2026-10-12T17:50:00Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33752291 2026-09-14T17:06:09Z category_4 category_734 category_132 category_133 portal_63 item_type_3 month_year_09_2026

Competition-Derived Relative Reactivity and 3D Electronic-State Analysis of Site- and Facial Selectivity in NaBH₄/MeOH Ketone Reductions Daimon Sakaguchi (18332040) Taisei Kawasaki (24896219) Mayu Itakura (24896222) Chihiro Tada (24896225) Hiroaki Gotoh (1771738) Biochemistry Biological Sciences not elsewhere classified Infectious Diseases Plant Biology testing broader applicability predicted product distributions lasso model trained every diketone examined driven analyses within derived model recovers unified kinetic scale independent kinetic scale derived relative reactivity 2 </ sup validation models reproducing >< sup r </ g </ kinetic data workflow integrates therefore may theoretical calculations steric congestion state analysis sodium borohydride side reactions indicative rather facial selectivity experimental measurements dimensional electron descriptors achieved based measures active reductant 3d electronic Yield-based measures of reactivity can be distorted by side reactions and reaction conditions and therefore may not accurately reflect intrinsic reaction rates. In this study, competition experiments, in which two substrates react simultaneously with the same reagent, were used to build a unified kinetic scale for the reduction of ketones by sodium borohydride (NaBH₄) in methanol, expressed as activation free energy differences (ΔΔ<i>G</i>^‡). Kinetic data for 89 structurally diverse ketone reaction faces tracked substituent electronic effects and steric congestion, and transition-state calculations identified methanolysis as the step that determines the identity of the active reductant. A Lasso model trained on 83 of these reaction faces with three-dimensional electron-density, electrostatic-potential, and carbonyl-centered projected CO π* descriptors achieved <i>R</i>² = 0.804 under strict nested outer leave-one-out cross-validation. The monoketone-derived model recovers the dominant site and face for every diketone examined, with 85.5% of the cross-validation models reproducing all assignments; however, the predicted product distributions are indicative rather than quantitative. The workflow integrates a yield-independent kinetic scale with experimental measurements, theoretical calculations, and data-driven analyses within the evaluated NaBH₄/MeOH domain and provides a basis for testing broader applicability through reaction-specific data, retraining, and validation. 2026-09-14T00:00:00Z Dataset Dataset 10.1021/jacsau.6c01269.s002 https://figshare.com/articles/dataset/Competition-Derived_Relative_Reactivity_and_3D_Electronic-State_Analysis_of_Site-_and_Facial_Selectivity_in_NaBH_sub_4_sub_MeOH_Ketone_Reductions/33752291 CC BY-NC 4.0