Versatile palladium-catalyzed arylation of organomanganese chlorides by aryl bromides

Article abstract of DOI:10.1016/S0022-328X(00)00891-3

In THF, a palladium-catalyzed cross-coupling reaction of organomanganese reagents with various aryl bromides including unreactive deactivated or hindered aryl bromides was performed successfully in the presence of a new catalytic system 1% PdCl₂(dppp)-four equivalents DME. The scope of the reaction is very broad since many functional groups are tolerated, moreover, even hindered O,O′-di- or trisubstituted diaryls were obtained in high yields. It is interesting to note that hindered aryl bromides are more reactive than the corresponding aryl iodides. Alkyl, alkenyl and alkynylmanganese chlorides also react under similar conditions.

Full text of DOI:10.1016/S0022-328X(00)00891-3

Journal of Organometallic Chemistry 624 (2001) 376–379
www.elsevier.nl/locate/jorganchem
Communication
Versatile palladium-catalyzed arylation of organomanganese
chlorides by aryl bromides
Eric Riguet, Mouaˆd Alami 1, Ge´rard Cahiez *
Laboratoire de Synthe`se Organique Se´lecti6e et de Chimie Organome´tallique CNRS-UCP-ESCOM, 13 boule6ard de 1’Hautil,
F-95092 Cergy-Pontoise cedex, France
Received 16 October 2000; accepted 10 November 2000
Dedicated to Professor Jean Normant for his 65th birthday
Abstract
In THF, a palladium-catalyzed cross-coupling reaction of organomanganese reagents with various aryl bromides including
unreactive deactivated or hindered aryl bromides was performed successfully in the presence of a new catalytic system 1%
PdCl2(dppp)–four equivalents DME. The scope of the reaction is very broad since many functional groups are tolerated,
moreover, even hindered O,O%-di- or trisubstituted diaryls were obtained in high yields. It is interesting to note that hindered aryl
bromides are more reactive than the corresponding aryl iodides. Alkyl, alkenyl and alkynylmanganese chlorides also react under
similar conditions. © 2001 Elsevier Science B.V. All rights reserved.
Keywords: Arylation; Cross-coupling reactions; Organomanganese reagents; Aryl bromides
Previously [1], we reported that functionalized un-
symmetrical biaryls can be prepared in high yields in
THF by reacting arylmanganese chlorides with aryl
halides or triflates (X=I, Br, OTf) in the presence of a
new catalytic system 1% PdCl2(PPh3)2–four equivalents
DME. We have shown that the presence of DME
greatly accelerates the coupling reaction rate and im-
proves the yields. Unfortunately, under these condi-
tions, all our attempts to prepare unsymmetrical biaryls
from unreactive aryl bromides such as hindered ortho-
substituted aryl bromides (i.e. 1) or deactivated aryl
bromides bearing an electron-donating group (i.e. 3)
resulted in unsatisfactory yields [2].
These results prompted us to undertake a more de-
tailed study to extend the scope of this coupling reac-
tion. Some preliminary experiments were performed in
the case of the first coupling reaction described above
(synthesis of 2 from 1). A very interesting result was ob-
tained by changing the nature of the catalyst (Table 1).
Table 1
Synthesis of ortho-cyanobiphenyl 2 from phenylmanganese chloride
and ortho-bromobenzonitrile 1; influence of the nature of the catalyst
a
PdLn
Entry
PdLn
Time (h)
Yield (%) b
1
2
3
4
5
6
7
PdCl2(PPh3)2
PdCl2(TMEDA)
PdCl2(PhCN)2
PdCl2(dppe)
PdCl2(dppb)
PdCl2(dppp)
15
24
24
24
21
3
47
0
0
0
15
98
91
Pd(OAc)2+dppp
7
* Corresponding author. Fax: +33-01-307560 21.
1 Present address: BIOCIS, Faculte´ de Pharmacie, rue Jean-Bap-
tiste Cle´ment, F-92296 Chaˆtenay-Malabry, France.
a PhMnCl was prepared from PhMgCl, all reactions were per-
formed at 20°C. For a general procedure see Ref. [4].
b Isolated yield based on 1.
0022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(00)00891-3

E. Riguet et al. / Journal of Organometallic Chemistry 624 (2001) 376–379
377
Table 2
ing an electron-donating group or/and a substituent in
the ortho-position (Table 2). In all cases, excellent
yields (91–98%) were obtained by varying only the
reaction time [3]. The results obtained by using
PdCl2(PPh3)2 are clearly inferior (Entries 8, 13 and 14).
As expected, under similar reaction conditions, the
coupling of arylmanganese chlorides with reactive aryl
bromides bearing an electron-withdrawing group gave
high yields (Table 3). Interestingly, the reaction is very
chemoselective since even a reactive keto group is toler-
ated (Entries 23 and 24).
Preparation of unsymmetrical biaryls from PhMnCl a and hindered or
deactivated aryl bromides
It should be noted that the reaction has also been
performed successfully with aryl triflates which can be
easily prepared from the corresponding phenols [4]
(Table 4).
On account of the large scope of this coupling proce-
dure, we have tried to synthesized various highly hin-
dered O,O%-substituted biaryls (Tables 5 and 6). Indeed,
these compounds are generally very difficult to obtain
via a palladium-catalyzed aryl–aryl coupling since such
reactions are not very efficient from sterically hindered
organometallic and/or aryl halides [5]. At first, we have
compared the reactivity of various ortho-substituted
aryl bromides and iodides with phenylmanganese chlo-
ride (Table 5). In all cases aryl bromides led to better
results (Entries 30–33). It is very surprising since, as a
rule, it is accepted that aryl iodides are more reactive.
The difference of reactivity increases along with the
steric hindrance. Thus, all our attempts to prepare
O,O%-di-or trisubstituted biphenyls from aryl iodides
were unsatisfactory whereas the corresponding aryl
bromides gave excellent yields (Entries 34–37). A simi-
lar difference was observed by comparing aryl bromides
and triflates (Entries 38 and 39). To our knowledge, it
is the first time that such a difference of reactivity is
reported.
Table 3
Preparation of unsymmetrical biaryls from ArMnCl and functional-
ized aryl bromides a
According to this observation, various O,O%-substi-
tuted biaryls were prepared in high yields from various
ortho-substituted arylmanganese chlorides and ortho-
substituted aryl bromides (Table 6). It should be under-
lined that this procedure is currently one of the most
efficient for the preparation of such hindered diaryls [5].
Finally, under these reaction conditions, it is also
possible to extend the scope of the reaction to benzyl,
alkenyl, alkynyl and alkylmanganese chlorides (Table
7). However, in some cases, it is necessary to use
PdCl2(dppf) as catalyst instead of PdC12(dppp), for
instance with alkyl derivatives having eliminable b-hy-
drogen atoms [6] (Entries 45 and 46).
In conclusion, we have reported a new catalytic
system 1% PdCl2(dppp)–four equivalents DME to per-
form efficiently the coupling of organomanganese chlo-
rides with aryl bromides or triflates. The reaction has a
very large scope, thus, many functional groups such as
esters, nitriles or ketones are tolerated and excellent
yields were obtained from both electron-rich and elec-
Indeed, in the presence of various palladium com-
plexes PdCl2L2 (L2=TMEDA, (PhCN)2, dppe, dppb)
the yield of 2 was lower than with PdCl2(PPh3)2. On the
other hand, in the presence of 1% PdCl2(dppp) the
reaction occurred quickly (3 h) at room temperature to
afford 2 in excellent yield (98%). Moreover, the forma-
tion of the homo-coupling product (biphenyl), which is
often a very annoying side-product for such cross-cou-
pling reactions, was almost completely avoided.
This very promising result encouraged us to extend
the reaction to various unreactive aryl bromides bear-

378
E. Riguet et al. / Journal of Organometallic Chemistry 624 (2001) 376–379
Table 6
tron-poor substrates. This new procedure is especially
interesting for the synthesis of hindered O,O%-substi-
tuted biaryls which were difficult to prepare until now
by using a palladium-catalyzed cross-coupling reaction
[5]. In addition, we have shown that, in our case,
Preparation of hindered O,O%-substituted unsymmetrical biaryls from
RMnCl and aryl bromides a
Table 4
Preparation of unsymmetrical biaryls from PhMnCl and aryl
triflates a
Table 7
Pd-cross-coupling reaction from various non-aromatic organoman-
ganese reagents and aryl bromides a
Table 5
Preparation of hindered O,O%-substituted unsymmetrical biaryls from
ArMnCl and Ar%X; influence of the nature of Ar%X (X=Br, I and
OTf) a
hindered aryl bromides are clearly more reactive than
the corresponding iodides. It is, to our knowledge, the
first report of such a reversal of reactivity. The use of
this new catalytic system with various organometallic
compounds (RMgX, RZnX) is currently under investi-
gation.
Acknowledgements
The CNRS and the Ecole Supe´rieure de Chimie
Organique et Mine´rale (ESCOM) are gratefully ac-
knowledged for financial support. Thanks are also to
the ESCOM for a doctoral fellowship to E.R.

E. Riguet et al. / Journal of Organometallic Chemistry 624 (2001) 376–379
379
Hayashi, Synlett (1997) 163–64. (b) P.G. Ciattini, E. Morera, G.
Ortar, Tetrahedron Lett. 33 (1992) 4815–18.
References
[5] See Ref. [2] and references quoted herein. Until now, few efficient
procedures were reported to prepare hindered diaryls, see for
instances; from arylboronic acids: (a) A.F. Littke, C. Dal, G.C.
Fu, J. Am. Chem. Soc. 122 (2000) 4020–4028. (b) T. Watanabe,
N. Miyaura, A. Suzuki, Synlett (1992) 207–210; from arylstan-
nanes: J.M. Saa´, O. Martorell, J. Org. Chem. 58 (1993) 1963–
1966.
[6] It is known that the use of PdCl2(dppf) as a catalyst allows us to
avoid or to limit the b-hydrogen elimination when an alkylmetal
having eliminable b-hydrogen atoms is used. See for instance: T.
Hayashi, M. Konishi, Y. Kobori, M. Kumada, T. Higuchi, K.
Hirotsu, J. Am. Chem. Soc. 106 (1984) 158–163.
[7] For reviews on the preparation and the reactivity of organoman-
ganese reagents see: (a) G. Cahiez, Butyl manganese chloride, in:
L. Paquette (Ed.), Encyclopedia of Reagents for Organic Synthe-
sis, vol. 2, Wiley, Chichester, 1995, pp. 925–928. (b) G. Cahiez,
Manganese(II) chloride, in: L. Paquette, (Ed.), Encyclopedia of
Reagents for Organic Synthesis, vol. 5, Wiley, Chichester, 1995,
pp. 3227–3228. (c) G. Cahiez, An. Quim. 91 (1995) 561–578.
[1] E. Riguet, M. Alami, G. Cahiez, Tetrahedron Lett. 38 (1997)
4397.
[2] For recent reviews about the transition metal-catalyzed aryl–aryl
coupling reactions see: (a) S.P. Stanforth, Tetrahedron 54 (1998)
263–303. (b) F. Diederich, P.J. Stang (Eds.), Metal-Catalyzed
Cross-Coupling Reactions, Wiley-VCH, New York, 1998.
[3] General procedure: To a solution of ArMnCl [7] (7.4 mmol) in 5
ml of THF were added, at 0°C, 1.5 ml (14.8 mmol) of distilled
DME, 1% of PdCl2(dppp) (0.037 mmol) and aryl bromide (3.7
mmol) in 2 ml of THF. After stirring (the reaction time and the
temperature are indicated in Tables 1–7), the reaction mixture
was hydrolyzed, at 0°C, with aqueous hydrochloric acid (1 M)
and the aqueous layer was extracted twice with Et2O. The com-
bined organic layers were then dried over MgSO4 and the solvents
were removed in vacuo. Pure unsymmetrical biaryl was isolated
by simple filtration through silica gel.
[4] For the preparation of triflates see: P.J. Stang, M. Hanack, L.R.
Subramanian, Synthesis (1982) 85–126. For cross-coupling reac-
tions from aryl triflates, see for instances: (a) T. Kamikawa, T.
.