CHAPTER 7: Asymmetric α-Selective and Remote γ-Selective Functionalization of Enals and Enones Through Serebryakov-Jørgensen Dienamines (1-Aminobuta-1,3-Dienes)

Abstract

Serebryakov-Jørgensen dienamine intermediates derived from enals, cyclic enones and allylic ketones with the aid of amine catalysts have found widespread applications in some highly appealing α-selective functionalizations and, far more intriguing, γ-selective functionalizations in recent times. Intramolecular Baylis-Hillman type reactions, asymmetric aza-Morita-Baylis-Hillman type products, chiral Michael adducts from addition to nitroolefins, intramolecular Rauhut-Currier cyclizations for the construction of chiral cyclopentenals, the asymmetric synthesis of cyclopentyl[b]indolines via the SN1 alkylation reaction of γ,γ-disubstituted α,β-unsaturated aldehydes with 3-indolylmethanols and the asymmetric benzoyloxylation of α-branched enals were attainable as α-selective functionalization. The category of γ-selective functionalization encompassed the asymmetric amination of α,β-unsaturated aldehydes, the synthesis of a key intermediate for α-tocopherol, aldol reactions with aldehydes, isatins (for the enantioselective synthesis of 3-substituted 3-hydroxyoxindole derivatives) and α-ketoesters (involving hydrogen-bond-directing dienamine catalysis), alkylation of α-branched enals, and the enantioselective Michael addition of cyclic enones to nitroalkenes and allyl alkyl ketones to maleimides. Moreover, γ-propargylation, γ-oxyamination and asymmetric γ-allylation of α,β-unsaturated aldehydes were achieved by combined dienamine and transition-metal catalysis. Enantioselective γ-alkylation of enals was also driven by the direct photoexcitation of dienamine intermediates. Further, γ-selective nitrone formation from an enal via a redox reaction is highlighted in this chapter.