Cobalt-Salen Catalyzed Electroreductive Alkylation of Activated Olefins

Institut de Chimie et des Matériaux Paris-Est (UMR 7182), CNRS, UPEC, Université Paris-Est, Equipe Electrochimie et Synthèse Organique, 2 Rue Henri Dunant, 94320 0iais, France Institut de Physique Nucléaire, CNRS, Université Paris Saclay, 91406 Orsay Cedex, France Chimie ParisTech PSL Research University, CNRS 2027, Institute of Chemistry for Life and Health Sciences (i-CLeHS), 75005 Paris, France


Introduction
In the context of sustainable organic chemistry, electrosynthesis has gained a renewable interest because of its relevant green aspects [1][2][3].is versatile process involves electrons as clean surrogates of dangerous, toxic, hazardous reductive or oxidative reagents.Furthermore, the possibility to generate in situ the active catalytic species, or the disposal of high valuable products in one step reaction pathway is on contemporary concerns.Various papers of our laboratory report the activation of aryl halides under cobalt or nickel catalysis for Csp2-Csp2 bond formation (biaryl access) [4][5][6] or Csp2-Csp3 bond formation (conjugate addition reaction) [7,8] by using the sacrificial anode process [9].However, less attention has been devoted to the Csp3-Csp3 bond formation.Some years ago, we have described the coupling of halogenated and pseudohalogenated glycerol carbonate with electron deficient olefins under nickel catalysis in greener solvent [10].
e most common method of alkylation of activated olefin is a multistep procedure requiring the preparation of the alkylcopper reagent and then its reaction with the activated olefin [11]. is can be circumvented advantageously by activation of the alkyl halide by a transition metal complex and its further reaction with the electrophile.Such reactions can be carried out in one step procedure, in mild conditions.In most cases, the transition metal complex is reduced in situ either chemically, by Zn [12][13][14] or Mn [15], or electrochemically [16].
e conjugate addition reactions catalyzed by transition metal complexes involve mainly nickel [8,[17][18][19] or cobalt [7,[20][21][22][23] complexes or chromium compounds [24][25][26].In the case of cobalt [20][21][22][23], the catalyst is generally coordinated to Schiff base ligands, such as the vitamine B 12 and cobaloximes, and the addition product is obtained with good yield in one step procedure.However, the reaction was generally conducted in a divided cell, by controlled potential electrolysis, and vitamin B 12 is an expensive catalyst [20][21][22][23].Few models of vitamin B 12 , such as N,N′ethylenebis(salicylideneiminato)-cobalt (noted CoSalen), more simple and cheaper, have been then used as catalyst for the heterocoupling of organic halides and alkylation of alkyl halides with activated olefins [23].In most cases, the reactions were carried out in hexamethylphosphoramide or hexamethylphosphoramide/tetrahydrofuran, in a double compartment electrochemical cell, on a mercury pool cathode and with poor and unsatisfactory yields.
us, in the course of our work on the electrochemical activation of organic halides using the sacrificial anode process [9], we have found that alkylation of activated olefins can be carried out with a simple and cheap cobalt complex formed in situ.
is allowed us to show that the combined use of cobalt-Salen (as catalyst) with the undivided electrochemical cell process offers substantial advantages in the reductive coupling of 2-bromooctane and methyl vinyl ketone (MVK) [27].We report here a systematic study of some examples of reductive coupling of alkyl halides and activated olefins using cobalt complexes to assess the influence of the experimental parameters (ligand, solvent, temperature, and electrolysis conditions) in order to optimize the yield and to get a better insight into the electroassisted catalytic mechanism.

Experimental
All solvents and reagents were purchased from commercial sources and used as received.Dimethylformamide (DMF) was stored under an argon atmosphere.Electrosyntheses were carried out either in a double compartment cell or in an undivided electrochemical cell.
Electrosyntheses carried out in a double compartment electrochemical cell equipped with a fritted glass separation were performed with an anode and a cathode made of carbon fibers (total geometric area of 30 cm 2 , from Prolabo).Both cathodic and anodic compartments were filled with 25 mL of DMF solution containing tetrabutylammonium bromide, noted TBABr (0.236 mol•L −1 ) and tetrabutylammonium iodide, noted TBAI (0.054 mol•L −1 ) and kept under argon atmosphere.
e catalyst precursor was introduced in the cathodic compartment (15 mmol•L −1 ), and the solution was stirred during 15 minutes.
In both cases, the electrolysis was run at constant current density (0.3 A•dm −2 ) or constant potential (−1.2 V or −1.6 V). e cathode potential was measured and referenced to a saturated calomel electrode (SCE) which was placed in a separate compartment containing the solvent and the supporting electrolyte.e reaction was monitored by gas chromatography analysis (GC) using ethyl undecanoate as internal standard and was stopped after 2-bromooctane was totally consumed.e reaction mixture was then hydrolyzed with hydrochloric acid (1 N, 30 mL). e aqueous layer was extracted with diethyl ether (2 × 30 mL).
e reaction products were identified by 1 H and 13 C-NMR (Brucker 200 MHz) in CDCl 3 and mass spectrometry (Finnigan ITD 800).GC analyses were carried out using a 25 m DB1-capillary column.Elemental analyses were made by the Service Central de Microanalyses (CNRS, Lyon).Physical and spectral data are given as follows.

Results and Discussion
Addition of 2-bromooctane to methylvinylketone (MVK) was studied as the model reaction in DMF as solvent (equation ( 1)): We have first analyzed the influence of the cobalt ligands on the conjugate addition reaction yield (Table 1).
In the absence of cobalt salt (run 1) or ligand (run 2), poor yields of alkylated product are obtained.Among the examined ligands, H 2 Salen (run 3 and 4) and ephedrine (run 7) are the most appropriate ones to provide highest chemical yields for the conjugate addition reaction.
erefore, the supposed active catalyst is a simple and cheap cobalt complex which can be prepared in situ.
Solvent influence was also examined (Table 2).We found that the best solvent is dimethylformamide either pure (run 1) or in the presence of proton donor.For example, in the case of NH 4 Cl (5.10 −2 mol•L −1 ) as supporting electrolyte added to DMF (run 2) or DMF/ethanol (EtOH) (1/1) mixture (run 4), the yields, calculated by GC analysis with internal standard, are, respectively, 55% and 59%.Despite the fact the coupling product was obtained with moderate yields in solvent mixtures such as DMF/EtOH (1/ 1) or DMF/Acetonitrile (AN) (1/1), pure EtOH and AN are not suitable solvents (see Table 2).
Anyhow, for reaction carried out in pure DMF (Table 1, run 3), we have found that the yield was very dependent on the temperature: 27% at 20 °C, 61% at 80 °C.Also, we have noticed that if the electrolysis potential was more negative than −1.2 V/SCE, both the chemical yield (26%) and the Faradaïc yield decrease.
is could be due to the direct reduction of the MVK which occurs at ca −1.7 V/SCE.In this case, other reactions, such as MVK polymerization, take place.
e stoichiometry of the reaction between MVK and 2bromooctane was examined.e results reported in Table 3 reveal the importance of using excess amount of MVK to improve the yield of the coupling product.However, a large excess of olefin does not improve significantly the yields (run 3 and 4).
Finally, we have observed that the nature of the anode is crucial to form selectively the addition product.Indeed, results in Table 4 show that an iron rod is the most efficient anode, indicating a possible role of the cations anodically generated by its oxidation during the electrolysis.
Such a crucial role of anodically generated cations has also been reported in other processes related to electroassisted reductions of organohalides catalyzed by nickel complexes [31].eir occurrence in this reaction was analyzed by cyclic voltammetry and showed the possible formation of a catalytically active Co-Salen-Fe binuclear complex [27].Indeed, Table 5 recapitulates the comparative analysis of the significant results obtained for reactions carried out with CoSalen, in various conditions, by using either a double compartment or an undivided electrochemical cell.It clearly appears from these results that both CoSalen complex and Fe II cations issued from the anode dissolution are needed to allow the product formation with satisfactory yields (Table 4, run 3).
Table 6 reports the results obtained in the reaction of the three classes of alkyl halides with electron deficient olefins under the optimized experimental conditions issued from the above described results.ese results show that the addition product yield is low for a primary alkyl bromide (run 1-3) and medium for a secondary (run 4 and 5) or a tertiary alkyl bromide (run 6).e best yields are obtained for the reaction of 2-octyl bromide as secondary alkyl halide either with acrylonitrile (run 9), MVK (run 8), and dimethyl maleate (run 10).e reaction yield is lower if the olefin is disubstitued (run 11-13).Note that same trend has previously been observed in the arylation of activated olefins [32].In view of these results, it appears that the coupling reaction is regioselective, without formation of 1, 2-addition product.Alkane and alkene which are produced, respectively, by a direct electrochemical reduction and by dehydrohalogenation reaction are the only byproducts observed.Finally, this study shows that the reaction procedure is more efficient when performed with secondary or tertiary alkyl halides than with primary alkyl halides.
is observation suggests that radical R • resulted from alkyl halide reduction may be involved in the reaction Journal of Chemistry mechanism [27]. is radical is trapped by the electron deficient olefin added in excess (2.5 equiv.).e heteronuclear Co II -Salen-Fe II complex prepared in situ from CoSalen and from the release of Fe II cations arising from the oxidation of the anode (equation ( 2)) is likely the key active species [27].
is complex is stable enough to promote the electroreductive coupling to some extent.Indeed, the continuous release of iron cations during the process is responsible for the Salen ligand displacement to produce Co II and Fe II Salen (equation ( 3)).ese two species do not catalyze the coupling reaction.
is unwanted reaction accounts for the relatively moderate yields, around 50% under the optimized conditions.

Conclusion
If β-elimination of HX from alkyl halides is a classic reaction in organic chemistry to get olefins, the described electrosynthesis procedure allows activation of alkyl halides and to some extent the further reaction with electron deficient olefins.From a methodological point of view, the conjugate       addition products are obtained from available substrates, and the catalyst is generated in situ from cheap cobalt salt and Salen in an undivided cell fitted with an iron rod. is method based on the use of electricity as green reagent is accompanied by inherent release of iron salt which is not considered as toxic.
is investigation also shows the crucial role of the anodically generated metallic cations with a particular emphasis on iron.
is study completes advantageously the described voltammetric analysis and confirms the hypothesis of the formation of a catalytically active binuclear Co-Salen-Fe complex during the electrosynthesis.

Data Availability
e NMR source data used to support the findings of this study are available from the corresponding author upon request.
Table 6: Electroreductive alkylation of activated olefins electrocatalyzed by cobalt-Salen in an undivided cell with an iron anode.

Table 2 :
Results of the reductive coupling reaction of 2-bromooctane with methylvinylketone in various solvents under CoCl 2 + H 2 Salen catalysis.

Table 3 :
Stoichiometric study of the reaction between MVK and 2bromooctane.

Table 5 :
Results of the conjugate addition of 2-bromooctane to methylvinylketone, catalyzed by Co I Salen − , in DMF solution and with various electrolysis conditions.