Bronsted or Lewis Acid Initiated Multicomponent Cascade Reaction: Diastereoselective Synthesis of Imidazolidinyl Spirooxindole Derivatives

One peculiar type of aza-hetero-imidazolidinyl spirooxindole derivatives was efficiently constructed by the three-component [2+2+1] cascade reaction of 1,4-oxazepines with diazo-oxindoles. Iron(II) trifluoromethanesulfonate [Fe(OTf)(2)] or p-toluenesulfonic acid monohydrate (p-TsOH center dot H2O) proved to be optimal catalysts for this transformation, providing the desired products in high yields (up to 94%) with excellent diastereoselectivity (up to 99:1 dr). Experimental studies showed that the reaction rate of Bronsted acid catalysis was faster than that of Lewis acids. Furthermore, the mechanism was theoretically investigated for Bronsted acid as the catalyst and a reaction pathway was proposed. DFT calculations suggested that the diazo-oxindole can act as a 1,3-dipole to add to a C=N double bond of 1,4-oxazepine, which forms a 4,5-dihydro-1H-1,2,3-triazole intermediate. Subsequently, the releasing of N-2 is the rate-limiting step of the whole catalytic cycle.