Regioselective Reactions on a Chiral Substrate Controlled by the Configuration of a Chiral Catalyst

Abstract

A racemic mixture may be partially transformed in the presence of a chiral catalyst by kinetic resolution and formation of products with new structural features. If the starting material is fully consumed the products may still be enantiomerically enriched. The situation is summarized in the Introduction. A brief discussion on the regioselective transformations occurring on a racemic mixture under the influence of a chiral catalyst is presented in Section 2. Often stereo-differences occur, each enantiomer of the starting material resulting in a different product. It allows one to predict what the behaviour of some enantiopure substrates should be in presence of each of the enantiomers of a chiral catalyst. Many examples are presented in Section 3. The chiral substrates under consideration have two different reacting sites, usually of the same nature (OH, CC, allylic positions, CH for carbene insertion, epoxide fragment, etc.). In some cases the absolute configuration of the catalyst allows an excellent control of the regioselectivity. This approach is promising for the selective transformation of chiral molecules.

1 Introduction

Non-enzymatic asymmetric catalysis has developed very much in the last thirty years and become a powerful method to create a chiral product,1–5 or to differentiate between the two enantiomers of a racemic mixture.6–9 The classical enantioselective synthesis10 involves an achiral substrate often equipped with a CO, CN or CC double bond. An enantioface is selectively attacked with the help of the catalyst. Another type of enantioselective transformation is related to the preferential selection of one site (topos)5 as described in Scheme 1. Asymmetric catalysts are also able to differentiate between two enantiomers of a racemic mixture by inducing a faster transformation of one of them (kinetic resolution). Processes in Scheme 1 involve substrates either devoid of stereogenic units or which are of meso-type structures where pairs of stereogenic centers are related by a plane or center of symmetry.

Scheme 1. Some examples of site selection on achiral compounds.

In a kinetic resolution the reaction may involve the formation of a stereogenic unit from a CX or CC double bond, giving a mixture of diastereomeric products and of enantioenriched starting material.

For a full transformation of the racemic substrate the products will consist of a mixture of enantioenriched diastereomers. Horeau and Guetté discussed this case in the asymmetric reduction of racemic camphor, they established that the mole ratio of the diastereomeric alcohols (dr) is equal to the inverse ratio of their corresponding enantiomeric excesses (ees).12 We subsequently considered the case of the partial transformation of racemates with a kinetic resolution or not of the remaining starting material. The system studied was the incomplete hydrogenation of a racemic dehydropeptide catalyzed by a chiral rhodium complex.13 We established Eq. (1) which relates the relative amounts and ees of the various components, it is a generalization of the above Horeau relation.12 In this equation the two diastereomers (ee₁ and ee₂) are present in the respective amounts n₁ and n₂, in addition the starting material is recovered in amount n₃ with ee₃.

• 

It is possible to deduce qualitatively or quantitatively the diastereoselectivity of the reaction on each enantiomer of the starting material for a given enantiomer of the catalyst.

An asymmetric catalyst can also transform a racemic mixture by a site-selection process instead of a face differentiation, giving a mixture of regioisomers instead of a mixture of diastereomers. This less frequent situation affords information on the behaviour of each enantiomer of the racemic substrate. Eq. (1) applies with n₁, n₂ and n₃ being the relative amounts of the recovered starting material and the two regioisomeric products. In the present article we intend to shortly review this area on some selected examples before considering the regioselective control on a chiral substrate under the influence of a chiral catalyst.

2 Regioselective Transformation on a Racemic Mixture

The first example of a non-enzymatic Baeyer–Villiger oxidation of a racemic ketone was described in mid-1990s.14,15 Bolm et al. used a copper complex (R)-4 to catalyze the oxidation of rac-1 by the mixture O₂/t-BuCHO. A mixture of normal Baeyer–Villiger lactone 2 and abnormal lactone 3 was obtained (Scheme 2).14 The results were measured for 50% conversion of racemic ketone 1, the remaining ketone having a close to racemic composition. From the experimental data reported in Scheme 2 it is easy to calculate the relative amounts of 2, 3, ent-2 and ent-3 (45.9/43.2/9.1/1.8). It shows that (R)-4 catalyst converted 1 into a mixture of regioisomeric lactones 2 and 3 in almost equivalent amounts (2/3=45.9/43.2=1.06) while the same catalyst transformed ketone ent-1 into the mixture of ent-2 and ent-3 where the normal lactone ent-2 was largely predominant (ent-2/ent-3=9.1/1.8=5.05). This last experiment leads to the conclusion that the couple catalyst (S)-4/ketone 1 should also generate the mixture of normal and abnormal lactones in the ratio 2/3=5.05 because of mirror-symmetry reasons. It is clear here that the regioselectivity of oxygen insertion on enantiopure ketone 1 depends to some extent on the absolute configuration of the catalyst.

Scheme 2. Baeyer–Villiger oxidation of a racemic ketone catalyzed by a chiral copper complex.14 The data have been discussed in refs.17,18

There are several reports of Baeyer–Villiger oxidations of racemic ketones catalyzed by chiral complexes.15 The Zr/Salen system of Katsuki et al. sometimes allowed the process to strongly favour the formation the abnormal lactones.16

Regioselective transformations have been detected in the Sharpless epoxidation of racemic bis-allylic alcohols.19 With the D-DIPT/Ti(O-i-Pr)₄ catalyst the racemic alcohol 5 gave monoepoxide 6 and acetal ent-8, the latter arising from epoxidation of the more substituted double bond and a subsequent rearrangement (Scheme 3). The experimental data suggest that enantiopure 5 and D-DIPT should lead mainly to 6 while L-DIPT will generate the regioisomeric epoxide 7.

Scheme 3. Sharpless epoxidation of racemic allylic alcohol 5.19

Diazoacetates of a racemic divinylcarbinol 9 gave rise to intramolecular cyclopropanation in presence of a chiral rhodium complex (Scheme 4).20 Racemic 9 was fully transformed into a mixture of isomeric cyclopropanes 10 and 11, each one derived from one enantiomer of 9. This is indicative that the two enantiomers of the catalyst should lead to products deriving from regioisomeric attack on the double bonds of the enantiopure 9.

Scheme 4. Intramolecular cyclopropanation of a racemic diene catalyzed by a chiral rhodium complex.20

Diazoacetates of racemic cyclohexenol 12 in presence of the Rh₂[(S)-MEOX]₄ catalyst were transformed into a mixture of lactone 13 and cyclohexenone 14 (Scheme 5).21 Compound 14 is derived from an intermediate β-lactone produced by a carbene insertion on the CH of the asymmetric center of (R)-12 followed by a fragmentation releasing ketene.

Scheme 5. Regiodivergent reaction on a racemic mixture: intramolecular cyclopropanation (a) on (S)-12 and CH insertion (b) followed by ketene extrusion on (R)-12.

Ethylzirconation and ethylalumination of the double bond of racemic 2-phenyl-3,4-dihydrofuran have been realized by the use of a chiral zirconium complex.22,23 The full conversion of the racemic substrate gave a mixture of two products, each one with >95–99% ee. The data indicate that the two enantiomers of the substrate have reacted differently with the organometallic reagent, with a regioselective control in the attack of the double bond.

3 Chiral Catalysts on Chiral Substrates

The use of chiral reagents or catalysts to create a new stereogenic center on a chiral substrate is very common. The concepts behind these reactions have been elaborated by Masamune et al., they are useful in stereocontrolled syntheses.24 The authors proposed that the inherent steric controls of a chiral susbtrate and a chiral catalyst for a given transformation cooperate (match pair)25 or are antagonist when the enantiomeric catalyst is involved (mismatch pair). The match/mismatch concept is very apparent in Scheme 3 where the pair 5/D-DIPT lead to 6 while the pair ent-5/D-DIPT gives the isomeric epoxide ent-7. The examples of Scheme 3 and Scheme 4 clearly indicate that the site selectivity on a chiral substrate can be controlled by the absolute configuration of the catalyst. This is a case of regiodivergent reactions under catalyst control.7,17,18

3.1 Sharpless Epoxidation

The transformations of Scheme 3 have been confirmed by a reaction carried out on enantiopure 5. D-DIPT gave epoxide 6 (from epoxidation on the a site) while L-DIPT exclusively led to attack on b site with formation of ent-6 (Scheme 6).

Scheme 6. Sharpless epoxidation of enantiopure allylic alcohol 5.19

3.2 Allylic Substitution

The allylic substitution in the presence of an organometallic catalyst is a complex process. It involves the formation of an intermediate π-allylic complex which may be able to interconvert into a stereoisomeric π-allylic system according to the conditions and the catalyst. Usually palladium catalysts favour the linear product, Mo and W catalysts give predominantly the branched product.26 In the course of a detailed mechanistic study involving chiral molybdenum catalysts Reider et al. found that enantiopure 15 (Scheme 7) gave a different product distribution according to the configuration of ligand 18.26 Some results are tabulated in Scheme 7. The match situation (R)-15/(R,R)-18 generated a large amount of the branched product in excellent ee while in the mismatch pair (R)-15/(S,S)-18 the regioselectivities and ees are lower. In this last case the rate of equilibration between π-allyl complexes was competitive with the subsequent malonate attack.

Scheme 7. Regioselective allylic substitution of (R)-15.

Kinetic resolution in palladium-catalyzed allylic substitution on racemic compounds is well documented. What is less common is the possibility to get regioisomeric products deriving from different enantiomers of the starting material (regiodivergent kinetic resolution).27–32 As expected, the chemical transformations performed on the enantiopure allylic substrates show a very strong catalyst control on the regioselectivity. It will be exemplified in Scheme 8, Scheme 9 and Scheme 10.

Scheme 8. Reaction of the anion of dimethyl malonate on allylic acetates catalyzed by a chiral Pd complex.

The reaction of dimethyl malonate on some enantioenriched allylic acetates allowed Pfaltz et al. to produce at will regioisomeric products in high ees (>99% ee).28 For example, 19 (94% ee) gave 20 or 21 with (S) or (R) catalyst 22, respectively (Scheme 8).

The substitution reaction of dimethyl malonate anion on a steroidal allylic acetate 23 (Scheme 9) has been studied by Shimizu et al.29 The palladium catalysts involving (S) or (R)-binap promoted different reactions. With (S)-binap the main product was derived by the substitution reaction at the C-3 position, with almost exclusive retention of configuration. The minor product was the diene 25. With (R)-binap (mismatch combination) the product distribution is different: diene 25 is predominant while the minor substitution product 24 was obtained as a mixture of epimers at C-3. These results were confirmed by similar reactions performed in the kinetic resolution of rac-26 with an (S)-binap-palladium catalyst.

Scheme 9. Substitution versus elimination in some Pd-binap-catalyzed reactions of steroidal allylic esters.

Cook et al. investigated the formation of vicinal diamines from racemic 5-vinyloxazolidinones 27 and phtalimide in presence of a chiral palladium complex.30 They also briefly studied the use of enantiopure substrate 27 (Scheme 10). They found that the two enantiomers of binap led to a different ratio of regioisomeric diamides 28 and 29, although there is not a reversal of the regioselectivity with the mismatch pair.

Scheme 10. Chiral Pd-binap-catalyzed synthesis of diamides.

Fiaud et al. have studied the catalytic nucleophilic substitution of allylic acetate (R)-30 by potassium dimethyl malonate (Scheme 11).31 The catalyst precursor was an equimolar amount of Pd(dba)₂ and a chiral bidentate ligand L*. Due to the harsh conditions (120 °C, DMSO) the initial product 31a or 32a was partially transformed into the monoesters 31b or 32b, respectively, with full conversion of the starting material 30. (E)-Configuration has been proposed for 32a and 32b. The authors found that (R)-30 and (S)-30 gave different regioselectivities for a chiral ligand of a given configuration (see data in Scheme 11). For example (S)-i-PrPhox provided predominantly products 32 derived from an S_N′-like process on (R)-30 (66:34) while (S)-30 gave mainly the formal S_N products (87:13). One can predict that (R)-i-PrPhox on (R)-30 must necessarily generate (S)-31b with an overall S_N/S_N′ ratio of 87:13 as mixture of (R)-31a and (R)-31b. It means that the regioselectivity of the nucleophilic substitution on enantiopure (R)-30 is to some extent controlled by the absolute configuration of i-PrPhox.

Scheme 11. Catalytic nucleophilic substitution of allylic acetate (R)-30.

Allylic substitution on some oxabicyclic systems 33 has been widely studied, especially by Lautens et al.32 Chiral rhodium complexes in methanol provided a regioselective cleavage according to the configuration of the diphosphine ligand 36 in the complex (Scheme 12). The isomeric alcohols formerly derived from the cleavage (a or b types) of the bridged oxygen, with endo attack of methanol on one or the other side of the double bond. Alcohol 34 is completely free of its isomer 35 and vice versa. These experiments have been confirmed by regiodivergent kinetic resolutions of racemic mixture.33

Scheme 12. Regioselective methanolysis of an oxabicyclic alkene under catalyst control.

3.3 Epoxide Opening

Gansäuer et al. described in 2007 the regiodivergent reductive opening of chiral epoxides 37 catalyzed by titanium complexes 40 or ent-41 (Scheme 13).37 Manganese metal and cyclohexadiene are the reducing system. Catalyst 40 afforded alcohol 38 (71%, 99% ee) as a major product while the minor alcohol 39 (13%) was obtained with 8% ee. With ent-40 it was alcohol 39 which predominated (76%, 94% ee) against the regioisomer 38 (10%, 50% ee). The authors provided many additional examples of regioselective opening of enantioenriched epoxides which strongly depend of chiral catalyst 40 or ent- 40.

Scheme 13. Regioselective reduction of a chiral epoxide.

3.4 CH Insertions

Doyle et al. brillantly developed in 1996 the controlled intramolecular CH insertion reaction of diazoacetates.38 The authors used the chiral dirhodium(II) carboxamidate catalysts 42–45 shown in Scheme 14. Enantiopure (1S,2R)-cis-cyclohexanol 46 was converted into its diazoacetate 47. Various sites are potentially available for the insertion reaction as shown in Scheme 15. Sites (a)–(d) may lead to lactones 48–51. Diazoacetates 47 in presence of catalyst 42 gave in excellent yield almost exclusively lactone 48, while catalyst ent-42 produced mainly lactone 49. Catalyst 43 gave 49 (82%) and some 50 (7%, Scheme 15).

Scheme 14. Some chiral dirhodium(II) carboximidate complexes.

Scheme 15. Lactone formation by catalyzed decomposition of diazoester 47.

The pair of enantiomeric catalysts 42 and ent-42 achieved a full control of regioselectivity of the carbene insertion into CH (a) versus CH (b). The catalyst ent-43 gave an excellent control in the diastereoselective insertion involving CH (b) versus CH (c). Catalyst 44 afforded mainly β-lactone 51 (56%) and a mixture of 48 and 49, while ent-44 generated almost exclusively 49.38

A similar study has been done with the decomposition of menthyl diazoacetate 52 (Scheme 16). An achiral rhodium catalyst gave an almost equivalent amount of lactones 53 and 54 (substrate control). Catalyst 42 slightly modified the product distribution; but 43 was able to almost fully give lactone 53 (match pair). The mismatch situation with ent-43 catalyst afforded a mixture of lactones 53, 54 and 55.

Scheme 16. Competitive intramolecular CH insertions in the decomposition of menthyl diazoacetate 52.

The regio- and diastereoselectivities of the insertion reaction of cyclohexyl or menthyl diazoacetates were discusssed taking into account the structure of the catalysts and the conformations of the substrates. A trend for the insertion into an equatorial CH bond was noticed. The results obtained with the cyclohexyl systems were extended to some steroidal diazoacetates.39 The experiments were done on various 3-hydroxy steroids, in Scheme 17 are indicated the product distributions observed for the decomposition of the diazoacetate of 3β-hydroxy-(5α)-androstane 56. In the presence of an achiral catalyst Rh₂(OAc)₄ the mixture of lactones 57–59 was obtained. Catalyst 43 gave β-lactone 58 as the main product whereas ent-43 generated a different distribution of lactones with 57 as the main component formed by the insertion to the equatorial CH bond at the 2-position. Clearly the structure and the absolute configuration of the rhodium catalysts play a key role in the regioselectivity and diastereoselectivity of the insertion reaction.

Scheme 17. Competitive carbene insertions in some CH bond of the (5α)-androstane series.

3.5 Nitroso Diels–Alder Reaction

The nitroso Diels–Alder reaction between an arylnitroso compound and a racemic diene can give rise to a regiodivergent reaction, which was studied by Studer et al.40 The reaction was catalyzed by a Cu(I)/chiral phosphine complex. The authors also studied the effect of various chiral diphosphines in the cycloaddition on the chiral diene 60. The best results were obtained with walphos 63 (Scheme 18). An almost perfect control of the regioselectivity was observed, together with the exclusive formation of the anti-adducts.

Scheme 18. Regioselective nitroso Diels–Alder reaction.

3.6 Intramolecular Hydroacylation on a Triple Bond

Tanaka and Fu discovered that the parallel kinetic resolution of a racemic 4-alkynal 64 catalyzed by a Rh(I)/Tol-binap complex generated a 1:1 mixture of enantioenriched cyclobutanone 65 and cyclopentanone 66.41 As a consequence they treated alkynal (R)-64 with (R)- or (S)-tolyl-binap rhdodium catalyst and obtained an excess of cyclobutanone (R)-65 or cyclopentanone (R)-66, each one in 99% ee (Scheme 19). As outlined by the authors the appropriate choice of the appropriate enantiomer of Tol-binap dictates if a cyclopentanone or a cyclobutanone is formed. This type of catalyst selectivity can be categorized as a catalyst control in the regioselective addition of an intermediate acylrhodium hydride on the triple bond (Scheme 19).

Scheme 19. Regioselective intramolecular hydroacylation.

3.7 Alcoholysis of Substituted Succinic Anhydrides

Regiodivergent kinetic resolution of racemic monosubstituted succinic anhydrides was established during alcoholysis catalyzed by a modified Cinchona alkaloid 70.42 This was a good indication that different regioselectivity should be achieved by each of the enantiomers of the catalyst. Since the enantiomer of the catalyst 70 was not available the reaction was done on each enantiomer of the anhydride (Scheme 20). Catalyst 70 [(DHQD)₂AQN] is based on the dihydroquinidine fragment. It is well documented that dihydroquinine, which is a diastereomer of dihydroquinidine, often leads in asymmetric synthesis to enantiomeric products.43 Consequently, the authors used (DHQ)₂AQN as a catalyst for alcoholysis of enantiopure (S)-2-methyl succinic anhydride (S)-67, they recovered the two monoesters (S)-68 and (S)-69 in a ratio 6:94. This is the opposite regioselectivity to that obtained with (DHQD)₂AQN 70 (see Scheme 20).

Scheme 20. Regioselectivity in catalytic alcoholysis of 2-methyl succinic anhydride.

Methanolysis of racemic lactone 71 mediated by quinidine gave quantitatively the mixture of monomethyl esters 72 and 73 (Scheme 21).44 The stereochemical analysis done by Bolm et al. indicated that 71 and ent-71 generated regioisomeric products 72 and 73 (99% ee versus 91% ee, respectively). It means that one expects quite high regioselectivity in the methanolysis of 71 with formation of 72 if quinidine is the catalyst, while quinine (a mimic of ent-quinidine) should mainly produce 73, in a process where the chiral base can be taken in catalytic amount as established in similar cases.45

Scheme 21. Regiodivergent methanolysis of a cyclic racemic anhydride.

3.8 Miscellaneous

Diols lead to various kinds of transformation in the presence of a chiral catalyst. Most of the reactions have been performed on a racemic mixture and may give rise to regiodivergent kinetic resolutions. An early report noticed that dehydrogenation of chiral unsymmetrical α,ω-diols catalyzed by a chiral complex should give rise to the formation of lactones with different regioselectivity (Scheme 22).46 Some experiments were carried out with a ruthenium/diop catalyst on (R)-74. A small difference of regioselectivity has been evidenced between the two enantiomeric catalysts.

Scheme 22. Formation of lactones from chiral diols.

Several racemic 1,2-diols have been monoacylated in presence of a chiral catalyst.47–50 It can be deduced from the product distribution of the kinetic resolution that some regioselectivities driven by the configuration of the catalyst are expected for a reaction on a chiral diol.49,50 An interesting study compared the monoacetylation of erythromycin A in the presence of catalytic amounts of N-methylimidazole or a small peptide analogue. A very large site selectivity was noticed, however there were no comparisons between the two enantiomers of the catalytic peptide.49

Catalytic silylation of racemic 1,2-diols in the presence of an organocatalyst (a peptide derivative) can be highly site and enantioselective.50 It gives some hope that, in such a type of reaction performed on a chiral diol, the regioselectivity could be closely linked to the absolute configuration of the catalyst.

There are various ways to screen enantioselective catalyst candidates by high throughput methods.51 The fast screening of new chiral catalysts for selective reactions on achiral substrates with two enantiotopic sites (such as in Scheme 1, for example) has been pioneered by Reetz et al.52 These authors used the transformation of pseudo-meso substrates 77 or pseudo-prochiral substrates 78 into chiral products (Scheme 23). For example, enantiopure pseudo-meso diester 79 was monohydrolyzed in the presence of a lipase to generate predominantly monoalcohol 80 with loss of deuterium. The regioselectivity can be then easily measured by mass spectroscopy on small amounts because of the deuterium labelling. The ability of the catalyst to desymmetrize the meso-diacetate of cis-cyclopentene 3,5-diol is then known.

Scheme 23. Enantiopure pseudo-meso or pseudo-prochiral substrates for evaluation of chiral catalysts.

4 Conclusions

The control of regioselective transformations of chiral compounds is an important problem which often needs several steps. In this review it was shown that the use of a chiral catalyst with the suitable absolute configuration is a straightforward approach to get the desired reaction on one or the other site. Much useful information has been afforded when a racemic mixture gives rise to a regiodivergent kinetic resolution.

Usually the regioselectivity involves two sites of the same kind, for example, two double bonds (Scheme 6), two carbonyl groups in an anhydride (Scheme 20) or two ester functionalities (Scheme 23). The regioselectivity can be observed in the reaction of a dissymmetric functional group as in the ring opening of some epoxides (Scheme 13) or in the Diels–Alder addition on a nitroso compound (Scheme 18). More unusual is the chiral catalyst control between two different kinds of reactive centers located at different sites of the chiral substrate as the carbene insertion into a CH bond versus a CC cyclopropanation (see Scheme 5 for the corresponding divergent kinetic resolution scenario).

An unselective catalytic reaction because of a dual reactivity (for example, epoxidation and allylic oxidation)53 should also be improved by the chiral catalyst control. It will be interesting to see to what extent this methodology will apply to polyhydroxylated compounds, for example, to trigger their regioselective oxidation or acylation. In conclusion, one can predict that the spectacular advances in enantioselective catalysis will indirectly contribute to a great extent to set up new approaches concerning selective transformations of chiral compounds under the chiral catalyst control.

Note Added in Proof

A highly regiodivergent ring opening of chiral aziridines by trimethylsilyl azide has been recently published.55 This reaction is catalyzed by a chiral Y complex and provides 1,2-diamine derivatives.

Acknowledgements

We thank Université Paris-Sud and CNRS for financial support. One of us (R.R.K.) acknowledges Institut des Substances Naturelles du CNRS (Gif-sur-Yvette) for its financial support.

Biographical Information

Henri B. Kagan was born in France in 1930. He graduated from the Sorbonne and Ecole Nationale Supérieure de Chimie de Paris in 1954. He prepared his Ph.D. under the supervision of Dr. J. Jacques. He joined Prof. A. Horeau at the Collège of France in Paris in 1962 as a research associate. In 1965 he worked with Prof. T. Mabry at the University of Texas, Austin. He joined the Université Paris-Sud, Orsay in 1968. He is emeritus Professor of Université Paris-Sud since 1999. He is a member of the French Academy of Sciences. H. B. Kagan developed investigations in various areas, such as asymmetric synthesis, asymmetric catalysis, lanthanide reagents (for example, diiodosamarium). His awards include the Prelog Medal, the August-Wilhelm-von-Hofmann Medal, the Chirality Medal, the Nagoya Medal of Organic Chemistry, the Tetrahedron Prize, the 2001 Wolf Prize for Chemistry (shared with K. B. Sharpless and R. Noyori), the 2002 Grand Prix de la Fondation de la Maison de la Chimie (shared with H. Yamamoto), the Ryoji Noyori Prize in 2002. He was the recipient of the Bower Award of Franklin Institute in 2005 and of the Horst-Pracejus Prize in 2007.

Biographical Information

Raju Ranjith Kumar was born in Udhagamandalam (India) in 1977. He obtained his M.Sc. (2001) in Chemistry from Government Arts College (Bharathiar University), Udhagamandalam and Ph.D. (2008) from Madurai Kamaraj University, India under the supervision of Prof. S. Perumal. His Ph.D. research included synthesis, structural elucidation and antimycobacterial evaluation of novel organic heterocycles obtained via 1,3-dipolar cycloaddition, cyclocondensation and one-pot multi-step reactions. Since September 2008, he has been working as a post-doctoral research fellow under Prof. Henri B. Kagan at Université Paris-Sud. His present research project involves the investigation of the influence of absolute configuration of chiral catalysts on the reactivity and selectivity of chiral substrates.