Enantioselective organocatalytic singly occupied molecular orbital activation: the enantioselective alpha-enolation of aldehydes.

Over the last 40 years, thousands of asymmetric catalytic reactions have been invented in accord with the increasing need for enantiopure medicinal agents and the rapid advancement of the field of chemical synthesis.1 Remarkably, however, the vast majority of these enantioselective processes are derived from a small number of long-established activation modes (e.g., Lewis acid catalysis,2 σ-bond insertion,3 π-bond insertion,4 atom-transfer catalysis,5 and hydrogen-bonding catalysis6). A critical objective, therefore, for the continued advancement of the field of asymmetric catalysis is the design and implementation of novel activation modes that enable the invention of unprecedented transformations. Recently, our laboratory introduced a new mode of organocatalytic activation, termed singly occupied molecular orbital (SOMO) catalysis,7-9 that is founded upon the mechanistic hypothesis that one-electron oxidation of a transient enamine intermediate (derived from aldehydes and chiral amine catalysts) will render a 3π-electron SOMO-activated species that can readily participate in a range of unique asymmetric bond constructions.10 In our original SOMO studies,7 we documented the first direct and enantioselective allylic alkylation of aldehydes (eq 1). In this Communication, we further advance this activation concept to describe the first asymmetric aldehyde R-enolation, a protocol that allows direct access to enantioenriched γ-ketoaldehydes from simple aldehydes, enolsilanes and a commercial catalyst (eq 2).