Intramolecular Dearomative Inverse-Electron-Demand Diels Alder Strategy for the Total Synthesis of (+)-Alstonlarsine A

Abstract

An evolution of a synthetic route leading to a successful enantioselective total synthesis of monoterpenoid indole alkaloid (+)-alstonlarsine A is represented. The unique 9-azatricyclo­[4.3.1.03,8]­decane core was assembled through an efficient domino sequence comprising enamine formation in situ, followed by intramolecular dearomative inverse-electron-demand Diels Alder reaction. The preparation of the tricyclic dihydrocyclohepta­[b]­indole key intermediate via the intramolecular Horner–Wadsworth–Emmons reaction required a development of a new general method for the introduction of the phosphonoacetate moiety into the indole C-2 position, through copper-carbenoid insertion. The modular nature of the represented synthetic approach makes it suitable for the synthesis of analogues with different substituents’ patterns.