Department of Chemistry & Biochemistry, South Dakota State University, Brookings, South Dakota 57007, United States.
J Org Chem. 2021 Feb 5;86(3):2369-2384. doi: 10.1021/acs.joc.0c02506. Epub 2021 Jan 19.
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 (δOR) 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 ,-acetals compared to ketene ,-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.
烷基烯酮缩醛是各种合成过程中有用的反应物，但作为可分离的产物，其合成途径有限。我们现在报告了通过亲电过氧化物向锂化苯并呋喃、吲哚和吡啶中的烷氧基（δOR）的分子间转移，成功合成和分离了杂芳基烯酮缩醛。一级和二级过氧缩醛能够以中等至高产率选择性转移非端基烷氧基；具有给电子取代基的底物对亲电氧表现出增强的反应性。杂芳基烯酮缩醛在传统的纯化技术中表现出非常稳定；与烯酮缩醛相比，烯酮，-缩醛的稳定性更高，这可能是由于吲哚和吡啶结构的芳香性增加。所提出的方法克服了与烷基烯酮缩醛合成相关的典型问题，因为报道的产物经受住了后处理和闪蒸柱色谱程序。
