Catalytic, Asymmetric Synthesis of 1,4-Benzoxazinones: A Remarkably Enantioselective Route to [alpha]-Amino Acid Derivatives from o-Benzoquinone ImidesT.L. thanks the NIH (GM064559); the Sloan, Guggenheim, and Dreyfus Foundations; and Merck & Co. for support

Molecules that serve as versatile branch points for the synthesis of pharmaceutically or biologically active products, besides being of interest in their own right, are especially valuable targets for asymmetric catalysis. The 1,4-benzoxazinone and 1,4-benzoxazine systems are intriguing because they are present in clinically significant pharmaceuticals and other biologically active molecules. On the basis of previous success in the preparation of a-oxygenated carboxylic acid derivatives from benzodioxinones, we speculated that chiral 1,4-benzoxazinone intermediates could also serve as flexible precursors for the efficient synthesis of highly enantiomerically enriched a-amino acids and related derivatives. Herein, we present the first catalytic, asymmetric synthesis of 1,4-benzoxazinones that relies on the highly enantioselective [4+2] cycloaddition of o-benzoquinone imides with chiral ketene enolates (derived from acid chlorides and cinchona alkaloid catalysts; Scheme 1). These cycloadducts can be