Electricity-Controlled Divergent Synthesis of CF3-Tethered Pyrazolines and Pyrazoles via Tandem Radical Trifluoromethylation and Annulation

Abstract

Electricity-controlled, diversity-oriented selective synthesis is a powerful strategy for accessing structurally distinct potential organic molecules. However, achieving this transformation remains a significant challenge in synthetic chemistry. Herein, we report a metal- and external-oxidant-free electrochemical strategy that enables the highly selective synthesis of CF3-tethered pyrazolines and pyrazoles (>45 examples) from readily available N-allyl-N’-benzylidenesulfonohydrazides and CF3SO2Na. This protocol operates via a tandem sequence involving regioselective radical trifluoromethylation, annulation, and oxidation. Notably, precise control over product selectivity is achieved simply by modulating the applied current under constant-current electrolysis conditions. As a result, N-sulfonyl pyrazolines, N-sulfonyl pyrazoles, and N–H pyrazoles are selectively synthesized from the same starting materials. The method features broad substrate scope and functional-group tolerance, including derivatives of fragrances, pharmaceuticals, and natural products. Electricity serves as the sole reagent, with H2 as a benign byproduct, demonstrating the protocol’s high sustainability. Mechanistic investigations support a radical-mediated pathway involving a •CF3-radical. Interestingly, electron-rich heteroaryl-substituted sulfonohydrazides preferentially undergo C–H trifluoromethylation of the heteroaryl moiety rather than annulation. This observation highlights the differential reactivity of the •CF3 radical toward (hetero)aryl-substituted N-allylsulfonohydrazides.