Imines asymmetric conjugate addition

Asides from the application of imines on conjugate addition reactions, Deng [87, 88] reported the first asymmetric chiral thiourea catalyzed Friedel-Crafts reaction of indoles with iV-tosyl imines (Scheme 35). The reaction was receptive to various aromatic, heteroaromatic, and aliphatic imines in good yield and high enantioselec-tivity (Scheme 36). 

TABLE 9. Asymmetric conjugate addition of organolithium reagents to a,/ -unsaturated esters and imines in the presence of chiral diether hgand 28 or (—)-sparteine (29) ... 

A highly enantioselective synthesis of a-dehydroamino acids (186) with a stereogenic centre at the y -position has been developed, which employs a copper-catalysed asymmetric conjugate addition of diethylzinc to a,j3-unsaturated imines (185) with the TADDOL-derived phosphoramidite (187) as a chiral ligand.234... 

Chiral Cuprate Reagents. This chiral amine has also found application in asymmetric conjugate addition of copper azaeno-lates to cyclic enones. Lithium azaenolates of optically active acetone imines have been used in the preparation of chiral cuprate reagents. However, the asymmetric induction is low (17-28% ee) when this amine is employed (eq 5). ... 

Reactions of chiral allylic boranes with carbonyl compounds Reactions of chiral allyl boranes with imines Asymmetric Addition of Carbon Nucleophiles to Ketones Addition of alkyl lithiums to ketones Asymmetric epoxidation with chiral sulfur ylids Asymmetric Nucleophilic Attack by Chiral Alcohols Deracemisation of arylpropionic acids Deracemisation of a-halo acids Asymmetric Conjugate Addition of Nitrogen Nucleophiles An asymmetric synthesis of thienamycin Asymmetric Protonation... 

Asymmetric conjugate addition reactions of carbonyl compounds with a, -unsaturated systems are known. The simple amine a-methylbenzylamine 68 acts as both the activator (to give the imine and hence the enamine required for alkylation) and as the chiral auxiliary to effect neutral asymmetric conjugate-addition reactions. " Thus, condensation of (5)-a-methylbenzylamine 68 with 2-methylcyclohexanone, followed by addition of methyl acrylate (and hydrolysis of the product imine), gave the 2,2-disubstituted cyclohexanone 69 with high enantiomeric purity (1.78). 

The chromium complex 46 of benzaldehyde imine is also a good substrate for asymmetric conjugate addition of organolithium reagents, where the reaction was mediated by a stoichiometric amount of chiral diether 18 in toluene to give, following propargylic electrophile incorporation, the cyclohexadienal 48 in up to 93% ee (Scheme 13) [38]. SAMP [(S)-l-amino-2-(methoxymethyl)pyrrolid-ine] hydrazones were used effectively in diastereoselective nucleophilic additions to (arene)Cr(CO)3 complexes [39]. 

Optically active sulfur containing compounds play a very important role in biochemistry as well as synthetic chemistry. The asymmetric conjugate addition of sulphur nucleophiles, or sulfa-Michael addition [379], provides a direct and versatile approach toward optically active sulfur compounds. This strategy is particularly valuable, since enantioselective nucleophilic additions to a C-S double bond, unlike those to carbonyls and imines, are not synthetically feasible. 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

Chiral Lewis acids derived from complexes between copper(I) chloride with phosphino sulfenyl ferrocenes are efficient catalysts for enantioselective aza-Diels-Alder reaction of A-sulfonyl imines with Danishefsky-type dienes (eq 47), and asymmetric conjugate addition of Grignard reagents to cyclic enones (eq 48).136... 

P-Borylation of a,P-Unsaturated imines. Fernandez and coworkers have also developed a route to y-ainino alcohols via a tandem sequence of enantioselective -borylation of a,p-unsaturated imines, followed by iterative imine reduction and boronic ester oxidation. In the presence of B2pin2, CuOTf and a binapthol-derived phosphoramidite ligand, asymmetric conjugate addition of (V-protected Q ,/3-unsaturated imines occurred in high yield and with excellent enantioselectivity. Diasteroselective reduction of the imine to the corresponding jyn-y-amino alcohol was achieved with BH3 THF (eq 56). The authors postulated that... 

Asymmetric Conjugate Addition with Carbonyls and Imines... 

A dihydroquinidine-derived chiral thiourea (DHQD-30), which demonstrated significantly better stereocontrol than other cinchona alkaloids, was utilized in the aza-Henry reaction with nitroalkanes and aldimines by Schaus and coworkers (Scheme 13.8) [26]. The utility of the nitroethane pronucleophile conveniently offers a tertiary stereogenic center in the P-nitroamine product 32. The methodology is also conveniently applicable to novel a,P-unsaturated aliphatic imines 29, which are difficult substrates in asymmetric conjugate addition reactions. Similar reaction conditions can be appHed towards to the use of dimethyl malonates as pronucleophiles that generate adducts in high enantioselectivity, which then convert smoothly into P-amino esters under the Nef conditions. 

Yamamoto et al. have described an asymmetric conjugate addition of copper azaenolates such as 56 derived from an acetone imine of optically active erythro-2-... 

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