Radical Cation Alkene Functionalization Using Anodic Oxidation

Abstract

Oxidative functionalization of alkenes is a promising molecular transformation technique, where intramolecular reactions enable the synthesis of saturated heterocycles1), which are often found in natural products and pharmaceuticals. In addition to the widely studied palladium-catalyzed oxidative functionalization of alkenes2), electrochemical3), 4) and photocatalytic5) methods have recently been developed. These one-electron oxidation-based methods have been applied to trisubstituted and tetrasubstituted alkenes with large steric hindrance, which is difficult to achieve with conventional palladium-catalyzed reactions. In many cases, these methods reported previously form rings as neutral radicals under basic conditions. On the other hand, radical cationic cyclization is relatively rare and have not yet been fully discussed. In this study, we developed an alkene oxidative functionalization using electrolysis for radical cationic cyclization.After optimizing the reaction conditions using trisubstituted alkene (1a) as a model substrate, we succeeded in obtaining the target compound (2a) in 90% yield (Scheme 1). In this reaction, a six-membered ring is formed as a byproduct, but the anion species of the supporting salt affects the reaction selectivity, and it was found that a five-membered ring was formed with high selectivity when ClO4- or TfO- were used. Furthermore, using a 1:9 mixture of highly polar CH3CN and low-polar 1,2-DCE as the reaction solvent improved the solubility and conductivity of the supporting salt, resulting in a significant increase in yield. The use of carbon felt, which has a large surface area, as the working electrode also contributed to the yield improvement by suppressing the voltage increase.For sulfonamides (1b-d) with various substituents on the aromatic ring, we were able to obtain five-membered ring compounds (2b-d) in good yields in all cases. In addition to these results, the details of the condition studies and other substrates will be discussed.1) Nakamura, I.; Yamamoto, Y. Chem. Rev. 2004, 104, 2127-2198.2) McDonald, R. I.; Liu, G.; Stahl, S, S. Chem. Rev. 2011, 111, 2981-3019.3) Xu, H.-C.; Moeller, K. D. J. Am. Chem. Soc. 2010, 132, 2839–2844.4) Huang, C.; Li, Z.-Y.; Song, J.; Xu, H.-C. Angew. Chem. Int. Ed. 2021, 60, 11237–11241.5) Reed, N. L.; Lutovsky, G. A.; Yoon, T. P. J. Am. Chem. Soc. 2021, 143, 6065-6070. Figure 1