F--Free Deoxyhydrotrifluoromethylation of α-Keto Esters with Ph3P+CF2CO2-: Synthesis of α-CF3-Substituted Esters.

The Journal of Organic Chemistry
Ying ZhengZhigang Yang

Abstract

Trifluoromethylated compounds are usually obtained via trifluoromethylation reaction by the use of CF3SiMe3 and NaSO2CF3, Umemoto's and Togni's reagents. Here, an external fluorine anion-free direct deoxyhydrotrifluoromethylation of α-keto esters with a difluoromethylating reagent has been achieved, in which the employment of water can promote the dissociation of the CF2 group to form a CF3 moiety, which provides the successful transformation. The current protocol demonstrates one of the most practical approaches to generate α-trifluoromethyl esters with a broad substrate scope and high functional group compatibility, in which it is applicable to late-stage modification of biologically active compounds and can be readily scaled up. Mechanistic investigation reveals that an in situ-generated gem-difluoroalkene intermediate is decomposed by water, giving rise to acid fluoride and HF.

References

Mar 4, 2003·Nature Reviews. Drug Discovery·J Milton Harris, Robert B Chess
Apr 1, 1994·Natural Product Reports·D B Harper, D O'Hagan
Sep 30, 2005·Anesthesiology·Max T Baker, Mohamed Naguib
Jan 13, 2006·Chemistry : a European Journal·Patrick EisenbergerAntonio Togni
May 5, 2007·Journal of Medicinal Chemistry·Andrew J CarnellSacha Ferdinandusse
Sep 29, 2007·Science·Klaus MüllerFrançois Diederich
Jan 17, 2008·Chemical Society Reviews·Sophie PurserVéronique Gouverneur
Apr 30, 2008·Angewandte Chemie·Hai-Feng DuanQi-Lin Zhou
May 9, 2009·Organic Letters·Thomas HameuryJanine Cossy
Dec 22, 2009·Chemical Communications : Chem Comm·Jinbo HuFei Wang
May 27, 2011·Nature·Takeru FuruyaTobias Ritter
Apr 19, 2012·Chemical Society Reviews·Cheng-Pan ZhangYu-Cheng Gu
Jun 15, 2012·Journal of the American Chemical Society·Qing-Hai DengLutz H Gade
Aug 24, 2012·Journal of the American Chemical Society·Mingyou HuJinbo Hu
Feb 12, 2013·The Journal of Organic Chemistry·Xiao Wang, Stephen L Buchwald
Jul 19, 2013·Chemical Communications : Chem Comm·Jian ZhengJi-Chang Xiao
Oct 12, 2013·Chemistry : a European Journal·Jian ZhengJi-Chang Xiao
Dec 4, 2013·Organic Letters·Bing GaoJinbo Hu
Jul 9, 2014·The Journal of Organic Chemistry·Yupu QiaoRyan A Altman
Aug 26, 2014·Chemical Reviews·Julie CharpentierAntonio Togni
May 28, 2015·Chemistry : a European Journal·Zhichao JinYonggui Robin Chi
Feb 20, 2016·Chemical Communications : Chem Comm·D KatayevA Togni
Oct 21, 2016·Bioscience Reports·María M Adeva-AndanyCristina Pazos-García
Dec 15, 2016·Journal of the American Chemical Society·Panpan TianTeck-Peng Loh
Jun 25, 2017·Angewandte Chemie·Hai-Jun TangTeck-Peng Loh
Nov 17, 2017·Angewandte Chemie·Jiao YuJi-Chang Xiao
Feb 6, 2018·Journal of Medicinal Chemistry·Nicholas A Meanwell
Feb 16, 2018·The Journal of Organic Chemistry·Yimin JiaZhigang Yang
Apr 18, 2018·Accounts of Chemical Research·Alexander D Dilman, Vitalij V Levin
Apr 26, 2018·Organic & Biomolecular Chemistry·Xiang-Zheng TangAlbert S C Chan
Sep 27, 2018·Chemical Communications : Chem Comm·Sanjib BanerjeeBruno Ameduri
Jan 30, 2019·Angewandte Chemie·Haidong LiuChao Feng
May 18, 2019·Chemistry : a European Journal·Haibo MeiVadim A Soloshonok
Aug 23, 2019·Chemical Reviews·Johann MoschnerBeate Koksch

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Citations

Mar 5, 2021·Organic Letters·Jinfeng HuangZhigang Yang

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