Chiral Hetero Diels−Alder Products by Enantioselective and Diastereoselective Zirconium Catalysis. Scope, Limitation, Mechanism, and Application to the Concise Synthesis of (+)-Prelactone C and (+)-9-Deoxygoniopypyrone

Abstract

Catalytic asymmetric hetero Diels−Alder (HDA) reactions using a chiral zirconium complex have been developed. The reactions of aldehydes with Danishefsky's dienes proceeded smoothly to afford the corresponding pyranone derivatives in high yields with high diastereo- and enantioselectivities in the presence of a chiral zirconium complex, which was prepared from zirconium tert-butoxide, (R)-3,3‘-diiodobinaphthol or its derivative, a primary alcohol, and a small amount of water. It is noted that 2,3-trans-pyranone derivatives were obtained with remarkably high diastereo- and enantioselectivities in the reaction with 4-methyl Danishefsky's diene. This is the first example of catalytic asymmetric trans-selective hetero Diels−Alder reactions of aldehydes. Furthermore, asymmetric HDA reactions with 4-benzyloxy Danishefsky's dienes were conducted to afford 2,3-cis-pyranone derivatives in high selectivities. Isolation of an intermediate of this asymmetric hetero Diels−Alder reaction indicated that the reaction proceeded in a stepwise cycloaddition pathway. Finally, these catalytic, asymmetric hetero Diels−Alder reactions were successfully applied to concise syntheses of biologically important natural pyranone derivatives, (+)-Prelactone C and (+)-9-deoxygoniopypyrone.