Synthesis of Benzoxazoles Using Electrochemically Generated Hypervalent Iodine

Abstract

The indirect ("ex-cell") electrochemical synthesis of benzoxazoles from imines using a redox mediator based on the iodine(I)/iodine(III) redox couple is reported. Tethering the redox-active iodophenyl subunit to a tetra-alkylammonium moiety allowed for anodic oxidation to be performed without supporting electrolyte. The mediator salt can be easily recovered and reused. Our "ex-cell" approach toward the electrosynthesis of benzoxazoles is compatible with a range of redox-sensitive functional groups. An unprecedented concerted reductive elimination mechanism for benzoxazole formation is proposed on the basis of control experiments and DFT calculations.

Iodophenylsulfonates and Iodobenzoates as Redox‐Active Supporting Electrolytes for Electrosynthesis

“…Since according to the linear sweep voltammograms shown in Figure , a direct oxidation of HFIP in presence of 1e‐NMe 4 is not possible, the generation of hexafluoroacetone most probably proceeds via an indirect pathway mediated by iodine(III). Assuming that the carboxylate group in 1e‐NMe 4 is a sufficiently strong nucleophile, such an indirect HFIP oxidation would be in agreement with our previous study, where we found that nucleophiles can induce the reduction of iodine(III) species of type 2 back to 1 . Consequently, a plausible explanation is provided by the sequence shown in Scheme , where 2e‐NMe 4 is initially formed, followed by nucleophilic attack of the carboxylate group of 1e (potentially forming a tetra‐coordinate [12‐I‐4] iodate) .…”

“…The abovementioned reduction of 2b‐NMe 4 to 1b‐NMe 4 upon removal of the solvent may be ascribed to a β‐elimination releasing one equiv. of HFIP and one equivalent of hexafluoroacetone, as previously observed for 1a‐ClO 4 …”

“…In the course of our ongoing studies on sustainable electrolysis concepts, we have developed the bifunctional mediator salt 1a‐ClO 4 (see Figure ), which is composed of an iodophenyl unit and a trimethylammonium group, attached to each other via an alkylene linker . Species 1a‐ClO 4 is prepared in three steps from phenyl iodide and 4‐chlorobutyryl chloride and was successfully applied for the synthesis of carbazoles and benzoxazoles . Since the oxidation potential of the iodoarene unit is higher than the one of the substrates, 1a was oxidized prior to the chemical transformation (ex‐cell process).…”

“…Furthermore, the anionic unit should not have a negative impact on the generation of the iodine(III) species and the mediated transformation, e. g. as a nucleophile. A deactivation pathway which can be induced by nucleophiles is the previously described reduction of 2 to 1 , potentially via a tetra‐coordinate I(III)‐intermediate and β‐elimination liberating hexafluoroacetone and HFIP . Considering all these requirements, we have selected iodobenzenesulfonates 1b and 1c as well as iodobenzoates 1d – 1f as promising candidates (see Figure ).…”

“…[13] Species 1a-ClO 4 is prepared in three steps from phenyl iodide and 4-chlorobutyryl chloride and was successfully applied for the synthesis of carbazoles and benzoxazoles. [13,14] Since the oxidation potential of the iodoarene unit is higher than the one of the substrates, 1a was oxidized prior to the chemical transformation (ex-cell process). The use of 1a instead of an uncharged iodoarene allows for electrolysis without supporting electrolyte additives and facilitates the recovery of the mediator after completion of electrolysis (a trituration of the crude product with common non-polar solvents yields 1a-ClO 4 in analytical purity with recovery rates � 95 %).…”