Enantioselective Formal [3 + 1 + 1] Cycloaddition Reaction by Ru(II)/Iminium Cocatalysis for Construction of Multisubstituted Pyrrolidines

A Ru­(II)/iminium
cocatalyzed asymmetric formal [3 + 1 + 1] cycloaddition
reaction of diazoacetophenones, anilines, and enals is disclosed to
construct multisubstituted pyrrolidines in one step with excellent
diastereoselectivity and enantioselectivity. The reaction mechanism
was postulated as a successful trapping of Ru­(II)-associated ammonium
ylides via a selective 1,4-addition to chiral amine activated enals
followed by a tandem aza-aldol process. The control experiments and
theoretical density functional theory investigation revealed that
the reversible NaOAc-facilitated aza-aldol process led to the diastereomeric
conversion to provide a stable product.