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Updated: Aug 22, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Pd-Catalyzed C-O Bond Formation Enabling the Synthesis of Congested N,N,O-Trisubstituted Hydroxylamines
Jiaxing Chen1, Yongzhuo Xu1, Wen Shao1
1Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, Hunan 411105, P. R. China.
Abstract:
A Pd-catalyzed C-O cross-coupling of O-acyl hydroxylamines and tertiary or secondary alkyl electrophiles was reported without the cleavage of the rather fragile N-O bond. The described strategy provides direct access to congested N,N,O-trisubstituted hydroxylamines bearing an α-quaternary carbon center under mild conditions in high yields and features exclusively chemoselective C-O bond formation, a broad substrate scope, and excellent functional group tolerance. The synthetic potential of the cross-coupling was established via pharmaceuticals derivatizations and a series of postcatalytic modifications.
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