New Insights into the Stereoselectivity of the Aryl Zinc Addition to Aldehydes

Abstract
The addition of Ph2Zn to aldehydes has been investigated by DFT calculations. The experimentally observed increase in enantioselectivity upon addition of Et2Zn to the reaction mixture is rationalized from calculations of all isomeric transition states. Spectator ethyl groups in the transition state do not lower the intrinsic activation barrier, but instead increase it. In the presence of a bulky ligand, the inherently preferred all-phenyl transition state is selectively disfavored. The paths with less sterically demanding spectator ethyl groups will experience a more drastic ligand acceleration, and thus the influence of the ligand would be expected to be stronger in the presence of Et2Zn, in agreement with experimental observations.
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