Indian Journal of Chemistry Vol. 52B, January 2013, pp 87-108

Advances in Contemporary Research

Asymmetric Henry reaction catalysed by transition metal complexes: A short review

Nallamuthu Ananthi & Sivan Velmathi* Organic and Polymer Synthesis Laboratory, Department of Chemistry, National Institute of Technology, Tiruchirappalli 620 015, India E-mail: [email protected] Received 22 June 2011; accepted (revised) 27 September 2012

An asymmetric Henry reaction, the coupling of a nitro alkane and a carbonyl group is an important C-C bond forming reaction in organic chemistry giving chiral nitro alkanols which are useful versatile intermediates in synthetic organic chemistry. It is well known that the chiral nitroaldol products find increasing applications in the pharmaceutical industry. These converted products are important precursors of biologically active compounds. Chiral nitroalcohols can be further transformed into synthetically useful derivatives such as carboxylic acids, polyamino alcohols, polyhydroxylated amides and amino alcohols. For the catalytic asymmetric Henry reaction, among the catalysts reported so far, the transition metal complexes catalyse asymmetric Henry reaction plays an important role. Transition metal complexes catalyse the asymmetric Henry reaction efficiently and in most of the cases give the product chiral nitro alkanols in good yield and enantiomeric excess. This review summarizes the reported remarkable transition metal complex catalysts for asymmetric Henry reaction, their advantages, limitations, mechanism for their catalytic activity and the challenges that need to be addressed in this research area.

Keywords: Asymmetric C-C bond forming reaction, asymmetric Henry reaction, chiral transition metal complexes, chiral nitroaldols

The first asymmetric version of the Henry reaction exemplified in the syntheses of various was reported by Sasai et al. in 1991(Ref 1). Since pharmaceuticals including the β-blocker (S)- then, interest in this area has been expanded upon propranolol6,7, the HIV protease inhibitor Amprenavir considerably and various reports have been (Vertex 478), and construction of the carbohydrate continuously appearing in the literature on subunit of the anthracycline class of antibiotics, L- development of various metal and nonmetal based Acosamine6. catalysts for the asymmetric Henry reaction. An Not only are aromatic chiral nitro aldols important, example for the asymmetric Henry reaction is shown aliphatic nitro aldols also play an essential role in in Scheme I. reacts with nitromethane synthetic organic chemistry. An early review of the in the presence of chiral ligand giving the product data on the synthesis, chemical transformations and chiral β-nitroaldols. practical use of aliphatic nitro alcohols have been It is well known that the chiral nitroaldol products described systematically and analysed by find increasing applications in pharmaceutical Shvekhgeimer in 1998 (Ref 8). The review outlines industries. The synthetic utility of the chiral nitro- the preparation of nitro alcohols by nitroaldol is based on the versatility of the 1,2- condensation (Henry reaction), the studies high- nitro alcohols, which can be converted into 1,2-amino lighting novelty either in the procedure of alcohols, amino sugars, nitroketones, nitroalkenes, condensation of nitro-compounds with carbonyl α,β-unsaturated nitrocompounds, ketones (Nef derivatives or in the use of the target compounds are reaction), carboxylic acids2,3, in the synthesis of discussed in greater detail. The data about other natural products, poly amino alcohols and known methods for the synthesis of nitro alcohols and polyhydroxylated amides4. These converted products new information on their chemical transformations are important precursors of biologically active are presented. The review also mentioned potential compounds5,6. Many of these uses have been practical applications of these compounds. 88 INDIAN J. CHEM., SEC B, JANUARY 2013

O OH Chiral ligand NO H * 2 + CH3-NO2

Scheme I — Asymmetric Henry reaction between benzaldehyde and nitromethane

One of the many features of the Henry Reaction A detailed review on asymmetric Henry reaction that makes it synthetically attractive is that it utilizes was done by Barua et al. in 2001 (Ref 10). This only a catalytic amount of base to drive the reaction. review consists of two parts. The first part includes Additionally, a wide variety of bases can be used the metal based catalyst so far reported in asymmetric including ionic bases such as alkali metal hydroxides, Henry reaction. The metal complexes reported are alkoxides, carbonates, and sources of fluoride anion lathanum, zinc, copper, cobalt and the supported [e.g. TBAF (tetra-n-butylammonium fluoride)] or metal complexes. The second part includes the nonionic organic amine bases including TMG (1,1,3,3- organocatalysts reported in asymmetric Henry tetramethylguanidine), DBU (1,8-diazabicyclo[5.4.0]- reaction. Organocatalysts include Guanidine derived undec-7-ene), DBN (1,5-diazabicyclo[4.3.0]non-5- organocatalysts, cinchona alkaloid derived catalysts ene), and PAP (2,8,9-trialkyL-2,5,8,9-tetraaza-1- and silyl nitronates as activated nitroalkanes. phospha-bicyclo[3.3.3]undecane). It is important to The metal-complex catalysts reported for note that the base and solvent used do not have a large enantioselective asymmetric Henry reaction include influence on the overall outcome of the reaction9. alkali metal complexes, alkaline metal complexes, Like all other catalytic asymmetric reactions, transition metal complexes and rare earth metal asymmetric Henry reaction has also been classified by complexes. Among the metal complexes reported to the major three types of catalysts which include catalyse the enantioselective Henry reaction, the biocatalysts, organocatalysts, and metal complex transition metal complexes occupy an important catalysts. Among the three types of catalytic place. Transition metal complexes often have the asymmetric Henry reaction, the metal complex advantage of providing high selectivity under mild catalyzed enantioselective Henry reaction is an reaction conditions. They are cost effective compared attractive and quite powerful method in asymmetric to the rare earth metal complexes. Their activity and synthesis of chiraly pure nitroalcohols. Well designed selectivity may be tailored by varying the ligand compact molecular catalysts that consist of a metallic attached to the metal. species and chiral organic ligands can precisely Asymmetric Henry reaction was successfully control the stereochemical outcome of any catalyzed by many transition metal complexes and the asymmetric transformation. The use of chiral metal product chiral nitroaldols were formed in excellent catalysts is one of the most frequently employed ways yield and selectivity. This review summarizes to induce enantio- or diastereoselectivity in the Henry transition metal complex catalysts reported so far for reaction in which the nitro group and carbonyl oxygen enantioselective Henry reaction, their advantages, coordinate to a metal that is bound to a chiral organic limitations and mechanism for their catalytic activity molecule. Suitably designed chiral metal complexes and selectivity. control the steric course in the sense that free energy difference between enantiomers of 10 KJ/mol Types of transition metal complex catalyzed asym- corresponds to 99:1 . metric Henry reaction The key features of any asymmetric metal complex The asymmetric Henry reaction using transition catalyst include the ability to catalyze the desired metal complex as catalyst can be carried out in two reaction, as well as induction of chirality into the ways. The first method involves the participation of products. The first criterion is fulfilled by allowing isolable transition metal complex as catalyst; the coordination sites on the metal center to be accessible second method involves the participation of in situ to the substrates during the catalytic transformation. formed transition metal complex as catalyst from an The second criterion is satisfied by transferring organic chiral ligand and a transition metal salt. stereochemical information to the products from the The metal complex catalysed asymmetric Henry chiral environment surrounding the metal. reaction was developed by Sasai et al. in 1992 who

ANANTHI et al.: ASYMMETRIC HENRY REACTION 89

OH + La (O-t-Bu) OH 3 9

1

H3C CH3 H3C CH3 O O O O O O Ph N N N N N N Ph

t-Bu t-Bu Ph Ph Ph Ph

(S)-t-Bu-BOX (R)-Ph-BOX (4R,5S)-DiPh-BOX 2 3 4

OH O Et3N + CH NO 3 2 R COOEt R COOEt BOX-Cu(II)-catalyst NO 2

Scheme II — Catalytic enantioselective Henry reaction of α-keto esters with nitromethane reported by Christensen et al.18 utilized (S)-(2,2′)-binaphthol in conjunction with a developed by Christensen et al. in 2001 (Ref 18). For lanthanum alkoxide 1 which is able to promote the the first time, it was shown that ketones undergo direct reaction between unmodified nitroalkanes and catalytic highly enantioselective Henry reactions enantioselectively11-14 by making use of the producing novel optically active β-nitro α-hydroxy general principle of two-center catalysis15-17. esters having a chiral quaternary carbon center. Of the Enantiomeric excesses (ee) between 79-91% were three chiral bisoxazoline–copper(II) catalysts obtained. presented for the reaction, the combination of (S)-t- A metal/chiral ligand complex was designed Bu-BOX 2 as ligand and Cu(OTf)2 as the Lewis acid possessing two sites of opposite character, a basic site gave the most promising result with greater than 95% and an acidic site, each capable of independently conversion and 92% ee of the Henry adduct at room activating in close proximity the nitro compound and temperature, compared to 95% conversion and 14% the substrate, respectively. ee for (R)-Ph-BOX (3)–Cu(OTf)2 and 11% conversion and 18% ee for (4R,5S)-DiPh-BOX (4)–Cu(OTf)2. Copper complexes The catalytic enantioselective Henry reaction of α- Among the chiral transition metal complexes used keto esters with nitromethane was also developed as catalysts for asymmetric Henry reaction, chiral using copper(II)−tert-butyl bisoxazoline complex in copper complexes play an important role. Most of the combination with triethylamine in 2002 (Ref 19) asymmetric Henry reactions reported are catalysed by (Scheme II). The product optically active β-nitro-α- chiral copper complexes. Due to the relative non hydroxy esters were formed in high yield with toxicity of the metal copper, its ready availability and excellent ee. The scope of the reaction is low cost makes it attractive to researchers for the demonstrated by the reaction of a wide variety of α- synthesis of chiral copper complexes. The first chiral keto esters. The catalytic enantioselective Henry copper complex catalysed enantioselective addition reaction of β,γ-unsaturated-α-keto esters proceeds reaction of α-keto esters with nitromethane was exclusively as a 1,2-addition reaction, in contrast to

90 INDIAN J. CHEM., SEC B, JANUARY 2013

TMSO O O 2- Cu(OTf) ,TBAT HO NO2 N + 2 Ph Py, CH2Cl2,RT Ph C2H5 C2H5

Scheme III — Catalytic enantioselective Henry reaction of silyl nitronates with aldehydes developed by Risgaard et al.20

H3C CH catalyst in the presence of tetrabutylammonium O 3 H3C CH3 O triphenylsilyldifluorosilicate (TBAT). In order to O O N N minimize the epimerization of the nitroaldol products, they were converted into the corresponding Mosher esters. The reaction proceeds well for different R R aromatic aldehydes reacting with alkyl nitronates. 5a-d 5e In 2003, Evans et al. reported copper complexes of 5a: R = Ph bis(oxazoline) (BOX) 5a-e derived from 5b: R = i-Pr Cu(OAc)2.H2O for enantioselective Henry reaction 5c: R = Bn 21 5d: R = t-Bu candidates . The substrate scope of the catalyst has H3C CH3 been extended to various prochiral aldehydes O O including aliphatic and substituted aromatic alde- N N hydes. The corresponding product chiral nitro aldols Cu were formed in good yield and ee. Benzaldehyde gave AcO OAc the product in 76% yield and 94% ee as maximum

5f among the aromatic aldehydes. Among aliphatic aldehydes, isobutyraldehyde gave the chiral product Table I — Asymmetric Henry reaction catalysed by copper in 86% yield and 94% ee as maximum. bisoxazoline complexes Ligands 5a-e catalysed the asymmetric Henry

Entry Ligand Solvent Configura- ee (%) reaction between p-nitrobenzaldehyde and nitro- tion methane in combination with Cu(OAc)2.H2O. The results are given in Table I. 1 5a Methanol S 43 2 5b Methanol S 67 The chiral ligands 5a-d catalysed the asymmetric 3 5c Methanol S 45 Henry reaction and gave the product chiral nitro aldol 4 5d Methanol S 37 with ‘S’ configuration (Table I, entries 1-4). The 5 5e Methanol R 74 enantiomeric excess of the chiral product is in the R 6 5e Ethanol 81 range of 43-67%. The chiral ligand 5e catalysed the

asymmetric Henry reaction and gave the product the uncatalysed reaction where both 1,2- and 1,4- chiral nitro aldol with ‘R’ configuration (Entries 5 and addition products are formed. In the proposed 6). They showed that the solvent played a remarkable mechanism for the reaction it was suggested that both effect on the enantiomeric excess of the chiral the α-keto ester and nitromethane/nitronate ion are product. Catalyst 5e gave the chiral product with 74% coordinated to the metal center during the reaction ee when the asymmetric Henry reaction was carried course. out in methanol as solvent (Entry 5). The same Catalytic enantioselective Henry reaction of silyl catalyst gave the chiral product with 81% ee when the nitronates with aldehydes was developed by Risgaard reaction was carried out in ethanol as solvent (Entry et al. in the same year20 (Scheme III). 6). Among the catalysts 5a-e, catalyst 5e catalysed the Different chiral Lewis acids have been tested for asymmetric Henry reaction efficiently and gave the the reaction and it has been found that a variety of product chiral nitro aldol in better ee (81%) as chiral copper–ligand complexes can catalyse the compared to the other catalysts. enantioselective Henry reaction. The best yield, The X-ray structure of the chiral copper-ligand diastereo- and enantioselectivity of the nitroalcohols complex 5f reveals the expected square planar formed are obtained by the application of a geometry with the acetate carbonyl moieties oriented copper(II)-diphenyl–bisoxazoline complex 4 as toward the vacant apical positions.

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5e L Cu Cu 5f L

Nu EI L L Nu L Cu Cu Cu EI L L EI L Nu

A (highest reactivity) B (intermediate reactivity) C (lowest reactivity)

H O H R OAc R R N N O O H H L O L O OAc L OAc Cu Cu Cu H H L O H L O L O R N R R O R R H R H A-1 A-2 B-1

Figure 1 — Plausible transition structures for the asymmetric Henry reaction

For those complexes that simultaneously bind to both electrophiles and nucleophiles, the most reactive N N transition states should position the nucleophile perpendicular to the ligand plane, while the electro- Cu N N phile, for maximal activation, should be positioned in one of the more Lewis acidic equatorial sites in the CNCH3 6 ligand plane as illustrated for complex A. By the same argument, complex C should exhibit the lowest

R reactivity (greatest stability). While transition states O O A-1 (boat), A-2 (chair), and B-1 (chair) all follow the Ph Cu observed sense of asymmetric induction, the pre- Ph N disposition is to favor A-1 on the basis of both steric R and electronic considerations. A new chiral Cu(II) complex of N,N′-bis(2- pyridylmethylidene)-(R,R)-1,2-cyclohexanediamine 6, a tetradentate chiral Schiff base ligand, was evaluated 7a,b a; R = H for its catalytic capacity for asymmetric Henry b; R = t-Bu reaction between benzaldehyde and nitromethane22. The yield of asymmetric Henry reaction between The asymmetric induction imparted from complex benzaldehyde and nitromethane in the presence of 5f could be rationalized with a statement of the impact triethylamine or diiospropylethylamine by using the of the Jahn-Teller (JT) effect on Cu(II) coordination. complex 6 as catalyst was high (94%), however, the As illustrated in Figure 1, JT distortion of an enantiomeric excesses were not greater than 30%. octahedral Cu(II) complex creates four strongly In 2006, Gan et al.23 reported the mild and efficient coordinating and two weakly coordinating sites enantioselective nitroaldol reactions of nitromethane labeled red and blue, respectively. Addition of a with various prochiral aldehydes catalyzed by chiral bidentate ligand 5e affords a complex positioning the copper Schiff-base complexes 7a,b which can be two cis-oriented strongly coordinating sites in the readily prepared from amino acid, yielding the ligand plane and two trans-oriented weakly corresponding adducts with high yields (87%) and coordinating sites perpendicular to the ligand plane. good enantiometric excess (80%). The two

92 INDIAN J. CHEM., SEC B, JANUARY 2013

R N N O R Cl Cu N N Cl Cl 2 N Cu O N Cl Cu N O Cl N Cl N R

Scheme IV — Copper complexes of chiral N,N′-bidentate ligands

NH2

+ BF3. Et2O N N N Toluene O 9a

N N N N N N N N OH 9b 9c 9d 9e Ph Ph Scheme V — Synthesis of iminopyridine ligands derived from monoterpenic ketones and pyridinylalkylamines and their application in asymmetric Henry reaction

H CO OCH3 3 OH CHO NO2 9a-e, M(OAc)n + CH3NO2 Base Scheme VI — Asymmetric Henry reaction of o-methoxy benzaldehyde with nitromethane catalysed by 9a-e

obtained. Among the chiral ligands 8a-f screened for R 8a:R = CH3 the copper catalysed asymmetric Henry reaction, N 8b:R = CH Ph N 2 chiral ligand 8b gave the chiral nitro aldol product in O 8c:R = CH2-2-Py N 8d:R = CH2CN high enantiomeric excess (18.6%). 8e:R = CH2COOC2H5 Chiral iminopyridines prepared by Blay et al. in 8f:R = CH CONH 2 2 2007 from monoterpenic (camphor-derived) ketones 8a-f and pyridinylalkylamines 9a-e (Scheme V) were

found to catalyse the enantioselective Henry reaction enantiomers of phenylalanine (D and L) were used, between nitromethane and o-methoxy benzaldehyde and catalysts of different configurations were (Scheme VI) in the presence of Cu(OAc) .H O. High prepared and utilized in the reaction. It was found that 2 2 yield and good ee (upto 86%) could be obtained under absolute configuration of the product can be straightforward experimental conditions without the controlled by the configuration of the catalyst. The 25 need for air or moisture exclusion . catalyst without substitution in the salicylaldehyde part catalysed the asymmetric Henry reaction better A new series of chiral hydrogenated salen catalysts than the catalyst with substitution. 10a-h was developed by Xiong et al. in 2007 for the Sedlak et al. introduced Cu(II) complexes of chiral asymmetric Henry reaction which produces the product chiral nitro aldol in moderate to high yield (upto 98%) N,N′-bidentate ligands 8a-f (Scheme IV) derived 26 from substituted 2-(4-isopropyl-4-methyl-5-oxo-4,5- with excellent enantiomeric excess (upto 96% ee) . dihydro-1H-imidazol-2-yl)pyridines to catalyse A variety of aromatic, heteroaromatic, enal, and asymmetric Henry reaction24. The overall yield of 41– aliphatic aldehydes were found to be suitable substrates in the presence of hydrogenated salen 10f 97% and maximum enantiomeric excess of 19% was

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NH HN NH HN N N

R1 OH HO R1 t-Bu OH HO t-Bu t-Bu OH HO t-Bu

R2 R2 t-Bu t-Bu t-Bu t-Bu

10a:R1 = H, R2 = H 10g 10h 10b:R1 = H, R2 = Ph 10c:R1 = Ph, R2 = H 10d:R1 = t- Bu, R2 = adamantyl 10e:R1 = Cl, R2 = H 10f:R1 = t- Bu, R2 = t-Bu

CH3NO2 TfOH L* L*Cu O (CuOTf)2. C7H8 Cu*L*OTf + O N OH NO R 2 H RCHO Cu*L O TfOH R O N H H O Figure 2 — Possible catalytic cycle proposed by Xiong et al.26

complex was a highly efficient catalyst for the Henry reaction. The reaction was performed in n-propyl alcohol at room temperature, and the Henry adducts were produced in high yield (99%) with excellent N N enantiomeric excess (95%) (Ref 27). In the same year Jiang et al. reported the asymmetric Henry reaction catalysed by chiral phosphine salen type ligands 12a-j. The chiral nitroaldols were formed with 80% ee as maximum with the chiral ligand 12d and (CuOTf)2.C6H6

11 (Ref 28). The chiral ligands 12g-j did not impart any asymmetry in the catalytic reaction. Gao et al. (10 mol%), (CuOTf)2·C7H8 (5 mol%), and molecular synthesized copper–Schiff base complexes 13a-e sieves. This process is air-tolerant and easily from Cu(OAc)2.H2O, salicylaldehydes, and amino manipulated with readily available reagents, and has alcohols. The complexes were shown to be effective been successfully extended to the synthesis of (S)- as catalysts in the asymmetric Henry reaction norphenylephrine in 67% overall yield, starting from affording nitro alkanols in 98% yield with moderate commercially available m-hydroxybenzaldehyde. to good enantiomeric excess (38.6% ee)29. Catalyst Based on experimental investigations and MM+ 13a gave the best ee and yield. calculations, a possible catalytic cycle (Figure 2) was A copper complex of N,N′-bis(pyridin-2- proposed to explain the origin of reactivity and ylmethyl)-(S,S)-1,2-cyclohexanediamine 14 was asymmetric inductivity. synthesized by Zhang et al. in 2008. The complex was The chiral diamine ligand 11 was designed and employed as catalyst in asymmetric Henry reaction synthesized from (R,R)-1,2-diphenylethylenediamine, between benzaldehyde and nitromethane with (S)-2,2′-bis(bromomethyl)-1,1′-binaphthalene, and o- triethylamine as promoter. The product chiral β- 30 xylene dibromide. The resulting 11-Cu(OAc)2.H2O nitroaldol was formed in 78% yield with 29% ee .

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R3

R2 N N HO R1 HO PPh 2 PPh2

12f 12a: R1 = H, R2 = H, R3 = H 12b: R1 = t-Bu, R2 = H, R3 = t-Bu 12c: R1 = Cl, R2 = H, R3 = Cl 12d: R1 = H, R2 = H, R3 = CH3 12e: R1 = H, R2 = OCH3, R3 = H

N N N R1 R2 PPh 2 PPh2

12g: R1 = H, R2 = H 12j 12h: R1 = Cl, R2 = H 12i: R1 = Cl, R2 = Cl

t-Bu t-Bu

CH3 CH3 OBu-t OC8H17 N OBu-t OC H N 8 17 Cu/2 O O Cu/2 O O

t-Bu t-Bu 13a 13b CH Ph 3 Ph Ph O O O Ph H Cu Cu H N O N N N Cu/2 O Cu/2 O O O

CH 3 13c 13d 13e

In the same year Kowalczyk et al. reported that Among the chiral ligands screened 15a-n for the chiral C2-symmetric, secondary bisamines 15a-n copper catalysed asymmetric Henry reaction, ligand based on the 1,2-diaminocyclohexane framework and 15k catalysed the reaction efficiently and gave the Cu(OAc)2.H2O could promote the asymmetric Henry product chiral nitroaldol in excellent ee (91%) and reaction. Aromatic and aliphatic aldehydes were yield (95%). reacted with nitromethane to provide the A series of new binaphthyl-containing sulfonyl- corresponding β-nitroalcohols in very good yield and diamine ligands-CuCl complex were used as catalysts enantioselectivity31. in asymmetric Henry reaction by Arai et al. in 2008.

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R H N N R Cu OH2 N O O N N Cu H O O N R Cl2

14

R 17a,b 17a: R = H 17b: R = t-Bu NH HN R R 15a-n

15a: R = furyl 15h: R = 2-(OH)C6H5 N N 15b: R = 1-naphthyl 15i: R = 2-ClC6H5 15c: R = 2-naphthyl 15j: R = 3-ClC H H H 6 5 18 15d: R = 9-anthryl 15k: R = 4-ClC6H5 15e: R = mesityl 15l: R = 2,6-ClC6H5 15f: R = 2-(OCH3)C6H5 15m: R = 2-BrC6H4 catalysed the asymmetric Henry reaction much better 15g 15n : R = 2-(C8H17O)C6H5 : R = 4-BrC6H5 than the complex 17a (38% yield, 12% ee).

Sanjeevakumar et al. in 2009 reported a new chiral C2-symmetric N,N′-bis(isobornyl)ethylenediamine– copper complex derived in situ from bis(isobornyl)- ethylenediamine 18 and Cu(OAc) .H O which O 2 2 catalysed the enantioselective Henry reaction between H3C S N N H nitromethane and various aldehydes to provide β- O hydroxy nitroalkanes with high chemical yield (95%) and high enantiomeric excess (90%)34. Zielinska-Blajet et al. reported copper (II) catalysed asymmetric Henry reaction using cinchona 16 alkaloids derived thiols and disulfides synthesised from cinchona alkaloids35. Commercially available

The (R,R)-diamine-(R)-binaphthyl ligand 16-CuCl cinchona alkaloids, namely cinchonidine (CD), complex smoothly catalysed the enantioselective quinine (QN), and quinidine (QD), the respective Henry reaction with the assistance of pyridine to give dihydro derivatives, and their synthetic C-9-epi- the corresponding adduct with high enantiomeric configured analogues (epi-QN/epi-QD) were used as excess (93%). Moreover, they showed that the starting materials. 16−CuCl−pyridine system promotes the A new series of Schiff bases derived from diastereoselective Henry reaction in syn-selective Cinchona alkaloids were developed and used as chiral manner to give the adduct in 99% yield with 92:8 ligands for the copper(II)-catalyzed asymmetric syn/anti selectivity. The reported enantiomeric excess Henry reaction by Zhang et al.36 The optimized of the syn-adduct was 84% (Ref 32). catalyst was found to promote the asymmetric Henry A novel catalytic enantioselective Henry reaction reaction of both aromatic and aliphatic aldehydes with was developed by Gan in 2008 using tetradentate nitromethane and nitroethane. These reactions could copper complexes 17a,b derived from D-tartaric acid afford the chiral β-nitro alcohol adducts with high to give β-nitroalkanols in moderate to high enantioselectivities (99%). enantioselectivity33. Quinine derived thiols 19 and disulfides 20 are They found that the tetradentate complex 17b (65% shown in Scheme VII. It was found that thiols gave yield, 72% ee), with a bulky tert-butyl substituent better enantioselectivity than disulfides in the

96 INDIAN J. CHEM., SEC B, JANUARY 2013

N OCH3 N OCH3

SH S

C H C H N 2 3 N 2 3 2

19 20 Scheme VII — Quinine alkaloid derived chiral thiol and disulfide

HO NRR 1- 2 O S

22a-f

H H3C NH2 CH3 i -Pr H

H C H CH H 3 N 3 N N Pr CH3 H H NH2 H a b, c d e f

Table II — Chiral amines used in the synthesis of chiral ligands 22a-f H H N N 22a (‒)-cis-myrtanylamine Cu 22b (‒)-(S)-1-(1′-naphthyl)ethylamine AcO OAc 22c (+)-(R)-1-(1′-naphthyl)ethylamine 22d 2,2-dimethylaziridine Cl Cl 22e (‒)-(S)-2-isopropylaziridine 21 22f (+)-(R)-2-isopropylaziridine asymmetric Henry reaction in all of the alkaloids tested. Among the alkaloids used, the thiol derived New tridentate enantiomerically pure heteroatom from quinine alkaloid catalysed the asymmetric Henry copper catalysts 22a-f, Table II, containing hydroxyl, reaction effectively and gave the chiral β-nitro aldols sulfinyl and amino groups, proved to be highly in good yield and enantiomeric excess (83%). efficient catalysts in the enantioselective Henry In 2009, Kowalczyk et al. reported the asymmetric reaction to give the desired adducts in high yield Henry reaction catalysed by copper- diamine (90%) and enantiomeric excess (98%) by Rachwalski complexes. The secondary bisamines 21 were derived et al. in 2009. The influence of the stereogenic centres 37 located on the sulfinyl sulfur atom and in the amine from 1,2-diaminocyclohexane . 38 The reactions were carried out in the presence of moiety with the enantioselectivity of the product were also discussed. 10 mol% of the Cu(II) complex with i-Pr2NEt as promoter. Good to excellent yield, 99% enantio- Among the chiral ligands 22a-f screened for the selectivity and moderate to excellent diastereoselecti- catalytic activity in the copper catalysed asymmetric vity were obtained for both aromatic and aliphatic Henry reaction, ligands 22b and 22c catalysed the aldehydes. Various prochiral nitro compounds reaction efficiently and gave the chiral products (S)-β- forming the corresponding β-nitroalcohols with two nitro aldol (90% yield, 98% ee) and (R)-β-nitro aldol contiguous stereocenters were also reported. (87% yield, 98% ee) respectively.

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NH HN NH HN

Cl Cl Cl Cl 23 24

NH HN NH HN H3C Br OH HO Ph N OEt HO 25 EtO 26 OH 27

Chiral copper (II) complexes generated in situ from Henry reaction resulted in secondary alcohols with C -symmetric chiral secondary bisamines 23-26 based high yield and excellent selectivity for active 2 40 on 1,2-diaminocyclohexane structure having H, t-Bu aldehydes (upto 94% ee) . In 2010 Noole et al. found that a complex derived and Cl substituents with Cu(OAc)2. H2O were reported by Khan et al. in 2010. They were used as from the enantiopure bipiperidine 28 and catalysts for an environmentally benign protocol for Cu(OAc)2.H2O was acting as an efficient catalyst for highly enantioselective Henry reaction of various enantioselective Henry reaction. Nitromethane and aldehydes with nitromethane in the presence of nitroethane were chosen to react with benzaldehyde. different ionic liquids as a greener reaction medium at The product chiral nitroaldols were obtained with a 0°C. Excellent yield (90%) of β-nitroalcohols with maximum of 96% ee (Scheme VIII). The easy high enantioselectivity (94% ee) were achieved when availability of the catalyst components, mild reaction [emim]BF4 was used as ionic liquid. This reported conditions, high yield and good to excellent ionic liquid mediated nitroaldol protocol is recyclable enantioselectivity make this catalyst useful for most 41 (upto five cycles) with no significant loss in its applications . performance39. An efficient in situ three component formation of chiral oxazoline-Schiff base copper(II) complexes In the same year Xin et al. reported the synthesis of (Scheme IX) were introduced by Du et al. in 2010 new planar chiral [2.2] para-cyclophane Schiff base (Ref 42). The product chiral nitro aldols were formed ligands of the type 27 and their application in in 97% yield and upto 92% ee. asymmetric Henry reaction. A series of new planar In 2010 the catalytic activity of the chiral ligands and central chiral ligands were synthesized based on synthesized from the amino acid L-valine in the [2.2] para-cyclophane backbones from enantiomeri- asymmetric Henry reaction were reported. Two chiral cally pure 4-amino-13-bromo [2.2] para-cyclophane salen ligands 29a and 29b have been synthesized and commercially available chiral amino alcohols. from L-valinol and L-diphenyl valinol with Their application in copper catalysed asymmetric salicylaldehyde respectively43.

NH N OH OH O 28 R R + R = H upto 96% ee H R = CH anti:syn = 4:1 NO NO 3 RCH2NO2 2 2 upto 96% ee Cu(OAc)2.H2O Scheme VIII — Asymmetric Henry reaction

98 INDIAN J. CHEM., SEC B, JANUARY 2013

A combinatorial library of catalyst generated in situ by Yang et al.

Scheme IX — Three component formation of chiral oxazoline-Schiff base copper (II) complexes by Du et al.42

H3C CH3 Ph Ph Ph Ph R OH N R N N OH HO OH

29a: R = H 29b: R = C6H5 30 31

The chiral ligands were employed as catalysts with reaction can be carried out without the need of air and Cu(OAc)2.H2O in the asymmetric Henry reaction moisture exclusion which makes the catalyst more between nitromethane and substituted banzaldehydes. attractive. The relationship of the enantiomeric excess of the Catalytic asymmetric Henry reaction has been product with the steric bulkinesss of the chiral ligands developed using a novel chiral Cu(II) complex was discussed. As the steric bulkiness of the ligand derived from L-proline and pyridine 30 with increases, the enantioselectivity of the asymmetric copper(II) acetate in ethanol under mild conditions by reaction increases. Chiral ligand 29a catalysed the Basi et al.44 The corresponding chiral 2-nitro-1- asymmetric Henry reaction and gave the product arylethanol derivatives could be obtained in high chiral nitro aldol in 99% yield and 54% ee. Whereas, yields with moderate to good enantiomeric excess the chiral ligand 29b catalysed the reaction and gave (upto 86% ee). It was found that the coordination of a the product nitro aldol in 99% yield with 70% ee. The metal atom to the nitrogen of the pyridine ring is substrate scope of the chiral ligand was explored by essential in determining the stereochemistry of the performing the reaction with variation of functional reaction. Out of the two copper sources, Cu(OTf)2 and groups on substituted . The product Cu(OAc)2.H2O used, copper(II) acetate provides chiral nitroaldols were formed with 77-95% ee and in better enantioselectivity. good yield. The mechanism for the formation of The catalytic asymmetric Henry reaction of nitro- particular enantiomer is also discussed. methane with various aldehydes was developed using First, the coordination of nitronate anion with chiral binaphthylazepine derived amino alcohol 31 copper takes place through the oxygen of the nitronate and Cu(OAc)2.H2O as catalyst by Guo et al. in 2011. anion near salicylaldimine part (a). Benzaldehyde High yield and good enantioselectivity (97%) were occupies the fourth equatorial position forming the obtained for both aromatic and aliphatic aldehydes. distorted square planar intermediate (b). The attack of Moreover, this catalytic system also works well for the nitronate anion on the carbonyl group of the diastereoselective Henry reaction to afford the benzaldehyde takes place at the si face, via a stable corresponding adducts in upto 95:5 syn/anti six membered transition state. The product (R)-(‒)-2- selectivity and 95% enantioselectivity45. nitro-1-phenylethanol (c) is formed after work up Zhou et al. synthesised a small library of C1- (Figure 3). symmetric chiral diamines 32-41 via condensing exo- This salen ligand 29b derived from L-diphenyl- (‒)-bornylamine or (+)-(1S,2S,5R)-menthylamine with 46 valinol and Cu(OAc)2.H2O system has been proven to various cbz-protected amino acids . Among these, be a good catalytic system for the asymmetric Henry ligand 32-CuCl2.2H2O complex (2.5 mol%) shows reaction, by providing the corresponding nitroalkanols outstanding catalytic efficiency in Henry reaction with good yield and high enantiomeric excess. This between a variety of aldehydes and nitroalkanes to

ANANTHI et al.: ASYMMETRIC HENRY REACTION 99

CH3 H3C H3C CH3

O N N O R H O O O Cu Cu O O O a b N N C R O CH O 2 H2 H O

N

O CH2

CH3 H3C CH3 H3C

N N O O O O Cu Cu O OH

N R O C H2 H OH O N O R c

Figure 3 — Possible mechanism for ligand 29b-Cu(OAc)2.H2O catalysed asymmetric Henry reaction between nitromethane and benzaldehyde

O O HN HN NH N N NH NH H NH H 35 32 33 34

Ph Ph O O

H2N HN H2N HN H2N HN H2N HN 39 36 37 38

O

N HN N HN Bn Bn 40 41 afford the expected products in high yields (upto 98%) dimethoxyphenyl)ethanol, a key intermediate for (S)- with excellent enantioselectivities (upto 99%) and epinephrine and (S)-norepinephrine. The low catalyst moderate to good diastereoselectivities (upto 90:10). loading, excellent yields and enantioselectivities, This process is air- and moisture tolerant and has been inexpensive copper salt and mild reaction conditions applied to the synthesis of (S)-2-amino-1-(3,4- has made this catalytic system practically useful.

100 INDIAN J. CHEM., SEC B, JANUARY 2013

NO OH 2 CHO NO2 32/CuCl 2H O * NO Ph PAu(OTf) * 2. 2 2 3 O * + O CH NO TfOH, CH Cl 2 2 2 2 R R R R 42a-o 43a-o 44a-o 45a-i

a (R = Ph) e (R = Ph) i (R = Ph) m (R = Ph) b (R = 4-Me-Ph) f (R = 4-Me-Ph) j (R = 4-Me-Ph) n (R = 4-Me-Ph) c (R = 3-Me-Ph) g (R = 3-Me-Ph) k (R = 3-Me-Ph) o (R = 3-Me-Ph) d (R = 2-Me-Ph) h (R = 2-Me-Ph) l (R = 2-Me-Ph)

Scheme X — Synthetic route to chiral 1H-isochromenes and 1,3-dihydridobenzofurans by combining the copper(II)-catalyzed asymmetric Henry reaction of o-alkynylbenzaldehydes 42 with subsequent gold(I)-catalyzed cycloisomerization47.

O 46, CuBr, Pyridine OH R' = H ee upto 99% + R'CH2NO2 R' = Et syn/anti upto 32.3:1 R H R R' (ee of syn 97%) R' = H, Me, Et, Ph NO2 NH HN Ph Ph NH HN O S O O S O 46

CH3 CH3

Scheme XI — Asymmetric Henry reaction between aldehyde and substituted nitro compounds using copper complex of bis(sulfonamide)diamine 46 as catalyst

Gong et al. reported a successful synthetic route to complex formation with ligand 31, the CuCl2.2H2O- chiral 1H-isochromenes and 1,3-dihydridobenzo- 31 combination gave the highest enantiomeric excess. furans by combining the copper(II)-catalyzed asym- A series of bis(sulfonamide)-diamine (BSDA) metric Henry reaction of o-alkynylbenzaldehydes 42 ligands were synthesised from commercially available with subsequent gold(I)-catalyzed cycloisomeriza- chiral α-amino alcohols and diamines by Jin et al. in tion47. The product optically active 1H-isochromenes 2011 (Ref 48). The chiral BSDA ligand 46, coordi- and 1,3-dihydroisobenzofurans were successfully nated with Cu(I), catalyses the enantioselective Henry synthesized in good overall yields with good to reaction with excellent enantioselectivity (upto 99%, excellent enantioselectivities (upto 98%, Scheme X). Scheme XI). Moreover, with the assistance of They were investigated with various substrates, and a pyridine, CuBr-46 system promotes the diastereo- correlation between the regioselectivity and electronic selective Henry reaction with various aldehyde nature of the substrates was studied. It was found that substrates and gives the corresponding syn-selective the substrates with electron donating groups at the adduct upto 99% yield and 32.3:1 syn/anti selectivity. alkynyl moiety preferred a 6-endo-dig manner to The enantiomeric excess of the syn adduct was 97%. generate 1H-isochromenes 44 as the main products In the same year an enantioselective Henry reaction (upto >30:1) while the ones with electron was efficiently carried out under mild reaction withdrawing groups were inclined to undergo 5-exo- conditions in the presence of catalytic 9-epi and dig cyclization to form 1,3-dihydroisobenzofurans 45 natural cinchona alkaloids and copper (II) acetate by 49 (upto 1:5). Among the copper salts, Cu(OAc)2.H2O, Zielinska-Blajet et al. Aromatic and aliphatic CuCl2.2H2O, CuBr2, CuSO4.5H2O, Cu(OTf)2 used for aldehydes with nitromethane and its α-substituted

ANANTHI et al.: ASYMMETRIC HENRY REACTION 101

OH OCH Cu(I)/47 3 O NO2 O R1 OCH3 R2 N R1 H H + O H H NO2 OH Zn(II)/47 N 47 R NO2 HO 2 R1 OH R2

ligands 50a-c and their application in asymmetric Henry reaction of aliphatic aldehydes with nitro- H H methane (Scheme XIII). Although the chiral NHN nitroaldols were formed in excellent yield (90%), the enantiomeric excess is very poor (2%) (Ref 53). N Chiral dinuclear zinc catalysts for the asymmetric aldol and nitroaldol (Henry) reactions which led to

48 efficient syntheses of the β-receptor agonists (−)- derivatives provided the corresponding β-nitroalco- denopamine 58 and (−)-arbutamine 59 was reported hols in good to reasonable yields, high syn-diastereo- by Trost et al. in 2002 (Ref 54). (‒)-Denopamine is a selectivity, and (S)-enantioselectivity upto 94%. cardiotonic drug which acts as a Beta-1 adrenergic Recently in 2009, Oh et al. reported a new receptor agonist. It is used in the treatment of angina approach to synthesise both enantiomers of Henry and may also have potential uses in the treatment of products chiral nitroaldols by the use of different congestive heart failure and for clearing pulmonary molecularities of metal-ligand complexes synthesised edema. (‒)-Arbutamine is a cardiac stimulant. It is from copper (I) and zinc (II) with readily available used to stimulate adrenergic receptors. Various Brucine derived amino alcohol 47 (Ref 50). modified chiral ligands 52a-d, 53a-b, 54, 55, 56 Out of the two complexes (copper and zinc (Figure 4) were synthesised for this purpose from L- complexes) copper complex gave the highest enantio- diphenylprolinol as chiral source (Scheme XIV). meric excess (95%). The two metal salts used for the (R)-(‒)-denopamine was synthesised by enantio- selective Henry reaction of substituted benzaldehyde complex formation were Cu(OAc)2 and Zn(OTf)2. Camphor derived annulated imidazole ligands 48 and nitromethane catalysed by zinc complex 57 have also been tested for the catalytic activity and synthesised from the chiral ligand 55 as initial step selectivity in the copper (II) catalyzed asymmetric (Scheme XV). Starting from the chiral product Henry reaction by Bures et al.51 Good enantio- nitroaldol, upon various transformations, the final selectivity upto 67% was achieved. Starting from (R)- product (R)-(‒)-denopamine 58 was obtained. camphordiamine, 13 new camphor-annulated imida- (R)-(‒)-Arbutamine was synthesised by enantio- zoline ligands were synthesized in good yields as two selective Henry reaction catalysed by the zinc regioisomeric series. The product stereoselectivity complex formed in situ from the chiral ligand 54 and varied according to the regioisomer used. Et2Zn as initial step (Scheme XVI). Starting from the A practical synthesis of (R)-salmeterol 49 has been chiral product nitroaldol upon various transforma- accomplished from 3-bromo salicylaldehyde, which tions, the final product (R)-(‒)-arbutamine 59 was involved a Cu(II)–sparteine complex catalyzed obtained as yellow coloured solid in 90% yield. asymmetric Henry reaction as the key step by Lu C2-Symmetric tridentate bis(oxazoline) 60 and bis- et al. this year52 (Scheme XII). (R)-Salmeterol 49 was (thiazoline) ligands with a diphenylamine backbone obtained in 39% overall yield and 95% ee. have been investigated in the catalytic asymmetric Henry reaction of α-keto esters with different Lewis Zinc and molybednum complexes acids by Du et al. in the year 2005 (Ref 55). It was

In 2005, Uwe Kohn, et al. reported the synthesis of found that the metal controlled reversal of three bidentate zinc (II) complexes and molybednum enantioselectivity. The Cu(OTf)2 complexes of the chiral ligand furnished ‘S’ enantiomers, while Et2Zn (0) complexes of tridentate neutral chiral guanidine

102 INDIAN J. CHEM., SEC B, JANUARY 2013

O OH CuCl .2H O, (-)-sparteine NO2 O H 2 2 O O CH3NO2, Et3N, MeOH O 79% yield, 96% ee

H H N HO O

HO 49

Scheme XII — Synthesis of (R)-salmeterol 49 via catalytic asymmetric Henry reaction

O N N NR1R2 N Zn Cl Mo CO N N N N CO H Cl H CO

1 2 50a R R = (CH2)4 51 1 2 50b R R = (CH2)2O(CH2)2 1 2 50c R R = (CH2)5 O OH

50a-c, 51 NO2 H + CH3NO2 * CH3CN Scheme XIII — Asymmetric Henry reaction of aliphatic aldehydes with nitromethane catalysed by Zn (II) and Mo (0) complexes 50a-c and 51 of chiral guanidine ligands

Ph Ph Ph OH HO Br OH Br Ph Ph N Ph H HO N OH N

CH 3 52a

54 Scheme XIV — Synthesis of chiral ligand from L-diphenylprolinol by Trost et al. complexes of the chiral ligand afforded ‘R’ Ferrocenyl-substituted aziridinylmethanol (Fam) enantiomers, both of them gave the product with 61 was used as catalyst with zinc for the asymmetric higher enantioselectivities (upto 85% ee, nitroaldol (Henry) reaction by Bulut et al. in 2008 Scheme XVII). Reversal of enantioselectivity in (Ref 56). This catalyst worked with a variety of asymmetric Henry reaction was achieved with the aldehydes (aromatic, aliphatic, α,β-unsaturated, and same chiral ligand by changing the Lewis acid heteroaromatic) and α-ketoesters to give the nitroaldol center from Cu(II) to Zn(II). It was reported that the product in 97% yield and 91% ee. It was found that NH group in C2-symmetric tridentate chiral ligands the recyclability of the chiral ligand was retained play a very important role in controlling both the without losing its activity. yield and enantiofacial selectivity of the Henry Zinc-based catalysts are especially interesting products. because they might be compatible with aqueous

ANANTHI et al.: ASYMMETRIC HENRY REACTION 103

Ph OH Ph Ph HO Ph OH HO Ph Ph Ph Ph

N OH N N OH N

R R

52a R = CH3, 52b R = Cl, 52c R = F, 52d R = OCH3 53a R = H, 53b R = Cl

F F

OH HO OH HO OH HO F F

N OH N N OH N N OH N

54 55 56

Figure 4 — Chiral ligands reported by Trost et al.54

bisoxazolidine-Me2Zn complex catalyzed nitroaldol formation requires relatively short reaction times, proceeds under mild conditions and the method can be applied to a wide range of substrates including sterically hindered aldehydes. To date, a few other zinc complexes bearing amino O Et O alcohol ligands60 and macrocyclic thioaza ligands61 have been described for the Henry reaction. Because Zn Zn the results are still poor, future developments in the N O N area can be expected.

57 Chromium complexes Kowalczyk et al. in 2007 prepared chiral chromium(III)–salen-type complexes 64a-c derived from 1,2-diaminocyclohexane and 1,2-diphenyl- systems in the light of the fact that zinc enolates have ethylenediamine and employed the chromium (III) been identified as intervening species in aldol complexes (2 mol%) as catalyst in the enantio- 57 reactions catalyzed by type II aldolases . selective Henry reaction62. Various arylaldehydes, The enantioselective Henry reaction between trans-cinnamaldehyde, and cyclohexanecarbaldehyde nitromethane and various aldehydes catalyzed by in reacted with nitromethane in the presence of (i- situ prepared chiral amino alcohol ligand 62–Zn Pr) NEt to give the corresponding adducts in 40-76% 58 2 (Me2Zn) complex was described by Guo et al. The ee and in moderate to good yield. resulting product β-nitroalcohols were obtained in Zulauf et al. in 2009 reported a new chiral high yields and with moderate to good enantiomeric thiophene-salen chromium complex 65 for the excesses. asymmetric Henry reaction of several aldehydes Symmetric bisoxazolidine 63-Me2Zn combination (Scheme XVIII) (Ref 63). The anodic polymerization was found to effectively catalyze the asymmetric of this complex led to an insoluble powder that was Henry reaction of aliphatic and aromatic aldehydes by successfully used as a heterogeneous catalyst for the 59 Wolf et al. β-Hydroxy nitroalkanes were produced transformation of 2-methoxybenzaldehyde with in upto 99% yield and 95% ee. It was found that the enantiomeric excess upto 85%.

104 INDIAN J. CHEM., SEC B, JANUARY 2013

OH OH CHO H NO2 57 N OCH3 TBSO CH3NO2 TBSO HO OCH3

(R)-(-)-denopamine 58

Scheme XV — Synthesis of (R)-(‒)-denopamine 58 by Henry reaction (Trost et al.54)

OH OH CHO HHCl NO2 54, Et2Zn N

TBSO CH NO TBSO 3 2 HO OH OTBDMS OTBDMS OH (R)-(-)-arbutamine 59 R

Scheme XVI — Synthesis of (R)-(‒)-arbutamine 59 by Henry reaction by Trost et al.54

OH O OH 60 60 R COOEt + CH3NO2 R COOEt Cu(Otf) R COOEt 2 Et2Zn NO2 NO2 (S) (R) Upto 82% ee Upto 85% ee N H O N N O 60 Bn Bn

Scheme XVII — Metal controlled reversal of enantioselectivity reported by Du et al.55

H CH3 Ph Ph H OH HN (R) N Ph O (S) N OH Fe (S) (S) H (S) NH O (R) O

61 62 63 The product chiral nitroaldols were formed in good Investigation of the catalytic activity of these yield and enantiomeric excess (85%). It was reported complexes revealed that in the presence of i-Pr2EtN, 2 that the polymerized catalyst can be recovered by an mol % of cobalt complexes, optically active 1,2- original multi substrate procedure. diarylethylene diamines 66 and 67 can mediate the reaction between nitromethane and aldehyde in ee Cobalt complexes upto 84%. They also employed commercially In 2004 Kogami et al. synthesised a few chiral available cobalt salen complexes 68 and 69 for the ketiminato cobalt complexes 66-69 and employed enantioselective Henry reaction65. In the presence of i- 64 them in the asymmetric Henry reaction . Pr2EtN, as little as 2 mol % of the cobalt salen

ANANTHI et al.: ASYMMETRIC HENRY REACTION 105

N N N N Cr Cr R O 2 O R2 t-Bu O O t-Bu Cl R 1 R1 t-Bu t-Bu 64c 64a R1,R2 = t-Bu 64b R1 = t-Bu, R2 = Me complexes promotes condensation of nitromethane nitro alcohols in 60-92% yields with 60-90% ee. This with aromatic aldehydes with enantioselectivity catalyst was separated by filtration and reused several ranging from 62% to 98%. times without any significant loss of reactivity or A chiral bimetallic Co(II)-salen catalyst (70, enantioselectivity. Figure 5) self-assembled through hydrogen bonding, Chiral bis(oxazoline) ligand 72 was immobilized was developed by Park et al. in 2008 which results in onto a magnetically separable hierarchically ordered significant rate acceleration as well as excellent mesocellular mesoporous silica (M-HMMS) and this enantioselectivity in Henry reaction66. The self- new catalytic system was examined in the asymmetric assembly through hydrogen bonding was confirmed Henry reaction between various aldehydes and by the X-ray structure and 1H NMR experiments. A nitromethane atambient temperature by Kim et al.68 bimetallic mechanism is suggested by the kinetic Good enantioselectivity (upto 86.0% ee) could be experiment. observed when the free silanol groups of the This result proves the validity of novel self mesoporous silica were capped by trimethylsilyl assembly based approaches toward the efficient group. The interesting aspect of this research is the construction of chiral bimetallic catalyst systems. The separation of the reused catalyst magnetically and it product chiral nitroaldol was formed in 87% yield has been used several times without significant loss of with 96% ee. reactivity or enantioselectivity. This magnetic separation of catalysts could lead to further Supported chiral catalysts for asymmetric Henry development towards practical industrial scale reaction application due to the simplicity of procedure without A new catalytic system of chirally modified MCM- cumbersome filtration. 41-Cu(salen) complex 71 has been prepared and Conclusion examined in the asymmetric Henry reaction between various aldehydes and nitromethane at room In this short review, an attempt has been made to temperature by Rajagopal et al. recently67. It was cover the different transition metal complex catalyst found that aromatic, aliphatic, and heterocyclic systems used for carrying out asymmetric Henry aldehydes can be converted into the corresponding

Scheme XVIII — Asymmetric Henry reaction catalysed by chiral thiophene-salen chromium complex

106 INDIAN J. CHEM., SEC B, JANUARY 2013

Ph Ph

N N N N Co Co O O O O O O O O

66 67

Ph Ph

N N N N Co Co i-Pr O O i-Pr i-Pr O O i-Pr

i-Pr i-Pr i-Pr i-Pr 68 69

N N O Co t-Bu O O N N N t-Bu t-Bu H O H t-Bu H O H N t-Bu N N O O t-Bu Co O N N

70 Figure 5 — Structure of self-complementary dinuclear Co(salen) complex

OTMS N N O OEt N N Cu H Si N O N O O O O O 5 O O N OTMS 2+ N O Cu O O N 2OAc- Si N O O H O OEt N 5 O N OTMS N O O O OTMS

MCM-41 71 72

ANANTHI et al.: ASYMMETRIC HENRY REACTION 107

reaction. Most of the catalytic asymmetric reactions 22 Nguyen Q T & Jeong J H, Polyhedron, 25, 2006, 1787. involve the participation of in situ formed catalysts. 23 Gan C, Lai G, Zhang Z, Wanga Z & Zhou M M, Tetrahedron: Asymmetry, 17, 2006, 725. From the current degree of development, it is 24 Sedlak M, Drabina P, Keder R, Hanusek J, Cisarova I & understandable that most of the catalysts developed Ruzicka A, J Organomet Chem, 691, 2006, 2623. for asymmetric Henry reaction are chiral copper 25 Blay G, Climent E, Fernandez I, Olmos V H & Pedro J R, complexes. Some chiral zinc, cobalt and chromium Tetrahedron: Asymmetry, 17, 2006, 2046. complexes are also reported. Studies on other chiral 26 Xiong Y, Wang F, Huang X, Wen Y & Feng X, Chem Eur J, 13, 2007, 829. transition metal complexes for the asymmetric Henry 27 Arai T, Watanabe M & Yanagisawa A, Org Lett, 9, 2007, reaction are in progress. Similarly, the substrates 3595. participating in the asymmetric Henry reaction should 28 Jiang J J & Shi M, Tetrahedron: Asymmetry, 18, 2007, 1376. also be challenging in order to synthesize novel chiral 29 Gao Y G, Chen N, Wu H J & Li X S, Russ J Org Chem, 43, 2007, 1754. compounds useful for synthetic organic chemistry. 30 Zhang Y, Xiang L,Wang Q, Duan X Z & Zi G, Inorg Chim Acta, 361, 2008, 1246. Acknowledgement 31 Kowalczyk R, Sidorowicz L & Skarzewski J, Tetrahedron: Authors thank Dr. M. Chidhambaram, former Asymmetry, 19, 2008, 2310. director, NITT for his encouragement and support. 32 Arai T, Takashita R, Endo Y, Watanabe M & Yanagisawa A, J Org Chem, 73, 2008, 4903. 33 Gan C, Can J Chem, 86, 2008, 261. References 34 Sanjeevakumar N & Periasamy M, Tetrahedron: Asymmetry, 1 Sasai H, Suzuki T, Arai T & Shibasaki M, J Am Chem Soc, 20, 2009, 1842. 114, 1992, 4418. 35 Zielinska-Blajet M & Skarzewski J, Tetrahedron: Asymmetry, 2 Norman B H & Morris M L, Tetrahedron Lett, 33, 1992, 20, 2009, 1992. 6803. 36 Wei Y, Yao L, Zhang B, He W & Zhang S, Tetrahedron, 67, 3 Matt C, Wagner A & Mioskowski C, J Org Chem, 62, 1997, 2011, 8552. 234. 37 Kowalczyk R & Skarzewski J, Tetrahedron: Asymmetry, 20, 4 Poupart M A, Fazal G, Goulet S & Mar L T, J Org Chem, 64, 2009, 2467. 1999, 1356. 38 Rachwalski M, Lesniak S, Sznajder E & Kiełbasinski P, 5 Ono N, The Nitro Group in Organic Synthesis (Wiley-VCH, Tetrahedron: Asymmetry, 20, 2009, 1547. New York), 2001. 39 Khan N H, Prasetyanto E A, Kim Y K, Ansari M B & Park S 6 Luzzio F A, Tetrahedron, 57, 2001, 915. E, Catal Lett, 140, 2010, 189. 7 Sasai H, Suzuki T, Itoh N, Arai S & Shibasaki M, 40 Xin D, Ma Y & He F, Tetrahedron: Asymmetry, 21, 2010, Tetrahedron Lett, 34, 1993, 855. 333. 8 Shvekhgeimer M G A, Russ Chem Rev, 67, 1998, 35. 41 Noole A, Lippur K, Metsala A, Lopp M & Kanger T, J Org 9 Kurti L & Czako B, Strategic Applications of Named Chem, 75, 2010, 1313. Reactions in Organic Synthesis, (Elsevier Academic Press M 42 Yang W, Liu H & Du D, Org Biomol Chem, 8, 2010, 2956. A, Burlington), 2005. 43 Ananthi N, Balakrishnan U & Velmathi S, ARKIVOC, xi, 10 Boruwa J, Gogoi N, Saikia P P & Barua N C, Tetrahedron: 2010, 370. Asymmetry, 17, 2006, 3315. 44 Basi S R, Madhusudana Reddy S, Manisha S & Madan C, 11 Shibasaki M & Grhger H, Comprehensive Asymmetric Tetrahedron: Asymmetry, 22, 2011, 530. Catalysis, Vol III (Springer, Berlin), 1999. 45 Guo Z L, Zhong S, Li Y B & Lu G, Tetrahedron: Asymmetry, 12 Shibasaki M, Grhger H & Kanai M, Comprehensive 22, 2011, 238. Asymmetric Catalysis, Supplement 1 (Springer, Heidelberg), 46 Zhou Y, Dong J, Zhang F & Gong Y, J Org Chem, 76, 2004. 2011,588. 13 Arai T, Yamada Y M A, Yamamoto N, Sasai H & Shibasaki 47 Lu D, Zhou Y, Li Y, Yan S & Gong Y, J Org Chem, 76, M, Chem Eur J, 2, 1996, 1368. 2011, 8869. 14 Sasai H, Watanabe S, Suzuki T & Shibasaki M, Org Synth, 48 Jin W, Li X & Wan B, J Org Chem, 76, 2011, 484. 10, 2004, 571. 49 Zielinska-Blajet M & Skarzewski J, Tetrahedron: Asymmetry, 15 Shibasaki M & Yoshikawa N, Chem Rev, 102, 2002, 2187. 22, 2011, 351. 16 Shibasaki M, Kanai M & Funabashi K, Chem Commun, 1, 50 Kim H U & Oh K, Org Lett, 11, 2009, 5682. 2002, 1989. 51 Bures F, Kulhanek J & Ruzicka A, Tetrahedron Lett, 50, 17 Rowlands G J, Tetrahedron, 57, 2001, 1865. 2009 , 3042. 18 Christensen C, Juhl K & Jorgensen K A, Chem Commun, 52 Guo Z, Deng Y, Zhong S & Lu G, Tetrahedron: Asymmetry, 2001, 2222. 22, 2011, 1395. 19 Christensen C, Juhl K, Hazell R G & Jorgensen K A, J Org 53 Kohn U, Schulz M, Gorlsb H & Anders E, Tetrahedron: Chem, 67, 2002, 4875. Asymmetry, 16, 2005, 2125. 20 Risgaard T, Gothelf K V & Jorgensen K A, Org Biomol 54 Trost B M, Yeh V S C, Ito H & Bremeyer N, Org Lett, 4, Chem, 1, 2003, 153. 2002, 2621. 21 Evans D A, Seidel D, Rueping M, Lam H W, Shaw J T & 55 Du D M, Lu S F, Fang T & Xu J, J Org Chem, 70, 2005, Wade Downey C, J Am Chem Soc, 125, 2003, 12692. 3712.

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