Two-step conversion of carboxylic esters into distally fluorinated ketones via ring cleavage of cyclopropanol intermediates: application of sulfinate salts as fluoroalkylating reagents?

Organic & Biomolecular Chemistry Pub Date: 2017-05-08 DOI: 10.1039/C7OB00680B

Abstract

Tertiary cyclopropanols easily available from carboxylic esters have been used in the synthesis of distally fluorinated ketones. Cyclopropane ring cleavage reactions in methanol with aqueous tert-butyl hydroperoxide in the presence of a copper(II) acetate catalyst and sodium triflinate (Langlois reagent) afford β-trifluoromethyl ketones in 16–74% isolated yields. Sodium triflinate serves as a precursor of reactive trifluoromethyl copper species, enabling ring-opening trifluoromethylation, as evidenced by mechanistic studies. We also demonstrate here that other sulfinate salts, such as sodium 1,1-difluoroethanesulfinate, sodium 2-(4-bromophenyl)-1,1-difluoroethanesulfinate and sodium 1-(trifluoromethyl)cyclopropanesulfinate, can be used as fluoroalkylation reagents, resulting in the corresponding fluorinated ketones.

Graphical abstract: Two-step conversion of carboxylic esters into distally fluorinated ketones via ring cleavage of cyclopropanol intermediates: application of sulfinate salts as fluoroalkylating reagents
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