Synthesis of imidazo[1,5-a]pyridines via I2-mediated sp3 C–H amination?

Organic & Biomolecular Chemistry Pub Date: 2018-07-17 DOI: 10.1039/C8OB01501E

Abstract

A transition-metal-free sp3 C–H amination reaction has been established for imidazo[1,5-a]pyridine synthesis employing molecular iodine from 2-pyridyl ketones and alkylamines. In the presence of sodium acetate (NaOAc), the I2-mediated oxidative annulations of readily available substrates produced a variety of imidazo[1,5-a]pyridine derivatives efficiently in a one-pot manner. The present synthetic approach is operationally simple and can be conveniently carried out on a gram scale. Moreover, under the optimal reaction conditions a series of 1-(2-pyridyl)imidazo[1,5-a]pyridine cysteine protease inhibitors were easily prepared from the corresponding di-2-pyridyl ketones and substituted benzylamines in satisfactory yields.

Graphical abstract: Synthesis of imidazo[1,5-a]pyridines via I2-mediated sp3 C–H amination
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