Trifluoromethyl ketones from enolizable carboxylic acids via enediolate trifluoroacetylation/decarboxylation.
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.
Reeves
Jonathan T
JT
Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Old Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, USA. jonathan.reeves@boehringer-ingelheim.com
Song
Jinhua J
JJ
Tan
Zhulin
Z
Lee
Heewon
H
Yee
Nathan K
NK
Senanayake
Chris H
CH
D000107:Acetylation; D000447:Aldehydes / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D002625:Chemistry, Organic / Q000379:methods*; D002845:Chromatography / Q000379:methods; D003653:Decarboxylation; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical
D000447:Aldehydes; D002264:Carboxylic Acids; D007659:Ketones; D002244:Carbon