Diastereo-and enantioselective oxa-hetero-Diels-Alder reactions of enones with aryl trifluoromethyl ketones that afford tetrahydropyranone derivatives catalyzed by an amine-based catalyst system are reported.The major diastereomers of the tetrahydropyranone products obtained in these reactions had the relative stereochemistry different from that of the previously synthesized tetrahydropyranone derivatives.Tetrahydropyran derivatives are found in bioactive natural products and pharmaceutical leads. 1 Concise access to enantiomerically enriched tetrahydropyran derivatives is of interest in the development of bioactive molecules. 1-3 A trifluoromethyl group is often used to improve the bioactivities. [3][4][5] Accordingly, methods for the concise synthesis of tetrahydropyran derivatives bearing a trifluoromethyl group are of interest. 3 We previously reported enantioselective oxa-hetero-Diels-Alder reactions of enones with aryl trifluoromethyl ketones that directly afford tetrahydropyranone derivatives using amine-based catalyst systems. 3 In these reactions, the enamines generated from the enones act as dienes and the ketone carbonyl groups of aryl trifluoromethyl ketones act as dienophiles in the [4+2] cycloaddition leading to the tetrahydropyranone derivatives. 3 In these reactions, two diastereomers can be formed. The use of a catalyst system composed of a proline-derivative and DABCO for the reactions led the formation of one type of the diastereomers as the major diastereomers with high enantioselectivities (Scheme 1a). 3Here we report enantioselective oxa-hetero-Diels-Alder reactions of enones with aryl trifluoromethyl ketones that afford the other type of the diastereomers as the main products (Scheme 1b).