Palladium-catalyzed oxidative arylation of chromones via a double C-H activation: An expedient approach to flavones

Article abstract of DOI:10.1016/j.tetlet.2012.03.100

A palladium-catalyzed oxidative arylation of chromones was examined. A regioselective 2-arylation of chromone was carried out via a double C-H activation process. The procedure provided an expedient approach for the preparation of flavone derivatives.

Full text of DOI:10.1016/j.tetlet.2012.03.100

Tetrahedron Letters 53 (2012) 2761–2764
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Tetrahedron Letters
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Palladium-catalyzed oxidative arylation of chromones via a double C–H
activation: an expedient approach to flavones
⇑
Ko Hoon Kim, Hyun Seung Lee, Se Hee Kim, Jae Nyoung Kim
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A palladium-catalyzed oxidative arylation of chromones was examined. A regioselective 2-arylation of
chromone was carried out via a double C–H activation process. The procedure provided an expedient
approach for the preparation of flavone derivatives.
Received 20 February 2012
Revised 16 March 2012
Accepted 26 March 2012
Available online 5 April 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Palladium
Chromones
Oxidative arylation
Flavones
C–H activation
Flavones (2-arylchromones) are a group of natural products
which occur as secondary metabolites in plants and exhibit
remarkable biological activity including anti-malarial, anti-oxi-
dant, and anti-inflammatory activities.1,2 Thus there have been re-
ported numerous approaches for the synthesis of flavones;1,2
however, a direct arylation of chromone with arenes to form flav-
ones has not been reported to the best of our knowledge. Numer-
ous palladium-catalyzed 3-arylations of chromones to isoflavones
have been reported most frequently by Suzuki–Miyaura coupling
reaction between 3-halochromones and arylboronic acids.3 Very
recently, a Pd(II)-catalyzed direct 2-arylation of chromone with
arylboronic acid was reported by Shafiee and co-workers.4
Although numerous Pd-catalyzed oxidative cross-coupling reac-
tions have been reported between arenes and heteroarenes includ-
ing indoles, benzofurans, xanthines, and various azoles,5 a direct
arylation of chromones has not been reported as described above.
Very recently, we reported an oxidative 6-arylation of 1,3-dimethyl-
uracil with arenes under the Pd(II)-catalyzed reaction conditions.6
The structural similarity of 1,3-dimethyluracil and chromone
prompted us to investigate 2-arylation of chromone derivatives,
as shown in Scheme 1.
1,3-dimethyluracil (entry 1).6a The reactions in the presence of
AcOH (entry 2) and without any acid additive (entry 3) were ineffi-
cient. The use of Pd(OAc)2 showed a similar result to that of Pd(TFA)2
(entries 4 and 5). As Fagnou and co-workers have noted,7 the use of
CsOPiv could increase the amounts of Pd(OPiv)2 species at the early
stage of the reaction, and this could facilitate the concerted metala-
tion–deprotonation (CMD) process that was required for the effec-
tive 2-arylation of chromone.6a Actually, the addition of CsOPiv
(20 mol %) increased the yield of 2a to 68% (entry 6). Replacement
of the oxidant AgOAc with Cu(OAc)2, K2S2O8, or Ag2CO3 was ineffec-
tive (entries 7–10). In some entries, very trace amount of 3-phen-
ylchromone (3a) was observed and isolated in low yields.
Thus we selected the conditions in entry 6 (Table 1) and exam-
ined 2-arylations of chromone (1a), 6-methylchromone (1b), and
7-benzyloxychromone (1c) with various arenes.8 As shown in Table
2, the reactions of 1a with m-xylene, o-xylene, p-xylene, o-dichloro-
benzene, m-dichlorobenzene, and m-bis(trifluoromethyl)benzene
produced flavones 2b–g in moderate yields (42–71%). The reaction
of p-xylene gave 2d in relatively lower yield (51%) than that of m-xy-
lene (71%) and o-xylene (66%), presumably due to the steric hin-
drance of an ortho-methyl group.9a–c It is interesting to note that
the reaction with m-dichlorobenzene, a regioisomer 2f0 was formed
in low yield (21%) along with a major product 2f (48%). The yield
was somewhat low when arene has a strong electron-withdrawing
group,9a,9b,9d as exemplified for the synthesis of 2g (42%). The reac-
tions of 6-methylchromone (1b) and 6-benzyloxychromone (1c)
also afforded 2h–j in good to moderate yields (56–71%).
In order to check the feasibility for the oxidative arylation of
chromone (1a), we examined a Pd(II)-catalyzed reaction in benzene,
and the representative screening results of the reaction conditions
are summarized in Table 1. To our delight, desired 2-phenylchro-
mone (2a) was formed; however, the yield was moderate (42%)
under the reaction conditions that were optimized in the case of
The plausible reaction mechanism is proposed in Scheme 2. A
regioselective palladation at the 2-position of chromone (1a) might
occur most likely by a CMD process (via I) to form the intermediate
⇑
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530 3389.
E-mail address: kimjn@chonnam.ac.kr (J.N. Kim).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.03.100

2762
K. H. Kim et al. / Tetrahedron Letters 53 (2012) 2761–2764
arene (60 equiv)
Pd(TFA)2 (5 mol%)
AgOAc (3.0 equiv)
arene (60 equiv)
Pd(OAc)2 (5 mol%)
AgOAc (3.0 equiv)
O
O
O
O
O
O
Me
O
Me
O
N
N
PivOH (6.0 equiv)
80-110 oC
N
Ar
PivOH (6.0 equiv)
CsOPiv (20 mol%)
80-110 oC, 12 h
(This Work)
N
Ar
Me
Me
1a
2
(Ref. 6a)
Scheme 1.
Table 1
Optimization of reaction conditions for 2-phenylation of chromone
O
O
benzene (60 equiv)
Ph
chromone (1a, 50 mg)
+
O
2a
Ph
O
3a
Entry
Conditions
2a(%)
3a(%)
1
2
3
4
5
6
7
8
9
10
Pd(TFA)2 (5 mol %), AgOAc (3.0 equiv), PivOH (6.0 equiv), reflux, 12 h
Pd(TFA)2 (5 mol %), AgOAc (3.0 equiv), AcOH (6.0 equiv), reflux, 24 h
Pd(TFA)2 (5 mol %), AgOAc (3.0 equiv), reflux, 12 h
Pd(OAc)2 (5 mol %), AgOAc (3.0 equiv), PivOH (6.0 equiv), reflux, 35 h
Pd(OAc)2 (10 mol %), AgOAc (3.0 equiv), PivOH (6.0 equiv), reflux, 24 h
Pd(OAc)2 (5 mol %), AgOAc (3.0 equiv), PivOH (6.0 equiv), CsOPiv (20 mol %) reflux, 12 h
Pd(OAc)2 (5 mol %), Cu(OAc)2 (3.0 equiv), PivOH(6.0 equiv), reflux, 12 h
Pd(OAc)2 (5 mol %), K2S2O8 (3.0 equiv), PivOH (6.0 equiv), reflux, 12 h
Pd(OAc)2 (5 mol %), Ag2CO3 (3.0 equiv), PivOH(6.0 equiv), CsOPiv (20 mol %) reflux, 24 h
Pd(OAc)2 (10 mol %), K2S2O8 (3.0 equiv), CF3COOH (6.0 equiv), reflux, 12 h
42
20
25
49
51
68
Trace
4
Trace
Trace
3
3
4
4
0
0
35
4
Trace
0
Table 2
Synthesis of flavones from chromone derivatives 1a–ca
O
O
O
O
O
O
O
O
Cl
Cl
O
O
2a (68%)b
2b (71%)
2c (66%)
2d (51%)
2e (70%)
O
O
O
O
O
O
Cl
CF3
Cl
Cl
O
O
O
O
BnO
2f (48%)c
2f' (21%)c
Cl
CF3
2g (42%)
2h (71%)
2i (70%)
2j (56%)
a
Conditions: Substrate (0.5 mmol), arene (60 equiv), Pd(OAc)2 (5 mol %), AgOAc (3.0 equiv), PivOH (6.0 equiv), CsOPiv (20 mol %), 110 °C (reflux for benzene), 12 h.
b3-Phenylchromone (3a) was isolated in 4%.
c3,5-Dichloro derivative 2f was isolated as a major product (48%) along with a low yield of 2,4-dichloro derivative 2f (21%).
II, as in the case of 1,3-dimethyluracil.6 A subsequent C–H bond
activation of benzene could occur via a CMD mechanism or an elec-
trophilic palladation (SEAr) process to generate the intermediate
III, which looses Pd(0) to form the product 2a. The reduced Pd(0)
was oxidized to Pd(II) by AgOAc and the catalytic cycle was carried
out. The regioselective formations of 2b, 2c, and 2e–j stated that
the conversion of II to III would involve a CMD process.9
In order to understand the mechanism more clearly, we carried
out the reaction of 1a in a mixed solvent of benzene/benzene-d6
(1:1), as shown in Scheme 3. The reaction of chromone and ben-
zene showed a primary kinetic isotope effect, kH/kD = 5.8, which
stated that the C–H (or C–D) bond cleavage of benzene is involved
in the rate-limiting step. Thus we tentatively concluded that the C–
H activation process of arene would be most likely a CMD process
although the SEAr mechanism cannot be ruled out completely.10
In order to check the feasibility for the selective synthesis of 3-
phenylchromone (3a), the reaction of 1a and bromobenzene was
examined, as shown in Scheme 4. Unfortunately, the reaction of
chromone in the presence of Pd(0) showed very complex and slug-
gish reaction, as compared to 1,3-dimethyluracil.6 Desired 3a was
isolated in only 24% along with 2a (12%), recovered 1a (11%), and
intractable side products. The reason might be due to the less elec-
trophilic nature of the C-3 position of chromone, thus an electro-
philic palladation of chromone at the C-3 position was less
efficient with PhPd(OPiv) that generated from PhPdBr and PivOH.
In summary, a palladium-catalyzed oxidative arylation of chro-
mones provided an easy route for the synthesis of flavones. The
regioselective 2-arylation of chromone might proceed via a double
C–H activation process. Further studies on the synthetic applica-
tions and the reaction mechanism are currently underway.

K. H. Kim et al. / Tetrahedron Letters 53 (2012) 2761–2764
2763
O
Pd(OAc)2
O
O
1a
H
OPiv
Pd
PivOH
CsOPiv
2 Ag0
O
O
2 AcOH
H
Pd(OPiv)2
O
I
2 AgOAc
2 PivOH
PivOH
O
Pd0
O
Pd(OPiv)
II
O
O
O
2a
Ph
PivOH
O
III
Pd
Scheme 2.
O
O
3. Pd-catalyzed 3-arylation of chromones to isoflavones was carried out most
frequently by Suzuki–Miyaura coupling between 3-halochromones and
arylboronic acids, see: (a) Gavande, N.; Karim, N.; Johnston, G. A. R.;
Hanrahan, J. R.; Chebib, M. ChemMedChem 2011, 6, 1340–1346; (b) Wei, G.;
Yu, B. Eur. J. Org. Chem. 2008, 3156–3163; (c) Eisnor, C. R.; Gossage, R. A.; Yadav,
P. N. Tetrahedron 2006, 62, 3395–3401; (d) Yokoe, I.; Sugita, Y.; Shirataki, Y.
Chem. Pharm. Bull. 1989, 37, 529–530; (e) Hoshino, Y.; Miyaura, N.; Suzuki, A.
Bull. Chem. Soc. Jpn. 1988, 61, 3008–3010; (f) Zheng, S.-Y.; Shen, Z.-W.
Tetrahedron Lett. 2010, 51, 2883–2887. Pd-catalyzed 2-arylation of
chromones was carried out by the coupling reaction between 2-
chlorochromones and arylboronic acids, see:; (g) Kraus, G. A.; Gupta, V. Org.
Lett. 2010, 12, 5278–5280.
D
D
same conditions
benzene (30 equiv)
benzene-d6 (30 equiv)
D
D
2a +
1a
+
D
2a-d5
2a/2a-d5 = kH/kD = 5.8
Scheme 3.
4. Khoobi, M.; Alipour, M.; Zarei, S.; Jafarpour, F.; Shafiee, A. Chem. Commun. 2012,
48, 2985–2987.
bromobenzene (2.0 equiv)
Pd(OAc)2 (10 mol%), PPh3 (20 mol%)
5. (a) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068–5083;
(b) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48,
9792–9826; (c) Dwight, T. A.; Rue, N. R.; Charyk, D.; Josselyn, R.; DeBoef, B. Org.
Lett. 2007, 9, 3137–3139; (d) Malakar, C. C.; Schmidt, D.; Conrad, J.; Beifuss, U.
Org. Lett. 2011, 13, 1378–1381; (e) Xi, P.; Yang, F.; Qin, S.; Zhao, D.; Lan, J.; Gao,
G.; Hu, C.; You, J. J. Am. Chem. Soc. 2010, 132, 1822–1824; (f) Bugaut, X.; Glorius,
F. Angew. Chem., Int. Ed. 2011, 50, 7479–7481; (g) He, C.-Y.; Fan, S.; Zhang, X. J.
Am. Chem. Soc. 2010, 132, 12850–12852.
+
2a (12%)
3a (24%)
1a
K2CO3 (3.0 equiv), PivOH (30 mol%)
DMF, 120 oC, 12 h
Scheme 4.
6. (a) Kim, K. H.; Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2011, 52, 6228–6233; (b)
Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2012, 53, 1323–
1327.
Acknowledgments
7. Cesium pivalate may interact with Pd(OAc)2 to generate Pd(OPiv)2 more
efficiently, see: (a) Stuart, D. R.; Fagnou, K. Science 2007, 316, 1172–1175; (b)
Liegault, B.; Lapointe, D.; Caron, L.; Vlassova, A.; Fagnou, K. J. Org. Chem. 2009,
74, 1826–1834.
This work was supported by the National Research Foundation
of Korea Grant funded by the Korean Government (2011-0002570).
Spectroscopic data were obtained from the Korea Basic Science
Institute, Gwangju branch.
8. Typical procedure for the synthesis of 2a: A stirred mixture of chromone (1a,
73 mg, 0.5 mmol), Pd(OAc)2 (6 mg, 5 mol %), AgOAc (251 mg, 1.5 mmol), PivOH
(306 mg, 3.0 mmol), and CsOPiv (23 mg, 0.1 mmol) in benzene (2.7 mL,
60 equiv) was heated to reflux for 12 h under nitrogen atmosphere. After
cooling to room temperature, the crude reaction mixture was filtered over a
pad of Celite and washed with CH2Cl2. The solvent was removed and the
residue was dissolved in EtOAc (150 mL) and washed with a saturated solution
of NaHCO3 (20 mL ꢀ 3). The combined organic layers were dried over MgSO4
and concentrated under vacuum. The residue was purified by column
chromatography (hexanes/EtOAc, 10:1) to afford 2a (76 mg, 68%) as a pale
yellow solid along with a trace amount of 3a (4 mg, 4%).3e Other compounds
were synthesized similarly, and the selected spectroscopic data of unknown
compounds 2b–d, 2f, 2g, 2i and 2j are as follows. The compounds 2a,2c 2e,2a
2f0,2l 2h1b are known, and the spectroscopic data are same with the reported.
Compound 2b: 71%; pale yellow solid, mp 130–131 oC; IR (KBr) 1642, 1567,
References and notes
1. For the biological activities of flavones and related compounds, see: (a)
Middleton, E., Jr.; Kandaswami, C.; Theoharides, T. C. Pharmacol. Rev. 2000, 52,
673–751. and further references cited therein; (b) Kahnberg, P.; Lager, E.;
Rosenberg, C.; Schougaard, J.; Camet, L.; Sterner, O.; Nielsen, E. O.; Nielsen, M.;
Liljefors, T. J. Med. Chem. 2002, 45, 4188–4201; (c) Fujita, Y.; Yonehara, M.;
Tetsuhashi, M.; Noguchi-Yachide, T.; Hashimoto, Y.; Ishikawa, M. Bioorg. Med.
Chem. 2010, 18, 1194–1203; (d) Eleya, N.; Malik, I.; Reimann, S.; Wittler, K.;
Hein, M.; Patonay, T.; Villinger, A.; Ludwig, R.; Langer, P. Eur. J. Org. Chem. 2012,
1639–1652.
2. For the general synthetic approaches of flavones, see: (a) Du, Z.; Ng, H.; Zhang,
K.; Zeng, H.; Wang, J. Org. Biomol. Chem. 2011, 9, 6930–6933; (b) Chee, C. F.;
Buckle, M. J. C.; Rahman, N. A. Tetrahedron Lett. 2011, 52, 3120–3123; (c) Maiti,
G.; Karmakar, R.; Bhattacharya, R. N.; Kayal, U. Tetrahedron Lett. 2011, 52, 5610–
5612; (d) Zhao, J.; Zhao, Y.; Fu, H. Angew. Chem., Int. Ed. 2011, 50, 3769–3773;
(e) Yoshida, M.; Fujino, Y.; Doi, T. Org. Lett. 2011, 13, 4526–4529; (f) Xue, L.; Shi,
L.; Han, Y.; Xia, C.; Huynh, H. V.; Li, F. Dalton Trans. 2011, 40, 7632–7638; (g)
Lorenz, M.; Kabir, M. S.; Cook, J. M. Tetrahedron Lett. 2010, 51, 1095–1098; (h)
Shimizu, M.; Tsurugi, H.; Satoh, T.; Miura, M. Chem. Asian J. 2008, 3, 881–886;
(i) Kumar, K. H.; Perumal, P. T. Tetrahedron 2007, 63, 9531–9535; (j) Ganguly, A.
K.; Mahata, P. K.; Biswas, D. Tetrahedron Lett. 2006, 47, 1347–1349; (k) Kabalka,
G. W.; Mereddy, A. R. Tetrahedron Lett. 2005, 46, 6315–6317; (l) Huang, X.;
Tang, E.; Xu, W.-M.; Cao, J. J. Comb. Chem. 2005, 7, 802–805.
1467, 1367 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 2.41 (s, 6H), 6.79 (s, 1H), 7.17 (s,
;
1H), 7.41 (ddd, J = 8.1, 6.9 and 0.9 Hz, 1H), 7.53 (s, 2H), 7.58 (dd, J = 8.4 and
0.9 Hz, 1H), 7.69 (ddd, J = 8.4, 6.9 and 1.8 Hz, 1H), 8.23 (dd, J = 8.1 and 1.8 Hz,
1H); 13C NMR (CDCl3, 75 MHz) d 21.33, 107.45, 118.05, 123.95, 124.06, 125.08,
125.62, 131.65, 133.30, 133.61, 138.66, 156.25, 163.80, 178.44; ESIMS m/z 251
[M+H]+. Anal. Calcd for C17H14O2: C, 81.58; H, 5.64. Found: C, 81.39; H, 5.81.
Compound 2c: 66%; pale yellow solid, mp 116–117 oC; IR (KBr) 1640, 1568,
1467, 1366 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 2.34 (s, 3H), 2.36 (s, 3H), 6.79 (s,
;
1H), 7.27 (d, J = 7.5 Hz, 1H), 7.41 (ddd, J = 8.1, 6.9 and 1.2 Hz, 1H), 7.55–7.59 (m,
1H), 7.63–7.72 (m, 3H), 8.23 (dd, J = 8.1 and 1.8 Hz, 1H); 13C NMR (CDCl3,
75 MHz) d 19.88, 19.92, 106.91, 118.03, 123.82, 123.98, 125.05, 125.63, 127.27,
129.26, 130.28, 133.57, 137.41, 140.97, 156.24, 163.77, 178.46; ESIMS m/z 251

2764
K. H. Kim et al. / Tetrahedron Letters 53 (2012) 2761–2764
[M+H]+. Anal. Calcd for C17H14O2: C, 81.58; H, 5.64. Found: C, 81.67; H, 5.61.
Compound 2d: 51%; pale yellow oil; IR (KBr) 1649, 1570, 1465, 1364 cmꢁ1 1H
NMR (CDCl3, 300 MHz) d 2.39 (s, 3H), 2.44 (s, 3H), 6.49 (s, 1H), 7.15–7.25 (m,
2H), 7.35 (s, 1H), 7.40–7.53 (m, 2H), 7.63–7.70 (m, 1H), 8.24–8.30 (m, 1H); 13
NMR (CDCl3, 75 MHz) d 20.04, 20.80, 111.77, 118.01, 123.72, 125.16, 125.68,
129.65, 131.17, 131.44, 132.33, 133.59, 133.70, 135.79, 156.43, 166.24, 178.32;
ESIMS m/z 251 [M+H]+. Anal. Calcd for C17H14O2: C, 81.58; H, 5.64. Found: C,
81.46; H, 5.83.
1435, 1354, 1136 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 2.46 (s, 3H), 6.73 (s, 1H),
;
;
7.44 (d, J = 8.4 Hz, 1H), 7.51 (dd, J = 8.4 and 2.1 Hz, 1H), 7.57 (d, J = 8.4 Hz, 1H),
7.69 (dd, J = 8.4 and 2.1 Hz, 1H), 7.92–8.01 (m, 2H); 13C NMR (CDCl3, 75 MHz) d
20.90, 107.86, 117.73, 123.38, 124.99, 125.10, 127.88, 130.97, 131.63, 133.54,
135.23, 135.52, 135.73, 154.22, 160.50, 178.04; ESIMS m/z 305 [M+H]+, 307
[M+2+H]+, 309 [M+4+H]+. Anal. Calcd for C16H10Cl2O2: C, 62.97; H, 3.30. Found:
C, 63.16; H, 3.48.
C
Compound 2j: 56%; pale yellow solid, mp 140–142 oC; IR (KBr) 1640, 1444,
Compound 2f: 48%; pale yellow solid, mp 201–202 °C; IR (KBr) 1658, 1607,
1364, 1270, 1167 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 2.40 (s, 6H), 5.17 (s, 2H),
;
1559, 1467, 1365 cmꢁ1
;
1H NMR (CDCl3, 300 MHz) d 6.78 (s, 1H), 7.45 (ddd,
6.74 (s, 1H), 7.02–7.06 (m, 2H), 7.15 (s, 1H), 7.30–7.50 (m, 7H), 8.13 (d,
J = 9.3 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 21.33, 70.43, 101.30, 107.33, 114.86,
117.93, 123.92, 127.01, 127.45, 128.33, 128.70, 131.63, 133.13, 135.67, 138.58,
157.88, 163.11, 163.46, 177.89; ESIMS m/z 357 [M+H]+. Anal. Calcd for
J = 8.1,7.2 and 1.2 Hz, 1H), 7.51 (t, J = 2.1 Hz, 1H), 7.58 (dd, J = 8.7 and 1.2 Hz,
1H), 7.73 (ddd, J = 8.7, 7.2 and 1.5 Hz, 1H), 7.78 (d, J = 2.1 Hz, 2H), 8.22 (dd,
J = 8.1 and 1.5 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 108.62, 118.06, 123.82,
124.59, 125.60, 125.75, 131.20, 134.16, 134.66, 135.91, 156.01, 160.27, 177.93;
ESIMS m/z 291 [M+H]+, 293 [M+2+H]+, 295 [M+4+H]+. Anal. Calcd for
C
24H20O3: C, 80.88; H, 5.66. Found: C, 80.67; H, 5.69.
9. For the selected examples of oxidative arylation involving a CMD mechanism,
see: (a) Li, H.; Liu, J.; Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Org. Lett. 2011, 13, 276–279; (b)
Potavathri, S.; Pereira, K. C.; Gorelsky, S. I.; Pike, A.; LeBris, A. P.; DeBoef, B. J.
Am. Chem. Soc. 2010, 132, 14676–14681; (c) Stuart, D. R.; Villemure, E.; Fagnou,
K. J. Am. Chem. Soc. 2007, 129, 12072–12073; (d) Wei, Y.; Su, W. J. Am. Chem. Soc.
2010, 132, 16377–16379; (e) Campbell, A. N.; Meyer, E. B.; Stahl, S. S. Chem.
Commun. 2011, 47, 10257–10259; (f) Li, B.-J.; Tian, S.-L.; Fang, Z.; Shi, Z.-J.
Angew. Chem., Int. Ed. 2008, 47, 1115–1118.
C
15H8Cl2O2: C, 61.88; H, 2.77. Found: C, 62.05; H, 2.96.
Compound 2g: 42%; white solid, mp 181–182 oC; IR (KBr) 1659, 1467, 1363,
1278, 1125 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 6.93 (s, 1H), 7.49 (ddd, = 7.8, 7.2
;
and 1.2 Hz, 1H), 7.63–7.68 (m, 1H), 7.77 (ddd, J = 8.7, 7.2 and 1.8 Hz, 1H), 8.05
(d, J = 0.6 Hz, 1H), 8.25 (dd, J = 7.8 and 1.8 Hz, 1H), 8.36 (t, J = 0.6 Hz, 2H); 13C
NMR (CDCl3, 75 MHz) d 109.17, 118.17, 122.80 (q, J = 271.3 Hz), 123.85, 124.82
(quintet, J = 3.5 Hz), 125.87, 126.20, 126.24, 132.77 (q, J = 33.8 Hz), 134.09,
134.42, 156.06, 159.79, 177.82; ESIMS m/z 359 [M+H]+. Anal. Calcd for
10. For the kinetic isotope effect of electrophilic palladation, see: Zhao, X.; Yeung,
C. S.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 5837–5844.
C
17H8F6O2: C, 57.00; H, 2.25. Found: C, 57.33; H, 2.51.
Compound 2i: 70%; pale yellow solid, mp 175–176 oC; IR (KBr) 1640, 1483,