Electrophilic Etherification of ɑ-Heteroaryl Carbanions with Monoper-oxyacetals as a Route to Ketene O,O- and N,O-Acetals

Timothy J. Paris, South Dakota State University


Alkyl ketene acetals are useful reactants in a variety of synthetic processes, and yet, there are limited routes to their formation as isolable products. I now report the successful synthesis, and isolation, of heteroaryl ketene acetals through intermolecular transfer of alkoxyl (δ+OR) from electrophilic peroxides to lithiated benzofurans, indoles, and pyridines. Pri-mary and secondary peroxyacetals enable selective transfer of the nonanomeric alkoxy group in moderate to high yield; sub-strates bearing an electron-donating substituent show enhanced reactivity towards electrophilic oxygen. Heteroaryl ketene acetals are remarkably stable throughout traditional purification techniques; the superior stability of ketene N,O-acetals, com-pared to ketene O,O-acetals, is presumably due to increased aromaticity of the indole and pyridine structures. The presented method overcomes typical problems associated with alkyl ketene acetal synthesis, as reported products withstood workup and flash column chromatography procedures.