A Pd(II)-catalyzed highly regiospecific ortho-amidation of benzyl thiocyanates with N,N-disubstituted oxamic acids has been developed using AgOAc as an oxidant. Thiocyanate (-SCN) has been introduced as a multicoordinating weak-directing group in C-H activation. The decarboxylative coupling proceeds under operationally simple conditions with a broad substrate scope and excellent functional group tolerance. A variety of substituted, secondary, and heterocyclic benzyl thiocyanates efficiently undergo ortho-amidation with diverse oxamic acids to afford a series of ortho-amidation products in moderate to excellent yields. Density functional theory (DFT) calculations established that the thiocyanate (-SCN) moiety acts as a bidentate directing group, coordinating to palladium through both nitrogen and sulfur atoms sequentially, thereby leading to the formation of an unusual monomeric Pd(III)-intermediate. This Pd(III)-intermediate preferentially undergoes reductive elimination to generate a Pd(I)-species rather than participating in single-electron oxidation or disproportionation pathways. The Pd(II)-catalyst is regenerated from Pd(I) using silver(I) as an oxidant. The established protocol offers an efficient and atom-economical route for C-H amidation, expanding the versatility of Pd-catalyzed C-H functionalization strategies.
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Singh et al. (2026) studied this question.
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