Asymmetric 1,2-Migration at Vicinal Tetrasubstituted Stereocenters Constructed from α-Keto Imines.

ABSTRACT

A carbonyl-assisted asymmetric 1,2-migratory allylation through in situ generation of vicinal tetrasubstituted stereocenters is reported to access enantiopure α-amino ketones and amino alcohols with excellent yields and diastereoselectivities. In a remarkable divergence, despite higher steric hindrance, the allylation exclusively occurs on ketones over imines in the first step, followed by a face-selective 1,2-allyl transfer, thus highlighting an exciting interplay between two distinct electrophiles. The methodology distinguishes itself through its adaptability to gram-scale synthesis, showcasing broad functional-group tolerance and stereodivergence. Density functional theory (DFT) analysis led to a deeper understanding of its selectivity and mechanistic framework. Highlighting its transformative potential, the method was applied to the total synthesis of hapalindole alkaloids.