通过烯醇羧酸的烯二酸盐三氟乙酰化/脱羧反应合成三氟甲基酮。

Trifluoromethyl ketones from enolizable carboxylic acids via enediolate trifluoroacetylation/decarboxylation.

机构信息

Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Old Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, USA.

出版信息

J Org Chem. 2008 Dec 5;73(23):9476-8. doi: 10.1021/jo801737c.

DOI:10.1021/jo801737c

PMID:18973383

Abstract

Primary and secondary (enolizable) carboxylic acids were converted in a single step to trifluoromethyl ketones. Treatment of the acid with 2.2 equiv of LDA generated an enediolate that was trifluoroacetylated with EtO(2)CCF(3). Quenching the reaction mixture with aqueous HCl resulted in rapid decarboxylation and provided the trifluoromethyl ketone product in good yield. The process may be performed at -20 degrees C with a slight reduction in yield. The reaction was extended to the preparation of pentafluoroethyl and chlorodifluoromethyl ketones.

摘要

一级和二级（烯醇化）羧酸可在一步转化为三氟甲基酮。用 2.2 当量的 LDA 处理酸，生成烯醇化物，然后用 EtO(2)CCF(3)三氟乙酰化。用盐酸水溶液淬灭反应混合物，可迅速脱羧，得到三氟甲基酮产物，产率良好。该过程可在-20°C下进行，产率略有降低。该反应还扩展到制备五氟乙基和氯二氟甲基酮。