Tuning the Reactivity of Ketones through Unsaturation: Construction of Cyclic and Acyclic Quaternary Stereocenters via Zn-ProPhenol Catalyzed Mannich Reactions

Introduction
of unsaturation adjacent to the carbonyl drastically
improves the reactivity of the Zn-ProPhenol catalyzed Mannich reactions
between N-carbamoyl imines and a-branched ketones. Despite only a small change in the substrate acidity,
the bimetallic catalyst can preferentially recognize and activate
unsaturated ketones over their fully saturated counterparts, providing
a chemo-, diastereo-, and enantioselective route to valuable β-aminoketones
bearing both cyclic and acyclic quaternary stereocenters, which are
common motifs in numerous biologically active alkaloids. Unsaturated
ketones and imines with various substitution patterns are viable substrates,
and the reaction can be performed on multi-millimole scale at low
catalyst loading without impacting its efficiency. More importantly,
the unsaturation introduced via the nucleophile provides a useful
platform for structural diversification.