Suzuki-Miyaura cross-coupling reactions of aryl tellurides with potassium aryltrifluoroborate salts

Article abstract of DOI:10.1021/jo052061r

Palladium(0)-catalyzed cross-coupling between potassium aryltrifluoroborate salts and aryl tellurides proceeds readily to afford the desired biaryls in good to excellent yield. The reaction seems to be unaffected by the presence of electron-withdrawing or electron-donating substituents in both the potassium aryltrifluoroborate salts and aryl tellurides partners. Biaryls containing a variety of functional groups can be prepared. A chemoselectivity study was also carried out using aryl tellurides bearing halogen atoms in the same compound. In addition, this new version of the Suzuki-Miyaura cross-coupling reaction was monitored by electrospray ionization mass spectrometry where some reaction intermediates were detected and analyzed.

Full text of DOI:10.1021/jo052061r

Suzuki-Miyaura Cross-Coupling Reactions of Aryl Tellurides with
Potassium Aryltrifluoroborate Salts
Rodrigo Cella,† Rodrigo L. O. R. Cunha,‡ Ana E. S. Reis,§ Daniel C. Pimenta,|
Cle´cio F. Klitzke,| and He´lio A. Stefani*,†,‡,§
Instituto de Qu´ımica, UniVersidade de Sa˜o Paulo, Sa˜o Paulo SP, Brazil, Departamento de Biof´ısica,
UniVersidade Federal de Sa˜o Paulo, Sa˜o Paulo SP, Brazil, Faculdade de Cieˆncias Farmaceˆuticas,
UniVersidade de Sa˜o Paulo, Sa˜o Paulo SP, Brazil, and Laborato´rio de Espectrometria de Massas, Centro
de Toxinologia Aplicada - CAT/CEPID, Instituto Butantan, Sa˜o Paulo SP, Brazil
hstefani@usp.br
ReceiVed September 30, 2005
Palladium(0)-catalyzed cross-coupling between potassium aryltrifluoroborate salts and aryl tellurides
proceeds readily to afford the desired biaryls in good to excellent yield. The reaction seems to be unaffected
by the presence of electron-withdrawing or electron-donating substituents in both the potassium
aryltrifluoroborate salts and aryl tellurides partners. Biaryls containing a variety of functional groups can
be prepared. A chemoselectivity study was also carried out using aryl tellurides bearing halogen atoms
in the same compound. In addition, this new version of the Suzuki-Miyaura cross-coupling reaction
was monitored by electrospray ionization mass spectrometry where some reaction intermediates were
detected and analyzed.
Introduction
The main way to obtain biaryl compounds is the Suzuki cross-
coupling reactions. Many protocols have been recently de-
scribed.5 The reaction is usually performed using a boronic acid
or boronate ester and aryl halides or aryl triflates in the presence
of a palladium catalyst, a ligand, and a base.6 These conditions,
however, can be changed in some cases. As an example, instead
of aryl halides or triflates, aryldiazonium7 or aryltrimethylam-
monium8 salts can be used. In other cases, transition-metal
Biaryl systems are an important class of compounds; they
are involved in many applications, especially in the pharma-
ceutical chemistry. For example, in the sartan family of drugs
for high blood pressure,1 vancomycin antibiotics,2 and flurbi-
profen antiinflammatories,3 biaryls comprise an important
feature. Moreover, the aryl-aryl bond is present in numerous
natural products as well as in biologically active agrochemicals.4
(5) For reviews, see: (a) Suzuki, A. J. Organomet. Chem. 2002, 653,
83. (b) Stanforth, S. P. Tetrahedron 1998, 54, 263. (c) Suzuki, A. In Metal-
Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.;
Wiley-VCH: New York, 1998; Chapter 2. (d) Miyaura, N.; Suzuki, A.
Chem. ReV. 1995, 95, 2457.
(6) (a) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122,
4020. (b) Lemo, J.; Heuze´, K.; Astruc, D. Org. Lett. 2005, 7, 2253. (c) Li,
J.-H.; Liu, W.-J. Org. Lett. 2004, 6, 2809 (d) Arentsen, K.; Caddick, S.;
Cloke, F. G. N.; Herring, A. P.; Hitchcock, P. B. Tetrahedron Lett. 2004,
45, 3511. (e) Barder, T. E.; Buchwald, S. L. Org. Lett. 2004, 6, 2649 (f)
Broutin, P.-E.; Cerna, I.; Campaniello, M.; Leroux, F.; Colobert, F. Org.
Lett. 2004, 6, 4419. (g) Cheng, J.; Wang, F.; Xu, J.-H.; Pan, Y.; Zhang, Z.
Tetrahedron Lett. 2003, 44, 7095. (h) Ito, T.; Iwai, T.; Mizuno, T.; Ishino,
Y. Synlett 2003, 1435.
† Instituto de Qu´ımica, Universidad de Sa˜o Paulo.
‡ Universidade Federal de Sa˜o Paulo.
§ Faculdade de Cieˆncias Farmaceˆuticas, Universidade de Sa˜o Paulo.
| Instituto Butantan.
(1) (a) Smith, G. B.; Dezeny, G. C.; Hughes, D. L.; King, A. O.;
Verhoeven, T. R. J. Org. Chem. 1994, 59, 8151. (b) Birkenhager, W. H.;
de Leeuw, P. W. J. Hypertens. 1999, 17, 873. (c) Goa, K. L.; Wagstaff, A.
J. Drugs 1996, 51, 820.
(2) Nicolaou, K. C.; Boddy, C. N. C.; Brase, S.; Winssinger, N. Angew.
Chem., Int. Ed. 1999, 38, 2096.
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Kushwaha, B. S. Asian J. Chem. 2004, 16, 558. (b) Gasparani, L.; Ongini,
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2002, 102, 1359. (b) Bringmann, G.; Gunther, C.; Ochse, M.; Schupp, O.;
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1996, 37, 3857. (c) Kikukawa, K.; Kono, K.; Wada, F.; Matsuda, T. J.
Org. Chem. 1983, 48, 1333.
10.1021/jo052061r CCC: $33.50 © 2006 American Chemical Society
Published on Web 11/25/2005
244
J. Org. Chem. 2006, 71, 244-250

Reactions of Aryl Tellurides with Potassium Aryltrifluoroborate Salts
catalysts, such as nickel8,9 or rhodium,10 can substitute palladium
as catalysts. Leadbeater et al. recently reported a “transition-
metal-free” Suzuki cross-coupling reaction11a using microwave
irradiation as an energy source and water as solvent. Recently,11c
the author discovered that the sodium carbonate used as a base
was contaminated with palladium (level of 50 ppb) and that
this contaminant is responsible for the cross-coupling reaction.
This alternative energy source was also studied by Yu et al.12
Boronic acids and boronate esters are the most commonly
used derivatives in Suzuki cross-coupling reactions. Recently,
Molander et al.13 have explored the use of potassium organo-
trifluoroborate salts as an alternative to these boron reagents in
Suzuki coupling reactions. These salts are readily prepared by
the addition of an aqueous solution of inexpensive, widely
available KHF2 to a wide variety of organoboron intermediates.14
In the past decade, organotellurium chemistry was extensively
explored, and many methods employing tellurium compounds
have been developed.15 Among these methods, organotellurium
reagents were successfully used as the electrophilic reagent16
in several metal-catalyzed cross-coupling reactions, such as
Sonogashira,17 Negishi,18 Heck,19 and Suzuki-Miyaura.20.
By taking advantage of the attractive features of potassium
organotrifluoroborate salts and the organotellurium compounds
in cross-coupling reactions, we report herein an efficient and
chemoselective method for the synthesis of important biaryl
compounds by the palladium-catalyzed cross-coupling reaction
of aryl tellurides and potassium aryl trifluoroborate salts (eq
1).
TABLE 1. Study of Catalyst Effect on Cross-Coupling Reaction
Using Aryl Telluride 1a and Potassium Phenyltrifluoroborate 2a
entry
catalyst
additivea
yield (%)
1
2
3
Pd/C
PdCl2
NiCl2(dppe)
Pd(acac)2
tracesb
<10
nr
Ag2O
CuI
4
30
5
6
7
8
Pd(acac)2
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
55
43
80
83
Pd (acetate)2
PdCl2(dppf)‚CH2Cl2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
9
80c
58d
40e
70f
65g
79h
57
10
11
12
13
14
15
Pd2(dba)3‚CHCl3
a 2 equiv was used. b Na2CO3 used as base. c 20 mol % of catalyst. d 5
mol % of catalyst. e 1 mol % of catalyst. f The reaction was performed at
room temperature. g 1 equiv of 2a. h 2 equiv of 2a.
reaction, electing to use 1-butyltellanyl-4-methoxybenzene 1a
and potassium phenyltrifluoroborate 2a as standard reagents.
First, we used a previous protocol described for Suzuki cross-
coupling reactions between alkynyltrifluoroborate salts and
vinylic tellurides20 (eq 2). Regarding this, treatment of com-
pound 1a with 2a in methanol at reflux temperature using Pd-
(acac)2 (15 mol %) as catalyst, in the presence of CuI (30 mol
%) and triethylamine, afforded the corresponding 4-methoxy-
biphenyl 3a in low yield (30%) (Table 1, entry 4).
Results and Discussion
Development. We initially focused our attention on the
determination of the best experimental conditions for the
(8) Blakey, S. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125,
6046.
(9) Tang, Z.-Y.; Hu, Q.-S. J. Am. Chem. Soc. 2004, 126, 3058.
(10) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2005, 7, 2229.
(11) (a) Leadbeater, N. E.; Marco, M. Angew. Chem., Int. Ed. 2003, 42,
1407. (b) Arvela, R. K.; Leadbeater, N. E. J. Org. Chem. 2005, 70, 1786.
(c) Arvela, R. K.; Leadbeater, N. E.; Sangi, M. S.; Williams, V. A.;
Granados, P.; Singer, R. D. J. Org. Chem. 2005, 70, 161.
(12) Miao, G.; Ye, P.; Yu, L.; Baldino, C. M. J. Org. Chem. 2004, 70,
2332.
(13) (a) Molander, G. A.; Felix, L. A. J. Org. Chem. 2005, 70, 3950.
(b) Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393. (c) Molander, G. A.;
Rivero, M. R. Org. Lett. 2002, 4, 107. (d) Molander, G. A.; Katona, B. W.;
Machrouhi, F. J. Org. Chem. 2002, 67, 8416. (e) Molander, G. A.; Biolatto,
B. Org. Lett. 2002, 4, 1867. (f) Molander, G. A.; Biolatto, B. J. Org. Chem.
2003, 68, 4302. (g) Molander, G. A.; Yun, C.; Ribagorda, M.; Biolatto, B.
J. Org. Chem. 2003, 68, 5534. (h) Molander, G. A.; Ribagorda, M. J. Am.
Chem. Soc. 2003, 125, 11148.
(14) (a) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf,
M. R. J. Org. Chem. 1995, 60, 3020. (b) Vedejs, E.; Fields, S. C.; Hayashi,
R.; Hitchcock, S. R.; Powell, D. R.; Schrimpf, M. R. J. Am. Chem. Soc.
1999, 121, 2460.
(15) For review: (a) Petragnani, N.; Stefani, H. A. Tetrahedron 2005,
61, 1613. (b) Petragnani, N.; Comasseto, J. V. Synthesis 1986, 1. (c)
Petragnani, N.; Comasseto, J. V. Synthesis 1991, 793, 897. (d) Comasseto,
J. V.; Ling, L. W.; Petragnani, N.; Stefani, H. A. Synthesis 1997, 373.
(16) Zeni, G.; Braga, A. L.; Stefani, H. A. Acc. Chem. Res. 2003, 36,
731.
In view of this result, we initiated an investigation to define
the best catalyst. The reactions were monitored by the consump-
tion of starting material and the appearance of the desired
product by GC or GC-MS. As can be seen in Table 1, both
Pd(0) and Pd(II) as well as the nickel catalyst were tested. The
best result was reached when Pd(PPh3)4 with Ag2O was used
(Table 1, entry 8). The desired product 3a was formed in 83%
yield.
When Pd(acac)2 and Ag2O were used (Table 1, entry 5) the
yield slightly increased in relation to when CuI (Table 1, entry
4) was used as the oxidant of palladium, but it remained less
than when palladium(0) tetrakis(triphenylphosphine) was used
as the catalyst. When PdCl2(dppf)‚CH2Cl2 was used, product
3a was obtained in 80% yield (Table 1, entry 7). We have tested
palladium on charcoal (Table 1, entry 1) using sodium carbonate
as the base and without an oxidant as described by Xu et al.,21
but only traces of 3a were detected by GC. When the nickel
(19) (a) Braga, A. L.; Rhoden, C. R. B.; Zeni, G.; Silveira, C. C.;
Andrade, L. H. J. Organomet. Chem. 2003, 682, 35. (b) Nishibayashi, Y.;
Cho, C.-S.; Ohe, K.; Uemura, S. J. Organomet. Chem. 1996, 507, 197. (c)
Nishibayashi, Y.; Cho, C.-S.; Ohe, K.; Uemura, S. J. Organomet. Chem.
1996, 526, 335.
(20) (a) Stefani, H. A.; Cella, R.; Do¨rr, F. A.; Pereira, C. M. P.; Zeni,
G., Jr.; Gomes, M. Tetrahedron Lett. 2005, 46, 563. (b) Kang, S.-K.; Hong,
Y.-T.; Kim, D.-H.; Lee, S.-H. J. Chem. Res. 2001, 283.
(21) Lu, G.; Franze´n, R.; Zhang, Q.; Xu, Y. Tetrahedron Lett. 2005, 46,
4255.
(17) (a) Zeni, G.; Perin, G.; Cella, R.; Jacob, R. G.; Braga, A. L.; Silveira,
C. C.; Stefani, H. A. Synlett 2002, 6, 975. (b) Braga, A. L.; Lu¨dtke, D. S.;
Vargas, F.; Donato, R. K.; Silveira, C. C.; Stefani, H. A.; Zeni, G.
Tetrahedron Lett. 2003, 44, 1779. (c) Braga, A. L.; Vargas, F.; Zeni, G.;
Silveira, C. C.; Andrade, L. H. Tetrahedron Lett. 2002, 43, 4399. (d) Zeni,
G.; Comasseto, J. V. Tetrahedron Lett. 1999, 40, 4619.
(18) Zeni, G.; Alves, D.; Braga, A. L.; Stefani, H. A.; Nogueira, C. W.
Tetrahedron Lett. 2004, 45, 4823.
J. Org. Chem, Vol. 71, No. 1, 2006 245

Cella et al.
TABLE 2. Study of Base Effect on Cross-Coupling Reaction Using
Aryl Telluride 1a and Potassium Trifluoroborate 2a
TABLE 3. Study of the Effect of Additive on the Cross-Coupling
Reaction Using Aryl Telluride 1a and Potassium Trifluoroborate 2a
entry
base
Et3N
DIPEA
K2CO3
Cs2CO3
EtNH2
(i-Pr)2NH
yield (%)
entry
additive
yield (%)
1
2
3
4
5
6
7
60
83
82
70
57
traces
traces
1
2
3
4
5
6
7
n.r.
83
Ag2O
Ag2O
Ag2O
AgOAc
CuIc
49a
30b
76
n.r.
n.r.
CuI
a 1 equiv of reoxidant was utilized. b 10 molar equiv of reoxidant was
utilized. c This reaction was performed in the presence of atmospheric air.
complex, NiCl2(dppe), was used as catalyst no reaction was
observed (Table 1, entry 3). Other Pd(0) catalysts were used,
e.g., Pd2(dba)3‚CHCl3 (Table 1, entry 15), but the yield
decreased in these cases.
revealed that the optimum conditions for the coupling were
found to be the use of 1-butyltellanyl-4-methoxybenzene 1a (0.5
mmol) and potassium phenyltrifluoroborate salt 2a (1.2 equiv),
Pd(PPh3)4 (10 mol %), Ag2O (1 mmol), Et3N (3 equiv) in MeOH
at reflux temperature for 90 min. Using these reaction conditions,
we were able to prepare the 4-methoxybiphenyl 3a in 83% yield.
To demonstrate the efficiency of this cross-coupling reaction,
we explored the generality of our method extending the coupling
reaction to a variety of aryl tellurides 1a-n. The results are
summarized in Table 4. The Pd(0)-catalyzed Suzuki reaction
proved to be exceptionally active. It is clear that this is a general
method that tolerates both electron-withdrawing and electron-
donating substituents. In addition, even an ortho-substituted
telluride afforded the corresponding biphenyl compound in good
yield (Table 4, entry 4). Unfortunately, this method was less
effective for the reaction of heteroaryl tellurides. The reaction
of 2-butyltellurium thiophene 1i with 2a afforded a 46% yield
of the corresponding coupled product 3i (Table 4, entry 9).
However, the 2-butyltellanylfuran 1j coupled with 2a in 63%
yield (Table 4, entry 10), while the 3-butyltellanylpyridine 1k
afforded the desired product 3k in 65% yield (Table 4, entry
11).
Study of the Relative Reactivity of the Tellurium Moiety
Compared to Halides in the Cross-Coupling Reaction. For
substrates that contain more than one halide/triflate, the selective
monofunctionalization through Suzuki cross-coupling can be a
great tool in organic synthesis.22 For previously described
palladium catalysts, the general order of reactivity as follows:
I > Br g OTf . Cl.5 However, to the best of our knowledge,
a chemoselective study between organotellurium compounds and
substrates that contain halides or triflates in the structure have
never been described.
The results of these studies indicated that the use of 20 and
10 mol % of Pd(PPh3)4, respectively, proved to be comparably
effective (Table 1, entries 9 and 8). However, when the loading
was dropped to 5 and 1 mol % (Table 1, entries 10 and 11), the
yield noticeably decreased. The cross-coupling reaction between
1a and 2a was performed at room temperature (Table 1, entry
12), but the yield was less than when reflux temperature was
applied (Table 1, entry 8). Only 90 min was required for total
consumption of the starting material as monitored by GC.
The homocoupling reaction of phenyltrifluoroborate 2a under
these conditions was observed on a small scale. Because of this,
the phenyltrifluoroborate 2a loading was studied. The result of
this study indicated that the use of 1.2 equiv of 2a (Table 1,
entry 8) is similar to that when 2 equiv of 2a was used (Table
1, entry 14). However, when 1 equiv of 2a was used (Table 1,
entry 13), the yield decreased.
After the determination of the best catalyst, we studied the
influence of the base. First, the reaction was carried out in the
absence of base (Table 2, entry 1). Biaryl 3a was obtained in
satisfactory yield. Inorganic bases, such as potassium carbonate
(Table 2, entry 4) and cesium carbonate (Table 2, entry 5), were
used but led to a reduction in the yield of the desired product
and to an increased formation of borate salt 3a homocoupling
product. Although the reaction yield remained high for the
tertiary amines, e.g., triethylamine (TEA) or diisopropylethyl-
amine (DIPEA) (Table 2, entries 2 and 3, respectively), when
secondary or primary amines were used only traces of the
product were detected by GC-MS analysis (Table 2, entries 6
and 7).
We observed that this cross-coupling reaction required the
use of an additive for Pd(0) to Pd(II), as can be seen in Table
3. When the reaction was performed in the absence of additive
(Table 3, entry 1) no reaction was observed. The best result
was observed using 2 equiv of Ag2O (Table 2, entry 2). When
the reaction was carried out with 1 equiv of Ag2O (Table 2,
entry 3) or a catalytic amount (Table 2, entry 4) of Ag2O, the
desired product 3a was obtained in lower yield. Silver acetate
(Table 2, entry 5) and cuprous iodide (Table 2, entries 6 and 7)
were tested also to improve the yield, but these additives were
not good alternatives, especially when cuprous reagents were
used wherein no reaction was observed.
As can be seen in Table 5, we have established that under
the optimal conditions for Suzuki coupling as described above,
the 1-butyltellanyl-4-chlorobenzene 1l and 1-butyltellanyl-4-
bromobenzene 1m have reacted with highly selective mono-
functionalization of difunctionalized arenes, affording the
4-chlorobiphenyl 3l (Table 5, entry 1) and 4-bromobiphenyl 3m
(Table 5, entry 2), respectively, in high yields. Unfortunately,
in the case of 1-butyltellanyl-4-iodobenzene 1n the chemose-
lectivity seems not to be very effective; the 4-iodobiphenyl 3n
(Table 5; entry 3) was obtained only in 42% yield. This low
(22) (a) Kawada, K.; Arimura, A.; Tsuri, T.; Fuji, M.; Komurasaki, T.;
Yonezawa, S.; Kugimiya, A.; Haga, N.; Mitsumori, S.; Inagaki, M.;
Nakatani, T.; Tamura, Y.; Takechi, S.; Taishi, T.; Kishino, J.; Ohtani, M.
Angew. Chem., Int. Ed. 1998, 37, 973. (b) Hird, M.; Gray, G. W.; Toyne,
K. J. Mol. Cryst. Liq. Cryst. 1991, 206, 187.
The influence of the reaction solvent was also investigated.
No reaction occurred in acetonitrile, and when THF-H2O (20:
1, v/v) was used the cross-coupling product was obtained in
63% yield. Thus, careful analysis of the optimized reaction
246 J. Org. Chem., Vol. 71, No. 1, 2006

Reactions of Aryl Tellurides with Potassium Aryltrifluoroborate Salts
TABLE 4. Cross-Coupling Reaction of Aryl Tellurides 1 and
Potassium Phenyltrifluoroborates 2
TABLE 5. Study of the Chemoselectivity on Cross-Coupling of
Halo-Substituted Aryl Tellurides and Potassium
Phenyltrifluoroborate 2a
a Terphenyl was formed in 15% isolated yield.
SCHEME 1
Suzuki-Miyaura cross-coupling reaction, we turned our atten-
tion to an investigation of this reaction in detail, taking
advantage of the electrospray ionization mass spectrometry
technique (ESI-MS) features. ESI-MS is a powerful tool for
detection and characterization in the gas phase of charged and
labile species in solution.23 The mildness of ionization of this
technique allows the detection and characterization of labile
species and reaction intermediates proving to be very useful
for probing mechanistic propositions of chemical reactions as
already demonstrated in some representative early reports.24 For
this reason, we found that an ESI-MS analysis of this cross-
coupling reaction can contribute to an understanding of the
reactivity of RBF3K reagents in this kind of reaction.
We began our study with a series of control experiments with
the starting materials and each of these in combination with
the catalyst. Species containing tellurium, palladium, phospho-
rus, and silver were detected by the characteristic isotopic
distribution of these elements or their combination; isotopic
abundance of the observed clusters was compared with calcu-
lated values. In the reaction monitoring, aliquots of 40 µL were
taken from the reaction mixture and diluted in 960 µL of
methanol containing 10 µL of formic acid for acid quenching.
yield is due to coupling of 3n with 2a affording the terphenyl
4 (Scheme 1). It is important to point out that no telluro-
substituted biphenyl 5 (Scheme 1) was detected by GC-MS.
To understand the scope of this reaction more clearly, we
tested a variety of potassium aryltrifluoroborate salts 3 under
the optimized procedure, and the results are summarized in Table
6. In the case of variation of the aryl tellurides 1, the reaction
proved to be a general method that tolerates both electron-rich
and electron-deficient substituents in the aryltrifluoroborate 2b-
d.
(23) (a) Colton, R.; D’Agostino, A.; Traeger, J. C. Mass Spectrom. ReV.
1995, 14, 79. (b) Henderson, W.; Nicholson, B. K.; McCaffrey, L. J.
Polyhedron 1998, 17, 4291.
(24) (a) Wilson, S. R.; Perez; Pasternak, A. J. Am. Chem. Soc. 1993,
115, 1994. (b) Furmeier, S.; Metzger, J. O. J. Am. Chem. Soc. 2004, 126,
14485. (c) Aliprantis, A. O.; Canary, J. W. J. Am. Chem. Soc. 1994, 116,
6985. (d) Aramend´ıa, M. A.; Lafont, F.; Moreno-Man˜as, M.; Pleixats, R.;
Roglands, A. J. Org. Chem. 1999, 64, 3592. (e) Raminelli, C.; Prechtl, M.
H. G.; Santos, L. S.; Eberlin, M. N.; Comasseto, J. V. Organometallics
2004, 23, 3990. (f) Chevrin, C.; Le Bras, J.; Henin, F.; Muzart, J.; Pla-
Quintana, A.; Roglans, A.; Pleixats, R. Organometallics 2004, 23, 4796.
ESI-MS Analysis of the Cross-Coupling Reaction. At the
conclusion of the systematic study of this new version of the
J. Org. Chem, Vol. 71, No. 1, 2006 247

Cella et al.
TABLE 6. Cross-Coupling Reaction of Various Aryl Telluride and
Potassium Aryltrifluoroborates
FIGURE 1. Potassium-bound aryltrifluoroborate dimers.
recently observed for vinylic tellurides,25b even when working
at low cone Voltages of 10-50 V in ESI-MS-(+) or ESI-MS-
(-). The major species in solution of the arylic tellurides were
the protonated telluroxide [ArTe(OH)Bu]+, formed by air
oxidation of the telluride, and the [ArTe]+ cation. The metha-
nolic solution of the palladium catalyst, [Pd(PPh3)4], showed
an ESI-MS-(+) spectrum similar to that described in a preceding
study of the palladium-catalyzed self-coupling of boronic
acids.25c Next, we examined the interaction of the palladium
catalyst with the aryltrifluoroborates and tellurides. These
experiments showed that both reagents are able to undergo an
oxidative addition with the palladium catalyst generating a
[(PPh3)2PdAr]+ species.
The reaction of telluride 1a and the trifluoroborate salt 2c
was monitored at 5, 20, 40, and 60 min by ESI-MS-(+). At the
beginning of the reaction, the silver cations [Ag(PPh3)]+ (4) of
m/z 368 and [Ag(PPh3)2‚MeOH]+ (5) of m/z 662 were detected,
after acid quench with formic acid. The products of the oxidative
addition of telluride 1a with the palladium catalyst were
[p-MeO(C6H4)PdTeBu‚H]+ (6) of m/z 400 and {[p-MeO(C6H4)]-
Pd(TeBu)(MeOH)(PPh3)]}+ (7) of m/z 692 and traces of the
palladium bis-aryl adducts [(p-MeOC6H4)2Pd(PPh3)2]+ (8) of
m/z 844 and [(p-MeOC6H4)(p-Cl C6H4)Pd(PPh3)2]+ (9) of m/z
848. The latter cation is less stable than the former, probably
by the stabilization conferred by two methoxy groups in
comparison with a chlorine group (Figure 2). During the course
of the reaction, a variation of the relative abundance of the
observed species was noted where the silver cations were always
present in solution and the oxidative addition products could
not be detected.
The ESI-MS-(+) spectra of the cross-coupling reaction shows
the presence of intermediates involved in the catalytic cycle of
the coupling reaction (6-9) and also the silver cations 4 and 5
because different aryl derivatives of the telluride and the
trifluoroborate salt were used. The obtained results suggest that
the oxidative addition of the telluride is preferred over that of
trifluoroborate salt. The product of the transmetalation of 2c to
the oxidative addition product of the telluride is likely to be a
labile, transient species due to their low concentration in the
reaction media. The role of Ag2O cannot be solely attributed to
that of an oxidant additive in the reaction because the presence
of the triphenylphosphine cations 4 and 5 suggests an interaction
of silver and the palladium catalyst or its intermediates leading
to soluble triphenylphosphine silver salts. This proposition is
supported by a demonstration of the interaction of soluble silver
salts with palladium complexes wherein the silver salt can assist
the halide removal and it can also assist the removal of
complexed tertiary phosphines to promote the catalytic cycle.26
These findings support the catalytic cycle depicted in Figure 3.
In the proposed catalytic cycle, the aryl telluride oxidatively
The solutions of the potassium trifluoroborates (2b and 2c)
in methanol were monitored by ESI-MS-(-), which showed
the presence of potassium-bound dimers [ArBF3 ‚‚‚K+‚‚‚-F3BAr]
-
(Figure 1). The presence of these dimers is in agreement of an
earlier observation of an 18-crown-6 potassium complex of a
nitrile-functionalized alkyltrifluoroborate salt in solution and in
the solid state.25
When the solutions of the tellurides were monitored, we were
not able to observe the protonated tellurides (1a, 1b, 1c, and
1e) as the major species in solution or its solvent adducts, as
(25) (a) Fei, Z.; Zhao, D.; Geldbach, T. J.; Scopelliti, R.; Dyson, P. J.
Eur. J. Inorg. Chem. 2005, 860. (b) Raminelli, C.; Prechtl, M. H. G.; Santos,
L. S.; Eberlin, M. N.; Comasseto, J. V. Organometallics 2004, 23, 3990.
(c) Aramed´ıa, M. A.; Lafont, F.; Moreno-Mana˜s, M.; Pleixats, R.; Roglands,
A. J. Org. Chem. 1999, 64, 3592.
(26) Kayaki, Y.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn. 1997,
70, 1140.
248 J. Org. Chem., Vol. 71, No. 1, 2006

Reactions of Aryl Tellurides with Potassium Aryltrifluoroborate Salts
FIGURE 2. ESI-MS(+) spectrum of the reaction between telluride 1a and trifluoroborate 2c under cross-coupling reaction conditions.
FIGURE 3. Proposed catalytic cycle of the cross-coupling reaction based on the ESI-MS observations.
adds to the PdL2 species leading to the tellurated palladium
intermediate A that can exchange one ligand by a solvent
molecule yielding the detected species B. In the transmetalation
step of the catalytic cycle, both species A or B can react with
the aryltrifluoroborate where the tellurium moiety would be
combined to the borate as its aryl group is transferred to
palladium forming to the detected bis-arylated palladium
intermediate C. At the end of the reaction, a black powder of
indeterminate composition was formed and only traces of
dibutyltelluride was observed by GC-MS analysis, with these
observations the fate of tellurium and the trifluoroborate could
not be rationalized. The labile trans intermediate C should
isomerize to the cis intermediate D, which suffers the reductive
elimination readily since its abundance in the solution is very
low; in this way, the bis-arylic product is formed regenerating
the starting zerovalent palladium catalyst. As pointed below,
the role of silver oxide can be attributed to the removal of
phosphine ligands of the catalyst or from one of the catalytic
intermediates formed in the course of the reaction; such a
process could therefore occur with the catalytic intermediate A
leading to the mono- and diphosphino silver complexes E and
G and the tellurated palladium species B and F, the main
palladium species observed in the ESI-MS-(+) spectrum
(Figure 2).
Conclusion
In summary, we have developed general and high-yielding
methods for accomplishing Suzuki cross-coupling reactions
between aryl tellurides and potassium aryltrifluoroborate salts.
The use of potassium aryltrifluoropotassium salts makes this
method useful and attractive for the synthesis of biaryl
compounds. One feature of this method was the tolerance of a
variety of functional groups, either electron-withdrawing or
electron-donating substituents in both substrates. The Suzuki-
Miyaura cross-coupling reaction was highly chemoselective, and
J. Org. Chem, Vol. 71, No. 1, 2006 249

Cella et al.
8.6 Hz, 4H), 7.39 (t, J 7.8 Hz, 2H), 7.28 (t, J 7.2 Hz, 1H), 6.95 (d,
J 8.7 Hz, 2H), 3.80 (s, 3H); 13C NMR (75 MHz, CDCl3) δ ppm
159.1, 140.8, 133.7, 128.7, 128.1, 126.7, 126.6, 114.2, 55.3; MS
m/z 185 (10), 184 (100), 169 (67), 152 (21), 76 (61).
we have demonstrated that aryl tellurides are more reactive than
aryl halides under these conditions.
Experimental Section
Representative Procedure of Suzuki-Miyaura Cross-Cou-
pling Reaction. To a suspension of butyl(4-methoxyphenyl)tellane
(1a) (0.146 g, 0.5 mmol), potassium phenyltrifluoroborate (2a)
(0.110 g, 0.6 mmol), Pd(Ph3P)4 (0.058 g, 0.05 mmol), and silver(I)
oxide (0.232 g, 1 mmol) in 3 mL of methanol was added
triethylamine (0.2 g, 2 mmol), and the reaction mixture was stirred
and heated at reflux for 90 min and then cooled to room temperature
and diluted with ethyl acetate (30 mL). The organic layer was
washed with saturated solution of NH4Cl (2 × 10 mL) and water
(2 × 10 mL), dried over MgSO4, and concentrated under vacuum.
Purification by silica gel chromatography (eluting with hexane/
ethyl acetate 9.5:0.5) yielded 4-methoxybiphenyl (3a)1 (0.076 g,
Acknowledgment. H.A.S. thanks FAPESP for Grant No.
03/01751-8; R.C., R.L.O.R.C., and C.F.K. thank FAPESP for
fellowships (03/13897-7, 04/14426-0, and 04/14526-5). CNPq
is also acknowledged for financial support.
Supporting Information Available: Experimental procedures,
1H and 13C NMR spectra for compounds listed in Tables 4-6, and
ESI-MS-(+), ESI-MS-(-), and ESI-MS/MS spectra of the studied
species and reactions. This material is available free of charge via
the Internet at http://pubs.acs.org.
1
83%): white solid; H NMR (300 MHz, CDCl3) δ ppm 7.52 (t, J
JO052061R
250 J. Org. Chem., Vol. 71, No. 1, 2006