Mechanistic Insights into Lewis Acid-Controlled Torquoselective Nazarov Cyclization of Activated Dienones Bearing a Chiral Sulfoxide

Abstract

This work provides a switchable strategy to access, through a Nazarov cyclization, two diastereomeric disubstituted 3,4,5,6-tetrahydrocyclopenta[b]pyran-7(2H)-ones from an activated dienone bearing a chiral sulfoxide. The switch in the torquoselectivity is controlled by the nature of the Lewis acid used as promoter. From the four possible stereoisomers, only the two trans were observed. The Lewis acids employed were achiral and the diastereoselectivities were dictated by the sulfinyl auxiliary. Density functional theory investigations shed light on the reaction mechanism. The experimental torquoselectivities were very closely reproduced and their inversion could be linked back to a change in the binding mode of the substrate.