Intramolecular 2-Pyrone Diels-Alder Reactions in the studies for the total syntheses of (-)-lycoposerramine R and (-)-vindoline

Abstract

Diels–Alder reaction is a chemical reaction between a conjugated diene and alkene, termed the dienophile, to produce a substituted cyclohexene derivative in a concerted process. The Diels-Alder reaction is stereospecific in nature concerning both the diene and the dienophile. By simultaneously constructing two new carbon-carbon bonds, the Diels–Alder reaction provides a reliable way to form six-membered rings with good control of the regio- and stereo-chemical outcomes. With those, it has been widely applied for introducing chemical complexity in synthesizing natural products, pharmaceuticals, and new functional materials. In the past few years, our research group has explored the reactivity of 3,5-dibromo2-pyrone. The 3,5-dibromo 2-pyrone undergoes various coupling reactions, including Heck, Stille, and Sonogashira coupling reactions. The resultant 3- or 5-substituted 2-pyrones are also potent neutral dienes and can undergo cycloaddition reactions to furnish densely functionalized substituted cyclohexenes. The cycloadducts generated from the 3,5-dibromo-2-pyrone were elaborated successfully in the total synthesis of diverse natural products. With this strategy, it was planned to utilize 3,5-dibromo-2-pyrone in the total synthesis of (-)-lycoposerramine R and towards the total synthesis of (-)-vindoline.