A Diels-Alder (DA) reaction of 3-hydroxy-2-pyrone (1) with electron-deficient dienophile (2) was catalyzed by base and gave adducts (3 and 4) under very mild conditions. The reaction with the reactive dienophiles (2a-d) afforded corresponding bicycloadducts in nearly quantitative yield with complete stereospecificity and regioselectivity. But with the less reactive dienophiles (2e and f), the reaction only afforded the adducts in 30-0 % yields. Enantioselective DA reaction of 1 and 2a was achieved by using chiral base. By a screening of several optically pure bases it was found that application of cinchonidine as the catalyst in PhCl afforded (-)-3a in 87 % ee. The reaction of 1 with an acrylate derivatives having a chiral auxiliaries (2g and h) afforded endo-adducts (3g and h) in high diastereoselectivity (>95 %de). The resulting adducts 3g and h are practical chiral building blocks for natural product synthesis since this reaction can be applied to large scale preparation. Actually, over 10 g of 3g has been prepared with >95 %de. By using these enantioselective and diastereoselective base catalyzed DA reaction, biologically active compounds, pseudo-sugar (5b), pericosine B (10b), and a key intermediate of substance P antagonist (18) are being synthesized as shown in scheme 2, 3, and 5, respectively.
