Nickel-catalyzed electrochemical carboxylation of unactivated aryl and alkyl halides with CO2

Electrochemical catalytic reductive cross couplings are powerful and sustainable methods to construct C−C bonds by using electron as the clean reductant. However, activated substrates are used in most cases. Herein, we report a general and practical electro-reductive Ni-catalytic system, realizing the electrocatalytic carboxylation of unactivated aryl chlorides and alkyl bromides with CO2. A variety of unactivated aryl bromides, iodides and sulfonates can also undergo such a reaction smoothly. Notably, we also realize the catalytic electrochemical carboxylation of aryl (pseudo)halides with CO2 avoiding the use of sacrificial electrodes. Moreover, this sustainable and economic strategy with electron as the clean reductant features mild conditions, inexpensive catalyst, safe and cheap electrodes, good functional group tolerance and broad substrate scope. Mechanistic investigations indicate that the reaction might proceed via oxidative addition of aryl halides to Ni(0) complex, the reduction of aryl-Ni(II) adduct to the Ni(I) species and following carboxylation with CO2.


General information
All starting materials and reagents are commercially available and were used directly without further purification. All of the reaction vials, stirring bars, carbon felt electrodes were heated to 120 °C under an oven for 2 hours and kept dry in a dryer before used. All the weighting procedures were performed in the glove box. Anhydrous solvents were purchased from Acros Organics and used as received. Molecular sieve (powder) should be heated at 500 °C for 3 hours under Muffle furnace and kept in the glove box. Commercially available chemicals were obtained from Acros Organics, Aldrich Chemical Co., Alfa Aesar, Adamas Beta, ABCR and Energy used as received unless otherwise stated, aryl sulfonates used in the research were provided from our lab 1 . Carbon dioxide (purity: 99.9%, industrial grade) was purchased from Chengdu Xuyuan Chemical Co., Ltd and used directly without further purification. 1 H, 13 C NMR and 19 F NMR spectra were recorded on a Brüker Advance 400 spectrometer ( 1 H: 400 MHz, 13 C: 101 MHz, 19 F: 376 MHz). Chemical shifts (δ) for 1 H, 13 C NMR and 19 F NMR spectra are given in ppm relative to TMS. The residual solvent signals were used as references for 1  GC-MS was obtained using electron ionization (Agilent Technologies 7890B/GC-System and 5977A/MSD). TLC was performed using commercially prepared 100-400 mesh silica gel plates (GF254), and visualization was affected at 254 nm. High revolution mass spectra (HRMS) were recorded on a SHIMADZU LCMS-IT-TOF. ESI-MS were obtained on a Thermo LTQ mass spectrometer. Cyclic voltammetry tests were performed by using CHI 600E potentiostat (CH Instruments, Inc. USA) equipped with the conventional three electrode system with sweep rate of 100 mV•s -1 . The working electrode was a glassy carbon disk electrode (d = 0.3 cm). The auxiliary and reference electrode consisted of a Pt wire and an Ag/AgNO3 (10 mM AgNO3 in CH3CN), respectively.
Glassy carbon should be polished with a polishing cloth before each measurement. Maynuo DC Source meter (M8831, 30V/1A) was applied in the electrolysis. UV-vis spectrophotometer (UV-1800) 4 HCl solution (20 mL) and extracted by EtOAc for 4 times (30 mL × 4). [Supplementary Note: since carbon felt can absorb a significant amount of reaction solution, it was necessary to wash the electrode with EtOAc so as to avoid the residues staying in the electrode.] The combined organic layers were washed with water (20 mL × 2) and brine (20 mL) and concentrated in vacuo. Then the residue was purified by silica gel column chromatography by using the petroleum ether/EtOAc to give out the carboxylic acid 2/4.

General procedure for the electrochemical carboxylation of aryl bromides, iodides and sulfonates
In a 50 mL three-neck flask equipped with a carbon felt cathode (1 cm × 1 cm × 2 cm) and a Zn plate (1 cm × 2 cm), aryl halides 3 (0.3 mmol), Ni(acac)2 (5 mol%, 0.015 mmol, purchased from Adamas), 4,4'-di-tert-butyl-2,2'-bipyridine (dtbbpy, 5 mol%, 0.015 mmol), KO t Bu (0.15 mmol), NaI (1.2 mmol) were loaded in the glove box. Then the mixture was taken out of the box, degassed under vacuum and back-filled with CO2 gas for 5 times (each time lasted for 1 min). After that, 6 mL dry 1methyl-2-pyrrolidinone (NMP, purchased from Acros, super dry grade) was injected into the flask via a syringe and dissolved the mixture under the strong stirring (1000 rp/min) until the mixture becoming transparent. Then two electrodes were submerged into the solution (the effective surface of cathode: approximately 1 cm × 1 cm × 1 cm; anode: approximately 1 cm × 1 cm). Constant current (8 mA) was passed until the starting material was consumed (monitored by Thin Layer Chromatography) at room temperature. After electrolysis, the mixture was acidized by 2 N HCl solution (20 mL) and extracted by EtOAc for 4 times (30 mL × 4). [Supplementary Note: since carbon felt can absorb a significant amount of reaction solution, thus it was necessary to wash the electrode with EtOAc so as to avoid the residues staying in the electrode.] The combined organic layers were washed with water (20 mL × 2) and brine (20 mL) and concentrated in vacuo. Then the residue was purified by silica gel column chromatography by using the petroleum ether/EtOAc to give out the carboxylic acid 4.

General procedure for the electrochemical carboxylation of aliphatic bromides
In a 50 mL three-neck flask equipped with a carbon felt cathode (1 cm × 1 cm × 2 cm) and a Zn plate (1 cm × 2 cm), alkyl bromide 5 (0.5 mmol), NiBr2•DME (10 mol%, 0.05 mmol, purchased from Aldrich), 6,6'-di-methyl-2,2'-bipyridine (20 mol%, 0.1 mmol), anhydrous CsF (0.5 mmol), LiClO4 (1.2 mmol) were loaded in the glove box. Then the mixture was taken out of the box, degassed under vacuum and back-filled with CO2 gas for 5 times (each time lasted for 1 min). After that, 6 mL dry 1-Methyl-2-pyrrolidinone (NMP, purchased from Acros, super dry grade) was injected into the flask via a syringe and dissolved the mixture under the strong stirring (1000 rp/min) until the solution becoming transparent. Then two electrodes were submerged into the solution (the effective surface of cathode: approximately 1 cm × 1 cm × 1 cm; anode: approximately 1 cm × 1 cm). Constant current (8 mA) was passed until the starting material was consumed (monitored by Thin Layer Chromatography) at room temperature. After electrolysis, the mixture was acidized by 2 N HCl solution (20 mL) and extracted by EtOAc for 4 times (30 mL × 4). [Supplementary Note: since carbon felt can absorb a significant amount of reaction solution, thus it was necessary to wash the electrode with EtOAc so as to avoid the residues staying in the electrode.] The combined organic layers were washed with water (20 mL × 2) and brine (20 mL) and concentrated in vacuo. Then the residue was purified by silica gel column chromatography by using petroleum ether/EtOAc to give out the aliphatic carboxylic acid 6.

General procedure for the electrochemical carboxylation of organo (pseudo)halides in nonsacrificial anode manner
In a H-type divided cell equipped with a carbon felt cathode (1 cm × 1 cm × 2 cm, in cathodic chamber) and a carbon felt anode (1 cm × 1 cm × 2 cm, in anodic chamber), organo (pseudo)halides 1/3/5 (0.3 mmol in general, 0.5 mmol of alkyl bromides was used in the experiment), Ni(acac)2 (10 mol%, 0.03 mmol, purchased from Adamas Beta), 4,4'-di-tert-butyl-2,2'-bipyridine (dtbbpy, 10 mol%, 0.03 mmol), KO t Bu (0.15 mmol), 4Å molecular sieve (100 mg), NaI (1. [Supplementary Note: since carbon felt can absorb a significant amount of reaction solution, thus it was necessary to wash the electrode with EtOAc so as to avoid the residues staying in the electrode.] The combined organic layers were washed with water (20 mL × 2) and saturated NH4Cl solution (20 mL) and concentrated in vacuo. Then the residue was purified by silica gel column chromatography by using petroleum ether/EtOAc to give out the carboxylic acids 2/4/6. ◼ Carbon felt was cut into a dice which was about 1 cm × 1 cm × 2 cm and Zn plate was cut into a 1 cm × 2 cm small part (See picture A and B).

Details of the reaction set-ups
◼ The carbon felt and Zn plate were pierced through by a copper hook so as to stabilize the electrode material and make sure the electrode conductible (8~10 cm of copper wire was recommended) (C). Then the prepared electrodes were inserted through a pierced septum, which had a good gas tightness and avoided the CO2 leakage, assembled on the left and right arm of the flask (50 mL

Divided cell setting
◼ The H-type divided cell was designed in our lab. The frit we use is G4 standard. Both carbon felt electrodes were inserted through a pierced septum and placed in each chamber (See picture A-C). It is noteworthy to mention that septum should be wrapped by the Parafilm to make sure the gas tightness.
◼ The divided cell connected with the rubber tude which was from the CO2 Schlenk tude system on the teen joint outlet (See picture D), then displacing the CO2 gas for 5 times (1 min per time).
CO2 airbag connected with the flask during electrolysis.

Reaction development and optimization
Supplementary

CVs and UV-vis spectroscopy for nickel-catalytic system
All of the cyclic voltammetry experiments were conducted via the three-electrode system. The

Reaction of pre-catalyst LNi(acac)2-catalyzed reaction of 3h with CO2
In a 50 mL three-neck flask equipped with a carbon felt cathode (1 cm × 1 cm × 2 cm) and a Zn plate Then the residue was purified by silica gel column chromatography using petrolumn ether/EtOAc to give out the final product 4h in 78% yield.

Reaction of Ni(COD)2-catalyzed reaction of 3h with CO2
In a 50 mL three-neck flask equipped with a carbon felt cathode (1 cm × 1 cm × 2 cm) and a Zn plate Then the residue was purified by silica gel column chromatography by using petrolumn ether/EtOAc to give out the final product 4h in 65% yield.

Preparation of adduct 1-1 3
The oxidative addition complex  38 (s, 9H). The spectra data was consistent with the reported literature.

Adduct 1-1 catalyzed carboxylation of 3ac with CO2
In a 50 mL three-neck flask equipped with a carbon felt cathode (1 cm × 1 cm × 2 cm) and a Zn plate Supplementary Note: Most of inert aryl halides, especially the inert aryl chlorides, have consumed large amount of electricity (up to 29.8 F/mol). Even the non-activated alkyl bromides have also consumed 13 F/mol electricity in average. It is also noted that it takes longer time for the carboxylation with inert aryl halides and alkyl bromides. We suppose that in the cases of inert aryl chlorides, the rate of oxidative addition between inert C-Cl bond and nickel(0) center is slow and other undesirable electrochemical processes might exist such as Zn 2+ precipitation (Zn 2+ dissolved from zinc anode may compete to reduce on the cathode since its reduction potential is -0.76 V (vs SHE)) or hydrogen evolution reaction of residual water on the cathodic surface, which reduces the electrolytic efficiency and causes the extra charge consumed. Such non-productive processes consumed the charge and did not help production formation. Compared to the inert aryl chloride substrates, some other relatively active aryl halides such as 3h, 3g, 3i (bromides), 3u, 3v, 3w (iodides), 3y, 3ab (sulfonates) are in less consumed electricity (5 F/mol average, see in Table S3). We suppose that the rate of oxidative addition in these substrates with nickel catalyst is faster than the inert ones, 22 which reduces the electricity loss from other electrochemical processes.         The spectra data was consistent with the reported literature.