Practical Broadly Applicable α-Selective Z-Selective Diastereoselective and Enantioselective Addition of Allylboron Compounds to Mono- Di- Tri- and Polyfluoroalkyl Ketones

摘要

A practical method for enantioselective synthesis of fluoroalkyl-substituted Z-homoallylic tertiary alcohols has been developed. Reactions may be performed with ketones containing a polylfluoro-, trifluoro-, difluoro- and monofluoroalkyl group along with an aryl, a heteroaryl, an alkenyl, an alkynyl, or an alkyl substituent. Readily accessible unsaturated organoboron compounds serve as reagents. Transformations were performed with 0.5–2.5 mol % of a boron-based catalyst, generated in situ from a readily accessible valine-derived aminophenol and a Z- or an E-γ-substituted boronic acid pinacol ester. With a Z organoboron reagent, additions to trifluoromethyl and polyfluoroalkyl ketones proceeded in 80–98% yield, 97:3 to >98:2 α:γ selectivity, >95:5 Z:E selectivity and 81:19 to >99:1 enantiomeric ratio. In notable contrast to reactions with unsubstituted allylboronic acid pinacol ester, additions to ketones with a mono- or a difluoromethyl group were highly enantioselective as well. Transformations were similarly efficient, α- and Z-selective when an E-allylboronate compound was used, but enantioselectivities were lower and, in certain cases, the opposite enantiomer was favored (up to 4:96 er). With a racemic allylboronate reagent that contains an allylic stereogenic center, additions were exceptionally α-selective, affording products, expected from γ-addition of a crotylboron compound, in up to 97% yield, 88:12 diastereomeric ratio and 94:6 enantiomeric ratio. Utility is highlighted by gram scale preparation of representative products through transformations that were performed without exclusion of air or moisture, and through applications in stereoselective olefin metathesis where Z-alkene substrates are required. Mechanistic investigations aided by computational (DFT) studies were carried out and offer insight into different selectivity profiles.