Analysis of Asymmetric Reduction of Ketones Using Three-Dimensional Electronic States

In this study, we introduced an approach combining transition
state
analysis and data-driven modeling that leverages the electronic states
of ketone substrates to systematically analyze the selectivity of
asymmetric reduction. Transition state analysis of the reduction of
acetophenone and trifluoroacetophenone using the Corey–Bakshi–Shibata
catalyst, B-chlorodiisopinocamphenylborane, and alpine
borane successfully explained the reaction selectivity. Analysis was
extended to a broader set of 315 asymmetric reduction reactions by
incorporating the grid-based electronic and electrostatic features
of the ketone substrates. The high predictive performance of the model
(rtest2 = 0.82) confirms its
generalizability and demonstrates its potential application in rational
reaction design and catalyst development.