Preferential oxidative addition in palladium(0)-catalyzed suzuki cross-coupling reactions of dihaloarenes with arylboronic acids

Article abstract of DOI:10.1021/ja052547p

The study of Pd(0)-/t-Bu₃P system as a powerful catalyst for the cross-coupling of n,m-dihaloarenes with 1 equiv of arylboronic acids is described. Our work demonstrated that the fate of the regenerated Pd(0) catalyst can be controlled when the appropriate ligand is employed. The results described here may lead to the development of new, efficient processes to conjugate polymers with controlled length which are potentially useful in molecular electronics. Copyright

Full text of DOI:10.1021/ja052547p

Published on Web 06/25/2005
Preferential Oxidative Addition in Palladium(0)-Catalyzed Suzuki
Cross-Coupling Reactions of Dihaloarenes with Arylboronic Acids
Cheng-Guo Dong and Qiao-Sheng Hu*
Department of Chemistry, College of Staten Island and the Graduate Center of the City UniVersity of New York,
Staten Island, New York 10314
Received April 19, 2005; E-mail: qiaohu@mail.csi.cuny.edu
Although Pd(0)-catalyzed cross-coupling polymerizations have
become extremely powerful tools for the synthesis of an array of
polydisperse conjugated polymers,1 controlled Pd(0)-catalyzed
cross-coupling polymerizations for the synthesis of conjugated
Scheme 1. Hypothetic Controlled Pd(0)-Catalyzed Cross-Coupling
Polymerization of AB-Type Monomers
,2
3
polymers with desired length remain elusive. Scrutiny of the cross-
coupling polymerization mechanism suggests that such controlled
polymerizations would be possible if the fate of the regenerated
Pd(0) catalyst could be controlled. For example, the polymerization
of AB-type monomers would be controllable if the regenerated Pd-
Scheme 2. Pd(0)-Catalyzed Cross-Couplings of Dihalobenzenes
with 1 equiv of Arylboronic Acids
(
0) catalyst could be oriented to undergo oxidative addition
preferentially with its homogenously generated coupling product
Scheme 1). Because Pd(0)-catalyzed cross-coupling polymeriza-
(
tions proceed via repeating the oxidative addition-transmetalation-
reductive elimination catalytic cycle, we reasoned that it should be
appropriate to study one particular catalytic cycle of a polymeri-
zation process to address whether and how the preferential oxidative
addition could be achieved. We also reasoned that cross-coupling
reactions that possess the same particular preferential oxidative
addition step as that of the hypothetical polymerization processes
should be appropriate model reactions. In this communication, we
report our study on one type of such model reactions, the cross-
coupling reactions of dihalobenzenes with 1 equiv of arylboronic
Table 1. Room-Temperature Pd(0)-Catalyzed Cross-Couplings of
1
,2-Dibromobenzene with p-Tolylboronic Acida
4
acids (Scheme 2) to establish that it is possible to achieve such
preferential oxidative addition when appropriate Pd(0) catalyst is
employed.
As shown in Scheme 2, mechanistically, the Pd(0) catalyst
regenerated from the first reductive elimination is expected to situate
nearby and interact with its homogenously formed 1-aryl-n-
5
halobenzene (AHB) (n ) 2, 3, or 4). It could undergo oxidative
addition with the AHB (Path A) or diffuse out of the vicinity of
the AHB (Path B). The diffused Pd(0) catalyst is expected to
undergo oxidative addition with a dihalobenzene, because the
amount of dihalobenzene is in excess relative to that of AHB due
to the use of a limited amount of arylboronic acid, and is more
reactive than AHB due to electronic and/or steric effects (Path B).
We envisioned that the key to achieve the preferential oxidative
addition would lie in how to achieve faster oxidative addition of
the regenerated Pd(0) with the AHB (Path A) over its diffusion
process (Path B), and the efficiency of the preferential oxidative
addition could be assessed by examining the ratio of the Path A
product (diarylbenzene) vs the Path B product (AHB). It has been
established that the nature of the ligands has great influence on the
a
Reaction conditions (not optimized): 1,2-dibromobenzene (1.0 equiv),
p-tolyboronic acid (1.0 equiv), K3PO4 (3 equiv), THF (2 mL), room
temperature. b Based on H NMR. Based on GC-MS.
1
c
7
3
entries 3-6). Bulky, electron-rich t-Bu P was found to give a very
satisfying result, with excellent conversion and excellent percentage
of diarylbenzene (Table 1, entry 7).8 These results clearly showed
that the preferential oxidative addition for the regenerated Pd(0)
can be achieved by careful selection of the catalyst system.
With Pd(0)-/t-Bu P as the catalyst system, the cross-coupling
reactions of a number of 1,2-dibromobenzenes with arylboronic
acids were examined, and our results are listed in Table 2. As shown
in Table 2, all tested 1,2-dibromobenzenes including those with
electron-withdrawing and electron-donating substitutents gave high
,9
3
2
oxidative addition rate of a Pd(0) catalyst. We thus began our study
by screening different ligands by using the cross-coupling of 1,2-
dibromobenzene with p-tolylboronic acid as the model reaction.
Our results are listed in Table 1. We found that triphenylphoshine
and bidentate DPPF or DPPE gave very poor results (Table 1,
entries 1-2). More electron-rich monodentate phosphines including
8
disubstituted/monsubstituted product ratio, suggesting the prefer-
ential oxidative addition occurred efficiently. As expected, the cross-
coupling of 1-chloro-2-iodobenzene with p-tolylboronic acid, which
involves the oxidative addition of an inert C-Cl bond, gave
exclusively the monosubstitued product (Table 2, entry 9), sug-
gesting the diffusion process was much faster than the oxidative
6
Buchwald-type monophosphines gave high conversions with
significant amount of diarylbenzene formations, suggesting the
preferential oxidative addition occurred to some extent (Table 1,
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J. AM. CHEM. SOC. 2005, 127, 10006-10007
10.1021/ja052547p CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Room-Temperature Pd(0)-Catalyzed Cross-Couplings of
observed for 1,4-dihalobenzenes (Table 3, entries 4-5). Interest-
ingly, the 1,4-dihalobenzenes underwent much slower Suzuki cross-
couplings than their 1,2- and 1,3-analogues (Table 3, entries 4-5).
Such unusual results suggest that the oxidative addition of the
regenerated Pd(0) to C-Br or C-I bond, although faster than the
diffusion process, occurs slower than the similar oxidative addition
processes for the 1,2- and 1,3-analogues, and serves as the rate-
limiting step.10 Finally, we have also carried out the Suzuki cross-
couplings of 2,5-dibromothiophene, and efficient preferential
oxidative addition was also observed (Table 3, entry 6).
a
1,2-Dihalobenzenes with Arylboronic Acids
In summary, we have demonstrated that the regenerated Pd(0)
catalyst in the cross-coupling of dihaloarenes with arylboronic acids
could undergo oxidative addition preferentially with its homog-
enously formed coupling product when the appropriate Pd(0)
catalyst system is employed. The Pd(0)/t-Bu P was identified as a
3
powerful catalyst system to achieve efficient preferential oxidative
addition. Our study may lead to the development of controlled Pd-
(0)-catalyzed cross-coupling polymerizations for the preparation of
conjugated polymers with desired lengths. Future work in this
direction is under active investigation.
Acknowledgment. We thank the NIH (GM69704) for funding.
Partial support from PSC-CUNY Research Award Program is
gratefully acknowledged. We thank Prof. Alec Greer at Brooklyn
College of CUNY for his help on GC-MS analysis, and the
Frontier Scientific for its generous gifts of boronic acids.
a
Reaction conditions (not optimized): dibromide (1.0 equiv), arylboronic
acids (1.0 equiv), K3PO4 (3 equiv), Pd2(dba)3 (2.5%), t-Bu3P (10%), THF
2 mL), room temperature. Ratio based on GC-MS. Isolated yields of
diarylbenzenes. Conversion of p-tolylboronic acid based on H NMR.
b
c
(
d
1
Table 3. Room-Temperature Pd(0)-Catalyzed Cross-Couplings of
Dihaloarenes with Arylboronic Acids
a
Supporting Information Available: The general procedure and
3
product characterization for Pd(0)-/t-Bu P-catalyzed cross-couplings of
dihalobenzenes with arylboronic acids. This material is available free
of charge via the Internet at http://pubs.acs.org.
References
(
1) Hu, Q.-S. In Synthetic Methods for Step-Growth Polymers; Rogers, M.,
Long, T., Eds.; Wiley: New York, 2003; pp 467-526.
(
2) (a) de Meijere, A.; Diederich, F. Metal-Catalyzed Cross-Coupling
Reactions, 2nd ed.;Wiley-VCH: New York, 2004. (b) Beller, M.; Bolm,
C. Transition Metals for Organic Synthesis; Wiley-VCH:New York, 1998.
(
c) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles
and Applications of Organotransition Metal Chemistry; University Science
Books: Mill Valley, CA, 1987.
(
3) For potential applications of conjugated molecules with desired length as
molecular electronics, see: (a) Carroll, R. L.; Gorman, C. B. Angew.
Chem., Int. Ed. 2002, 41, 4378. (b) Tour, J. M. Acc. Chem. Res. 2000,
33, 791-804.
a
Reaction conditions (not optimized): dihalide (1.0 equiv), arylboronic
b
(4) The use of 1 equiv or less of boronic acids is important for differentiating
products of the preferential oxidative addition pathway from the nonpref-
erential oxidative addition pathway. For cross-couplings of dihalobenzenes
with 2 equiv (or more) of arylboronic acids: (a) Berthiol, F.; Kondolff,
I.; Doucet H.; Santelli. M. J. Organomet. Chem. 2004, 689, 2786-2798.
(b) Simoni, D. et al., Tetrahedron Lett. 2003, 44, 3005-3008. (c) Basu,
B.; Das, P.; Bhuiyan, M. M. H.; Jha, S. Tetrahedron Lett. 2003, 44, 3817-
acid (1.0 equiv), K3PO4 (3 equiv), THF (2 mL), room temperature. Ratio
based on GC-MS. Isolated yields of diarylarenes.
c
addition process for the regenerated Pd(0) catalyst. Surprisingly,
the coupling of 1,2-diiodobenzene with p-tolylboronic acid, which
involves the oxidative addition with a very reactive C-I bond,7
gave only a 21:79 ratio of mono:di product (Table 2, entry 10).
This less efficient preferential oxidative addition might suggest that
the larger size of the second iodo group destabilizes the interaction
of the regenerated Pd(0) catalyst with the homogenously generated
product, leading to a formally faster diffusion process.
c
3820. (d) van der Vlugt, J. I.; Bonet, J. M.; Mills, A. M.; Spek A. L.;
Vogt. D. Tetrahedron Lett. 2003, 44, 4389-4392. (e) Paul, S.; Clark, J.
H. Green Chem. 2003, 5, 635-638. (f) Oh, C. H.; Lim, Y. M. Bull. Korean
Chem. Soc. 2002, 23, 663-664. (g) Eastmond, G. C.; Paprotny, J.; Steiner,
A.; Swanson, L. New J. Chem. 2001, 379-384.
(
5) Recent examples: (a) Yin, J.; Rainka, M. P.; Zhang, X.-X.; Buchwald,
S. L. J. Am. Chem. Soc. 2002, 124, 1162-1163. (b) Kocovsky, P.;
Vyskocil, S.; Cisarova, I.; Sejbal, J.; Tislerova, I.; Smrcina, M.; Lloyd-
Jones, G. C.; Stephen, S. C.; Butts, C. P.; Murray, M.; Langer, V. J. Am.
Chem. Soc. 1999, 121, 7714-7715.
To address whether the preferential oxidative addition could
occur for substrates with spatially separated reactive sites, we have
examined the cross-couplings of 1,3- and 1,4-dihalobenzenes with
(6) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am. Chem.
Soc. 1999, 121, 9550-9561.
7) Pd(0)/t-Bu P for cross-coupling reactions: for a review: (a) Littke, A.
3
(
1
equiv of arylboronic acids. We found that excellent ratios of
F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176-4211. Selected recent
examples: (b) Stambuli, J. P.; Kuwano, R.; Hartwig, J. F. Angew. Chem.,
Int. Ed. 2002, 41, 4746-4748. (c) Littke, A. F.; Dai, C.; Fu, G. C. J. Am.
Chem. Soc. 2000, 122, 4020-4028.
diarylbenzenes vs monoarylbenzenes were observed for both 1,3-
diiodobenzene and 1,3-dibromobenzene, suggesting the preferential
oxidative addition also occurred efficiently (Table 3, entries 1-3).
That the preferential oxidative addition occurred more efficiently
for 1,3-diiodobenzene than for 1,2-diiodobenzene and 1,3-dibro-
mobenzene suggests that the size of the second iodo group no longer
interferes with the diffusion process and is consistent with the
established results of C-I bonds having a higher oxidative addition
rate with Pd(0) than C-Br bonds do.2 Such a trend was also
(8) Self-coupling products of boronic acids were observed in low yields (0-
3
%). See Supporting Information.
9) 1,2-Dibromobenzene exhibited higher reactivity than 2-bromobiphenyl in
Pd(0)-/t-Bu P-catalyzed Suzuki cross-coupling reaction. See Supporting
Information.
(
3
(
10) Completed conversion was observed when the reaction was carried out
at 60 °C for 20 h, with 79% isolated yield and 9:91 of mono:di product
ratio.
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