We have examined three N-heterocyclic carbene (NHC) catalyzed kinetic resolutions (KR) and one dynamic kinetic resolution (DKR) using modern density functional theory methods to investigate the origin of catalytic activity, selectivity, non-covalent interactions and the role of co-catalysts in these reactions. Out study has provided several intriguing new insights that cannot be achieved through experiments alone. The results reveal electrostatic interactions as the common driver of selectivity. Furthermore, in the case of a recently described KR of BINOL-derivatives, a computational examination of the full catalytic cycle reveals that a benzoic acid by-product changes the turnover limiting transition step, obviating the need for an added co-catalyst. We have offered a sound theoretical rational behind frequnt use of protic additives in these transformations and importance of non-covalent interactions to enhance stereoselectivity when work in concert with electrostatic interaction. Moreover, we have also illustrated how even small molecules can behave like enzymes to control an overall catalytic transformation. Together, our study has not only unravel several aspects related to activity and selectivity of NHC-catalyzed kinetic resolutions but also underscores the importance of electrostatic interactions as a driver of selectivity that can be exploited for future rational reaction design using NHC catalysis.

Importance of electrostatic effects in the stereoselectivity of NHC-catalyzed kinetic resolutions

256th National Meeting (2018)

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