B. R. Park et al. / Tetrahedron Letters 52 (2011) 4405–4407
4407
Br
Spectroscopic data were obtained from the Korea Basic Science
Institute, Gwangju branch.
MeO
Table 3
3g
+
From PPh3
MeO
5
References and notes
1g
Condition A: 53%
Condition B: 79%
12%
0%
1. For the leading references on the synthesis of biaryls, see: (a) Hassan, J.;
Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359–
1469; (b) Fanta, P. E. Synthesis 1974, 9–21; (c) Sainsbury, M. Tetrahedron 1980,
36, 3327–3359; (d) Bringmann, G.; Walter, R.; Weirich, R. Angew. Chem., Int. Ed.
Engl. 1990, 29, 977–991.
2. For the leading references on metal-mediated homocoupling reactions, see: (a)
Nelson, T. D.; Crouch, R. D. Org. React. 2004, 63, 265–555; (b) Jutand, A.; Mosleh,
A. J. Org. Chem. 1997, 62, 261–274.
Ph PPh2
Ar Pd Br
PPh3
Ar PPh2
Ph Pd Br
PPh3
(Ar = m-methoxyphenyl)
Aryl-aryl interchange reaction of
ArPdL2Br (L = PPh3) complexes
3. For the palladium-catalyzed reductive homocouplings in the presence of
reducing agents, see: (a) Hennings, D. D.; Iwama, T.; Rawal, V. H. Org. Lett. 1999,
1, 1205–1208; (b) He, H. S.; Zhang, C.; Ng, C. K.-W.; Toy, P. H. Tetrahedron 2005,
61, 12053–12057; (c) Mukhopadhyay, S.; Rothenberg, G.; Wiener, H.; Sasson, Y.
Tetrahedron 1999, 55, 14763–14768; (d) Wan, Y.; Chen, J.; Zhang, D.; Li, H. J.
Mol. Catal. A: Chem. 2006, 258, 89–94; (e) Mukhopadhyay, S.; Rothenberg, G.;
Qafisheh, N.; Sasson, Y. Tetrahedron Lett. 2001, 42, 6117–6119; (f) Li, J.-H.; Xie,
Y.-X.; Yin, D.-L. J. Org. Chem. 2003, 68, 9867–9869; (g) Venkatraman, S.; Li, C.-J.
Org. Lett. 1999, 1, 1133–1135; (h) Venkatraman, S.; Huang, T.; Li, C.-J. Adv.
Synth. Catal. 2002, 344, 399–405; (i) Venkatraman, S.; Li, C.-J. Tetrahedron Lett.
2000, 41, 4831–4834; (j) Brenda, M.; Knebelkamp, A.; Greiner, A.; Heitz, W.
Synlett 1991, 809–810; (k) Hassan, J.; Hathroubi, C.; Gozzi, C.; Lemaire, M.
Tetrahedron 2001, 57, 7845–7855; (l) Chang, Y. M.; Lee, S. H.; Cho, M. Y.; Yoo, B.
W.; Rhee, H. J.; Lee, S. H.; Yoon, C. M. Synth. Commun. 2005, 35, 1851–1857; (m)
Lee, P. H.; Seomoon, D.; Lee, K. Org. Lett. 2005, 7, 343–345; (n) Kuroboshi, M.;
Waki, Y.; Tanaka, H. Synlett 2002, 637–639; (o) Kuroboshi, M.; Waki, Y.; Tanaka,
H. J. Org. Chem. 2003, 68, 3938–3942; (p) Qi, C.; Sun, X.; Lu, C.; Yang, J.; Du, Y.;
Wu, H.; Zhang, X.-M. J. Organomet. Chem. 2009, 694, 2912–2916; Wang and Lu
have reported a Pd(II)-catalyzed cross-coupling of aryl iodides in the absence of
an additional reducing agent, see: (q) Wang, L.; Lu, W. Org. Lett. 2009, 11, 1079–
1082.
4. For palladium-catalyzed oxidation of alcohols, see: (a) Stahl, S. S. Angew. Chem.,
Int. Ed. 2004, 43, 3400–3420; (b) Peterson, K. P.; Larock, R. C. J. Org. Chem. 1998,
63, 3185–3189; (c) Mueller, J. A.; Jensen, D. R.; Sigman, M. S. J. Am. Chem. Soc.
2002, 124, 8202–8203; (d) Steinhoff, B. A.; Stahl, S. S. J, Am. Chem. Soc. 2006,
128, 4348–4355.
5. For the alcoholic reducing agents in palladium-catalyzed homocoupling of aryl
halides, see: (a) Monopoli, A.; Calo, V.; Ciminale, F.; Cotugno, P.; Angelici, C.;
Cioffi, N.; Nacci, A. J. Org. Chem. 2010, 75, 3908–3911; (b) Ram, R. N.; Singh, V.
Tetrahedron Lett. 2006, 47, 7625–7628; (c) Wang, L.; Zhang, Y.; Liu, L.; Wang, Y.
J. Org. Chem. 2006, 71, 1284–1287; (d) Shao, L.; Du, Y.; Zeng, M.; Li, X.; Shen, W.;
Zuo, S.; Lu, Y.; Zhang, X.-M.; Qi, C. Appl. Organomet. Chem. 2010, 24, 421–425;
(e) Zeng, M.; Du, Y.; Shao, L.; Qi, C.; Zhang, X.-M. J. Org. Chem. 2010, 75, 2556–
2563; (f) Penalva, V.; Hassan, J.; Lavenot, L.; Gozzi, C.; Lemaire, M. Tetrahedron
Lett. 1998, 39, 2559–2560; (g) Hassan, J.; Penalva, V.; Lavenot, L.; Gozzi, C.;
Lemaire, M. Tetrahedron 1998, 54, 13793–13804.
Scheme 2.
Ar-Br
Ar-Ar
Pd0
(i)
(iv)
Ar-Pd-Ar
Ar-Pd-Br
I
III
Ph
O
HBr
Ph
O
stabilization
O
(ii)
Ph
(iii)
O
Ph
Ar
O
Pd
Ph
O
H
Ph
Ar-Br
Br
II
acidic
Scheme 3.
increased to 79%. The reaction of 1h under the same conditions
afforded 3h in 70%. The reactions of 3-bromobenzaldehyde (1i),
methyl 3-bromobenzoate (1j), and 3-bromopyridine (1k) afforded
moderate yields of products 3i–k (55–88%). It is interesting to note
that a 5,50-diuracilyl derivative 3l10 was synthesized through the
reductive coupling protocol in moderate yield (57%) from 5-iodo-
1,3-dimethyluracil (1l) for the first time.
The reaction mechanism could be proposed as shown in Scheme
3.5c–e Oxidative addition of aryl bromide to Pd0 produced arylpalla-
dium intermediate I. Ligand exchange of bromide with the anion of
benzoin produced a stabilized palladium intermediate II, which re-
acted with another molecule of aryl bromide to form diarylpalladi-
um intermediate III with liberation of benzil. From III, the biaryl
product is finally formed via the reductive elimination process
with the generation of Pd0 to furnish the catalytic redox cycle. By
using benzoin in a redox cycle, relative to simple alcohol such as
ethanol or 2-propanol, formation of intermediate II (step ii), and/
or subsequent formation of intermediate III (step iii) could be facil-
itated. The carbonyl group of benzoin might stabilize intermediate
II, and the acidic hydrogen of benzoin moiety of intermediate II
makes the oxidation to benzil easier6.
6. For the base-mediated aerobic oxidation of benzoin to benzil, see: (a)
Muthupandi, P.; Sekar, G. Tetrahedron Lett. 2011, 52, 692–695; (b) Joo, C.;
Kang, S.; Kim, S. M.; Han, H.; Yang, J. W. Tetrahedron Lett. 2010, 51, 6006–6007;
(c) Kang, S.; Joo, C.; Kim, S. M.; Han, H.; Yang, J. W. Tetrahedron Lett. 2011, 52,
502–504; (d) Lee, H. S.; Kim, K. H.; Kim, Y. M.; Kim, J. N. Bull. Korean Chem. Soc.
2010, 31, 1761–1764.
7. Very recently, we reported an expedient synthetic procedure of benzil
derivatives from aryl bromides using vinylene carbonate in
a palladium-
catalyzed reaction. During the reaction we found that aryl bromides could be
converted to biaryls by benzoin via a palladium-catalyzed redox process. Thus
we examined the same conditions for the reductive aryl coupling of
bromobenzene, see: Kim, K. H.; Park, B. R.; Lim, J. W.; Kim, J. N. Tetrahedron
Lett. 2011, 52, 3463–3466.
8. Typical procedure for the synthesis of biphenyl (3a):
A stirred mixture of
bromobenzene (157 mg, 1.0 mmol), Pd(OAc)2 (11 mg, 5 mol%), PPh3 (26 mg,
10 mol%), Cs2CO3 (359 mg, 1.1 mmol), and benzoin (127 mg, 0.6 mmol) in DMF
(1.5 mL) was heated to 120 °C for 1 h under nitrogen atmosphere. After the
usual aqueous extractive workup and column chromatographic purification
process with hexane biphenyl (3a) was obtained as a white solid, 69 mg
(90%).3a,3b Further elution with hexane/ether (5:1) afforded benzil (115 mg,
91%) as a yellow solid. Other biaryls 3b,3p,5a 3c,3b,p 3d,5a 3e,3a,b 3f,3p,5c 3g,3a,h
3h,3a,5a 3i,3l,5g 3j,5c 3k,5c 3l10 and 53q were synthesized similarly and identified
by comparison with the reported melting points, IR, 1H NMR and/or mass
spectral data.3,5,10
In summary, an expedient procedure for the synthesis of biaryl
derivatives was developed using a palladium-catalyzed, benzoin-
mediated redox process from aryl halides.
9. For the aryl–aryl interchange reaction of ArPdL2X (L = PPh3) complexes, see: (a)
Goodson, F. E.; Wallow, T. I.; Novak, B. M. J. Am. Chem. Soc. 1997, 119, 12441–
12453; (b) Sakamoto, M.; Shimizu, I.; Yamamoto, A. Chem. Lett. 1995, 1101–
1102.
Acknowledgments
10. For the synthesis of 5,50-diuracilyl derivatives, see: (a) Zamora, F.; Amo-Ochoa,
P.; Fischer, B.; Schimanski, A.; Lippert, B. Angew. Chem., Int. Ed. 1999, 38, 2274–
2275; (b) Kruger, O.; Wille, U. Org. Lett. 2001, 3, 1455–1458; (c) Senga, K.;
Ichiba, M.; Nishigaki, S. J. Org. Chem. 1978, 43, 1677–1683.
This work was supported by the National Research Foundation
of Korea Grant funded by the Korean Government (2010-0015675).