Synthesis of 5-Trifluoromethyl-Substituted (Z)-N,N-Dimethyl-N′-(pyrazin-2-yl)formimidamides from 2-Aminopyrazines, LiI/Selectfluor, FSO₂CF₂CO₂Me and DMF under Cu Catalysis

Abstract

The synthesis of 5-trifluoromethyl-substituted (Z)-N,N-dimethyl-N′-(pyrazin-2-yl)formimidamides via the iodination of 2-aminopyrazines with Selectfluor/LiI followed by a domino trifluoromethylation with FSO₂CF₂CO₂Me and a condensation with DMF in the presence of CuI is realized under mild conditions. This three-step method offers CF₃-substituted (Z)-N,N-dimethyl-N′-(pyrazin-2-yl)formimidamides in yields of 55–70% and with high regioselectivities. LiI serves as an iodine source, whilst DMF functions as both a solvent and a condensation reagent. The regioselectivity of these trifluoromethylation reactions is strongly dependent upon the substituent pattern on the 2-aminopyrazines. A possible mechanism for this method is also discussed.

Key words

trifluoromethylation - pyrazines - lithium iodide - Selectfluor - regioselectivity

Publication History

Received: 17 September 2021

Accepted after revision: 15 December 2021

Article published online:
09 February 2022

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