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Mechanistic investigation of the iron-mediated electrochemical formation of β-hydroxyesters from α-haloesters and carbonyl compounds
Journal of
Electroanalytical Chemistry Journal of Electroanalytical Chemistry 578 (2005) 63–70 www.elsevier.com/locate/jelechem
Mechanistic investigation of the iron-mediated electrochemical formation of b-hydroxyesters from a-haloesters and carbonyl compounds Olivier Buriez *, Muriel Durandetti *, Jacques Pe´richon Laboratoire dÕElectrochimie, Catalyse et Synthe`se Organique, UMR CNRS 7582, Universite´ Paris 12, 2-8 Rue Henri Dunant, 94320 Thiais, France Received 22 September 2004; received in revised form 29 November 2004; accepted 6 December 2004 Available online 8 February 2005
Abstract The electrochemical behavior of FeI in the presence of a-haloesters has been studied by means of cyclic voltammetry and preparative-scale electrolyses with the intent to investigate the electrochemical coupling reaction between a-haloesters and carbonyl compounds performed in the presence of FeBr2 and a sacrificial iron anode. It is established that the reaction is initiated by the electrogeneration of an iron (I) species, which has to be stabilized by the presence of 2,2 0 -bipyridine (bpy). However, the reactivity of the electrogenerated FeI is governed by the bpy concentration. Indeed, for bpy/Fe ratios higher than or equal to 3, an outersphere electron transfer has been shown between FeI and a-haloesters, but no coupling product was obtained under these conditions. Conversely, for smaller bpy/Fe ratios the coupling reaction occurs, suggesting the existence of an oxidative addition between FeI and a-haloesters. The presence of a sacrificial iron anode in preparative-scale experiments is useful to decrease the bpy/Fe ratio by generation of Fe2+ cations. 2005 Elsevier B.V. All rights reserved. Keywords: Cyclic voltammetry; Cyclohexanone; 2,2 0 -Bipyridine; a-Haloesters; Iron
1. Introduction Among the numerous coupling reactions leading to carbon–carbon bond formation, the Reformatsky reaction is still of high current interest [1–3]. This reaction, discovered in 1887, allows the preparation of b-hydroxyester compounds from a-haloesters and aldehydes or ketones in the presence of zinc [4]. Since the reaction is initiated by insertion of zinc into the halogen–carbon bond, most efforts have been focused on the activation of zinc [5–9]. Nevertheless, in the past decade, replacement of zinc with another metal such as chromium *
Corresponding authors. Tel.: +33 1 49 78 11 41; fax: +33 1 49 78 11
48. E-mail addresses: [email protected] (O. Buriez), [email protected] (M. Durandetti). 0022-0728/$ - see front matter 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.jelechem.2004.12.020
[10], indium [11,12], or manganese [13,14] has been attracting increased attention. Furthermore, and alternatively to these chemical processes, we developed in our group an electrochemical method for the Reformatsky reaction. This was formerly achieved in the presence of a nickel–bipyridine complex as the catalyst and a sacrificial zinc anode [15]. Then, we discovered an electrochemical method catalytic in both chromium and nickel salts using a sacrificial stainless steel or iron rod anode, which raised the question of the role of the iron salts [16]. More recently, we reported an original version of the Reformatsky reaction using FeBr2 in the presence of 2,2 0 -bipyridine and a sacrificial iron rod anode (Scheme 1) [17]. This last electrochemical method, which uses very simple experimental conditions in comparison with known chemical processes, enables the formation of
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O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70
R
R' +
Cl
-
1) e , FeBr2,bpy
O
O
R' R HO
DMF, Fe anode
O
2) H+
2. Experimental
O O
Scheme 1. Reformatsky-type reaction using an electro-assisted ironcomplex.
[Fe(bpy)3]2+
+ e-
E˚= -1.25 V
[Fe(bpy)3]+
[Fe(bpy)3]+
+ e-
E˚= -1.43 V
[Fe(bpy)3]
[Fe(bpy)3]
+ e-
E˚= -1.71 V
[Fe(bpy)3] -
Scheme 2. Reduction of [Fe(bpy)3]X2 in dimethylformamide; potentials vs. the saturated calomel electrode.
b-hydroxyesters in good to high yields (60–80%) [17]. However, the mechanism leading to the coupling product under these conditions remains to be elucidated. This work is required to improve our reactions and to discover other useful syntheses using iron as the catalyst. This study has been investigated by means of cyclic voltammetry and preparative-scale electrolyses. The electrochemical behavior of iron (II) in the presence of 3 molar equivalents of 2,2 0 -bipyridine (bpy) is well documented. In dimethylformamide, the cyclic voltammogram of [Fe(bpy)3]X2 exhibits three successive reversible monoelectronic steps (Scheme 2). It is admitted that the reductive processes on [Fe(bpy)3]2+ are all ligand-based and the oxidation process is metal-centered [18–23]. Despite their stability on the time-scale of cyclic voltammetry, the [Fe(bpy)3]+ and [Fe(bpy)3] complexes are rather unstable on a longer time-scale and dissociate according to Scheme 3 [24]. More importantly, it has been shown that the complex formed between Fe2+ ions and 2,2 0 -bipyridine in the molar ratio 1:1 is exclusively the entity [Fe(bpy)3]2+ [25]. To our knowledge, no studies have yet been conducted with a-haloesters and carbonyl compounds in the presence of iron (II). Herein, we report the electrochemical behavior of FeBr2 in dimethylformamide, in the presence of 2,2 0 -bipyridine, a-haloesters, and cyclohexanone. We show especially that the reaction leading to the formation of b-hydroxyesters is governed by the bpy/Fe ratio.
2 [Fe(bpy)3]+
[Fe(bpy)3]2+ + [Fe(bpy)3]
[Fe(bpy)3]
bpy
[Fe(bpy)2]
Fe(s) + 2 bpy
Scheme 3.
+
[Fe(bpy)2]
2.1. Chemicals Dimethylformamide (from SDS) was used without purification. Iron bromide (Aldrich), 2,2 0 -bipyridine (Acros), methyl 2-chloropropanoate (Aldrich), methyl 2-bromopropanoate (Janssen), and cyclohexanone (Aldrich) were used as received. TBABF4 (Fluka), used as the supporting electrolyte, was recrystallized from diethylether and dried at 60 C under vacuum. 2.2. Instrumentation Cyclic voltammetry experiments were performed at room temperature (RT) under argon in a 3-electrode cell using an EG&G model 273A potentiostat. The reference electrode was an SCE (Tacussel), which was separated from the solution by a bridge compartment filled with the same solvent/supporting electrolyte solution used in the cell. The counter electrode was a gold wire. The working electrode was a disk obtained from a cross-section of platinum wire (diameter 500 lm) sealed in glass. Preparative-scale electrolyses in the presence of iron (II), at a constant concentration, were carried out in a divided H cell. The cathode was a gold grid, with an approximately 10 cm2 apparent surface area, and the counter electrode (anode) was an iron rod. A SCE was used as the reference. The in situ cyclic voltammetry was performed at a microelectrode set in the cathodic compartment, the gold grid then being used as a counter electrode. Preparativescale electrolyses in the presence of increasing amounts of iron (II) were carried out in an undivided electrochemical cell with a nickel-sponge cathode (20 cm2) and an iron rod (1 cm diameter) as the sacrificial anode. A SCE was used as the reference. In both cases a GC with a 5-m capillary column was used to detect and quantitate the bhydroxyester formation and the a-haloester and ketone consumptions. Dodecane was used as the internal standard. Mass spectra were recorded with a spectrometer coupled to a gas chromatograph.
3. Results and discussion 3.1. Study of the electrochemical behavior of FeBr2 in the presence of various amounts of 2,2 0 -bipyridine (bpy) in dimethylformamide (DMF) The cyclic voltammogram obtained by reduction of FeBr2 in the presence of 3 molar equivalents of 2,2 0 bipyridine, at a platinum disk electrode and at a scan rate of 0.2 V s1 in dimethylformamide (DMF) containing 0.10 M tetra-n-butylammonium tetrafluoroborate (TBABF4) exhibits the well documented 3 monoelectronic waves (Fig. 1(c); Scheme 4) [18–21].
O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70
Ω
O1 2
8
O2 O3
4
I / µA
I / µA
0
-4
Ω
12
4
-2
65
(a) (b) (c)
0
R1 -4
R2 -2.5 -6
-2
R3
-1.5
-1
-0.5
0
0.5
-2.5 -8
-2
-1.5
R2
-1
-0.5
0
0.5
E / V vs. SCE
E / V vs. SCE
Fig. 1. Cyclic voltammograms of FeBr2 (5 mM) in the presence of 1 (a), 2 (b) and 3 (c) molar equivalents of 2,2 0 -bipyridine recorded with a platinum disk electrode (0.5 mm diameter) at 0.2 V s1 in DMF containing 0.10 M TBABF4.
R1 / O1 :
[Fe(bpy)3]2+
+ e-
-1.30V
[Fe(bpy)3]+
R2 / O2 :
[Fe(bpy)3]+
+ e-
-1.50V
[Fe(bpy)3]
R3 / O3 :
[Fe(bpy)3]
+ e-
-1.75V
[Fe(bpy)3] -
Scheme 4. Reduction of [Fe(bpy)3]Br2 in dimethylformamide.
Under these conditions (i.e., in the presence of 3 molar equivalents of 2,2 0 -bipyridine per mole of iron (II)), the intensities of the reduction waves (R1, R2 and R3) and the oxidation waves (O1, O2 and O3) are identical, and the iron species are free of halogen [18–21]. In the presence of 2 molar equivalents of 2,2 0 -bipyridine, the intensities of the reduction and oxidation waves (except R2) decrease by the same factor (Fig. 1(b)). In addition, a new oxidation wave X appears at 0.38 V. This behavior is more prominent in the presence of one molecule of 2,2 0 -bipyridine per molecule of iron (II) (Fig. 1(a)). In this latter case, the intensities of the reduction and oxidation waves (except R2) are equal to approximately a third of the initial intensities observed in the presence of 3 molar equivalents of 2,2 0 -bipyridine. Interestingly, the oxidation wave X does not exist when reversing the potential scan after R1, indicating the electrogeneration of a stable FeI species. This is true even for a bpy/Fe ratio of 1/1. Note that the wave X can be assigned to the oxidation of electrodeposited iron by comparison with the cyclic voltammogram obtained by reduction of FeBr2 (Fig. 2). More importantly, we note that the reduction and oxidation waves remain located at the same potential values whatever the 2,2 0 -bipyridine concentration, suggesting that the species involved in the redox processes are the same ones. The only difference is the concentrations of these species, in agreement with the observed intensities. This would be supported by the fact that the complex formed between Fe2+ and 2,2 0 -bipyridine
Fig. 2. Cyclic voltammogram of FeBr2 (5 mM) recorded with a platinum disk electrode (0.5 mm diameter) at 0.2 V s1 in DMF containing 0.10 M TBABF4.
taken in the molar ratio 1:1 is exclusively the entity [Fe(bpy)3]2+, the remaining Fe2+ (2/3 mole) being unreacted [25]. However, the cyclic voltammogram obtained by reduction of FeBr2 exhibits a 2 electron irreversible wave at ca. 1.35 V (Fig. 2). Therefore, the potential value and the intensity observed for R2 in Fig. 1 cannot allow us to assign the reduction to unreacted Fe2+. This would suggest that the equilibrium between Fe2+ and bipyridine is not kinetically ‘‘frozen’’ during the cyclic voltammetry scan leading thus to a more complicated system. In summary, addition of 2,2 0 -bipyridine in a solution containing FeBr2 leads to an equilibrium mixture of [Fe(bpy)3]2+ and iron(II) species free of bpy. The amount of these species depends on the 2,2 0 -bipyridine concentration. Nevertheless, with 3 molar equivalents of bpy per mole of iron (II), [Fe(bpy)3]2+ is the sole present species. In the following, we will not always write the 2,2 0 bipyridine molecules ligated to the iron metal centre for simplification. Although, on a long time-scale, the low-valent FeI and Fe0 species are rather unstable and disproportionate [24], their high stability observed on the time-scale of cyclic voltammetry prompted us to study it on the time-scale of an electrolysis. Preparative electrolyses of FeBr2 were performed at the potential of R1, at room temperature in DMF, in the presence of 3 molar equivalents of 2,2 0 -bipyridine. After a charge of 1.3 electrons per molecule of FeII was passed, the solution was studied by in situ cyclic voltammetry. Compiled in Fig. 3 are the positive and negative scans obtained from the opencircuit voltage. The presence of a small amount of FeII detected after the electrolysis (wave R1) can be explained by the disproportionation of the electrogenerated FeI. Comparison with the cyclic voltammogram obtained before the electrolysis allows one to quantitate the FeI produced
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O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70 0.3
2
O1
0.2
O1 1
(a)
(I)
-2
-1.8
-1.6
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
E / V vs. SCE -0.1 -0.2 -0.3
0 -1
R1 (b)
-2
R2
-3 -1.8 -4
-0.4
(wave R2). In the present case, 50% of FeI with respect to the starting FeII was electrogenerated. As expected, when the same experiment is performed at 0 C in the presence of 5 molar equivalents of 2,2 0 -bipyridine, the yield of FeI increases to 80% since, under these conditions, the disproportionation has to be kinetically frozen. Indeed, and as described in Scheme 3, the decomposition of the Fe(I) species at room temperature leads to inactive solid iron. More interestingly, preparative electrolyses performed at 1.55 V (wave R2) and at room temperature in the presence of 3 equivalents of ligand allow the production of Fe0 (10–20%) after a charge of 2 electrons per molecule of iron bromide is passed. These results demonstrate the feasibility of preparing low-valent iron complexes for further in situ reactions. 3.2. Electrochemical behavior of FeBr2 in the presence of 2,2 0 -bipyridine and a-haloesters-evidence for an electron transfer As mentioned above, Fig. 2 depicts the cyclic voltammogram of a DMF solution containing 0.10 M TBABF4 with 5 mM FeBr2 at a scan rate of 0.2 V s1. Under these conditions, the addition of increasing amounts of methyl 2-chloropropanoate causes no change in the cyclic voltammogram, indicating no reaction between the electrogenerated iron (0) and the a-chloroester because of a fast nucleation reaction of Fe0 leading to solid iron. Conversely, when the same experiment was run in the presence of 15 mM 2,2 0 -bipyridine (bpy/Fe = 3/1), the addition of increasing amounts of a-chloroester leads both to a decrease of the intensity of O1 and an increase in the intensity of R1, indicating a reaction between the electrogenerated FeI and the a-chloroester (Fig. 4(I)). It must be pointed out that, in a separate experiment performed under the same conditions (electrode, scan rate, concentration, etc.), methyl 2-chloropropanoate
R1 -1.2
-0.6
3 2 1 0 -1 -2 -3 -4 -5 -1.8 -6
O1
(II)
(a) (b) (c) (d)
R1 -1.3 -0.8
-0.3
0.2
0.7
1.2
E / V vs. SCE
0
0.6
1.2
E / V vs. SCE Fig. 4. (I) Cyclic voltammograms of FeBr2 (5 mM) in the presence of 2,2 0 -bipyridine (15 mM) recorded with a platinum disk electrode (0.5 mm diameter) at 0.2 V s1 in DMF containing 0.10 M TBABF4. (a) In the absence of and (b) in the presence of 1, (c) 3, (d) 5, and (e) 7 molar equivalents of methyl 2-chloropropanoate. (II) Cyclic voltammograms of fluorenone (5 mM) recorded under the same conditions as for (I). (a) In the absence of and (b) in the presence of 1, (c) 5, and (d) 10 molar equivalents of methyl 2-chloropropanoate.
was found to be reducible at 2.2 V. Therefore, the increase in the current of R1 is not due to the direct electrochemical reduction of the a-chloroester. With the addition of excess a-chloroester, the wave R1 becomes completely irreversible and its intensity keeps increasing, suggesting a catalytic scheme involving regeneration of the starting material iron (II). Compiled in Fig. 5 are the ratios R = IO1/IR1, where IO1 and IR1 are the peak currents of waves O1 and R1, respectively, plotted versus the concentration of methyl 2-chloropropanoate and calculated for a bpy/Fe ratio higher than 3 at a scan rate of 0.2 V s1. Interestingly, for a given concentration of a-chloroester, the ratio R is similar whatever the ligand concentration. Since an
1
0.8
0.6
R
Fig. 3. Voltammograms obtained after electrolysis (1.3 electrons/ molecule of Fe(II)) of a DMF + TBABF4 (0.1 M) solution containing FeBr2 (10 mM), 2,2 0 -bipyridine (30 mM) and recorded with a platinum disk electrode (0.5 mm diameter) at 0.2 V s1. (a) Positive scan and (b) negative scan performed from open-circuit voltage.
(a) (b) (c) (d) (e)
I / µA
-2.2 0
I / µA
I / µA
0.1
0.4
0.2
0 -2.4
-2.2
-2
-1.8
-1.6
-1.4
log ([chloroester] / mol dm-3)
Fig. 5. Study of the effect of 2,2 0 -bipyridine concentration on the reaction rate between the electrogenerated FeI and methyl 2-chloropropanoate from the variation of the peak current ratio R = IO1/IR1 as a function of log [chloroester] in DMF + TBABF4 (0.1 M), and performed at v = 0.2 V s1 in the presence of 5 mM FeBr2. bpy/Fe ratio equal to 3 (r), 5 (n), and 10 (m), respectively.
O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70
oxidative addition of the a-chloroester to the [Fe(bpy)3]+ has little chance to occur because of a too hindered iron (I) species, an equilibrium, in which less ligated iron (I) species are present, has to be considered. But, in such a case, the rate of reaction should depend on the 2,2 0 bipyridine concentration. Therefore, our results suggest an outer-sphere electron transfer from the electrogenerated FeI towards the a-chloroester rather than an oxidative addition. In order to consolidate this hypothesis, we have studied by cyclic voltammetry the electrochemical behavior of methyl 2-chloropropanoate in the presence of fluorenone (F) as a typical redox mediator. The reversible oneelectron F/F redox couple (E = 1.25 V) is located at the same potential as the FeII/FeI redox couple. The difference between the reduction peak potentials of the catalyst and the substrate are therefore similar. With the addition of increasing amounts of a-chloroester, the peak current of R1 increases and the oxidation wave O1 disappears in the same manner as in the presence of iron, in agreement with identical E values (compare Figs. 4(I) and (II)). This demonstrates an indirect reduction of methyl 2-chloropropanoate carried out via homogeneous redox catalysis. This is also supported by results reported by Inesi and Zeuli dealing with the reduction of b, c, and d-bromoesters in the presence of various redox mediators [26–28]. Moreover, when electrogenerated FeI (see the above part) was treated with 1 molar equivalent of methyl 2-chloropropanoate under argon, iron(II) was regenerated and detected by in situ cyclic voltammetry. These results further validate the reduction of methyl 2-chloropropanoate by the electrogenerated FeI leading to the regeneration of FeII. Importantly, it must be pointed out that such a mechanism is
67
valid for bpy/Fe ratios higher than 3. Indeed, for lower values, the ratio R = IO1/IR1 could not be accurately measured because of ill-defined cyclic voltammograms. In the latter cases, an oxidative addition of the a-chloroester to a low ligated FeI species cannot, therefore, be excluded. Since the FeI species can be prepared by electrolysis, we measured the rate constant for the reaction between FeI(bpy)3 and methyl 2-chloropropanoate by steady state amperometry by recording the decay of the oxidation current of electrogenerated FeI versus time in the presence of methyl 2-chloropropanoate (Fig. 6(a)). The plot of ln(I0/I) versus time gives a slope of 0.46 and leads to a rate constant value equal to kapp. = 24 ± 5 M1 s1 (Fig. 6(b)). This confirms the value determined elsewhere by cyclic voltammetry [17]. As expected, replacement of methyl 2-chloropropanoate with methyl 2-bromopropanoate gives more spectacular results (Fig. 7(I)). Indeed, in the presence of increasing amounts of a-bromoester the reduction wave R1 becomes irreversible and its intensity increases rapidly. In addition, the same electrochemical behavior is obtained after replacement of FeBr2 with fluorenone (Fig. 7(II)). However, comparison of both the potential shifts of R1 and the variations in the intensities of O1 and R1, respectively, with those obtained in the presence of the a-chloroester reveals a faster electron transfer in the presence of the brominated ester. This is due to a smaller difference between the reduction peak potentials of the redox mediator and the substrate, leading to a faster electron-exchange rate [29]. It must be pointed out that methyl 2-bromopropanoate is reducible at 1.8 V under the same conditions (electrode, scan rate, etc.).
-16
+ methyl 2-chloropropanoate
-14 -12
I0
-3
(b)
-2.5 -2
ln (I0 /I)
I / µA
-10 -8
-1.5 -1
(a)
-6
-0.5
time / s 0 0
-4
0.1
0.2
0.3
0.4
0.5
0.6
-2 0 0
5
10
15
20
25
30
35
40
45
50
Time / s
Fig. 6. (a,b) Kinetics monitored by amperometry at a platinum rotating disk electrode (2 mm diameter, x = 210 rad s1) with a solution of FeI (3 mM) and methyl 2-chloropropanoate (20 mM) in DMF + TBABF4 (0.1 M). (a) Variation of the oxidation current of FeI at 1.0 V vs. time in the presence of CH3CH(Cl)CO2CH3. (b) Plot of ln(I0/I) = ln([FeI]0/[FeI]) vs. time (I = oxidation current of [FeI] at t, I0 = initial oxidation current of [FeI]).
68
O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70 2
rent interruption, indicating the presence of an enolate likely to be stabilized by the presence of iron(II).
(I)
O1
0 4
-2
3.3. Study of FeBr2 in the presence of 2,2 0 -bipyridine, methyl 2-chloropropanoate, and cyclohexanone
O1
(a)
(b)
-6
-4
-8
(c) (d)
-8 -10
I / µA
I / µA
0
-4
-2
-1.5
(a) (b) (c) (d)
(II) R1
-2 -12
-1.5
-0.5
-1
0
0.5
1
E / V vs. SCE
R1 -1
-0.5
0
0.5
1
E / V vs. SCE Fig. 7. (I)Cyclic voltammograms of FeBr2 (5 mM) in the presence of 2,2 0 -bipyridine (15 mM) recorded with a platinum disk electrode (0.5 mm diameter) at 0.2 V s1 in DMF containing 0.10 M TBABF4. (a) In the absence of and (b) in the presence of 1, (c) 2, and (d) 3 molar equivalents of methyl 2-bromopropanoate. (II) Cyclic voltammograms of fluorenone (5 mM) recorded under the same conditions as for (I). (a) In the absence of and (b) in the presence of 1, (c) 2, and (d) 3 molar equivalents of methyl 2-bromopropanoate.
On the basis of our results and of those reported by Zeuli and Inesi dealing with the indirect and direct reduction of bromoesters, the reduction of a-haloesters therefore leads to the corresponding radical-anion along with the regeneration of FeII [26–30]. The radical-anion then undergoes a cleavage affording an ester radical and a free halide ion. The radical can then be reduced in two different ways: (1) it can accept an electron from the cathode or (2) it can undergo a homogeneous electrontransfer reaction with iron(I). In either case, an ester anion is produced. The reactivity of carbanions of the type (CH2CO2Et), obtained by electrochemical reduction of CH2(Br)CO2Et, has been widely studied by means of cyclic voltammetry and coulometry [30]. Evidence was found for coupling reactions leading to the formation of hydrogenated ester and dimeric products. In order to study the reactivity of (CH3CHCO2CH3) in the presence of iron, we carried out a controlled-current (I = 0.25 A) electrolysis, in DMF, of methyl 2-chloropropanoate (10 mmol) in the presence of FeBr2 prepared electrochemically (1.25 mmol; see below), 2,2 0 -bipyridine (5 mmol) and a sacrificial iron anode. Under these conditions the potential value remains constant and equal to 1.15 V corresponding to the foot of wave R1 (reduction of FeII into FeI). After 90% of the a-chloroester was consumed, the analysis of the crude solution, with the aid of GC and GC–MS, indicates the formation of methyl propionate as the major product along with dimers and Claisen-type products. The presence of the latter confirms the existence of the anion (CH3CHCO2CH3) obtained by reduction of (CH3CHCO2CH3). Interestingly, a small portion of the remaining a-chloroester was still consumed after cur-
To ascertain the role of iron in the coupling reaction between a-haloesters and carbonyl compounds, a preparative electrolysis of fluorenone has been carried out in a divided cell in the presence of cyclohexanone and methyl 2-chloropropanoate. A GC analysis of the solution at the end of the electrolysis did not reveal any trace of coupling product, confirming that iron is required for the coupling reaction. Preparative electrolyses of FeBr2 (5 mmol) in the presence of cyclohexanone (5 mmol) and various amounts of 2,2 0 -bipyridine have been performed in a divided cell and at a potential of 1 V corresponding to the foot of R1. To minimize self-condensation reactions, the a-chloroester was added in 3 portions: before starting the experiment (1.75 mmol) and after a charge of 340 C and 680 C were passed (2 · 1.75 mmol). In the presence of 5 molar equivalents of 2,2 0 -bipyridine no coupling product was observed whereas in the presence of 3 molar equivalents of ligand, traces of the b-hydroxy-ester were obtained. Furthermore, in the presence of 1 molar equivalent of bpy, and after a charge of 2 electrons per molecule of FeBr2 was passed (ca. 1000 C), only 50% of the initial ketone was consumed, and the coupling product was obtained in 50% yield. Interestingly, the a-chloroester was completely consumed, indicating an efficient condensation reaction probably due to a non-constant addition of the substrate. These experiments suggest the existence of two mechanisms depending on the bpy concentration. An indirect reduction of the achloroester by the electrogenerated FeI is involved when the bpy/Fe ratio is higher than 3, whereas an oxidative addition would occur for smaller ratios. A low-ligated iron (I) species must therefore exist in the latter case. Even though the use of a divided cell allows preparation of the b-hydroxyester with moderate yields, the presence of a stoichiometric amount of iron(II) is not convenient. To simplify the procedure, electrolyses were then carried out at a constant current of 0.25 A in an undivided cell and in the presence of a sacrificial iron anode. First, a pre-electrolysis of 1,2-dibromoethane (1.25 mmol) was run in the undivided cell in the presence of an iron rod to prepare FeBr2 electrochemically (1.25 mmol). The 2,2 0 -bipyridine ligand was then added along with the carbonyl compound (10 mmol) and a portion of the a-chloroester (0.3 mmol). During the experiment, the ester was also constantly added in the solution using a syringe pump with a rate of addition of 4.46 mmol/h.
O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70
When the electrolysis is run in the presence of one molecule of 2,2 0 -bipyridine per molecule of FeBr2 (Fig. 8 - curve A), the coupling product is formed throughout the experiment but more slowly than in the experiment performed in the divided cell as described above. Indeed, after a charge of 2 electrons per molecule of ketone was passed (ca. 2000 C), the b-hydroxyester is obtained in 35% yield instead of 50%. In addition, the formation of the coupling product slows down after a charge of 3600 C was passed. In terms of yield and faradaic yield, this result is not as good as that obtained in the divided cell. The origin of this is very likely due to the continuous generation of Fe2+ ions leading to a decrease of the bpy/Fe ratio and therefore to a less stable FeI. This drawback can be overcome with the use of a higher amount of 2,2 0 bipyridine. Curve B in Fig. 8 depicts the formation of b-hydroxyester when starting the electrolysis in the presence of 4 moles of ligand per mole of FeBr2. In this case, a better faradaic yield is obtained, but the coupling product arises after an induction period of approximately 470 C, corresponding to a bpy/Fe ratio equal to 1.35 instead of 4 before starting the electrolysis. As mentioned above, this suggests a change in the mechanism. The use of a sacrificial iron anode allows the decrease of the bpy / Fe ratio by the electrogeneration of Fe2+, and favours the oxidative addition reaction of the a-chloroester to FeI versus the electron transfer. Replacement of methyl 2-chloropropanoate with methyl 2-bromopropanoate leads to the same results, and the coupling product is not formed faster. Assuming a faster oxidative addition than in the presence of the chloroester, the coupling reaction is therefore the rate-limiting step. On the basis of these results, the electrochemical coupling reaction between a-haloesters and carbonyl compounds in the presence of FeBr2 and a sacrificial iron
69
anode could be improved by maintaining a bpy/Fe ratio close to one. This could be achieved by addition of 2,2 0 bipyridine throughout the experiment and at the same rate at which Fe2+ is generated and which depends on the current supplied. Scheme 5 shows a sequence of mechanistic steps that can account for the iron-mediated electrochemical reaction of a-haloesters with carbonyl compounds and an iron sacrificial anode in DMF. Note that 2,2 0 -bipyridine ligands have been omitted for simplification. The reaction is initiated with the reduction of FeII to I Fe which is stabilized by the presence of 2,2 0 -bipyridine. As long as the bpy/Fe ratio is higher than 3, an electron transfer occurs from the electrogenerated FeI to the ahaloester, leading to the regeneration of FeII and to the corresponding anion-radical (Path (A)). The cleavage of the latter, which may be concerted or not, produces an ester radical and a free chloride ion. The radical is readily reducible either at the electrode by a single electron uptake at the same potential as FeII or in solution by the electrogenerated FeI. Finally, the anion obtained mainly gives the protonated product. However, when the bpy/Fe ratio is close to 1, an oxidative addition of the a-haloester to FeI would occur (Path (B)). This would lead to the corresponding [ClFeIIICH(CH3)CO2CH3]. By analogy with the numerous Reformatsky reactions performed in the presence of zinc, chromium or indium, etc., we may then envisage the formation of an enolate followed by the reaction with the ketone leading to an iron-alkoxide [31,32].
FeII eFeI
10
(B)
CH3CH(Cl)CO2CH3
β-hydroxyester / mmol
(A) 8
(B)
(A)
6
FeII + [CH3CH(Cl)CO2CH3]
4
. [CH CHCO CH ] 3
2
2
3
. ClFeIIICH(CH3)CO2CH3
+ Cl -
e- or FeI
0 0
1000
2000
3000
4000
5000
6000
[CH3CHCO2CH3] - FeII
Charge / C 0
1
2
3
4
5
RCOR’, eR Fe O or FeIII
R'
O
II
O H+
6
Time / h
Fig. 8. Preparative electrolyses of FeBr2 (1.25 mmol) in the presence of cyclohexanone (10 mmol) and methyl 2-chloropropanoate (0.3 mmol at t = 0 then added to the solution at a rate of 4.46 mmol h1) in DMF. Formation of the coupling product (b-hydroxyester) as a function of the charge consumed. In the presence of 1 (A), and 4 (B) molar equivalents of 2,2 0 -bipyridine with respect to the starting FeBr2.
CH3CH2CO2CH3 +
dimers and Claisen products
R HO
R'
O O
+ Fe II or FeIII
Scheme 5. Reactions involved in the iron-mediated electrochemical coupling reaction between a-haloesters and carbonyl compounds. Path (A) bpy/Fe P 3 and path (B) bpy/Fe < 3.
70
O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70
The latter is then easily converted into the corresponding b-hydroxyester by hydrolysis with 2M HCl. However, the presence of an additional electroreductive step in such a scheme cannot be totally excluded. More importantly, Scheme 5 indicates that the Reformatsky product is obtained only if both the carbonyl compound and the a-haloester are in the coordination sphere of the iron metal centre. If this condition is not fulfilled, the hydrogenation product is then formed.
4. Conclusion The use of cyclic voltammetry and preparative-scale electrolyses allowed us to investigate the mechanism leading to the synthesis of b-hydroxyesters via an electrochemical method in the presence of iron (a Reformatsky-type reaction) [17]. We showed especially that iron(I) is the species involved in the reaction with a-haloesters and that the presence of 2,2 0 -bipyridine is required to allow its stabilization. Under our analytical conditions (bpy/Fe P 3), an electron transfer from the electrogenerated FeI to the a-haloesters has been observed. Nevertheless, under these conditions, the coupling reaction does not occur, suggesting the existence of another mechanism. The presence of a sacrificial iron anode is therefore useful since the continuous generation of Fe2+ cations decreases the bpy/Fe ratio. When the bpy/ Fe ratio becomes lower than 3, an oxidative addition between the electrogenerated FeI and the a-haloesters may occur. We thus demonstrated that the key-point for the coupling reaction relies on the bpy/Fe ratio. In terms of faradaic yield, the best conditions for this electrosynthesis would be to keep a constant bpy/Fe ratio close to one. To perform this, the 2,2 0 -bipyridine should be continuously added in solution and at the same rate at which Fe2+ ions are electrogenerated.
Acknowledgment The authors are grateful to Pr. J.N. Verpeaux for helpful discussions.
References [1] A. Fu¨rstner, Synthesis (1989) 571. [2] M.W. Rathke, P. Weipert, in: B.M. Trost, I. Fleming (Eds.), Comprehensive Organic Synthesis, vol. 2, Pergamon, New York, 1991, p. 277. [3] A. Fu¨rstner, in: P. Knochel, P. Jones (Eds.), Organozinc Reagents, Oxford University Press, New York, 1999, p. 287. [4] S. Reformatsky, Chem. Ber. 20 (1887) 1210. [5] R.D. Rieke, S.J. Uhm, Synthesis (1975) 452. [6] E. Santaniello, A. Manzocchi, Synthesis (1977) 698. [7] R. Csuk, A. Fu¨rstner, H. Weidmann, J. Chem. Soc., Chem. Commun. (1986) 775. [8] B. Han, P. Boudjouk, J. Org. Chem. 47 (1982) 5030. [9] A. Durant, J. Delplanche, V. Libert, J. Reisse, Eur. J. Org. Chem. (1999) 2845. [10] L. Wessjohann, T. Gabriel, J. Org. Chem. 62 (1997) 3772. [11] T. Hirashita, K. Kinoshita, H. Yamamura, M. Kawai, S. Araki, J. Chem. Soc., Perkin Trans. 1 5 (2000) 825. [12] P. Lee, K. Bang, S. Sung, S. Chang, Synth. Commun. 31 (2001) 3781. [13] H. Kahiga, S. Nishimae, H. Shinokubo, K. Oshima, Tetrahedron 57 (2001) 8807. [14] G. Cahiez, P.-Y. Chavant, Tetrahedron Lett. 30 (1989) 7373. [15] A. Conan, S. Sibille, J. Pe´richon, J. Org. Chem. 56 (1991) 2018. [16] M. Durandetti, J.-Y. Ne´de´lec, J. Pe´richon, Org. Lett. 3 (2001) 2073. [17] M. Durandetti, C. Meignein, J. Pe´richon, Org. Lett. 5 (2003) 317. [18] T. Saji, S. Aoyaguy, J. Electroanal. Chem. 58 (1975) 401. [19] J.M. Rao, M.C. Hughes, D.J. Macero, Inorg. Chim. Acta 35 (1979) L369. [20] T. Saji, T. Yamada, S. Aoyaguy, J. Electroanal. Chem. 61 (1975) 147. [21] T. Saji, S. Aoyaguy, J. Electroanal. Chem. 60 (1975) 1. [22] P.S. Braterman, J.I. Song, R.D. Peacock, Inorg. Chem. 31 (1992) 555. [23] S.A. Richert, P.K.S. Tsang, D.T. Sawyer, Inorg. Chem. 28 (1989) 2471. [24] W. Lau, J.C. Huffman, J.K. Kochi, Organometallics 1 (1982) 155. [25] M. Ocafrain, M. Devaud, M. Troupel, J. Pe´richon, Electrochim. Acta 42 (1997) 99. [26] A. Inesi, E. Zeuli, J. Electroanal. Chem. 195 (1985) 129. [27] A. Inesi, J. Electroanal. Chem. 165 (1984) 293. [28] A. Inesi, A. Zeppa, E. Zeuli, J. Electroanal. Chem. 126 (1981) 175. [29] A.J. Bard, L.R. Faulkner, Electrochemical Methods, Wiley, New York, 1980. [30] A. Inesi, E. Zeuli, J. Electroanal. Chem. 149 (1983) 167, and Refs. therein. [31] L. Wessjohann, T. Gabriel, J. Org. Chem. 62 (1997) 3772. [32] T. Hirashita, K. Kinoshita, H. Yamamura, M. Kawai, S. Araki, J. Chem. Soc., Perkin. Trans. 1 (2000) 825.
Electroanalytical Chemistry Journal of Electroanalytical Chemistry 578 (2005) 63–70 www.elsevier.com/locate/jelechem
Mechanistic investigation of the iron-mediated electrochemical formation of b-hydroxyesters from a-haloesters and carbonyl compounds Olivier Buriez *, Muriel Durandetti *, Jacques Pe´richon Laboratoire dÕElectrochimie, Catalyse et Synthe`se Organique, UMR CNRS 7582, Universite´ Paris 12, 2-8 Rue Henri Dunant, 94320 Thiais, France Received 22 September 2004; received in revised form 29 November 2004; accepted 6 December 2004 Available online 8 February 2005
Abstract The electrochemical behavior of FeI in the presence of a-haloesters has been studied by means of cyclic voltammetry and preparative-scale electrolyses with the intent to investigate the electrochemical coupling reaction between a-haloesters and carbonyl compounds performed in the presence of FeBr2 and a sacrificial iron anode. It is established that the reaction is initiated by the electrogeneration of an iron (I) species, which has to be stabilized by the presence of 2,2 0 -bipyridine (bpy). However, the reactivity of the electrogenerated FeI is governed by the bpy concentration. Indeed, for bpy/Fe ratios higher than or equal to 3, an outersphere electron transfer has been shown between FeI and a-haloesters, but no coupling product was obtained under these conditions. Conversely, for smaller bpy/Fe ratios the coupling reaction occurs, suggesting the existence of an oxidative addition between FeI and a-haloesters. The presence of a sacrificial iron anode in preparative-scale experiments is useful to decrease the bpy/Fe ratio by generation of Fe2+ cations. 2005 Elsevier B.V. All rights reserved. Keywords: Cyclic voltammetry; Cyclohexanone; 2,2 0 -Bipyridine; a-Haloesters; Iron
1. Introduction Among the numerous coupling reactions leading to carbon–carbon bond formation, the Reformatsky reaction is still of high current interest [1–3]. This reaction, discovered in 1887, allows the preparation of b-hydroxyester compounds from a-haloesters and aldehydes or ketones in the presence of zinc [4]. Since the reaction is initiated by insertion of zinc into the halogen–carbon bond, most efforts have been focused on the activation of zinc [5–9]. Nevertheless, in the past decade, replacement of zinc with another metal such as chromium *
Corresponding authors. Tel.: +33 1 49 78 11 41; fax: +33 1 49 78 11
48. E-mail addresses: [email protected] (O. Buriez), [email protected] (M. Durandetti). 0022-0728/$ - see front matter 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.jelechem.2004.12.020
[10], indium [11,12], or manganese [13,14] has been attracting increased attention. Furthermore, and alternatively to these chemical processes, we developed in our group an electrochemical method for the Reformatsky reaction. This was formerly achieved in the presence of a nickel–bipyridine complex as the catalyst and a sacrificial zinc anode [15]. Then, we discovered an electrochemical method catalytic in both chromium and nickel salts using a sacrificial stainless steel or iron rod anode, which raised the question of the role of the iron salts [16]. More recently, we reported an original version of the Reformatsky reaction using FeBr2 in the presence of 2,2 0 -bipyridine and a sacrificial iron rod anode (Scheme 1) [17]. This last electrochemical method, which uses very simple experimental conditions in comparison with known chemical processes, enables the formation of
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O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70
R
R' +
Cl
-
1) e , FeBr2,bpy
O
O
R' R HO
DMF, Fe anode
O
2) H+
2. Experimental
O O
Scheme 1. Reformatsky-type reaction using an electro-assisted ironcomplex.
[Fe(bpy)3]2+
+ e-
E˚= -1.25 V
[Fe(bpy)3]+
[Fe(bpy)3]+
+ e-
E˚= -1.43 V
[Fe(bpy)3]
[Fe(bpy)3]
+ e-
E˚= -1.71 V
[Fe(bpy)3] -
Scheme 2. Reduction of [Fe(bpy)3]X2 in dimethylformamide; potentials vs. the saturated calomel electrode.
b-hydroxyesters in good to high yields (60–80%) [17]. However, the mechanism leading to the coupling product under these conditions remains to be elucidated. This work is required to improve our reactions and to discover other useful syntheses using iron as the catalyst. This study has been investigated by means of cyclic voltammetry and preparative-scale electrolyses. The electrochemical behavior of iron (II) in the presence of 3 molar equivalents of 2,2 0 -bipyridine (bpy) is well documented. In dimethylformamide, the cyclic voltammogram of [Fe(bpy)3]X2 exhibits three successive reversible monoelectronic steps (Scheme 2). It is admitted that the reductive processes on [Fe(bpy)3]2+ are all ligand-based and the oxidation process is metal-centered [18–23]. Despite their stability on the time-scale of cyclic voltammetry, the [Fe(bpy)3]+ and [Fe(bpy)3] complexes are rather unstable on a longer time-scale and dissociate according to Scheme 3 [24]. More importantly, it has been shown that the complex formed between Fe2+ ions and 2,2 0 -bipyridine in the molar ratio 1:1 is exclusively the entity [Fe(bpy)3]2+ [25]. To our knowledge, no studies have yet been conducted with a-haloesters and carbonyl compounds in the presence of iron (II). Herein, we report the electrochemical behavior of FeBr2 in dimethylformamide, in the presence of 2,2 0 -bipyridine, a-haloesters, and cyclohexanone. We show especially that the reaction leading to the formation of b-hydroxyesters is governed by the bpy/Fe ratio.
2 [Fe(bpy)3]+
[Fe(bpy)3]2+ + [Fe(bpy)3]
[Fe(bpy)3]
bpy
[Fe(bpy)2]
Fe(s) + 2 bpy
Scheme 3.
+
[Fe(bpy)2]
2.1. Chemicals Dimethylformamide (from SDS) was used without purification. Iron bromide (Aldrich), 2,2 0 -bipyridine (Acros), methyl 2-chloropropanoate (Aldrich), methyl 2-bromopropanoate (Janssen), and cyclohexanone (Aldrich) were used as received. TBABF4 (Fluka), used as the supporting electrolyte, was recrystallized from diethylether and dried at 60 C under vacuum. 2.2. Instrumentation Cyclic voltammetry experiments were performed at room temperature (RT) under argon in a 3-electrode cell using an EG&G model 273A potentiostat. The reference electrode was an SCE (Tacussel), which was separated from the solution by a bridge compartment filled with the same solvent/supporting electrolyte solution used in the cell. The counter electrode was a gold wire. The working electrode was a disk obtained from a cross-section of platinum wire (diameter 500 lm) sealed in glass. Preparative-scale electrolyses in the presence of iron (II), at a constant concentration, were carried out in a divided H cell. The cathode was a gold grid, with an approximately 10 cm2 apparent surface area, and the counter electrode (anode) was an iron rod. A SCE was used as the reference. The in situ cyclic voltammetry was performed at a microelectrode set in the cathodic compartment, the gold grid then being used as a counter electrode. Preparativescale electrolyses in the presence of increasing amounts of iron (II) were carried out in an undivided electrochemical cell with a nickel-sponge cathode (20 cm2) and an iron rod (1 cm diameter) as the sacrificial anode. A SCE was used as the reference. In both cases a GC with a 5-m capillary column was used to detect and quantitate the bhydroxyester formation and the a-haloester and ketone consumptions. Dodecane was used as the internal standard. Mass spectra were recorded with a spectrometer coupled to a gas chromatograph.
3. Results and discussion 3.1. Study of the electrochemical behavior of FeBr2 in the presence of various amounts of 2,2 0 -bipyridine (bpy) in dimethylformamide (DMF) The cyclic voltammogram obtained by reduction of FeBr2 in the presence of 3 molar equivalents of 2,2 0 bipyridine, at a platinum disk electrode and at a scan rate of 0.2 V s1 in dimethylformamide (DMF) containing 0.10 M tetra-n-butylammonium tetrafluoroborate (TBABF4) exhibits the well documented 3 monoelectronic waves (Fig. 1(c); Scheme 4) [18–21].
O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70
Ω
O1 2
8
O2 O3
4
I / µA
I / µA
0
-4
Ω
12
4
-2
65
(a) (b) (c)
0
R1 -4
R2 -2.5 -6
-2
R3
-1.5
-1
-0.5
0
0.5
-2.5 -8
-2
-1.5
R2
-1
-0.5
0
0.5
E / V vs. SCE
E / V vs. SCE
Fig. 1. Cyclic voltammograms of FeBr2 (5 mM) in the presence of 1 (a), 2 (b) and 3 (c) molar equivalents of 2,2 0 -bipyridine recorded with a platinum disk electrode (0.5 mm diameter) at 0.2 V s1 in DMF containing 0.10 M TBABF4.
R1 / O1 :
[Fe(bpy)3]2+
+ e-
-1.30V
[Fe(bpy)3]+
R2 / O2 :
[Fe(bpy)3]+
+ e-
-1.50V
[Fe(bpy)3]
R3 / O3 :
[Fe(bpy)3]
+ e-
-1.75V
[Fe(bpy)3] -
Scheme 4. Reduction of [Fe(bpy)3]Br2 in dimethylformamide.
Under these conditions (i.e., in the presence of 3 molar equivalents of 2,2 0 -bipyridine per mole of iron (II)), the intensities of the reduction waves (R1, R2 and R3) and the oxidation waves (O1, O2 and O3) are identical, and the iron species are free of halogen [18–21]. In the presence of 2 molar equivalents of 2,2 0 -bipyridine, the intensities of the reduction and oxidation waves (except R2) decrease by the same factor (Fig. 1(b)). In addition, a new oxidation wave X appears at 0.38 V. This behavior is more prominent in the presence of one molecule of 2,2 0 -bipyridine per molecule of iron (II) (Fig. 1(a)). In this latter case, the intensities of the reduction and oxidation waves (except R2) are equal to approximately a third of the initial intensities observed in the presence of 3 molar equivalents of 2,2 0 -bipyridine. Interestingly, the oxidation wave X does not exist when reversing the potential scan after R1, indicating the electrogeneration of a stable FeI species. This is true even for a bpy/Fe ratio of 1/1. Note that the wave X can be assigned to the oxidation of electrodeposited iron by comparison with the cyclic voltammogram obtained by reduction of FeBr2 (Fig. 2). More importantly, we note that the reduction and oxidation waves remain located at the same potential values whatever the 2,2 0 -bipyridine concentration, suggesting that the species involved in the redox processes are the same ones. The only difference is the concentrations of these species, in agreement with the observed intensities. This would be supported by the fact that the complex formed between Fe2+ and 2,2 0 -bipyridine
Fig. 2. Cyclic voltammogram of FeBr2 (5 mM) recorded with a platinum disk electrode (0.5 mm diameter) at 0.2 V s1 in DMF containing 0.10 M TBABF4.
taken in the molar ratio 1:1 is exclusively the entity [Fe(bpy)3]2+, the remaining Fe2+ (2/3 mole) being unreacted [25]. However, the cyclic voltammogram obtained by reduction of FeBr2 exhibits a 2 electron irreversible wave at ca. 1.35 V (Fig. 2). Therefore, the potential value and the intensity observed for R2 in Fig. 1 cannot allow us to assign the reduction to unreacted Fe2+. This would suggest that the equilibrium between Fe2+ and bipyridine is not kinetically ‘‘frozen’’ during the cyclic voltammetry scan leading thus to a more complicated system. In summary, addition of 2,2 0 -bipyridine in a solution containing FeBr2 leads to an equilibrium mixture of [Fe(bpy)3]2+ and iron(II) species free of bpy. The amount of these species depends on the 2,2 0 -bipyridine concentration. Nevertheless, with 3 molar equivalents of bpy per mole of iron (II), [Fe(bpy)3]2+ is the sole present species. In the following, we will not always write the 2,2 0 bipyridine molecules ligated to the iron metal centre for simplification. Although, on a long time-scale, the low-valent FeI and Fe0 species are rather unstable and disproportionate [24], their high stability observed on the time-scale of cyclic voltammetry prompted us to study it on the time-scale of an electrolysis. Preparative electrolyses of FeBr2 were performed at the potential of R1, at room temperature in DMF, in the presence of 3 molar equivalents of 2,2 0 -bipyridine. After a charge of 1.3 electrons per molecule of FeII was passed, the solution was studied by in situ cyclic voltammetry. Compiled in Fig. 3 are the positive and negative scans obtained from the opencircuit voltage. The presence of a small amount of FeII detected after the electrolysis (wave R1) can be explained by the disproportionation of the electrogenerated FeI. Comparison with the cyclic voltammogram obtained before the electrolysis allows one to quantitate the FeI produced
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O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70 0.3
2
O1
0.2
O1 1
(a)
(I)
-2
-1.8
-1.6
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
E / V vs. SCE -0.1 -0.2 -0.3
0 -1
R1 (b)
-2
R2
-3 -1.8 -4
-0.4
(wave R2). In the present case, 50% of FeI with respect to the starting FeII was electrogenerated. As expected, when the same experiment is performed at 0 C in the presence of 5 molar equivalents of 2,2 0 -bipyridine, the yield of FeI increases to 80% since, under these conditions, the disproportionation has to be kinetically frozen. Indeed, and as described in Scheme 3, the decomposition of the Fe(I) species at room temperature leads to inactive solid iron. More interestingly, preparative electrolyses performed at 1.55 V (wave R2) and at room temperature in the presence of 3 equivalents of ligand allow the production of Fe0 (10–20%) after a charge of 2 electrons per molecule of iron bromide is passed. These results demonstrate the feasibility of preparing low-valent iron complexes for further in situ reactions. 3.2. Electrochemical behavior of FeBr2 in the presence of 2,2 0 -bipyridine and a-haloesters-evidence for an electron transfer As mentioned above, Fig. 2 depicts the cyclic voltammogram of a DMF solution containing 0.10 M TBABF4 with 5 mM FeBr2 at a scan rate of 0.2 V s1. Under these conditions, the addition of increasing amounts of methyl 2-chloropropanoate causes no change in the cyclic voltammogram, indicating no reaction between the electrogenerated iron (0) and the a-chloroester because of a fast nucleation reaction of Fe0 leading to solid iron. Conversely, when the same experiment was run in the presence of 15 mM 2,2 0 -bipyridine (bpy/Fe = 3/1), the addition of increasing amounts of a-chloroester leads both to a decrease of the intensity of O1 and an increase in the intensity of R1, indicating a reaction between the electrogenerated FeI and the a-chloroester (Fig. 4(I)). It must be pointed out that, in a separate experiment performed under the same conditions (electrode, scan rate, concentration, etc.), methyl 2-chloropropanoate
R1 -1.2
-0.6
3 2 1 0 -1 -2 -3 -4 -5 -1.8 -6
O1
(II)
(a) (b) (c) (d)
R1 -1.3 -0.8
-0.3
0.2
0.7
1.2
E / V vs. SCE
0
0.6
1.2
E / V vs. SCE Fig. 4. (I) Cyclic voltammograms of FeBr2 (5 mM) in the presence of 2,2 0 -bipyridine (15 mM) recorded with a platinum disk electrode (0.5 mm diameter) at 0.2 V s1 in DMF containing 0.10 M TBABF4. (a) In the absence of and (b) in the presence of 1, (c) 3, (d) 5, and (e) 7 molar equivalents of methyl 2-chloropropanoate. (II) Cyclic voltammograms of fluorenone (5 mM) recorded under the same conditions as for (I). (a) In the absence of and (b) in the presence of 1, (c) 5, and (d) 10 molar equivalents of methyl 2-chloropropanoate.
was found to be reducible at 2.2 V. Therefore, the increase in the current of R1 is not due to the direct electrochemical reduction of the a-chloroester. With the addition of excess a-chloroester, the wave R1 becomes completely irreversible and its intensity keeps increasing, suggesting a catalytic scheme involving regeneration of the starting material iron (II). Compiled in Fig. 5 are the ratios R = IO1/IR1, where IO1 and IR1 are the peak currents of waves O1 and R1, respectively, plotted versus the concentration of methyl 2-chloropropanoate and calculated for a bpy/Fe ratio higher than 3 at a scan rate of 0.2 V s1. Interestingly, for a given concentration of a-chloroester, the ratio R is similar whatever the ligand concentration. Since an
1
0.8
0.6
R
Fig. 3. Voltammograms obtained after electrolysis (1.3 electrons/ molecule of Fe(II)) of a DMF + TBABF4 (0.1 M) solution containing FeBr2 (10 mM), 2,2 0 -bipyridine (30 mM) and recorded with a platinum disk electrode (0.5 mm diameter) at 0.2 V s1. (a) Positive scan and (b) negative scan performed from open-circuit voltage.
(a) (b) (c) (d) (e)
I / µA
-2.2 0
I / µA
I / µA
0.1
0.4
0.2
0 -2.4
-2.2
-2
-1.8
-1.6
-1.4
log ([chloroester] / mol dm-3)
Fig. 5. Study of the effect of 2,2 0 -bipyridine concentration on the reaction rate between the electrogenerated FeI and methyl 2-chloropropanoate from the variation of the peak current ratio R = IO1/IR1 as a function of log [chloroester] in DMF + TBABF4 (0.1 M), and performed at v = 0.2 V s1 in the presence of 5 mM FeBr2. bpy/Fe ratio equal to 3 (r), 5 (n), and 10 (m), respectively.
O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70
oxidative addition of the a-chloroester to the [Fe(bpy)3]+ has little chance to occur because of a too hindered iron (I) species, an equilibrium, in which less ligated iron (I) species are present, has to be considered. But, in such a case, the rate of reaction should depend on the 2,2 0 bipyridine concentration. Therefore, our results suggest an outer-sphere electron transfer from the electrogenerated FeI towards the a-chloroester rather than an oxidative addition. In order to consolidate this hypothesis, we have studied by cyclic voltammetry the electrochemical behavior of methyl 2-chloropropanoate in the presence of fluorenone (F) as a typical redox mediator. The reversible oneelectron F/F redox couple (E = 1.25 V) is located at the same potential as the FeII/FeI redox couple. The difference between the reduction peak potentials of the catalyst and the substrate are therefore similar. With the addition of increasing amounts of a-chloroester, the peak current of R1 increases and the oxidation wave O1 disappears in the same manner as in the presence of iron, in agreement with identical E values (compare Figs. 4(I) and (II)). This demonstrates an indirect reduction of methyl 2-chloropropanoate carried out via homogeneous redox catalysis. This is also supported by results reported by Inesi and Zeuli dealing with the reduction of b, c, and d-bromoesters in the presence of various redox mediators [26–28]. Moreover, when electrogenerated FeI (see the above part) was treated with 1 molar equivalent of methyl 2-chloropropanoate under argon, iron(II) was regenerated and detected by in situ cyclic voltammetry. These results further validate the reduction of methyl 2-chloropropanoate by the electrogenerated FeI leading to the regeneration of FeII. Importantly, it must be pointed out that such a mechanism is
67
valid for bpy/Fe ratios higher than 3. Indeed, for lower values, the ratio R = IO1/IR1 could not be accurately measured because of ill-defined cyclic voltammograms. In the latter cases, an oxidative addition of the a-chloroester to a low ligated FeI species cannot, therefore, be excluded. Since the FeI species can be prepared by electrolysis, we measured the rate constant for the reaction between FeI(bpy)3 and methyl 2-chloropropanoate by steady state amperometry by recording the decay of the oxidation current of electrogenerated FeI versus time in the presence of methyl 2-chloropropanoate (Fig. 6(a)). The plot of ln(I0/I) versus time gives a slope of 0.46 and leads to a rate constant value equal to kapp. = 24 ± 5 M1 s1 (Fig. 6(b)). This confirms the value determined elsewhere by cyclic voltammetry [17]. As expected, replacement of methyl 2-chloropropanoate with methyl 2-bromopropanoate gives more spectacular results (Fig. 7(I)). Indeed, in the presence of increasing amounts of a-bromoester the reduction wave R1 becomes irreversible and its intensity increases rapidly. In addition, the same electrochemical behavior is obtained after replacement of FeBr2 with fluorenone (Fig. 7(II)). However, comparison of both the potential shifts of R1 and the variations in the intensities of O1 and R1, respectively, with those obtained in the presence of the a-chloroester reveals a faster electron transfer in the presence of the brominated ester. This is due to a smaller difference between the reduction peak potentials of the redox mediator and the substrate, leading to a faster electron-exchange rate [29]. It must be pointed out that methyl 2-bromopropanoate is reducible at 1.8 V under the same conditions (electrode, scan rate, etc.).
-16
+ methyl 2-chloropropanoate
-14 -12
I0
-3
(b)
-2.5 -2
ln (I0 /I)
I / µA
-10 -8
-1.5 -1
(a)
-6
-0.5
time / s 0 0
-4
0.1
0.2
0.3
0.4
0.5
0.6
-2 0 0
5
10
15
20
25
30
35
40
45
50
Time / s
Fig. 6. (a,b) Kinetics monitored by amperometry at a platinum rotating disk electrode (2 mm diameter, x = 210 rad s1) with a solution of FeI (3 mM) and methyl 2-chloropropanoate (20 mM) in DMF + TBABF4 (0.1 M). (a) Variation of the oxidation current of FeI at 1.0 V vs. time in the presence of CH3CH(Cl)CO2CH3. (b) Plot of ln(I0/I) = ln([FeI]0/[FeI]) vs. time (I = oxidation current of [FeI] at t, I0 = initial oxidation current of [FeI]).
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O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70 2
rent interruption, indicating the presence of an enolate likely to be stabilized by the presence of iron(II).
(I)
O1
0 4
-2
3.3. Study of FeBr2 in the presence of 2,2 0 -bipyridine, methyl 2-chloropropanoate, and cyclohexanone
O1
(a)
(b)
-6
-4
-8
(c) (d)
-8 -10
I / µA
I / µA
0
-4
-2
-1.5
(a) (b) (c) (d)
(II) R1
-2 -12
-1.5
-0.5
-1
0
0.5
1
E / V vs. SCE
R1 -1
-0.5
0
0.5
1
E / V vs. SCE Fig. 7. (I)Cyclic voltammograms of FeBr2 (5 mM) in the presence of 2,2 0 -bipyridine (15 mM) recorded with a platinum disk electrode (0.5 mm diameter) at 0.2 V s1 in DMF containing 0.10 M TBABF4. (a) In the absence of and (b) in the presence of 1, (c) 2, and (d) 3 molar equivalents of methyl 2-bromopropanoate. (II) Cyclic voltammograms of fluorenone (5 mM) recorded under the same conditions as for (I). (a) In the absence of and (b) in the presence of 1, (c) 2, and (d) 3 molar equivalents of methyl 2-bromopropanoate.
On the basis of our results and of those reported by Zeuli and Inesi dealing with the indirect and direct reduction of bromoesters, the reduction of a-haloesters therefore leads to the corresponding radical-anion along with the regeneration of FeII [26–30]. The radical-anion then undergoes a cleavage affording an ester radical and a free halide ion. The radical can then be reduced in two different ways: (1) it can accept an electron from the cathode or (2) it can undergo a homogeneous electrontransfer reaction with iron(I). In either case, an ester anion is produced. The reactivity of carbanions of the type (CH2CO2Et), obtained by electrochemical reduction of CH2(Br)CO2Et, has been widely studied by means of cyclic voltammetry and coulometry [30]. Evidence was found for coupling reactions leading to the formation of hydrogenated ester and dimeric products. In order to study the reactivity of (CH3CHCO2CH3) in the presence of iron, we carried out a controlled-current (I = 0.25 A) electrolysis, in DMF, of methyl 2-chloropropanoate (10 mmol) in the presence of FeBr2 prepared electrochemically (1.25 mmol; see below), 2,2 0 -bipyridine (5 mmol) and a sacrificial iron anode. Under these conditions the potential value remains constant and equal to 1.15 V corresponding to the foot of wave R1 (reduction of FeII into FeI). After 90% of the a-chloroester was consumed, the analysis of the crude solution, with the aid of GC and GC–MS, indicates the formation of methyl propionate as the major product along with dimers and Claisen-type products. The presence of the latter confirms the existence of the anion (CH3CHCO2CH3) obtained by reduction of (CH3CHCO2CH3). Interestingly, a small portion of the remaining a-chloroester was still consumed after cur-
To ascertain the role of iron in the coupling reaction between a-haloesters and carbonyl compounds, a preparative electrolysis of fluorenone has been carried out in a divided cell in the presence of cyclohexanone and methyl 2-chloropropanoate. A GC analysis of the solution at the end of the electrolysis did not reveal any trace of coupling product, confirming that iron is required for the coupling reaction. Preparative electrolyses of FeBr2 (5 mmol) in the presence of cyclohexanone (5 mmol) and various amounts of 2,2 0 -bipyridine have been performed in a divided cell and at a potential of 1 V corresponding to the foot of R1. To minimize self-condensation reactions, the a-chloroester was added in 3 portions: before starting the experiment (1.75 mmol) and after a charge of 340 C and 680 C were passed (2 · 1.75 mmol). In the presence of 5 molar equivalents of 2,2 0 -bipyridine no coupling product was observed whereas in the presence of 3 molar equivalents of ligand, traces of the b-hydroxy-ester were obtained. Furthermore, in the presence of 1 molar equivalent of bpy, and after a charge of 2 electrons per molecule of FeBr2 was passed (ca. 1000 C), only 50% of the initial ketone was consumed, and the coupling product was obtained in 50% yield. Interestingly, the a-chloroester was completely consumed, indicating an efficient condensation reaction probably due to a non-constant addition of the substrate. These experiments suggest the existence of two mechanisms depending on the bpy concentration. An indirect reduction of the achloroester by the electrogenerated FeI is involved when the bpy/Fe ratio is higher than 3, whereas an oxidative addition would occur for smaller ratios. A low-ligated iron (I) species must therefore exist in the latter case. Even though the use of a divided cell allows preparation of the b-hydroxyester with moderate yields, the presence of a stoichiometric amount of iron(II) is not convenient. To simplify the procedure, electrolyses were then carried out at a constant current of 0.25 A in an undivided cell and in the presence of a sacrificial iron anode. First, a pre-electrolysis of 1,2-dibromoethane (1.25 mmol) was run in the undivided cell in the presence of an iron rod to prepare FeBr2 electrochemically (1.25 mmol). The 2,2 0 -bipyridine ligand was then added along with the carbonyl compound (10 mmol) and a portion of the a-chloroester (0.3 mmol). During the experiment, the ester was also constantly added in the solution using a syringe pump with a rate of addition of 4.46 mmol/h.
O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70
When the electrolysis is run in the presence of one molecule of 2,2 0 -bipyridine per molecule of FeBr2 (Fig. 8 - curve A), the coupling product is formed throughout the experiment but more slowly than in the experiment performed in the divided cell as described above. Indeed, after a charge of 2 electrons per molecule of ketone was passed (ca. 2000 C), the b-hydroxyester is obtained in 35% yield instead of 50%. In addition, the formation of the coupling product slows down after a charge of 3600 C was passed. In terms of yield and faradaic yield, this result is not as good as that obtained in the divided cell. The origin of this is very likely due to the continuous generation of Fe2+ ions leading to a decrease of the bpy/Fe ratio and therefore to a less stable FeI. This drawback can be overcome with the use of a higher amount of 2,2 0 bipyridine. Curve B in Fig. 8 depicts the formation of b-hydroxyester when starting the electrolysis in the presence of 4 moles of ligand per mole of FeBr2. In this case, a better faradaic yield is obtained, but the coupling product arises after an induction period of approximately 470 C, corresponding to a bpy/Fe ratio equal to 1.35 instead of 4 before starting the electrolysis. As mentioned above, this suggests a change in the mechanism. The use of a sacrificial iron anode allows the decrease of the bpy / Fe ratio by the electrogeneration of Fe2+, and favours the oxidative addition reaction of the a-chloroester to FeI versus the electron transfer. Replacement of methyl 2-chloropropanoate with methyl 2-bromopropanoate leads to the same results, and the coupling product is not formed faster. Assuming a faster oxidative addition than in the presence of the chloroester, the coupling reaction is therefore the rate-limiting step. On the basis of these results, the electrochemical coupling reaction between a-haloesters and carbonyl compounds in the presence of FeBr2 and a sacrificial iron
69
anode could be improved by maintaining a bpy/Fe ratio close to one. This could be achieved by addition of 2,2 0 bipyridine throughout the experiment and at the same rate at which Fe2+ is generated and which depends on the current supplied. Scheme 5 shows a sequence of mechanistic steps that can account for the iron-mediated electrochemical reaction of a-haloesters with carbonyl compounds and an iron sacrificial anode in DMF. Note that 2,2 0 -bipyridine ligands have been omitted for simplification. The reaction is initiated with the reduction of FeII to I Fe which is stabilized by the presence of 2,2 0 -bipyridine. As long as the bpy/Fe ratio is higher than 3, an electron transfer occurs from the electrogenerated FeI to the ahaloester, leading to the regeneration of FeII and to the corresponding anion-radical (Path (A)). The cleavage of the latter, which may be concerted or not, produces an ester radical and a free chloride ion. The radical is readily reducible either at the electrode by a single electron uptake at the same potential as FeII or in solution by the electrogenerated FeI. Finally, the anion obtained mainly gives the protonated product. However, when the bpy/Fe ratio is close to 1, an oxidative addition of the a-haloester to FeI would occur (Path (B)). This would lead to the corresponding [ClFeIIICH(CH3)CO2CH3]. By analogy with the numerous Reformatsky reactions performed in the presence of zinc, chromium or indium, etc., we may then envisage the formation of an enolate followed by the reaction with the ketone leading to an iron-alkoxide [31,32].
FeII eFeI
10
(B)
CH3CH(Cl)CO2CH3
β-hydroxyester / mmol
(A) 8
(B)
(A)
6
FeII + [CH3CH(Cl)CO2CH3]
4
. [CH CHCO CH ] 3
2
2
3
. ClFeIIICH(CH3)CO2CH3
+ Cl -
e- or FeI
0 0
1000
2000
3000
4000
5000
6000
[CH3CHCO2CH3] - FeII
Charge / C 0
1
2
3
4
5
RCOR’, eR Fe O or FeIII
R'
O
II
O H+
6
Time / h
Fig. 8. Preparative electrolyses of FeBr2 (1.25 mmol) in the presence of cyclohexanone (10 mmol) and methyl 2-chloropropanoate (0.3 mmol at t = 0 then added to the solution at a rate of 4.46 mmol h1) in DMF. Formation of the coupling product (b-hydroxyester) as a function of the charge consumed. In the presence of 1 (A), and 4 (B) molar equivalents of 2,2 0 -bipyridine with respect to the starting FeBr2.
CH3CH2CO2CH3 +
dimers and Claisen products
R HO
R'
O O
+ Fe II or FeIII
Scheme 5. Reactions involved in the iron-mediated electrochemical coupling reaction between a-haloesters and carbonyl compounds. Path (A) bpy/Fe P 3 and path (B) bpy/Fe < 3.
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O. Buriez et al. / Journal of Electroanalytical Chemistry 578 (2005) 63–70
The latter is then easily converted into the corresponding b-hydroxyester by hydrolysis with 2M HCl. However, the presence of an additional electroreductive step in such a scheme cannot be totally excluded. More importantly, Scheme 5 indicates that the Reformatsky product is obtained only if both the carbonyl compound and the a-haloester are in the coordination sphere of the iron metal centre. If this condition is not fulfilled, the hydrogenation product is then formed.
4. Conclusion The use of cyclic voltammetry and preparative-scale electrolyses allowed us to investigate the mechanism leading to the synthesis of b-hydroxyesters via an electrochemical method in the presence of iron (a Reformatsky-type reaction) [17]. We showed especially that iron(I) is the species involved in the reaction with a-haloesters and that the presence of 2,2 0 -bipyridine is required to allow its stabilization. Under our analytical conditions (bpy/Fe P 3), an electron transfer from the electrogenerated FeI to the a-haloesters has been observed. Nevertheless, under these conditions, the coupling reaction does not occur, suggesting the existence of another mechanism. The presence of a sacrificial iron anode is therefore useful since the continuous generation of Fe2+ cations decreases the bpy/Fe ratio. When the bpy/ Fe ratio becomes lower than 3, an oxidative addition between the electrogenerated FeI and the a-haloesters may occur. We thus demonstrated that the key-point for the coupling reaction relies on the bpy/Fe ratio. In terms of faradaic yield, the best conditions for this electrosynthesis would be to keep a constant bpy/Fe ratio close to one. To perform this, the 2,2 0 -bipyridine should be continuously added in solution and at the same rate at which Fe2+ ions are electrogenerated.
Acknowledgment The authors are grateful to Pr. J.N. Verpeaux for helpful discussions.
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