The present invention relates generally to the field of ligand development, particularly, chiral (P,N)-ligands. The present invention is furtherconcerned with the gold(I) complexes of said chiral (P,N)-ligands. The present invention is further concerned with the method of preparing and the uses of said chiral (P, N)-ligands and their respective Au(I) complexes.

BACKGROUND OF THE INVENTION

Homogeneous gold catalysis evolved as one of the most dynamic areas of research in organic and organometallic chemistry. Myriad of reactions have been developed based on the activation of C-C multiple bonds, however accessing enantioselective transformations remained highly elusive in gold catalysis.

This is mainly due to the linear geometry favoured by Au(I) complexes, which places the chiral ligand and substrate at opposite direction rendering an inefficient enantio-control. Interestingly, enantioselective Au(III) catalysis offer an attractive alternative to Au(I) catalysis. The square- planar geometry adopted by Au(III) species places the chiral ligand closer to the substrate thus allowing a better enantio-control.

Rodriguez, J.; Borissou, D. Well-Defined Chiral Gold(III) Complexes: New Opportunities in Asymmetric Catalysis. Angew. Chem., Int. Ed. 2018, 57, 386-388disclosesthe potential of chiral Au(III) complexes to achieve enantioselective transformations.

In a parallel space, the past decade has witnessed a significant efforts to overcome the high redox potential of gold (E = 1.41 eV) and to facilitate the Au(I)/Au(III) redox catalysis. Wegner, H. A.; Auzias, M. Gold for C-C Coupling Reactions: A Swiss-Army-Knife Catalyst. Angew. Chem., Int. Ed. 2011, 50, 8236-8247 discloses plethora of gold-catalyzed cross-coupling reactions and 1,2- difunctionalization of C-C multiple bonds by utilizing external oxidants, merged gold/photoredox catalysis and ligand-enabled strategy.

Recently, Zeineddine, A.; Estevez, L.; Mallet-Ladeira, S.; Miqueu, K.; Amgoune, A.; Bourissou, D. Rational development of catalytic Au(I)/Au(III) arylation involving mild oxidative addition of aryl halides. Nat. Commun. 2017, 8, 565discloses the use of a (P, N)-ligand, MeDalPhos, found to be very prominent to access Au(I)/Au(III) redox catalysis by facilitating the bottleneck oxidative addition of organohalides with Au(I) catalyst.

However, to date there is no efficient method reported to achieve enantioselective version of Au(I)/Au(III) redox catalysis.

OBJECTIVES OF THE INVENTION

The main objective of the present invention is to provide chiral hemilabile (P, N)-ligands.

Another objective of the present invention is to develop corresponding Au(I) complexes of the said chiral hemilabile (P, N)-ligands.

Yet another objective of the present invention is to provide a method for producing the chiral hemilabile (P,N)-ligands and the corresponding Au(I) complexes of the said chiral hemilable (P,N)-ligands.

Yet another objective of the present invention is to provide an efficient method reported to achieve enantioselective version of Au(I)/Au(III) redox catalysis.

Further another objective of the present invention is to provide anapplication of the chiral (P, N)- ligands in developing Au(I)/Au(III)-catalyzed enantioselective 1 ,2-heteroarylation of alkenes.

Further another objective of the present invention is to tackle the typical geometrical restrictions and distinct coordination behaviour exhibited by Au(I) and Au(III) species during facilitation of enantioselective Au(I)/Au(III) redox catalysis.

SUMMARY OF THE INVENTION

The invention relates to the development of chiral hemilabile (P, N)-ligands (Figure 1).

Figure 1. Markush’s structures of chiral (P, N)-ligands

In one another aspect, the invention relates to the development of corresponding Au(I) complexes of the said chiral hemilabile (P, N)-ligands.

Figure 2. Markush’s structures of chiral Au(I) complexes

Another aspect of invention deals with the method of synthesis of said chiral hemilabile (P, N)- ligands and their corresponding gold(I) complexes.

In one of the aspects, the present disclosure provides application of chiral (P, N)-ligands in developing Au(I)/Au(III)-catalyzed enantioselective 1 ,2-heteroarylation of alkenes.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1 illustrates Markush’s structures of chiral (P, N)-ligands.

Figure 2 illustrates Markush’s structures of chiral Au(I) complexes.

Figure 3 illustrates Scheme 1A Challenges in realizing enantioselective Au(I)/Au (III) catalysis Figure 4 illustrates Scheme IB. Design of new chiral (P, N)-ligand to facilitate enantioselective Au(I)/Au (III) catalysis

Figure 5 A illustrates Synthetic route to new chiral P,N-ligands

Figure 5B illustrates Structure of new gold(I) complexes

Figure 6 illustratesGold-catalyzed enantioselective 1,2-oxyarylation of alkenes

Figure 7 illustrates Scheme 2. Scope of 1 ,2-oxyarylation of alkenes

Figure 8 illustrates Scheme 3. Scope of 1 ,2-aminoarylation of alkenesa,b

Figure 9 illustrates (a) Post synthetic modifications and (b) applications of the chiral hemilabile (P,N)-ligands and their corresponding Au(I) complexes.

Figure 10 illustrates a schematic flowchart of the methodology for producing compounds of formula (i) and their salt thereof, and formula (ii) and their salt thereof.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

It is to be understood that the present disclosure is not limited in its application to the details of compound set forth in the following description. The present disclosure is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.

The use of “including”, “comprising” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.

Before the present invention is described in greater detail, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

Certain ranges are presented herein with numerical values being preceded by the term "about." The term "about" is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described.

All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.

It is noted that, as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely," "only" and the like in connection with the recitation of claim elements or use of a "negative" limitation.

As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention.

For convenience, certain terms used in the specification, examples, and appended claims are collected in this section.

As used herein, the term 'compound(s)' comprises the compounds disclosed in the present invention.

Each embodiment is provided by way of explanation of the invention and not by way of limitation of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made to the compounds, compositions and methods described herein without departing from the scope or spirit of the invention. For instance, features illustrated or described as part of one embodiment can be applied to another embodiment to yield a still further embodiment. Thus, it is intended that the present invention includes such modifications and variations and their equivalents. Other objects, features, and aspects of the present invention are disclosed in or are obvious from, the following detailed description. It is to be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only and is not to be construed as limiting the broader aspects of the present invention.

The main challenge in facilitating enantioselective Au(I)/Au(III) redox catalysis is to tackle the typical geometrical restrictions and distinct coordination behaviour exhibited by Au(I) and Au(III) species. The Au(I) complexes are generally dicoordinated and linear, while Au(III) complexes prefer tetracoordinated square-planar geometry. Therefore, in order to realize enantioselective Au(I)/Au(III) redox catalysis one has to control four-coordination sites of in situ generated Au(III) intermediate by only one modulatory ligand (L) present in LAuX catalyst. Further, the linear geometry favoured by Au(I) complexes hinder the use of chelating chiral bidentate ligands. Be noted that chiral bidentate ligands are imperative to provide structural rigidity to the metal complex which is the key for their high success in achieving excellent enantioselectivity in several transition metal- catalyzed transformation. Moreover, the tetracoordinated Au(III) intermediate generated in the presence of strong external oxidants and photocatalysts remain structurally non-rigid and hold multiple substrate binding possibilities which in turn leads to very poor or no enantio-induction.

In an embodiment, a compound according to formula (i), or its salt thereof, and formula (ii), or its salt thereof, in which R ¹ independently are alkyl groups; R ² , R ³ , and R ⁴ independently are cycloalkyl, aryl, H, polycarbon chain, vinyl, amino, and alkoxy groups. The compounds according to formula (i) and formula (ii) are chiral hemilabile (P,N)-ligands. Preferably, the chiral hemilabile (P,N)-ligands are selected from a group of Ad-ChetPhos, ^z Bu-ChetPhos, Ad-(H8)ChetPhos, and ^z Bu- (H8)ChetPhos, Ad-(5-OMe)Chetphos and Ad-(4-COMe)chetphos. Preferably, the R independently is selected from H, OMe, and COMe.

In another embodiment, a process for producing the compounds according to formula (i), or its salt thereof, and formula (ii), or its salt thereof, comprises the steps of treating dibromo compounds S4 and S9, as referred to in Figure 5, derived from BINOL with condition ‘a’ to obtain dinaphthoazipine derivatives S5 and S10, as referred to in Figure 5. The dinaphthoazipine derivatives S5 and S10 (as referred to in Figure 5) are subjected to palladium-catalyzed C-P coupling by reacting phosphines with condition ‘b’ to obtain the compounds according to formula (i), or its salt thereof, and formula (ii), or its salt thereof. Preferably, the condition ‘a’ is carried out by treating dibromo compounds S4 and S9 (as referred to in Figure 5) with 2- bromoaniline. The phosphines are selected from di-adamantyl phosphines or di- tertbutylphosphines.

In another embodiment, a process for producing compounds of formula (iii) or its salt thereof, and formula (iv) or its salt thereof,

1 2 3 4 wherein R independently are alkyl groups; andR , R , and R independently are cycloalkyl, aryl, H, polycarbon chain, vinyl, amino, and alkoxy groups, comprises reacting a compound according to formula RSAuX with condition ‘c’, wherein R independently is an alkyl group and X independently is a halogen group. Preferably, the R ² independently is selected from H, OMe, and COMe. The compounds of formula (iii) and formula (iv) are corresponding Au(I) complexes of the compounds according to formula (i) and formula (ii) respectively. Preferably, the compound according to formula RSAuX is Me2SAuCl. The condition ‘c’ is carried out in the presence of an organohalogen compound at RT for a period of time. Preferably, the organohalogen compound is dichloromethane.

In a preferred embodiment, the inventors of present invention synthesized the chiral (P, bpligands as described herein. The dibromo compounds S4 and S9 were derived from BINOL by following the literature known procedures. These compounds were then treated with 2- bromoaniline (condition ‘a’) to afford dinaphthoazipine derivatives S5 and S10. The palladium- catalyzed C-P coupling of these compounds with different phosphines (condition ‘b’) such as di- adamantylphosphines or di-/ /7-butylphosphines afforded desired (P,N)-ligands (L1-L4). Based on the substituents attached on the phosphorus and the nature of dinaphthoazipine skeleton the newly synthesized ligands have been named as: Ad-ChetPhos, ^z Bu-ChetPhos Ad-(H8)ChetPhos, and ^z Bu-(H8)ChetPhos. These ligands were then subjected to Me2SAuCl (condition ‘c’) to afford the respective gold(I) complexes. Structure of these ligands and gold(I) complexes was unambiguously confirmed by obtaining the X-ray crystallographic data for Ad-ChetPhos and ^z Bu-(H8)ChetPhosAuCI.

For determining catalytic activity of newly developed chiral hemilabile (P, N)-ligated Au(I) complexes (viz. Ad-ChetPhosAuCl, ^z Bu-ChetPhosAuCI, Ad-(H8)ChetPhosAuCl, and ^z Bu- (H8)ChetPhosAuCl), iodoaryl alkene la as a substrate and methanol 2a as a simple nucleophilic partner (Table 1) were taken.

Different chiral (P,N)-ligated Au(I) complexes were tested in presence of AgSbFe, K3PO4 in DCE at 80 °C. The synthesized Au(I) complexes catalyzed the desired 1,2-oxyarylation reaction in moderate yield and excellent enantiomeric excess (entries 1-4). Among all chiral (P, bpligands, the use of Ad-ChetPhos afforded excellent enantioselectivity and better yield for 3- methoxychromane 3a (97% ee, 64%).

It was observed, when different silver salts were tested (entries 5-8), the use of AgOTf improved the yield of the reaction to 78% (98% ee). The variation of bases did not further improve the yield of the reaction (entries 9-12). Interestingly, the desired 3 -methoxy chromane was isolated in highest 86% yieldand 99% ee when the reaction was performed in absence of base.

Now referring to Figure 7, thereafter, the generality of enantioselective 1,2-oxyarylation reaction were evaluated. (Scheme 2). Various derivatives of 3 -methoxy chromane (3a-3i) were obtained in excellent enantiomeric excess (81-99% ee) and moderate to good yields (47-86%) when differently substituted iodoaryl alkene (la-li) were subjected to optimized reaction conditions. For instance, halo, nitro and keto substituted 3 -methoxy chromane 3b-3e were obtained in 72- 80% yield and 98-99% ee when corresponding iodoaryl alkene lb-le were used as substrates. Further, substrates If and lg were also reacted smoothly to afford corresponding products (3f and 3g) in 99% ee and good yield (88% and 72%, respectively). Considerable drop in yield and ee was observed in case of 3h (51%, 81% ee) and 3i (47%, 90% ee), suggesting that the ortho substitution in substrate lh and naphthalene core in li hamper the reaction outcome.

Other alcohols such as ethanol, /.w-propanol, 2-bromobenzylacohol were also reacted well with la to afford the desired products 3j-31 in excellent enantioselectivity (98-99% ee) and moderate to good yield (45-73%). Interestingly, water was also found to be compatible in the current reaction conditions. 3 -hydroxy chromane derivatives 3m-3o were readily obtained when corresponding 2-iodoallyloxybenzene were treated under standard reaction conditions using water as a nucleophile.

Amines were used as nucleophilic partners to obtain 3-aminochromane derivatives, as 3- aminochromans represents the core structure of several marketed drug molecules. However, conventional approaches to obtain these compounds in enantiopure form still rely on the chiral resolution. The inventors used iodoaryl alkene la as substrate and 4-nitroaniline as amine source. After a brief survey of chiral Au(I) complexes, halide scavengers, bases and solvents, it was found that the desired product 5a could be obtained in highest 84% yield and 99% ee when 5 mol% Ad-ChetPhosAuCl, 1.15 equiv. AgSbF ₆ , and 0.1 equiv. K ₃ PO4 were used in 0.1 M DCE.

In general, wide array of anilines coupled smoothly with idoaryl alkene la to furnish the desired 3-aminochromane derivatives 5a-51 in moderate to good yield (42-86%) and excellent enatiomeric excess (96-99%). For instance, various substitutions at ortho and para position of aniline are well tolerated to afford the desired products 5a-5e in 56-86% yield. Interestingly, in all cases 99% ee was obtained highlighting the excellent level of enantio-control offered by newly developed (P, N)-ligand in the present gold-catalyzed transformation. Moreover, various disubstituted anilines bearing electron-donating and withdrawing groups as well as heteroaromatic amine also reacted well, giving products 5f-51 in 48-77% yield and 96-99% ee. The structure and absolute configuration of products was unambiguously confirmed by obtaining the X-ray crystal structure of 5k.

Next, the scope of iodoaryl alkenel was verified against 2-nitroaniline. Interestingly, all the desired 3-aminochromaes were obtained in 99% ee (68-80% yield) when iodoaryl alkenes substituted with electron-donating group, withdrawing group and halo substituents (5m-5q) were used as substrates. However, sudden drop in yield and ee was noticed (48%, 91% ee) in case of 5r when disubstituted iodoaryl alkene was used, clearly suggesting that the substituent ortho to allyloxy group hampers the reaction outcome (compare 5n and 5r).

The synthetic utility of newly developed protocol was demonstrated by performing few postsynthetic modifications of 3-oxychromanes. The C-N and C-B coupling with 3c could be readily performed under Pd catalysis to obtain the functionalized 3-aminochromanes 6 and 7 in 84% and 78% yield without sacrificing the ee. Besides, the hydroxyl group of 3n could be converted to mesylate which could readily undergo SN2 displacement with azide to afford 3-azidochromane 8 with complete stereochemical inversion. Be noted that organic azides are very important substrates as they find wide applications in bio-orthogonal click chemistry.Further, a Wittig reaction could be readily performed with 3n and phthalimide to obtain the corresponding product 9

The methodology provides an easy access to enantio-enriched 6-bromo-3-aminochromane 10 which is a precursor for the synthesis of serotonin 5-HT ₇ receptor 11 and MALT1 inhibitor 12. The known approaches to obtain 10 still rely on the chiral resolution pathway. The inventors have developed a powerful approach for accessing asymmetric Au(I)/Au(III) redox catalysis. The developed hemilabile (P, N)-ligand having C2-symmetric chiral environment around nitrogen center proved to be the ring-master in this case. The application of this ligand-enabled strategy has been shown to achieve highly enantioselective 1,2-oxy- and aminoarylation of alkenes. Various 3-oxychromanes and 3-aminochromanes which represent the core structure of several drug molecules could be readily accessed in enantio-enriched form.

EXAMPLES:

Non-limiting examples of adhesive composition of the present invention are provided in the following tables.

Experimental procedures:

(5)-[l,l'-binaphthalene]-2,2'-diyl bis(trifluoromethanesulf onate) (S2):

To a stirred mixture of fS')-BINOL (SI) (5 g, 17.46 mmol, 1 equiv) in dichloromethane (DCM) (80 mL) was added pyridine (4.22 mL, 52.38 mmol, 3 equiv) at room temperature. The reaction mixture was cooled to 0 °C before the drop-wise addition of trifluoromethanesulfonic anhydride (Tf ₂ O) (6.44 mL, 38.41 mmol, 2.2 equiv) under N ₂ atmosphere. It was then allowed to warm at room temperature and stirred for additional 6 h. After complete consumption of SI, as monitored by TLC, the reaction was quenched with 1 M HC1 (aq.) (30 mL) at 0 °C and then extracted with dichloromethane (3 x 50 mL). The combined organic extracts were washed with sat. NaHCO,(aq.) (30 mL), dried over Na ₂ SO_i, and the solvent was removed in vacuo. The resultant residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 95/5) to afford fS')-[ l , l '-binaphthalene]-2,2'-diyl bis(trifluoromethanesulfonate) (S2) as a white solid (8.35 g, 87% yield). The product was characterized by and ¹³ C NMR spectroscopy and the data is in agreement with that reported in the literature by Ooi, T.; Kameda, M.; Maruoka, K.

J. Am. Chem. Soc.2003, 125, 5139.

(5)-2,2'-dimethyl-l,l'-binaphthalene (S3):

To a stirred mixture of (S)-[l,T-binaphthalene]-2,2'-diyl bis(trifluoromethanesulfonate) (S2) (8.35 g, 15.16 mmol, 1 equiv) and (dppp)NiCl ₂ (411.12 mg, 0.75 mmol, 0.05 equiv) in diethyl ether (100 mL) was added methyl magnesium bromide (3.0 M in diethyl ether) (15.16 mL, 45.48 mmol, 3 equiv) at 0 °C over a period of 30 min. After the reaction mixture was stirred for 12 h at room temperature under N2 atmosphere, it was cooled to 0 °C and quenched by drop-wise addition of water (30 mL) followed by 1 M HC1 (aq.) (30 mL). The reaction mixture was then extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were washed with sat. NaHCO, (aq.) (50 mL), dried over NaiSCL, and the solvent was removed in vacuo. The resultant residue was purified by silica gel column chromatography (eluent: petroleum ether) to afford (5)- 2,2'-dimethyl-l,l'-binaphthalene (S3) as a white solid (3.99 g, 95% yield). The product was characterized by and ¹³ C NMR spectroscopy and the data is in agreement with that reported in the literature: Ooi, T.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc. 2003, 125, 5139.

(5)-2,2'-bis(bromomethyl)-l,l'-binaphthalene (S4):

A mixture of (5)-2,2'-dimethyl-l,l'-binaphthalene (S3) (3.99 g, 14.12 mmol, 1 equiv), N- bromosuccinimide (NBS) (5.27 g, 29.65 mmol, 2.1 equiv), and 2,2'-Azobis(2- methylpropionitrile) (AIBN) (231.53 mg, 1.41 mmol, 0.1 equiv) in degassed benzene (80 mL) was refluxed for 3 h under N2 atmosphere. After being cooled to room temperature, water (30 mL) was added to the reaction mixture and it was extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were dried over Na2SO4 and the solvent was removed in vacuo. The resultant residue was filtered through the pad of silica gel (eluent: petroleum ether/ethyl acetate = 98/2). The solvent was removed in vacuo and the crude material was recrystallized in DCM/petroleum ether to afford the pure product as a white solid (4.23 g, 68% yield). The product was characterized by H and C NMR spectroscopy and the data is in agreement with that reported in the literature by Ooi, T.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc.2003, 125, 5139.

4-(2-bromophenyl)-4,5-dihydro-3H-dinaphtho[2,l-c:l',2'-e] azepine (S5):

A mixture of (5)-2,2'-bis(bromomethyl)-l,l'-binaphthalene (S4) (4.23 g, 9.60 mmol, 1 equiv), 2- bromoaniline (4.96 g, 28.82 mmol, 3 equiv), K2CO3 (5.30 g, 38.40 mmol, 4 equiv), and Nal (287.79 mg, 1.92 mmol, 0.2 equiv) in freshly dried acetonitrile (200 mL) was refluxed for 36 h under N2 atmosphere. After being cooled to room temperature, the solvent was evaporated under vacuum. Water (50 mL) was added to the resultant residue and the organic material was extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were washed with 2 M HC1 (aq.) (3 x 30 mL) and then with sat. NaHCO? (aq.) (50 mL). After being dried over Na2SO4, the solvent was removed in vacuo. The resultant residue was then purified by silica gel column chromatography (eluent: petroleum ether/DCM = 90/10 and then petroleum ether/ethyl acetate = 98/2) to afford 4-(2-bromophenyl)-4,5-dihydro-3H-dinaphtho[2,l-c:T,2'-e]azep ine (S5) as a white solid (2.42 g, 56% yield). 'H NMR (500 MHz, CHLOROFORM- d) 5 = 7.97 (dd, J= 5.1, 8.2 Hz, 4 H), 7.65 (dd, J= 1.4, 7.9 Hz, 1 H), 7.55 (d, J= 8.5 Hz, 2 H), 7.53 - 7.46 (m, 4 H), 7.32 (ddd, J= 1.1, 6.9, 8.4 Hz, 2 H), 7.20 - 7.14 (m, 1 H), 6.97 - 6.89 (m, 2 H), 4.13 (d, J= 12.2 Hz, 2 H), 3.98 (d, J = 12.2 Hz, 2 H); ¹³ C NMR (125 MHz, CHLOROFORM-d)S = 149.9, 135.0, 134.0, 133.5, 133.2, 131.3, 128.8, 128.3, 127.8, 127.7, 127.5, 125.9, 125.6, 124.0, 122.2, 119.4, 54.8.

Representative procedure for C-P coupling:

In a sealed tube, 4-(2-bromophenyl)-4,5-dihydro-3H-dinaphtho[2,l-c:l',2'-e]aze pine(S5) (500 mg, 1.11 mmol, 1 equiv), Pd(OAc)2 (12.46 mg, 0.0555 mmol, 0.05 equiv), dippf (27.85 mg, 0.0666 mmol, 0.06 equiv), and NaO ^z Bu (128 mg, 1.332 mmol, 1.2 equiv) were added. After the tube was degassed with N2 for 15 min, the freshly dried and degassed toluene (12 mL) was added and the mixture was stirred at room temperature for 20 min. Then, di-l-adamantylphosphine (369.34 mg, 1.22 mmol, 1.1 equiv) was added to the reaction mixture in one portion under N2 atmosphere and the tube was heated to 110 °C for 24 h. After being cooled to room temperature, the solvent was removed in vacuo and the resultant residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 95/5) to afford Ad-ChetPhos(Ll ) as a white solid (500 mg, 67% yield).

Characterization data:

Ad-ChetPhos (LI): White solid, 500 mg, 67% yield; R/= 0.30 (petroleum ether/ethyl acetate = 95/5); 'H NMR (700 MHz, CHLOROFORM-d)S = 7.97 (d, J= 8.2 Hz, 2 H), 7.94 (d, J= 8.2 Hz, 2 H), 7.79 (d, J = 7.5 Hz, 1 H), 7.55 (d, J= 8.6 Hz, 2 H), 7.51 - 7.46 (m, 2 H), 7.42 (d, J= 8.2 Hz, 2 H), 7.32 - 7.28 (m, 2 H), 7.21 - 7.16 (m, 1 H), 7.05 (t, J = 7.0 Hz, 1 H), 6.89 (dd, J = 4.3, 7.3 Hz, 1 H), 4.09 - 3.96 (m, 4 H), 2.09 (br. s., 6 H), 1.94 (br. s., 9 H), 1.91 - 1.84 (m, 3 H), 1.78 - 1.65 (m, 12 H); ¹³ C NMR (175 MHz, CHLOROFORM-d)S = 158.8 (d, J= 22.9 Hz), 137.7 (d, J = 2.5 Hz), 134.8, 134.2, 133.0, 131.4, 130.8 (d, J = 25.4 Hz), 128.8, 128.5, 128.2, 127.9, 127.5, 125.6, 125.3, 121.9 (d, J= 3.8 Hz), 121.7, 56.3, 42.5 (d, J= 14.0 Hz), 41.2 (d, J = 12.7 Hz), 37.6 (d, J = 26.7 Hz), 37.1 (d, J = 5.1 Hz), 36.4 (d, J = 28.0 Hz), 29.0 (d, J = 7.6 Hz), 28.9 (d, J = 7.6 Hz); ³¹ P NMR (202 MHz, CHLOROFORM-d)S = 22 5

Bu-C hetPhos (L2):

White solid, 389 mg, 68% yield; R = 0.40 (petroleum ether/ethyl acetate = 95/5); ¹ H NMR (700 MHz, CHLOROFORM-d)S = 7.97 (d, J= 8.2 Hz, 2 H), 7.94 (d, J= 8.2 Hz, 2 H), 7.78 (d, J = 7.7 Hz, 1 H), 7.56 (d, J = 8.4 Hz, 2 H), 7.49 (t, J= 7.2 Hz, 2 H), 7.43 (d, J = 8.0 Hz, 2 H), 7.30 (t, J= 7.3 Hz, 2 H), 7.19 (t, J= 7.1 Hz, 1 H), 7.07 (t, J= 7.1 Hz, 1 H), 6.88 (dd, J= 4.4, 7.2 Hz, 1 H), 3.99 - 4.07 (m, 4 H), 1.34 (d, J= 11.4 Hz, 9 H), 1.18 (d, J= 11.4 Hz, 9 H); ¹³ C NMR (175 MHz, CHLOROFORM- d) 5 = 158 1 (d, J= 21.6 Hz), 136.5 (d, J= 3.8 Hz), 134.8, 134.1, 133.2 (d, J= 26.7 Hz), 133.0, 131.4, 129.0, 128.5, 128.2, 127.9, 127.5, 125.7, 125.3, 122.1, 121.6 (d, J = 3.8 Hz), 56.3, 33.1 (d, J = 25.4 Hz), 31.6 (d, J = 25.4 Hz), 31.5 (d, J = 15.3 Hz), 30.0 (d, J = 15 3 HZ); ³¹ P NMR (162 MHz, CHLOROFORM-d)S = 20 3

(N)-5,5',6,6',7,7',8,8'-octahydro-[l,l'-binaphthalene]-2, 2'-diylbis(trifluoromethanesulfonate)

(S7): To a stirred mixture of fS')-H8-BINOL (S6) (obtained from the partial hydrogenation of Al using H PtCh) (5 g, 16.98 mmol, 1 equiv) in dichloromethane (80 mL) was added pyridine (4.11 mL, 50.96 mmol, 3 equiv) at room temperature. The reaction mixture was cooled to 0 °C before the drop-wise addition of trifluoromethanesulfonic anhydride (Tf2O) (6.27 mL, 37.37 mmol, 2.2 equiv) under N2 atmosphere. It was then allowed to warm at room temperature and stirred for additional 6 h. After complete consumption of S6, as monitored by TLC, the reaction was quenched with 1 M HC1 (aq.) (30 mL) at 0 °C and then extracted with dichloromethane (3 x 50 mL). The combined organic extracts were washed with sat. NaHCO, (aq.) (30 mL), dried over NaoSO-i, and the solvent was removed in vacuo. The resultant residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 95/5) to afford (6)- 5,5',6,6',7,7',8,8'-octahydro-[l,r-binaphthalene]-2,2'-diyl bis(trifluoromethanesulfonate) (S7) as a white solid (8.72 g, 92% yield). The product was characterized by and ¹³ C NMR spectroscopy and the data is in agreement with that reported in the literature by Jennifer Kan, S. B.; Maruyama, H.; Akakura, M.; Kano, T.; Maruoka, K. Angew. Chem., Int. Ed.2017, 56, 9487.

Dimethyl (5)-5,5',6,6',7,7',8,8'-octahydro-[l,l'-binaphthalene]-2,2'- dicarboxylate (S8):

A mixture of (5)-5,5',6,6',7,7',8,8'-octahydro-[l,r-binaphthalene]-2,2'-d iyl bis(trifhioromethanesulfonate) (S7) (2 g, 3.58 mmol, 1 equiv), Pd(OAc)2 (120.59 mg, 0.53 mmol, 0.15 equiv), dppp (221.53 mg, 0.53 mmol, 0.15 equiv), diisopropylethylamine (2.74 mL, 15.75 mmol, 4.4 equiv), and methanol (7.23 mL, 179.04 mmol, 50 equiv) in DMSO (18 mL) was stirred at 80 °C for 84 h under an atmosphere of CO (1 atm). After complete consumption of S7, as monitored by TLC, ice-cold water was added to the reaction mixture and the organic material was extracted with ethyl acetate (3 x 20 mL). The combined organic extracts were washed with brine, dried over Na2SO4, and the solvent was removed in vacuo. The resultant residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 90/10) to afford dimethyl (5)-5,5',6,6',7,7',8,8'-octahydro-[l,l'-binaphthalene]-2,2'- dicarboxylate (S8) as a white solid (948.7 mg, 70% yield). The product was characterized by and ¹³ C NMR spectroscopy and the data is in agreement with that reported in the literature by Jennifer Kan, S. B.; Maruyama, H.; Akakura, M.; Kano, T.; Maruoka, K. Angew. Chem., Int. Ed.2017, 56, 9487.

(5)-2,2'-bis(bromomethyl)-5,5',6,6',7,7',8,8'-octahydro-l ,l'-binaphthalene (S9): Step 1: To a stirred mixture of dimethyl (5)-5,5',6,6',7,7',8,8'-octahydro-[l,T-binaphthalene]- 2,2'-dicarboxylate (S8) (4.13 g, 10.91 mmol, 1 equiv) in dry THF (80 mL), LiAITU (1.65 g, 43.64 mmol, 4 equiv) was added portion-wise at 0 °C under N2 atmosphere. The reaction was then stirred at 40 °C for 3 h. After complete consumption of S8, as monitored by TLC, the reaction mixture was cooled to 0 °C and quenched by drop-wise addition of water (4 mL) followed by 10% NaOH (aq.) (2 mL) solution. The mixture was filtered through a short pad of celite which was successively washed with ethyl acetate several times. The filtrate was collected and dried over NaoSO-i. The solvent was removed in vacuo and the resultant crude diol was directly used in the next step.

Step 2: To a stirred mixture of crude diol in dry THF (120 mL), a solution of PBrs (2.32 mL, 24 mmol, 2.2 equiv) in dry DCM (60 mL) was added drop-wise at -40 °C. The reaction mixture was allowed to warm at room temperature and stirred for 1 h. After complete consumption of diol, as monitored by TLC, the reaction was quenched by addition of water (20 mL) followed by sat. NaHCO? (aq.) (20 mL). The organic material was extracted with ethyl acetate (3 x 30 mL). The combined organic extracts were washed with brine, dried over NaiSCL, and the solvent was removed in vacuo. The resultant residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 99/1) to afford (N)-2,2'-bis(bromomethyl)- 5,5',6,6',7,7',8,8'-octahydro-l,r-binaphthalene (S9) as a white solid (4.01 g, 82% yield). The product was characterized by ’H and ¹³ C NMR spectroscopy and the data is in agreement with that reported in the literature by Jennifer Kan, S. B.; Maruyama, H.; Akakura, M.; Kano, T.; Maruoka, K. Angew. Chem., Int. Ed.2011, 56, 9487.

(5)-4-(2-bromophenyl)-4,5,8,9,10,ll,12,13,14,15-decahydro -3H-dinaphtho[2,l-c:l',2'- ejazepine (S10):

A mixture of (S -2,2'-bis(bromomethyl)-5,5',6,6',7,7',8,8'-octahydro-l,r-bin aphthalene (S9) (4.01 g, 8.94 mmol, 1 equiv), 2-bromoaniline (4.61 g, 26.83 mmol, 3 equiv), K2CO3 (4.94 g, 35.78 mmol, 4 equiv), and Nal (268.18 mg, 1.78 mmol, 0.2 equiv) in freshly dried acetonitrile (200 mL) was refluxed for 36 h under N2 atmosphere. After being cooled to room temperature, the solvent was evaporated under vacuum. Water (50 mL) was added to the resultant residue and the organic material was extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were washed with 2 M HC1 (aq.) (3 x 30 mL) and then with sat. NaHCO? (aq.) (50 mL). After being dried over Na2SO4, the solvent was removed in vacuo. The resultant residue was then purified by silica gel column chromatography (eluent: petroleum ether/diethyl ether = 99.7/0.3) to afford (5)-4-(2-bromophenyl)-4, 5,8,9, 10, 11 , 12, 13 , 14, 15-decahydro-3H-dinaphtho[2, 1 -c: 1 ',2'- e]azepine (S10) as a white solid (2.54 g, 62% yield). 'H NMR (500 MHz, CHLOROFORM- d)S = 7.60 (d, J= 7.8 Hz, 1 H), 7.16 (t, J = 7.5 Hz, 1 H), 7.08 (d, J = 7.5 Hz, 2 H), 7.00 (d, J = 7.5 Hz, 2 H), 6.91 (d, J= 7.8 Hz, 1 H), 6.87 (t, J= 7.6 Hz, 1 H), 3.84 (d, J= 12.0 Hz, 2 H), 3.72 (d, J= 12.0 Hz, 2 H), 2.95 - 2.83 (m, 4 H), 2.80 - 2.70 (m, 2 H), 2.38 - 2.25 (m, 2 H), 1.90 - 1.78 (m, 6 H), 1.69 - 1.57 (m, 2 H); ¹³ C NMR (125 MHz, CHLOROFORM-d)S = 150.2, 138.1, 136.9, 135.5, 133.8, 132.1, 128.4, 127.6, 126.1, 123.5, 122.2, 119.4, 54.5, 29.5, 27.8, 22.9, 22.8.

Representative procedure for C-P coupling:

In a sealed tube, (5)-4-(2-bromophenyl)-4,5,8,9,10,l l,12,13,14,15-decahydro-3H- dinaphtho[2,l-c:r,2'-e]azepine (S10) (500 mg, 1.09 mmol, 1 equiv), Pd(OAc)2 (12.24 mg, 0.054 mmol, 0.05 equiv), dippf (27.37 mg, 0.065 mmol, 0.06 equiv), and NaO ^z Bu (125.77 mg, 1.30 mmol, 1.2 equiv) were added. After the tube was degassed with N2 for 15 min, the freshly dried and degassed toluene (12 mL) was added and the mixture was stirred at room temperature for 20 min. Then, di- 1 -adamantylphosphine (362.84 mg, 1.19 mmol, 1.1 equiv) was added to the reaction mixture in one portion under N2 atmosphere and the tube was heated to 110 °C for 24 h. After being cooled to room temperature, the solvent was removed in vacuo and the resultant residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 95/5) to afford Ad-(H8)ChetPhos (L3) as a white solid (408 mg, 55% yield).

Ad-(H8)ChetPhos (L3):

White solid, 408 mg, 55% yield; R/= 0.30 (petroleum ether/ethyl acetate = 95/5); ¹ H NMR (500

MHz, CHLOROFORM-d)S = 7.75 (d, J = 7.5 Hz, 1 H), 7.17 (t, J = 7.6 Hz, 1 H), 7.06 - 6.97 (m, 3 H), 6.87 (d, J = 7.5 Hz, 2 H), 6.81 (dd, J = 4.3, 7.7 Hz, 1 H), 3.75 (d, J = 11.9 Hz, 2 H), 3.69 (d, J = 11.9 Hz, 2 H), 2.95 - 2.81 (m, 4 H), 2.80 - 2.70 (m, 2 H), 2.35 - 2.25 (m, 2 H), 2.10 (br. s., 6 H), 1.99 - 1.88 (m, 9 H), 1.88 - 1.79 (m, 9 H), 1.78 - 1.69 (m, 6 H), 1.69 - 1.59 (m, 8 H); ¹³ C NMR (125 MHz, CHLOROFORM-d)S = 158.9 (d, J = 20.9 Hz), 138.1, 137.6 (d, J = 2.7 Hz), 136.4, 135.4, 132.7, 130.4 (d, J = 23.6 Hz), 128.7, 128.2, 126.2, 121.9 (d, J = 3.6 Hz), 121.2, 56.0, 42.7, 42.6, 41.2, 41.1, 37.7 (d, J = 25.4 Hz), 37.1, 36.4 (d, J = 27.2 Hz), 29.6, 29.1 (d, J = 9.1 Hz), 29.0 (d, J = 8.0 Hz), 27.8, 23.0, 22.9; ³¹ P NMR (162 MHz, CHLOROFORM- d)S = 22.9. ^z Bu-(H8)ChetPhos (L4):

White solid, 348 mg, 61% yield; R = 0.20 (petroleum ether/ethyl acetate = 90/10); ¹ H NMR (700 MHz, CHLOROFORM-d)S = 7.72 (td, J = 1.5, 7.7 Hz, 1 H), 7.20 - 7.13 (m, 1 H), 7.06 - 6.96 (m, 3 H), 6.86 (d, J = 6.9 Hz, 2 H), 6.80 (ddd, J = 1.1, 4.5, 8.0 Hz, 1 H), 3.80 - 3.65 (m, 4H), 2.89 - 2.84 (m, 4 H), 2.78 - 2.70 (m, 2H), 2.34 - 2.25 (m, 2 H), 1.88 - 1.78 (m, 6 H), 1.64 - 1.54 (m, 2 H), 1.32 (d, J = 11.4 Hz, 9 H), 1.12 (d, J = 11.4 Hz, 9 H); ¹³ C NMR (175 MHz, CHLOROFORM-d)S = 158.2 (d, J= 21.6 Hz), 138.1, 136.5, 136.4 (d, J= 3.8 Hz), 135.3, 132.9 (d, J= 24.2 Hz), 132.5, 128.8, 128.2, 126.2, 121.7, 121.6 (d, J = 3.8 Hz), 55.9, 33.2 (d, J= 25.4 Hz), 31.6 (d, J= 15.3 Hz), 31.5 (d, J= 25.4 Hz), 29.8 (d, J= 14.0 Hz), 29.5, 27.8, 22.9, 22.8; ³¹ P

NMR (162 MHz, CHLOROFORM-d)S = 204

(N)-4-(2-bromo-5-methoxyphenyl)-4,5-dihydro-3H-dinaphtho[ 2,l-c:l',2'-e]azepine (Sil):

A mixture of (S)-2,2'-bis(bromomethyl)-l J '-binaphthalene (S4) (4.23 g, 9.60 mmol, 1 equiv), 2- bromo-5-methoxyaniline (5.83 g, 28.83 mmol, 3 equiv), K2CO3 (5.31 g, 38.40 mmol, 4 equiv), and Nal (287.79 mg, 1.92 mmol, 0.2 equiv) in freshly dried acetonitrile (200 mL) was refluxed for 36 h under N2 atmosphere. After being cooled to room temperature, the solvent was evaporated under vacuum. Water (50 mL) was added to the resultant residue and the organic material was extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were washed with 2 M HC1 (aq.) (3 x 30 mL) and then with sat. NaHCO, (aq.) (50 mL). After being dried over NaiSCL, the solvent was removed in vacuo. The resultant residue was then purified by silica gel column chromatography (eluent: petroleum ether/DCM = 90/10 and then petroleum ether/ethyl acetate = 98/2) to afford (5')-4-(2-bromo-5-methoxyphenyl)-4,5-dihydro-3H- dinaphtho[2,l-c:l',2'-e]azepine (Sil) as a white solid (3.33 g, 72% yield). ¹ H NMR (500MHz, CHLOROFORM-d) 5 = 7.97 (dd, J = 4.0, 8.3 Hz, 4 H), 7.59 - 7.45 (m, 7 H), 7.37 - 7.28 (m, 2 H), 6.53 - 6.46 (m, 2 H), 4.15 (d, J= 12.2 Hz, 2 H), 3.93 (d, J= 12.2 Hz, 2 H), 3.74 - 3.66 (m, 3 H); ¹³ C NMR (126 MHz, CHLOROFORM-d) 5 = 159.4, 150.8, 135.0, 134.1, 133.4, 133.2, 131.3, 128.8, 128.3, 127.7, 127.5, 125.9, 125.6, 109.7, 108.8, 108.8, 55.4, 54.8.

Ad-(5-OMe)ChetPhos (L5):

In a sealed tube, (S)-4-(2-bromo-5-methoxyphenyl)-4,5-dihydro-3H-dinaphtho[2,l -c: r,2'- e]azepine (Sil) (500 mg, 1.04 mmol, 1 equiv), Pd(OAc)i (11.67 mg, 0.052 mmol, 0.05 equiv), dippf (26.10 mg, 0.0624 mmol, 0.06 equiv), and NaO ^z Bu (120 mg, 1.248 mmol, 1.2 equiv) were added. After the tube was degassed with N2 for 15 min, the freshly dried and degassed toluene (12 mL) was added and the mixture was stirred at room temperature for 20 min. Then, di-1- adamantylphosphine (346 mg, 1.14 mmol, 1.1 equiv) was added to the reaction mixture in one portion under N2 atmosphere and the tube was heated to 110 °C for 24 h. After being cooled to room temperature, the solvent was removed in vacuo and the resultant residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 95/5) to afford Ad-(5- OMe)ChetPhos (L5) as a white solid (413 mg, 57% yield). White solid, 413 mg, 57% yield; Ry = 0.50 (petroleum ether/ethyl acetate = 90/10); 'H NMR (500 MHz,CHLOROFORM-d) 8 = 7.96 (d, J= 8.1 Hz, 2 H), 7.93 (d, J= 8.2 Hz, 2 H), 7.68 (d, J = 8.5 Hz, 1 H), 7.54 (d, J = 8.5 Hz, 2 H), 7.51 - 7.40 (m, 4 H), 7.29 (t, J = 7.6 Hz, 2 H), 6.63 (dd, J = 2.4, 8.5 Hz, 1 H), 6.44 (t, J= 3.4 Hz, 1 H), 4.05 (d, J= 12.1 Hz, 2 H), 3.97 (d, J = 12.2 Hz, 2 H), 3.72 (s, 3 H), 2.07 (br. s., 6 H), 1.97 - 1.88 (m, 9 H), 1.87 - 1.80 (m, 3 H), 1.77 - 1.65 (m, 12 H); ¹³ C NMR (126 MHz,CHLOROFORM-d) 8 = 160.3 (d, J = 23.6 Hz), 160.1, 138.4 (d, J= 2.7 Hz), 134.8, 134.1, 133.1, 131.4, 128.5, 128.2, 128.0, 127.5, 125.6, 125.3, 121.2 (d, J = 22.7 Hz), 107.8 (d, J = 4.5 Hz), 107.1, 55.0, 53.4, 42.6 (d, J = 13.6 Hz), 41.2 (d, J = 12.7 Hz), 37.6 (d, J = 25.4 Hz), 37.1(d, J = 4.5 Hz), 36.4 (d, J = 26.3 Hz), 29.0 (d, J = 18.2 Hz), 29.0; ³¹ P

NMR (202 MHz,CHLOROFORM-d) 8 = 20 74

(N)-l-(3-bromo-4-(3,5-dihydro-4H-dinaphtho[2,l-c:l',2'-e] azepin-4-yl)phenyl)ethan-l-one (S12):

A mixture of (S)-2,2'-bis(bromomethyl)-l J '-binaphthalene (S4) (4.23 g, 9.60 mmol, 1 equiv), 1- (4-amino-3-bromophenyl)ethan-l-one(6.17 g, 28.82 mmol, 3 equiv), K2CO3 (5.31 g, 38.40 mmol, 4 equiv), and Nal (287.79 mg, 1.92 mmol, 0.2 equiv) in freshly dried acetonitrile (200 mL) was refluxed for 72 h under N2 atmosphere. After being cooled to room temperature, the solvent was evaporated under vacuum. Water (50 mL) was added to the resultant residue and the organic material was extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were washed with 2 M HC1 (aq.) (3 x 30 mL) and then with sat. NaHCO, (aq.) (50 mL). After being dried over Na2SO4, the solvent was removed in vacuo. The resultant residue was then purified by silica gel column chromatography (eluent: petroleum ether/DCM = 90/10 and then petroleum ether/ethyl acetate = 96/4) to afford (5)-l-(3-bromo-4-(3,5-dihydro-4H-dinaphtho[2,l- c: l',2'-e]azepin-4-yl)phenyl)ethan-l-one (S12) as a white solid (2.1 g, 45% yield). ¹ H NMR (500 MHz,CHLOROFORM-d) 8 = 8.25 (d, J = 1.8 Hz, 1 H), 7.97 (t, J= 7.9 Hz, 4 H), 7.77 (dd, J = 1.8, 8.4 Hz, 1 H), 7.58 - 7.48 (m, 4 H), 7.46 (d, J= 8.2 Hz, 2 H), 7.36 - 7.30 (m, 2 H), 6.90 (d, J = 8.5 Hz, 1 H), 4.26 (d, J = 12.2 Hz, 2 H), 4.04 (d, J = 12.2 Hz, 2 H), 2.56 (s, 3 H); ¹³ C NMR (126 MHz,CHLOROFORM-d) 8 = 195.8, 153.6, 135.0, 134.9, 133.3, 133.0, 131.9, 131.3, 129.0, 128.3, 127.4, 126.0, 125.8, 120.2, 117.1, 54.7, 26.3.

Ad-(4-COMe)ChetPhos (L6): In a sealed tube, (S -l-(3-bromo-4-(3,5-dihydro-4H-dinaphtho[2,l-c:T,2'-e]azepin- 4- yl)phenyl)ethan-l-one (S12) (500 mg, 1.02 mmol, 1 equiv), Pd(OAc)2 (11.45 mg, 0.051 mmol, 0.05 equiv), dippf (25.59 mg, 0.0612 mmol, 0.06 equiv), and NaO ^z Bu (117.63 mg, 1.224 mmol, 1.2 equiv) were added. After the tube was degassed with N2 for 15 min, the freshly dried and degassed toluene (12 m ) was added and the mixture was stirred at room temperature for 20 min. Then, di- 1 -adamantyl phosphine (339.34 mg, 1.12 mmol, l.lequiv) was added to the reaction mixture in one portion under N2 atmosphere and the tube was heated to 110 °C for 24 h. After being cooled to room temperature, the solvent was removed in vacuo and the resultant residue was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 95/5) to afford Ad-(4-COMe)ChetPhos (L6) as an off-white solid (403 mg, 56% yield).

Off-white solid, 403 mg, 56% yield; R/ = 0.60 (petroleum ether/ethyl acetate = 90/10); ¹ H NMR (500 MHz,CHLOROFORM-d)8 = 8.42 (s, 1 H), 7.96 (d, J = 8.1 Hz, 2 H), 7.93 (d, J = 8.2 Hz, 2 H), 7.78 (dd, J = 1.8, 8.5 Hz, 1 H), 7.58 - 7.53 (m, J = 8.5 Hz, 2 H), 7.49 (t, J = 7.4 Hz, 2 H), 7.41 - 7.35 (m, J= 8.2 Hz, 2 H), 7.34 - 7.28 (m, 2 H), 6.87 (dd, J= 4.1, 8.5 Hz, 1 H), 4.24 (d, J = 12.2 Hz, 2 H), 4.06 (d, J = 12.1 Hz, 2 H), 2.60 (s, 3 H), 2.15 (br. s., 6 H), 1.98 (br. s., 3 H), 1.91 (br. s., 3 H), 1.80 (br. s., 6 H), 1.76 (br. s., 6 H), 1.71 - 1.60 (m, 6 H); ¹³ C NMR (126 MHz,CHLOROFORM-d) 8 = 197.0, 162.5 (d, J = 21.8 Hz), 139.2(d, J= 2.7 Hz), 134.8, 133.7, 133.2, 131.4, 129.5, 129.3, 128.8, 128.3, 128.1 (d, J = 30.9 Hz), 127.6, 127.5, 125.9, 125.5, 119.6(d, J= 4.5 Hz), 56.5(d, J= 11.8 Hz), 53.4, 42.9(d, J= 13.6 Hz), 41.0(d, J= 12.7 Hz), 38.0 (d, J= 26.3 Hz), 37.0(d, J= 9.1 Hz), 36.7 (d, J= 27.3 Hz), 28.9(d, J= 29.1 Hz), 28.9 (d, J= 12.7 Hz), 26 5; ³¹ P NMR (202 MHz,CHLOROFORM-d)8 = 25 39 The inventors have been working to develop the invention, so that advantage can be achieved in an economical, practical, and facile manner. While preferred aspects and example configurations have been shown and described, it is to be understood that various further modifications and additional configurations will be apparent to those skilled in the art. It is intended that the specific embodiments and configurations herein disclosed are illustrative of the preferred nature of the invention and should not be interpreted as limitations on the scope of the invention.

ADVANTAGES OF THE PRESENT INVENTION

Exemplary embodiments for providing chiral hemilabile (P,N)-ligands and the corresponding Au(I) of the said hemilabile (P,N)-ligands discussed above may provide certain advantages. Though not required to practice aspects of the disclosure, these advantages may include those provided by the following features.

An advantage of the present invention is to provide hemilabile (P,N)-ligands and the corresponding Au(I) of the said chiral hemilabile (P,N)-ligands.

Another advantage of the present invention is to provide an efficient method reported to achieve enantioselective version of Au(I)/Au(III) redox catalysis.

Another advantage of the present invention is to provideexcellent synthetic utility of newly developed protocol of the chiral hemilabile (P,N) ligands.

Yet another advantage of the present invention is to be able to provide chiral hemilabile (P, bpligands that are able to produce 3-aminochromane derivatives in moderate to good yield (42- 86%) and excellent enatiomeric excess (96-99%).

Yet another advantage of the present invention is to provide an easy access to enantio-enriched 6-bromo-3-aminochromane which is a precursor for the synthesis of serotonin 5-HT? receptor and MALT1 inhibitor.

Yet another advantage of the present invention is to provide a powerful approach for accessing asymmetric Au(I)/Au(III) redox catalysis. Yet another advantage of the present invention is to provide an application of the ligand-enabled strategy has been shown to achieve highly enantioselective 1,2-oxy- and aminoarylation of alkenes. Various 3-oxychromanes and 3-aminochromanes which represent the core structure of several drug molecules could be readily accessed in enantio-enriched form.