Copper/TEMPO Redox Redux: Analysis of PCET Oxidation of TEMPOH by Copper(II) and the Reaction of TEMPO with Copper(I)

Abstract

Copper salts and organic aminoxyls, such as TEMPO (2,2,6,6-tetra­methyl­piper­idine-N-oxyl), are versatile catalysts for aerobic alcohol oxidation. Previous reports in the literature contain conflicting proposals concerning the redox interactions that take place between copper­(I) and copper­(II) salts with the aminoxyl and hydroxylamine species, TEMPO and TEMPOH, respectively. Here, we reinvestigate these reactions in an effort to resolve the conflicting claims in the literature. Under anaerobic conditions, CuIIX2 salts [X = acetate (OAc), trifluoroacetate (TFA), and triflate (OTf)] are shown to promote the rapid proton-coupled oxidation of TEMPOH to TEMPO: CuIIX2 + TEMPOH → CuIX + TEMPO + HX. In the reaction with acetate, however, slow reoxidation of CuIOAc occurs. This process requires both TEMPO and HOAc and coincides with the reduction of TEMPO to 2,2,6,6-tetra­methyl­piper­idine. Analogous reactivity is not observed with trifluoroacetate and triflate species. Overall, the facility of the proton-coupled oxidation of TEMPOH by CuII salts suggests that this process could contribute to catalyst regeneration under aerobic oxidation conditions.

One-Pot Difunctionalization of Aryldiazonium Salts for Synthesis of para-Azophenols

“…To obtain the information of this difunctionalization pathway, free radical trap experiments ( Liu et al, 2019 ; Liu et al, 2020 ) with using 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) or 2,6-di-tert-butyl-4-methylphenol (BHT) did not give the target product 2a or the corresponding radical coupling byproduct with the assistance of HRMS ( Supplementary Scheme S1A in SI). Those inhibited results might ascribe to the acidity of BHT ( Huang and Lumb, 2019 ) or oxidability of TEMPO ( Ryan et al, 2019 ) influencing on the stability of diazonium salts in the standard reaction. So an ionic process was still heavily weighted in the optimal process.…”

CuII/TEMPO‐Catalyzed Enantioselective C(sp3)–H Alkynylation of Tertiary Cyclic Amines through Shono‐Type Oxidation

“…Addition of chiral acetylide species 10 (derived from Cu I and alkyne 2 in the presence of base) to electrophilic 9 results in the formation of product 3 or 4 . Active Cu I could be obtained by either Cu II reacting with TEMPO‐H or cathodic reduction of Cu II . Alternatively, other cooperative mode involving both Cu II and TEMPO in the key oxidative step for the iminium formation could not be ruled out at this stage …”

“…Active Cu I could be obtained by either Cu II reacting with TEMPO-H or cathodic reduction of Cu II . [29] Alternatively, other cooperative mode involving both Cu II and TEMPO in the key oxidative step for the iminium formation could not be ruled out at this stage. [30] In summary, we have demonstrated the first example of Cu/TEMPO co-catalyzed electrochemical enantioselective oxidative cross-coupling between cyclic tertiary amines and terminal alkynes using a novel chiral bisoxazoline ligand in an undivided cell, affording diverse chiral C1-alkynylated THIQs with good to excellent enantioselectivity.…”

Paramagnetic species in catalysis research: a unified approach towards (the role of EPR in) heterogeneous, homogeneous and enzyme catalysis

“…183 Considering the dominance of paramagnetic species in copper-containing alcohol oxidation catalysts, Stahl et al, recently explored the mechanism of aerobic alcohol oxidation with Cu/nitroxyl systems. [208][209][210][211] In a series of studies, the authors evaluated the performance of various Cu/nitroxyl catalytic systems containing Cu/TEMPO (where TEMPO ¼ 2,2,6,6-tetramethylpiperidine-N-oxyl) and Cu/DBED, DMAP (where DBED ¼ N-N 0 -di-tert-butylendiamine, and DMAP ¼ p-(N,N-dimethylamino) pyridine). 210,212 Combined EPR, UV-vis and cyclic voltammetry (CV) indicated a two-stage catalytic mechanism involving catalyst oxidation, in which Cu 11 and TEMPO-H are react with O 2 and substrate oxidation, mediated by Cu 21 and the nitroxyl radical via a Cu 21 -alkoxide intermediate.…”