Selective Newman-Kwart Rearrangement Under Mild Conditions Enabled by Heterogeneous Photocatalysis and Electrochemical Catalysis
Authors: Francke Robert , Enders Patrick , Taeufer Tobias , Prane Katrina , Prudlik Adrian 
Published: February 2024

The Newman-Kwart Rearrangement (NKR), the key-step in the three-stage conversion of phenols 1 into thiophenols 4 (see figure below), holds numerous applications in various fields [1]. Usually, the NKR proceeds via thermally induced intramolecular nucleophilic ipso substitution. High temperatures up to 300 °C are required to facilitate the rearrangement, especially for electron-rich substrates, causing side reactions and high energy consumption [1].
Over the past decade, several improved protocols have appeared that enable selective conversion under milder conditions. These methods are based either on homogeneous photocatalysis [2], thermochemical Pd catalysis [3], or on the use of reagents [4]. In this context, a new approach was developed in our group, in which heterogeneous electron transfer enables a radical cation pathway and thereby catalyzes the rearrangement (“hole catalysis”, see figure) [5].
The radical cation mechanism is driven by catalytic amounts of charge, either induced by anodic oxidation (“electrochemical catalysis”, e-NKR) [5,6] or in a photochemical reactor using suspended titanium dioxide nanoparticles as photocatalyst (p-NKR) [7].The resulting radical cation 2∙+
then undergoes intramolecular electrophilic aromatic substitution (ArSE) to form the product radical cation 3∙+
, which reacts either in a chain process with another substrate molecule 2 (see figure, case A) or undergoes backward electron exchange with the electrode/titanium dioxide particle (case B) to form product 4 [6,7].
For both the e-NKR and the p-NKR, highly selective transformation proceeds at room temperature under aerobic conditions. A variety of different substrates can be rearranged, whereby the scope is complementary to the thermal NKR with respect to electron-donating and -withdrawing aryl substituents. For the e-NKR, an electrochemical micro-flow reactor can overcome the need for supporting electrolyte due to a small distance between the electrodes [6,7].
Both for the p- and the e-NKR, detailed mechanistic studies were carried out using cyclic voltammetry, operando spectroscopy, computational analysis, and control experiments. In the present contribution, both practical and mechanistic aspects will be discussed with particular focus on the photocatalytic approach [6,7], along with recent applications to biomass-derived compounds[8].
References
[1] a) G. C. Lloyd-Jones, J. D. Moseley, J. S. Renny, Synthesis.
2008, 5, 661 – 689; b) C. Zonta, O. de Lucchi, R. Volpicelli, L. Cotarca, Top.
Curr. Chem.
2006, 275, 131 – 161.
[2] A. J. Perkowski, C. L. Cruz, D. A. Nicewicz, J. Am. Chem. Soc.
2015, 137, 50, 15684 – 15687.
[3] J. N. Harvey, J. Jover, G. C. Lloyd-Jones, J. D. Moseley, P. Murray, J. S. Renny, Angew. Chem. Int. Ed.
2009, 48, 7612 – 7615.
[4] a) S. K. Pedersen, A. Ulfkjaer, M. N. Newman, S. Yogarasa, A. U. Petersen, T. I. Sølling, M. Pittelkow, J. Org. Chem.
2018, 83, 12000 – 12006; b) T. Gendron, R. Pereira, H. Y. Abdi, T. H. Witney, E. Årstad, Org.
Lett.
2020, 22, 274 – 278.
[5] a) T. Broese, A. F. Rösel, A. Prudlik, R. Francke, Org. Lett. 2018, 20, 7483 – 7487; b) A. F. Rösel, M. Ugandi, N. T. T. Huyen, M. Májek, T. Broese, M. Roemelt, R. Francke, J. Org.
Chem. 2020, 85, 8029 – 8044.
[6] R. Francke, R. D. Little, ChemElectroChem. 2019, 6, 4373 – 4382.
[7] P. Enders, T. Taeufer, K. Prane, E. Schönke, R. Francke, manuscript in preparation.
[8] P. Enders, S. Caby, J. Bardagí, R. Francke, manuscript in preparation.

Figure 1