Regioselective Suzuki-Miyaura cross-coupling reactions of 4-methyl-6,7-bis(trifluoromethanesulfonyloxy)coumarin

Article abstract of DOI:10.1016/j.tetlet.2013.04.123

Arylated coumarins were prepared by site-selective Suzuki-Miyaura cross-coupling reaction of the bis(triflate) of 4-methyl-6,7-dihydroxycoumarin.

Full text of DOI:10.1016/j.tetlet.2013.04.123

Tetrahedron Letters 54 (2013) 3568–3571
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Regioselective Suzuki–Miyaura cross-coupling reactions
of 4-methyl-6,7-bis(trifluoromethanesulfonyloxy)coumarin
Aws M. Hamdy a, Nadi Eleya a,b, Hamid H. Mohammed a,c, Zien Khaddour a, Tamás Patonay d,
Alexander Villinger a, Peter Langer a,e,
⇑
a Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b Zakho University, Department of Chemistry, College of Science, Kurdistan Region, Iraq
c Department of Chemistry, University Al-Mustansiriyah, Baghdad, Iraq
d Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Egyetem tér 1, Hungary
e Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Arylated coumarins were prepared by site-selective Suzuki–Miyaura cross-coupling reaction of the
bis(triflate) of 4-methyl-6,7-dihydroxycoumarin.
Received 28 February 2013
Revised 23 April 2013
Accepted 29 April 2013
Available online 9 May 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Coumarin
Regioselectivity
Palladium
Catalysis
Suzuki–Miyaura reaction
Coumarin and its derivatives are one of the most important clas-
ses of heterocyclic compounds which occur in many natural prod-
ucts.1 For example, wedelolactone and other coumarins were
isolated from the roots of Hedysarum multijugum, which is a plant
in Hedysarum Linn. of the family Leguminosae used as a folk herbal
drug in northwest China.1a Many compounds were isolated from
plants, such as alternariol, umbelliferone (7-hydroxycoumarin),
scoparone (6,7-dimethoxycoumarin), osthole (7-methoxy-8-(3-
methylbut-2-en-1-yl)coumarin), and others.2 Coumarins are
known to possess a wide range of biological activities, such as
anti-HIV, antibiotic, antifungal, anti-bacterial (including antituber-
culotic), antiviral, anticancer, immunosuppressive, muscle relaxant,
anticlotting, and anticoagulant activity.3 In addition, they are
widely used as additives in food chemicals, perfumes, agrochemi-
cals, cosmetics, pharmaceuticals,4 insecticides, optical brightening
agents, and dispersed fluorescent and laser dyes.5 Coumarins can
be synthesized by various methods, such as the Pechmann,6 Perkin,7
Knoevenagel,8 and Wittig9 reaction. Because of its preparative sim-
plicity and relatively inexpensive starting materials, the Pechmann
reaction has been widely used for the synthesis of coumarins. This
method involves the reaction of phenols with b-ketoesters in the
presence of acidic catalysts.10–12 Transition-metal catalyzed reac-
tions have also been applied to the synthesis of coumarins substi-
tuted at positions three or four. Cross-coupling reactions of
4-tosyloxycoumarins have been widely investigated. Palladium,13
nickel,14 and rhodium catalysts15 have been used in Suzuki–Miya-
ura reactions of arylboronic acids. Suzuki–Miyaura reactions using
potassium aryltrifluoroborates have also been reported.16 Likewise,
the applicability of Negishi,17 Sonogashira,17 Stille,18 and Heck19
reactions in the coumarin series has been demonstrated. On the
other hand, not much is known about palladium catalyzed cross-
coupling reactions of more complex coumarins. A study related to
reactions of 3-bromo-4-(trifluoromethanesulfonyloxy)- and 3-bro-
mo-4-tosyloxy-coumarin has been previously reported.20 Cross-
coupling reactions of 5,7-bis(trifluoromethanesulfonyloxy)-couma-
rin and of 3- and 6-bromo-4-(trifluoromethane-sulfonyloxy)
coumarin have also been reported.21
Herein, we report a new and convenient synthesis of arylated
coumarins by what are, to the best of our knowledge, the first Su-
zuki–Miyaura cross-coupling reactions of the bis(triflate) of 4-
methyl-6,7-dihydroxycoumarin. The reactions proceed with very
good regioselectivity and the products are not readily available
by other methods.
4-Methyl-6,7-dihdroxycoumarin (1) was transformed to its
bis(triflate) 2 in 75% yield by reaction with triflic anhydride
(2.4 equiv) and triethylamine (4.0 equiv) (Scheme 1).22 It proved
⇑
Corresponding author. Tel.: +49 381 4986410; fax: +49 381 4986412.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.04.123

A. M. Hamdy et al. / Tetrahedron Letters 54 (2013) 3568–3571
3569
Me
Me
O
TfO
TfO
i
HO
HO
O
O
O
2 (75%)
1
Scheme 1. Synthesis of 2. Reagents and conditions: (i)
1
(1.0 equiv), Et3N
(4.0 equiv), (CH2Cl2, 20 °C; 2) Tf2O (2.4 equiv), À78 to 20 °C, 6 h.
Me
Me
O
ArB(OH)2
Ar
Ar
TfO
TfO
3a-e
O
O
O
i
2
4a-e
Scheme 2. Synthesis of 4a–e. Reagents and conditions: (i)
2
(1.0 equiv), 3
(2.0 equiv), K3PO4 (3.0 equiv), Pd(PPh3)4 (6 mol %), 1,4-dioxane, 120 °C, 6 h.
Table 1
Synthesis of 4a–e
3, 4
Ar
4a (%)
a
b
c
d
e
3,5-Me2C6H3
4-(MeO)C6H4
4-ClC6H4
C6H5
4-(EtO)C6H4
75
83
83
70
88
Figure 1. Molecular structure of 4e.
a
Yields of isolated products.
ArB(OH)2
Me
O
Me
O
to be important that the addition of triflic anhydride was per-
formed at À78 °C.
TfO
TfO
3a-m
TfO
Ar
The Suzuki–Miyaura reaction of 2 with arylboronic acids 3a–e
(2.0 equiv) afforded the 4-methyl-6,7-diarylcoumarins 4a–e in
73–88% yield (Scheme 2, Table 1).23,24 Both electron-poor and elec-
tron-rich arylboronic acids were successfully employed. The best
yields were obtained using Pd(PPh3)4 (6 mol %) as the catalyst,
K3PO4 (3.0 equiv) as the base, and 1,4-dioxane as the solvent
(120 °C, 6 h). The structure of 4e was independently confirmed
by X-ray crystal structure analysis (Fig. 1).25
O
i
O
2
5a-m
Scheme 3. Synthesis of 5a–m. Reagents and conditions: (i)
(1.2 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3 mol %), 1,4-dioxane, 70 °C, 6 h.
2
(1.0 equiv), 3
Table 2
The Suzuki–Miyaura reaction of 2 with 1.2 equiv of arylboronic
acids 3 afforded the 4-methyl-7-aryl-6-(trifluoromethanesulfonyl-
oxy)coumarins 5a–m in 70–90% yield with very good regioselec-
tivity (Scheme 3, Table 2).23,26 During the optimization, it proved
to be important to use 1.2 equiv of the arylboronic acid and to car-
ry out the reaction at 70 instead of 120 °C to avoid double coupling.
Both electron-poor and electron-rich arylboronic acids were suc-
cessfully employed. The structure of 5b was confirmed by HMBC
experiments (Fig. 2). The structure of 5f was independently con-
firmed by X-ray crystal structure analysis (Fig. 3).25
The one-pot Suzuki–Miyaura reaction of bis(triflate) 2 with two
different arylboronic acids (sequential addition of 1.2 equiv of each
arylboronic acid) afforded the 4-methyl-6,7-diarylcoumarins 6a–d
in 73–81% yields (Scheme 4, Table 3).23,27 The reactions were car-
ried out at 70 °C for the first step (to avoid double coupling) and at
120 °C for the second step.
Synthesis of 5a–m
3, 5
Ar
5a (%)
a
b
c
d
e
f
g
h
i
3,5-Me2C6H3
4-(MeO)C6H4
4-ClC6H4
C6H5
4-(EtO)C6H6
4-EtC6H4
75
80
85
72
90
84
78
83
75
80
70
90
77
4-FC6H4
4-(F3C)C6H4
4-MeC6H4
3-MeC6H4
3-(MeO)C6H4
2,3,4-(MeO)3C6H2
4-tBuC6H4
j
k
l
m
a
Yields of isolated products.
Palladium catalyzed cross-coupling reactions usually occur at
the electronically more deficient and sterically less hindered
position.28,29 Positions six and seven of bis(triflate) 2 are sterically
similar. However, the regioselectivity of Suzuki reactions of bis(tri-
flate) 2 in favor of position seven can be explained by electronic rea-
sons. Position seven is located para to the electron-withdrawing
vinylogous ester group, while position six is located para to the elec-
tron-donating oxygen atom.
CH3
TfO
O
O
MeO
Figure 2. Important HMBC correlations of 5b.
In conclusion, we have reported a convenient synthesis of ary-
lated coumarins by Suzuki–Miyaura cross-coupling reactions of

3570
A. M. Hamdy et al. / Tetrahedron Letters 54 (2013) 3568–3571
Mecklenburg-Vorpommern is gratefully acknowledged. The pro-
ject is implemented through the New Hungary Development
Plan, co-financed by the European Social Fund and the European
Regional Development Fund. The project was also funded by the
EFRE program of the EU.
References and notes
1. (a) Wang, W.; Zhao, Y. Y.; Liang, H.; Jia, Q.; Chen, H. B. J. Nat. Prod. 2006, 69, 876;
(b) Murray, R. D. H. The Natural Coumarins; Wiley: New York, 1986; (c) Murray,
R. D. H. Nat. Prod. Rep. 1995, 12, 477; (d) Estevez-Braun, A.; Gonzalez, A. G. Nat.
Prod. Rep. 1997, 14, 465–475; (e) Donnelly, D. M. X.; Boland, G. In The
Flavonoids: Advances in Research Since 1986; Harborne, J. B., Ed.; Chapman and
Hall: London, 1994; p 239; (f) Monachep, G. D.; Borr, B.; Neto, A. S.; De Lima, R.
A. Phytochemistry 1983, 22, 1657–1658; (g) Donnelly, D. M. X.; Finet, J.-P.;
Guiry, P. J.; Hutchinson, R. M. J. Chem. Soc., Perkin Trans. 1990, 2851.
2. (a) Raistrick, H.; Stilkings, C. E.; Thomas, R. Biochemistry 1953, 55, 421; (b)
Abaul, J.; Philogene, E.; Bourgeois, P. J. Nat. Prod. 1994, 57, 846.
3. (a) Murakami, A.; Gao, G.; Omura, M.; Yano, M.; Ito, C.; Furukawa, H.;
Takahashi, D.; Koshimizu, K.; Ohigashi, H. Bioorg. Med. Chem. Lett. 2000, 10, 59;
(b) Xia, Y.; Yang, Z.-Y.; Xia, P.; Hackl, T.; Hamel, E.; Mauger, A.; Wu, J.-H.; Lee,
K.-H. J. Med. Chem. 2001, 44, 3932; (c) Itoigawa, M.; Ito, C.; Tan, H. T.-W.;
Kuchide, M.; Tokuda, H.; Nishino, H.; Furukawa, H. Cancer Lett. 2001, 169, 15;
(d) Yamaguchi, T.; Fukuda, T.; Ishibashi, F.; Iwao, M. Tetrahedron Lett. 2006, 47,
3755; (e) Yamamoto, Y.; Kurazono, M. Bioorg. Med. Chem. Lett. 2007, 17, 1626;
(f) Kayser; OKolodziej, H. Planta Med. 1997, 63, 508; (g) Wang, C. J.; Hsieh, Y. J.;
Chu, C. Y.; Lin, Y. L.; Tseng, T. H. Cancer Lett. 2002, 183, 163; (h) Huang, H. C.;
Weng, Y. I.; Lee, C. R.; Jan, T. R.; Chen, Y. L.; Lee, Y. T. Br. J. Pharmacol. 1993, 110,
1508; (i) Huang, H. C.; Huang, Y. L.; Chang, J. L.; Chen, C. C.; Lee, Y. T. Eur. J.
Pharmacol. 1992, 217, 143; (j) Zhang, L.; Jiang, G.; Yao, F.; He, Y.; Liang, G.;
Zhang, Y.; Hu, B.; Wu, Y.; Li, Y.; Lin, H. PLoS One 2012, 7, e37865; (k) Kashman,
Y.; Gustafson, K. R.; Fuller, W. R.; Cardellina, J. H.; MacMahon, J. B.; Currens, M.
J.; Buckheit, R. W.; Hughes, S. H.; Cragg, G. M.; Boyd, M. R. J. Med. Chem. 1992,
35, 2735; (l) Spino, C.; Dodier, M.; Sotheeswawaran, S. Bioorg. Med. Chem. Lett.
1998, 8, 3475; (m) Nayyar, A.; Jain, R. Curr. Med. Chem. 1873, 2005, 12.
4. O’Kennedy, R.; Thornes, R. D. Coumarins: Biology, Applications, and Mode of
Action; Wiley: Chichester, 1997.
Figure 3. Molecular structure of 5f.
1) Ar1B(OH)2
Me
Me
O
Ar2
Ar1
2) Ar2B(OH)2
TfO
TfO
i,ii
O
O
O
6a-d
2
Scheme 4. Synthesis of 6a–d. Reagents and conditions: (i) 2 (1.0 equiv), Ar1B(OH)2
(1.2 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3 mol %), dioxane, 70 °C, 6 h; (ii)
Ar2B(OH)2 (1.2 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3 mol %), 1,4-dioxane, 120 °C,
6 h.
5. Murray, R. D. H.; Méndez, J.; Brown, S. A. The Natural Coumarins: Occurrence,
Chemistry, and Biochemistry; Wiley: New York, 1982.
6. Sethna, S. M.; Phadke, R. Org. React. 1953, 7, 1.
7. Donnelly, B. J.; Donnelly, D. M. X.; O’Sullivan, A. M. Tetrahedron 1968, 24, 2617.
8. (a) Jones, G. Org. React. 1967, 15, 204; (b) Bigi, F.; Chesini, L.; Maggi, R.; Sartori,
G. J. Org. Chem. 1999, 1033, 64.
9. Yavari, I.; Hekmat-Shoar, R.; Zonuzi, A. Tetrahedron Lett. 1998, 39, 2391.
10. Nadkarni, A. J.; Kudav, N. A. Indian J. Chem. 1981, 20B, 719.
11. Bose, D. S.; Rudradas, A. P.; Babu, M. H. Tetrahedron Lett. 2002, 43, 9195.
12. Smitha, G.; Reddy, C. S. Synth. Commun. 2004, 34, 3997.
Table 3
Synthesis of 6a–d
13. (a) Santana, M. D.; Garcia-Bueno, R.; Garcia, G.; Sánchez, G.; Gárcia, J.; Kapdi,
A.; Naik, M.; Pednekar, S.; Pérez, J.; Gárcia, L.; Pérez, E.; Serrano, J. L. Dalton
Trans. 2012, 41, 3842; (b) Wong, P. Y.; Chow, W. K.; Chung, K. H.; So, C. M.; Lau,
C. P.; Kwong, F. Y. Chem. Commun. 2011, 47, 8328; (c) Gallagher, B. D.; Taft, B.
R.; Lipshutz, B. H. Org. Lett. 2009, 11, 5374; (d) Song, F.; Lu, S.; Gunnet, J.; Xu, J.
Z.; Wines, P.; Proost, J.; Liang, Y.; Baumann, C.; Lenhard, J.; Murray, W. V.;
Demarest, K. T.; Kuo, G.-H. J. Med. Chem. 2007, 50, 2807; (e) Wu, J.; Wang, L.;
Fathi, R.; Yang, Z. Tetrahedron Lett. 2002, 43, 4395.
14. (a) Xing, C.-H.; Lee, J.-R.; Tang, Z.-Y.; Zheng, J. R.; Hu, Q.-S. Adv. Synth. Catal.
2011, 353, 2051; (b) Kuroda, J.-I.; Inamoto, K.; Hiroya, K.; Doi, K. Eur. J. Org.
Chem. 2009, 2251; (c) Tang, Z.-Y.; Hu, Q.-S. Adv. Synth. Catal. 2004, 346, 1635.
15. Wu, J.; Zhang, L.; Gar, K. Eur. J. Org. Chem. 2006, 5260.
3
6
Ar1
Ar2
6a (%)
b,c
b,g
b,j
a
b
c
4-(MeO)C6H4
4-(MeO)C6H4
4-(MeO)C6H4
4-(MeO)C6H4
4-ClC6H4
4-FC6H4
3-MeC6H4
3,5-Me2C6H3
73
78
75
81
b,a
d
a
Yields of isolated products.
16. (a) Wu, J.; Zhang, L.; Xia, H.-G. Tetrahedron Lett. 2006, 47, 1525; (b) Wu, J.;
Zhang, L.; Luo, Y. Tetrahedron Lett. 2006, 47, 6747.
17. Wu, J.; Liao, Y.; Yang, Z. J. Org. Chem. 2001, 66, 3642.
Me
TfO
TfO
18. Schio, L.; Chatreaux, F.; Klich, M. Tetrahedron Lett. 2000, 41, 1543.
19. Hansen, A. L.; Skydstrup, T. Org. Lett. 2005, 7, 5585.
20. Zhang, L.; Meng, T.; Fan, R.; Wu, J. J. Org. Chem. 2007, 72, 7279.
21. (a) Wang, L.; Xia, J.; Tian, H.; Qian, C.; Ma, Y. Indian J. Chem., Sect B 2003, 42,
2097; (b) Akrawi, O. A.; Nagy, G.; Patonay, T.; Villinger, A.; Langer, P.
Tetrahedron Lett. 2012, 53, 3206; (c) Eleya, N.; Khaddour, Z.; Patonay, T.;
Langer, P. Synlett 2012, 223.
O
O
More
electron deficient
Figure 4. Possible explanation for the site-selectivity of 2.
22. 4-Methyl-2-oxo-2H-chromene-6,7-diyl bis(trifluoromethane-sulfonate) (2): To a
solution of 4-methyl-6,7-dihydroxycoumarin (1) (0.5 g, 2.60 mmol) in CH2Cl2
(30 mL) was added triethylamine (0.36 mL, 10.4 mmol) at room temperature
under an argon atmosphere. After 10 min, Tf2O (1.0 mL, 6.2 mmol) was added
at À78 °C. The mixture was allowed to warm to 20 °C and stirred for 6 h. The
reaction mixture was filtered and the filtrate was concentrated in vacuo. The
residue was purified by chromatography (flash silica gel, heptane/EtOAc = 8:2)
without aqueous work up to give (1) as a white solid (0.9 g, 75%); mp 125–
127 °C. 1H NMR (300 MHz, CDCl3): d = 2.41 (d, J = 1.5 Hz, CH3), 6.37 (d,
the bis(triflate) of 4-methyl-6,7-dihydroxycoumarin. The reactions
proceed with excellent regioselectivity in favor of the electroni-
cally more deficient position (Fig. 4).
J = 1.2 Hz, 1H), 7.41 (br s
,
1H, ArH), 7.59 (br s, 1H, ArH). 13C NMR
Acknowledgments
(75.46 MHz, CDCl3): d = 18.6 (CH3), 110.9, 112.7, 113.1 (CH), 116.0 (q,
JF,C = 317.0 Hz, CF3), 117.3 (q, JF,C = 317.0 Hz, CF3), 118.1, 136.4, 141.7, 150.5,
152.6 (C), 158.2 (CO). 19F NMR (282.4, MHz): d = À72.8, À72.7. IR (KBr, cmÀ1):
v = 3124, 3053, 2964, 2926 (w), 1740 (s), 1673, 1625, 1613, 1570 (w), 1498 (m).
GC–MS (EI, 70 eV): m/z (%) = 456 ([M]+, 100), 324 (10), 323 (84), 232 (10), 203
Financial support by the DAAD (scholarships for A.M.H.
and N.E.), by the Ministry of Higher Education and Scientific
Research Iraq (scholarship for H.M.), and by the State of

A. M. Hamdy et al. / Tetrahedron Letters 54 (2013) 3568–3571
3571
(33), 162 (13), 134 (26), 69 (55). HRMS (EI, 70 eV) calcd for C12H6F6O8S2 ([M]+):
455.94028, found: 455.94130.
1H), 6.67 (br s, 1H, ArH), 7.17 (d, J = 8.8 Hz, 3H, ArH), 7.33 (d, J = 8.4 Hz, 1H,
ArH), 7.48 (br s, 1H, ArH). 13C NMR (75.47 MHz, CDCl3): d = 17.6 (2CH3), 20.1
(CH3), 113.9, 115.2, 118.7 (CH), 125.4 (q, JF,C = 320.4 Hz, CF3), 126.4, 127.9 (CH),
129.8, 132.8, 136.3, 137.3, 138.4, 141.5, 149.8, 151.3 (C), 160.1 (CO). 19F NMR
(282.4 MHz): d = À73.8. IR (KBr, cmÀ1): v = 3057, 2950, 2910, 2838 (w), 1721
(s), 1611, 1606 (m),1538 (w), 1509, 1491 (m). GC–MS (EI, 70 eV): m/z (%) = 412
([M]+, 100), 280 (20), 279 (30), 264 (12), 235 (11). HRMS (EI, 70 eV) calcd for
23. General procedure for Suzuki–Miyaura reactions: A solution of K3PO4, Pd(PPh3)4,
and arylboronic acid in the solvent indicated was stirred at the indicated
temperature and for the indicated time. After cooling to 20 °C, distilled H2O
was added. The organic and the aqueous layers were separated and the latter
was extracted with CH2Cl2. The combined organic layers were dried (Na2SO4),
filtered, and the filtrate was concentrated in vacuo. The residue was purified by
column chromatography (flash silica gel, heptanes–EtOAc).
24. 6,7-Bis(3,5-dimethlyphenyl)-4-methyl-2H-chromen-2-one (4a): Starting with 2
(70 mg, 0.153 mmol), 3,5-dimethlyphenylboronic acid (3a) (51 mg,
0.337 mmol), Pd(PPh3)4 (11 mg, 6 mol %, 0.009 mmol), K3PO4 (98 mg,
C
19H15F3O5S [M]+: 412.05868; found: 412.05840.
27. 6-(4-Chlorophenyl)-7-(4-methoxyphenyl)-4-methyl-2H-chromen-2-one (6a): The
reaction was carried out in a one-pot procedure with sequential addition of the
boronic acids to the substrate 2. Catalyst and base had to be added two times.
Starting with
2 (70 mg, 0.153 mmol), 4-methoxyphenylboronic acid (3b)
0.460 mmol), and 1,4-dioxane (3 mL), 4a was isolated as
a
white solid
(28 mg, 0.153 mmol), Pd(PPh3)4 (5 mg, 3 mol %, 0.005 mmol), K3PO4 (49 mg,
0.2301 mmol), 4-chlorophenylboronic acid (3c) (28 mg, 0.153 mmol),
Pd(PPh3)4 (5 mg, 3 mol %, 0.005 mmol), K3PO4 (49 mg, 0.230 mmol), and
dioxane (3 mL), 6a was isolated as a white solid (42 mg, 73%); mp 172–
174 °C. 1H NMR (300 MHz, CDCl3): d = 2.39 (d, J = 1.1 Hz, 3H, CH3), 3.73 (s, 3H,
OCH3), 6.24 (d, J = 1.3 Hz, 1H), 6.72 (d, J = 8.1 Hz, 2H, ArH), 6.95–6.99 (m, 5H,
ArH), 7.16 (d, J = 8.1 Hz, 2H, ArH), 7.46 (br s, 1H, ArH). 13C NMR (75.46 MHz,
CDCl3): d = 17.6 (CH3), 54.2 (OCH3), 112.7, 114.1, 117.4 (CH), 117.8 (C), 125.3,
127.4, 129.8, 130.0 (CH), 130.5, 132.0, 134.7, 137.8, 143.1, 151.0, 151.9, 158.1
(C), 159.7 (CO). IR (KBr, cmÀ1): v = 3115, 3092, 3076, 2966, 2932, 2845 (w),
1731 (s), 1620, 1600 (m), 1580, 1540, 1522, 1493 (w). GC–MS (EI, 70 eV): m/z
(%) = 376 ([M]+, [35Cl], 100), 348 (13). HRMS (EI, 70 eV) calcd for C23H1735ClO3
([M]+): 376.08607; found 367.08589.
(42 mg, 75%); mp 121–122 °C. 1H NMR (300 MHz, CDCl3): d = 2.13 (s, 6H,
CH3), 2.14 (s, 6H, CH3), 2.39 (d, J = 1.3 Hz, 3H, CH3), 6.24 (d, J = 1.2 Hz, 1H),
6.67–6.80 (m, 6H, ArH), 7.30 (br s, 1H, ArH) , 7.49 (br s, 1H, ArH). 13C NMR
(75.46 MHz, CDCl3): d = 17.6 (2CH3), 20.1 (2CH3), 26.1 (CH3), 113.9, 117.2 (CH),
117.7, 120.1 (C), 125.1, 126.4, 126.6, 127.4, 127.9 (CH), 136.3, 136.3, 138.5,
139.1, 143.7, 151.2, 151.5, 154.4, 156.1 (C), 160.9 (CO). IR (KBr, cmÀ1): v = 3015,
3082, 3066, 2868, 2732, 2645 (w), 1722 (s), 1618, 1607 (m), 1573, 1537, 1516,
1485 (w). GC–MS (EI, 70 eV): m/z (%) = 368 ([M]+,100), 353 (12), 338 (10).
HRMS (EI, 70 eV) calcd for C26H24O2 [M]+: 368.17708; found: 368.17685.
25. CCDC-934927 and 934928 contain all crystallographic details of this
publication and is available free of charge at http://ccdc.cam.ac.uk/conts/
retrieving.html or can be ordered from the following address: Cambridge
Crystallographic Data Centre, 12 Union Road, GB-Cambridge CB21EZ; fax: +44
1223 336 033; or deposit@ccdc.cam.ac.uk.
28. For reviews of cross-coupling reactions of polyhalogenated heterocycles and
triflates, see: (a) Schröter, S.; Stock, C.; Bach, T. Tetrahedron 2005, 61, 2245; (b)
Schnürch, M.; Flasik, R.; Khan, A. F.; Spina, M.; Mihovilovic, M. D.; Stanetty, P.
Eur. J. Org. Chem. 2006, 3283; (c) Rossi, R.; Bellina, F.; Lessi, M. Adv. Synth. Catal.
2012, 354, 1181.
26. 7-[(3,5-Dimethylphenyl)-4-methyl-2-oxo-2H-chromen-6-yl]
trifluoromethanesulfonate (5a): Starting with
2 (70 mg, 0.153 mmol), 3,5-
dimethlyphenylboronic acid (3a) (28 mg, 0.184 mmol), Pd(PPh3)4 (5 mg,
3 mol %, 0.005 mmol), K3PO4 (49 mg, 0.230 mmol), and dioxane (3 mL), 5a
was isolated as a white solid (47 mg, 75%); mp 165–167 °C. 1H NMR (300 MHz,
CDCl3): d = 1.45 (s, 6H, 2CH3), 2.31 (d, J = 1.4 Hz, 3H, CH3), 6.31 (d, J = 1.4 Hz,
29. For a simple guide to predict the regioselectivity of Pd catalyzed cross-coupling
reactions, see: Handy, S. T.; Zhang, Y. Chem. Commun. 2006, 299.