Base-catalyzed aryl halide isomerization enables the 4-selective substitution of 3-bromopyridines?

Chemical Science Pub Date: 2020-09-09 DOI: 10.1039/D0SC02689A

Abstract

The base-catalyzed isomerization of simple aryl halides is presented and utilized to achieve the 4-selective etherification, hydroxylation and amination of 3-bromopyridines. Mechanistic studies support isomerization of 3-bromopyridines to 4-bromopyridines proceeds via pyridyne intermediates and that 4-substitution selectivity is driven by a facile aromatic substitution reaction. Useful features of a tandem aryl halide isomerization/selective interception approach to aromatic functionalization are demonstrated. Example benefits include the use of readily available and stable 3-bromopyridines in place of less available and stable 4-halogenated congeners and the ability to converge mixtures of 3- and 5-bromopyridines to a single 4-substituted product.

Graphical abstract: Base-catalyzed aryl halide isomerization enables the 4-selective substitution of 3-bromopyridines
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