⁴ is H.

[160] In one embodiment the invention provides a method for producing at least one

A ^!2 -Prostagiandin J product represented by Formula (IV),

wherein: R' is OH and wherein at ieast one carbon-carbon double bond has a

Z/E-selectivity of 95/5, or 96/4, or 97/3, or 98/2. or 99/1 , or >99/<l ; comprising submitting an alcohol product of Formula (III),

wherein R ^v is OTBS ; to oxidation in the presence of tetrapropylammomum peiTuthenate and 4-methy!morphoiine N-oxide monohydrate; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and cis-ocien-l-ol in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I); wherein: X is S; Y is S; 2 is N; W is O; R ^! is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is i-Pr; R ⁶ is H; R ⁷ is H; R ⁸ is H; R ⁹ is i-Pr; R ¹⁰ is j-Pr; R ^{5 5} is H; R ¹⁷ · is H; R ¹³ is H; R ^M is i-Pr; R ^{; s} is Cl; R ⁵⁶ is H; R' ⁷ is H; R ¹⁸ is Cl; R ^!9 is i-Pr; R ²⁰ is H; R ²¹ is H; R ⁷⁷ is H; R ²³ is H; and R ⁷⁴ is H.

[161] In one embodiment, the invention provides a method for producing at least one

Y ^l2 -Prostaglandin J product represented by Formula (IV),

wherein: R ⁷ is OH ; and wherein at least one carbon-carbon double bond has a

Z/X-seleetivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l ; comprising, submitting an a lcohol product of Formula (III), wherein

R ^v is s OTBS , to oxidation in the presence of tetrapropylanunonium perruthenate and 4-methylmorphofme N-oxide monohydrate; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and cis-octen-1 -o3 in the presence of a siereoretentive ruthenium olefin metathesis catalyst represented by Formula (I); wherein X is S; Y is S; Z is N; W is O; R ^’: is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is Me; R ⁶ is H; R ⁷ is Me; R ⁸ is H; R ⁹ is Me; R ^{f 0} is Me; R ⁵⁵ is H; R ¹² is Me; R ¹³ is H; R ¹⁴ is Me; R ^{, 5} is Cl; R ¹⁶ is H; R ⁱ⁷ is H; R ¹⁸ is Cl: R ^!9 is i-Pr; R ²⁰ is H; R ²ⁱ is H; R ²² is H; R ²³ is H; and R ²⁴ is H.

[162] In one embodiment the invention provides a method for producing at least one

A ^l -Prostagiandin J product represented by Formula (IV)

wherein: R ² is selected from and wherein at least one carbon-carbon double bond has a Zΐ-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<i ;

comprising, submitting an alcohol product of For wherein R ^v is

to oxidation in the presence of teirapropyiammonium perruthenate and 4-methy!morphoiine N~ oxide monohydrate; wherein the alcohol product of Formula (III) is formed during the cross- metathesis reaction between a substrate represented by Formula (I

Formula (II)

and cis-octen-1 -oi in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I); wherein X is Si Y is S; Z is N; W is O; R ^? is H; R ² is H; R ³ is H; R is H; R ^s is i-Pr; R ⁶ is H; R ⁷ is H; R ^s is H; R ⁹ is i-Pr; R ¹⁰ is i-Pr; R ^u is H; R ¹² is H; R ⁱ³ is H; R ^M is i-Pr; R ^iS is Cl; R ⁵⁶ is H; R ⁵⁷ is H; R ⁵⁸ is Cl; R ¹⁹ is i-Pr; R ²⁰ is H; R ²¹ is H; R ²² is H; R ²³ is H; and R ²⁴ is H. In one embodiment the invention provides a method tor producing at least one A ⁱ² -Prostaglandin j product represented by

wherein: R ^z is selected from and wherein at !east one carbon-carbon double bond has a Z/E-seiectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<i; by submitting an alcohol product of F wherein R ^v is

to oxidation in the presence of teirapropylammomum perruthenate and 4~methylmorpholme bi- oxide monohydrate; wherein the alcohol product of Formula (ill) is formed during the cross- metathesis reaction between a substrate represented by Formula (II)

Formula (II)

and cis-oeten-l-ol in the presence of a stereoretentive ruthenium olefin metathesis catalyst represented by Formula (I); wherein X is S; Y is S; Z is N; W is O; R. ^! is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is Me; R ⁶ is H; R ⁷ is Me; R ⁸ is H; R ⁹ is Me; R ⁱ⁰ is Me; R ⁿ is H: R ¹² is Me; R ¹³ is H; R ^J4 is Me; R ^!S is Cl; R ⁱ⁶ is H; R ¹⁷ is H; R ¹⁸ is Cl; R ^{! 9} is ί-Pr; R ²⁰ is H; R ²ⁱ is H; R ²² is H; R ²³ is H; and R ²⁴ is H.

[164] In one embodiment the invention provides a method for producing at least one¾ ^l2 ~Prostaglandin I product represented by Formula (IV), wherein: R ^z is wherein at least one carbon-carbon double bond has a

Z/E-seleetivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1 , or >99/<l : comprising, submitting an

alcohol product of For Simla (Hi), wherein R ^v is

to oxidation in the presence of teirapropyiammonmm perruthenate and d-methylmorpholine N~ oxide monohydrate; w'herein the alcohol product of Formula (Hi) is formed during the cross- metathesis reaction between a substrate represented by Formula (II)

and cis-oeten-1 ~ol in the presence of a Z-seleetive ruthenium olefin metathesis catalyst represented by Formula (V); wherein W is O; X ¹ is nitrate; R ⁵ is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is i-Pr; R ⁶ is H; R ⁷ is H; ⁸ is H; R ⁹ is i-Pr; R ^{i s} is i-Pr; R ²⁰ is H; R ²ⁱ is H; R ²² is H; R ²³ is H; R ²⁴ is H.

|16S| In one embodiment, the invention provides a method for producing at least one

A ¹² -ProstagIandin J product represented by Formula (IV),

wherein: R ^z is OH and wherein at least one carbon-carbon double bond has a

Z/Z-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1 , or >99/<! ; comprising, submitting an

alcohol product of wherein R ^v is OTBS

to oxidation in the presence of tetrapropylarnmonium perruthenate and 4-metbyImorphoIine N- oxide monohydrate; wherein the alcohol product of Formula (ill) is formed during the cross- metathesis reaction between a substrate represented by Formula (II)

and eis-octen- l-ol in the presence of a Z-selective ruthenium olefin metathesis cataiyst represented by Formula (V); wherein: W is O; X ¹ is nitrate; R ^! is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is Me; R ^ft is H; R ⁷ is Me; R ⁸ is H; R ⁹ is Me; R ^{f 9} is i-Pr; R ²⁰ Is H; R ² ’· is H; R ²² is H; R ²³ is H; R ²⁴ Is H.

[166J in one embodiment, the invention provides a method for producing at. least one

A ^{l 2} -Prostaglandin J product represented by Formula (IV),

wherein: R ^z is selected from ; and wherein at least one carbon-carbon double bond has a Z/E-seieetivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l;

comprising, submitting an alcohol product of Formula (III), wherein R ^v is

to oxidation in the presence of pyridinium ehlorochromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

Formula (II)

and cis-oeten-l -ol in the presence of a Z~seleetive ruthenium olefin metathesis catalyst represented by Formula (V); wherein W is O; X ¹ is nitrate; R ⁵ Is H; R ² Is H; R ³ is H; R ⁴ is H; R ⁵ is i-Pr; R ⁶ is H; R ⁷ is H; R ⁸ is H; R ⁹ is i-Pr; R ¹⁹ is i-Pr; R ²⁰ is H; R ^2! is H; R ²² Is H; R ²³ is H: R ²⁴ is I-L

In one embodiment, the invention provides a method for producing at least one A ^,2 ~ProsiaglandIn J product represented by Formula (IV),

wherein: R ^z is ; and wherein at least one carbon-carbon double bond has a 7JE- selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<i ; comprising, submitting an alcohol product of Formula (III), wherein R ^v is

to oxidation in the presence of pyridimum chlorochromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and cis-oeten-l-ol in the presence of a Z-seieetive ruthenium olefin metathesis catalyst represented by Formula (V); wherein W is O; X ^! is nitrate; R ⁵ is H; R ² is H; R ³ is H; R ⁴ is l-I;

In one embodiment, the invention provides a method for producing at least one A ⁱ² ~ProstagIandin j product represented by Formula (IV),

wherein: R" is ; and wherein at least one carbon-carbon double bond has a ZZB-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l : comprising, submitting an alcohol product of Formula (MI), wherein R ^v is ;

to oxidation in the presence of pyridinium chiorochromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and cis-octen-l-o! in the presence of a stereoreteniive ruthenium olefin metathesis catalyst represented by Formula (I); wherein X is S; Y is S; Z is N; W is O; R ^; is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is i-Pr; R ⁶ is H; R ⁷ is H; R ⁸ is H; R ⁹ is i-Pr; R ¹⁰ is i-Pr; R ^{1 1} is H; R ⁱ² is H; R ¹³ is H; R ⁵⁴ is i-Pr; R ^!5 is Cl; R ^!6 is H; R ⁱ⁷ is H; R ^':S is Cl; R ¹⁹ is i-Pr; R ²⁰ is H; R ²¹ is H; R ²² is H; R ²³ is H; and R ²⁴ is H.

[169J in one embodiment, the invention provides a method for producing at least one

A’ Rprostagiandin I product represented by Formula (IV),

wherein: R ^z is ; and wherein at least one carbon-carbon double bond has a Z E-selectivity of 95/5, or 96/4, or 97/3, or 98/2, or 99/1, or >99/<l; comprising, submitting an alcohol product of Formula (III), wherein K ^v is

to oxidation in the presence of pyridinium chiorochromate and sodium chlorite; wherein the alcohol product of Formula (III) is formed during the cross-metathesis reaction between a substrate represented by Formula (II)

and cis-octen-l-ol in the presence of a stereoselective ruthenium olefin metathesis catalyst represented by Formula (I); wherein X is S; Y is S; Z is N; W is Q: R ¹ is H; R ² is H; R ³ is H; R ⁴ is H; R ⁵ is Me; R ⁶ is H; R ⁷ is Me; R ⁸ is H; R ⁹ is Me; R ⁱ⁰ Is Me; R ⁿ is H; R ^’:2 is Me; R ¹³ is H; R ¹⁴ is Me; R ^,s is Cl; R' ⁶ is H; R’ ⁷ is H; R ¹⁸ is Cl; R ¹⁹ is i-Pr; R ²⁰ is H; R ²¹ is H: R ²² is H; R ²³ is H; and R ²⁴ s H.

[170] In the following examples, efforts have beers made to ensure accuracy with respect to numbers used (e.g., amounts, temperature, etc.) but some experimental error and deviation should be accounted for, Unless indicated otherwise, temperature is in degrees Celsius and pressure is at or near atmospheric. The examples are to be considered as not being limiting of the invention as described herein and are instead provided as representative examples of the catalyst compounds of the invention, of the methods that may be used in their preparation, and of the methods of using the inventive catalysts.

Materials and Methods

[171 ] Unless noted in the specific procedure, reactions were performed in flame-dried glassware under argon atmosphere. All metathesis reactions were carried out under air-free conditions in dry glassware in a Vacuum Atmospheres Glovebox filled with N ₂ . General solvents were purified by passing through solvent purification columns. Commercially available substrates were used as received. Ail solvents and substrates were sparged with Ar before bringing into the glovebox and filtered over basic alumina (Brockmann I) prior to use. Reaction progress was monitored by thin-layer chromatography (TLC) using E. Merck silica gel 60 F254 precoated plates (0.25 ) and visualized by UV fluorescence quenching, potassium

permanganate, or p-anisaldehyde staining. Siiicycle Sili&F!ash P60 Academic Silica gel (particle size 0.040-0.063 mm) was used for flash chromatography. Analytical chiral HPLC was performed with an Agilent 1 100 Series HPLC utilizing a Chiralcei OD-H column (4.6 mm x 25 cm) obtained from Daieel Chemical industries, Ltd. with visualization at 254 nm. Analytical SFC was performed with a Mettler SFC supercritical CO2 analytical chromatography system utilizing Chiralcel (1C) column (4,6 mm x 25 cm) obtained from Daicel Chemical industries,

Ltd. with visualization at 210 nm. GC conversion data was obtained using an HP-5 capillary column with an Agilent 6850 FID gas chromatograph, ^l H and ^< C NMR spectra were recorded on a Yarian Inova 500 spectrometer (500 MHz and 126 MHz, respectively), a Broker AY III HD spectrometer equipped with a Prodigy liquid nitrogen temperature cryoprobe (400 MHz and 101 MHz, respectively), or a Varian Mercury' 300 spectrometer (300 MHz. and 75 MHz, respectively)

and are reported in terms of chemical shift relative to residual CHCh (d 7,26 and d 77.16 pp , respectively). Data for ^! H NMR spectra are reported as follows: chemical shift (8 ppm) (multiplicity, coupling constant (Hz), integration). Abbreviations are used as follows: s = singlet bs ^::: broad singlet, d ^:::: doublet, t ^::: triplet, q = quartet, quint = quintet, m = complex multiple!. Infrared (1R) spectra were recorded on a Perkin Elmer Paragon 1000 spectrometer using neat samples on ATR diamond, and are reported in frequency of absorption (cm ¹ ). High-resolution mass spectra FIRMS were acquired from the Caltech Mass Spectral Facility using fast-atom bombardment (FAB ¹ ), eleetrospray ionization (TOP ES ^÷ ) or electron impact (EI ⁺ ). Optical rotations were measured on a Jasco P-2000 polarimeter using a 100 nun path-length ceil at 589 nm.

[172] The following abbreviations are used herein:

RT or r.t. room temperature

CDCh deuierated chloroform

CHCb chloroform

CfiHe benzene

THE tetrahydrofuran

MaH ₂ P0 _4« H ₂ 0 sodium dihydrogen phosphate monohydrate NaClOs sodium chlorite

NMOFEO 4-methylmorphoHnc K -oxide monohydrate TPAP tetrapropylammonium perruthenate MeCN acetonitrile

Et ₂ 0 diethyl ether

NaHCGa sodium bicarbonate

t-BuOH tert-butyiaicohol

DCM/CH2CI2 dichloromethane

DMAP 4-dimethylammopyridine S1O2 silicagel

[173) In a nitrogen-filled glovebox, c¾?~5-octen-l~oi (150 mg, 1.17 mmol, 8.0 equiv) was dissolved in toluene (2 ml,) in a 50 mL Schlenk flask, and a solution of catalyst Ru-4 (9.9 mg, 1 1 ,7 mhioΐ, 1 mol%) in THF (0.7 mL) was added. The Schlenk flask was sealed and brought out of the glovebox, and then connected to high vacuum. The valve was gradually opened (Caution: open slowly and stir well to avoid splashing). After 15 minutes stirring, the flask was refilled with argon and sealed, and was brought back into the glovebox. The residue was diluted with THF (0.5 mL), and an aliquot was taken for G€ analysis (conversion of homodimerization step was >98% by GC analysis). A solution of 11 [CAS 2135628-52-1 ] (53 mg, 0.146 mmol, 1.0 equiv) in THF (0.5 mL) w¾s added into the Schlenk flask and an additional portion of catalyst Hu-4 (6 2 mg, 7.3 prnol, 5 moI%) solution in THF (0.3 mL) was added. The Schlenk flask was sealed and brought out of glovebox. The reaction was stirred for 24 h at 40°C before a few drops of ethyl vinyl ether were added. The solvent was removed under reduced pressure. The residue was purified by flash chromatography (SiCfc, hexanes/EtOAc 2: 1 ) to give 14 (60 mg, 95%,

>99: 1 Z'Έ)

TLC (3:1 hexanes/EtOAc): R/ ^:: 0.23 (UV).

lH NMR (400 MHz, CDCb): 5 7.50 (ddd, J = 6.0, 2.6, 1.0 Hz, 1H), 6.59 (ddt, J= 8.3, 7.0, 1.3 Hz, 1H), 6.33 (dd, J= 6 0, 1.8 Hz, 1 H), 5.49 (dddt, J - 8.6, 7.2, 5.5, 1.5 Hz, !H), 5.35 (dtt. J- 11.0, 8.4, 1.6 Hz, 1 H), 3.84 (quint, J - 5.9 Hz, 1 H), 3.63 (t, J - 6.5 Hz, 2H), 3.46 (ddt, J = 11.0, 4.2, 2.2 Hz, !H), 2,63 (dddd, J= 13.8, 6.5, 4.2, 1,5 Hz, 1H), 2.50 - 2.34 (m, 2H), 2.17 (dddd, J-

14.5, 9.4, 8.0, 1.3 Hz, 1H), 2.07 - 1.97 (m, 2H), 1.60 - 1.51 (m, 2H), 1.47 - 1.34 (m, 6H), 1.32 - 1.19 (m, 5H), 0.95 - 0.81 (m, 12H), 0.05 (s, 3H), 0,05 (s. 3H).

i ³ C NMR (101 MHz, CDCb): d 196.5, 161.8, 138.8, 135.0, 132.7, 132.5, 125.4, 71.7, 62.9, 43.6,

37.5, 37.5, 32.5, 32.0, 30.7, 27.2, 26.0, 25.8, 25, 1, 22.8, 18.2, 14.2, -4.2, -4.5.

FTIR (ATR): 3443, 2956, 2928, 2856, 1703, 1652, 1580, 1472, 1360, 1251 , 1206, 1 127, 1048, 1005, 975, 866, 834, 806, 773, 726, 664 cmfo

HRMS (TOF, ES ⁺ , m/z): ca ’d for C ₂₆ H ₄₇ O ₃ S1 [M+H] ⁺ 435.3289, found: 435.3298,

(«]¾: +83.5° (c - 1.0, CHCb).

Example 2:

Preparation of A°~prosi:agIandiis J2 (1)

(174] To a stirred solution of 14 (26 mg, 0.06 mmol, 1.0 equiv) in MeCN (0,3 mL) was added NMOH2O (81 mg, 6 mmol, 10.0 equiv). Tetrapropylammonium perruthenate (2.1 mg, 6 pmol, 0.1 equiv) was added until NMOH ₂ O was folly dissolved, and the reaction was stirred at 23 ^,; C for 3 hours. The solution was diluted with Eί ₂ 0 (5 ml,), passed through a short pad of silica gel, concentrated and was subjected to the next reaction without further purification.

The residue was dissolved in MeCN (1.0 mL) and cooled to 0 °C. A solution of hydrofluoric add

(48 wt % in I NO, 0.2 mL) in MeCN (0.4 mL) was added dropwisely. The solution was stirred in the same temperature for 30 min before saturated aHCCb solution (1.5 mL) and brine (1.5 mL) were added. The aqueous phase was extracted with EtOAc (5 x 5 mL). The combined organic phases were dried over magnesium sulfate, littered and concentrated (not to dryness). The residue was purified by flash chromatography (S1O2, CTfeCk/MeOH 20: 1) to give 1 (18 mg,

89%

over 2 steps) as a colorless liquid.

TLC (20: 1 C; !A VMeO! f): R/ ^: 0.14 (CL V).

^! H NMR (500 MHz, CDCb): d 7.57 (ddd, J= 6.0, 2.6, i.O Hz, 1 H), 6.58 (ddt, 8.4, 7.2, 1.3 Hz, 1H), 6.36 (dd, J= 6.0, 1.8 Hz, IH), 5.54 5.38 (m, 2H), 3.86 (dtt, ./ === 7.9, 6.4, 4.0 Hz, 1 H), 3.47 (ddt, J - 9.5, 4.0, 2.1 Hz, IH), 2.78 - 2.68 (m, IH), 2.57 (dt, J = 14.8, 6.8 Hz, IH), 2.52 - 2.42 (m, I H), 2.40 - 2.33 (m, 2H), 2.20 - 2.02 (m, 3H), 1.77 - 1.64 (m, 2H), 1.61 - 1.41 (m,

3H), 1.40 - 1.24 (m, 5H), 0.90 (t, J= 6.8 Hz, 3 IT). ^{, 3} C NMR. (126 MHz, CDCb): d 196 6, 177.3, 162,0, 139,8, 135.0, 131.8, 131.7, 126.2, 71.5, 43,9, 37.3, 36.7, 33.1, 31.9, 30.6, 26,6, 25.4, 24.6, 22.8, 14.2.

FUR (ATR): 3445, 2960, 2929, 2858, 1699, 1646, 1579, 1463, 1406, 1265, 1237, 1135, 1084,

[175] In a nitrogen-filled glovebox, eA-5-octen-l-ol (1 13 mg, 0.88 mmol, 8.0 equiv) was dissolved in toluene (1 mL) in a 50 rnL Sehlenk flask and a solution of catalyst Ka~4 (7.5 mg, 8.8 p ol, mol%) in THE (0.6 mL) was added. The Sehlenk flask was sealed and brought out of the glovebox, and then connected to high vacuum. The valve was gradually opened ( Caution : open slowly and stir well la avoid splashing). After 15 minutes stirring, the flask was refilled with argon and sealed, and was brought hack into the glovebox. The residue was diluted with THF (0,5 mL), and an aliquot was taken for GC analysis (conversion of homodimerization step was >98% by GC analysis). A solution of 16 [CAS 2254448-24-1 ] (25 mg, 0,1 1 mmol, 1.0 equiv) in THF (0.5 mL) was added into the Sehlenk flask and an additional portion of catalyst Rts~4 (4.6 mg, 5.5 pmol, 5 mol%) solution in THF (0.2 mL) was added. The Sehlenk flask was sealed and brought out of glovebox. The reaction was stirred for 24 h at 40 °C before a few drops of ethyl vinyl ether were added. The solvent was removed under reduced pressure. The residue was purified by fash chromatography (SiO _? „ hexanes/EtOAc 2:1) to give 17 (31 mg, 93%, >99: 1 Z/E, 87% ee by chiral HPLC analysis).

TLC (4: 1 hexanes/EtOAc): f- 0,2 (XJV).

^! H NMR (400 MHz, CDCL) d 7.48 (ddd, J ^~ 6.0, 2.6, 1 ,0 Hz, 1H), 6.95 (dt, J= 1 1.0, 1.3 Hz, 1H), 6.35 (dd, - 6.0, 1.8 Hz, IH), 6.34 - 6.19 (m, 2H), 5.52 - 5,44 (m, IH), 5,38 - 5,30 (m, 1H), 3.63 (t, J - 6.5 Hz, 2H), 3.60 - 3.55 (m, IH), 2.60 (dddd, J = 14.0, 6.2, 4.3, 1.4 Hz, IH), 2.30 (did, J = 14,4, 8.6, 1.2 Hz, IH), 2.25 - 2.17 (m, 2H), 2.01 (qd, - 7.3, 1.4 Hz, 2H), 1.59 - 1.49 (in, 2H), 1 ,48 - 1 ,37 (m, 5H), 1.34 - 1.29 (m, 4H), 0.89 (1, J - 7.0 Hz, 3H).

^!3 C NMR (101 MHz, CDCb): d 197,6, 160,9, 147,0, 135.4, 135.3, 132.6, 131.8, 125.8, 125.3, 62 9, 43.7, 33.6, 32.5, 31.5, 30.9, 28,6, 27.2, 25.8, 22.6, 14.2.

FOR (ATR): 3445, 2960, 2930, 2862, 1690, 1629, 1580, 1447, 1264, 1207, 1054, 979, 732 cnr

HRMS (TOP, ES ⁺ , m/z): caic’d for C20H31O2 [M+H] ^* 303.2319, found: 303.2320.

[a]¾: ÷1 15.8° (c = 0.5, CHCb).

HPLC Conditions: 30% IPA, 1.0 rnL/ in, Chiralecl OD-H column, l = 254 nm, tR (min): majpr = 10.12, minor = 13.57.

Example 4

Preparation of 15~deoxy~A ^12,14 ~prGstaglasidm _> h (2):

[176] To a stirred solution of 17 (14 mg, 0.046 mrnol, 1.0 equiv) in MeCN (0.5 mL) was added NMOH2O (65 mg, 0,46 mmol, 10.0 equiv). Tetrapropyiamraonium perruihenate (1.7 mg, 4.6 pmoL 0.1 equiv) was added until NMOH2O was fully dissolved, and the reaction was stirred at 23 °C for 3 hours. The reaction mixture was stirred for 3 hours and the solvent was removed in vacuo The residue was loaded onto a silica gel column, flushed with CH2CI2 then ClfcCh/MeOH (20:1). 15-deoxy-A ⁱ² - ⁱ⁴ -prostagIandin J ₂ (2) was obtained as a colorless oil (10 mg, 68% yield).

TLC (100% EtOAe): R == 0.70 (UV).

^! H NMR (400 MHz.. CDCU): d 7.47 (ddd, J= 6.0, 2.6, 1.0 Hz, IH), 6.95 (d, J= 13.0 Hz, IH), 6.38 - 6.35 (m, IH), 6.33 - 6.20 (m, 2H), 5.50 - 5.33 (m, 2H), 3.59 (ddd, J- 8.4, 4.1, 2.2 Hz, 1 H), 2,59 (m, 1 H), 2.36 - 2.19 (rn, 5H), 2.05 (q, 7.3 Hz, 2H), 1.68 (quint, J= 7.5 Hz, 2H),

1.50 - 1.41 (m, 2H), 1.34 - 1.28 (m, 4H), 0.90 (t, J = 7.0 Hz, 3H).

¹³ C NMR (101 MHz, CDCb): d 197.6, 177.9, 160.8, 147.2, 135.5, 335.1, 131 .9, 131.5, 126.2, 125.8, 43.6, 33.6, 33.2, 31.6, 30.8, 28.6, 26.7, 24.6, 22.6, 14.2,

FTIR (ATR): 2960, 2928, 2850, 1708, 1692, 1629, 1456, 1265, 1207, 978, 734, 703 cm-1. HRMS (TOF, ES+, m/z): calc’d for CSeHjgCh [M+H] ⁴ 317.2111, found: 317.2127.

[a]¾: 4-106.2° (c - 0.2, CHCb).

Spectral data (“H NMR, ¹³ € NMR, HRMS) matched with the published data:

Acharya, H. P.; Kobayashi, Y. Highly Efficient Total Synthesis of A12-PGJ ₂ , 15-Deoxy- D ^1,2>!4 -R<¾ and Their Analogues. Tetrahedron 2006, 62, 3329-3343.

Brummond, K. M.; Sill, P. C.; Chen, H. The First Total Synthesis of 15-Deoxy-A ^!2>!4 - Prostaglandin J ₂ and the Unambiguous Assignment of the Cl 4 Stereochemistry. Org.

Lett. 2004, 6, 149-152. Kim, N.-J.; Moon, H.; Park, T.; Yun, H.; Jung, J.-W.; Chang,

D.-J.; Kim, D.-F3.; Suh, Y.~G Concise and Enantioselective Total Synthesis of 15-Deoxy- A ^{i 2} _’ ^{f 4} -Prostaglandin J ₂ . J. Org . Chem. 2010, 75, 7458-7460. Egger, J.; Fischer, S.;

Bretscher, P.; Freigang, S.; Kopf, M.; Carreira, E. M. Total Synthesis of Prostaglandin

15d-PGJ ₂ and Investigation of Its Effect on the Secretion of IL-6 and IL-12. Org. Lett.

2015, 17, 4340-4343.

Preparation of alcohol 23 in the presence ef Ru-4

[177] In a nitrogen-filled glovebox, cw-5-octen-l-o! (72 mg, 0.55 mmol 6.7 equiv) was dissolved in toluene (1 rnL) in a 50 ml.· Schlenk flask and a solution of catalyst Ras-4 (4.7 mg,

5.6 pmol 1 moi%) in THF (0,6 mL) was added. The Schlenk flask was sealed and brought out of the glovebox, and then connected to high vacuum. The valve was gradually opened (Caution: ope slowly and stir well to avoid splashing). After IS minutes stirring, the flask was refilled with argon and sealed, and was brought back into the glovebox, The residue was diluted with 0.5 mL THF, and an aliquot was taken for GC analysis (conversion of homodimerization step was >98% by GC analysis). A solution of 22 [CAS 2254448-26-3] (30 rag, 0,083 mmol, 1 equiv) in 0,5 ml, THF was added into the Schlenk flask and an additional 0.4 mL of catalyst solution with Ris-4 (2.9 rag, 3.5 pmol, 5 mol%) was added. The Schlenk flask was sealed and brought out of glovehox. The reaction was stirred for 12 h at 23 °C before a few drops of ethyl vinyl ether were added, The solvent was removed under reduced pressure. The residue was purified by flash chromatography (hexanes/EtOAc 10: 1 to 2:1). 23 (16 mg, 44%) and 24 (8 mg, 31%) was isolated as two products.

Compound 23:

TLC (2:1 hexanes/EtOAc): l f = 0.28 (UV).

¾ NMR (400 MHz, CDCh) d 7.50 (ddd, 6.0, 2.7, 1.0 Hz, 1 H), 6.60 (ddt, - 8.2, 7.0, 1.3 Hz, 1 H), 6.32 (dd, ,/ ~ 6.0, i 8 Hz, 1 H), 5.53 - 5,43 (m, 2H), 5.41 - 5.31 (m, 2H), 3.89 (quint, J - 6.1 Hz, I H), 3.64 (t, J= 6.5 Hz, 2H), 3.45 (ddq, J = 8.4, 4.3, 2.2 Hz, 1H), 2.68 - 2.55 (m, 1H), 2,43 (ddd, J = 7.7, 6.4, 2.3 Hz, 21 1). 2.29 - 2, 11 (m, 311), 2,08 - 1 .91 (m, 4H), 1.62 -- 1.51 (m, 2H), 1.48 - 1.36 (m, 2H), 0.94 (t, J ------ 7.6 Hz, 3H), 0.88 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H).

nC NMR (101 MHz, CDCb) d 196.5, 161.8, 138.9, 135.0, 134.2, 132.7, 132.5, 125.5, 124.4, 71.7, 62.9, 43.6, 37.0, 35.3, 32.5, 30.8, 27.2, 26.0, 25.9, 20.9, 18.2, 14.3, -4,4, -4.4.

FTIR (AIR): 3429, 2956, 2928, 2856, 2361, 2327, 1702, 1652, 1580, 1472, 1360, 1251, 1213, 1066, 1 05, 968, 834, 807, 774, 721 , 668 em ^: .

HRMS (FAB ⁴ , m/z): calculated for C ₂₀ H ₄₅ O ₃ S1 1M÷H] ⁺ 433.3132, found: 433.3121.

{<¾]¾: ÷136.3° (c - 1.0, Cel-fc).

Compound 24:

TLC (2: 1 hexanes/EtOAc): RT 0.6 (UV).

Ή NMR (400 MHz, CDCh): d 7.43 (ddd, J 5,9, 2.8, 1.0 Hz, IH), 6.80 (ddt,V=== 10.8, 8.8, 1.3 Hz, IH), 6,31 (dd, J ^~ 5.9, 1.7 Hz, IH), 5.76 (q, = 9.1 Hz, IH), 5.61 (dddd, J= 11.9, 10.7, 5.2, 1.2 Hz, IH), 4.08 - 4.02 (m, IH), 3.27 (d, = 9.6 Hz, IH), 2.38 (dd, ,/= 9.5, 3.0 Hz, 2H), 2.24 (q, J = 1 1.6 Hz, 2H), 2.17 - 1 ,95 (m, 2H), 0.91 (s, 9H), 0.1 1 (s, 3H), 0.08 (s, 3H).

nC NMR (101 MHz, CDCh): d 196.4, 162.3, 141,3, 134.0, 132.4, 130.6, 129.6, 73.1, 44.2, 34.7, 34.5, 32.6, 26.0, 18.3, -4.6, -4.7.

FTIR (ATR): 2952, 2926, 2886, 2855, 2359, 2339, 1705, 1654, 1586, 1471 , 1369, 1251 , 1 190, 1077, 1039, 997, 980, 938, 855, 835, 808, 790, 774, 727, 668 era ^'1 .

HRMS (FAB ⁴ , m/z): calculated for Cigl-feThSi [M+H] ⁺ 305.1931, found: 305.1942.

[a]¾: -27.8° (e - 0.8, CHCb)

Example 6

[ 178] In a nitrogen-filled glovebox, 22 (64 mg, 0.1 8 mmol, 1.0 equiv) and 5-hexen- 1 - ol (142 mg, 1 ,42 mmol 8.0 equiv) were weighed into a 4 mL vial. THF (0.3 mL) was added to dissolve the mixture. Catalyst Mu-2 (24 mg, 20 raol%) was dissolved in THF (0.4 ml.) and 0.1 mL of this catalyst solution was transferred into the vial. The vial was sealed with a 14/20 septum and brought out of the glovebox, The reaction was stirred at 40 °C with a stream of argon (saturated with anhydrous THF) bubbling through a needle, A portion of the catalyst solution (0.1 mL) was added into the vial in each 1 hour. After all the catalyst was added, the reaction mixture was continued to stir for 4 h with argon bubbling. A few drops of ethyl vinyl ether were added, and the reaction mixture rvas concentrated in vacuo The residue was purified by column chromatography (SiC , hexanes/EtOAc 2: 1) to afford 23 (40 mg, 52%) as a colorless liquid. Compund 26 was the proposed by-product (molar ratio of 23:26 was 32:1 as determined by crude NMR analysis).

Compound 23: Characterization data w¾re in agreement with previously obtained data.

Compound 26: Characterization data not available due to the difficulty in separation, mass data was obtained by LC-MS (TOF, ES ⁺ , m/z): calculated for C^EUtChSi [M+H] ⁺ 405,2 19. found: 405.2801 .

[P9] To a stirred solution of 23 (21 ,6 mg, 0.05 mmol, 1.0 equiv) in MeCN (0.5 mL) was added NMGfi-bO (67.5 mg, 0.5 mmol, 10.0 equiv). Tetrapropylammonium perruthenate (1.8 g, 5 pmol, 0.1 equiv) was added until NMOFfiO was fully dissolved, and the reaction was stirred at 23 °C for 3 hours. The solution was diluted with Et _? .0 (5 mL), passed through a short pad of silica get concentrated and was subjected to the next reaction without further purification.

The residue was dissolved in MeCN (1.0 ml.,) and cooled to 0 °C A solution of hydrofluoric acid (48 wt % in ¾0, 0,2 mL) in MeCN (0,4 ml.,) was added dropwisely. The solution was stirred in the same temperature for 30 min before saturated NaHCOs solution (1.5 mL) and brine (1.5 mL) were added. The aqueous phase was extracted with EtOAc (5 x 5 mL). The combined organic phase was dried over magnesium sulfate, filtered and concentrated (not to dryness). The residue was purified by flash chromatography (SI0 ₂ , CH ₂ Ch/MeOH 20:1) and through

BiotageR SNAP Ultra CI S column (H ₂ 0/Me()H) to give 3 (10 mg, 60% over 2 steps) as a colorless liquid.

TLC (100% EtOAc): Rf 0.55 (IN)

Ή NMR (400 MHz, CDCh): d 7.58 (ddd, ./= 6.0, 2.6, 1.0 Hz, 1H), 6.57 (ddt, ./= 8.4, 7.0, 3.2 Hz, 1H), 6.36 (dd, J- 6.0, 1.8 Hz, !H), 5.69 - 5.60 (m, 1 II), 5.60 - 5.45 (m, 2H), 5.45 - 5.35 (m,

3H), 3.93 (quint J - 6.8 Hz, 1H), 3.50 - 3.44 (m, 1H), 2.75 (ddd, J- 13,9, 6.9, 4.4 Hz, 1H),

2.68

- 2.58 (m, 1 H), 2.49 (ddd, J - 15.2, 8.4, 7.0 Hz, 1H), 2.36 (t, J- 6.8 Hz, 2H), 2.33 - 2,28 (ra, 2H), 2.20 - 1.98 (m, 5H), 1.68 (quint, J= 7.0 Hz, 2H), 0.96 (t, J = 7.5 Hz, 3H).

¹³ C NMR (101 MHz, CDCh): d 196.4, 175.8, 163.8, 139.9, 136.4, 135.1, 131.7, 131.2, 126.3, 123.6, 71.1, 44.0, 36.3, 34.5, 32.9, 30.7, 26.6, 24,7, 20.9, 14.4,

FTIR (ATR): 3449, 3010. 2956, 2919, 2850, 1728, 1703, 1650, 1579, 1455, 1375, 1222, 1 182, 1046, 959, 838, 809, 721 em-i.

HRMS (FAB ⁺ , m/z): calc’d for C ₂₀ H ₂₉ O4 [M+Hf 333.2060, found: 333.2060.

[a]¾: +322,6° (c - 0.5, C ₆ H ₆ ).

Spectral data ( ^! H NMR, ^;3 C NMR, HRMS) matched with the published data.6 Comparisons of Ή NMR data of natural and synthetic A ¹² ~prostaglandin Jr, (3) are listed in Table S2 of J. Am . Chem. Soc.,

[180] In a nitrogen-filled giovebox, effiS-oeten-l -oI (205 mg, 1.6 mmol, 8.0 equiv) was dissolved in toluene (1 mL) in a 50 mL Schlenk flask and a solution of catalyst Ra-4 (13.6 mg,

16 g oL 1 mol%) in THF (0.6 mL) was added The Schlenk flask was sealed and brought out of the giovebox, and then connected to high vacuum. The valve was gradually opened {Caution: open slowly and stir well to avoid splashing). After 15 minutes stirring, the flask was refilled with argon and sealed, and was brought back into the giovebox. The residue was diluted with 0.5 mL THF, and an aliquot was taken for GC analysis (conversion of homodimeriza tion step was >98% by GC analysis) A solution of 28 [CAS 2254448-29-6] (46 mg, 0.2 mmol, 1.0 equiv) in 0.5 mL THF was added into the Schlenk flask and an additional 0.4 mL of catalyst solution with Ra-4 (8.5 mg, 10 mthoΐ, 5 tnol%) was added The Schlenk flask was sealed and brought out of giovebox The reaction was stirred for 12 h at 23 °C before a few drops of ethyl vinyl ether were added. The solvent was removed under reduced pressure. The residue was purified by column chromatography (SIO2, hexanes/EtOAc 2: 1). Compounds 29 (22 mg, 36%) and 36 were separated as a mixture (28 mg, molar ratio of 29:30 was 3:1 as determined by crude NMR analysis).

Compound 29: Characterization data not available due to the difficulty in separation.

Mass data was obtained by LC-MS (TOP, ESC ra/z): calc’d for C ₂₀ H ₂₉ O ₂ [M+H] 301.2162, found: 301.2080.

Compound 30: Characterization data not available due to die difficulty in separation, mass data was obtained by LC-MS (TOP, ES ⁺ , m/z): calculated for CisHjsCh [M+H] ⁴ 273.1849, found: 273.1759.

[1811 In a nitrogen-filled giovebox, 28 (23 mg, 0.1 mmol, 1.0 equiv) and 5-hexen-l-oi

(80 mg, 0.8 mmol, 8.0 equiv) were weighed into a 4 mL vial. THF (0.3 mL) was added to dissolve the mixture. Catalyst Ru-2 ( 13.6 mg, 20 mol%) was dissolved in THE (0.4 ml,) and 0.1 mL of this catalyst solution was transferred into the vial. The vial was sealed with a 14/20 septum and brought out of the giovebox. The reaction was stirred at 40 °C with a stream of argon (saturated with anhydrous THF) bubbling through a needle. A portion of the catalyst solution (0.1 ml.) was added into the vial in each 1 hour. After all the catalyst was added, the reaction mixture was continued to stir for 2 h with argon bubbling, A fe r drops of ethyl vinyl ether were added, and the reaction mixture was concentrated in vacuo . The residue was purified by column chromatography (S1O2, hexanes/EtOAc 2: 1), Compounds 29 (9,2 rng, 31 %) and 30 were separated as a mixture (12 mg, molar ratio of 29:30 was 3:1 as determined by crude NMR analysis),

Compound 29: Characterization data not available due to the difficulty in separation. Mass datawas obtained by LC-MS (TOP, ESA m/z): calc'd for CjgftsO _? . [M+H] ⁺ 273.1849, found: 273.1855.

[182] Pyridimum chlorochromate (22 mg, 0,1 mmol, 3.0 equiv) was added to a solution of 29 (mixed with by-product 39) (10 rng, 0,033 mmol, 1.0 equiv) in CH2CI2 (0,5 ml) at 23 oC, The reaction was monitored by TLC and was diluted with EfeO (3 ml.) after stirring for 3 h. The resulting solution was filtered through a short pad of silica gel and was subjected to the next step without further purification. The residue was dissolved in r-BuOfl (0.5 mL) at 23 °C, and 2- methyI-2-hutene (35 pL, 0.33 mmol, 10 equiv), a solution ofNaHzPCb'HjO (6.9 mg, 0,05 mmol, 1.5 equiv) in ¾0 (0.12 mL) and a solution of NaC10 ₂ (80 %, 5.6 mg, 0.05 mmol, 1.5 equiv) in H ₂ 0 (0, 12 ml,) was added sequentially. After stirring at 23 °C for 30 minutes, the reaction mixture was diluted with a solution of NaFfcPO^HjO (108 mg) in H _? .0 (2 mL) and extracted with EtOAc (5 x 5 mL). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. Flash column chromatography (SiO _? ., CHjCb/ eOH 20: 1) and purification through BiotageR SNAP Ultra (71 column (HjO/McOH) afforded pure compound 4 (4 mg, 0.013 mmol, 12% yield from 28) as a colorless oil. TLC (10: 1 Ci-feCb/MeOH): RC 0,44 (UV),

^! H NMR (500 MHz, CDCb): d 7.48 (ddd, J= 6.1, 2.6, 1.0 Hz, 1H), 6.96 (d, J= 11.5 Hz, 1H), 6.42 - 6.31 (m, 2H), 6.22 (dt, J= 14 9, 6.3 Hz, 1H), 5.57 - 5.S 1 (m, ! H), 5.50 - 5.43 (m, 1 H), 5.37 (dtt, J= 30.1, 6.8, 1.7 Hz, 2H), 3.64 -- 3.55 (m, 1 H), 2.98 (1, J - 6.8 Hz, 2H), 2.60 (dt, J ·· 12.3, 5.9 Hz, Hi), 2.43 - 2.25 (m, 3H), 2.12 - 2.00 (m, 4H), 1.69 (quint, J = 7.4 Hz, 2H), 0.99 (t, J 7,5 Hz, 3H).

nC NMR (101 MHz, CDCb): d 197.6, 176.6, 160.9, 144.5, 135.5, 335.5, 134.2, 13 1.6, 131,5, 126.1, 125.8, 124.6, 43,6, 33,0, 31.2, 30.9, 26.7, 24.6, 20.7, 14.3.

FTIR (ATR): 3010, 2960, 2926, 2874, 2854, 1710, 1693, 1626, 1578, 1512, 1455, 1208, 1154, 1087, 1024, 977, 817, 728 cmC

1-IRMS (FAB+, ml·/): cak’d for C20H27O3 [M+H] ⁺ 315.1955, found: 315.1968.

[a]¾: -H 29.6 ⁰ (c - 0.07, C ₆ Hg),

Spectral data ( ^f H NMR, ^!3 C NMR, FIRMS) matched with the published data:

Nieoiaou, K. C,; Pukskuri, K. K,; Rigol, S.; Heretsch, P.; Yu, R.; Grove, C. L; Hale. C. R.

H.; ElMarrouni, A.; Fetz, V.; Bronstrup, M.; Aujay M.; Sandoval J,; Gavriiyuk J.

Synthesis and Biological Investigation of A ⁱ² ~Prostaglandin J3 (A ^{f 2} -PCs.b) Analogues and Related Compounds. J Am. Chem. Sec. 2016, 138, 6550-6560.