Copper(I)-catalyzed asymmetric alkylation of α-imino-esters.

Abstract

Asymmetric alkylation of enolates is one of the most direct and important reactions to prepare α-chiral carbonyl compounds. Except for the classical methods that rely on the use of chiral auxiliaries, asymmetric catalysis emerged as a powerful tool, especially asymmetric phase-transfer catalysis. However, in the field of transition metal catalysis, only limited success with asymmetric alkylation of enolates was achieved. Hereby, we disclose a copper(I)-catalyzed asymmetric alkylation of α-imino-esters with various alkyl halides, including allyl bromides, propargyl bromide, benzyl bromides, α-bromo carbonyl compounds, and alkyl iodides. Both linear and cyclic α-imino-esters serve as competent pronucleophiles in the alkylation, which affords α-amino acid derivatives bearing either a trisubstituted or a tetrasubstituted stereogenic carbon center in high to excellent enantioselectivity. Control experiments indicate that the α-imino-ester is activated by a chiral copper(I)-phosphine complex through coordination, thus enabling facile deprotonation to provide a stabilized copper(I)-enolate in the presence of a mild base. Finally, the mildly basic nature allows the asymmetric alkylation of chiral dipeptides with excellent both chemo- and enantioselectivities.