Organocatalytic insertion into C-B bonds by in situ generated carbene: mechanism, role of the catalyst, and origin of stereoselectivity

The origin of stereoselectivity for BINOL-catalyzed insertion into the C(sp(2))-B bond of alkylboronic ester by in situ generated carbene has been investigated using density functional theory (DFT). The reaction to form chiral alpha-CF3 allylboronic acid includes three stages: (1) formation of chiral alkenyl boronate, (2) carbene insertion into the C-B bond, and (3) dissociation of the BINOL catalyst. The carbene insertion has been proved to be the stereoselectivity-determining step, and the S-configurational pathway is more energetically favorable than the R-configurational approach. The quantum theory of atoms in molecules (QTAIM) analyses suggest that the C-HMIDLINE HORIZONTAL ELLIPSISX (X = I, Br) hydrogen bond interactions are the key factors for determining enantiomeric outcomes, and further electron localization function (ELF) and frontier molecular orbital (FMO) analyses reveal electronic structure changes over the carbene insertion coordinate. The obtained insights will be valuable for understanding other similar asymmetric constructions of C-B bonds, which helps design a better catalyst.

Automated summary

This study employs DFT to investigate the origin of stereoselectivity for BINOL-catalyzed insertion into the C(sp(2))-B bond of alkylboronic ester by in situ generated carbene, finding that the carbene insertion is the key determining step for stereoselectivity, with the S-configurational pathway being more energetically favorable. Additionally, QTAIM analyses suggest that hydrogen bond interactions are crucial for determining enantiomeric outcomes.