Enantioselective iridium-catalyzed carbonyl allylation from the alcohol or aldehyde oxidation level via transfer hydrogenative coupling of allyl acetate: departure from chirally modified allyl metal reagents in carbonyl addition.
Under the conditions of transfer hydrogenation employing an iridium catalyst generated in situ from [Ir(cod)Cl]2, chiral phosphine ligand (R)-BINAP or (R)-Cl,MeO-BIPHEP, and m-nitrobenzoic acid, allyl acetate couples to allylic alcohols 1a-c, aliphatic alcohols 1d-l, and benzylic alcohols 1m-u to furnish products of carbonyl allylation 3a-u with exceptional levels of asymmetric induction. The very same set of optically enriched carbonyl allylation products 3a-u are accessible from enals 2a-c, aliphatic aldehydes 2d-l, and aryl aldehydes 2m-u, using iridium catalysts ligated by (-)-TMBTP or (R)-Cl,MeO-BIPHEP under identical conditions, but employing isopropanol as a hydrogen donor. A catalytically active cyclometallated complex V, which arises upon ortho-C-H insertion of iridium onto m-nitrobenzoic acid, was characterized by single-crystal X-ray diffraction. The results of isotopic labeling are consistent with intervention of symmetric iridium pi-allyl intermediates or rapid interconversion of sigma-allyl haptomers through the agency of a symmetric pi-allyl. Competition experiments demonstrate rapid and reversible hydrogenation-dehydrogenation of the carbonyl partner in advance of C-C coupling. However, the coupling products, which are homoallylic alcohols, experience very little erosion of optical purity by way of redox equilibration under the coupling conditions, although isopropanol, a secondary alcohol, may serve as terminal reductant. A plausible catalytic mechanism accounting for these observations is proposed, along with a stereochemical model that accounts for the observed sense of absolute stereoinduction. This protocol for asymmetric carbonyl allylation transcends the barriers imposed by oxidation level and the use of preformed allyl metal reagents.
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.
In Su
IS
Kim
Ming-Yu
MY
Ngai
Michael J
MJ
Krische
D000085:Acetates / Q000737:chemistry*; D000438:Alcohols / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D000498:Allyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D006865:Hydrogenation; D007495:Iridium / Q000737:chemistry; D010084:Oxidation-Reduction; D020005:Propanols / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000085:Acetates; D000438:Alcohols; D000447:Aldehydes; D000498:Allyl Compounds; D020005:Propanols; C006463:allyl alcohol; D007495:Iridium; C498551:allyl acetate