Theoretical investigation of direct amination of beta-ketoesters catalyzed by copper(II)-bisoxazoline(BOX).

The mechanism of the direct amination of beta-keto esters catalyzed by copper(II)-bisoxazoline has been studied by means of density functional theory of B3LYP method. The computational results support the present mechanism, which involves (i) the generation of the enol from beta-keto esters, which coordinates to copper(II)-bisoxazoline. The coordination step appears to be fast, exothermic, and irreversible. (ii) The formation of the sigma(N-C) bond via a six-membered ring transition state after azo dicarboxylate coordination with the chiral catalyst. This step is chirality-control step. (iii) Intramolecular hydrogen migration generates a catalyst-product complex, which can finally yield product. The hydrogen shift is the rate-determining step, which affords the experimentally observed (R)-product. The stereochemical predictions have been rationalized in terms of steric repulsions, showing good agreement with experimental data.