2-Mercaptobenzaldehyde, cascade reaction

The Michael-aldol cascade reaction of2-mercaptobenzaldehyde with a,/ -unsaturated A-acyl imides (293) (R = alkyl, Ar, hetero-Ar), giving rise to thiochromanes (294), has been attained using the thiourea derivative (295) as a chiral organocatalyst. The key factor here is the presence of the pyrazole moiety as H-bond acceptor, which facilitates the activation and contributes to a better organization of the transition state. 

Novel aldol-type reactions under Cinchona-deriwed chiral thiourea catalysis was reported by Wang et al. [78]. In their report, a novel cascade Michael-aldol reaction was presented. The reaction involves a tandem reaction catalyzed via hydrogen-bonding with as little as 1 mol% catalyst loading to generate a product with three stereogenic centers (Scheme 28). hi the reaction of 2-mercaptobenzaldehyde 128 and a,P-unsatnrated oxazolidinone 129, the desired benzothiopyran 130 was formed smoothly in high yield and excellent stereoselectivity. 

Wang et al. [49] obtained enantioenriched thiochromenes through a cascade sulfa-Michael-aldol-dehydration reaction between 2-mercaptobenzaldehydes and a,p-unsaturated aldehydes, catalyzed by 17a (Scheme 14.17a). Cordova and coworkers [50] obtained comparable results despite some minor changes of the reaction conditions. An analogous process with cyclic enones afforded tetrahydrothioxanthe-nones in only moderate enantioselectivities (Scheme 14.17b). In this case, chiral pyrrolidines 18 and 19 gave the best results in terms of enantioselectivities [51]. 

Cascade Michael-aldol reaction of mercaptobenzaldehyde with a,P-unsaturated oxazolidinone was realized by a cinchona-alkaloid catalyst (15b) to give benzoth-iopyran in high yields with excellent diastereoselectivity (Scheme 2.57). Contiguous three stereogenic centers were controlled [112]. 

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