weight PEGs, in combination with carboxylic acids 4,
improved catalytic efficacy significantly (entries 5-9).
Interestingly, optimal reaction conditions, hence, involved
the use of a phosphine ligand-free palladium catalyst
modified with carboxylic acid MesCO2H (4a)15 in PEG-
20000 (entry 8).
Scheme 1. Ruthenium-Catalyzed Direct Arylations in PEG-2000
Having identified reaction conditions for user-friendly
direct arylations in the presence of air, we probed the scope
of this C-H bond functionalization protocol (Table 2).16
Valuable functional groups were tolerated by the catalytic
(3) For representative recent examples of palladium(0)-catalyzed direct
arylations with aryl (pseudo)halides, see: (a) Miyasaka, M.; Fukushima,
A.; Satoh, T.; Hirano, K.; Miura, M. Chem.sEur. J. 2009, 15, 3674–3677.
(b) Campeau, L.-C.; Stuart, D. R.; Leclerc, J.-P.; Bertrand-Laperle, M.;
Villemure, E.; Sun, H.-Y.; Lasserre, S.; Guimond, N.; Lecavallier, M.;
Fagnou, K. J. Am. Chem. Soc. 2009, 131, 3291–3306. (c) Bellina, F.; Benelli,
F.; Rossi, R. J. Org. Chem. 2008, 73, 5529–5535. (d) Caron, L.; Campeau,
L.-C.; Fagnou, K. Org. Lett. 2008, 10, 4533–4536. (e) Lebrasseur, N.;
Larrosa, I. J. Am. Chem. Soc. 2008, 130, 2926–2927. (f) Laleu, B.; Lautens,
M. J. Org. Chem. 2008, 73, 9164–9167. (g) Bedford, R. B.; Betham, M.;
Charmant, J. P. H.; Weeks, A. L. Tetrahedron 2008, 64, 6038–6050. (h)
Iwasaki, M.; Yorimitsu, M.; Oshima, K. Chem. Asian J. 2007, 2, 1430–
1435. (i) Chiong, H. A.; Pham, Q.-N.; Daugulis, O. J. Am. Chem. Soc.
2007, 129, 9879–9884. (j) Chuprakov, S.; Chernyak, N.; Dudnik, A. S.;
Gevorgyan, V. Org. Lett. 2007, 9, 2333–2336. (k) Garc´ıa-Cuadrado, D.;
de Mendoza, P.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J. Am.
Chem. Soc. 2007, 129, 6880–6886, and references cited therein.
(4) For selected examples of palladium(0)-catalyzed direct arylations
from our laboratories, see: (a) Ackermann, L.; Althammer, A.; Fenner, S.
Angew. Chem., Int. Ed. 2009, 48, 201–204. (b) Ackermann, L.; Barfu¨sser,
S. Synlett 2009, 808–812. (c) Ackermann, L.; Althammer, A. Angew. Chem.,
Int. Ed. 2007, 46, 1627–1629.
1 bearing Lewis basic directing groups (DG) could be
regoioselectively arylated with [RuCl3(H2O)n]12 as an inex-
pensive ruthenium source. Unfortunately, attempts to perform
these ruthenium-catalyzed direct arylations under an atmo-
sphere of air provided thus far unsatisfactory results.
Therefore, we focused our attention on the development
of palladium(0)-catalyzed direct arylations of 1,2,3-triaz-
ole13,14 in the presence of air (Table 1).
(5) Miura, M.; Satoh, T. In Modern Arylation Methods; Ackermann,
L., Ed.; Wiley-VCH: Weinheim, Germany, 2009; pp 335-362.
(6) For representative examples of the development of C-H bond
functionalizations that were proposed to proceed through palladium(II)/
palladium(IV) catalysis, see: (a) Tremont, S. J.; Rahman, H. U. J. Am. Chem.
Soc. 1984, 106, 5759–5760. (b) Byers, P. K.; Canty, A. L.; Skelton, B. W.;
White, A. H. J. Chem. Soc., Chem. Commun. 1986, 1722–1724. (c) Catellani,
M.; Frignani, F.; Rangoni, A. Angew. Chem., Int. Ed. Engl. 1997, 36, 119–
122. (d) Canty, A. L.; Denney, M. C.; van Koten, G.; Skelton, B. W.; White,
A. H. Organometallics 2004, 23, 5432–5439. (e) Kalyani, D.; Deprez, N. R.;
Desai, L. V.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127, 7330–7331. (f)
Daugulis, O.; Zaitsev, V. G. Angew. Chem., Int. Ed. 2005, 44, 4046–4048.
(g) Giri, R.; Liang, J.; Lei, J.-G.; Li, J.-J.; Wang, D.-H.; Chen, X.; Naggar,
I. C.; Guo, C.; Foxman, B. M.; Yu, J.-Q. Angew. Chem., Int. Ed. 2005, 44,
7420–7424. (h) Deprez, N. R.; Kalyani, D.; Krause, A.; Sandford, M. S.
J. Am. Chem. Soc. 2006, 128, 4972–4973. (i) Racowski, J. M.; Dick, A. R.;
Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 10974–10983, and references
cited therein.
Table 1. Palladium(0)-Catalyzed Direct Arylations under Aira
(7) For selected examples of ruthenium-catalyzed direct arylations, see:
(a) Kitazawa, K.; Kochi, T.; Sato, M.; Kakiuchi, F. Org. Lett. 2009, 11,
1951–1954. (b) Ackermann, L.; Born, R.; Vicente, R. ChemSusChem 2009,
2, 546–549. (c) Ackermann, L.; Mulzer, M. Org. Lett. 2008, 10, 5043–
¨
5045. (d) Ozdemir, I.; Demir, S.; Cetinkaya, B.; Gourlaouen, C.; Maseras,
F.; Bruneau, C.; Dixneuf, P. H. J. Am. Chem. Soc. 2008, 130, 1156–1157.
(e) Oi, S.; Funayama, R.; Hattori, T.; Inoue, Y. Tetrahedron 2008, 64, 6051–
entry
solvent
NMP
NMP
DMA
1,4-dioxane
PEG-400
PEG-2000
PEG-20000
PEG-20000
PEG-20000
additive
yield
´
1
2
3
4
5
6
7
8
9
25%
42%
42%
45%
6059. (f) Ackermann, L.; Born, R.; Alvarez-Bercedo, P. Angew. Chem.,
Int. Ed. 2007, 46, 6364–6367. (g) Ackermann, L.; Althammer, A.; Born,
R. Angew. Chem., Int. Ed. 2006, 45, 2619–2622. (h) Kakiuchi, F.; Matsuura,
Y.; Kan, S.; Chatani, N. J. Am. Chem. Soc. 2005, 127, 5936–5945. (i) Oi,
S.; Aizawa, E.; Ogino, Y.; Inoue, Y. J. Org. Chem. 2005, 70, 3113–3119.
(j) Ackermann, L. Org. Lett. 2005, 7, 3123–3125 and references cited
therein.
MesCO2H (4a)
MesCO2H (4a)
MesCO2H (4a)
MesCO2H (4a)
MesCO2H (4a)
39%
39%
74%
62%
(8) Turner, G. L.; Morris, J. A.; Greaney, M. F. Angew. Chem., Int. Ed.
2007, 46, 7996–8000.
MesCO2H (4a)
t-BuCO2H (4b)
(9) Ohnmacht, S. A.; Mamone, P.; Culshaw, A. J.; Greaney, M. F. Chem.
Commun. 2008, 1241–1243.
(10) For recent selected reviews on applications of sustainable PEGs,
see: (a) Candeias, N. R.; Branco, L. C.; Gois, P. M. P.; Afonso, C. A. M.;
Trindade, A. F. Chem. ReV. 2009, 109, 2703–2802. (b) Bergbreiter, D. E.;
Tian, J.; Hongfa, C. Chem. ReV. 2009, 109, 530–582. (c) Andrade, C. K. Z.;
Alves, L. M. Curr. Org. Chem. 2005, 9, 195–218. (d) Chen, J.; Spear, S. K.;
Huddleston, J. G.; Rogers, R. D. Green Chem. 2005, 7, 64–82 and references
cited therein. Sigma-Aldrich: PEG-400 (380-420 g/mol, mp ) 4-8 °C);
PEG-2000(1900-2200g/mol,mp)52-54°C);PEG-20000(16 000-24 000
g/mol, mp ) 63-66 °C).
a Reaction conditions: 1a (0.50 mmol), 2a (0.75 mmol), Pd(OAc)2 (5.0
mol %), additive (30 mol %), solvent, K2CO3 (1.00 mmol), 120 °C, 24 h,
under air, yields of isolated products.
While commonly employed organic solvents gave rise to
low conversions (entries 1-4), the use of high molecular
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