Direct formylation of phenols using difluorocarbene as a safe CO surrogate

A convenient method to prepare aryl formates is reported herein that exploits difluorocarbene to serve as a CO surrogate. This reaction is proposed to occur through a sequential O-difluoromethylation of phenol, followed by alpha-C-F bond functionalization of the resulting aryl difluoromethyl ether intermediate by phenol or moisture through fluorosemiacetal or orthoformate intermediates. Late-stage modification of biologically and materially active compounds is demonstrated.

Automated summary

A convenient method for preparing aryl formates using difluorocarbene as a CO surrogate is described. This reaction proceeds through sequential O-difluoromethylation of phenol, followed by alpha-C-F bond functionalization of the resulting aryl difluoromethyl ether intermediate by phenol or moisture through fluorosemiacetal or orthoformate intermediates. Late-stage modification of biologically and materially active compounds is demonstrated.