Electrochemistry and Reactivity of Chelation-stabilized Hypervalent Bromine(III) Compounds

Abstract

Hypervalent bromine(III) reagents possess a higher electrophilicity and a stronger oxidizing power compared to their iodine(III) counterparts. Despite the superior reactivity, bromine(III) reagents have a reputation of hard-to-control and difficult-to-synthesize compounds. This is partly due to their low stability, and partly because their synthesis typically relies on the use of the toxic and highly reactive BrF₃ as a precursor. Recently, we proposed chelation-stabilized hypervalent bromine(III) compounds as a possible solution to both problems. First, they can be conveniently prepared by electro-oxidation of the corresponding bromoarenes. Second, the chelation endows bromine(III) species with increased stability while retaining sufficient reactivity, comparable to that of iodine(III) counterparts. Finally, their intrinsic reactivity can be unlocked in the presence of acids. Herein, an in-depth mechanistic study of both the electrochemical generation and the reactivity of the bromine(III) compounds is disclosed, with implications for known applications and future developments in the field.

Keywords: bromane; cyclic voltammetry; hypervalent halogen; oxidative coupling; unified pH.

Scheme 1

Electrochemical generation of aryl‐λ ³‐bromanes 2 (Eq. (1)) and applications as reagent (Eq. (2)).

Figure 1

A and B: Background and iR drop‐corrected CVs of 5 mM 1  a and 5 mM 1  e at different scan rates (solvent: HFIP, working electrode: glassy carbon, supporting electrolyte: 0.1 M Bu₄NBF₄). C: Plot of the peak current densities (j _P) vs. v ^0.5.

Figure 2

Proposed mechanism for anodic bromane formation.

Figure 3

Comparison between the spin density distributions of 1  a ^.+ and 1  e ^.+.

Figure 4

Top: Absorption spectra of pure 1  e (green line) and 2  e (blue line) recorded in HFIP along with the predicted spectrum of 1  e ^.+ (dotted red line). Bottom: Spectroelectrochemical analysis of the anodic oxidation of 1  e at E=2.0 V vs. Ag/AgNO₃ (anode: Pt grid).

Figure 5

Top: Background and iR drop corrected linear sweep voltammograms (LSV) of bromanes 2  a‐g (c = 5 mM) recorded at 10 mV s⁻¹ in CH₃CN. Bottom left: Half‐peak potentials E _P/2(obs.) measured in CH₃CN and the values predicted using σ _R and σ _F substituent constants (E _P/2(pred.), for details see the Supporting Information). Bottom right: Correlation between E _P/2(obs.) and E _P/2(pred.) for 2 in CH₂Cl₂ and CH₃CN.

Scheme 2

Results of preparative‐scale cathodic reduction of 2  a in CH₃CN.

Scheme 3

Mechanistic studies of oxidative aminations induced by 2  a (calculated free energies in kcal mol⁻¹).

Scheme 4

Activation of 2  a for oxidative biaryl homo‐coupling.

Figure 6

A) Adduct formation between TfOH and 2  a with calculated Gibbs free energy in kcal mol⁻¹. B) Comparison between the observed shifts of ¹H and ¹⁹F signals for 2  a upon the addition of TfOH (2.0 equiv) in CD₂Cl₂ (trifluorotoluene as the internal standard) and the computed shifts. The positive signs refer to downfield displacements. ^a Averaged chemical shifts. C) Computed optimized geometry of 2  a‐TfOH. D) Displacement of ¹⁹F chemical shifts for 2  a in the presence of various amounts of TfOH. E) Reference compounds for titration experiments.