Using Three-Dimensional Information to Predict and Interpret the Facial Selectivities of Nucleophilic Additions to Cyclic Ketones

In this study, we devised a new method to predict facial
selectivity
by quantifying steric and orbital factors for the nucleophile approaching
both π-plane faces. Using this method, we quantified the total
electron density and frontier orbital distributions of 163 cyclic
ketones with various structures and quantitatively explained the surface
selectivity of 323 reactions with eight nucleophiles (BH3, LiAlH4, NaBH4, LiAl(OMe)3H, MeLi,
MeMgI, PhLi, and PnMgI). Importance analysis showed a large orbital
effect for BH3, LiAlH4, and NaBH4 and the dominance of the steric effect for LiAl(OMe)3H, MeLi, MeMgI, PhLi, and PhMgI. Our method analyzes three-dimensional
features based on Gaussian cube files, which can be easily obtained
using mainstream computational chemistry software packages, and this
approach should prove useful for predicting the rates and facial selectivity
of other reactions.