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. 2020 Jan 2;59(1):409-417.
doi: 10.1002/anie.201910300. Epub 2019 Nov 18.

Electrochemistry Broadens the Scope of Flavin Photocatalysis: Photoelectrocatalytic Oxidation of Unactivated Alcohols

Wen Zhang  1 , Keith L Carpenter  1 , Song Lin  1
Affiliations

Electrochemistry Broadens the Scope of Flavin Photocatalysis: Photoelectrocatalytic Oxidation of Unactivated Alcohols

Wen Zhang et al. Angew Chem Int Ed Engl. .

Abstract

Riboflavin-derived photocatalysts have been extensively studied in the context of alcohol oxidation. However, to date, the scope of this catalytic methodology has been limited to benzyl alcohols. In this work, mechanistic understanding of flavin-catalyzed oxidation reactions, in either the absence or presence of thiourea as a cocatalyst, was obtained. The mechanistic insights enabled development of an electrochemically driven photochemical oxidation of primary and secondary aliphatic alcohols using a pair of flavin and dialkylthiourea catalysts. Electrochemistry makes it possible to avoid using O2 and an oxidant and generating H2 O2 as a byproduct, both of which oxidatively degrade thiourea under the reaction conditions. This modification unlocks a new mechanistic pathway in which the oxidation of unactivated alcohols is achieved by thiyl radical mediated hydrogen-atom abstraction.

Keywords: alcohols; electrochemistry; oxidation; photocatalysis; radicals.

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Figures

Figure 1.
Figure 1.
(A) Cyclic voltammetry of 1a and 1b. Conditions: alcohol (5.71 mM), LiOTf (0.1 M in MeCN), scan rate = 100 mV/s. (B) Fluorescence quenching of RFT with 1a, 1b.
Figure 2.
Figure 2.
13C-NMR spectrum of A) thiourea dioxide (TU-1•O2); B) white precipitate in reaction system; C) thiourea, all in D2O with MeCN as internal standard.
Figure 3.
Figure 3.
Photo-quenching of RFT by thiourea TU-2.
Figure 4.
Figure 4.
Reaction time course data with different concentrations of TU-2.
Figure 5.
Figure 5.
(A) Cyclic voltammetry of TU-2 in the presence and absence of 1b; (B) Radical probe experiment. Standard conditions: see Scheme 6A, entry 9.
Scheme 1.
Scheme 1.
General mechanistic depiction of photoredox catalysis, electrocatalysis, and molecular photoelectrocatalysis for oxidative transformations.
Scheme 2.
Scheme 2.
RFT-catalyzed photochemical oxidation of alcohols.
Scheme 3.
Scheme 3.
Computed bond dissociation energy of isothiouronium and isothiourea [M06-2x/6-311+G(d,p)/CPCM(CH3CN)//B3LYP/6-31G(d)].
Scheme 4.
Scheme 4.
RFT-catalyzed photochemical oxidation of alcohols.
Scheme 5.
Scheme 5.
Decomposition of thiourea under RFT-promoted photooxidation conditions.
Scheme 6.
Scheme 6.
Photoelectrocatalytic oxidation of alcohols. aConditions: alcohol (0.2 mmol, 1 equiv), RFT (5 mol%), TU (10 mol%), electrolyte (3.5 mL, 0.1 M in MeCN), H2O (0.2 mL), cell voltage Ucell = 2.5 V (initial anodic potential Eanode ≈ 0.8 V vs SCE), blue LED. bYield determined by 1H NMR. cIsolated yield. dWithout blue LED. eWithout RFT. fWithout electricity. gElectrolysis at a constant anodic potential of 0.58 V. gReaction time 36 h.
Scheme 7.
Scheme 7.
Formation and role of thiyl radicals in the photoelectrocatalytic alcohol oxidation.
Scheme 8.
Scheme 8.
Proposed catalytic cycles for the photoelectrocatalytic oxidation.
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