Cobalta‐Electrocatalyzed C−H Activation in Biomass‐Derived Glycerol: Powered by Renewable Wind and Solar Energy

Abstract Aqueous glycerol was identified as a renewable reaction medium for metalla‐electrocatalyzed C−H activation powered by sustainable energy sources. The renewable solvent was employed for cobalt‐catalyzed C−H/N−H functionalizations under mild conditions. The cobalta‐electrocatalysis manifold occurred with high levels of chemo‐ and positional selectivity and allowed for electrochemical C−H activations with broad substrate scope. The resource economy of this strategy was considerably substantiated by the direct use of renewable solar and wind energy.

During the last decade, the development of efficient electrocatalysis for the interconversion of renewable energies, such as wind and solar energy,into value-added products has attracted significant attention. [1] Ap romising approacht oc onvert the sustainable energy into chemical energy is the conversion of small molecules (e.g.,b yw ater oxidation) into alternative fuels. [2] The splitting of water by electrolysis is separatedi n two half-cell reactions, namely the cathodic hydrogen evolution reaction (HER) and the anodic oxygen evolution reaction (OER). [3] In case of the OER, however,k inetic limitations result in ah igh-overpotential, [4] which renders the overall process highly energy consuming and as of yet too costly for largescale applications. Also, the resulting oxygen is of minor value, which lowers the overall economic footprint. [5] Of greater interest would be the production of value-added productso nt he anodic half-cell reaction. [6] In the meantime, CÀHa ctivation [7] has emerged as at ransformativetool in molecular sciencesb yits applications towards materials ciences, [8] drug discovery, [9] and complex bioactive natural product synthesis. [10] Despite indisputable advances, in the scenario of oxidative CÀHf unctionalization stoichiometric amountso fm etal-based, often costly,a nd toxic oxidants are commonlyr equired. Therefore, the merger of electrosynthe-sis [11] and oxidative CÀHa ctivation has recently enabledt he use of electricity as the terminal oxidant, obviating the use of chemicalr edox reagents. [12] In this context, our group as well as Lei and co-workers recently reported on ac obalta-electrocatalyzed [13] CÀH/NÀHa lkyne annulation at ambient temperature. [14] An energy-relevant, beneficial asset of this strategy was represented by the HER as the cathodic half reaction. Nevertheless, most of the metal-catalyzedC ÀHa ctivations rely on the use of harmful, fossil-derived, and noxious solvents, such as halogenated solvents. [15] To address these major challenges, continuous efforts wered irected towards the identification of less hazardous, environmentally benign solvents for the inherently sustainable CÀHactivation approach. [16] Competing undesired cobalt-catalyzed methoxygenation reactions [17] wereo bserved when methanol was used as ag reen solvent. In stark contrast, glycerolh as arguably thus far not been employed as ab iomass-derived reactionm edium in CÀHf unctionalization processes.H owever,i tw ould serve as an ideal candidate in sustainable electrochemical transformationsb ecause of its high conductivity,o bviating the use of additional conducting salts. [18] Biocompatibleg lycerol can be classifieda san on-flammable solvent, and it is produced on large scale as the waste product of biodiesel production. [19] Importantly,t oi mprove the overall resource economy [20] of the strategy,w ed ecided to power the desired oxidative transformation with renewable solar and wind energy (Figure1). [21] We initiated our studies by probing variousr eactionc onditions for the envisioned electrochemical CÀHt ransformation of substrate 1a with alkyne 2a in biomass-derived glycerol (Table 1a nd Table S1 in the Supporting Information). [22] Thus, the desired product 3aa was obtained in excellent yield when 10 mol %C o(OAc) 2 ·4 H 2 Ow as used as the catalyst (Table 1, entry 1). Here, au ser-friendly and cost-efficients etup in an undivided cell, with graphite felt (GF) and platinum plate (Pt) as   anode and cathode material, respectively,p rovedv iable. The robust cobalt catalyst waso perative under protic conditions and fully tolerant of H 2 Oa nd glycerol. The addition of H 2 Ow as found to be essential because ah igher concentration of glycerol led to ad ramatic decrease in the product yield (entry 2). Sodium pivalate proved to be the optimal additive (entries3 and 4). It is particularly noteworthy that commonly used toxic solvents as well as alternative renewable solvents, other than glycerol, were less efficient (entries [5][6][7][8][9][10][11][12]. This can be explained by the high dielectric constant of glycerol (e = 42.5 at 25 8C), [23] which renders it as uitable solvent for organic electrochemistry,a nd furthera ddition of expensive conductinge lectrolytes can thereby be avoided (entries 9-11). Owing to the high viscosity of glycerol, the reaction temperature neededt ob es lightly adjusted to 40 8Ct od eliver the desired product 3aa in high yield, [22] followingt he Stokes-Einstein equation. Notably,t he reactione ven proceeded efficiently with lower loadings of the cobalt(II) catalyst (entry 13), whereas the use of cobalt(III) salts yielded product 3aa in similar yields (entry 14). Controle xperimentsv erified the necessity of the cobalt catalysta nd of the electric current (entries 15 and 16). Furthermore, cyclic voltammetry clearly indicated ac obalt oxidation, prior to substrateors olvent degradation. [22,24] With the optimized reaction conditions in hand, we probed its versatility in the CÀH/NÀHf unctionalizationso fb enzamides 1 in biomass-derived glycerol( Scheme 1a). Thus,t he robust cobalta-electrocatalysis enabled the efficient CÀHa cti-vation of differently decorated amides 1 in aqueous glycerol. Notably,v arious functional groups, such as ether and fluoro groups,w ere fully tolerated. Owing to the lower solubility of amide 1b,t he reaction was performed under sonification [19c] to furnish improved yields.F urther,i odoarene (1f)w as smoothly converted to the desired product 3fa,a lbeit with slightly diminished yield. The positional selectivity for meta-substituted arene 3ja in the electrochemical CÀHa ctivation wasc ontrolled by repulsive steric interactions. The use of glycerol/H 2 Oa sa solventm ixture extendedt he scope to thioethers 3ga,a nd even furan 3ka was converted likewise (Scheme 1b). Finally, the robustness of the sustainable cobalta-electrocatalyzed CÀH/NÀHf unctionalization could further be illustrated by the step-economical synthesis of pyridones 3la and 3ma through alkenylic CÀHa ctivation.
The robustness of the broadlya pplicable electrochemical CÀH/NÀHa ctivation in biomass-derived glycerolw as further probedw ith substituted alkynes 2 (Scheme 2). Hence, the generality of the green cobalta-electrocatalytic CÀHa ctivation was reflected by the effective annulation of aw ealth of alkynes 2, fully tolerant of valuablef unctional groups,i ncluding cyclopropyla nd ether groups as well as sensitive alkyl chloride and nitrile substituents.
Moreover,w ew ere pleased to find that the cobalta-electrocatalyzed CÀH/NÀHa ctivation in biomass-derived glycerol was not limited to alkynes 2.I ndeed, oxidative CÀHa nnulation was also accomplished with the challenginga llene 4,using as lightly lower constant current of 2mA( Scheme3). Finally,w ew anted to significantly improvet he resource economy of our sustainable electrocatalysis in ar enewable solvent by the directu se of renewable energy sources, such as photovoltaics or wind power. In general, applying ac onstantcurrent electrolysis, the potential at the workinge lectrode, hence the anode,w ill adjust until the substrate with the lowest oxidation potential gets consumed. In stark contrast, in the presentedc obalta-electrocatalytic approach, the working potentialr emains constant until the reaction is completed, owing to its catalytic nature.This offers the possibility to utilize electric current from inexpensive and diversep owers ources. With this in mind, we were inspired by the direct use of inexpensive and commercially availablep hotovoltaic cells as the power supply for the depicted constant-current electrolysis (Scheme 4). [20] The applied current was thereby fixed and regulated by ac ustom-made constant-current regulator.T oo ur delight, the user-friendlys unlight-powered setupd elivered the product 3aa in ac omparable yield of 73 %. The reaction with the solar panel was performed on the 20th of December 2018, the shortest day of the year.
The direct utilization of sunlight for chemical bond transformations has recently attracted considerable attention. [25] In contrast, the direct exploitationofwind powertodrive electrocatalytic transformationsi s, to the best of our knowledge, thus far unprecedented. Applying ac ommerciallya vailable wind turbine andad igital current regulator in ap roof-of-concept study,w ep erformed the desired cobalta-electrocatalyzed CÀH/ NÀHa ctivation in biomass-derived glycerol to generate isoquinolone 3aa in comparable yields (Scheme 5). The slightly diminished reaction outcome can be explained by small current variations. These results clearly show that the envisionedm etalla-electrocatalyzed CÀHa ctivation can be put into practice with as imple and renewable power source to drive to the desired transformation.
In summary,w eh ave disclosed the unprecedented application of biomass-derived glycerol as ar eaction medium for electro-enabled CÀHa ctivation reactions. The resource economy of our strategy was substantiated by the direct use of renewable energies for chemical CÀC/NÀCb ond formations, with H 2 as the only side product by facile HER. [6] Thus, aC p*-free cobalt catalyst enabled the sustainable CÀHa ctivation of amides in the absence of toxic metal oxidants. The mild CÀH/ NÀHf unctionalization readily occurred in aqueous glycerol at 40 8C. Importantly,w ea lso demonstrated that renewable solar and wind energy can directly be employed for electrocatalytic CÀHa ctivations. The merger of renewable solvents and alternative forms of energy for molecular catalysis should prove invaluablef or establishing more sustainable future energy economies.
gel for the synthesiso fs tarting material and RainerE hrhardt for the constant currentr egulators.

Conflict of interest
The authors declare no conflict of interest.