Synthesis of trifluoromethylpyrrolopyrazole derivatives via [3+2] cycloaddition of trifluoromethyl N-acylhydrazones or trifluoroacetohydrazonoyl bromides with maleimides

An efflcient and practical protocol for the preparation of trifluoromethylpyrrolopyrazole derivatives were developed from the [3 + 2] cycloaddition reaction of readily available trifluoromethyl building blocks such as trifluoromethyl N-acylhydrazones or trifluoroacetohydrazonoyl bromides with maleimides. The methods give 3-trifluoromethylated pyrrolidino [3,4-c]pyrazolidin-4,6-dione and 3-trifluoromethylated dihydropyrrolo [3,4-c]pyrazole-4,6(1H,5H)-diones in good to excellent yields under mild reaction con-ditions. The 3-trifluoromethylated dihydropyrrolo [3,4-c]pyrazole-4,6(1H,5H)-diones can be smoothly oxidized to 3-trifluoromethylated pyrrolo [3,4-c]pyrazole-4,6(1H,5H)-diones by TCCA under mild reac-tion conditions.(c) 2023 Elsevier Ltd. All rights reserved.