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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
MgO-Promoted [4 + 2] Cyclization Using HFA·3H2O/SOCl2/PPh3: Modular Synthesis of
Zhengwu Zeng1,2, Junyi Rao2, Meng Pei2
1School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan430070, China.
Abstract:
The present study reports an unprecedented [4 + 2] annulation for the modular synthesis of gem-bis(trifluoromethyl)-3,6-dihydro-2H-thiopyrans. The transformation employs readily available HFA·3H2O and SOCl2 as a convenient (CF3)2C═S surrogate in the presence of PPh3, with MgO promoting the subsequent thia-Diels-Alder reaction of 1,3-dienes. The method features a broad substrate scope, excellent practicality for gram-scale synthesis and late-stage functionalization of biologically active molecules, as well as versatile product derivatization. Mechanistic studies identify hexafluoroisopropyl polysulfide species as key intermediates in this process.
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