Asymmetric Intramolecular Hydroacylation of Unactivated Alkenes

Abstract

Glorius, Grimme, and co-workers report a highly enantioselective hydroacylation of unactivated alkenes (cyclization of 1) using N-heterocyclic carbene (NHC) precatalyst 2. The resulting chromanones 3 featuring a quaternary carbon stereocenter were formed with essentially perfect enantioselectivity (er > 99.5:0.5) for a broad range of aromatic substrates. Deuterium experiments suggest a mechanism that does not involve the allylic oxygen. Furthermore, quantum mechanical calculations indicate a concerted but highly asynchronous transition state. These calculations also explain the superb enantioselectivity observed in the reaction as the cyclized intermediate resulting from the minor product enantiomer was calculated to be higher in energy than the starting material.