Enantioselective Carbonyl Reverse Prenylation from the Alcohol or Aldehyde Oxidation Level Employing 1,1-Dimethylallene as the Prenyl Donor

Abstract

Enantioselective transfer hydrogenation of 1,1-dimethylallene 1a in the presence of aromatic, α,β-unsaturated, or aliphatic aldehydes 2a−i mediated by 2-propanol and employing a cyclometalated iridium C,O-benzoate derived from allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS delivers reverse-prenylation products 4a−i in good to excellent isolated yields (65−96%) and enantioselectivities (87−93% ee). In the absence of 2-propanol, enantioselective carbonyl reverse prenylation is achieved directly from the alcohol oxidation level to furnish an equivalent set of adducts 4a−i in good to excellent isolated yields (68−94%) and enantioselectivities (86−91% ee). Competition and isotopic labeling experiments suggest rapid alcohol−aldehyde redox equilibration in advance of carbonyl addition along with capture of the kinetically formed π-allyl complex at a higher rate than reversible β-hydride elimination−hydrometalation. This protocol represents an alternative to the use of allylmetal reagents in enantioselective carbonyl reverse prenylation and represents the first use of allenes in enantioselective C−C bond-forming transfer hydrogenation.