Tungsten-Catalyzed Transamidation of Tertiary Alkyl Amides

Transamidation has recently emerged as a straightforward and convenient means to diversify amides. However, the kinetically and thermodynamically demanding transamidation of notoriously robust, fully alkyl-substituted tertiary amides still remains a longstanding challenge. Here, we describe a method for the activation of tertiary alkyl amides to streamline transamidation using simple tungsten(VI) chloride as a catalyst and chlorotrimethylsilane as an additive. The highly electrophilic and oxophilic tungsten catalyst enables the selective scission of a C-N bond of tertiary alkyl amides to effect transamidation of a myriad of structurally and electronically diverse tertiary alkyl amides and amines. Mechanistic study implies that the synergistic effect of the catalyst and the additive could pronouncedly induce the nucleophilic acyl substitution of tertiary alkyl amide with amine to realize transamidation.

Automated summary

Transamidation has been emerging as a convenient method to diversify amides, but remains challenging for structurally robust tertiary alkyl amides. A new method is described here using tungsten(VI) chloride as a catalyst and chlorotrimethylsilane as an additive to streamline transamidation of tertiary alkyl amides. The synergistic effect of the catalyst and additive enables the nucleophilic acyl substitution of tertiary alkyl amides with amines, leading to successful transamidation.