H-Bonding Mediated Asymmetric Intramolecular Diels-Alder Reaction in the Formal Synthesis of (+)-Aplykurodinone-1

Abstract

An asymmetric formal total synthesis of (+)-aplykurodinone-1 was achieved using a route, in which hydrogen bonding serves as a stereochemical control element governing the pi-facial selectivity of intramolecular Diels-Alder (IMDA) reaction of an enone tethered 2-pyrone. In the IMDA process, the configuration at a stereogenic, hydroxyl bearing an alpha-carbon in the enone dienophile is conveyed in a highly effective manner through intramolecular hydrogen bonding with the enone carbonyl oxygen. The tricyclic lactone, generated in this process, was successfully converted to a late stage intermediate in Danishefsky's synthesis of aplykurodinone-1.