Enantioselective reduction of C=O and C=N bonds by TADDOL-containing aluminum hydride reagents based on NaAlH4 and AlH3

Abstract

Prochiral substrates (alkyl aryl ketones, cyclopropyl methyl ketone, 1-indanone, 1-tetralone, ethyl 2-oxo-4-phenylbutyrate, and N-(diphenylphosphinyl)acetophenoneimine) were subjected to asymmetric reduction with aluminum hydride reagents, which were prepared by modifications of NaAlH4 or AlH3 with chiral α,α,α",α"-tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOL). The effects of the nature of the substituents in TADDOL, the structure of the prochiral substrate, and the reaction conditions on the stereochemistry of reduction were investigated. The highest enantioselectivity (70—90% ee) was achieved upon reduction of alkyl aryl ketones and N-(diphenylphosphinyl)acetophenoneimine with NaAl(TADDOLate)H2 in THF or diglyme at a temperature from –70 to –20 °C. The mechanism of asymmetric induction in the reduction reactions of ketones with aluminum hydride reagents is discussed. The stereochemical results of reduction were explained by comparing three-dimensional models of the most probable transition states.