Organocatalyzed diastereoselective cyclization of β-alkyl nitroolefins with alkylidene malononitriles: new approach to azetidine nitrones and isoxazoles

Abstract

An efficient, organocatalytic, diastereoselective, atom-economic domino method has been established for rapid access to a wide range of highly strained azetidine nitrones with a tetra-substituted chiral carbon center in promising yields and good diastereomeric ratios (up to ≤93 : 7). This C–C/C–N/CO bond-creation process proceeded selectively between β-alkyl nitroolefins and β-aryl/heteroaryl/alky-substituted alkylidene malononitriles, when catalyzed by an organobase, via a sequence of Michael/cyclization/1,3-sigmatropic shift reactions at room temperature. Interestingly, further addition of an inexpensive Brønsted acid catalyst into this reaction facilitated a ring expansion of in situ-generated azetidines, with the expansion occurring via a C–N bond cleavage and C–O bond formation successively, leading to a novel class of fully substituted isoxazoles.