Organocatalytic C–H fluoroalkylation of commodity polymers

Lewis, Sally E.; Wilhelmy, Bradley E.; Leibfarth, Frank A.

doi:10.1039/c9py01884k

“… [45] Since this pioneering study, the method has successfully been implemented towards the synthesis of various classes of organic structures, including complex molecules and materials. [ 46 , 47 , 48 , 49 , 50 ] Based on voltammetric measurements and augmented with calculations, we assumed that trifluoroacetic anhydride with an observable reduction onset at around −1.2 V (vs. SCE) should undergo an irreversible, exergonic, and reductive single electron transfer (SET) process to afford the corresponding radical ion species in the presence of a photocatalyst operating under oxidative quenching conditions. The ensuing (O)C−O bond fragmentation could preferentially afford the CF 3 CO radical species (Δ G =−20.1 kJ mol −1 in favor of the trifluoroacyl radical) and trifluoroacetate anion.…”

Section: Resultsmentioning

confidence: 99%

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

Zhang

¹

,

Rombach

²

,

Nötel

³

et al. 2021

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“…43 Since this pioneering study, the method has successfully been implemented towards the functionalization of various classes of organic structures, including complex molecules and materials. [44][45][46][47][48] Based on voltammetric measurements and augmented with in silico work, we assumed that trifluoroacetic anhydride with an observable reduction onset at around −1.1 V (vs. SCE) should undergo an irreversible, exergonic, and reductive single electron transfer (SET) process to afford the corresponding radical ion species in the presence of a photocatalyst operating under oxidative quenching conditions. The ensuing (O)C−O bond fragmentation could preferentially afford the CF3(CO) radical species (G = -20.1 kJ/mol in favor of the trifluoroacyl radical) and trifluoroacetate anion.…”

Section: Resultsmentioning

confidence: 99%

Radical Trifluoroacetylation of Alkenes Triggered by a Visible-Light-Promoted C−O Bond Fragmentation of Trifluoroacetic Anhydride

Zhang¹,

Rombach²,

Nötel³

et al. 2021

Preprint

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Trifluoromethyl ketones are not only found in drug like substances, but are also considered as key synthons for the preparation of various fluorinated heterocyclic molecules. Access to such trifluoromethyl ketone derivatives typically requires the incorporation of the trifluoromethyl group, or a surrogate moiety, at the beginning of a multi-step synthetic sequence. However, direct trifluoroacylation of alkenes could potentially provide a highly efficient and straightforward method for the synthesis of a,b-unsaturated trifluoromethyl ketones. Here we report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low-cost and readily available reagent. This light-mediated process is fundamentally different from conventional methodologies and occurs through an trifluoroacyl radical mechanism promoted by a photocatalyst. Beyond simple alkenes, this method allows for chemo- and regioselective functionalization of small-molecule drugs and common pharmacophores.

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“…The photocatalytic decarboxylative strategy reported by Stephenson and co‐workers for the perfluoroalkylation of hetero(aromatic) compounds demonstrated a conceptual platform to generate fluoroalkyl radical species from cheap and readily available reagents, for example, perfluoroalkyl anhydrides [45] . Since this pioneering study, the method has successfully been implemented towards the synthesis of various classes of organic structures, including complex molecules and materials [46–50] . Based on voltammetric measurements and augmented with calculations, we assumed that trifluoroacetic anhydride with an observable reduction onset at around −1.2 V (vs. SCE) should undergo an irreversible, exergonic, and reductive single electron transfer (SET) process to afford the corresponding radical ion species in the presence of a photocatalyst operating under oxidative quenching conditions.…”

Section: Resultsmentioning

confidence: 99%

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

Zhang

¹

,

Rombach

²

,

Nötel

³

et al. 2021

Angewandte Chemie

5

0

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Trifluoromethyl ketones are not only found in drug like substances, but are also considered as key synthons for the preparation of various fluorinated heterocyclic molecules.Access to such trifluoromethyl ketone derivatives typically requires the incorporation of the trifluoromethyl group, or a surrogate moiety, at the beginning of a multi-step synthetic sequence. However, direct trifluoroacylation of alkenes could potentially provide a highly efficient and straightforward method for the synthesis of -unsaturated trifluoromethyl ketones. Here we report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low-cost and readily available reagent. This light-mediated process is fundamentally different from conventional methodologies and occurs through an trifluoroacyl radical mechanism promoted by a photocatalyst. Beyond simple alkenes, this method allows for chemo-and regioselective functionalization of small-molecule drugs and common pharmacophores. . 90's, Balenkova and co-workers reported the method for the activation of TFAA by in situ generated BF3(gas)/Me2S complex at -60 ºC, allowing direct olefinic trifluoroacetylation ostensibly via an effect of kH/kD= 1.3 per deuterium further hints on the existence of conjugation effects (for extensive discussions, see ESI). However, this step might also directly employ a proton coupled electron transfer as previously described for the corresponding anions. [62][63][64] On basis of these electrochemical characteristics, we propose a slow depopulation of the equilibrium 59/61 through the reductive quenching by the Ir(IV) ground state. The subsequent irreversible deprotonation of the strongly acidic cation 62 with trifluoroacetate or the TFAA-radical anion occurs with the concurrent formation of the reaction product. ConclusionIn summary, we have developed an efficient and practical protocol where the simple reagent TFAA undergoes chemo-and regioselective trifluoroacylation reaction with a broad range of alkenes including complex natural products to access -unsaturated trifluoromethyl ketone derivatives. Detailed mechanistic studies have provided evidence that C-CF3 and C-COCF3 bond formation can be controlled under different reaction conditions. With this remarkable disclosure, we anticipate that this trifluoroacetylation approach will be a valuable tool for the synthetic chemist in drug discovery and development. MethodsGeneral procedure for photocatalytic trifluoroacetylation of alkenes. A 10-mL glass microwave vial was charged with photocatalyst (1 mol%). The contents of the vial were then subject to 3x argon/vacuum cycles. Anhydrous EtOAc was added and the reaction mixture was sparged with argon for 3 min. Finally, the substrate (1.0 equiv) and TFAA (2.0 equiv) were introduced to the reaction mixture via microsyringe.The obtained red solution was stirred at room temperature under blue LED irradiation. After 12 hours, water was added to the reaction mixture and the product was extracted with CH2Cl2 (...

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Organocatalytic C–H fluoroalkylation of commodity polymers

Abstract: Organocatalytic post-polymerization modification of commodity aromatic polymers diversifies their material properties.

Cited by 40 publications

References 33 publications

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

Radical Trifluoroacetylation of Alkenes Triggered by a Visible-Light-Promoted C−O Bond Fragmentation of Trifluoroacetic Anhydride

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

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