Hydrofluoromethylation of alkenes with fluoroiodomethane and beyond

Abstract

A process for the direct hydrofluoromethylation of alkenes is reported for the first time. This straighforward silyl radical-mediated reaction utilises CH2FI as a non-ozone depleting reagent, traditionally used in electrophilic,...

C–C Bond Fluorination via Manganese Catalysis

“…Gouverner and coworkers recently developed an orthogonal hydrofluoroalkylation approach to γ-fluorinated ketones, allowing for these molecules to be prepared from activated alkenes, fluoroalkyl radical precursors, and silanes; however, this reaction does not involve direct C−F bond formation. 7 Toward developing a truly general approach to distally fluorinated ketones using Earth-abundant-element catalysis, our initial efforts toward C−F bond formation via C−C cleavage centered on cerium compounds, because of the recognized ability of Ce(IV) species to mediate the oxidative cleavage of strained cycloalkanols to produce carbon-centered radicals and Ce(III) byproducts (Figure 2b). 4m,n,p,aa Taking inspiration from Sammis and co-workers, we reasoned that these radical intermediates could be intercepted by an electrophilic fluorine source, such as Selectfluor or Nfluorobenzenesulfonimide (NFSI) to deliver alkyl fluorides and oxidizing aminyl radical cation or neutral radicals.…”

“…While presenting many advantages, including low catalyst loadings of an inexpensive and abundant catalyst, moderate (2.2 equiv) loadings of Selectfluor, and high substrate tolerance, this method requires UV irradiation to proceed and is not amenable to cyclobutanols, presenting challenges to its widespread adoption. Gouverner and co-workers recently developed an orthogonal hydrofluoroalkylation approach to γ-fluorinated ketones, allowing for these molecules to be prepared from activated alkenes, fluoroalkyl radical precursors, and silanes; however, this reaction does not involve direct C–F bond formation …”

The synthetic versatility of fluoroiodomethane: recent applications as monofluoromethylation platform

“…Recently, CH 2 FBr has been adopted for the generation of FCH 2 • radical species. 78,79 In this context, very recently, Gouverneur 80 and Gaunt 81 independently proposed the use of fluoroiodomethane (CH 2 FI) as a convenient platform for the generation of monofluoromethyl radical through silyl radical-mediated transformations under blue LED activation. 82 Both protocols adopted tris Gouverneur et al described the hydrofluoromethylation of several electron-deficient alkenes including biologically active unsaturated acceptors through a blue LED irradiation for 16 hours in acetonitrile.…”

Fluoroiodomethane: A CH2F‐Moiety‐Delivering Agent Suitable for Nucleophilic‐, Electrophilic‐, and Radical‐Harnessed Operations

“…Very recently, Gouverneur and co‐workers introduced the first direct hydrofluoromethylation of electron‐deficient alkenes with fluoroiodomethane under mild reaction conditions (Scheme 26). [85c] The transformation relies on the employment of tris(trimethylsilyl)silane [(TMS) 3 SiH], as the supersilyl radical precursor and requires blue LED activation to initiate the process by photolytic C−I cleavage of FCH 2 ‐I. The blue light induced homolysis of the C−I bond releases the competent fluoromethyl radical which is delivered via a Giese addition to the electron‐deficient olefin, thus affording an electrophilic carbon‐centered radical intermediate.…”