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. 2020 Mar 16:16:398-408.
doi: 10.3762/bjoc.16.38. eCollection 2020.

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

Affiliations

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

Kaj M van Vliet et al. Beilstein J Org Chem. .

Abstract

Where monochloroacetic acid is widely used as a starting material for the synthesis of relevant groups of compounds, many of these synthetic procedures are based on nucleophilic substitution of the carbon chlorine bond. Oxidative or reductive activation of monochloroacetic acid results in radical intermediates, leading to reactivity different from the traditional reactivity of this compound. Here, we investigated the possibility of applying monochloroacetic acid as a substrate for photoredox catalysis with styrene to directly produce γ-phenyl-γ-butyrolactone. Instead of using nucleophilic substitution, we cleaved the carbon chlorine bond by single-electron reduction, creating a radical species. We observed that the reaction works best in nonpolar solvents. The reaction does not go to full conversion, but selectively forms γ-phenyl-γ-butyrolactone and 4-chloro-4-phenylbutanoic acid. Over time the catalyst precipitates from solution (perhaps in a decomposed form in case of fac-[Ir(ppy)3]), which was proven by mass spectrometry and EPR spectroscopy for one of the catalysts (N,N-5,10-di(2-naphthalene)-5,10-dihydrophenazine) used in this work. The generation of HCl resulting from lactone formation could be an additional problem for organometallic photoredox catalysts used in this reaction. In an attempt to trap one of the radical intermediates with TEMPO, we observed a compound indicating the generation of a chloromethyl radical.

Keywords: ATRA; catalysis; chloroacetic acid; lactone; photoredox.

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Figures

Figure 1
Figure 1
A part of the industry around monochloroacetic acid.
Scheme 1
Scheme 1
Redox based activation of haloacetic acid.
Figure 2
Figure 2
Cyclic voltammogram of monochloroacetic acid and ferrocene with 0.1 M [TBA][PF6] in MeCN. The potential is referenced to the Fc/Fc+ redox couple (0 V). The excited state reduction potentials of two different reducing photoredox catalysts (in red and green) are shown in the figure.
Scheme 2
Scheme 2
Initial attempts for lactone formation by photoredox catalysis.
Scheme 3
Scheme 3
The photoredox reaction of TEMPO with monochloroacetic acid catalyzed by fac-[Ir(ppy)3].
Figure 3
Figure 3
EPR spectra measured (black) and simulated (red) based on the structure of the oxidized photoredox catalyst shown on the right.
Scheme 4
Scheme 4
Two possible acid-assisted, reductive activation pathways of monochloroacetic acid (A–H = acid).
Figure 4
Figure 4
Reaction mixtures after overnight irradiation of (A) 4-chloro-4-phenylbutanoic acid (3) and fac-[Ir(ppy)3]; (B) 3, fac-[Ir(ppy)3] and monochloroacetic acid; (C) 3; (D) 3 and monochloroacetic acid. In none of the vials lactone 1 was formed.
Scheme 5
Scheme 5
Substrate scope of styrene derivatives in the photoredox reaction with monochloroacetic acid. Yields have been determined by 1H NMR spectroscopy of the crude reaction mixture, using 1,3,5-trimethoxybenzene as the external standard.
Scheme 6
Scheme 6
Proposed reaction mechanism.
Scheme 7
Scheme 7
The photoredox formation of 1-(chloromethoxy)-2,2,6,6-tetramethylpiperidine.

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