New Strategies for Organic Catalysis:  The First Enantioselective Organocatalytic 1,3-Dipolar Cycloaddition

Our laboratory has been engaged in the design of broadly useful new strategies for enantioselective catalysis that utilize organic chemicals as reaction catalysts. In our recent study, we reported that the LUMO-lowering activation of α,β-unsaturated aldehydes using the reversible formation of iminium ions with chiral imidazolidinones 1 (eq 1) is a valuable platform for the development of enantioselective organocatalytic Diels−Alder reactions (eq 2). In this work, we reveal that this catalytic strategy is also amenable to 3 + 2 cycloadditions between nitrones and α,β-unsaturated aldehydes to provide isoxazolidines (eq 3), useful synthons for the construction of biologically important amino acids, β-lactams, amino carbohydrates, and alkaloids. To our knowledge, this is the first example of an organocatalytic 1,3-dipolar cycloaddition. Moreover, this study further documents that chiral amines can be employed as asymmetric catalysts for a range of transformations that traditionally utilize metal salts.