Regioselective synthesis of 1,4-disubstituted imidazoles?

Organic & Biomolecular Chemistry Pub Date: 2011-12-15 DOI: 10.1039/C1OB06690K

Abstract

A short and efficient synthesis of 1,4-disubstituted imidazoles has been developed which provides the desired products with complete regioselectivity. This protocol allows preparation of compounds which are challenging to prepare by current literature methods in a regioselective fashion, a sterically and electronically diverse range of N-substituents being accessible. The sequence involves an unusual double aminomethylenation of a glycine derivative, to yield a 2-azabuta-1,3-diene, onto which addition of an amine nucleophile results in a transamination/cyclization to prepare the substituted imidazole. The cyclization event is surprisingly insensitive to steric and electronic variations on the amine component, enabling a diverse range of imidazoles to be prepared.

Graphical abstract: Regioselective synthesis of 1,4-disubstituted imidazoles
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