Regioselective Synthesis of 5-Trifluoromethylpyrazoles by [3+2] Cycloaddition of Nitrile Imines and 2-Bromo-3,3,3-trifluoropropene

A general and practical method for the synthesis of 5-trifluoromethylpyrazoles is reported that occurs by the coupling of hydrazonyl chlorides with environmentally friendly and large-tonnage industrial feedstock 2-bromo-3,3,3-trifluoropropene (BTP). This exclusively regioselective [3 + 2] cycloaddition of nitrile imines and with BTP is catalyst-free and operationally simple and features mild conditions, high yields, gram-scalable, a broad substrate scope, and valuable functional group tolerance. Significantly, our method has been applied for the synthesis of the key intermediate of an active agonist of sphingosine 1-phosphate receptor.

Automated summary

A general and practical method for the synthesis of 5-trifluoromethylpyrazoles has been reported, using a coupling reaction between hydrazonyl chlorides and the industrial feedstock 2-bromo-3,3,3-trifluoropropene (BTP). This catalyst-free [3 + 2] cycloaddition shows high regioselectivity, mild conditions, high yields, scalability, broad substrate scope, and tolerance for various functional groups, with application in synthesizing key intermediates for an active agonist of sphingosine 1-phosphate receptor.