a-Isocyanoacetates are well-known glycine templates for the synthesis of racemic a,a-disubstituted a-amino acids. [1] However, catalytic enantioselective alkylation of a-isocyanoacetates remains underexploited. Ito, Hayashi, and co-workers pioneered the field by discovering the first palladiumcatalyzed enantioselective allylation of methyl a-phenyl-aisocyanoacetate [Eq. (1), Scheme 1; DBU = 1,8-diazabicyclo-[5.4.0]undec-7-ene]. [2] 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 a-isocyanoacetates with aldehydes, [3] imines, [4] azodicarboxylates, [5] and polarized carboncarbon double bonds, such as nitroalkenes, [6] a,b-unsaturated ketones, [7] and maleimides, [8] have been developed to access enantioenriched five-membered heterocycles. In contrast, catalytic enantioselective Michael addition of a-isocyanoacetates was met with only limited success. Indeed, it has been established that any Lewis acid catalyzed nucleophilic addition of a-isocyanoacetates to polarized double bonds inevitably provided the [2+3] cycloadducts. The same trend holds true for organocatalytic processes. [8] However, a recent paper from Xu, Wang, and co-workers [9] on a tertiary amine thiourea catalyzed enantioselective Michael addition of aphenyl-a-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].In connection with our ongoing total synthesis project, we needed rapid access to enantiomerically enriched a-aryl-a-(2'-FG-alkyl)-a-amino acids (FG = functional group). [10] We were aware of the seminal contributions of Deng and coworkers on the enantioselective Michael addition of aphenyl-a-cyanoacetate to vinyl phenylsulfone and the subsequent conversion of the enantiomerically enriched adduct into a,a-disubstituted amino acids [Eq. (3), Scheme 1]. [11] However, six steps were needed to convert both the cyano and sulfone groups into other organic residues. Stimulated by this observation, we became interested in examining the chiral Brønsted base catalyzed nucleophilic addition of aaryl-a-isocyanoacetates (1) to vinyl phenyl selenone (2) [12][13][14] for the synthesis of the enantiomerically enriched a-aryl-a-(2'-FG-alkyl)-a-amino acids 3 [Eq. (4), Scheme 1]. [15] The advantage of this approach is that the resulting adduct can be readily converted into an array of functionalized amino acids. Indeed, phenylselenonyl is an excellent leaving group, [16] while the isocyano group is easily hydrolyzed under mild acidic conditions into the free amino function. We report herein the successful development of an organocatalytic enantioselective Michael addition of 1 to 2 for the synthesis of the enantiomerically enriched a,a-disubstituted a-isocyanoacetates 3 and their subsequent transformations into the linear and the cyclic quaternary a-amino acids. Enantioselective total synthe...