Amide Bond Formation via the Rearrangement of Nitrile Imines Derived from N-2-Nitrophenyl Hydrazonyl Bromides

We report how the rearrangement of highly reactive nitrile imines derived from N-2-nitrophenyl hydrazonyl bromides can be harnessed for the facile construction of amide bonds. This amidation reaction was found to be widely applicable to the synthesis of primary, secondary, and tertiary amides and was used as the key step in the synthesis of the lipid-lowering agent bezafibrate. The orthogonality and functional group tolerance of this approach was exemplified by the N-acylation of unprotected amino acids.

Automated summary

The rearrangement of highly reactive nitrile imines derived from N-2-nitrophenyl hydrazonyl bromides can be used for the facile construction of amide bonds, with broad applicability to the synthesis of primary, secondary, and tertiary amides. This method demonstrates orthogonality and functional group tolerance, as shown by the N-acylation of unprotected amino acids.