Merging Fluorine Incorporation and Functional Group Migration

Abstract

Fluorine incorporation by concomitant fluoroalkyl radical addition to alkene or alkyne and functional group migration (FGM) represents an ingenious and robust strategy for the synthesis of structurally diverse fluorinated compounds. This account gives an overview of related studies in our group, in which three main reaction modes are discussed: 1) radical fluoroalkylative difunctionalization of unactivated alkenes via intramolecular FGM; 2) alkene difunctionalization by docking‐migration process using fluoroalkyl‐containing bifunctional reagents; 3) incorporation of fluoroalkyl group into C(sp3)−H bond via consecutive hydrogen atom transfer (HAT) and FGM. Relying on these methods, a variety of trifluoromethylation and di‐/mono‐fluoroalkylation reactions along with the migration of cyano, heteroaryl, oximino, formyl, alkynyl, and alkenyl groups have been accomplished under mild conditions.

Direct Synthesis of 2-Hydroxytrifluoroethylacetophenones via Organophotoredox-Mediated Net-Neutral Radical/Polar Crossover

“…Undoubtedly, the trifluoromethyl group is widely prevalent in many agrochemicals and pharmaceuticals, and extensive attention has been devoted toward the design and development of efficient synthetic methods to provide access to CF 3 -containing organic architectures. In recent years, developments in radical, nucleophilic and electrophilic approaches have advanced in the field using CF 3 I, Langlois, Ruppert–Prakash, Togni, Umemoto reagents, and others.…”

Mechanoredox Enabled the Difunctionalization of Unactivated Alkenes via Distal Functional Group Migration

“…Radical-mediated difunctionalization of alkenes via functional group migration provides a powerful tool for the manipulation of olefins and has become a hot topic. − In recent years, trifluoromethyl-based radical cascade reactions via functional group migration for difunctionalization of unactivated alkenes have become more and more attractive as a powerful and atom-economical approach to improve the complexity, solubility, lipophilicity, permeability, and metabolic stability of molecules. − For instance, photocatalytic and electrocatalytic strategies have been successfully applied to the trifluoromethylation/alkynylation of unactivated alkenes via 1,4-alkynyl migration reported by Zhu and Wang, respectively (Scheme B). However, these techniques have some drawbacks such as expensive catalysts, bulk solvent consumption, inert atmosphere, and long reaction time.…”

N-Heterocyclic Carbene and Manganese Synergistic Catalysis: A Three-Component Radical Acylmonofluoroalkylation of Alkenes

“…Recently, the Molander group 5 disclosed the preparation of monofluoromethylene-containing benzyl bromides via a similar ATRA approach. Furthermore, a functional group migration strategy was leveraged by the Zhu group 6 to achieve carbomonofluoroalkylation of alkenes (Scheme 1b, left). However, a bifunctional monofluoroalkyl reagent is typically employed, rendering these protocols two-component processes.…”