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 center dot 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 Bronsted base for the activation of the substrate. By taking advantage of this novel concerted Lewis/ Bronsted base catalysis by BINAP dioxide, we achieved the first regio- and chemodivergent parallel kinetic resolutions (PKRs) of racemic unsymmetrical bisallylic amides via bromocyclization.

Automated summary

The mechanism of the catalytic asymmetric bromocyclization reactions using BINAP monoxide was investigated in this study. A key catalyst precursor, POHOP center dot Br, was formed by the transformation of chiral BINAP monoxide in the presence of NBS and water. This precursor further reacted with NBS to produce BINAP dioxide and molecular bromine simultaneously. By utilizing the dual functionality of BINAP dioxide, the regio- and chemodivergent parallel kinetic resolutions of racemic unsymmetrical bisallylic amides via bromocyclization were successfully achieved.