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.
We report the use of N-2,4-dinitrophenyltetrazoles as latent active esters (LAEs) in the synthesis of amide bonds. Activating the tetrazole generates an HOBt-type active ester without the requirement for exogenous coupling agents. The methodology was widely applicable to a range of substrates, with up to quantitative yields obtained. The versatility and functional group tolerance were exemplified with the one-step synthesis of various pharmaceutical agents and the N-acylation of resin-bound peptides.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.