Thia-Michael-aldol reactions

Scheme 7.66 Domino thia-Michael/aldol reaction.

The access toward tetrahydrothiophenes via domino thia-Michael/aldol reactions has been well studied recently [29]. Jorgensen et al. [29d] introduced an organocat-alytic approach toward optically active and highly substituted tetrahydrothiophenes by the treatment of a,fi-unsaturated aldehydes with 2-mercapto ketones. The corresponding products were obtained as single diastereomers in moderate yields and very good enantioselectivities (Table 8.8). Depending on the additive, they... 

Table 8.8 Organocatalytic domino thia-Michael/aldol reaction by Jorgensen et al. [29d].

SCHEME 16.49. Enantioselective thia-Michael/aldol reactions leading to tetrahydrothio-... 

Scheme 1.77 Domino thia-Michael-aldol reactions.

Scheme 10.27 Three-component domino Michael/Michael/aldol reaction followed by thia-...

Alternatively, Wang and coworkers reported a highly enantioselective domino thia-Michael/aldol sequence using bifunctional thiourea-tertiary amine catalysts to afford spirocyclic compound 76 [43]. ( )-Benzylidene chromanone derivatives 74 reacted with 2-mercaptobenzaldehydes 75 in the presence of a bifunctional tertiary amine-thiourea catalyst XVIII. The thia-Michael addition to the benzylidene was followed by an intramolecular aldol reaction between the resulting enolate and the aldehyde moiety. As shown in Scheme 10.26, the reaction afforded the highly functionalized spirocycles in excellent yields and stereoselectivities. 

A thia-Michael/aldol cascade [92] of ot,P-unsaturated aldehydes with 3-mercapto a-carbonyl esters or l,4-dithiane-2,5-diol and aza-Michael/aldol reactions of a,P-unsaturated aldehydes with indole-2-carbaldehydes or pyrroles [93] was also developed. 

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