Nitrone cycloaddition reactions to α,β-unsaturated carbonyl acceptors catalyzed by a pinhole Lewis acid catalyst. Dramatic rate acceleration and improvement of regioselectivity and diastereoselectivity

A catalytic amount of aluminum tris(2,6-diphenylphenoxide), designated as ATPH, catalyzes nitrone cycloaddition reactions between N-benzylideneaniline N-oxide and α,β-unsaturated carbonyl acceptors and induces a dramatic rate enhancement showing high to exclusive control of regioselectivity in favor of the formation of isoxazolidine-4-carboxaldehydes. Such high regioselectivities leading to electronically controlled cycloadducts provides a striking contrast to the selectivities generally observed for the uncatalyzed reactions in which regioselectivities result from a competition between steric and electronic factors. Thus, the use of a pinhole catalyst is effective for a selective activation of electrophiles in the catalyzed reactions using strongly coordinating bulky nucleophiles.