Kinetic resolutions (KR) and dynamic kinetic resolutions (DKR) are powerful methodologies to install functional groups with pronounced selectivities. Recently, we discovered that amide bases with alkali metals activate tri- and tetrasubstituted olefins to yield stereodefined polysubstituted olefins via KR or DKR. We have investigated the mechanistic details of the transformations using density functional theory (DFT) calculations. The reactions begin with the deprotonation of racemic mixture of the starting material via the amide bases to afford carbanion intermediates. The intermediates are then subject to the electrophilic substitution or the isomerization between the E/Z-isomers. The DFT calculations and the numerical simulations of the reaction kinetics confirmed that the isomerization of the activated E-olefins is faster than the addition reaction, that explained the observed DKR that results in the enantiopure production of the Z-olefin products. Additional DFT calculations suggested that lithium anions substantially lowers the activation barrier for the conformational isomerization of E- and Z-olefins. We also found that the isomerization barrier in the presence of sodium anion is significantly higher than that of lithium anion, that affords KR in lieu of DKR. The influences of α- and β- substituents to the viability of DKR is discussed.

Computational studies of kinetic and dynamic resolution of polysubstituted olefins activated by amine bases bearing alkali metals

2019 Spring National Meeting

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