ABSTRACT This paper reports the utility of Pd(II)‐catalyzed bidentate directing group picolinamide‐aided ( ortho ) γ ‐ or δ ‐C‐H oxygenation and trideuteromethoxylation of aromatic rings, as a route for constructing new entities of trideuteromethyl‐aryl ethers. Accordingly, the introduction of the O ‐CD 3 unit in the ortho position of aromatic rings in α ‐alkylbenzylamines, amino alcohols, and amino acids with CD 3 OD or CD 3 CD 2 OD was accomplished. Apart from the picolinamide directing group, other directing groups, such as 5‐methylisoxazole‐3‐carboxamide (MICA), quinoline‐2‐carboxamide, and benzamide directing groups, were used for conducting the trideuteromethoxylation of aromatic rings of the target compound, and the picolinamide DG was found to be efficient in all reactions. We have described the synthetic utility of the trideuteromethoxylated aryl ethers obtained in this work by synthesizing aromatic motif‐based peptides using deuteromethoxylated compounds and trideuteromethoxylated α ‐methylbenzylamine‐derived sulfamoylcarbamate motifs. Various deuterium‐containing compounds, particularly aromatic rings containing N ‐CD 3 or O ‐CD 3 units, are known as potential drug candidates in the literature. Accordingly, this work contributes to enriching the library of O ‐CD 3 or O ‐CD 2 CD 3 unit‐containing aromatic motifs and a method for their preparation through directing group‐aided trideuteromethoxylation or pentadeuteroethoxylation of ortho C(sp 2 )─H bonds of aromatic rings.
Aggarwal et al. (Sun,) studied this question.