Copper-mediated Regioselective C-H Cyanation of Phenols with Assistance of Bipyridine-type Bidentate Auxiliary

A Cu-mediated ortho-selective C-H cyanation of phenols with ethyl cyanoformate as the cyano source has been developed. The key to success is the introduction of 4,4'-di-tent-butyl-2,2'-bipyridine (dtbpy) bidentate auxiliary on the phenol oxygen, which is easily attachable, detachable, and recyclable. The newly developed protocol is tolerant of several carbonyl functional groups, which are incompatible with previous Lewis-acid-promoted cyanation of phenols.

Automated summary

A new method for the cyanation of phenols with ortho-selectivity has been developed using Cu-mediated C-H activation and ethyl cyanoformate. The success of this method lies in the introduction of a bidentate auxiliary that is easily attachable, detachable, and recyclable. This protocol shows tolerance towards various carbonyl functional groups, which were incompatible with previous methods using Lewis acid promoters.