Prenyl Praxis: A Method for Direct Photocatalytic Defluoroprenylation

Abstract

The prenyl fragment represents the most basic building block in terpenoids, a family of numerous and structurally diverse natural products that are known to possess interesting biological properties. In contrast, multifluorinated arenes are an important class of compounds that have found great utility in agricultural, material, and pharmaceutical industries. Fluorine substitution has been shown to impart a number of positive attributes including resistance to metabolic degradation, enhanced lipophilicity, and improved binding and passive diffusion of compounds across membranes. While allylation chemistry is well developed, effective prenylation strategies have been less forthcoming. Herein, we describe the defluoroprenylation via photocatalysis, a powerful method that provides access to "hybrid molecules" containing both the functionality of a prenyl group and fluorinated arenes. This approach involves direct prenyl group transfer under very mild conditions, displays excellent functional group tolerance, and relatively short reaction times (<4 h), which is the fastest photocatalytic C-F functionalization developed to date. Additionally, the strategy can be further extended to include allyl and geranyl (10 carbon fragment) transfer. Another prominent finding is a reagent dependent switch in regioselectivity of the major product from para to ortho C-F functionalization.