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.