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Updated: Aug 10, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
ortho-C(sp3)-H arylation of aromatic aldehydes using 2-amino-N-methyl-acetamide as a L,L-type transient directing
Jinyuan Wang1, Yunzhi Liu1, Nan Han1
1School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China. yuan.gao@njust.edu.cn.
Abstract:
Pd-catalyzed ortho-C(sp3)-H arylation of aromatic aldehydes using 2-amino-N-methyl-acetamide as a simple, efficient and commercially available L,L-type transient directing group (TDG) is reported. The reaction exhibited excellent substrate compatibility and generated the desired products in moderate-to-high yields up to 78%. Further acid-catalyzed cyclization and dehydrative aromatization were also tested, and furnished some polycyclic aromatic hydrocarbons with excellent yields up to 96%. The X-ray crystal structure of a 2-methylbenzaldehyde ortho-C(sp3)-H palladation intermediate was obtained. Then, a plausible reaction mechanism involving the formation of a [5,6]-fused palladacycle was proposed. This approach offers valuable insights for exploiting novel L,L-type TDGs.
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