Pyrone Diels-Alder Routes to Indolines and Hydroindolines: Syntheses of Gracilamine, Mesembrine, and Δ(7) -Mesembrenone

Although the Diels-Alder reaction has long been utilized for the preparation of numerous heterocycles, opportunities to extend its power remain. Herein, we detail a simple, modular, and robust approach that combines various amines regioselectively with 4,6-dichloropyrone to create substrates which, under appropriate conditions, can directly deliver varied indolines and hydroindolines through [4+2] cycloadditions with substitution patterns difficult to access otherwise. As an initial demonstration of the power of the strategy, several different natural products have been obtained either formally or by direct total synthesis, with efforts toward one of these-the complex amaryllidaceae alkaloid gracilamine-affording the shortest route to date in terms of linear step count.