Mechanism of the nickel-catalyzed electrosynthesis of ketones by heterocoupling of acyl and benzyl halides

Article abstract of DOI:10.1007/s007060070008

The mechanism of the nickel-catalyzed electrosynthesis of ketones by heterocoupling of phenacyl chloride and benzyl bromide has been investigated by fast scan rate cyclic voltammetry with [Ni(bpy)²⁺₃](BF^-₄)₂ as the catalytic precursor (bpy = 2,2′-bipyridine). The key step is an oxidative addition of Ni⁰(bpy) (electrogenerated by reduction of the Ni(II) precursor) to PhCH₂Br whose rate constant is found to be 10 times higher than that of PhCH₂COCl. The complex PhCH₂Ni^IIBr(bpy) formed in the oxidative addition is reduced at the potential of the Ni^II/Ni⁰ reduction by a two-electron process which affords an anionic complex PhCH₂Ni⁰(bpy)^- able to react with PhCH₂COCl to generate eventually the homocoupling product PhCH₂COCH₂Ph. The formation of the homocoupling product PhCH₂COCOCH₂Ph is prevented because of the too slow oxidative addition of Ni⁰(bpy) to PhCH₂COCl compared to PhCH₂Br. The formation of the homocoupling product PhCH₂CH₂Ph is also prevented because PhCH₂Ni⁰(bpy)^- does not react with PhCH₂Br. This explains why the electrosynthesis of the ketone can be performed selectively in a one-pot procedure, starting from an equal mixture of PhCH₂COCl and PhCH₂Br and a nickel catalyst ligated by the bpy ligand.

Full text of DOI:10.1007/s007060070008

Monatshefte f uÈ r Chemie 131, 1293±1304 (2000)
Mechanism of the Nickel-Catalyzed
Electrosynthesis of Ketones by Heterocoupling
of Acyl and Benzyl Halides
Christian Amatore1 , Anny Jutand , Jacques P e richon2,
;Ã
1;Ã
and Yolande Rollin1
1
Ecole Normale Sup e rieure, D e partement de Chimie, UMR CNRS 8640, F-75231 Paris, France
Laboratoire d'Electrochimie, Caytalyse et Synth eÁ se Organique (LECSO), CNRS, F-94320 Thiais,
2
France
Summary. The mechanism of the nickel-catalyzed electrosynthesis of ketones by heterocoupling of
phenacyl chloride and benzyl bromide has been investigated by fast scan rate cyclic voltammetry with
2
3
‡
�
0
[
Ni(bpy) ](BF )2 as the catalytic precursor (bpy ˆ 2; 2 -bipyridine). The key step is an oxidative
4
0
addition of Ni (bpy) (electrogenerated by reduction of the Ni(II) precursor) to PhCH Br whose rate
2
II
constant is found to be 10 times higher than that of PhCH COCl. The complex PhCH Ni Br(bpy)
2
2
II
0
formed in the oxidative addition is reduced at the potential of the Ni /Ni reduction by a two-electron
0
process which affords an anionic complex PhCH Ni (bpy) able to react with PhCH COCl to generate
�
2
2
eventually the homocoupling product PhCH COCH Ph. The formation of the homocoupling product
2
2
0
PhCH COCOCH Ph is prevented because of the too slow oxidative addition of Ni (bpy) to
2
2
PhCH COCl compared to PhCH Br. The formation of the homocoupling product PhCH CH Ph is also
2
2
2
2
0
prevented because PhCH Ni (bpy) does not react with PhCH Br. This explains why the electro-
�
2
2
synthesis of the ketone can be performed selectively in a one-pot procedure, starting from an equal
mixture of PhCH COCl and PhCH Br and a nickel catalyst ligated by the bpy ligand.
2
2
Keywords. Electron transfer; Heterocoupling; Kinetics; Mechanism; Nickel.
Introduction
The synthesis of symmetrical biaryls by homocoupling of aryl halides [1] or tri¯ates
[2] requires a nickel or palladium catalyst and a reducing agent: a metallic powder
or the electrons delivered by a cathode (Eq. (1)).
Ni or Pd
ArX ‡ 2e ꢀor Zn† ����! ArAr ‡ 2X ꢀor ZnX †
�
�
2
ꢀ1†
The detailed mechanism of such reactions has been established under catalytic
2
conditions [3] for a nickel catalyst ligated by a bidentate phosphine (dppe ˆ 1,2-bis-
(diphenylphophino)-ethane) in which monoelectronic transfers are involved (Scheme
1) [4a,b] and for a palladium catalyst ligated by a monodenate phosphine (PPh ) in
which the reaction proceeds via bielectronic transfers (Scheme 2) [5]. When the
3
à Corresponding author

1294
C. Amatore et al.
Scheme 1. Mechanism of the Ni-catalyzed homocoupling of aryl halides
II
Pd X L
2
2
−
+
2e −X
ArAr
ArX
0
−
Pd L X
2
(4)
(1)
−
X
II
−
2
Ar Pd XL
2
(3)
II
ArPd XL
2
ArX
0
−
ArPd L
2
(2)
−
X
2e
Scheme 2. Mechanism of the Pd-catalyzed homocoupling of aryl halides
0
nickel catalyst is ligated by PPh [4c] or by 2,2 -bipyridine (bpy) [4d], the
3
mechanism is similar to that reported in Scheme 1.
In both mechanisms, two sequential oxidative additions are involved: between
0
ArX and an M complex (steps 1 in Schemes 1 and 2) and between ArX and an Ar-
M complex (step 3 in Scheme 1) or an Ar-M complex (step 3 in Scheme 2). Those
I
0�

Ni-Catalyzed Electrosynthesis of Ketones
1295
oxidative additions are separated by either a monoelectronic transfer (step 2 in
Scheme 1) or by a bielectronic transfer (step 2 in Scheme 2).
The rate of oxidative additions strongly depends on the aryl derivatives
(reactivity order: ArI > ArOTf > ArBr > ArCl [6]) as well as on the Ar structure,
Aryl derivatives being more reactive when substituted by electron-withdrawing
groups [6b,c, 7]. For these reasons, starting with a stoichiometric mixture of two
0
0
differently reactive substrates ArX and Ar X affords a mixture of symmetrical and
unsymmetrical biaryls [5, 8] (Eq. (2)).
Ni or Pd
0
0
�
0
0
0
�
0�
ArX ‡ Ar X ‡ 2e ����! ArAr ‡ ArAr ‡ Ar Ar ‡ X ‡ X
ꢀ2†
Therefore, the synthesis or electrosynthesis of unsymmetrical biaryls by hetero-
coupling of two different aryl derivatives is problematic. This dif®culty may be by-
passed by starting with the less reactive aryl halide in a batch process [5] or by a
slow controlled introduction of the more reactive aryl halide during the course of the
electrosynthesis using a syringe pump [8]. However, the Ni- or Pd-catalyzed cross-
0
0
coupling of an aryl halide ArX and an organometallic derivative Ar MX (M ˆ Mg,
Zn) remains the most ef®cient process for the synthesis of unsymmetrical biaryls
(Eq. (3)) [9]. Indeed, only the ®rst oxidative addition step is required, the second
one being replaced by a transmetallation step of the ArM XL complex by the
II
2
0
0
organometallic derivative Ar MX , which of course requires to be preliminary
0
0
synthesized from Ar X .
Ni or Pd
ArX ‡ Ar MX �� �� ! ArAr ‡ MXX
0
0
0
0
ꢀ3†
On the contrary, the Ni-catalyzed heterocoupling of acyl and benzyl halides can
be achieved in a one-pot procedure starting from an equal amount of the two
0
organic reagents and a nickel catalyst ligated by the 2,2 -bipyridine ligand; the
electrosyntheses afford selectively the corresponding ketones (Eq. (4)) [10].
Ni
0
0
�
0
�
0�
RCOX ‡ R X ‡ 2e �! RCOR ‡ X ‡ X
ꢀ4†
This result necessarily requires that a different mechanism operates in which at least
one step is not an oxidative addition. We report herein a mechanistic investigation of
this reaction starting from an acyl chloride, a benzyl bromide, and a nickel catalyst
ligated by the bpy ligand (Eq. (5)).
2
3
‡
�
‰
Niꢀbpy† ŠꢀBF †
2
�
4
�
�
PhCH COCl ‡ PhCH Br ‡ 2e �������������! PhCH COCH Ph ‡ Cl ‡ Br
2
2
2
2
�
1:2 V vs: SCE; CH3CN
ꢀ
5†
Results and Discussion
Rate and mechanism of the oxidative addition of Ni (bpy) to PhCH Br
0
2
2
The mechanism of the electrochemical reduction of NiX (bpy) (X ˆ Cl, Br) in polar
2
solvents such as NMP [11] or DMF [4d] has been reported. Depending on the
halide ligated to the Ni(II) complex and the solvent, the electrochemical reduction
may proceed in two one-electron steps (X ˆ Cl in DMF or X ˆ Br in NMP [4d, 11])
or in one two-electron step (X ˆ Br in DMF [4d] or in NMP in the presence of

1296
C. Amatore et al.
excess bpy [11]). When the reduction is performed in the presence of excess bpy,
the resulting Ni(0) complex is ligated by two bpy ligands (Ni (bpy) ). However, the
0
2
0
reactive complex in oxidative additions in the low-ligated complex Ni (bpy), as
evidenced by a negative (� 1) reaction order in bpy (Eqs. (6, 7)) [11].
0
0
Ni ꢀbpy† „ Ni ꢀbpy† ‡ bpy
ꢀ6†
ꢀ7†
2
0
II
Ni ꢀbpy† ‡ PhBr �! PhNi Brꢀbpy†
The cyclic voltammogram of a solution of [Ni(bpy) ](BF ) (2 mM in acetonitrile
2
3
‡
�
4
2
�
3
containing 0.3 mol Á dm n-Bu NBF as supporting electrolyte) at a steady gold disk
4
4
electrode in the presence of excess bpy (40 mM) exhibited a single quasi-reversible
reduction peak R at � 1.25 V vs. SCE (Fig. 1a, solid line), followed by a second
1
quasi-reversible reduction peak R at � 1.94 Vof half magnitude [12]. Determination
2
of the absolute number of electron(s) involved in the ®rst process revealed a two
electron transfer at R [13] (Eq. (8)) under the conditions of Fig. 1a. Consequently,
1
R involves a one-electron transfer, the electron being presumably transferred to the
2
bpy ligand (Eq. (9)) as already observed for the reduction of NiBr (bpy) [11].
2
II
2‡
�
0
Ni ꢀbpy† ‡ 2e �! Ni ꢀbpy† ‡ bpy at R
ꢀ8†
ꢀ6†
ꢀ9†
1
3
2
0
0
Ni ꢀbpy† „ Ni ꢀbpy† ‡ bpy
2
0
0
ꢁ�
Ni ꢀbpy† ‡ 1e �! Ni ꢀbpy†
at R2
The Ni(0) complex formed in the electrochemical reduction at R was characterized
1
by its oxidation peak O at � 1.15 V (Fig. 1a, solid line). The mechanism of the
1
‡
2
3
�
4
2
NiBr (bpy) in the presence of excess bpy in DMF or NMP [4d, 11].
reduction of [Ni(bpy) ](BF ) in acetonitrile is thus very similar to that of
2
2
3
‡
�
When the electrochemical reduction of [Ni(bpy) ](BF ) was performed at low
2
4
scan rate (0.5 V s ) in the presence of PhCH Br (from 1 to 12 equivalents), the
�
1
2
0
oxidation peak O of the electrogenerated Ni (bpy) was no longer observed (Fig. 1a,
1
2
0
dashed line) as well as the reduction peak at R , evidencing a reaction of Ni (bpy)
2
2
with PhCH Br. Under these conditions, the reduction peak current intensity of
2
2
‡
Ni(bpy) ](BF ) at R exactly doubled (Fig. 1a, dashed line; note the twofold
3
1
�
[
4
2
increased scaling) independent of the excess of PhCH Br. These experiments show
2
0
that the electrogenerated Ni (bpy) complex undergoes an oxidative addition to
2
II
PhCH Br affording a 16-electron complex PhCH Ni Br(bpy) whose electrochemical
2
2
2
3
‡
�
reduction occurs at the same reduction potential as that of [Ni(bpy) ](BF ) (or at
2
4
less negative potential) and also involves two electrons, resulting in an overall four-
electron process at R (Eqs. (10, 11)).
1
app
k1
0
II
Ni ꢀbpy† ‡ PhCH Br �! PhCH Ni Brꢀbpy† ‡ bpy
PhCH Ni Brꢀbpy† ‡ 2e �! PhCH Ni ꢀbpy† ‡ Br
ꢀ10†
ꢀ11†
2
2
2
II
�
0
�
�
at R1
2
2
This four-electron reduction ends up with the formation of an anionic 16-electron
0
complex PhCH Ni (bpy) , formally a Ni complex ligated by the anion PhCH .
�
0
�
2
2
0
Similar anionic ArPd (PPh ) complexes have been characterized during the
�
II
3
2
0
bielectronic reduction of ArPd Br(PPh ) [14]. Although ArPd (PPh ) complexes
�
3
2
3
2
are involved in an equilibrium with the anion Ar and Pd (PPh ) this is not the
�
0
3
2

Ni-Catalyzed Electrosynthesis of Ketones
1297
2
‡
Fig. 1. Cyclic voltammetry performed in acetonitrile (containing 0.3 M n-Bu NBF ) at a steady
4
4
�
1
ꢂ
2‡
�
gold disk electrode (i.d.: 0.5 mm) at a scan rate of 0.5 V Á s at 25 C; a) (Ð): [Ni(bpy) ](BF )
3
4
2
0
2‡
�
4
2
0
(
2 mM) and 2,2 -bipyridine (40 mM); ( Á ± Á ± Á ): [Ni(bpy) ](BF ) (2 mM), 2,2 -bipyridine (40 mM),
3
and PhCH Br (8 mM); b) same experimental conditions as in Fig. 1a except that both
2
�
1
voltammograms were performed at a faster scan rate (500 V Á s ), at a smaller gold disk electrode
i.d.: 0.125 mm), and recorded at the same current scaling
(
0
�
�
2
case for PhCH Ni (bpy) since the anion PhCH , if present, would easily react
2
with PhCH Br producing PhCH CH Ph in a catalytic process. This reaction can be
2
2
2
excluded since (i) the reduction peak R is not a catalytic peak (i.e. its current
1
intensity does not increase with PhCH Br concentration provided it is over-
2
stoichiometric) and (ii) no PhCH CH Ph was formed during an electrosynthesis
2
2
performed at the potential of R (� 1.2 V).
1
�
1
When the scan rate ꢀ was progressively increased (from 0.2 to 2000 V Á s ), the
reduction peak at R became more and more reversible (Fig. 1b, dashed line), and its
1
reduction peak current relatively decreased, going from 4 to 2 electrons, as evidenced
by the plot of i (R )/i (R ) vs. log([PhCH Br]/ꢀ) (Fig. 2a); i (R ) is the reduction
red
red
red
1
1 0
2
1
red
peak current at R in the presence of PhCh Br, i (R ) is the reduction peak current
1
2
1 0
at R in the absence of PhCH Br; both currents were determined at the same scan
2
1
rate) [15]. This behavior is characteristic of the progressive suppression of a
subsequent chemical step involving PhCH Br with a reaction order of unity when the
2
time scale of the experiment is decreased (i.e. when the scan rate ꢀ is increased). The
curves shown in Fig. 2a are thus representative of the kinetics of the oxidative
0
addition of PhCH Br to the electrogenerated Ni (bpy) (Eq. (10)). The higher the
2
2

0
Fig. 2. a) Kinetics of the oxidative addition of PhCH Br to the Ni (bpy) complex generated by the
2
2
2
3
‡
�
reduction of [Ni(bpy) ](BF ) (2 mM) in the presence of 2,2-bipyridine (40 mM) in acetonitrile
4
2
ꢂ
containing 0.3 M, n-Bu NBF ) at 25 C: variation of i (R )/i (R ) vs. log([PhCH Br]/ꢀ). i (R1)
4 4 1 1 0 2
red
red
red
(
is the reduction peak current at R (see Fig. 1) in the presence of PhCH Br ([PhCH Br] ˆ 4 mM (‡),
1
2
2
red
mM (&), 12 mM (o)), i (R ) is the reduction peak current at R in the absence of PhCH Br. Both
1
8
1
0
1
2
�
currents were determined at the same scan rate in the range 0.2 < ꢀ < 2000 V Á s . The solid line is
app
the theoretical kinetic curve [15] with k ˆ 6  10 M
4
� 1 � 1
s [15a]. b) Kinetics of the catalysis of
1
0
the homocoupling of PhCH Br by the Ni (bpy) complex generated by the reduction of
2
2
2
‡
� 0
Ni(bpy) ](BF ) (2 mM) in the presence of 2,2 -bipyridine (40 mM) in acetonitrile (containing
3
4
2
[
ꢂ
.3 M, n-Bu NBF ) at 25 C: variation of i (R )/i (R ) vs. log([PhCH Br]/ꢀ). i (R ) is the
4 4 3 1 0 2 3
red
red
red
0
reduction peak current at R (see Fig. 1) in the presence of PhCH Br ([PhCH Br] ˆ 4 mM (‡), 8 mM
3
2
2
red
&), 12 mM (o)), i (R ) is the reduction peak current at R in the absence of PhCH Br. Both
1
(
1
0
1
2
currents were determined at the same scan rate in the range 0.2 < ꢀ < 1000 V Á s�
.

C. Amatore et al.: Ni-Catalyzed Electrosynthesis of Ketones
1299
scan rate, the smaller the time scale for the oxidative addition, and consequetly the
smaller the amount of PhCH Ni Br(bpy) formed during the voltammetric scan. The
II
2
rate constant of the overall oxidative addition (Eq. (10)) was determined after a
� 1 � 1
app
simulation of the theoretical kinetic curve [15b] to k1 ˆ 8  10 M s . In the
5
presence of added bpy (20 equivalents), the rate of the oxidative addition was smaller
4
app
� 1 � 1
(
k1 ˆ 6  10 M s ).
0
Mechanism of the Ni (bpy) -catalyzed homocoupling of PhCH Br
2
2
2
3
‡
�
When the electrochemical reduction of [Ni(bpy) ](BF ) was performed at low
2
4
�
1
scan rate (0.5 V Á s ) in the presence of an excess of PhCH Br, a new irreversible
2
reduction peak R was observed at � 1.57 V (Fig. 1a, dashed line) whose peak
3
current was found to increase when the PhCH Br concentration was increased (Fig.
2
2
b). Since peak R does not pertain to the electrochemistry of PhCH Br whose
3 2
reduction potential is more negative than � 1.6 V, it features a catalytic process. The
reduction current of this catalytic peak relatively decreased when the scan rate was
increased. The decrease of the reduction current of R was concomitant with the
3
�
�
decrease of the current R from 4e to 2e (compare Fig. 1a, dashed line, with Fig.
1
1b, dashed line). This coincidence is better seen in Fig. 2b which shows the plot of
i (R )/i (R ) vs. log([PhCH Br]/ꢀ) (i (R ) is the reduction peak current at R in
red
red
red
3
1 0
2
3
3
red
the presence of PhCH Br, i (R ) is the reduction peak current at R in the absence
2
1 0
1
of PhCH Br; both currents were determined at the same scan rate). Peak R corre-
2
3
sponds therefore to the second reduction step of the complex formed in the oxidative
addition, presumably through injection of one electron to the bpy ligand (Eq. (12)).
0
�
�
0
2�
PhCH Ni ꢀbpy† ‡ e �! PhCH Ni ꢀbpy†
at R3
ꢀ12†
As recalled above, an electrolysis performed at the reduction potential of R1
2
2
(
� 1.2 V) did not afford any PhCH CH Ph, whereas the latter was formed when the
2
2
electrolysis was performed at the reduction potential of R (� 1.6 V) according to
3
the overall reaction given in Eq. (13).
2
3
‡
�
4
2
‰
Niꢀbpy† ŠꢀBF † ; � 1:6 V
�
�
2
PhCH Br ‡ 2e �������������� �� ! PhCH CH Ph ‡ 2Br ꢀ13†
To account for the catalytic current, the 17-electron complex PhCH Ni (bpy) ,
2
2
2
0
2�
2
electrogenerated at R , must then react with PhCH Br (Eq. (14)) in a reaction
3
2
0
which should ultimately regenerate PhCH Ni (bpy) (Eq. (15)).
2�
2
0
2�
0
�
�
PhCH Ni ꢀbpy† ‡ PhCH Br !! PhCH CH Ph ‡ Ni ꢀbpy† ‡ Br
ꢀ14†
2
2
2
2
�
2
e
0
�
II
�
0
2�
�
Ni ꢀbpy† ‡ PhCH Br ! PhCH Ni Brꢀbpy† �! PhCH Ni ꢀbpy† ‡ Br
2
2
2
ꢀ
15†
0
�
However, at the potential of � 1.6 V, Ni (bpy) should be oxidized (Fig. 1a, solid line).
0
This suggests that either Ni (bpy) undergoes a fast oxidative addition to PhCH Br
�
2
(Eq. (15)) before being oxidized or that the mechanism of the Ni(bpy)-catalyzed
homocoupling of PhCH Br (Eq. (13)) is more complex (formation of Ni Br(bpy) ).
0
2�
2
Since PhCH CH Ph was not formed during the electrosynthesis of the ketone
2
2
by the heterocoupling of PhCH Br and PhCH COCl (Eq. (5)) because the
2
2
electrolysis potential was less negative (� 1.2 V) than the reduction potential

1300
C. Amatore et al.
required for the formation of PhCH CH Ph (� 1.6 V), the mechanism of the Ni-
2
2
catalyzed homocoupling of PhCH Br (Eq. (13)) has not been investigated in much
2
more details, focusing our attention on the mechanism of the heterocoupling.
Nevertheless, it is worthwhile noting that the mechanism observed for the Ni(bpy)-
catalyzed homocoupling of benzyl halides differs from the mechanism of the
NiCl (dppe) or PdCl (PPh ) -catalyzed homocoupling of aryl halides (Schemes 1
2
2
3 2
and 2). This is due to the aptitude of the bpy ligand to accept electrons, a feature
which cannot not occur with dppe or PPh . This property enables the formation of
3
0
the 17-electron complex PhCH Ni (bpy) which is a key intermediate at the
2�
2
origin of the catalytic cycle of the PhCH Br homocoupling.
2
0
Rate and mechanism of the oxidative addition of Ni (bpy) to PhCH COCl
2
2
2
3
‡
�
When the electrochemical reduction of [Ni(bpy) ](BF ) (2 mM in acetonitrile)
2
4
�
1
was performed at low scan rate (0.5 V Á s ) in the presence of bpy (40 mM) and an
excess of PhCH COCl (in the range from 1 to 12 equivalents), the oxidation peak
2
0
O of the electrogenerated Ni (bpy) was no longer observed (Fig. 3a, dashed line),
1
2
0
evidencing a reaction of Ni (bpy) with PhCH COCl. Concomitantly, the reduction
2
2
2
‡
�
peak current of [Ni(bpy) ](BF ) at R increased (Fig. 3a, dashed line) to reach a
2
2
value independent of the PhCH COCl concentration and corresponding to an overall
4
1
2
process involving three electrons [16]. These experiments show that the electro-
generated Ni (bpy) complex undergoes an oxidative addition to PhCH COCl, afford-
0
2
2
II
ing a 16-electron complex PhCH CONi Cl(bpy) whose electrochemical reduction
2
2
3
‡
�
occurs at the same reduction potential as that of [Ni(bpy) ](BF ) (or at less negative
2
4
potential) and involves one electron, resulting in an overall three electron process at
I
R (Eq. (16, 17)). This ends up with the formation of an acyl-Ni complex.
app
1
k2
0
II
Ni ꢀbpy† ‡ PhCH COCl ���! PhCH CONi Clꢀbpy† ‡ bpy
ꢀ16†
ꢀ17†
2
2
2
II
�
I
�
PhCH CONi Clꢀbpy† ‡ 1e �! PhCH CONi ꢀbpy† ‡ Cl at R
2
2
1
0
A kinetic investigation of the oxidative addition of Ni (bpy) to PhCH COCl (Eq.
2
2
(
16)) by varying the scan rate as done with PhCH Br (see above) allows the
2
app
4
� 1 � 1
determination of the rate constant. It amounts to k2 ˆ 8  10 M s , i.e. it is ten
0
times smaller than the rate constant of the oxidative addition of Ni (bpy) to
2
PhCH Br under the same conditions. This establishes that in the presence of identical
2
0
concentrations of PhCH Br and PhCH COCl the electrogenerated Ni (bpy) pre-
2
2
2
ferentially undergoes an oxidative addition to PhCH Br.
2
0
Mechanism of the Ni (bpy) -catalyzed heterocoupling of PhCH COCl
2
2
and PhCH Br (Eq. (5))
2
From the kinetic investigations described above it ensures that the ®rst step of the
heterocoupling catalytic cycle is the oxidative addition of Ni (bpy) to PhCH Br
0
2
2
II
affording PhCH Ni Br(bpy). This complex is simultaneously reduced at R by a
2
1
0
two-electron process. As discussed above, the complex PhCH Ni (bpy) electro-
�
2
generated at R does not react with PhCH Br.
1
2
2
3
‡
�
When [Ni(bpy) ](BF ) (2 mM in acetonitrile) was reduced at low scan rates
2
4
in the presence of PhCH Br (12 mM) but in the absence of PhCH COCl, the cyclic
2
2

Ni-Catalyzed Electrosynthesis of Ketones
1301
Fig. 3. Cyclic voltammetry performed in acetonitrile (containing 0.3 M, n-Bu NBF ) at a steady gold
4
4
�
1
ꢂ
2‡
�
0
disk electrode (i.d.: 0.5 mm) at a scan rate of 0.5 V Á s at 25 C. a) [Ni(bpy) ](BF ) (2 mM), 2,2 -
3
4
2
2
3
‡
�
4
2
0
bipyridine (40 mM), and PhCH COCl (8 mM); b) [Ni(bpy) ](BF ) (2 mM), 2,2 -bipyridine
2
(
40 mM), PhCH Br (8 mM), and PhCH COCl (0 mM (Ð), 6 mM (-ꢁ-ꢁ-ꢁ-), 12 mM ( Á ± Á ± Á ),
2
2
2
4 mM (- - - -))
voltammogram exhibited the four-electron reduction peak R (Fig. 3b, solid line),
1
0
featuring the formation of PhCH Ni (bpy) . The reduction peak current of R
�
2
1
increased in the presence of increasing amounts of PhCH COCl (in the range of 6
2
0
to 24 mM) (Fig. 3b, dotted and dashed lines), although Ni (bpy) was no longer
2
available for a reaction with PhCH COCl [17]. Therefore, in the presence of both
2
PhCH Br and PhCH COCl, a catalytic process was initiated at R . This agrees with
2
2
1
the fact that the electrosynthesis of PhCH COCH Ph by the Ni(bpy)-catalyzed
2
2
heterocoupling of PhCH Br and PhCH COCl was indeed performed at � 1.2 V, i.e.
2
2
at the reduction potential of R (Eq. (5)) [10], thus giving clear evidence that the
1
0
second step of the catalytic cycle is a reaction of PhCH Ni (bpy) (i.e. the species
�
2
electrogenerated at R in the presence of PhCH Br) with PhCH COCl. This
1
2
2
reaction must eventually yield the heterocoupling product PhCH COCH Ph,
2
2
0
together with a Ni complex able to initiate a second catalytic cycle at the potential
of R (Eq. (18)).
1
0
�
0
�
PhCH Ni ꢀbpy† ‡ PhCH COCl !! PhCH COCH Ph ‡ Ni ꢀbpy† ‡ Cl ꢀ18†
2
2
2
2

1302
C. Amatore et al.
Scheme 3. Mechanism of the Ni-catalyzed heterocoupling of benzyl bromide and phenacyl chloride
0
Since PhCH Ni (bpy) does not react with PhCH Br and since the oxidative
�
2
2
addition of Ni(0) is even slower with phenacyl chloride than with benzyl bromide,
we propose that the reaction described by Eq. (18) is a nucleophilic substitution of
PhCH COCl by the anionic PhCH Ni (bpy) (step 3 in Scheme 3), followed by the
0
�
2
2
reductive elimination of PhCH COCH Ph (step 4 in Scheme 3) to regenerate the
2
2
0
Ni (bpy) complex which closes the catalytic cycle.
Conclusions and final remarks
The success of the Ni(bpy)-catalyzed heterocoupling of benzyl bromide and
phenacyl chloride comes from the fact that the oxidative addition of Ni (bpy) to
0
2
0
PhCH Br is faster than that to PhCH COCl and also that PhCH Ni (bpy) cannot
�
2
2
2
undergo a second oxidative addition to PhCH Br to produce PhCH CH Ph as it
2
2
2
0
was observed for ArPd (PPh ) which is able to react with ArX (Scheme 2). The
�
3
2
mechanism established here for the Ni-catalyzed heterocoupling (Scheme 3) is,
however, very reminiscent of the Pd-catalyzed homocoupling mechanism (Scheme
2
) in the sense that only bielectronic transfers are involved.

Ni-Catalyzed Electrosynthesis of Ketones
1303
The catalytic heterocoupling of benzyl bromide and acyl chlorides to form
ketones PhCH COR can therefore be selectively achieved in one pot, starting from
2
an equal mixture of the two organic reagents and a catalytic amount of a nickel
catalyst ligated by the bpy ligand [10]. These reactions afford selectively ketones
because the electrolyses can be conducted at a low potential: the reduction
potential of Ni(II) to Ni(0). This prevents the formation of the homocoupling
product PhCH CH Ph which requires a more negative potential. The homocou-
2
2
pling product RCOCOR is not formed as well, due to the too slow oxidative
addition of Ni (bpy) to RCOCl derivatives compared to PhCH Br.
0
2
2
Experimental
General
All experiments were performed under argon using Schlenk techniques. The chemicals were standard
reagent grade. They were used without further puri®cation except for PhCH COCl which was
2
distilled before use. PhCH Br and acetonitrile were ®ltered over alumina under inert atmosphere.
2
2
‡
Ni(bpy) ](BF ) was synthesized according to the literature [18].
3
�
[
4
2
Electrochemical set-up and electrochemical procedure for voltammetry
Cyclic voltammetry was performed with a wave-form generator PAR Model 175 and a home-made
potentiostat equipped with an ohmic drop compensation. The cyclic voltammograms were recorded
with a Nicolet 3091 digital oscilloscope. Experiments were carried out in a three-electrode cell
2
connected to Schlenk line. The counter electrode was a platinum wire of ca. 1 cm apparent surface
area; the reference was a saturated calomel electrode (Radiometer Analytical Tacussel) separated
� 3
3
from the solution by a bridge ®lled with 3 cm of acetonitrile containing n-Bu NBF (0.3mol Á dm ).
4
4
3
� 3
1
2 cm of acetonitrile containing n-Bu NBF (0.3mol Á dm ) were poured into the cell, followed by
4
4
2
‡
� 0
Ni(bpy) ](BF ) (16.8 mg, 0.024 mmol), 2,2 -bipyridine (75 mg, 0.48 mmol), and suitable amounts
3 4
2
[
of PhCH Br (or/and PhCH COCl). Cyclic voltammetry was performed at a steady gold disk electrode
2
2
i.e.: 0.5 mm, scan rates: 0.2±10 V Á s� , i.d.: 0.125 mm, scan rates: 20±2000 V Á s� 1).
1
(
Acknowledgements
This work was supported by the Centre National de la Recherche Scienti®que (CNRS, UMR 8640
PASTEUR) and the Minist eÁ re de la Recherche (Ecole Normale Sup e rieure). Y. Rollin thanks the
Universit e de Cr e teil for ®nancial support of her post-doctoral position.
References
[
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(
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[
2] (a) Yamashita J, Inoue Y, Kondo T, Hashimoto H (1986) Chem Lett 407; (b) Jutand A, Negri S,
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(
d) Jutand A, Mosleh A (1997) J Org Chem 62: 261

1304
C. Amatore et al.: Ni-Catalyzed Electrosynthesis of Ketones
[
3] Under stoichiometric conditions (Ni:ArX ˆ 1:1), a different mechanism may operate, involving
II III
scrambling reactions between aryl-Ni and aryl-Ni species; see: Tsou TT, Kochi JK (1979) J
Am Chem Soc 101: 7547
4] (a) Amatore C, Jutand A (1988) Organometallics 7: 2203; (b) Amatore C, Jutand A, Mottier L
[
(
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[
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7] (a) Fauvarque JF, P¯ uÈ ger F, Troupel M (1981) J Organomet Chem 208: 419; (b) Amatore C,
Azzabi M, Jutand A (1991) J Am Chem Soc 113: 8375
[
[
[
8] Meyer G, Troupel M, P e richon J (1990) J Organomet Chem 393: 137
9] (a) Negishi EI, Hayashi T, King AO (1987) Org Synth 66: 67; (b) Amatore C, Jutand A, N e gri S,
Fauvarque JF (1990) J Organomet Chem 390: 389
[
[
10] Marzouk H, Rollin Y, Folest JC, N e d e lec JY, P e richon J (1989) J Organomet Chem 369: C47
[
11] Troupel M, Rollin Y, Sock O, Meyer G, P e richon J (1986) Nouv J Chim 10: 593
[12] For a given electroactive species, at a given scan rate, the value of the peak current is proportional
to the concentration of the species and to the number of electron(s) involved in the overall
reaction initiated by the initial electron transfer at the scan rate of the measurement. Yet, the
proportional constant depends on the mechanism at hand.
[
[
[
13] Amatore C, Azzabi M, Calas P, Jutand A, Lefrou C, Rollin Y (1990) J Electroanal Chem 288: 45
14] Amatore C, Jutand A, Khalil F, Nielsen MF (1992) J Am Chem Soc 114: 7076
red red
15] a) The ratio i (R )/i (R ) went from 2.2 to 1, corresponding to the passage of an irreversible
1
1 0
peak involving four electrons to a reversible one involving two electrons [15b]; b) Nadjo L,
Sav e ant JM (1973) J Electroanal Chem 48: 113
[
16] The reduction potential of PhCH COCl alone under identical experimental conditions is � 2.48 V
2
vs. SCE. It is worthwhile to note that PhCH COCl undergoes a slow reaction with 2,2-bipyridine
2
to form a bipyridinium salt which was redued at � 0.98 V. This is why the mechanistic
investigation in the presence of the nickel catalyst was performed on freshly prepared solutions.
The solutions were renewed as soon as the reduction peak of the bipyridinium salt appeared at
�
0.98 V.
[
[
17] If a competitive reaction between PhCH Br and PhCH COCl would occur, a decrease of the peak
2
2
current of R should be observed since R involves a three-electron process with PhCH COCl vs.
1
1
2
a four-electron process with PhCH Br.
2
18] Garnier L, Rollin Y, P e richon J (1989) J Organomet Chem 13: 53
Received June 27, 2000. Accepted July 11, 2000