Table 3 Cross-coupling of propiophenone with various aryl bromidesa
Notes and references
1 (a) E. Negishi and A. de Meijire, Organopalladium Chemistry for
Organic Synthesis, Wiley, New York, 2002; (b) J. Tsuji, Palladium
Reagents and Catalysts. New Perspectives for the 21st Century,
Wiley, Chichester, 2004; (c) R. H. Crabtree, The Organometallic
Chemistry of the Transition Metals, Wiley, New Jersey, 2009;
(d) J. Hartwig, Organotransition Metal Chemistry, University
Science Books, Sausalito, CA, 2010.
Entry
Ar
Product No.
Yield (%)b
2 C. J. Moulton and B. L. Shaw, J. Chem. Soc., Dalton Trans., 1976,
1020–1024.
3 G. Van Koten, K. Timmer, J. G. Noltes and A. L. Spek, J. Chem.
Soc., Chem. Commun., 1978, 250–252.
4 D. Morales-Morales and C. M. Jensen, The Chemistry of Pincer
Compounds, Elsevier, Amsterdam, 2007.
5 N. Selander and K. J. Szabo, Chem. Rev., 2011, 111, 2048–2076.
6 A. C. B. Burtoloso, Synlett, 2009, 320, 327.
7 M. Palucki and S. L. Buchwald, J. Am. Chem. Soc., 1997, 119,
11108–11109.
8 B. C. Hamann and J. F. Hartwig, J. Am. Chem. Soc., 1997, 119,
12382–12383.
9 T. Satoh, Y. Kawamura, M. Miura and M. Nomura, Angew.
Chem., Int. Ed. Engl., 1997, 36, 1740–1742.
10 (a) C. C. C. Johansson and T. J. Colacot, Angew. Chem. Int. Ed.,
2010, 49, 676–707; (b) F. Bellina and R. Rossi, Chem. Rev., 2010,
110, 1082–1146.
11 (a) S.-L. You, X.-L. Hou, L.-X. Dai and X.-Z. Zhu, Org. Lett.,
2000, 3, 149–151; (b) W. A. Moradi and S. L. Buchwald,
J. Am. Chem. Soc., 2001, 123, 7996–8002; (c) F. Churruca,
R. SanMartin, I. Tellitu and E. Dominguez, Org. Lett., 2002, 4,
1591–1594; (d) Y. Terao, Y. Fukuoka, T. Satoh, M. Miura and
M. Nomura, Tetrahedron Lett., 2002, 43, 101–104;
(e) L. Ackermann, R. Vicente and N. Hofmann, Org. Lett.,
2009, 11, 4274–4276.
1
Ph–
5
6
6
7
8
9
10
11
12
13
14
15
16
17
17
96
49
88
96
94
97
95
94
91
89
93
85
87
55
92
2
2-MeO-C6H4–
2-MeO-C6H4–
3-MeO-C6H4–
4-MeO-C6H4–
3-Me-C6H4–
4-Me-C6H4–
4-F-C6H4–
4-Me2N-C6H4–
4-MeS-C6H4–
4-CF3-C6H4–
4-CH2CH-C6H4–
1-Naphthyl–
1,3-CF3-C6H4–
1,3-CF3-C6H4–
3c
4
5
6
7
8
9
10
11
12
13
14
15c
a
Reaction details: 0.33 mmol propiophenone in 1.5 mL solvent
b
(0.22 M). Isolated yield after purification by silica gel chromatography.
c
2 mol% of II was used.
range of electron-poor to electron-rich ketones. Reactions
utilizing isovalerophenone showed a slower reaction rate,
delivering only 60% conversion after 1 h, but increasing the
catalyst loading to 2 mol% resulted in a subsequent increase in
product yield to 95% (entries 3 and 4).
12 G. Chen, F. Y. Kwong, H. O. Chan, W.-Y. Yu and A. S. C. Chan,
Chem. Commun., 2006, 1413–1415.
In summary, we have introduced a highly active, air and
water stable, (NCN)-Pd(II) pincer catalyst for the a-arylation
of ketones with a variety of aryl bromides. Complex II, at
1 mol% loading, is an excellent catalyst for this reaction,
delivering the desired adducts in only 1 h at 70 1C. Challenging
substrates are easily accommodated by minor increases in
reaction time or catalyst loading. Only monoarylated products
are produced, and no other side reactions of potentially labile
functionality are observed.
13 C. He, S. Guo, L. Huang and A. Lei, J. Am. Chem. Soc., 2010, 132,
8273–8275.
14 (a) L. V. Desai, D. T. Ren and T. Rosner, Org. Lett., 2010, 12,
1032–1035; (b) J. M. Fox, X. Huang, A. Chieffi and
S. L. Buchwald, J. Am. Chem. Soc., 2000, 122, 1360–1370;
(c) T. Hamada, A. Chieffi, J. Ahman and S. L. Buchwald, J. Am.
Chem. Soc., 2002, 124, 1261–1268; (d) N. A. Powell, T. J. Hagen,
F. L. Ciske, C. Cai, J. E. Duran, D. D. Holsworth, D. Leonard,
R. M. Kennedy and J. J. Edmunds, Tetrahedron Lett., 2010, 51,
4441–4444.
15 J. Ahman, J. P. Wolfe, M. V. Troutman, M. Palucki and
S. L. Buchwald, J. Am. Chem. Soc., 1998, 120, 1918–1919.
16 M. S. Viciu, R. F. Germaneau and S. P. Nolan, Org. Lett., 2002, 4,
4053–4056.
The Robert A. Welch Foundation (A-1623) is gratefully
acknowledged for support of this research.
17 G. A. Grasa and T. J. Colacot, Org. Process Res. Dev., 2008, 12,
522–529.
18 J. Aleman, B. Richter and K. A. Jørgensen, Angew. Chem., Int. Ed.,
2007, 46, 5515–5519.
Table 4 Cross-coupling of bromobenzene with various ketonesa
19 J. Aleman, S. Cabrera, E. Maerten, J. Overgaard and
K. A. Jørgensen, Angew. Chem., Int. Ed., 2007, 46,
5520–5523.
20 F. Churruca, R. SanMartin, I. Tellitu and E. Dominguez,
Tetrahedron Lett., 2006, 47, 3233–3237.
21 A. Fraboni, M. Fagnoni and A. Albini, J. Org. Chem., 2003, 68,
4886–4893.
Entry
Ar
R
Product No.
Yield (%)b
1
2
Ph–
Ph–
Ph–
Ph–
Me-
Et-
5
96
91
60
95
98
82
99
84
83
46
22 M. Limbeck, H. Wamhoff, T. Rolle and N. Griebenow, Tetrahedron
Lett., 2006, 47, 2945–2948.
23 V. K. Aggarwal and B. Olofsson, Angew. Chem., Int. Ed., 2005, 44,
5516–5519.
24 A. Bugarin and B. T. Connell, Organometallics, 2008, 27,
4357–4369.
25 S. E. Denmark, R. A. Stavenger, A.-M. Faucher and
J. P. Edwards, J. Org. Chem., 1997, 62, 3375–3389.
26 M. A. Stark and C. J. Richards, Tetrahedron Lett., 1997, 38,
5881–5884.
18
19
19
20
21
22
23
24
5
3
i-Pr-
i-Pr-
PhCH2-
Me-
Me-
Me-
Me-
Me-
4c
5
Ph–
6
7
8
4-MeO-C6H4–
4-CF3-C6H4–
4-MeC6H4–
2-F-C6H4–
Ph–
9
10d
a
27 The structure of complex II was confirmed by single crystal X-ray
analysis. X-Ray data is summarized in the ESI and has been
deposited with The Cambridge Crystallographic Data Centre
(CCDC 821200).
Reaction details: 0.33 mmol ketone in 1.5 mL solvent (0.22 M).
Isolated yield after purification by silica gel chromatography.
2 mol% of II was used. 2.8 equiv of Hg0 added; see ESIz for details.
b
c
d
c
7220 Chem. Commun., 2011, 47, 7218–7220
This journal is The Royal Society of Chemistry 2011