Synthesis of 1,2-diarylanthraquinones by site-selective suzuki-miyaura reactions of the bis(triflate) of alizarin

Article abstract of DOI:10.1055/s-0029-1219586

1,2-Diarylanthraquinones were prepared by Suzuki-Miyaura reactions of the bis(triflate) of 1,2-dihydroxyanthraquin-one (alizarin). The reactions proceed with excellent site selectivity. The first attack occurs at the sterically more hindered position 1, d

Full text of DOI:10.1055/s-0029-1219586

LETTER
1085
Synthesis of 1,2-Diarylanthraquinones by Site-Selective Suzuki–Miyaura
Reactions of the Bis(triflate) of Alizarin
S
ynthesis of 1,2-D
h
iarylanthraqu
m
inones ed Mahal,a Alexander Villinger,a Peter Langer*a,b
a
Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Fax +49(381)4986412; E-mail: peter.langer@uni-rostock.de
b
Received 11 January 2010
vor of the sterically more hindered position 1, due to elec-
tronic reasons.
Abstract: 1,2-Diarylanthraquinones were prepared by Suzuki–
Miyaura reactions of the bis(triflate) of 1,2-dihydroxyanthraquin-
one (alizarin). The reactions proceed with excellent site selectivity.
The first attack occurs at the sterically more hindered position 1, due
to electronic reasons.
1,2-Dihydroxyanthraquinone (alizarin) (1) was trans-
formed in good yield into the novel bis(triflate) 2
(Scheme 1).12
Key words: catalysis, palladium, Suzuki–Miyaura reaction, regio-
selectivity, anthraquinones
O
OTf
O
OH
OTf
OH
i
Anthraquinones are of considerable pharmacological rel-
evance and occur in various natural products.1 For exam-
ple, the anthracyclines are important as antitumor agents
and antibiotics (e.g., the natural products daunorubicin,
adriamycin, and aclarubicin).2 Anthracyclines have been
mainly isolated as O-glycosides, but also as aglycons
(e.g., saintopin).3 Simple hydroxylated anthraquinones
have also been isolated as natural products (e.g.,
chrysophanic acid, vismiaquinone, anthragallol, questin
and several others).4 While most of them are found as
aglycons, a few derivatives, such as pulmatin,5 occur in O-
glycosylated form.5 Mumbaistatin, isolated from a culture
of streptomyces DSM 11641, is known today as the stron-
gest inhibitor of glucose-6-phosphate translocase (G6P-
T1).6 Aryl-substituted anthraquinones possess many ap-
plications in material sciences, due to their redox,7a,b UV
O
O
1
2
Scheme 1 Synthesis of 2. Reagents and conditions: (i) CH2Cl2, 1
(1.0 equiv), –78 °C, pyridine (4.0 equiv), Tf2O (2.4 equiv), –78 °C →
20 °C, 14 h.
O
OTf
O
Ar
OTf
Ar
ArB(OH)2
3a–f
i
O
O
2
4a–f
Scheme 2 Synthesis of 4a–f. Reagents and conditions: (i) 2 (1.0
equiv), 3a–f (2.4 equiv), Pd(PPh3)4 (6 mol%), K3PO4 (3.0 equiv), 1,4-
and luminescence properties.7c,d They have also been used dioxane, 110 °C, 10 h.
as stabilizers of light-modulating fluids.7e
The Suzuki–Miyaura reaction of 2 with arylboronic acids
Polyhalogenated molecules represent interesting sub-
strates in palladium(0)-catalyzed cross-coupling reac-
tions.8 Recently, we have reported Suzuki and Heck
reactions of tetrabromothiophene, tetrabromo-N-meth-
ylpyrrole, tetrabromoselenophene and other polyhaloge-
nated heterocycles.9 We have also reported the synthesis
3a–f (2.4 equiv) afforded the 1,2-diarylanthraquinones
4a–f (Scheme 2, Table 1). Good yields were obtained for
the reactions of both electron-rich and electron-poor aryl-
boronic acids (except for 3b). The best yields were ob-
of tetraaryl-p-benzoquinones by Suzuki reactions of tetra- Table 1 Synthesis of 4a–f
bromo-p-benzoquinone.10 Recently, we have reported that
3,4
a
Ar
Yield (%) of 4a
Suzuki–Miyaura reactions of the bis(triflate) of methyl
2,5-dihydroxybenzoate proceed with very good site selec-
tivity in favor of the sterically less hindered position 5.11
Herein, we report, for the first time, the synthesis of 1,2-
diarylanthraquinones by Suzuki–Miyaura reactions of the
bis(triflate) of 1,2-dihydroxyanthraquinone. Interestingly,
the reactions proceed with excellent site selectivity in fa-
4-(F3C)C6H4
4-(MeO)C6H4
4-t-BuC6H4
4-ClC6H4
4-MeC6H4
4-EtC6H4
77
40
76
81
77
60
b
c
d
e
SYNLETT 2010, No. 7, pp 1085–1088
x
x.
x
x.
2
0
1
0
f
Advanced online publication: 16.03.2010
DOI: 10.1055/s-0029-1219586; Art ID: G02010ST
a Yields of isolated products.
© Georg Thieme Verlag Stuttgart · New York

1086
A. Mahal et al.
LETTER
Table 3 Synthesis of Anthraquinones 6a–f
tained when the reactions were carried out using
Pd(PPh3)4 as the catalyst and K3PO4 as the base.13,14
3
6
a
b
c
d
e
f
Ar1
Ar2
Yield (%) of 6a
The Suzuki–Miyaura reaction of 2 with arylboronic acids
3a–d and 3g–j (1.0 equiv) afforded the 1-aryl-2-trifluoro-
sulfonyloxyanthraquinones 5a–h in good yields
(Scheme 3, Table 2).13,15 Good yields were obtained for
the reactions of both electron-rich and electron-poor aryl-
boronic acids (except for 3i,j). During the optimization, it
proved to be important to carry out the reaction at 90 °C
instead of 110 °C.
a,c
b,c
c,a
d,c
g,a
g,c
4-(F3C)C6H4
4-(MeO)C6H4
4-t-BuC6H4
4-ClC6H4
4-t-BuC6H4
4-t-BuC6H4
4-(F3C)C6H4
4-t-BuC6H4
4-(F3C)C6H4
4-t-BuC6H4
65
50
60
61
68
61
3-(F3C)C6H4
3-(F3C)C6H4
O
OTf
O
Ar
a Yields of isolated products.
ArB(OH)2
3a–d, g–j
OTf
OTf
i
All products were characterized by spectroscopic meth-
ods. The constitution was established by 2D NMR exper-
iments (HMBC, NOESY). The structures of 4c, 5b, and
6a were independently confirmed by X-ray crystal struc-
ture analyses (Figures 1– 3).18
O
O
2
5a–h
Scheme 3 Synthesis of 5a–h. Reagents and conditions: (i) 2 (1.0
equiv), 3a–d,g–j (1.0 equiv), Pd(PPh3)4 (3 mol%), K3PO4 (1.5 equiv),
1,4-dioxane, 90 °C, 10 h.
Table 2 Synthesis of 5a–h
3
a
b
c
d
g
h
i
5
a
b
c
d
e
f
Ar
Yield (%) of 5a
4-(CF3)C6H4
4-(MeO)C6H4
4-t-BuC6H4
4-ClC6H4
74
67
61
85
84
79
50
52
3-(CF3)C6H4
3-(MeO)C6H4
4-FC6H4
g
Figure 1 Crystal structure of 4c
j
h
4-(OCF3)C6H4
a Yields of isolated products.
The one-pot reaction of 2 with two different arylboronic
acids afforded the 1,2-diarylanthraquinones 6a–f which
contain two different aryl groups (Scheme 4, Table 3).16,17
The boronic acids were added in a sequential manner.
During the optimization, it proved to be important to carry
out the first step of the one-pot reaction at 90 °C and the
second step at 110 °C.
Ar1
O
OTf
O
Ar1B(OH)2
Ar2B(OH)2
Ar2
OTf
i
O
O
Figure 2 Crystal structure of 5b
2
6a–f
Scheme 4 Synthesis of 6a–f. Reagents and conditions: (1) 2 (1.0
equiv), 3a–d,g (1.0 equiv), Pd(PPh3)4 (3 mol%), K3PO4 (1.5 equiv),
1,4-dioxane, 90 °C, 10 h; (2) 3a,c (1.1 equiv), K3PO4 (1.5 equiv), 1,4-
dioxane, 110 °C, 10 h.
Synlett 2010, No. 7, 1085–1088 © Thieme Stuttgart · New York

LETTER
Synthesis of 1,2-Diarylanthraquinones
1087
References and Notes
(1) Römpp Lexikon Naturstoffe; Steglich, W.; Fugmann, B.;
Lang-Fugmann, S., Eds.; Thieme: Stuttgart, 1997.
(2) Review: Krohn, K. Angew. Chem., Int. Ed. Engl. 1986, 25,
790; Angew. Chem. 1986, 98, 788.
(3) Ishiyama, D.; Futamata, K.; Futamata, M.; Kasuya, O.;
Kamo, S. J. Antibiot. 1998, 51, 1069.
(4) (a) El-Beih, A. A.; Kawabata, T.; Koimaru, K.; Ohta, T.;
Tsukamoto, S. Chem. Pharm. Bull. 2007, 55, 1097.
(b) Nguemeving, J. R.; Azebaze, A. G. B.; Kuete, V.; Carly,
N. N. E.; Beng, V. P.; Meyer, M.; Blond, A.; Bodo, B.;
Nkengfack, A. E. Phytochemistry 2006, 67, 1341.
(c) Dhananjeyan, M. R.; Milev, Y. P.; Kron, M. A.; Nair,
M. G. J. Med. Chem. 2005, 48, 2822. (d) Liu, R.; Zhu, W.;
Zhang, Y.; Zhu, T.; Liu, H.; Fang, Y.; Gu, Q. J. Antibiot.
2006, 59, 362. (e) Wu, T.-S.; Lin, D.-M.; Shi, L.-S.; Damu,
A. G.; Kuo, P.-C.; Kuo, Y.-H. Chem. Pharm. Bull. 2003, 51,
948. (f) Feng, Z.-M.; Jiang, J.-S.; Wang, Y.-H.; Zhang, P.-C.
Chem. Pharm. Bull. 2005, 53, 1330. (g) Nicolaou, K. C.;
Yee, H. L.; Piper, J. L.; Papageorgiou, C. D. J. Am. Chem.
Soc. 2007, 129, 4001. (h) El-Gamal, A. A.; Takeya, K.;
Itokawa, H.; Halim, A. F.; Amer, M. M. Phytochemistry
1995, 40, 245.
(5) Diaz, F.; Chai, H.-B.; Mi, Q.; Su, B.-N.; Vigo, J. S.; Graham,
J. G.; Cabieses, F.; Farnsworth, N. R.; Cordell, G. A.;
Pezzuto, J. M.; Swanson, S. M.; Kinghorn, A. D. J. Nat.
Prod. 2004, 67, 352.
(6) Vertesy, L.; Kurz, M.; Paulus, E. F.; Schummer, D.;
Hammann, P. J. Antibiot. 2001, 54, 354.
(7) (a) Gautrot, J. E.; Hodge, P.; Cupertino, D.; Helliwell, M.
New J. Chem. 2006, 30, 1801. (b) Showalter, H. D. H.;
Berman, E. M.; Johnson, J. L.; Hunter, W. E. Tetrahedron
Lett. 1985, 26, 157. (c) Shcheglova, N. A.; Shigorin, D. N.;
Dokunikhin, N. S. Zh. Fiz. Khim. 1966, 40, 1048; Chem.
Abstr. 1966, 65, 9958b. (d) Shcheglova, N. A.; Shigorin, D.
N.; Dokunikhin, N. S. Zh. Fiz. Khim. 1965, 39, 3039; Chem.
Abstr. 1965, 64, 12058f. (e) Orser, D. A. (General Electric
Company, Schenectady, N.Y., USA) US Patent, 3764549,
1973; Chem. Abstr. 1973, 79, 141431j.
(8) For reviews of cross-coupling reactions of polyhalogenated
heterocycles, 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.
Figure 3 Crystal structure of 6a
The site-selective formation of 5a–h and 6a–f can be ex-
plained by electronic reasons. The first attack of palladi-
um(0)-catalyzed cross-coupling reactions generally
occurs at the electronically more deficient and sterically
less hindered position.8,19 Position 1 of bis(triflate) 2 is
sterically more hindered than position 2 (Scheme 5).
However, position 1 (located in b-position to the carbonyl
group) is more electron-deficient than position 2. In fact,
1
the H NMR signals of aromatic protons located at posi-
tion 1 are generally shifted to lower field compared to the
protons located at position 2.19 In addition, a neighboring
group effect by the quinone carbonyl group onto position
1 or on the approaching palladium complex might play a
role. In conclusion, the first attack occurs at the sterically
more hindered position, due to electronic reasons.
sterically more hindered
electronically more deficient
O
O
OTf
OTf
sterically less hindered
electronically less deficient
(9) (a) Dang, T. T.; Dang, T. T.; Ahmad, R.; Reinke, H.; Langer,
P. Tetrahedron Lett. 2008, 49, 1698. (b) Dang, T. T.;
Villinger, A.; Langer, P. Adv. Synth. Catal. 2008, 350, 2109.
(c) Hussain, M.; Nguyen, T. H.; Langer, P. Tetrahedron Lett.
2009, 50, 3929. (d) Tengho Toguem, S.-M.; Hussain, M.;
Malik, I.; Villinger, A.; Langer, P. Tetrahedron Lett. 2009,
50, 4962. (e) Dang, T. T.; Dang, T. T.; Rasool, N.; Villinger,
A.; Langer, P. Adv. Synth. Catal. 2009, 351, 1595.
(10) Ullah, I.; Khera, R. A.; Hussain, M.; Langer, P. Tetrahedron
Lett. 2009, 50, 4651.
Scheme 5 Possible explanation for the site selectivity of the reac-
tions of bis(triflate) 2
In conclusion, we have reported an efficient synthesis of
1,2-diarylanthraquinones by Suzuki–Miyaura reactions of
the bis(triflate) of 1,2-dihydroxyanthraquinone (alizarin).
The reactions proceed with excellent site selectivity.
(11) Nawaz, M.; Farooq Ibad, M.; Obaid-Ur-Rahman, A.; Khera,
R. A.; Villinger, A.; Langer, P. Synlett 2010, 150.
(12) Synthesis of 1,2-Bis(trifluoromethylsulfonyloxy)-
anthraquinone (2): To a solution of 1 (1.0 equiv) in CH2Cl2
(10 mL/mmol) was added pyridine (4.0 equiv) at r.t. under
an argon atmosphere. After 10 min, Tf2O (2.4 equiv) was
added at –78 °C. The mixture was allowed to warm to r.t. and
stirred for overnight. The reaction mixture was filtered and
the filtrate was concentrated in vacuo. The products of the
reaction mixture were isolated by rapid column chromatog-
raphy (flash silica gel, heptanes–EtOAc). Starting with 1
(1.90 g, 8.0 mmol), pyridine (2.6 mL, 32.0 mmol), CH2Cl2
(80 mL), Tf2O (3.2 mL, 19.2 mmol), 2 was isolated as a
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
We are grateful to Mr. Munawar Hussain and Mr. Muhammad
Farooq Ibad for their support. Financial support by the DAAD
(scholarship for A.M.) is gratefully acknowledged.
Synlett 2010, No. 7, 1085–1088 © Thieme Stuttgart · New York

1088
A. Mahal et al.
LETTER
yellow solid (3.25 g, 81%); mp 152–154 °C. 1H NMR (300
MHz, CDCl3): d = 7.80–7.85 (m, 3 H, ArH), 8.23–8.26 (m,
1 H, ArH), 8.29–8.32 (m, 1 H, ArH), 8.46 (d, J = 8.7 Hz, 1
(CH), 134.1 (C), 134.5 (CH), 134.6, 137.6, 151.2, 151.8 (C),
181.9, 182.0 (CO). 19F NMR (282 MHz, CDCl3): d = –74.2
(3 × F, CF3). IR (KBr): 2960, 2930, 2869, 1675, 1665, 1590,
1580, 1573, 1429 (w), 1410 (m), 1362, 1329, 1316, 1297
(w), 1267 (m), 1205 (s), 1165 (m), 1129 (s), 1079, 1040,
1017, 997 (w), 946, 879, 843 (m), 820 (s), 792, 775, 767,
757, 745 (w), 725 (m), 713 (s), 683, 671 (w), 642 (m), 603
(s), 573 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 488 (18)
[M]+, 473 (100), 431 (31), 325 (58), 299 (26), 239 (8).
HRMS (EI, 70 eV): m/z [M+] calcd for C25H19O5F3S:
488.08998; found: 488.090070.
H, ArH). 13C NMR (75 MHz, CDCl3): d = 118.5 (q, JCF
=
320.9 Hz, CF3), 118.6 (d, JCF = 320.7 Hz, CF3), 127.4 (CH),
127.8 (C), 128.0, 128.1, 128.9 (CH), 132.0, 133.7, 134.1 (C),
135.1, 135.2 (CH), 139.2, 145.0 (C), 180.2, 180.5 (CO). 19
F
NMR (282 MHz, CDCl3) d = –73.4 (q, JCF = 3.0, 6.0 Hz,
CF3), –72.58 (q, JCF = 2.8, 5.8 Hz, CF3). IR (KBr): 1674 (s),
1601, 1587, 1472 (w), 1427 (s), 1330, 1316, 1282, 1249 (w),
1208 (s), 1164, 1150 (m)1124 (s), 1007, 998, 901, 856 (m),
807 (s), 795, 738 (m), 721, 708 (s), 684, 676, 655, 643 (w),
618, 606 (m), 589, 575, 569 (s), 543, 529 (m) cm–1. GC–MS
(EI, 70 eV): m/z (%) = 504 (36) [M]+, 435 (05), 375 (08), 348
(23), 279 (100), 251 (76), 223 (26), 154 (26), 126 (60).
HRMS (EI, 70 eV): m/z [M+] calcd for C16H6O8F6S2:
503.94028; found: 503.94011.
(16) General Procedure for the Synthesis of 6a–f: The reaction
was carried out in a pressure tube. To a dioxane suspension
(3 mL) of 2 (250 mg, 0.5 mmol), Ar1B(OH)2 (0.5 mmol) and
Pd(PPh3)4 (3 mol%) was added K3PO4 (160 mg, 0.75 mmol),
and the resultant solution was degassed by bubbling argon
through the solution for 10 min. The mixture was heated at
90 °C under an argon atmosphere for 10 h. The mixture was
cooled to 20 °C. Ar2B(OH)2 (0.55 mmol), Pd(PPh3)4 (3
mol%), K3PO4 (160 mg, 0.75 mmol) and dioxane (2 mL)
were added. The reaction mixtures were heated under an
argon atmosphere for 10 h at 110 °C. They were diluted with
H2O and extracted with CH2Cl2 (3 × 25 mL). The combined
organic layers were dried (Na2SO4), filtered and the filtrate
was concentrated in vacuo. The residue was purified by flash
chromatography (silica gel, EtOAc–heptanes).
(13) General Procedure for Suzuki–Miyaura Reactions: A
1,4-dioxane solution (4 mL per 3 mmol of 2) of 2, K3PO4,
Pd(PPh3)4 and arylboronic acid 3 was stirred at 110 °C or 90
°C for 10 h. 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.
(14) Synthesis of 1,2-Bis(4-(tert-butylphenyl)anthraquinone
(4c): Starting with 2 (250 mg, 0.5 mmol), 4-tert-butyl-
phenylboronic acid (3c; 213 mg, 1.2 mmol), Pd(PPh3)4 (34
mg, 6 mol%, 0.03 mmol), K3PO4 (320 mg, 1.5 mmol) and
1,4-dioxane (4 mL), 4c was isolated by rapid column
chromatography (flash silica gel, heptanes–EtOAc) as
yellow crystals (180 mg, 76%); mp 234–236 °C. 1H NMR
(300 MHz, CDCl3): d = 1.15 (s, 9 H, 3 × Me), 1.20 (s, 9 H, 3
× Me), 6.75–6.83 (m, 4 H, ArH), 7.01–7.14 (m, 4 H, ArH),
7.60–7.65 (m, 2 H, ArH), 7.70 (d, J = 8.0 Hz, 1 H, ArH),
8.01–8.03 (m, 1 H, ArH), 8.17–8.20 (m, 1 H, ArH), 8.34 (d,
J = 8.1 Hz, 1 H, ArH). 13C NMR (62.9 MHz, CDCl3): d =
31.2 (3 × Me), 31.4 (3 × Me), 34.4 (C), 34.4 (C), 124.2,
124.3, 126.6, 127.0, 127.5, 129.0, 129.0 (CH), 131.3, 132.9
(C), 133.5 (CH), 133.6 (C), 134.1, 134.9 (CH), 135.0, 136.9,
137.2, 142.7, 149.1, 149.8, 149.8 (C), 183.4, 183.7 (CO). IR
(KBr): 2959 (m), 2901, 2866 (w), 1675 (s), 1663, 1588 (m),
1575, 1566, 1548, 1513, 1475, 1456, 1410, 1394, 1360 (w),
1330, 1315 (m), 1298 (s), 1280, 1262, 1253, 1211, 1199 (m),
1185, 1160 (w), 1113 (m), 1072 (w), 1016 (m), 979 (w), 956
(m), 942, 904 (w), 860, 836 (m), 822 (s), 795 (m), 774, 768,
755, 745 (w), 719 (s), 690 (m), 682 (w), 662, 645 (m), 587
(s), 568, 559, 543 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) =
472 (45) [M]+, 457 (93), 439 (4), 415 (100), 401 (23), 383
(11). HRMS (EI, 70 eV): m/z [M+] calcd for C34H32O2:
472.23968; found: 472.23868.
(15) Synthesis of 1-(4-tert-Butylphenyl)-2-(trifluoromethyl-
sulfonyloxy)anthraquinone (5c): Starting with 2 (250 mg,
0.5 mmol), 4-tert-butylphenylboronic acid (3c; 90 mg, 0.5
mmol), Pd(PPh3)4 (17 mg, 3 mol%, 0.015 mmol), K3PO4
(160 mg, 0.75 mmol) and 1,4-dioxane (3 mL), 5c was
isolated by rapid column chromatography (flash silica gel,
heptanes–EtOAc) as yellow crystals (149 mg, 61%); mp
160–162 °C. 1H NMR (250 MHz, CDCl3): d = 1.31 (s, 9 H,
3 × Me), 7.07 (d, J = 8.4 Hz, 2 H, ArH), 7.42 (d, J = 8.5 Hz,
2 H, ArH), 7.58–7.67 (m, 3 H, ArH), 7.96–8.00 (m, 1 H,
ArH), 8.11–8.14 (m, 1 H, ArH), 8.36 (d, J = 8.8 Hz, 1 H,
ArH). 13C NMR (75.4 MHz, CDCl3): d = 31.3 (3 × Me), 34.7
(C), 118.2 (q, JCF = 318.5 Hz, CF3), 125.2, 126.3, 126.9,
127.7, 128.3, 129.3 (CH), 130.5, 132.4, 133.4 (C), 134.1
(17) Synthesis of 1-[4 (Trifluoromethyl)phenyl]-2-(4-tert-
butylphenyl)anthraquinone (6a): Starting with 2 (252 mg,
0.5 mmol), 4-(trifluoromethyl)phenylboronic acid (3a; 95
mg, 0.5 mmol), Pd(PPh3)4 (17 mg, 3 mol%, 0.015 mmol),
K3PO4 (160 mg, 0.75 mmol), 1,4-dioxane (3 mL), and 4-tert-
butylphenylboronic acid (3c; 98 mg, 0.55 mmol), 6a was
isolated by rapid column chromatography (flash silica gel,
heptanes–EtOAc) as yellow crystals (157 mg, 65%); mp
225–227 °C. 1H NMR (300 MHz, CDCl3): d = 1.15 (s, 9 H,
3 × Me), 6.76–6.80 (m, 2 H, ArH), 7.03–7.10 (m, 4 H, ArH),
7.38 (d, J = 8.1 Hz, 2 H, ArH), 7.61–7.66 (m, 2 H, ArH), 7.70
(d, J = 8.0 Hz, 1 H, ArH), 7.94–7.98 (m, 1 H, ArH), 8.16–
8.20 (m, 1 H, ArH), 8.36 (d, J = 8.0 Hz, 1 H, ArH). 13C NMR
(75.4 MHz, CDCl3): d = 31.2 (3 × Me), 34.4 (C), 124.3 (q,
J = 272.3 Hz, CF3), 124.4 (dq, J = 7.6, 2.2 Hz), 124.7, 126,7,
127.4, 127.6 (CH), 128.5 (q, J = 32.8 Hz, C), 129.0, 129.7
(CH), 131.3, 132.8, 133.6 (C), 133.8, 134.3 (CH), 134.6 (C),
135.4 (CH), 136.3, 140.8, 144.0 (d, J = 1.7 Hz,), 149.1, 150.5
(C), 183.0, 183.6 (CO). 19F NMR (282 MHz, CDCl3): d =
–62.33 (3 × F, CF3). IR (KBr): 2962, 2905, 2869 (w), 1672
(m), 1613, 1588, 1552, 1513, 1462, 1409, 1399, 1363 (w),
1321 (s), 1300, 1278, 1263 (m), 1213, 1186 (w), 1158 (s),
1118 (m), 1105 (s), 1087, 1075, 1059, 1016 (m), 976 (w),
954 (m), 899, 864 (w), 837, 824 (m), 796, 784, 767, 758, 744
(w), 718 (s), 688, 671, 662, 640, 605 (w), 584 (m), 566, 564,
532 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 484 (43) [M]+,
469 (100), 449 (10), 427 (08), 383 (02), 357 (03). HRMS
(EI, 70 eV): m/z [M+] calcd for C31H23O2F3: 484.16447;
found: 484.164850.
(18) CCDC 766105, CCDC 766106 and CCDC 766107 contain
all crystallographic details of this publication and is
available free of charge at www.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)336033; or
deposit@ccdc.cam.ac.uk.
(19) For a simple guide for the prediction of the site selectivity of
palladium(0)-catalyzed cross-coupling reactions based on
the 1H NMR chemical shift values, see: Handy, S. T.; Zhang,
Y. Chem. Commun. 2006, 299.
Synlett 2010, No. 7, 1085–1088 © Thieme Stuttgart · New York

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