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

Angew Chem Int Ed Engl. 2024 May 9:e202405212. doi: 10.1002/anie.202405212. Online ahead of print.

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 having 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. The density functional theory (DFT) analysis elucidates a deeper understanding of its selectivity and mechanistic framework. Highlighting its transformative potential, the total synthesis of hapalindole alkaloids were adeptly achieved.

Keywords: vicinal stereocenters * 1,2-migration * α-amino ketones * sulfinyl imines * indole alkaloids.