Practical, Broadly Applicable, α‑Selective, <i>Z</i>‑Selective, Diastereoselective, and Enantioselective Addition of Allylboron Compounds to Mono‑, Di‑, Tri‑, and Polyfluoroalkyl Ketones

A practical method for enantioselective synthesis of fluoroalkyl-substituted <i>Z</i>-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 <i>Z</i>- or an <i>E</i>-γ-substituted boronic acid pinacol ester. With a <i>Z</i> organoboron reagent, additions to trifluoromethyl and polyfluoroalkyl ketones proceeded in 80–98% yield, 97:3 to >98:2 α:γ selectivity, >95:5 <i>Z</i>:<i>E</i> 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 and α- and <i>Z</i>-selective when an <i>E</i>-allylboronate compound was used, but enantioselectivities were lower. 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 <i>Z</i>-alkene substrates are required. Mechanistic investigations aided by computational (DFT) studies and offer insight into different selectivity profiles.