CuH-Catalyzed Enantioselective Ketone Allylation with 1,3-Dienes: Scope, Mechanism, and Applications

• DOI: 10.1021/jacs.9b01784
• Publication Date: 2019-02-28T20:44:18Z
• Authors: Chengxi Li; Richard Y. Liu; Luke T. Jesikiewicz; Yang Yang; Peng Liu; Stephen L. Buchwald
• Keywords: Models, Molecular; Organic Chemistry; Molecular Conformation; Molecular; Stereoisomerism; General Chemistry; Alkenes; Ketones; 01 natural sciences; Catalysis; 0104 chemical sciences; Inorganic Chemistry; Engineering; Chemical sciences; Models; Chemical Sciences; Copper

Chiral tertiary alcohols are important building blocks for the synthesis of pharmaceutical agents and biologically active natural products. The addition carbon nucleophiles to ketones is most common approach alcohol but traditionally relies on stoichiometric organometallic reagents that difficult prepare, sensitive, uneconomical. We describe a mild efficient method copper-catalyzed allylation using widely available 1,3-dienes as allylmetal surrogates. Homoallylic bearing wide range functional groups obtained in high yield with good regio-, diastereo-, enantioselectivity. Mechanistic investigations density theory (DFT) implicate situ formation rapidly equilibrating mixture isomeric copper(I) allyl complexes, from which Curtin–Hammett kinetics determine major isomer product. A stereochemical model provided explain diastereo- enantioselectivity this process. Finally, was applied preparation an drug, (R)-procyclidine, key intermediate several pharmaceuticals.