Radical hydrodifluoromethylation of unsaturated C−C bonds via an electroreductively triggered two-pronged approach

Seonyoung Kim, Keon Ha Hwang, Hyeong Gyu Park, Jaesung Kwak, Hyuk Lee, Hyunwoo Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Due to its superior ability in controlling pharmaceutical activity, the installation of difluoromethyl (CF2H) functionality into organic molecules has been an area of intensive research. In this context, difluoromethylation of C−C π bonds mediated by a CF2H radical have been pursued as a central strategy to grant access to difluoromethylated hydrocarbons. However, early precedents necessitate the generation of oxidative chemical species that can limit the generality and utility of the reaction. We report here the successful implementation of radical hydrodifluoromethylation of unsaturated C−C bonds via an electroreductively triggered two-pronged approach. Preliminary mechanistic investigations suggest that the key distinction of the present strategy originates from the reconciliation of multiple redox processes under highly reducing electrochemical conditions. The reaction conditions can be chosen based on the electronic properties of the alkenes of interest, highlighting the hydrodifluoromethylation of both unactivated and activated alkenes. Notably, the reaction delivers geminal (bis)difluoromethylated products from alkynes in a single step by consecutive hydrodifluoromethylation, granting access to an underutilized 1,1,3,3-tetrafluoropropan-2-yl functional group. The late-stage hydrodifluoromethylation of densely functionalized pharmaceutical agents is also presented.

Original languageEnglish
Article number96
JournalCommunications Chemistry
Volume5
Issue number1
DOIs
StatePublished - Dec 2022

Fingerprint

Dive into the research topics of 'Radical hydrodifluoromethylation of unsaturated C−C bonds via an electroreductively triggered two-pronged approach'. Together they form a unique fingerprint.

Cite this