Application of fluoroform in trifluoromethylation and difluoromethylation reactions

Abstract

Recent development in the trifluoromethylation and difluoromethylation of organic compounds employing fluoroform is reviewed. Eight approaches to trifluoromethylation and difluoromethylation are summarized: (i) trifluoromethylation or difluoromethylation of carbonyl compounds, (ii) trifluoromethylation of sulfonyl fluorides, (iii) trifluoromethylation of epoxides, (iv) nucleophilic trifluoromethylation of silicon, boron, and sulfur-based compounds, (v) CuCF3 derived from fluoroform for the trifluoromethylation of aryl or heteroaryl halides, aryl boronic acids, arenediazonium salts and alkynes, (vi) difluoromethylation of alkynes, (vii) difluoromethylation of phenols, thiophenols and heterocyclic compounds, and (viii) difluoromethylation of nitriles.

Scalable Continuous Flow Process for the Synthesis of Eflornithine Using Fluoroform as Difluoromethyl Source

“…Nevertheless, this has been an unyielding endeavor for a long time, partially caused by the very low reactivity of the gas (p K a = 25–28 in water) . Recently the first synthetically valuable transformations using fluoroform as CF 3 -source − and CHF 2 -source , have been reported . Trifluoromethylation reactions were conducted by deprotonating fluoroform with either an electrogenerated or a strong base and trapping of CF 3 – (trifluoromethyl anion) with a suitable acceptor (TMSCl, DMF, , or Cu­(I)).…”