Copper-Catalyzed O-Difluoromethylation of Functionalized Aliphatic Alcohols: Access to Complex Organic Molecules with an OCF2H Group

Kostiantyn Levchenko; Olexandr P Datsenko; Oleh Serhiichuk; Andrei Tolmachev; Viktor O Iaroshenko; Pavel K Mykhailiuk

doi:10.1021/acs.joc.6b00628

Copper-Catalyzed O-Difluoromethylation of Functionalized Aliphatic Alcohols: Access to Complex Organic Molecules with an OCF2H Group

J Org Chem. 2016 Jul 15;81(14):5803-13. doi: 10.1021/acs.joc.6b00628. Epub 2016 May 11.

Authors

Kostiantyn Levchenko¹, Olexandr P Datsenko¹, Oleh Serhiichuk², Andrei Tolmachev¹, Viktor O Iaroshenko³, Pavel K Mykhailiuk^{1

4}

Affiliations

¹ Enamine, Ltd., 78 Chervonotkatska str., 02094 Kyiv, Ukraine.
² Department of Organic Chemistry, Kiev Polytechnic Institute , Pr. Pobedy 37, 03056 Kiev, Ukraine.
³ Homogeneous Catalysis and Molecular Design Research Group at Center of Molecular and Macromolecular Studies, Polish Academy of Sciences , Sienkiewicza 112, PL-90-363 Łódź, Poland.
⁴ Department of Chemistry, Taras Shevchenko National University of Kyiv , Volodymyrska Street, 64, Kyiv 01601, Ukraine.

PMID: 27150198
DOI: 10.1021/acs.joc.6b00628

Abstract

A two-step synthetic strategy toward difluoromethyl ethers via a CuI-catalyzed reaction of the alcohols, bearing additional protected functionalities, with FSO2CF2CO2H has been developed. The high potential of the developed protocol has been shown by preparing novel OCF2H-analogues of GABA and l-proline. The described transformation has good functional group compatibility and can serve as a powerful synthetic tool for late-stage preparation of complex OCF2H-containing organic compounds as well as building blocks for drug discovery.