Continuous‐Flow Electrochemical Generator of Hypervalent Iodine Reagents: Synthetic Applications

Abstract

An efficient and reliable electrochemical generator of hypervalent iodine reagents has been developed. In the anodic oxidation of iodoarenes to hypervalent iodine reagents under flowconditions,the use of electricity replaces hazardous and costly chemical oxidants.U nstable hypervalent iodine reagents can be prepared easily and coupled with different substrates to achieve oxidative transformations in high yields. The unstable,e lectrochemically generated reagents can also easily be transformed into classic bench-stable hypervalent iodine reagents through ligand exchange.T he combination of electrochemical and flow-chemistry advantages largely improves the ecological footprint of the overall process compared to conventional approaches.

Electrochemical‐Induced Ring Transformation of Cyclic α‐(ortho‐Iodophenyl)‐β‐oxoesters

“…The latter were obtained by oxidation of the corresponding iodobenzene derivatives with oxone by following a literature protocol . As also observed by others, donor‐substituted PIFA reagents (e.g. with R 3 =OMe) cannot be obtained by this procedure.…”

Reactions between Diazo Compounds and Hypervalent Iodine(III) Reagents

“…Gaining a clear understanding of the detailed reaction mechanisms will facilitate new reaction design and the unique accessibility of valuable molecules toward practical and atom‐efficient processes. Synthetic applications. The further application of this combination concept in large‐scale manufacturing and new synthetic technologies including flow chemistry and electrochemistry deserves more attention. In addition, the compatibility of polypeptides or proteins with diazo compounds and hypervalent iodine(III) compounds (Scheme ) hints at a prolific future for the practical late‐functionalization of drugs and native proteins.…”

C−H Oxygenation Reactions Enabled by Dual Catalysis with Electrogenerated Hypervalent Iodine Species and Ruthenium Complexes

“…This combination of electrochemistry and in situ spectroscopy enabled us to study the generation of otherwise unstable electrochemically generated iodine(III) reagents. Initially, the anodic oxidation of iodobenzene in trifluoroethanol (TFE) was monitored and showed almost full conversion of the aryl halide after 2.5 h at 10 mA (Figure a, i) . Subsequently, the anodic generation of hypervalent iodine 11 b from TFA and iodobenzene was completed with only slightly prolonged reaction times within 3 h (Figure a, ii).…”

“…[4] Despite indisputable advances by the groups of Mei, Sanford, and Ackermann, [5] electrochemical CÀHo xygenations [6] of challenging arenes by weak coordination [7] have thus far proven elusive.T he reported metalcatalyzed C À Ho xygenations largely require cost-intensive palladium complexes and were inherently limited to strongly coordinating N-directing groups,s uch as oximes and pyr-idines. [5] In sharp contrast, CÀHoxygenations by synthetically useful weak O-coordination have not been realized in terms of sustainable electrocatalysis.Instead, highly reactive hypervalent iodine(III) reagents, [8,9] such as (diacetoxyiodo)benzene and [bis(trifluoroacetoxy)iodo]benzene,a re required in overstoichiometric quantities,which calls for strong chemical oxidants for their synthesis and leads to equimolar amounts of undesired halogenated waste products during the CÀH functionalization process.C ontrarily,w eh erein present am echanistically distinct strategy to address this molecular challenge,w hich orchestrates the catalytic electro-regeneration [10] of hypervalent iodine(III) reagents with ruthenium-(II)-catalyzed [11,12] CÀHf unctionalizations ( Figure 1). Salient features of our findings include a) the first electrocatalyzed CÀHoxygenations by weak coordination, b) the user-friendly electrochemical generation of hypervalent iodine reagents, c) ioda/ruthena-electrocatalyzedC À Hfunctionalizations that combine the advantages of ruthenium-catalyzed C À Hactivation with electrocatalytic hypervalent iodine chemistry,a nd d) mechanistic studies by experiment, computation, cyclic voltammetry,a nd in operando NMR spectroscopy.…”