Nickel-Catalyzed Diastereoselective Synthesis of Oxazolidines

Significance

Reported is the nickel(II)-catalyzed synthesis of oxazolidines 3 from aziridines 1 and aldehydes 2. The reaction proceeds via the Lewis acid mediated ring opening of aziridine 1 (by C-C bond heterolysis) to give an intermediate azo­methine ylide, followed by [3+2] cycloaddition. In general, electron-rich aromatic aldehydes give better yields than electron-deficient ones. ortho-Substituted benzaldehydes also afford lower product yields (cf. R^² = 4-MeOC₆H₄, 92% yield and R^² = 2-MeOC₆H₄, 55% yield). Both EDGs and EWGs are equally well tolerated on the aromatic ring in the aziridine. All reactions delivered exclusively the cis isomers. A brief attempt to perform an asymmetric variant of this reaction using a ­pybox ligand gave the product in a modest 60% ee, demonstrating the future potential of accessing chiral oxazolidines via this method.