DESCRIPTION

SYNTHESIS OF PENTAFLUOROSULFANYL (SFs)-SUBSTITUTED HETEROCYCLES AND ALKYNES

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application Serial No. 60/781,817, filed March 13, 2006, the disclosure of which is hereby incorporated by reference in its entirety.

BACKGROUND OF INVENTION

There is currently great interest in methods for the preparation of selectively fluorinated organic compounds. This interest results from the profound influence that fluorine incorporation can have on the physical properties, chemical properties, and biological activity of molecules. For example, methods for putting the bulky, highly electronegative and generally inert trifluoromelhyl group into organic compounds have received much research attention during recent years.

Another fluorinated substituent that could attract interest among synthetic organic chemists is the pentafluorosulfanyl (SF ₅ ) group (Winter et al, Inorganic Fluorine Chemistry - Toward the 21st Century (1994) 555:128-47, Pub: American Chemical Society:

Washington (Thrasher, J. S., Strauss, S. H., Eds.); Lentz et al , Chemistry of Hypervalent

Compounds (1999) 295-326; Pub: Wiley-VCH: New York (Akiba, K., Ed.); Verma et al ,

Advances in Inorganic Chemistry (1994) 41 : 125-69, Pub: Academic Press: San Diego

(Sykes, A. G., Ed.); pentafluorosulfanyl groups bear some similarity to trifluoromethyl groups, however, SF ₅ is more electronegative (σ _p = +0.68 versus +0.54 for CF ₃ ; Sheppard,

W. A., J. Am. Chem. Soc. (1962) 84:3072-6) and more sterically demanding.

However, until the development of the subject invention, many methods required the use of elemental F ₂ or oxidative fluorination by AgF ₂ (Sheppard, W. A., J. Am. Chem. Soc. (1962) 84:3064-3072; Chambers et al.. Chem. Commun. (1999) 883-884; Bowden et al, Tetrahedron (2000) 56:3399-3408; Sipyagin et al. , J. Fluorine Chem. (2001) 1 12:287-295) to incorporate an SF ₅ group into aliphatic compounds (that is, the methodologies relied on high pressure autoclave or specialized photochemical procedures) (Case et al, J. Chem. Soc.

(1961) 2066-2070; Wessel et al., Chem. Ber. (1983) 116:2399-2407; Winter et al, J. Fluorine Chem. (1994) 66: 109-116; Fokin ef α/. , Russ. Chem. Bull. (1996) 45:2804-6). U.S. Patent No. 6,919,484 provided methods for incorporating an -SF ₅ group into alkanes, alkenes, and aromatics by condensing SF ₅ CI into a hexane solution that also contains the alkane, alkene, or aromatic of interest. However, the introduction SF5 into alkynyl and heterocyclic compounds has not been widely practiced by synthetic organic chemists.

SF ₅ CI is presently the only commercially available "reagent" that can be used to introduce the SF ₅ substituent into aliphatic compounds. As a gaseous pseudo halogen, this reagent cannot be used as an electrophilic source of SF ₅ . It has, however, been used in free radical chain alkene/alkyne addition processes (Sidebottom et al. , Trans. Faraday Soc. (1969) 65:2103-2109). These processes are generally done thermally, in an autoclave, with or without an initiator, or using room temperature gas phase or low temperature solution phase photochemical processes. For example (Case et ah, J. Chem. Soc. (1961) 2066-2070):

SF ₅ CI 9O ⁰ C ₁ I O h

+ - SF ₅ CH ₂ CHCICH ₃ autoclave CH ₂ =CHCH ₃ 78%

In order for SFs-derivatives to become incorporated into the day-to-day strategic planning of working synthetic organic chemists, a convenient bench-top procedure for the introduction of SF ₅ substitucnts into organic substrates is needed. The subject invention provides such a method - one that will allow convenient addition of SF ₅ CI to a large variety of heterocyclic and alkynyl compounds in excellent yield.

BRIEF SUMMARY OF THE INVENTION

One aspect of the subject invention relates to novel pentafluorosulfanyl containing compounds. Specifically, the subject invention relates to pentafluorosulfanyl substituted heterocycles, alkynes, and intermediate products of the processes of the subject invention along with analogues of each of the aforementioned compounds. Exemplary compounds of the subject invention include, without limitation, 3 -pentafluorosulfanyl furan, 2-methyl-4- pentafluorosulfanylfuran, 3-pentafluoro-sulfanyl-4-butylfuran, 3-phenyl-4- pentafluorosulfanyl-5-butyl-isoxazole, 2,3-diphenyl-4-pentafluorosulfanyl-5- butylisooxazoline, 3 ,5-diphenyl-4-pentafluorosulfanylisooxazole, 4-pentafluorosulfanyl-

2,3,4-tripenyl-4-isooxazoline, and 2-butyl-3-pentafluorosulfanylbicyclo[2.2.1 ]hepta-2,5- diene.

Another aspect of the subject invention pertains to processes used to synthesize heterocycles and alkynes substituted with a pentafluorosulfanyl group along with any pentafluorosulfanyl substituted intermediate products of the subject processes.

DETAILED DISCLOSURE OF THE INVENTION

The subject invention provides pentafluorosulfanyl (SF ₅ ) substituted heterocyclic and alkynyl compounds, their analogues, and processes for their preparation.

The simplicity of the new processes provided by the subject invention, combined with the generally excellent yields that are obtained, constitutes a breakthrough in SF ₅ synthetic methodology that opens the door to the convenient, bench top preparation of a multitude of SF ₅ -containing heterocyclic and alkynyl compounds by synthetic organic chemists. Thus, the subject invention has application to broad applicability to any compound containing heterocyclic or alkynyl groups, including functionalized or substituted compounds.

Compounds of the subject invention include, without limitation,: compound (1):

compound (2):

FsS- -R 11 ; or

compound (3):

; or

compound (4):

compound (5):

wherein R ₆ , R ₇ , Rs, Rn, R12, Ro, R14, R15, Ri6, and R _{! 7} are, independently, hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, substituted or unsubstituted substituted or unsubstituted trialkylsilyl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen.

In a specific embodiment, R ₆ , R ₇ , and Rs of compound (1) are each hydrogen. In yet another specific embodiment, R ₆ and Rg of compound (1) are each hydrogen while R ₇ is an unsubstituted alkyl group, preferably a methyl group.

In a specific embodiment for compound (2), Ru is hydrogen, substituted or unsubstituted substituted or unsubstituted trialkylsilyl, an unsubstituted alkyl, preferably butyl, or an unsubstituted aryl, preferably a phenyl group.

R _H and R] ₂ of compound (3) are each hydrogen in one embodiment. In yet another embodiment, Rn and Ri ₂ have the same substituent group, preferably hydrogen, substituted or unsubstituted trialkylsilyl, or an unsubstituted or substituted alkyl or aryl, more preferably butyl or phenyl. In another specific embodiment, Rn and Rn are each different substituents.

For example, Ri j is an unsubstituted alkyl group or substituted or unsubstituted trialkylsilyl, and Ri ₂ is an unsubstituted phenyl group, or vice versa.

Regarding the substituents of compound (4) of the subject invention, Rn and R ₁₂ have the same substituent group, and Rn has a different subslituent group in one embodiment. For example, Rn and R ₁₂ may each be substituted or unsubstituted trialkylsilyl. an unsubstituted or substituted alkyl, and R1 ₃ may be hydrogen. Preferably, Ru and R ₁₂ are each substituted or unsubstituted trialkylsilyl, butyl or phenyl, and R _B is hydrogen. In another specific embodiment, Rn, Rj ₂ , and Rj ₃ are each different substituents. For example, Rn is an unsubstituted alkyl group or substituted or unsubstituted trialkylsilyl, Ri 2 is an unsubstituted phenyl group, and R) ₃ is hydrogen, or Ru is phenyl or substituted or unsubstituted trialkylsilyl, Ri ₂ is alkyl, and Rj ₃ is hydrogen. In yet another specific embodiment, Rn and R ₁₃ may be the same substituent, and Ri ₂ may be different. R] ₂ and Ri ₃ may be the same substituent, and Ru may be a different substituent in another embodiment.

Preferably, Rn of compound (5) is hydrogen, substituted or unsubstituted trialkylsilyl, an unsubstituted alkyl, preferably butyl, or an unsubstituted aryl, preferably a phenyl group, and Ri ₄ , R ₁₅ , Rj ₆ , and Rn are each hydrogen.

As used herein, the term "substituted" is used to refer to a functional group substituent like a halogen, an aliphatic chain, an aryl, a ketone, an ether, a hydroxy, an alkoxy, an amino, an aldehyde, a carboxyl group, a phosphate, or a thio. In a specific embodiment, the preferred compounds include 3- pentafluorosulfanylfuran, 2-methyl-4-pentafluorosulfanylfuran, 3-pentafluoro-sulfanyl-4- butylfuran, 3-phenyl-4-pentafluorosulfanyl-5-butyl-isoxazole, 2,3-diphenyl-4- pentafluorosulfanyl-5-butylisooxazoline, 3,5-diphenyl-4-pentafluorosulfanylisooxazole, 4- pentafluorosulfanyl-2,3,4-tripenyl-4-isooxazoline, and 2-butyl-3- pentafluorosulfanylbicyclo[2.2.1]hepta-2,5-diene.

Another aspect of the subject invention is directed to the synthesis of the compounds of the subject invention. In one embodiment, an SF ₅ substituted alkene is converted to an SF ₅ substituted alkyne, as shown below in Scheme I,

SCHEME I

wherein Scheme I takes place in the presence of DMSO and lithium hydroxide monohydrate. The SFs substituted alkene is prepared according to the methods of U.S. Patent 6,919,484, which is herein incorporated by reference in its entirety. Rn is a substituent selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen. In one specific embodiment, Rn is a butyl group or substituted or unsubstituted trialkylsilyl. In yet another specific embodiment, Rn is a phenyl group. In another embodiment, Rn is hydrogen.

The elimination reaction of Scheme I includes contacting the substituted or substituted alkenyl compound with lithium hydroxide monohydrate. The contacting between the two reagents can be enhanced by stirring the mixture for a sufficient amount of time for the reaction to initiate and in some instances, proceed to completion or equilibrium. In a preferred embodiment, the mixture is stirred for about 2 hours. In one embodiment, the contacting step advantageously takes place at room temperature (typically about 20 ⁰ C to about 23 ⁰ C).

The processes of the subject invention also pertain to reacting the SF ₅ substituted alkynyl prepared in Scheme I with the appropriate rcactants and/or at least one radical initiator to prepare SF5 substituted azole, azoline, bridge ring, or furan compounds. An azole compound (3) of the subject invention is prepared by contacting a solution of an SF ₅ substituted alkyne in a solvent, preferably tetrahydrofuran, with a Ri ₂ substituted hydroxyiminoyl chloride and at least one radical initiator as shown in Scheme II,

SCHEME II

wherein Rn and Ri ₂ are substituents independently selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl,

disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen. Rn and Ri ₂ are preferably and independently hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, preferably butyl, or unsubstituted aryl, preferably phenyl.

The radical initiator is selected from a group consisting of dialkylboranes, trialkylboranes, Et ₃ N, Et ₃ N-IiHF, and 9-boracicyclo[3.3.1.]nonane, and mixtures of any of the foregoing. Preferably, the initiator is Et ₃ N, which is added to the alkynyl/Ri ₂ substituted hydroxyiminoyl chloride solution in a dropwise fashion. In one embodiment, when the initiator is Et ₃ N, then it is combined with a solvent to form a solution before addition to the reaction mixture. The preferred solvent for an Et ₃ N solution is tetrahydrofuran (THF).

The contacting step is optionally enhanced by stirring or other forms of mixing for a sufficient amount of time for the reaction to initiate, or in some instances, to proceed to completion or to equilibrium. In one embodiment, additional amounts of both the Rj ₂ substituted hydroxyiminoyl chloride and the Et ₃ N initiator are added periodically. For example, additional amounts are added at the sixteen and the twenty hour marks. Advantageously, the processes for producing SF ₅ substituted azole compounds takes place at room temperature (about 20 ⁰ C to about 23 ⁰ C).

The processes of the subject invention also pertain to the synthesis of an SF ₅ substituted furan compound from an SF ₅ substituted alkyne as shown in Scheme III,

SCHEME III

, which takes place in the presence of an azole compound, preferably 4-phenyloxazole, and heat. Rn, Ri ₈ , and Rj ₉ are each substituents independently selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether,

ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen. Preferably, R] ₈ and R^ are each hydrogen. The preferred Rn substituent is hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, preferably butyl, or unsubstituted aryl, preferably phenyl.

In one embodiment, the reaction mixture of the SF ₅ substituted alkyne and the azole compound are heated to a temperature between about 170 ⁰ C to about 200 ⁰ C, preferably about

180 ⁰ C and about 190 ⁰ C. The heated temperature is maintained for a sufficient amount of time for the reaction to proceed to completion or equilibrium, preferably about 20 hours.

Another aspect of the processes of the subject invention pertains to the synthesis of SF ₅ substituted compounds like compound (4) of the subject invention. As illustrated in Scheme IV, the subject method advantageously utilizes the SF ₅ substituted alkyne (compound

(2)) produced by Scheme I. Preferably, the SF ₅ substituted alkyne (compound (2)) is in solution with a solvent preferably, tetrahydrofuran. This embodiment of the processes of the subject invention comprises contacting a solution of compound (2) in a solvent, preferably tetrahydrofuran, with an R1 ₂ , Rn-disubstituted aniline N-oxide and stirring at room temperature (about 20 ⁰ C to about 23 ⁰ C) for a sufficient period of time to initiate a reaction . or in some instances, until the reaction reaches completion or equilibrium. Preferably, the reaction mixture is stirred for about 16 hours. Scheme IV is illustrated below:

SCHEME IV.

RiI, R12, and R13 are substituents independently selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl. unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen. Rn and Ri ₂ have the same substituent group, and R13 has a different substituent group. For example, Rn and Ri ₂ may each be substituted or unsubstituted trialkylsilyl or an unsubstituted or substituted alkyl, and

Ri ₃ may be a hydrogen. Preferably, R ₁₁ and Ri ₂ are each butyl or phenyl, and R ₁₃ is hydrogen. In another specific embodiment, Rn, R12, and R ₁₃ are each different substituents. For example, Rn is an unsubstituted alkyl group or substituted or unsubstituted trialkylsilyl, Ri ₂ is an unsubstituted phenyl group, and R ₁₃ is hydrogen, or Rj ₁ is phenyl or substituted or unsubstituted trialkylsilyl, R] ₂ is alkyl, and Rj ₃ is hydrogen. In yet another specific embodiment, R _{1 1} and R ₁₃ may be the same substituent, and Ri ₂ may be different. R ₁₂ and R ₁₃ may be the same substituent, and Rn may be a different substituent in another embodiment.

Compound (5) of the subject invention is synthesized by Scheme V of the processes of the subject invention. Briefly, an SF ₅ substituted alkyne is reacted under heat with a substituted or unsubstituted cyclopentiadiene. In one embodiment, the reaction mixture is heated to a temperature within the range of 100 ⁰ C to about 130 ⁰ C, preferably about 120 ⁰ C, and maintained at that temperature for a sufficient period of time for the reaction to initiate and in some instances, proceed to completion or equilibrium.

SCHEME V

Rn, Ri4, R1 ₅ , R] ₆ , and Rn, are each independently selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen. Preferably, Rn of compound (5) is hydrogen, substituted or unsubstituted trialkylsilyl, an unsubstituted alkyl, preferably butyl, or an unsubstituted aryl, preferably a phenyl group, and Rj ₄ , R ₁₅ , R ₁₆ , and Rj ₇ are each hydrogen. The processes of the subject invention also pertain to synthesizing SF ₅ substituted furans using bridged ring compounds as the reactants. In another embodiment, bridged ring compounds, wherein the two rings have two atoms in common, are mixed with SF ₅ CI gas at

a depressed temperature, for example, about -40 ⁰ C. The method also comprises contacting the bridged ring compounds and SF ₅ Cl with one or more radical initiators. The radical initiators are selected from a group consisting of dialkylboranes, trialkylboranes, Et ₃ N, Et ₃ N- nHF, and 9-boracicyclo[3.3.1.]nonane, and mixtures of any of the foregoing. Preferably, the initiator is Et ₃ B. In a preferred contacting step, the radical initiator is added to the reaction mixture in a dropwise manner. Optionally, additional amounts of SF ₅ CI and/or Et ₃ B are periodically added to the reaction mixture.

A suitable bridge ring compound useful as a reactant in this embodiment of the subject processes is:

wherein R ₁ -R ₅ are each substituents independently selected from hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen. In a one embodiment, Ri-R ₅ are each hydrogen. λn enantiomeric mixture of the first intermediate SF ₅ substituted compound shown below is prepared:

wherein Rig is Cl or SF ₅ , Ri ₉ is Cl or SF ₅ , and R] ₈ and Rj ₉ are not the same substituent; and wherein R ₂ o, R21, and R22 are each independently hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes,

cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen.

The resulting SF ₅ substituted intermediate product undergoes further reaction with lithium hydroxide monohydrate in the presence of DMSO, thereby eliminating the halogen substituent on either R ₁₈ and R ₁₉ . This elimination takes place advantageously at room temperature (about 20 ⁰ C to about 23 ⁰ C) and involves the adequate mixing of the intermediate products and the additional reagents. Preferably, the mixing mechanism is stirring. The resulting second intermediate SF ₅ substituted intermediate product is:

wherein Rj ₈ is hydrogen or SF ₅ , R ₁₉ is hydrogen or SF ₅ , and R ₁₈ and Ri ₉ are not the same substituent. R ₂ o, R ₂₁ , and R ₂₂ each remain independently hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen.

The second intermediate SF ₅ substituted product is further processed with a heat treatment, thereby converting the bridge ring compound to a furan compound (1) of the subject invention, followed by a cooldown to room temperature (about 20 ⁰ C to about 23 ⁰ C). The various enantiomeric forms of the compounds and intermediate compounds of the subject invention may be isolated according to methods well known to the skilled artisan.

Optionally, the SF ₅ substituted compounds and intermediate products prepared according to the processes of the subject invention can undergo neutralization, extraction, washing, purification, and/or distillation using techniques known in the art. Preferably, any neutralization is performed with the addition of a sufficient amount of sodium bicarbonate

(HNaCO ₃ ) or acid, preferably hydrochloric acid (I ICl). Any drying is preferably performed over a suitable desiccant. for example, MgSO ₄ . The compounds may be purified by passing through a separation column, for example, a silica gel column, to remove contaminants like unreacted reagents and intermediate products. Purity and/or analysis of the compounds of the

subject invention may be determined using techniques known in the art including without limitation NMR analysis. For the intermediate products, any neutralization, extraction, washing, purification, and/or distillation takes place before the next reaction sequence. In the above-described compounds and intermediate products of the subject invention, bond line notation has been used. Thus, the skilled artisan would understand that although not always depicted, hydrogen atoms are present in an amount to satisfy the requirement that each carbon atom has four bonds.

The terms "comprising", "consisting of, and "consisting essentially of are defined according to their standard meaning and may be substituted for one another throughout the instant application in order to attach the specific meaning associated with each term.

As used in this specification and the appended claims, the singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "an alkyne" includes more than one such alkyne, a reference to "the method" includes more than one such method, and the like.

The subject invention also provides the following non-limiting embodiments:

1. A compound selected from: compound (1):

compound (2):

FsS- -R 11 or

compound (3):

compound (4):

compound (5):

wherein R^, R ₇ , R ₈ , Rn, Ri ₂ , R13, Ru, Ris, Ri ₆ , and Rj ₇ are, independently, hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; with the proviso that compound (2) excludes:

1) compounds of the formula: R

R'- -Si- -SF,

R" or liquid crystals thereof; wherein: i) substituents R, R ¹ , and R" arc selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, or combinations thereof and at least one of the substituents is hindered; ii) R, R', or R" comprises an alkyl and at least one of the substituents is hindered; iii) at least one of R, R ¹ , or R" comprises t-butyl and at least one of the substituents is hindered;

iv) R and R' comprises CH ₃ and R" comprises t-butyl and at least one of the substituents is hindered; v) at least one of R, R', or R" comprises isopropyl and at least one of the substituents is hindered; and/or vi) the molecular weight of the compound ranges from about 225 to about 800 or about 225 to 400; or

2) compounds or liquid crystals thereof comprising: i) a sulfurpentafluoride group and a substituted silyl group having substituents selected from the group consisting of an alkyl. a substituted alkyl, an aryl, a substituted aryl, or combinations thereof and at least one of the substituents is hindered, wherein the substituted silyl group is bonded to the sulfurpentafluoride group by a C--C triple bond; ii). a sulfurpentafluoride group and a substituted silyl group having substituents selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, or combinations thereof and at least one of the substituents is hindered, wherein the substituted silyl group is bonded to the sulfurpentafluoride group by a C--C triple bond and wherein at least one of the substituents comprises an alkyl group; iii) a sulfurpentafluoride group and a substituted silyl group having substituents selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, or combinations thereof and at least one of the substituents is hindered, wherein the substituted silyl group is bonded to the sulfurpentafluoride group by a C-C triple bond and wherein at least one of the substituents comprises t-butyl; iv) a sulfurpentafluoride group and a substituted silyl group having substituents selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, or combinations thereof and at least one of the substituents is hindered, wherein the substituted silyl group is bonded to the sulfurpentafluoride group by a C-C triple bond and at least one of the substituents comprises CH ₃ ; v) a sulfurpentafluoride group and a substituted silyl group having substituents selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, or combinations thereof and at least one of the substituents is hindered, wherein the substituted silyl group is bonded to the sulfurpentafluoride group by a C--C triple bond and wherein at least one of the substitutents comprises isopropyl; and/or vi) a sulfurpentafluoride group and a substituted silyl group having substituents selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl,

or combinations thereof and at least one of the substituents is hindered, wherein the substituted silyl group is bonded to the sulfurpentafluoride group by a C-C triple bond;

2. A compound according to embodiment 1, wherein said compound is compound (1) and R ₆ , R ₇ , and Rg are each hydrogen, R ₆ and Rg are each hydrogen and R ₇ is an unsubstituted alkyl group;

3. A compound according to embodiment 1, wherein said compound is compound (2) and: a) R _H is hydrogen, substituted or unsubstituted trialkylsilyl, an unsubstituted alkyl, or an unsubstituted aryl, or a phenyl group; or b) R _H and R ₁₂ are each, independently, hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen;

4. A compound according to embodiment 1, wherein said compound is compound (3) and: a) Rn and R ₁₂ are each, independently, hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; b) R _H and R] ₂ are each hydrogen; c) Rn and Rn are the same substituent group and are selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen;

d) Ru and Ri ₂ have the same substituent group selected from hydrogen, substituted or unsubstituted trialkylsilyl, an unsubstituted or substituted alkyl or an unsubstituted or substituted aryl; e) Rn and Ri ₂ have the same substituent group selected from butyl or phenyl; f) Rn and Ro are each different substituents selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; or g) Rn and Ri ₂ are each different substituents and are selected from an unsubstituted alkyl group, substituted or unsubstituted trialkylsilyl, or an unsubstituted aryl group;

5. A compound according to embodiment 1, wherein said compound is compound (4) and : a) Rn and Rn have the same substituent group selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen and Rn is different than Rn and Rj ₂ and is selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; b) Rn, Rj ₂ and Rj ₃ are each different and are, independently selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl,

substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; c) Rn and Ri ₂ are the same and are selected from substituted or unsubstituted trialkylsilyl, an unsubstiluted or substituted alkyl and Rn is hydrogen; d) Rn and Ri ₂ are substituted or unsubstituted trialkylsilyl, butyl or phenyl and R^ is hydrogen; e) Rn, R ₁₂ , and Ri ₃ are each different substituents and are selected from an unsubstituted alkyl group, substituted or unsubstituted trialkylsilyl, an unsubstituted phenyl group or hydrogen; f) Rn is an unsubstituted alkyl group or substituted or unsubstituted trialkylsilyl, Ri ₂ is an unsubstituted phenyl group, and Rn is hydrogen; g) Rn is phenyl or substituted or unsubstituted trialkylsilyl, R] ₂ is alkyl, and Ri ₃ is hydrogen; h) Rn and Ro have the same substituent group selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen and Ri ₂ is different than Ri ₁ and Rn and is selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; or i) Ri ₂ and R ₁₃ have the same substituent group selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl,

unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen and Rn is different than Rj ₂ and Rj ₃ and is selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl. cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; 6. A compound according to embodiment 1, wherein said compound is compound (5) and: a) R] ], Ri ₄ , Ri ₅ , Rj ₆ , and Rn are each are, independently, hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; or b) Rn is hydrogen, substituted or unsubstituted trialkylsilyl, an unsubstituted alkyl or an unsubstituted aryl and R _H , R _{J 5} , Ri ₆ , and Rn are each hydrogen;

7. A compound according to embodiments 1-6, wherein a substituted substituent is substituted with a halogen, an aliphatic chain, an aryl, a ketone, an ether, a hydroxy, an alkoxy, an amino, an aldehyde, a carboxyl group, a phosphate, or a thio group; 8. A compound according to embodiment 1, wherein said compound is 3- pentafluorosulfanylfuran, 2-methyl-4-pentafluorosulfanylfuran, 3 -pentafluoro-sulfanyl-4- butylfuran, 3-phenyl-4-pentafluorosulfanyl-5-butyl-isoxazole, 2,3-diphenyl-4- pentafluorosulfanyl-5-butylisooxazoline, 3,5-diphenyl-4-pentafluorosulfanylisooxazole, 4- pentafluorosulfanyl-2,3,4-tripenyl-4-isooxazoline or 2-butyl-3- pentafluorosulfanylbicyclo[2.2.1 ]hepta-2,5-diene;

9. A method of making a compound according to embodiments 1-8 comprising: a) contacting an SF ₅ substituted alkene with lithium hydroxide monohydrate in the presence of DMSO to form an SF ₅ substituted alkyne,

1

SCHEME I wherein Rn is a substituent selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; b) contacting a SF ₅ substituted alkynyl or alkyne with reactants and/or at least one radical initiator to form SF ₅ substituted azole, azoline, bridge ring or furan compounds,

SCHEME II

wherein Rn and Ri ₂ are substituents independently selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen. Rn and Ri ₂ are preferably and independently hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, preferably butyl, or unsubstituted aryl, preferably phenyl and the radical initiator is selected from the group consisting of dialkylboranes, trialkylboranes, Et ₃ N, Et ₃ N-IiHF, and 9- boracicyclo[3.3.1.]nonane, and mixtures thereof; c) contacting an SF ₅ substituted alkyne with an azole compound to form a SF ₅ substituted furan compound,

SCHEME III wherein Rn, Rj ₈ , and Rig are each substituents independently selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; d) contacting a SF ₅ substituted alkyne with an R] ₂ , Rπ-disubstituted aniline N- oxide to form a compound of structure (4),

SCHEME IV

wherein Rn, R] ₂ , and Ro are substituents independently selected from hydrogen, substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; e) contacting a SF ₅ substituted alkyne with a substituted or unsubstituted cyclopentiadiene and heating the mixture to form a compound of structure (5),

SCHEME V

wherein Rn, R _H , R _{I 5} , Ri ₆ ,and Rn, are each independently selected from hydrogen,

K) substituted or unsubstituted trialkylsilyl, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; or f) contacting bridged ring compounds, wherein the two rings have two atoms in

15 common, with SF ₅ CI gas and an initiator to form a SF ₅ substituted furan, said initiator being selected form selected from dialkylboranes, trialkylboranes, Et ₃ N, Et ₃ N-nHF, and 9- boracicyclo[3.3.1.]nonane, or mixtures thereof;

10. A method according to embodiment 9, wherein said bridged ring compound is:

wherein R1-R5 are each substituents independently selected from hydrogen, unsubstituted

25 alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen;

11. A method according to embodiment 9, wherein said method of making a SF ₅

30 substituted furan forms an intermediate compound of the formula:

wherein Rj s is Cl or SF ₅ , R ₁₉ is Cl or SF ₅ ; and R ₁₈ and R ₁₉ are not the same substituent; and wherein R ₂₀ , R21, and R ₂₂ are each independently hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkencs, cyclodialkcnes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen;

12. A method according to embodiment 11 wherein said first intermediate product is contacted with lithium hydroxide monohydrate in the presence of DMSO to eliminate the halogen substituent on either Ri ₈ and R ₁₉ to form a second intermediate product of formula:

wherein Ri ₈ is hydrogen or SF ₅ , Ri ₉ is hydrogen or SF ₅ , Rj ₈ and R ₁₉ are not the same substituent and R20, R21, and R ₂₂ each remain independently hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen;

13. A method according to embodiment 12, further comprising heating said second intermediate compound to form compound (1);

14. A method according to embodiments 9-13, further comprising the separation or isolation of enantiomers of said compounds;

15. A method according to embodiments 9-13, further comprising the separation or isolation of intermediate compounds formed in said method;

16. A method according to embodiment 15, further comprising the separation or isolation of enantiomeric forms of said intermediate compounds; or

17. A compound of the following formula:

wherein R^ is Cl or SF ₅ , Ri ₉ is Cl or SF ₅ ; and Rig and R ₁₉ are not the same substituent; and wherein R _2O , R ₂ i, and R ₂₂ are each independently hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, hydroxy, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen; or

wherein Rig is hydrogen or SFs, Ri9 is hydrogen or SF ₅ , R ₁₈ and R ₁₉ are not the same substituent and R20, R ₂ 1, and R ₂₂ each remain independently hydrogen, unsubstituted alkyl, substituted alkyl, unsubstituted alkenyl, disubstituted alkenyl, substituted alkenyl, unsubstituted alkynyl, substituted alkyl, unsubstituted aryl, substituted aryl, cycloalkanes, cycloalkenes, cyclodialkenes, alkoxy, ether, ketone, carboxyl, aldehyde, amino, thio, phosphate, or halogen.

All patents, patent applications, provisional applications, and publications referred to or cited herein are incorporated by reference in their entirety, including all figures and tables, to the extent they are not inconsistent with the explicit teachings of this specification.

Following are examples which illustrate procedures for practicing the invention. These examples should not be construed as limiting. All percentages are by weight and all solvent mixture proportions are by volume unless otherwise noted.

EXAMPLE 1— SYNTHESIS OF 3 -PENT AFLUOROSULF ANYLFURAN

1 2a 2b

To a solution of 1 (2.2g, 18.16mmol) in dry CH ₂ Cl ₂ (20ml) was added SF ₅ Cl gas(8.1g, 2.7 equiv.) at -40 ⁰ C. 0.26ml(0.1 equiv.) of BEt ₃ (triethylborane) was added drop wise to the mixture over 30 minutes at -40 ⁰ C. After stirring for 2 hours at a temperature between -40 ⁰ C to -3O ⁰ C, extra SF ₅ Cl gas(2.0g, 0.67 equiv.) was added to the reaction mixture at -4O ⁰ C, and then 0.26ml of BEt ₃ was added to the mixture dropwise over 30 minutes at - 4O ⁰ C. The reaction mixture was stirred for 2 hours at a temperature between -4O ⁰ C to -3O ⁰ C, and then left in a freezer (-25 ⁰ C) overnight. The resultant mixture was poured into ice water, neutralized with NaIICO ₃ , and extracted twice with CH ₂ Cl ₂ . The organic layers were combined, washed with brine, and dried over MgSθ ₄ . The solvent was removed under reduced pressure.

The crude product was purified by silica gel column chromatography (elution with n- Hexane/Ethyl acetate=4/l). 4.4g of a mixture of 2a and 2b (2a : 2b = 2 : 1) was obtained (86% ), and the mixture had the following characteristics: 2 (2a:2b=2: l); ¹ H NMR, δ 2.10-2.38 (m, 2a; 2H, -CH ₂ - and 2b; IH, -CH ₂ -), 2.77 (dd, 2b; IH, -CH ₂ -, J=13.5, 9.0 Hz), 2.91 (dd, 2b; IH, -CH(CN)-, J=9.0, 3.9 Hz), 3.53 (dd, 2a; IH, - CH(CN)-, J=8.7, 5.1 Hz), 3.74-3.90 (m, 2a; IH, -CII(SF ₅ )- and 2b; IH, -CH(SF ₅ )-) 4.72 (t, 2b; I H, -CHCl-, J=5.1 Hz), 4.76 (dd, 2a; IH, -CHCl-, J=5.1 Hz), 4.87 (t, 2b; IH, bridge-CFI-, J=5.3 Hz), 4.96 (d, 2a; IH, bridge-CH-, J=5.3 Hz), 5.27 (d, 2a; IH, bridge-CH-, J=5.3 Hz), 5.32 (s, 2b; IH, bridge-CH-); ¹⁹ F NMR, 5 58.9 (d, 2a; 4F, J=I 52Hz), 59.6 (d, 2b; 4F, J=153Hz), 81.3 (p, 2b; IF, J=153Hz), 81.5 (p, 2a; IF, J=I 52Hz)

2a 2b 3a 3b

To a solution of 2 (2a : 2b = 2: 1, 1.Og, 3.52mmol) in DMSO (60ml) was added LiOH-H ₂ O (0.74g, 17.6mmol) at room temperature. The mixture was stirred for 1 hour at room temperature. The resultant mixture was poured into ice-water, neutralized with NaHCO ₃ , and extracted twice with ethyl acetate. The organic layers were combined, washed with water and brine, and then dried over MgSO ₄ . The solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography (elution with n-Hexane/Ethyl acetate=4/l). 0.54g of 3a and 0.3Og of 3b were obtained (96%), and the mixture of 3a and 3b had the following characteristics:

3a; ¹ H NMR, δ 2.1 1 (dd, IH, -CH ₂ -, J=12.0, 8.4 Hz), 2.29 (dt, IH, -CH ₂ -, J=12.0, 4.0 Hz), 2.67 (dd, IH, -CH(CN)-, J=8.4, 4.0 Hz), 5.36 (s, IH, bridge-CH-), 5.37 (d, IH, bridge-CH-, J=4.0), 6.74 (s, IH, -CH=C(SF ₅ )-); ¹⁹ F NMR, 6 65.9 (d, 4F, J=I 6 IHz), 80.2 (p, IF, J=I 61Hz); ¹³ C NMR, δ 27.6, 31.5, 79.1, 81.9, 120.5, 135.0, 161.2

3b; ¹ H NMR, δ 1 .99 (dd, I H, -CH ₂ -, J=12.0, 8.7 Hz), 2.26-2.40 (m, IH, -CH ₂ -), 2.78 (dd, IH, -CH(CN)-, J=8.7, 3.9 Hz), 5.32 (bs, IH, bridge-CH-), 5.44 (s, IH, bridge-CH-, J=4.0), 6.87 (s, IH, -CH=C(SF ₅ )-); ¹⁹ F NMR, δ 66.2 (d, 4F, J=161Hz), 80.2 (p, IF, J=161Hz); ¹³ C NMR, δ 28.2, 31.1, 79.0, 81.8, 120.5, 139.0, 157.8

2.86g of a mixture of 3 (3a : 3b = 2 : 1) was heated in a sealed tube at a temperature between 150 ⁰ C to 16O ⁰ C for 30 minutes. The reaction mixture was cooled to room temperature. The reaction mixture contained 1.6g (71%) of 3-pentafluorosulfanylfuran, as determined by NMR. The reaction mixture was purified by silica gel column chromatography

(elution with n-pentane). 1.4Og of 3-pentafluorosulfanylfuran was obtained (57%), and it had the following characteristics:

3-pentafluorosulfanylfuran; ¹ H NMR, δ 6.67 (m, IH), 7.42 (s, IH), 7.84 (s, IH); ¹⁹ F NMR, δ 70.4 (d, 4F, J=I 65Hz), 82.4 (p, IF, J=165Hz)

EXAMPLE 2— SYNTHESIS OF 2-METHYL-4-PENTAFLUOROSULF ANYLFURAN

To a solution of a mixture of 4 (4a:4b=4: l, 1.Og, 7.4mmol) in dry CH ₂ Cl ₂ (10ml) was added SF ₅ Cl gas (5.4g, 4.5 equiv.) at a temperature between -40 ⁰ C to -5O ⁰ C. 0.1ml (0.1 equiv.) of BEt ₃ was added dropwise to the mixture over 30 minutes at -4O ⁰ C, stirred for 4 hours at -40 ⁰ C to -3O ⁰ C, and then left in a freezer at -25 ⁰ C overnight. The reaction mixture was poured into ice water, neutralized with NaHCO ₃ , and extracted twice with CH ₂ Cl ₂ . The organic layers were combined, washed with brine, and dried over MgSO ₄ . The solvent was removed under reduced pressure.

The crude product was purified by silica gel column chromatography (elution with n- Hexane/Ethyl acetate=4/l). 2.Og of a mixture of 5a and 5b (5a : 5b = 4 : 1) was obtained (90% ), and the mixture had the following characteristics: 5 (5a:5b=4: l); ¹ H NMR, δ 1.64 (s, 5b; 3H, Me), 1.77 (s, 5a; 3H, Me), 1.80-1.90 (m, 5b; IH, - CH ₂ -), 2.22-2.24 (m, 5a; 2H, -CH ₂ -), 2.80 (dd, 5b; IH, -CH ₂ -, J=13.2, 9.0 Hz), 2.95 (dd, b; IH, -CH(CN)-, J=9.0, 4.0 Hz), 3.49 (dd, 5a; IH, -CH(CN)-, J=8.9, 6.2 Hz), 3.82-4.00 (m, 5a ; IH, -CH(SF ₅ )- and 5b; IH, -CH(SF ₅ )-) 4.36 (m, 5b; IH, -CHCl-), 4.45 (d, 5a; IH, -CHCl-, J=5.4 Hz), 5.14 (d, 5a; IH, bridge-CH-, J=5.7 Hz), 5.22 (s, 5b; IH, bridge-CH-); ¹⁹ F NMR, δ 58.6 (d, 5a; 4F, J=I 56Hz), 59.3 (d, 5b; 4F, J=156Hz), 81.4 (p, 5b; IF, J=156Hz), 81.8 (p, 5a; IF, J=I 56Hz)

To a solution of 5 (5a : 5b = 4 : 1, 2.Og, 6.7mmol) in DMSO(7.5ml) was added LiOH^H ₂ O (1.55g, 36.9mmol) at room temperature. The mixture was stirred for 1 hour at room temperature. The resultant mixture was poured into ice-water, neutralized with NaHCO ₃ , and extracted twice with Ethyl acetate. The organic layers were combined, washed with water and brine, and then dried over MgSO ₄ . The solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography (elution with n-Hexane/Ethyl acetate=4/l). 1.66g of a mixture of 6 (6a, 6b, and one more isomer) was obtained (95%), and the mixture had the following characteristics:

6; ¹ H NMR, δ 1.76, 1.82, 1.88 (s, 3H, -CH ₃ ), 1.98-2.88 (m, 2H, -CH ₂ -), 5.23-5.36 (m, IH, bridge-CH-), 6.54, 6.67, 6.72 (s, IH, -CH-C(SF ₅ )-); ¹⁹ F NMR, 5 65.3, 65.6, 65.7 (d, 4F ₅ J=161Hz), 78.0-81.2 (p, IF)

1.12g of a mixture of 6 (6a, 6b and one more isomer) was heated in sealed tube at a temperature between 150 ⁰ C to 16O ⁰ C for 30 minutes. The reaction mixture was cooled to room temperature. The reaction mixture contained 0.78g (87%) of 3- pentafluorosulfanylfuran, as determined by NMR. The reaction mixture was purified silica gel column chromatography (elution with n-pentane). 0.7Og of 2-methyl-4- pentafluorosulfanylfuran was obtained (78%), and it had the following characteristics: 2-methyl-4-pentafluorosulfanylfuran; ¹ H NMR, δ 2.29 (s, 3H), 6.25 (m, IH), 7.65 (s, IH); ¹⁹ F NMR, δ 69.9 (d, 4F, J=I 63Hz), 83.1 (p, IF, J=I 63Hz)

EXAMPLE 3— SYNTHESIS OF 1-PENTAFLUOROSULFANYLHEXYNE

C ₄ 4H ^π 9 F _K S- -C ₄ 4H ^π 9

2

To a solution of 1 (2.2g, 18.16mmol) in dry n-Hexane (30ml) was added SF ₅ Cl gas(8.1g, 2.7 equiv.) at -40 ⁰ C. 0.26ml (0.1 equiv.) of BEt ₃ was added dropwise to the mixture over 30 minutes at -4O ⁰ C. The reaction mixture was stirred for 1 hour at -40 ⁰ C to -30 ⁰ C and then was warmed to room temperature. The resultant mixture was poured into water, neutralized with NaHCO ₃ , and extracted twice with n-Hexane. The organic layers were combined, washed with brine, and dried over MgSO ₄ . The solvent was removed under reduced pressure. 4.4g of 2 was obtained (86% ), and 2 had the following characteristics:

2; ¹ H NMR, δ 0.95 (t, ; 3H, -CH ₃ , J=7.2Hz), 1.25-1.45 (m, ; 2H, -CH ₂ -), 1.45-1.70 (m, 2H, - CH ₂ -), 2.68 (t, 2H, KXl-CH ₂ -, J=7.7Hz), 6.60 (p, IH, =CH(SF ₅ ), J=8.4Hz); ¹⁹ F NMR, δ 66.9 (d, 4F, J=157Hz), 82.5 (p, IF, J=157Hz)

To a solution of 2 (1.Og, 3.52mmol) in DMSO (60ml) was added LiOH H ₂ O (0.74g, 17.6mmol) at room temperature. The mixture was stirred for 2 hours at room temperature. The resultant mixture was poured into ice-water, neutralized with 2M HCl, and extracted twice with ethyl ether. The organic layers were combined, washed with water and brine, and then dried over MgSO ₄ . The solvent was removed by distillation, and 3 was distilled at 120- 125 ⁰ C. 5.8g of 3 was obtained (68% ), and it had the following characteristics: 3; ¹ H NMR, δ 0.94 (t, 3H, -CH ₃ , J=7.2Hz), 1.43 (m, 2H, -CH ₂ -), 1.51-1.64 (m, 2H, -CH ₂ -), 2.32 (m, 2H, SF ₅ CCH ₂ -); ¹⁹ F NMR, δ 77.8 (p, IF, J=I 69Hz), 83.0 (p, 4F, J=169Hz)

EXAMPLE 4— SYNTHESIS OF 3-PHENYL-4-PENTAFLUOROSULFANYL-5- BUTYLISOOXAZOLE

To a solution of 3 (0.21g, l .Ommol) in THF (5ml) was added 0.77g (5.0mmol, 5equiv.) of Benzohydroxyiminoyl chloride(4). A solution Of NEt ₃ (0.51g, 5.0mmol, 5 equiv.) in 5ml of THF was added dropwise to the mixture at room temperature over 30 minutes. After stirring for 16 hours at room temperature, five more equivalents of 4 and NEt ₃ were added dropwise.

After stirring for 20 hours at room temperature, ten more equivalents of 4 and NEt ₃ were added dropwise. The reaction mixture was stirred for 3 more days at room temperature. The resultant mixture was poured into water and extracted twice with ethyl acetate. The organic layers were combined, washed with brine, and then dried over MgSO ₄ . The solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography (elution with n-Hexane/CHCl ₃ = 7/3). 0.15g of 3-phenyl-4- pentafluorosulfanyl-5-butylisooxazole was obtained (45% ), and it had the following characteristics: 3-phenyl-4-penlafluorosulfanyl-5-butylisooxazole; ¹ H NMR, δ 0.99 (t, 3H, -CH ₃ , J=7.2Hz), 1.47 (m, 2H, -CH ₂ -), 1.81 (p, 2H, -CH ₂ -, J=7.8Hz), 3.04 (t, 2H, -CH ₂ -, J=7.8Hz), 7.3-7.6 (m,

5H, Ph); ¹⁰ F NMR, δ 75.1 (d, 4F, J=I 65Hz), 83.1 (p, IF, J=165Hz)

EXAMPLE 5— SYNTHESIS OF 2,3-DIPHENYL-4-PENTAFLUOROSULFANYL-5- BUTYLISOOXAZOLINE

To a solution of 3 (0.2 Ig, l.Ommol) in THF (5ml) was added 0.50g(2.0mmol, 2 equiv.) of N-benzylideneaniline N-oxide(5). The reaction mixture was stirred for 16 hours at room temperature. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (elution with n-hexane/CHCl ₃ = 7/3). 0.27g of 2,3-diphenyl-4-pentafluorosulfanyl-5-butyl-4-isooxazoline was obtained (67% ), and it had the following characteristics:

2,3-diphenyl-4-ρentafluorosulfanyl-5-butylisooxazoline; ¹ H NMR, δ 1.00 (t, 3H, -CH ₃ , J=7.4Hz), 1.40-1.60 (m. 2H, -CH ₂ -), 1.70-1.84 (m, 2H, -CH ₂ -), 2.75 (t, 2H, -CH ₂ -, J=7.8IIz), 5.60 (s, IH), 7.28-7.48 (m, 5H, Ph); ¹⁹ F NMR, 5 73.5 (d, 4F, J=161Hz), 86.7 (p, IF, J=161Hz)

EXAMPLE 6— SYNTHESIS OF 1 -PENTAFLUOROSULFAN YL-2-

PHENYLλCETYLENE

To a solution of 6 (2.2ml, 20.0mmol) in dry n-hexane (30ml) was added SF ₅ CI gas

(4.Og, 1.2 equiv.) at -40 ⁰ C. 0.29ml (0.1 equiv.) Of BEt ₃ was added dropwise to the mixture over 30 minutes at -4O ⁰ C. The reaction mixture was stirred for 1 hour at -40 ⁰ C to -3O ⁰ C and then was warmed to room temperature. The resultant mixture was poured into water, neutralized with NaHCO ₃ , and extracted twice with n-hexane. The organic layers were combined, washed with brine, and dried over MgSO ₄ . The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (elution with n-hexane). 1.5g of 7 was obtained (28% ), and 7 had the following characteristics: 7; ¹ H NMR, δ 6.93 (p, IH, =CH(SF ₅ ), J=7.7Hz), 7.30-7.44 (m, 5H, Ph); ¹⁹ F NMR, δ 68.5 (d, 4F, J=I 6 IHz), 80.9 (p, IF, J=161Hz) To a solution of 7 (1.5g, 5.67mmol) in DMSO (5ml) was added LiOH»H ₂ O (1.2g,

28.6mmol. 5 equiv.) at room temperature. The mixture was stirred for 2 hours at room temperature. The resultant mixture was poured into ice- water, neutralized with 2M HCl, and extracted twice with ethyl ether. The organic layers were combined, washed with brine, and

then dried over MgSO ₄ . The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (elution with n-hexane). 1.2g of 8 was obtained (93%), and 8 had the following characteristics:

8; ¹ H NMR, δ 7.30-7.50 (m, 3H), 7.55 (d, 2H, J=8.3Hz); ¹⁹ F NMR, δ 76.7 (p, IF, J=I 70Hz), 83.1 (p, 4F, . T=I 70Hz)

EXAMPLE 7— SYNTHESIS OF 3,5-DIPHENYL-4- PENTAFLUOROSULFANYLISOOXAZOLE

To a solution of 8 (0.5Og, 2.2mmol) in THF (5ml) was added 0.68g (4.4mmol, 2 equiv.) of benzohydroxyiminoyl chloride(4). A solution of NEt ₃ (0.44g, 4.4mmol, 2 equiv.) in 5ml of THF was added dropwise to the mixture at room temperature over 30 minutes. After stirring for 16 hours at room temperature, the 3.5equivalent of 4 and NEt ₃ were added dropwise. The reaction mixture was stirred for 20 hours at room temperature. The resultant mixture was poured into water and extracted twice with ethyl acetate. The organic layers were combined, washed with brine, and then dried over MgSO ₄ . The solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography (elution with n-hexane/CHCl ₃ = 7/3). 0.4g of 3,5-diphenyl-4-pentafluorosulfanylisooxazole was obtained (53% ), and it had the following characteristics:

3,5-diphenyl-4-ρentafluorosulfanylisooxazole; ¹ H NMR, δ 0.99 (t, 3H, -CH ₃ , J=7.2Hz), 1.47 (m, 2H, -CH ₂ -), 1.81 (p, 2H, -CH ₂ -, J=7.8Hz), 3.04 (t, 2H, -CH ₂ -, J=7.8Hz), 7.3-7.6 (m, 5H, Ph); ¹⁹ F NMR, δ 75.1 (d, 4F, J=165Hz), 83.1 (p, IF, J=165Hz)

EXAMPLE 8— SYNTHESIS OF 4-PENTAFLUOROSULFANYL-2,3,5-TRIPHENYL-4- ISOOXAZOLINE

To a solution of 8 (0.36g, 1.57mmol) in THF (5ml) was added 0.62g (3.14mmol, 2 equiv.) of N- benzylideneaniline N-oxide(5). The reaction mixture was stirred for 20 hours at room temperature. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (elution with n-hexane/CHCl ₃ = 7/3). 0.6g of 4- pentafluorosulfanyl-2,3,5-triphenyl-4-isooxazoline was obtained (90% ), and it had the following characteristics:

4-pentafluorosulfanyl-2,3,5-triphenyl-4-isooxazoline; ¹ H NMR, 5.80 (s, IH), 7.16 (t, IH), 7.24 (d, 2H), 7.35-7.60 (m, 1011), 7.75 (dd, 2H, J=7.5, 2.0Hz); ¹⁹ F NMR, δ 74.8 (d, 4F, J=I 6 IHz), 85.1 (p, IF, J=IOlHz)

EXAMPLE 9— SYNTHESIS OF 2-BUTYL-3-PENTAFLUOROSULFANYL-2,5- NORBORNADIENE

A mixture of 3 (0.5g, 2.4mmol) and freshly distilled cyclopentidiene (1.58g,

24.0mmol, 10 equiv.) was heated in a sealed tube at 12O ⁰ C for 18 hours. The reaction mixture was cooled to room temperature. The reaction mixture contained 0.46g (70%) of 2-butyl-3- ρentafluorosulfanyl-2,5-norbornadiene, as determined by NMR. Unreacted cyclopentadiene

and dicyclopentadiene, which were formed during the reaction, was removed under reduced pressure. The residue was purified by silica gel column chromatography (elution with n- hexane). 0.3g of 2-butyl-3-pentafluorosulfanyl-2,5-norbornadiene was obtained (50%), and it had the following characteristics: 2-butyl-3-pentafluorosulfanyl-2,5-norbornadiene; ¹ H NMR, 0.91 (t, 3H, J=7.2Hz), 1.20-1.60 (m, 4H), 1.97 (d, IH, J=6.6Hz), 2.18 (dt, IH, 3=6.6, 1.7Hz), 2.43 (m, 2H), 3.51 (bs, IH), 3.88 (bs, IH), 6.78 (m, IH), 6.90 (m, IH); ¹⁹ F NMR, 5 64.9 (d, 4F, J=161Hz), 87.5 (p, I F, J=I 6 IHz)

EXAMPLE 10— SYNTHESIS OF 3-BUTYL-4-PENTAFLUOROSULF ANYLFUR AN

A mixture of 3 (0.36g, 1.7mmol) and 4-phenyloxazole (0.5g, 3.4mmol, 2.0 equiv.) was heated in sealed tube at 18O ⁰ C to 19O ⁰ C for 20 hours. The reaction mixture was cooled to room temperature. The reaction mixture contained 0.30g (69%) of 3-butyl-4- pentafluorosulfanylfuran, as determined by NMR, and purified by silica gel column chromatography (elution with n-Hexane). 0.25g of 3-bButyl-4-pentafluorosulfanylfuran was obtained (58%), and it had the following characteristics: 3-butyl-4-pentafluorosulfanylfuran; ¹ H NMR, 0.95 (t, 3H, J=7.3Hz), 1.46 (m, 2H), 1.50-1.64 (m, 2H), 2.53 (t, 2H, J=8.0), 7.16 (d, IH, J=0.9Hz), 7.79 (s, IH); ¹⁹ F NMR, 6 73.4 (d, 4F, J=I 61Hz), 84.2 (p, IF, J=IOlHz)

It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and the scope of the appended claims. In addition, any elements or limitations of any invention or embodiment thereof disclosed herein can be combined with any and/or all other elements or limitations (individually or in any combination) or any other

invention or embodiment thereof disclosed herein, and all such combinations are contemplated with the scope of the invention without limitation thereto.