Thiourea-Catalyzed Intramolecular [5+2] Cycloadditions

Significance

The authors report a catalytic enantioselective intramolecular [5+2] cycloaddition of pyrylium intermediate B derived from enone 1. Highly functionalized tricyclic compounds 4 could be obtained with good enantioselectivity (er up to 97.5:2.5). With the aid of the achiral thiourea 3, chiral diamine-based thiourea 2 could catalyze the reaction with reasonable conversion. The reaction could be accelerated by employing p-thiomethylbenzoate as a leaving group (due to the low solubility of the corresponding acid). Then the leaving group could be stabilized by thiourea 3 via a hydrogen bonding interaction (A). Intensive computational studies supported the proposed aminopyrylium reaction intermediate.