anti-Diastereo- and Enantioselective Carbonyl Crotylation from the Alcohol or Aldehyde Oxidation Level Employing a Cyclometallated Iridium Catalyst: α-Methyl Allyl Acetate as a Surrogate to Preformed Crotylmetal Reagents

Abstract

Under the conditions of transfer hydrogenation employing an ortho-cyclometallated iridium catalyst generated in situ from [Ir(cod)Cl]₂, 4-cyano-3-nitrobenzoic acid and the chiral phosphine ligand (S)-SEGPHOS, α-methyl allyl acetate couples to alcohols 1a−1j with complete levels of branched regioselectivity to furnish products of carbonyl crotylation 3a−3j, which are formed with good levels of anti-diastereoselectivity and exceptional levels of enantioselectivity. An identical set of optically enriched carbonyl crotylation products 3a−3j is accessible from the corresponding aldehydes 2a−2j under the same conditions, but employing isopropanol as the terminal reductant. Experiments aimed at probing the origins of stereoselection establish a matched mode of ionization for the (R)-acetate and the iridium catalyst modified by (S)-SEGPHOS, as well as reversible ionization of the allylic acetate with rapid π-facial interconversion of the resulting π-crotyl intermediate in advance of C−C bond formation. Additionally, rapid alcohol−aldehyde redox equilibration in advance of carbonyl addition is demonstrated. Thus, anti-diastereo- and enantioselective carbonyl crotylation from the alcohol or aldehyde oxidation level is achieved in the absence of any stoichiometric metallic reagents or stoichiometric metallic byproducts.