Core-Labeling (Radio) Synthesis of Phenols

Org Lett. 2023 Oct 6;25(39):7230-7235. doi: 10.1021/acs.orglett.3c02838. Epub 2023 Sep 26.

Abstract

We report a method that enables the fast incorporation of carbon isotopes into the ipso carbon of phenols. Our approach relies on the synthesis of a 1,5-dibromo-1,4-pentadiene precursor, which upon lithium-halogen exchange followed by treatment with carbonate esters results in a formal [5 + 1] cyclization to form the phenol product. Using this strategy, we have prepared 12 1-13C-labeled phenols, show proof-of-concept for the labeling of phenols with carbon-14, and demonstrate phenol synthesis directly from cyclotron-produced [11C]CO2.