Interrupted Houben-Hoesch Nucleophilic Cascade Strategy for the Synthesis of 6,7-Oxoannulated Indoles.

Abstract

An interrupted Houben-Hoesch cascade strategy is reported for the synthesis of 6,7-oxoannulated indoles, analogs of 6,7-carboannulated indole natural products, from pyrrolyl succinonitrile silyl ethers. The cascade proceeds through an initial nucleophilic attack by the pyrrole on a Lewis acid-activated nitrilium, followed by a second nucleophilic attack on the resulting iminium intermediate by an in situ-deprotected alcohol. The strategy enables the synthesis of a broad range of substituted dihydrofurano- and tetrahydropyranoindoles, scaffolds that are synthetically challenging by other means, in a single step.