16 - Synthetic Elaboration of Indole Derivatives using Cycloaddition Reactions

Abstract

Two types of cycloaddition reactions have found application for the synthetic elaboration of indoles. One is Diels–Alder reactions of 2- and 3-vinylindoles, which yield partially hydrogenated carbazoles. The second is cycloaddition reactions of 2,3-indolequinodimethane intermediates, which also construct the carbazole framework. Diels–Alder reactions reported for both 2-vinyl and 3-vinylindoles involve typical electrophilic dienophiles, such as benzoquinone, N-phenylmaleimide and dimethyl acetylenedicarboxylate. These symmetrical dienophiles raise no issues of regioselectivity. 2-Vinylindoles have been of interest in the synthesis of both aspidosperma and iboga alkaloids. The structural relationship between these two groups can be illustrated by two alternative intramolecular Diels–Alder reactions of the putative (biosynthetic) intermediate dehydrosecodine. Despite several efforts, the closest synthetic approach to dehydrosecodine that has been achieved is release of the N-benzyl derivative from a Cr(CO)3 complex. Under these conditions, the aspidosperma pathway dominates over the iboga. Addition of a 4-silyloxy substituent to the dihydropyridine ring makes the iboga pathway the preferred one. The retrosynthetic concept embodied in the disconnection of both the aspidosperma and iboga structures to dehydrosecodine has been used to develop syntheses of both types of alkaloids.