Direct formylation of phenols using difluorocarbene as a safe CO surrogate

Abstract

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...

Formylation of Propargylic Alcohols with Difluorocarbene

“…Based on control experiments and related literatures, [1b,6a,c,7] a possible reaction mechanism is proposed as shown in Scheme 5. Difluorocarbene (:CF 2 ) is firstly generated from sodium chlorodifluoroacetate 2 a in the presence of a base.…”

“…The formate group is a prevalent motif in natural products and medicinal molecules, and has certain biological activities and pharmacological properties [1] . For example, Cefamandole nafate is a substance that inhibits the growth or reproduction of bacteria (anti‐bacterial agent), [1a] and Formylated estrone is an inhibitor of human steroid sulfatase [1b] . Meanwhile, formate compounds are a kind of important intermediates in organic synthesis, which are widely used in natural flavoring food ingredients and fragrances fields.…”

“…Meanwhile, our group also reported that difluorocarbene participated in the reaction as a carbonyl source (Scheme 1d) [7] . In 2023, Zhang and coworkers [1b] reported the formylation of phenols using difluorocarbene instead of CO as formylating reagent (Scheme 1e). However, the formylation of alcohols with difluorocarbene as carbonyl source has not been reported.…”

C–F bond functionalizations via fluorinated carbenes

“…This method was further applied in the synthesis of biological and materials science related molecules (Scheme 16). 59…”