Chiral Bifunctional Amine-Squaramide-Catalyzed Highly Diastereo- and Enantioselective Michael/Aldol Cascade Reaction of 2-Mercaptobenzaldehyde and α,β-Unsaturated 7-Azaindoline Amides

A highly diastereo- and enantioselective Michael/aldol cascade reaction of 2-mercaptobenzaldehyde and α,β-unsaturated 7-azaindoline amides has been developed. Using as low as 1 mol % cinchonidine-derived bifunctional squaramide as the catalyst, a range of enantioenriched thiochromenes containing three contiguous stereogenic centers were smoothly obtained in excellent results (all cases >20:1 dr, 88–99% yield and ≥99% ee). The 7-azaindoline moiety of α,β-unsaturated 7-azaindoline amides has been demonstrated to be vital for the high reactivity and excellent stereoselectivity.