Catalytic Enantioselective Michael Addition of α-Aryl-α-Isocyano-acetates to Vinyl Selenone: Synthesis of α,α-Disubstituted α-Amino Acids and (+)- and (-)-Trigonoliimine A

摘要

α-Isocyanoacetates are well-known glycine templates for the synthesis of racemic α,α-disubstituted α-amino acids. However, catalytic enantioselective alkylation of α-isocyanoace-tates remains underexploited. Ito, Hayashi, and co-workers pioneered the field by discovering the first palladium-catalyzed enantioselective allylation of methyl α-phenyl-α-isocyanoacetate [Eq. (1), Scheme 1; DBU = 1,8-diazabicyclo-[5.4.0]undec-7-ene]. The enantioselectivity of this reaction was, however, moderate (< 39 % ee). In contrast, a number of Lewis-acid- and small-organomolecule-catalyzed enantioselective [2+3] cycloadditions of α-isocyanoacetates with aldehydes, imines, azodicarboxylates, and polarized carbon-carbon double bonds, such as nitroalkenes, α,β-unsaturated ketones, and maleimides, have been developed to access enantioenriched five-membered heterocycles. In contrast, catalytic enantioselective Michael addition of α-isocyanoacetates was met with only limited success. Indeed, it has been established that any Lewis acid catalyzed nucleophilic addition of α-isocyanoacetates to polarized double bonds inevitably provided the [2+3] cycloadducts. The same trend holds true for organocatalytic processes. However, a recent paper from Xu, Wang, and co-workers on a tertiary amine thiourea catalyzed enantioselective Michael addition of α-phenyl-α-isocyanoacetate to N-aryl maleimides demonstrated that the aforementioned reaction can be stopped at the Michael adduct stage under appropriate reaction conditions [Eq. (2), Scheme 1].