Mechanistic Details of Asymmetric Bromocyclization with BINAP Monoxide: Identification of Chiral Proton-Bridged Bisphosphine Oxide Complex and Its Application to Parallel Kinetic Resolution.

The mechanism of our previously reported catalytic asymmetric bromocyclization reactions using 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) monoxide was examined in detail by the means of control experiments, NMR studies, X-ray structure analysis, and CryoSpray electrospray ionization mass spectrometry (ESI-MS) analysis. The chiral BINAP monoxide was transformed to a key catalyst precursor, proton-bridged bisphosphine oxide complex (POHOP·Br), in the presence of N -bromosuccinimide (NBS) and contaminating water. The thus-formed POHOP further reacts with NBS to afford BINAP dioxide and molecular bromine (Br 2 ) simultaneously in equimolar amounts. While the resulting Br 2 is activated by NBS to form a more reactive brominating reagent (Br 2 ─NBS), BINAP dioxide serves as a bifunctional catalyst, acting as both a Lewis base that reacts with Br 2 ─NBS to form a chiral brominating agent (P═O + ─Br) and also as a Brønsted base for the activation of the substrate. By taking advantage of this novel concerted Lewis/Brønsted base catalysis by BINAP dioxide, we achieved the first regio - and chemodivergent parallel kinetic resolutions (PKRs) of racemic unsymmetrical bisallylic amides via bromocyclization.