An electrochemical coupling of organic halide with aldehydes, catalytic in chromium and nickel salts. the Nozaki-Hiyama-Kishi reaction.

Article abstract of DOI:10.1021/ol016033g

[reaction: see text] Electrochemical arylation of arenecarboxaldehydes using an iron sacrificial anode in the presence of chromium and nickel catalysts afforded the corresponding arylated secondary alcohols in moderate to good yields. The chromium and nickel salts as catalysts are obtained by oxidation of a stainless steel rod during a preelectrolysis in 7% and 3%, respectively. The process was also applied to the addition of vinyl halide, allyl acetate, or alpha-chloroester to aromatic aldehydes.

Full text of DOI:10.1021/ol016033g

ORGANIC
LETTERS
2001
Vol. 3, No. 13
2073-2076
An Electrochemical Coupling of Organic
Halide with Aldehydes, Catalytic in
Chromium and Nickel Salts. The
Nozaki−Hiyama−Kishi Reaction
Muriel Durandetti,* Jean-Yves Ne´de´lec, and Jacques Pe´richon
Laboratoire d’Electrochimie, Catalyse et Synthe`se Organique, CNRS, UMR 7582,
UniVersite´ Paris 12, 2 rue Henri-Dunant 94320 Thiais, France
durandetti@glVt-cnrs.fr
Received April 26, 2001
ABSTRACT
Electrochemical arylation of arenecarboxaldehydes using an iron sacrificial anode in the presence of chromium and nickel catalysts afforded
the corresponding arylated secondary alcohols in moderate to good yields. The chromium and nickel salts as catalysts are obtained by
oxidation of a stainless steel rod during a preelectrolysis in 7% and 3%, respectively. The process was also applied to the addition of vinyl
halide, allyl acetate, or r-chloroester to aromatic aldehydes.
The addition of vinyl, allyl, or aryl halides to aldehydes (the
Nozaki-Hiyama-Kishi reaction) via an intermediate chro-
mium(III) species is generally achieved by CrCl2 with a
catalytic amount of nickel chloride. This reaction has been
widely applied in organic synthesis.1 As a matter of fact, it
combines some rather unique features such as high aldehyde
chemoselectivity. Also, organochromium(III) compounds are
compatible with a large variety of functional groups. With
regards to the nucleophile, a wide range of substrates
including allyl, propargyl, aryl, or alkenyl halides, alkenyl
triflates, or allyl phosphates2 were found to be suitable
precursors for the formation of organochromium intermedi-
ates.
poisonous, this precludes any application of such transforma-
tions to industrial processes. Furthermore, the rather high
cost of CrCl2 makes large-scale syntheses less attractive.
Several groups have already tried to minimize the amount
of chromium reagent. Notably, the regeneration of CrII by
electroreduction,3 or by introduction of a reducing metal such
as Mn4 or Al,5 was recently reported. The reaction, with 20%
of chromium, has been applied to the alkenylation of
aromatic aldehydes bearing electron-donating substituents,
(2) For the use of substrates other than halides, see the following. (a)
For alkenyl triflates: Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.;
Utimoto, K.; Nozaki, H. J. Am. Chem. Soc. 1986, 108, 6048-6050. (b)
For allylic phosphates: Nowotny, S.; Tucker, C. E.; Jubert, C.; Knochel,
P. J. Org. Chem. 1995, 60, 2762-2772.
(3) (a) Grigg, R.; Putnikovic, B.; Urch, C. J. Tetrahedron Lett. 1997,
38, 6307-6308. (b) Kurobashi, M.; Tanaka, M.; Kishimoto, S.; Tanaka,
H.; Torii, S. Synlett 1999, 69-70.
(4) Fu¨rstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 12349-12357.
(5) Kurobashi, M.; Tanaka, M.; Kishimoto, S.; Goto, K.; Tanaka, H.;
Torii, S. Tetrahedron Lett. 1999, 40, 2785-2788.
This reaction, however, has serious drawbacks in that a
large amount of toxic CrII reagent, sometimes up to 400 mol
%, must be used. Since chromium salts are physiologically
(1) Wessjohann, L. A.; Scheid, G. Synthesis 1999, 1-36, and references
cited therein.
10.1021/ol016033g CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/07/2001

whereas electron-poor aromatic aldehydes gave poor results,
affording the corresponding pinacol predominantly. Finally,
although this reaction occurs with alkenyl halides, only a
few examples with aryl halides have been reported and those
are limited to aryl iodides. We report here an electrochemical
arylation of an aromatic aldehyde using only 7% of
chromium and applicable to aldehyde-bearing electron-
withdrawing substituents. We have previously described an
electrochemical version of the Nozaki-Hiyama-Kishi reac-
tion, catalytic in both chromium and nickel, applied to aryl
bromides and chlorides on one hand and to aromatic
aldehydes bearing electron-withdrawing groups on the other.6
We have shown that it is possible to realize this reaction
with a nickel catalyzed and a sacrificial stainless steel rod
anode, made in the weighting proportions Fe/Cr/Ni: 72/18/
10 (Scheme 1).
Table 1. Electroreductive Cross-Coupling between
Bromobenzene and Benzaldehyde
methoda
entry
(%Cr/%Ni released)
% alcoholb
% ketoneb,c
1
2
3
A (50/25)
B (20/10)
C (7/3)
50
52
65
6
5
3
a Method A: the electrolysis was totally conducted with the stainless
steel anode (Fe/Cr/Ni 72/18/10). Method B: the electrolysis was conducted
with the stainless steel anode for 1500 C and then continued with an iron
rod. Method C: a preelectrolysis is run with the stainless steel rod for 500
C and then the stainless steel rod is replaced by an iron rod. b Isolated yields,
based on the initial benzaldehyde. c Ketone is obtained by a Meerwein-
Pondorf-Verley reduction between PhCHO and Ph-CHO--Ph.
room temperature, at a constant current density of 0.3 A for
500 C. Afterward, the stainless steel rod was replaced by an
iron rod, and 3% of 2,2′-bipyridine (0.039 g 0.25 mmol) was
added along with 7.5 mmol of ArCHO and a portion of ArX
(0.3 mmol). The electrolysis was then conducted at constant
current density (0.15 to 0.25 A) so that the potential of the
working electrode remained ) -1.2 V/SCE. During the
electrolysis ArX was constantly added in the solution via a
syringe pump at a rate of 2-2.5 mmol/h, to minimize its
dimerization. A charge of 3-4 F/mol was necessary to
consume the aldehyde. The amount of chromium and nickel
released during the preelectrolysis was obtained by weighing
the stainless steel rod anode before and after the preelec-
trolysis. In all cases, 0.150 g of the sacrificial anode were
consumed. The weighting proportions of Fe/Cr/Ni were 72/
Scheme 1. Addition of Aryl Halides to Aromatic Aldehydes
via a Nickel and Chrome Catalysis
A charge of 4-5 F/mol was necessary to consume
benzaldehyde. A 5 F/mol charge corresponded to the release
of 50% of chromium and 25% of nickel vs PhCHO. We
have shown that it was possible to reduce the amount of
chromium and nickel released to 20% and 10%, respectively,
by replacing an iron rod for the stainless steel rod after
passing 2 F/mol and then continuing the electrolysis until
4-5 F/mol. In all cases, chemical yields are good (50-80%)
and approximately the same as those obtained with the other
process.
Table 2. Electroreductive Cross-Coupling between
Benzaldehyde and Aryl Halides
With the intent to further reduce the amount of chromium,
we found that it is possible to make a preelectrolysis with
the stainless steel rod to obtain 7% of chromium and 3% of
nickel. This solution is used as catalyst with 3% of 2,2′-
bipyridine, while the electrolysis is run with an iron rod.
We obtained thus the same yield of addition products as
when the electrolysis was run with the stainless steel rod
anode, as illustrated in Table 1 for the cross-coupling reaction
between benzaldehyde and bromobenzene.
This led us to a typical procedure: in an one-compartment
cell fitted with a nickel sponge as the cathode (20 cm2) and
a stainless steel rod (Fe/Cr/Ni 72/18/10) as the anode7 was
introduced DMF (40 mL) as solvent, NBu4BF4 (0.2 g 0.6
mmol) as supporting electrolyte, and CH2Br-CH2Br (220
µL 2.5 mmol). The preelectrolysis was run under argon, at
a Isolated yield, based on initial PhCHO; spectroscopic data for all
products are in agreement with the given structures. b 1.6 mmol of ArBr is
initially introduced. c 8 mmol of ArBr is initially introduced.
(6) Durandetti, M.; Pe´richon, J.; Ne´de´lec, J.-Y. Tetrahedron Lett. 1999,
40, 9009-9013.
(7) Stainless steel was purchased from Weber (ref. 304L) and nickel
sponge from Nitech (ref. Mn110.050.020, grade 110).
2074
Org. Lett., Vol. 3, No. 13, 2001

18/10, corresponding to 0.52 mmol of chromium (7%) and
0.26 mmol of nickel (3.5%). We applied this method to a
large variety of aryl halides. The results with benzaldehyde
are reported in Table 2.
Table 3. Electroreductive Cross-Coupling between Aromatic
Aldehyde Bearing EWG and Aryl Halides
Chemical yields are moderate to good and approximately
the same as those obtained with the stainless steel rod used
as the anode. Therefore, the use of chromium and nickel
salts obtained during the preelectrolysis allows the cross-
coupling between benzaldehyde and aryl halides using a
catalytic amount of chromium (7% based on initial PhCHO).
This method is efficient with aryl halides bearing electron-
donating as well as electron-withdrawing substituents. With
electron-donating substituents, aryl bromides must be used
(no cross-coupling occurs with aryl chloride), and with an
ortho-substituent, a larger amount of ArX is introduced
(Table 2, entries 4-5). With electron-withdrawing groups
aryl chlorides (Table 2, entry 6) or bromides (Table 2, entries
2, 7) could be used. The reaction is highly aldehyde selective,
as no addition products with ester or ketone groups are
detected (Table 2, entries 6-7). During the electrolysis, the
formation of benzyl alcohol in the same amount as the ketone
indicates that a Meerwein-Pondorf-Verley reduction occurs
between PhCHO and the alkoxide PhCHO--Ar leading to
benzyl alkoxide PhCH2O- and the ketone Ph-CO-Ar (Scheme
2). It is interesting to note that this reaction occurs mainly
a Isolated yield, based on initial ArCHO; spectroscopic data for all
products are in agreement with the given structures. b 1.4 mmol of Ar′Br
is initially introduced. c 2 mmol of Ar′Br is initially introduced. d 3.2 mmol
of Ar′Br is initially introduced.
donating substituents than with electron-withdrawing groups.
For all the reactions reported in Table 3, only 3 F/mol were
necessary and ketone Ar-CO-Ar′ is always < 1%.
We also applied this process to the cross-coupling reaction
of benzaldehyde with vinyl bromide, allyl acetate, and
R-chloroester (Table 4), and we have found that the cross-
Scheme 2. The Meerwein-Pondorf-Verley Reduction
Table 4. Electro Reductive Cross-coupling between Aldehyde
and Different Subsituents
with alkoxides bearing electron-donating substituents (Table
2, entries 3-5).
We also applied this process to the cross-coupling reaction
of aldehydes bearing electron-withdrawing substituents (Table
3). As these aldehydes are more reactive than benzaldehyde,
the aromatic halide can be introduced in the cell, before the
electrolysis, with only a small excess with respect to the
aldehyde. The reduction of aromatic aldehydes bearing
electron-withdrawing groups occurs before that of PhCHO
(-1.55 V/SCE for p-CF3-PhCHO, -1.45 V/SCE for p-
MeOCO-PhCHO compared to -1.95 V/SCE for PhCHO).
Therefore, the addition of aromatic aldehyde in several
portions to the reaction mixture avoids pinacolization. This
requires also the portionwise addition of the aryl halide. So
the initial mixture is prepared with 1 mmol of ArCHO and
1.5-2 mmol of Ar′Br and the syringe pump. Aryl bromides
must be used (only a small amount of cross-coupling is
detected with an aryl chloride, with a large amount of
pinacol). Yields are moderate to good and do not seem to
depend on the substituent of the aromatic halide provided
that the excess of the aryl halide is larger with electron-
a Isolated yield, based on initial RCHO; spectroscopic data for all products
are in agreement with the given structures. b 15 mmol of RX is initially
introduced. c Reaction is carried out at 50 °C. d 4% of the corresponding
ketone is equally obtained.
coupling between vinyl halides and benzaldehyde can be
performed using the general procedure described for the
coupling between benzaldehyde and aryl halides, except that
2 equiv of vinyl bromide is initially introduced. Under these
conditions yields are moderate (Table 4, entries 1-2). The
Org. Lett., Vol. 3, No. 13, 2001
2075

reaction also seems stereoselective. Thus, starting from
commercial (Z)-2-bromo-2-butene which contains 25% of
the E-isomer, the Z/E isomer ratio in the coupling product
is 66/34 (Table 4, entry 1). If the starting material has mainly
an E geometry (Z/E ) 31/69), it is the same for the cross-
coupling product (Z/E ) 35/65) (Table 4, entry 2), thus
indicating that the reaction is stereoselective. Chemical yield
could be increased by heating the solution at 50 °C, but
unfortunately at this temperature stereoselectivity is lost
(Table 4, entry 3).
This method can also be applied to allyl acetate or methyl
2-chloropropanoate: these yields of these products is as good
as the yield of the aryl halide. In the case of 2-chloropro-
panoate, we obtained the two diastereoisomers with moderate
diastereoselectivity (Table 4, entries 5-7), depending on the
nature of the aldehyde. The reaction is efficient with
benzaldehyde (Table 4, entry 5) as well as aromatic alde-
hydes bearing electron-withdrawing groups (Table 4, entry
6) or aliphatic aldehydes (Table 4, entry 7). In the three cases,
only 1.1 equiv of 2-chloropropanoate was used, and only 2
F/mol were necessary to consume the aldehyde.
In conclusion, various substituted benzhydrols can be
prepared in good yields in one step by a very simple
electrochemical method where chromium salts are released
by oxidation of the anode, thus avoiding the use of CrCl2,
which is toxic, air and moisture sensitive, and expensive.
The reaction is catalytic in chromium salt (only 7%/PhCHO).
This process was extended to the alkenylation of aromatic
aldehydes as well as to the coupling with allyl acetate or
methyl 2-chloropropanoate.
OL016033G
2076
Org. Lett., Vol. 3, No. 13, 2001