Manganese-catalyzed oxidative cross-coupling of grignard reagents with oxygen as an oxidant

Full text of DOI:10.1002/anie.200902188

Angewandte
Chemie
DOI: 10.1002/anie.200902188
Cross-Coupling
Manganese-Catalyzed Oxidative Cross-Coupling of Grignard Reagents
with Oxygen as an Oxidant**
Gꢀrard Cahiez,* Christophe Duplais, and Julien Buendia
Until now, only rare examples of oxidative cross-coupling
reactions have been described.[1–4] Lipshutz et al.[1] and, more
recently, Knochel et al.[2] showed that, at low temperature,
oxidation of mixed organocuprates RR’CuLi gives the
ride does not give the expected homocoupling product, while
hindered mesitylmagnesium bromide gives only a trace.
Interestingly, in the case of mesitylmagnesium bromide,
coupling is only prevented by steric effects, since p-anisyl-
magnesium bromide, which is less hindered, readily reacts
under the same conditions (Scheme 1).
On the other hand, alkynyl magnesium halides easily
couple in excellent yields under manganese catalysis. How-
ever, the reaction is less rapid than with aromatic Grignard
reagents (p-anisylmagnesium bromide: 93% yield after 4–
5 min; phenylethynylmagnesium chloride: 90% yield after
10 min). Clearly, such a difference is essentially due to
electronic factors.
À
heterocoupling product R R’ in good yield. Both reactions
use a stoichiometric amount of copper. Two metal-catalyzed
procedures were also reported. Lei et al.[3] coupled an alkyl
zinc with an alkynyl stannane under palladium catalysis by
using desyl chloride as an oxidant. Lately, we have described
iron-catalyzed oxidative heterocoupling between aryl and
alkyl zinc compounds by using 1,2-dibromoethane as oxi-
dant.[4] Moreover, some interesting results involving C H
À
activation were recently described.[5]
In the framework of our research program to develop new
iron-,[6] manganese-,[7] and cobalt-catalyzed[8] coupling proce-
dures, we recently reported a very efficient manganese-
catalyzed homocoupling reaction of Grignard reagents using
atmospheric oxygen as an oxidant.[9] We noted that the
reaction rate closely depends on the nature of the organic
group of RMgX. In the light of these observations, we thought
that it would be possible to perform an oxidative heterocou-
pling reaction with a mixture of two Grignard reagents RMgX
and R’MgX by choosing judiciously the nature of the R and R’
groups. We now disclose the first manganese-catalyzed
oxidative heterocoupling reaction of Grignard reagents.
Treating an aryl Grignard reagent with air in the presence
of manganese chloride readily forms a biaryl. As a rule,
coupling is rapid, but the reaction rate is highly dependent on
both steric[10] and electronic[11] factors. Thus, as shown in
Scheme 1, electron-poor pentafluorophenylmagnesium chlo-
By considering the two examples above, we thought that it
would be possible to disfavor the formation of the homocou-
pling products to the profit of the heterocoupling product by
combining an electron-rich but sterically hindered aryl group
with an alkynyl group that couples more slowly but is not
bulky.
Preliminary experiments in which one equivalent of
mesityl- or 1-naphthylmagnesium bromide was coupled with
one equivalent of phenylethynylmagnesium chloride were
consistent with our hypothesis (Scheme 2).
Scheme 1. Influence of electronic and steric factors on Mn-catalyzed
homocoupling of aryl Grignard reagents.
Scheme 2. Oxidative heterocoupling of aryl- and alkynyl Grignard
reagents.
[*] Dr. G. Cahiez, Dr. C. Duplais, J. Buendia
Department of Chemistry, CNRS - Universitꢀ de Paris 13
74 Rue Marcel Cachin, 93017 Bobigny (France)
E-mail: gerard.cahiez@univ-paris13.fr
A tentative mechanism is presented in Scheme 3. The
reaction of the two Grignard reagents 1 and 2 with manganese
chloride can lead to a mixture of three organomanganese(II)
compounds 3, 4, and 5 and then, after oxidation, to
manganese(IV) species 6, 7, and 8. The reductive elimination
step mainly leads to cross-coupling product 10, since the
[**] We thank the CNRS for a financial support and ESCOM (Fondation
de France) for a grant to C.D. and J.B.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200902188.
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negligible and a statistical mixture
(1:2:1) of the three coupling products
13, 14, and 15 was finally obtained.
However, by monitoring the course of
the reaction, we observed that aryl–
aryl coupling clearly takes place first
(Figure 1). Next, heterocoupling prod-
uct 14 is formed more and more quickly
as the concentration of the aromatic
Grignard reagent 12 decreases. Finally,
after 8–10 min, alkynyl–alkynyl cou-
pling product 15 is obtained, since
anisylmagnesium bromide 12 is com-
pletely consumed. The evolution of the
reaction is fully compatible with the
mechanism presented in Scheme 3.
Interestingly, we have shown that
satisfactory yields of heterocoupling
product 14 can be obtained by using
an excess of either
2
(Table 1,
entries 1–4) or 12 (Table 1, entries 1
and 5–7). By considering the final yield
of 14 it seems that the influence of an
excess of Grignard reagent 2 or 12 is
very similar. However, in agreement
with the above considerations, the
course of the reaction is very different
in the two cases.[13]
Scheme 3. Tentative mechanism for Mn-catalyzed oxidative heterocoupling.
Under these conditions, we have
prepared various aryl acetylenes in
good yields (Table 2). Interestingly,
formation of the homocoupling products is clearly disfavored
for steric (9) or electronic reasons (11).
Next, we studied the reaction between Grignard reagents
2 and 12 (Figure 1). In this case, the steric factors are
functionalized aryl and alkynyl magnesium halides react
successfully (Table 2, entries 4–8). The less expensive
Grignard reagent was always used in excess (2.5 equiv).
Note that the excess of Grignard reagent was not optimized
for each example; for example, the yield of o-
cyanodiphenylacetylene (Table 2, entry 6) only
drops from 77 to 71% by using 1.5 equiv of
phenylethynylmagnesium chloride instead of
2.5 equiv.
The oxidative heterocoupling procedure was
also used to synthesize biaryls (Table 3), which
have numerous applications,[14] in satisfactory
yields. Coupling is chemoselective, and various
functionalized aryl Grignard reagents were used
successfully (Table 3, entries 5–8).
The results presented in Tables 2 and 3 show
that preferential formation of the heterocoupling
product is not only due to a statistical effect.
Indeed, when using 2.5 equiv of R2MgX, the
statistical R1R2/R1R1 ratio should be about 70/30.
In fact, in most cases, the reaction takes place
selectively, since the ratio is significantly higher. In
accordance with the above discussion, the selec-
tivity is very dependent on the nature of the R1
and R2 groups.
The procedure was extended to alkynyl–
Figure 1. Manganese-catalyzed oxidative coupling of p-anisylmagnesium bromide
and phenylethynylmagnesium chloride: Competition between homo- and hetero-
coupling reactions.[12]
alkynyl, alkenyl–alkynyl
(Scheme 4),
and
alkenyl–alkenyl coupling (Scheme 5). 4-Pivaloy-
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Table 1: Influence of an excess of Grignard reagent 2 or 12 on the yield of
heterocoupling product 14.[a]
Entry
Equiv of 2
Equiv of 12
Yield of 14 [%][b]
1
2
3
4
5
6
7
1
2
2.5
3
1
1
1
1
1
2
2.5
3
52
65[c]
74[c]
77[c]
63[d]
74[d]
77[d]
Scheme 5. Preparation of conjugated dienes by Mn-catalyzed oxidative
heterocoupling.[a] [a] For the stereoselective preparation of (Z)-1-non-
enylmagnesium bromide, see Supporting Information. [b] For selectiv-
ity, see Table S1 in the Supporting Information.
1
1
[a] The reactions were performed on a 5 mmol scale. [b] Yield was
determined by GC with pentadecane as internal standard. [c] 12 is the
limiting reagent. [d] 2 is the limiting reagent.
Table 3: Manganese-catalyzed oxidative cross-coupling of aryl Grignard
reagents.[a]
Ar1MgX
Coupling
product
Yield Yield Ar1Ar2/
[%][b,c] Ar1Ar1 Ar1Ar1
[%][b,c]
Table 2: Manganese-catalyzed oxidative cross-coupling of aryl- and alkynyl
Grignard reagents.[a]
87.0/
13.0
1
2
80
76
12
13
R1MgX
Coupling
product
Yield Yield R1R2/
85.4/
14.6
[%][b,c] R1R1
[%][b,c]
R1R1
91.9/
8.1
80.9/
19.1
3
68
6
1
2
72
74
17
82.2/
17.8
16
76.5/
23.5
4
5
6
65
20
8
88.1/
11.9
87.1/
12.9
3
4
74[d]
81
10
12
91.0/
9.0
81[d]
85.5/
14.5
59[e,f] 10
94.7/
5.3
5
6
89
5
7
90.8/
9.2
7
8
69[e,f]
63[g]
7
91.6/
8.4
77[e]
80.8/
19.2
15
92.8/
7.2
7
8
78
68
6
[a] Reactions were performed on a 5 mmol scale. [b] Yield of isolated
product (limiting reagent: Ar1MgX). [c] Yields of R2R2 range from 60 to 70%
(limiting reagent: Ar2MgX). See Table S1 in the Supporting Information.
[d] Br/Mg exchange was performed with iPrMgCl·LiCl. [e] The reaction was
carried out at À208C. [f] Br/Mg exchange was performed with iPrMgCl. [g] I/
Mg exchange was performed with Et2CHMgCl.
87.2/
12.8
10
[a] The reactions were performed on a 5 mmol scale. [b] Yield of isolated
product (limiting reagent: R1MgX). [c] Yields of R2R2 range from 60 to 70%
(limiting reagent: R2MgX). See Table S1 in the Supporting Information.
[d] 5 equiv of alkynyl magnesium reagent were used to perform the reaction.
[e] Br/Mg exchange was performed with iPrMgCl·LiCl.
loxy-1-butynylmagnesium chloride can be coupled chemo-
selectively (Scheme 4). The reaction is also highly stereose-
lective: (Z)-1-nonenylmagnesium bromide was
coupled with a good retention of configuration
(Scheme 5).
In conclusion, we have reported a new
general procedure for the manganese-catalyzed
oxidative cross-coupling of alkynyl, alkenyl, and
aryl magnesium halides. To the best of our
knowledge, it is the first metal-catalyzed proce-
dure for coupling two Grignard reagents. The
selectivity between hetero- and homocoupling
reactions is highly dependent on the nature of
the two Grignard reagents. In many cases, the
outcome of the reaction is not statistical and it is
Scheme 4. Preparation of conjugated diynes and enynes by Mn-catalyzed oxidative
heterocoupling reaction. [a] For selectivity, see Table S1 in the Supporting Information.
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Communications
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Alkenyl Grignard reagents couple stereoselectively, and the
presence of various functional groups (ester, nitrile, etc.) is
tolerated. The reaction readily takes place under mild
conditions (08C, 1 h). The results described above pave the
way to new applications of MnCl2/O2 as a cheap and
environmental friendly catalytic system.
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Received: April 23, 2009
Revised: June 5, 2009
Published online: August 7, 2009
Keywords: cross-coupling · Grignard reagents · manganese ·
.
oxidation · synthetic methods
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[12] 3% of 14 and 3% of 15 are formed during the addition of MnCl2,
before introduction of O2 commences
[13] See Supporting Information (Figure S1).
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6734
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