Boron Trifluoride Induced Palladium-Catalyzed Cross-Coupling Reaction of 1-Aryltriazenes with Areneboronic Acids

Article abstract of DOI:10.1021/ol036436b

(Matrix presented) Aryltriazenes are directly coupled with areneboronic acids in the presence of a catalytic amount of Pd₂(dba)₃ and P(tBu)₃ together with 1 equiv of BF₃·OEt ₂ in DME to afford the corresponding biaryl products in up to 98% yield. A carbonylative cross-coupling reaction under a carbon monoxide atmosphere is also found to give the corresponding diaryl ketone with a similar catalyst system.

Full text of DOI:10.1021/ol036436b

ORGANIC
LETTERS
2004
Vol. 6, No. 4
617-619
Boron Trifluoride Induced
Palladium-Catalyzed Cross-Coupling
Reaction of 1-Aryltriazenes with
Areneboronic Acids
Tomoyuki Saeki,* Eun-Cheol Son, and Kohei Tamao*
International Research Center for Elements Science, Institute for Chemical Research,
Kyoto UniVersity, Uji, Kyoto 611-0011, Japan
tamao@scl.kyoto-u.ac.jp
Received December 15, 2003
ABSTRACT
Aryltriazenes are directly coupled with areneboronic acids in the presence of a catalytic amount of Pd2(dba)3 and P(tBu)3 together with 1 equiv
of BF3‚OEt2 in DME to afford the corresponding biaryl products in up to 98% yield. A carbonylative cross-coupling reaction under a carbon
monoxide atmosphere is also found to give the corresponding diaryl ketone with a similar catalyst system.
Nickel- or palladium-catalyzed cross-coupling reactions have
been widely used as one of the most powerful synthetic tools
for the construction of carbon-carbon and carbon-hetero-
atom bonds.1 Although a variety of organometallic reagents
have been explored, electrophilic counterparts have been
substantially limited to organic halides and triflate.
Heck-type reactions.3 Since then, coupling reactions of
arenediazonium salts with organometallic reagents have also
been developed.4 The arenediazonium salts, however, are
prone to decompose upon storage, which is a critical
disadvantage for practical use. Recently, 1-aryltriazenes,
which can be easily prepared from the corresponding
arylamines,5 have been employed by Sengupta et al. as an
arenediazonium surrogate in the Mizoroki-Heck-type reac-
tion;6 the triazenes are pretreated with trifluoroacetic acid
(TFA) or tetrafluoroboric acid (HBF4) to revert to the
(3) (a) Kikukawa, K.; Matsuda T. Chem. Lett. 1977, 159. (b) Sengupta,
S.; Bhattacharya, S. J. Chem. Soc., Perkin Trans. 1 1993, 1943. (c) Sengupta,
S.; Bhattacharya, S.; Sadhukkan, S. K. J. Chem. Soc., Perkin Trans. 1 1998,
275. (d) Sengupta, S.; Sadhukkan, S. K. J. Chem. Soc., Perkin Trans. 1
1999, 2235. (e) Andrus, M. B.; Song, C.; Zhang, J. Org. Lett. 2002, 4,
2079.
(4) (a) Kikukawa, K.; Ikenaga, K.; Wada, F.; Matsuda, T. Chem. Lett.
1983, 1337. (b) Kikukawa, K.; Kono, K.; Wada, F.; Matsuda, T. J. Org.
Chem. 1983, 48, 1333. (c) Ikenaga, K.; Matsumoto, S.; Kikukawa, K.;
Matsuda, T. Chem. Lett. 1990, 185. (d) Sengupta, S.; Bhattacharya, S. J.
Org. Chem. 1997, 62, 3405. (e) Andrus, M. B.; Song, C. Org. Lett. 2001,
3, 3761.
Carbon-nitrogen compounds may be a third candidate as
electrophilic counterparts in cross-coupling reactions.2 In
1977,3a Kikukawa et al. reported the synthetic utility of
arenediazonium salts in palladium-catalyzed Mizoroki-
(1) (a) Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: Weinheim, 1998. (b) Cross-Coupling Reactions:
A Practical Guide; Miyaura, N., Ed.; Springer-Verlag: Heidelberg, 2002;
Top. Curr. Chem., Vol. 219. (c) 30 Years of Cross-Coupling Reaction.
Tamao, K.; Hiyama, T.; Negishi, E.-i., Eds., J. Organomet. Chem. 2002,
653 (Special Issue).
(5) Kimball, D. B.; Haley, M. M. Angew. Chem., Int. Ed. 2002, 41, 3338
and references therein.
(2) In addition to the arenediazonium salts and aryltriazenes as the main
subject of this paper, arylammonium salts have been recently used for the
Suzuki-Miyaura-type coupling reaction: Blakey, S. B.; MacMillan, D. W.
C. J. Am. Chem. Soc. 2003, 125, 6046.
(6) (a) Bhattacharya, S.; Majee, S.; Mukherjee, R.; Sengupta, S. Synth.
Commun. 1995, 25, 651. (b) Sengupta, S.; Sadhukkan, S. K. Tetrahedron
Lett. 1998, 39, 715. (c) Sengupta, S.; Sadhukkan, S. K. Org. Synth. 2002,
79, 52.
10.1021/ol036436b CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/20/2004

corresponding diazonium species and subsequently coupled
with olefins. This methodology was extended by Bra¨se et
al. to solid-phase organic synthesis.7 However, the use of
strong protic acids such as TFA and HBF4 should still be a
significant limitation considering their compatibility with
functional groups and organometallic reagents. Actually, the
Suzuki-Miyaura-type coupling reaction with phenylboronic
acid was attempted, but the results were not necessarily
satisfactory, as described by the authors themselves.7a
Reported herein is the first observation that the 1-aryl-
triazenes can be directly coupled with areneboronic acids in
the presence of a palladium catalyst, phosphine ligand, and
boron trifluoride. Our working hypothesis for the Lewis acid
induced cross-coupling reaction, in which a diaryl-palladium
intermediate is formed in a concerted process, is depicted in
Figure 1. It can be expected here that the boron trifluoride
The Lewis acid was essential for the formation of the
biphenyl product; without BF3‚OEt2, no reaction occurred
at all. In a control reaction, the 1-aryltriazenes did not react
with boron trifluoride in the absence of either the palladium
catalyst or boronic acids, implying that a concerted process
may be involved. The choice of solvent also significantly
affected the product yield, as shown by the results [solvent
and GC yield (1 h): DME, 98%; THF, 96%; dioxane, 94%;
toluene, 66%; DMF, trace; NMP, 0%]; satisfactory results
were obtained only in ethereal solvents and we chose DME
as the general solvent on the basis of the reaction rate.
The screening of catalysts and phosphine ligands re-
vealed that the catalyst system with Pd2(dba)3 and P(tBu)3
was the most effective, regardless of their ratio, giving rise
to the coupling product in a yield of 98% (Table 1, entries
1 and 2).
Table 1. Optimization of Catalyst Systema
entry
Pd complex
ligand
yield [%]b 10 min, 1 h
1
2
3
4
5
6
7
8
9
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd(PPh3)4
Pd(OAc)2
P(tBu)3
P(tBu)3
none
PPh3
dppb
dppf
PBiph(tBu)2
P(tBu)3
98, 98 (91)d
95, 95
69, 79
80, 83
64, 70
72, 79
28, 47
49, 59
19, 37
c
c
Figure 1. Schematic representation of a direct formation of diaryl-
palladium intermediate in a concerted mechanism.
P(tBu)3
a Reaction conditions: 1 (0.50 mmol), 2 (1.0 mmol), catalyst [Pd content]
(4 mol %), ligand (8 mol %), BF3‚OEt2 (0.50 mmol), room temperature,
DME (5.0 mL). b Yields are determined by GC analysis with eicosane as
an internal standard. c Using 4 mol %. d Isolated yield.
plays two roles during the reaction: (1) the boron trifluoride
serves as a Lewis acid toward the 1-aryltriazene to form an
aryltriazene-boron trifluoride complex to enhance the reac-
tivity of the sp2-carbon-nitrogen bond, and then (2) the
resulting aminotrifluoroborate moiety serves as a fluoride
base to promote a transmetallation of the areneboronic acid.
Hence, the diaryl-palladium species can be directly formed
from the zerovalent palladium complex.
After several tentative experiments, the desired cross-
coupling of 1-(p-tolyl)triazene (1) with p-anisylboronic acid
(2) was achieved with a catalytic amount of Pd2(dba)3 (4
mol %) and P(tBu)3 (8 mol %) together with 1 equiv of
BF3‚OEt2 in DME to afford the biphenyl product 3 in 98%
GC yield within 10 min at room temperature, as shown in
Scheme 1.8
The phosphine-free Pd(0) catalyst gave the coupling
product in 79% yield (entry 3). Whereas the addition of PPh3
and bisphosphines hardly influenced the yield (entries 4-6),
the more bulky ligand, PBiph(tBu)2, significantly sup-
pressed the reaction process (entry 7). Other precatalysts
such as Pd(PPh3)4 and Pd(OAc)2 were less effective (entries
8 and 9).
The scope of the coupling reaction with respect to the
substituent on the 1-aryltriazenes and areneboronic acids was
examined (Table 2).
Aryltriazenes having electron-donating groups at the ortho,
meta, and para positions and a sterically hindered mesityl
and naphthyl groups smoothly underwent the coupling
reaction (entries 1-5 and 13). On the other hand, electron-
withdrawing groups such as halogens, triflate, and acetyl
substituents decreased the yields to some extent (entries
6-11). Notably, the triazene moiety showed a higher
chemoselectivity over the triflate group as well as the
bromine atom9,10 as a leaving group under the stated reaction
Scheme 1
(7) (a) Bra¨se, S.; Schroen, M. Angew. Chem., Int. Ed. 1999, 38, 1071.
(b) Bra¨se, S.; Kirchhoff, J. H.; Ko¨bberling, Tetrahedron 2003, 59, 885.
(8) Triazenes having a diethylamino or morpholino moiety at the
3-position were less effective under the reaction conditions, and areneboronic
esters were completely inert.
618
Org. Lett., Vol. 6, No. 4, 2004

the Lewis acidic conditions (entries 4, 12, and 14), whereas
the furyl group showed a lack of compatibility (entry 15).
A carbonylative cross-coupling reaction12 was also exam-
ined under a carbon monoxide atmosphere. The reaction con-
dition was not optimized, but the carbonylative cross-coup-
ling of 1 and 2 was found to give the corresponding diaryl
ketone in 70% isolated yield (77% GC yield) as shown in
Scheme 2.
Table 2. Cross-coupling Reaction of 1-Aryltriazenes with
Areneboronic Acidsa
entry
R
Ar
yield [%]b 10 min, 1 h
1
2
3
4
5
6
7
8c
9c
10
11
12
13
14
15
o-Me
m-Me
p-Me (1)
p-MeO
2,4,6-Me3
p-F
p-Cl
p-Br
p-I
p-TfO
p- MeCO
p-Et2N
p-Me (1)
p-Me (1)
p-Me (1)
p-MeO-C6H4 (2)
p-MeO-C6H4 (2)
p-MeO-C6H4 (2)
p-Me-C6H4
p-MeO-C6H4 (2)
p-MeO-C6H4 (2)
p-MeO-C6H4 (2)
p-MeO-C6H4 (2)
p-MeO-C6H4 (2)
p-MeO-C6H4 (2)
p-MeO-C6H4 (2)
p-MeO-C6H4 (2)
1-naphthyl
81, 91(72)d
88, 92(80)d
98, 98(91)d
94, 94
85, 90
73, 81
64, 74(68)d
30, 40
tr, tr
43, 52(41)d
31, 58
97, 97
88, 90(78)d
94, 94(84)d
0, 0
Scheme 2
In summary, we have shown that the 1-aryltriazenes can
be directly employed in Lewis acid induced palladium-
catalyzed cross-coupling reactions with areneboronic acids.
Although the actual reaction mechanism is not yet clear at
the present time, the present reaction with a nitrogen-based
leaving group has a potential utility in organic synthesis,
providing a quick and halogen-free cross-coupling process
under very mild conditions.
2-thienyl
2-furyl
a Reaction conditions: 1-aryltriazene (0.50 mmol), areneboronic acid (1.0
mmol), Pd2(dba)3 (2 mol %), P(tBu)3 (8 mol %), BF3‚OEt2 (0.50 mmol),
room temperature, DME (5.0 mL). b Yields are determined by GC analysis
with eicosane as an internal standard. c Using 5 mol % of Pd2(dba)3 without
phosphine ligand. See ref 11. d Isolated yields.
Acknowledgment. We thank the Ministry of Education,
Culture, Sports, Science and Technology, Japan, for the
Grant-in-Aid for COE Research on Elements Science, no.
12CE2005, and Hokko Chemical Industry Co., Ltd. for the
gift of phosphine ligands.
conditions, giving the corresponding products in moderate
yields (entries 8 and 10).11 The lack of reactivity of the
iodophenyltriazene (entry 9) remained to be clarified. It is
noted that the electron-rich substituents such as the methoxy,
diethylamino, and thienyl groups were also tolerated under
Supporting Information Available: Detailed descrip-
tions of experimental procedures and spectroscopic data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(9) The competitive reaction of aryltriazene 1 with p-bromotoluene in
the reaction with areneboronic acid 2 afforded biphenyl product 3 in 90%
yield, together with the aryl bromide being recovered unchanged.
(10) Chemoselective differential reactions of 4-bromobenzene diazonium
salt and 4-bromophenyltriazene have been already reported; see refs 4a,d
and 6c.
(11) An increased amount of catalyst (5 mol %) without phosphine ligand
was necessary: only a trace amount of product was obtained in the presence
of phosphine ligand. The reason is not clear.
OL036436B
(12) (a) Kikukawa, K.; Kono, K.; Wada, F.; Matsuda, T. Chem. Lett.
1982, 35. (b) Kikukawa, K.; Idemoto, T.; Katayama, A.; Kono, K.; Wada,
F.; Matsuda, T. J. Chem. Soc., Perkin Trans. 1 1987, 1511. (c) Andrus, M.
B.; Ma, Y.; Zang, Y.; Song, C. Tetrahedron Lett. 2002, 43, 9137.
Org. Lett., Vol. 6, No. 4, 2004
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