Cobalt-catalyzed cross-coupling reaction between functionalized primary and secondary alkyl halides and aliphatic Grignard reagents

Article abstract of DOI:10.1002/adsc.200800166

The coupling of primary and secondary unactivated alkyl bromides with alkyl-Grignard reagents was performed in good yields under mild conditions by using a new catalytic system: consisting of cobalt chloride and tetramethylethylenediamine (CoCl₂·2 LiI, 4TMEDA). The reaction is very chemoselective since ketone, ester and nitrile functions are tolerated.

Full text of DOI:10.1002/adsc.200800166

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DOI: 10.1002/adsc.200800166
Cobalt-Catalyzed Cross-Coupling Reaction between
Functionalized Primary and Secondary Alkyl Halides and
Aliphatic Grignard Reagents
GØrard Cahiez,a,* Christophe Chaboche,a Christophe Duplais,a Arianna Giulliani,a
and Alban Moyeuxa
a
Laboratoire de Synth›se Organique SØlective et de Chimie OrganomØtallique (SOSCO), UMR 8123
CNRS-UCP-ESCOM, 5 Mail Gay-Lussac, Neuville s/Oise, 95092 Cergy-Pontoise, France
Fax : (+33)-1-3425-7383; e-mail: gerard.cahiez@u-cergy.fr
Received: March 18, 2008; Published online: June 3, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The coupling of primary and secondary
unactivated alkyl bromides with alkyl-Grignard re-
agents was performed in good yields under mild
conditions by using a new catalytic system: consist-
ing of cobalt chloride and tetramethylethylenedi-
phisticated tridentate diamino-organomanganese(II)
complex (NCN-MnCl·LiCl) is used as a co-catalyst.
Few coupling reactions between alkyl-Grignard re-
agents and secondary alkyl halides under palladi-
A
A
Moreover, the reactions are mainly limited to cyclo-
alkyl halides that give better yields than linear secon-
dary alkyl halides.[9] In fact, after many decades, the
coupling of unactivated secondary alkyl halides is still
a challenge since it is well-known that these substrates
undergo very slow oxidative addition whereas the sec-
ondary alkyl-metal intermediates involved in the cata-
lytic cycle undergo rapid b-elimination.[9,10] Thus,
there is no general method for the metal-catalyzed
coupling of unactivated secondary alkyl halides with
aliphatic Grignard reagents.[11]
very chemoselective since ketone, ester and nitrile
functions are tolerated.
Keywords: aliphatic Grignard reagents; alkyl-alkyl;
cobalt-catalyzed reaction; cross-coupling; secondary
alkyl bromides
Transition metal-catalyzed cross-coupling reactions
As a solution to this problem, we report herein our
have been extensively developed in the last years. results concerning the first example of a cobalt-cata-
They are frequently used on a laboratory as well as lyzed alkyl-alkyl cross-coupling reaction from unacti-
on an industrial scale and they are irreplaceable tools vated secondary halides.[11b]
for the elaboration of carbon-carbon bonds.[1,2] Alkyl-
Recently, we[12] and others[13] have reported that
alkyl cross-coupling using unactivated primary alkyl secondary alkyl halides can be coupled with aryl-
halides is one of the oldest reactions in this field.[3]
Grignard reagents in the presence of a catalytic
Thus, it has been known since 1968 that copper- amount of iron or cobalt salts. The presence of an
mediated alkyl-alkyl coupling reactions (stoichiome- amine like TMEDA,[13c] or even better tandem
tric[4a,b] or catalytic[4c] amounts of copper) are very ef- TMEDA-HMTA,[12] is essential in order to obtain
ficient with primary alkyl halides.[4] Recently, we,[5a] good yields. Thus, we decided to evaluate the poten-
then Kambe,[5b] have shown that the use of additives tial of such catalytic systems to couple alkyl-Grignard
(respectively, NMP and 1-phenylpropyne) allows the reagents with secondary alkyl halides. Our attempts
yield and the chemoselectivity of the reaction to be to couple 2-bromobutane with decylmagnesium bro-
improved, sometimes dramatically. Nevertheless, only mide in the presence of iron salts [Fe
primary alkyl halides can be coupled successfully ac- and Fe
(acac)3-TMEDA-HMTA] resulted in failure.[14]
cording to the previous procedures. It is interesting to With cobalt chloride or an ate complex CoCl2·2LiX
A
AHCTREUNG
note that the only example of copper-catalyzed cou- (X=Cl or I)[15] as a catalyst, the expected coupling
pling reactions between a Grignard reagent and an product was only obtained in a trace amount (Table 1,
unactivated secondary alkyl halide was performed entries 1 and 2). However, we were pleased to note
using Mn/Cu catalysis.[6] It should be noted that a so- that in the presence of 20 mol% TMEDA, the reac-
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Cobalt-Catalyzed Cross-Coupling Reaction
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Table 1. Comparison of various catalytic systems.
This is the first time that such a beneficial influence
of iodide anion as a ligand has been evidenced in the
case of cobalt-catalyzed coupling reactions.[16]
This interesting observation prompted us to explore
the scope of the cobalt-catalyzed alkyl-alkyl coupling
reaction by using CoCl2·2LiI, 4TMEDA as a catalytic
system (Table 2).
Acyclic secondary alkyl bromides (Table 2, entries 1
to 10) gave moderate to good yields of cross-coupling
product. It is important to note that the influence of
steric effects is determinant. Thus, 2-bromopentane
gave a better yield than 3-bromopentane (Table 2, en-
Entry
Catalytic System[a]
Yield [%][b,c]
1
2
3
4
5
6
7
CoCl2
Traces
Traces
35
27
30
CoCl2·2LiX (X=Cl or I)
CoCl2, 4TMEDA
CoCl2·2LiCl, 4TMEDA
CoCl2·2LiBr, 4TMEDA
CoCl2·2LiI, 4TMEDA
CoCl2·2MgI2, 4TMEDA
79
79
Table 2. Cobalt-catalyzed cross-coupling reaction between
unactivated primary and secondary alkyl halides and ali-
phatic Grignard reagents.
8
28
75
9
Entry Alkyl
Halide
Grignard
Reagent
Yield
[%][a]
[a]
5 mol% of catalyst were used.
[b]
[c]
GC yield (pentadecane as an internal standard).
The starting halide was completely consumed in all ex-
periments.
1
2-Bromopropane
n-OctMgBr
n-DecMgBr
n-OctMgBr
n-DecMgBr
n-DecMgBr
n-DecMgBr
n-OctMgBr
n-DecMgBr
n-DecMgBr
n-BuMgBr
82
89
2
3
2-Bromopropane
2-Bromobutane
69
4
5
6
X=Cl
X=Br
X=I
ꢀ1[b]
79
75
62[c]
45[c]
47[c]
57[c]
87
tion led to a 35% yield (Table 1, entry 3). This result
encouraged us to continue our investigations. We thus
tried to combine TMEDA and ate complexes such as
CoCl2·2LiX. No significant change was observed by
using lithium chloride or bromide (respectively
CoCl2·2LiCl and CoCl2·2LiBr. Table 1, entries 4 and
5). On the other hand, with lithium iodide or magne-
sium iodide (Table 1, entries 6 and 7) the yield
jumped from 35 to 79%. It is important to note that,
contrary to the results reported by Oshima[13g] in the
case of the coupling of secondary alkyl halides with
aryl-Grignard reagents, the use of N,N,N’N’-tetra-
methyl-1,2-cyclohexanediamine in place of TMEDA
does not allow us to improve the yield of the alkyl-
alkyl coupling product (Table 1, entries 8 and 9).
With 2-iodobutane, the coupling can be performed
successfully in the presence of CoCl2·2LiI or
CoCl2·2LiCl (Scheme 1). This is not very surprising
since, in this case, metallic iodides are formed in situ
as soon as the reaction begins.
7
2-Bromopentane
8
9
3-Bromopentane
2-Bromoheptane
2-Bromodecane
10
11
12
13
14
Cyclohexyl bromide n-OctMgBr
n-PentBr
n-OctBr
n-DecBr
n-BuBr
n-BuBr
n-OctMgBr
n-PentMgBr
n-PentMgBr
96
97
98
15
70
16
17
18
t-PentBr
n-DecBr
n-DecBr
n-OctMgBr
s-BuMgBr
t-BuMgBr
0[b]
20[d]
0[d]
[a]
[b]
[c]
Yield of isolated product.
No reaction.
A mixture R (ÆH) was obtained as side product from
RBr.
[d]
A mixture of decane and 1-decene was mainly obtained.
Scheme 1. Reaction from 2-iodobutane.
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tries 7 and 8). Similarly, the results obtained with vari- Currently, sustainable development must be taken
ous 2-bromoalkanes clearly depend on the length of into account in the development of new chemical pro-
the alkyl chain (Table 2, entries 2, 5 and 9). As ex- cedures. Thus, in the last few years considerable ef-
pected,[10] cyclic alkyl bromides gave higher yields forts have been made to replace palladium or nickel
than acyclic secondary alkyl bromides (Table 2, en- complexes by iron or manganese salts that are less ex-
tries 7 and 11). Finally, it is possible to use alkyl io- pensive and more acceptable for the environment. As
dides in place of the bromides whereas the corre- catalysts, cobalt salts are probably the most interest-
sponding chlorides do not react (Table 2, entries 4 to ing candidates after iron and manganese derivatives.
6). The reaction has been extended to primary alkyl Moreover, it should be noted that the three metals
bromides, for which it should be noted that excellent deserve to be studied in parallel since they can exhibit
yields were obtained (Table 2, entries 12 to 15). On some specific reactivities. The results reported above
the other hand, tertiary alkyl bromides do not react in the case of the alkyl-alkyl coupling are good evi-
(Table 2, entry 16). It should be noted that only pri- dence for such a difference between iron- and cobalt-
mary alkyl-Grignard reagents gave satisfactory yields catalyzed reactions. The cobalt-catalyzed cross-cou-
(Table 2, entries 17 and 18).
pling reaction presented above is part of our efforts
Interestingly, the presence of various functional to propose new eco-friendly and economical metal-
groups like ester, nitrile and even ketone is tolerated catalyzed procedures.
(Table 3).
The reaction depicted in Scheme 2 is the first exam-
ple of a chemoselective alkyl-alkyl coupling from a Experimental Section
functionalized secondary alkyl bromide.
In summary, we have disclosed herein the first ex- Typical Procedure: Preparation of 3-Methyltridecane
ample of a cobalt-catalyzed chemoselective alkyl- (Scheme 1)
alkyl coupling reaction. It is worthy of note that this
A dry and nitrogen-flushed 250-mL four-necked flask,
procedure is now the best way to couple secondary
equipped with a mechanical stirrer, a thermometer, a nitro-
alkyl halides with alkyl-Grignard reagents in satisfac-
gen inlet and a septum, was charged with THF (25 mL), 2-
tory yields. An unprecedented and beneficial influ-
ence of iodides on this coupling reaction is described.
bromobutane (6.85 g, 50 mmol), CoCl2 (325 mg, 5 mol%),
TMEDA (1.16 g, 20 mol%) and LiI (700 mg, 10 mol%). The
reaction mixture was cooled to 108C then a solution of n-de-
cylmagnesium bromide in THF (61 mL, 0.9M, 55 mmol)
was added in 80 min. After the end of the addition, the reac-
tion mixture was stirred for 30 min then quenched with
aqueous HCl (1M, 100 mL). The aqueous phase was extract-
ed with ether (3”50 mL). The combined organic layers
were dried with MgSO4 and concentrated under vacuum.
The crude product was purified by distillation at a reduced
pressure (1168C, 10 Torr) affording 3-methyltridecane as a
colorless oil; yield: 7.8 g (79%).
Table 3. Cobalt-catalyzed cross-coupling reaction between
unactivated functionalized primary alkyl halides and aliphat-
ic Grignard reagents.
Entry
Alkyl
Halide
Grignard
Reagent
Yield
[%][a]
1
2
EtMgBr
n-DecMgBr
78
75
Acknowledgements
3
n-BuMgBr
82
73
We thank the CNRS for its financial support and a grant to
A. Giulliani and the Minist›re de l’Education Nationale et de
la Recherche for its financial support and a grant to A.
Moyeux. The Fondation de France is also acknowledged for
a grant to C. Duplais.
4
n-PentMgBr
[a]
Yield of isolated product.
Scheme 2. Cobalt-catalyzed chemoselective alkylation of methyl 4-bromopentanoate.
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[16] We have verified that bromine-iodine exchange is very
slow under our conditions. Thus, by stirring our catalyt-
ic system (CoCl2·2LiI, 4TMEDA) with 2-bromooctane
(ratio LiI/s-OctBr=1:1), only 4% of 2-iodobutane were
detected after 16 h at room temperature.
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the reaction is performed in the presence of 3 mol%
Fe(OAc)2-Xantphos (1:2) in diethyl ether at room tem-
A
perature. Yields are moderate (46–64%), in addition,
the use of cyclic secondary alkyl bromides resulted in
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