Conjugate additions bifunctional catalysts

A highly enantioselective and diastereoselective addition of trisubstituted carbon donors, such as (166), to 2-chloroacrylonitrile (167), catalysed by bifunctional Cin- chona alkaloid catalysts, e.g. (169), has been reported as the first example of an asymmetric cascade that includes conjugate addition and protonation with efficient (g) catalytic control at two non-adjacent stereocentres (168).218... 

Despite the importance of the Michael addition in organic synthesis, the tandem conjugate addition/enantioselective protonation has been little explored [14] and only a few publications have involved cinchona alkaloids as bifunctional catalysts B for controlling the configuration of the chiral carbon created during protonation (Scheme 7.9). 

Using the bifunctional chiral primary amine thiourea catalyst 41 (20 mol%) in CH Clj and in the presence of five equivalents of H O as additive, a highly enanti-oselective direct conjugate addition of a wide range of a,a-unsymmetrically dis-ubstituted aldehydes (only a twofold excess of aldehyde relative to nitroaUcene) to nitroolefins is obtained (see Table 2.1, entry 15, for a representative example) [61], The beneficial role of water is proposed to lie in increasing turnover by eliminating potential catalyst deactivation pathways, and accelerating the final imine hydrolysis. 

Bifunctional alkaloid-derived thiourea catalyst 79 promotes the conjugate addition of nitroalkanes to l,l-bis(benzenesulfonyl)ethylene in toluene to afford the corresponding enantiomerically enriched y-sulfonyl derivatives at-10°C [183]. Although... 

In 2003, Takanoto et al. reported the first highly enantioselective organocatalytic conjugate addition of 1,3-dicarbonyl compounds to nitroolefins catalyzed by bifunctional thiourea-amine catalyst 142 (Fig. 2.15)[238]. After Takemoto s report a wide... 

On the other hand, the enantioselective conjugate addition of a-substituted cyano-acetates and cyanoketones to a,P-unsaturated sulfones has been reported by Deng et al. using bifunctional cupreine 127 as catalyst [270]. Substoichiometric amounts of 127 (20 mol%) catalyze the synthesis of chiral sulfones containing all-carbon... 

From the various conjugate addition reactions of nucleophiles to a,p-unsaturated carbonyl compounds, the use of maleimides as the Michael acceptor deserves special mention. Xue and coworkers developed a highly sustainable protocol for the Michael addition of a,a-disubstituted aldehydes to maleimides (Scheme 19.52). Remarkably, using 1 mol% of the simple bifunctional thiourea catalyst 46 and water as additive, the reaction proceeded smoothly to afford oc-branched succinimides in high yields and with... 

---