Regioselective Synthesis of 3-Trifluoromethylpyrazole by Coupling of Aldehydes, Sulfonyl Hydrazides, and 2-Bromo-3,3,3-trifluoropropene

Article abstract of DOI:10.1021/acs.orglett.9b04228

A general and practical strategy for 3-trifluoromethylpyrazole synthesis is reported that occurs by the three-component coupling of environmentally friendly and large-tonnage industrial feedstock 2-bromo-3,3,3-trifluoropropene (BTP), aldehydes, and sulfonyl hydrazides. This highly regioselective three-component reaction is metal-free, catalyst-free, and operationally simple and features mild conditions, a broad substrate scope, high yields, and valuable functional group tolerance. Remarkably, the reactions could be performed on a 100 mmol scale and smoothly afforded the key intermediates for the synthesis of celecoxib, mavacoxib, SC-560, and AS-136A. Preliminary mechanism studies indicated that a 1,3-hydrogen atom transfer process was involved in this transformation.