Enantioselective synthesis of 3,4-dihydropyran-2-ones by domino Michael addition and lactonization with new asymmetric organocatalysts: cinchona-alkaloid-derived chiral quaternary ammonium phenoxides.

Chiral quaternary ammonium phenoxides were readily prepared from commercially available cinchona alkaloids and proved to be useful new asymmetric organocatalysts. Among various chiral quaternary ammonium phenoxides, a cinchonidine-derived catalyst that bears both a sterically hindered N1-9-anthracenylmethyl group and a strongly electron withdrawing 9-O-3,5-bis(trifluoromethyl)benzyl group were found to be highly effective for the Michael addition of ketene silyl acetals (derived from phenyl carboxylates) and alpha,beta-unsaturated ketones followed by lactonization. Optically active 3,4-dihydropyran-2-one derivatives were obtained in high yields with excellent control of enantio- and diastereoselectivity. This catalyst can be handled in air and stored at room temperature in a sealed bottle without decomposition for at least one month.