Phosphine-Catalyzed Intramolecular Vinylogous Aldol Reaction of α-Substituted Enones

We demonstrate the first phosphine-catalyzed intramolecular vinylogous aldol reaction (IVAR) of alpha-substituted enones. This strategy provides access to various pentannulated (hetero)arenes and dibenzocycloheptanones incorporated with two contiguous stereocenters, one of which is an all-carbon quaternary center. The scope of this work is further broadened through elaborations of the IVAR adducts to (i) benzannulated nine-membered carbocyclic systems, (ii) interesting classes of 1,3-dienes, 1,3,5-trienes, and 1-yn-3,5-dienes, and (iii) the analogs of echinolactone D and russujaponol F.

Automated summary

This study demonstrates a novel strategy for the phosphine-catalyzed intramolecular vinylogous aldol reaction of alpha-substituted enones, leading to the synthesis of various novel cyclic compounds and dibenzocycloheptanones with two contiguous stereocenters. The scope of this work is further expanded through transformations of the IVAR adducts, resulting in the synthesis of benzannulated nine-membered carbocyclic systems, interesting classes of dienes, trienes, and dienynes, as well as analogs of echinolactone D and russujaponol F.