Domino Synthesis of α,β-Unsaturated γ-Lactams by Stereoselective Amination of α-Tertiary Allylic Alcohols

Abstract

Tertiary allylic alcohols equipped with a carboxyl group can be smoothly aminated under ambient conditions by a conceptually new and stereoselective protocol under palladium catalysis. The in situ formed Z-configured γ-amino acid cyclizes to afford an α,β-unsaturated γ-lactam, releasing water as the only byproduct. This practical catalytic transformation highlights the use of a carboxyl group acting as an activating and stereodirecting functional group to provide a wide series of pharma-relevant building blocks. Various control reactions support the crucial role of the carboxyl group in the substrate to mediate these transformations.

Keywords: allylic compounds; amination; lactams; palladium; stereoselectivity.