American Chemical Society
jo0c02506_si_001.pdf (6.78 MB)

Electrophilic Etherification of α‑Heteroaryl Carbanions with Monoperoxyacetals as a Route to Ketene O,O- and N,O‑Acetals

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journal contribution
posted on 2021-01-19, 21:14 authored by Timothy J. Paris, Chris Schwartz, Rachel Willand-Charnley
Alkyl ketene acetals are useful reactants in a variety of synthetic processes, and yet, there are limited routes to their formation as isolable products. We 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. Primary and secondary peroxyacetals enable selective transfer of the nonanomeric alkoxy group in moderate to high yield; substrates bearing an electron-donating substituent show enhanced reactivity toward electrophilic oxygen. Heteroaryl ketene acetals are remarkably stable throughout traditional purification techniques; the superior stability of ketene N,O-acetals compared 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.