Transition metal-free organocatalyzed direct <i>N</i> -benzylation of amides <i>via</i> a hydrogen borrowing strategy

The development of a versatile methodology for the <i>N</i>-benzylation of amides is challenging due to the relatively poor nucleophilicity of the amide nitrogen. Herein, we report the first transition metal-free, broad catalytic methodology for the <i>N</i>-benzylation of amides using alcohols <i>via</i> a hydrogen borrowing methodology. The crucial step is the oxidation of the benzyl alcohol by the <i>in situ</i> generated N-heterocyclic carbene (NHC) to form 3-(2-(2-methoxyphenyl)-2-oxoethyl)-1-(pyridin-2-yl)-1<i>H</i>-imidazol-3-ium bromide (HL₁Br). The carbene-based organocatalyst (HL₁Br) efficiently sequesters hydrogen (as 2H+ + 2e-) produced during the dehydrogenation of the alcohol <i>via</i> a single-electron transfer (SET) process and returns the same to the <i>in situ</i> generated imine intermediate to yield the final <i>N</i>-benzylated product. The developed protocol is also applied for <i>N</i>-benzylation of aniline and selective mono-benzylation of benzene-1,2-diamine to form <i>N</i>1-benzylbenzene-1,2-diamine. Control experiments, available literature, and HRMS characterization support the plausible mechanism.