Organocatalytic Domino Michael-Aldol Reaction to Chiral Benzothiopyrans

Significance

Reported is a facile organocatalytic assembly of chiral benzothiopyrans containing succinimide motifs. This efficient transformation, utilizing as low as 1 mol% of the chiral bifunctional thiourea catalyst A, results in the formation of three new stereogenic centers in a one-pot process. The yields are high, the dr and ee values range from moderate to high and the reaction conditions appear optimized. Not unexpectedly, Diels-Alder and domino-Michael-aldol mechanisms were proposed and the former was ruled out on the basis of analysis of the stereochemistry of the products and the transition states. The activity of the catalyst derives from the non-covalent hydrogen-bonding interactions (see review below), activating both the nucleo- and the electrophile, which mimics many enzymatic catalysts.