Efficient asymmetric synthesis of aryl difluoromethyl sulfoxides and their use to access enantiopure α-difluoromethyl alcohols

TETRAHEDRON

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Article

Batisse, Chloe¹  Davila, Maria F. Cespedes^1,3  Castello, Marco²  Messara, Amelia¹  Vivet, Bertrand³  Marciniak, Gilbert³  Panossian, Armen¹  Hanquet, Gilles¹  Leroux, Frederic R.¹ 

[1] Univ Strasbourg, Univ Haute Alsace, CNRS, ECPM,UMR LIMA 7042, 25 Rue Becquerel, F-67087 Strasbourg, France

[2] Univ Basilicata, Dipartimento Sci, Via Nazario Sauro 85, I-85100 Potenza, Italy

[3] Sanofi Aventis R&D, 16 Rue Ankara, F-67080 Strasbourg, France

关键词: Fluorine chemistry;    Chiral sulfoxides;    Enantioselective difluoromethylation;    Diastereoselective reduction of alpha, alpha-difluoro-beta-ketosulfoxides;    Desulfinylation;    Desulfonylation;   

DOI  :  10.1016/j.tet.2019.04.037

来源: Elsevier

【 摘 要 】

The -CHF2 moiety has shown a growing interest in pharmaceutical and agrochemical applications over the last few years. Its introduction is therefore a current research topic for organic chemists. Several groups have reported the synthesis of difluoromethylated compounds. However, the more challenging enantioselective introduction of the difluoromethyl group has been scarcely described yet. We recently developed a new strategy, based on the use of an enantiopure difluoromethyl sulfoxide used as chiral and traceless auxiliary, for the synthesis of highly enantioenriched alpha-difluoromethyl alcohols. The first method developed in our laboratory aims to access highly stereoenriched alpha,alpha-difluoro-beta-hydroxysulfoxides through the condensation of the enantiopure difluoromethyl sulfoxide on carbonyl derivatives. It is noteworthy that highly diastereo- and enantioenriched alpha,alpha-difluoro-beta-hydroxysulfoxides can also be accessed after the diastereoselective reduction of highly enantioenriched alpha,alpha-difluoro-beta-ketosulfoxides. Finally, the expected difluoromethyl-substituted alcohols can be obtained after removal of the chiral auxiliary with complete retention of stereoenrichment at carbon. (C) 2019 Elsevier Ltd. All rights reserved.

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