Synergistic Lewis Acid and Photoredox-Catalyzed Trifluoromethylative Difunctionalization of Alkenes with Selenium Ylide-Based Trifluoromethylating Reagent

Abstract

Trifluoromethylative difunctionalization of alkenes with a variety of nucleophiles including amine, azide, alcohol, water, and electron-rich arenes using reagent 1 as trifluoromethyl radical source in the presence of a synergistic catalyst including a Lewis acid scandium­(III) trifluoromethanesulfonate (Sc­(OTf)3) and a photoredox catalyst [fac-Ir­(ppy)3] was described. Mechanistic studies showed that the role of Sc­(OTf)3 in the reaction is to activate reagent 1 via Lewis acid–Lewis base interaction to form complex [Sc­(OTf)3•3­(1)], which was fully characterized by nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and elemental analysis. Cyclic voltammetry (CV) experiments and density functional theory (DFT) calculation showed that the reduction potential of complex [Sc­(OTf)3•3­(1)] is much higher than that of reagent 1, thus suggesting complex [Sc­(OTf)3•3­(1)] is much easier to accept electron through single-electron-transfer (SET) process, and consequently, much easier to generate trifluoromethyl radical.

Zinc acetate-promoted blocking of the ATRA process with alkyl halides enabling photochemical alkylamination of olefins

“…Although highly successful in integrating various functionalities, the incorporation of amino groups in this ORPC process is rare. 8 This is because amines are easily oxidized under photoredox conditions to electrophilic amine radical cations 9 and thereby lose their nucleophilicity under the ORPC process. Strategically, trapping of this carbocation with nitrile reagent followed by hydrolysis, Ritter type amination, would solve the above issue and allow an amino-functionality to be installed onto alkenes under mild conditions.…”

Rational Design and Development of Low‐Price, Scalable, Shelf‐Stable and Broadly Applicable Electrophilic Sulfonium Ylide‐Based Trifluoromethylating Reagents

“…Consequently, Radical anion 2a –• quickly undergoes Se—C cleavage to give trifluoromethyl radical. [ 4 ] Presumptively, Sc(OTf) 3 may play a similar role to activate reagent 1g to generate trifluoromethyl radical. In addition, excess methanol was required to ensure high conversion and typically methanol was used as cosolvent with acetonitrile in a ratio of 1 : 10.…”

“…In the presence of a photoredox catalyst and a Lewis acid cocatalyst, reagent 2a was enabled to react with alkenes and a variety of nucleophiles to give trifluoromethylative difunctionlized products in good to excellent yields. [ 4 ] Structure‐activity studies showed the installation of the strong electron‐withdrawing nitro group on the selenium ylide skeleton of reagent 2a plays a pivotal role in enhancing its reactivity, since less than 2% conversion was observed when a para ‐ methoxyphenyl substituted selenium ylide 2b was subjected to the identical reaction conditions for the α‐trifluoromethylation reaction of β‐ketoesters. [ 3 ] Moreover, related studies on other sulfonium ylides based electrophilic difluoromethylating, [ 5 ] monomethylating [ 6 ] and pentafluoroethylating reagents [ 7 ] also disclosed that reagents with a strong electron‐withdrawing group exhibit much higher reactivities than those parent ylides in the absence of such a group.…”

Branching out: redox strategies towards the synthesis of acyclic α-tertiary ethers

“…Since Koike & Akita's report of alkoxytrifluoromethylation using Umemoto's reagent in 2012, 71 several reaction manifolds have been published that achieve this transformation using alternative haloalkyl radical precursors. [72][73][74][75] In general, these reactions proceed via the RPC mechanism depicted in Scheme 2, yielding halogenated a-tertiary ethers in moderate to excellent yields. A noteworthy example was disclosed by Masson in 2019, involving a four-component coupling to forge a nitrile-substituted a-tertiary ether in 59% yield.…”