Electrochemistry of Chelation-Stabilized Hypervalent Bromine(III) Compounds

Abstract

Compared to hypervalent iodine(III) reagents, the bromine(III) counterparts provide attractive features such as higher electrophilicity, better nucleofugality of the bromanyl unit, and more driving force for oxidation processes.[1] Unprecedented synthetic transformations such as the Hofmann rearrangement of sulfonamides to the corresponding N-arylsulfamoyl fluorides,[2] oxidative coupling of alkynes and primary alcohols to conjugated enones,[3] regioselective C-H functionalization of non-activated alkanes[4] and a rare Bayer-Villinger-type oxidation of open-chain aliphatic aldehydes[5] show the great potential for hypervalent bromine(III). Unfortunately, conventional bromine(III) reagents are associated with poor stability, resulting in difficult-to-control reactivity and low compatibility with functional groups. Moreover, difficult preparation protocols, almost exclusively starting from the highly toxic and corrosive BrF3 precursor, currently limit the accessibility.[1b] In a previous study, we demonstrated chelation-stabilized hypervalent bromine(III) compounds possessing enhanced stability through the coordinating hexafluoro-2-hydroxypropanyl substituents, prepared through mild synthesis via an electrochemical approach (see Figure A). Anodic oxidation of bromoarene precursor 1 under galvanostatic conditions in an undivided cell leads to a benchtop-stable series of para-substituted derivatives of λ3-bromanes 2 that showed flexibly tunable redox potentials in a range from 1.86 V to 2.60 V vs. Ag/0.01 M AgNO3 making it possible to adjust the mediator to the substrate of interest. Based on electroanalytical, spectroscopic, and quantum chemical studies, mechanistic insights into the electrochemical generation and the reactivity of chelation-stabilized bromine(III) were obtained (Figure B),[6] which will be discussed in the present contribution.The utility of 2 was demonstrated with several synthetic applications, including C(sp 3)-H amidation of anilines to yield adduct 3 and oxidative coupling of anisoles yielding symmetric biaryls 4 (see Figure C). However, through the high stability of doubly chelated structure of bromanes, the number of synthetic applications remains relatively limited. In this context, we currently investigate the electrochemistry and reactivity of benzbromoxoles which are stabilized by only one chelating hexafluoro-2-hydroxypropanyl substituent.[7] The results of the mechanistic studies will be presented in this contribution.[1] (a) K. Miyamoto, M. Saito, S. Tsuji, T. Takagi, M. Shiro, M. Uchiyama, M. Ochiai, J. Am. Chem. Soc. 2021, 143, 9327-9331; (b) T. Wirth, T. Patra, B. Winterson, Synthesis 2021, 54, 1261-1271.[2] M. Ochiai, T. Okada, N. Tada, A. Yoshimura, K. Miyamoto, M. Shiro, J. Am. Chem. Soc. 2009, 131, 8392-8393.[3] M. Ochiai, A. Yoshimura, T. Mori, Y. Nishi, M. Hirobe, J. Am. Chem. Soc. 2008, 130, 3742-3743.[4] M. Ochiai, K. Miyamoto, T. Kaneaki, S. Hayashi, W. Nakanishi, Science 2011, 332, 448-451.[5] M. Ochiai, A. Yoshimura, K. Miyamoto, S. Hayashi, W. Nakanishi, J. Am. Chem. Soc. 2010, 132, 9236-9239.[6] N. Mohebbati, I. Sokolovs, P. Woite, M. Lokov, E. Parman, M. Ugandi, I. Leito, M. Roemelt, E. Suna, R. Francke, Chem. Eur. J. 2022, 28, e202200974.[7] I. Sokolovs, E. Suna, Org. Lett. 2023. Figure 1