Chemical reactions via radical cation intermediates are of great interest in photoredox catalysis and electrosynthesis, while their reactivities are not clearly understood. For example, how the counter anions correlate with the reactivity of radical cations is still ambiguous. Here we report the effect of anions and fluorinated alcohols on the reactivity of organic radical cations in hole catalysis. The addition of salts in a radical cation Diels-Alder reaction under photoredox catalysis demonstrates that common anions significantly decease the efficiency of hole catalysis. The use of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) restores the reaction efficiency in the presence of salts, presumably due to solvation of the anions by HFIP to reduce their nucleophilicity. These findings enable hole catalysis under electrolytic conditions with greatly improved efficiency. The effect of anions and fluorinated alcohol described in this paper gives important insights on the fundamental understanding for the reactivity of arene radical cations.

The large amount of waste derived from coupling reagents is a serious drawback of peptide synthesis from a green chemistry viewpoint. To overcome this issue, we report an electrochemical peptide...

Electrochemical reduction of amides was achieved by using a hydrosilane without any toxic or expensive metals. The key reactive ketyl radical intermediate was generated by cathodic reduction. Continuous reaction with anodically generated silyl radicals or zinc bromide resulted in chemoselective deoxygenation to give the corresponding amines.

Photocatalytic cycloadditions involving carbon–carbon bond formation in the absence of an external sensitizer are described. The use of a lithium perchlorate/nitromethane electrolyte solution exhibiting remarkable Lewis acidity is the key for the successful transformations. According to the UV/Vis measurements, an electron donor–acceptor complex did not form and nitromethane was expected to function as the initial sensitizer for the reactions. Although the mechanisms are still under debate, both electron‐ and energy‐transfer processes could be involved, both of which are triggered by excited nitromethane in combination with molecular oxygen.

Recently, peptides have been recognized as candidates for medium molecular medicines, which refers to pharmaceutical compounds whose molecular weights are roughly in the 1000 to 5000 range. This class of medicines has more specificity and fewer side effects than conventional small molecular medicines. However, an amount of waste derived from coupling reagents is regarded as a serious drawback of peptide synthesis from a green chemistry viewpoint.1 To address this issue, we have developed an electrochemical peptide synthesis utilizing triphenylphosphine (Ph3P) in a biphasic system (MeCN-c-Hex).2 Anodic oxidation of Ph3P generates a phosphine radical cation, which serves as the coupling reagent to activate carboxylic acids followed by peptide bond formation and production of triphenylphosphine oxide (Ph3PO) as a stoichiometric byproduct.3 Given that methods to reduce Ph3PO to Ph3P have been reported,4 Ph3P can be a recyclable byproduct unlike byproducts from typical coupling reagents. In the optimized condition, we found that all canonical amino acids can be applied to electrochemical peptide bond formation and succeeded in the selective recovery of desired peptides and Ph3PO in combination with a soluble tag-assisted liquid-phase peptide synthesis. Moreover, a commercial peptide active pharmaceutical ingredient (API), leuprorelin, was successfully synthesized without the use of traditional coupling reagents. Reference 1. M. C. Bryan, P. J. Dunn, D. Entwistle, F. Gallou, S. G. Koenig, J. D. Hayler, M. R. Hickey, S. Hughes, M. E. Kopach, G. Moine, P. Richardson, F. Roschangar, A. Steven and F. J. Weiberth, Green Chem., 2018, 20, 5082–5103. 2. S. Nagahara, Y. Okada, Y. Kitano, K. Chiba, Chem. Sci., 2021, 12, 12911–12917. 3. A. Palma, J. Cardenas and B. A. Frontana-Uribe, Green Chem., 2009, 11, 283–293. 4. D. Hérault, D. H. Nguyen, D. Nuel and G. Buono, Chem. Soc. Rev., 2015, 44, 2508–2528. Figure 1