Regioselective Suzuki-Miyaura Cross-Coupling Reactions of the Bis(triflate) of 1,4-Dihydroxy-9 H -fluoren-9-one

Article abstract of DOI:10.1055/s-0035-1560211

1,4-Diaryl-9H-fluoren-9-ones were prepared by regioselective Suzuki-Miyaura cross-coupling reaction of the bis(triflate) of 1,4-dihydroxy-9H-fluoren-9-one. The reactions proceeded with excellent site selectivity. The first attack occurs at position 1, due to electronic reasons.

Full text of DOI:10.1055/s-0035-1560211

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2016, 27, 75–79
letter
75
M. Sonneck et al.
Letter
Synlett
Regioselective Suzuki–Miyaura Cross-Coupling Reactions of the
Bis(triflate) of 1,4-Dihydroxy-9H-fluoren-9-one
Marcel Sonnecka,b
David Kuhrta,b
Krisztina Kónyac
Tamás Patonayc
Alexander Villingera
Peter Langer*a,b
O
O
1) Ar1B(OH)2
2) Ar2B(OH)2
Ar1
OTf
one-pot
Ar2
TfO
Pd(PPh3)4 (3 mol%)
K3PO4 (2.0 equiv)
1,4-dioxane, 60–100 °C
yields: 42–99%
22 examples
a Institut für Chemie, Universität Rostock,
Albert-Einstein-Str. 3a, 18059 Rostock, Germany
peter.langer@uni-rostock.de
b Leibniz-Institut für Katalyse an der Universität Rostock e.V.,
Albert-Einstein-Str. 29a, 18059 Rostock, Germany
c Department of Organic Chemistry, University of Debrecen,
4032 Debrecen, Egyetem tér 1, Hungary
Dedicated to Professor Steven V. Ley on the occasion of his 70th birthday
Received: 24.06.2015
Accepted after revision: 08.08.2015
Published online: 23.09.2015
O
H
HO
HO
OH
DOI: 10.1055/s-0035-1560211; Art ID: st-2015-d0468-l
OH
Abstract 1,4-Diaryl-9H-fluoren-9-ones were prepared by regioselec-
tive Suzuki–Miyaura cross-coupling reaction of the bis(triflate) of
1,4-dihydroxy-9H-fluoren-9-one. The reactions proceeded with excel-
lent site selectivity. The first attack occurs at position 1, due to elec-
tronic reasons.
MeO
MeO
OH
HO
HO
B
A
O
MeO
Key words Catalysis, Suzuki–Miyaura reaction, regioselectivity, palla-
dium, heterocycles
OH
HO
Fluorenones from natural and synthetic sources show a
wide spectrum of biological properties.1 Amidofluo-
renones2 are inhibitors of telomerase enzyme, kinamycin
derivatives show antitumor and antimicrobial activity
against Gram-positive bacteria.3 Other fluorenone deriva-
tives also exhibit pharmaceutical properties and are im-
portant components of many naturals products.4–7 Dendro-
florin (A), denchrysan A (B), and 1,4,5-trihydroxy-7-me-
thoxyfluoren-9-one (C) are natural products (Figure 1) that
have been isolated from the orchid Dendrobium chrysotoxum
and show a wide range of biological activities.6
These natural products were examined for their inhibi-
tory activity against the growth of human lung adenocarci-
noma and human stomach cancer. Furthermore, they are
used as drugs for the treatment of viral diseases, such as di-
arrhea, herpes, and hepatitis.8,9 Fluorenes, arylated fluo-
renones, and benzofluorenones have been incorporated in
oligomers and polymers which have been examined widely
for potential applications as organic light-emitting devices
(OLED).10
C
Figure 1 Structure of biologically active dendroflorin (A), denchrysan
A (B), and 1,4,5-trihydroxy-7-methoxyfluoren-9-one (C)
We have reported a synthetic approach to functional-
ized fluorenones based on formal [3+3] cyclizations of
1,3-bis(silyloxy)-1,3-butadienes.11 Since the importance
of fluorenones and benzofluorenones are obvious, the de-
velopment of efficient and regioselective methods for the
synthesis of aryl-substituted derivatives is of actual impor-
tance. Herein, we show a convenient pathway to 1,4-diaryl-
9H-fluoren-9-one by site-selective12 Suzuki–Miyaura reac-
tions of the bis(triflate)13 of 1,4-dihydroxy-9H-fluoren-9-
one (1). The preparation of these products is difficult by
other methods.
The reaction of 1,4-dihydroxy-9H-fluoren-9-one (1)
with triflic anhydride provided bis(triflate) 2 (Scheme 1).14
The Suzuki–Miyaura reaction of 2 with arylboronic acids
3a–h (2.4 equiv) gave 1,4-diaryl-9H-fluoren-9-ones 4a–h in
86–98% yield (Scheme 2,Table 1).15,16 In addition, the appli-
cation of DMF (instead of dioxane) was important in the
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76
M. Sonneck et al.
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case of 4g due to the low solubility of the starting material.
Both electron-rich and electron-poor arylboronic acids
were successfully employed in these transformations.
O
O
Ar
OTf
ArB(OH)2
3a–h
i
O
O
OTf
OH
TfO
5a–h
TfO
2
i
Scheme 3 Synthesis of 5a–h. Reagents and conditions: i) 2 (1.0 equiv),
3a–h (1.2 equiv), Pd(PPh3)4 (3 mol%), K3PO4 (2.0 equiv), 1,4-dioxane,
60 °C, 12 h.
82%
TfO
HO
1
2
Scheme 1 Synthesis of 2. Reagents and conditions: i) 1 (1.0 equiv), abs.
pyridine, CH2Cl2, Tf2O (2.4 equiv), 20 °C, 20 h.
Table 2 Synthesis of Compounds 5a–h
Entry
3
Ar
3,4-(MeO)2C6H3
Yield of 5 (%)a
O
O
OTf
Ar
ArB(OH)2
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
5a 66
5b 84
5c 85
5d 92
5e 85
5f 86
5g 83
5h 73
3a–d,f–h
4-MeOC6H4
4-MeC6H4
Ph
i
TfO
Ar
4a–h
2
3-(CH2=CH)C6H4
4-HOC6H4
5-F-2-MeOC6H3
4-F3CC6H4
Scheme 2 Synthesis of 4a–h. Reagents and conditions: i) 2 (1.0 equiv),
3a–d,f–h (2.4 equiv), Pd(PPh3)4 (6 mol%), K3PO4 (3.0 equiv), 1,4-diox-
ane, 100 °C, 12 h.
3g
3h
a Yield of isolated products.
Table 1 Synthesis of Compounds 4a–h
The reaction of 5 with different arylboronic acids 3a–g
provided 1,4-diarylated 9H-fluoren-9-ones 6a–g in high
yields (Scheme 4,Table 3).20,21 These transformations were
successful even at lower temperature and with shorter re-
action time.
In conclusion, we have report the first Suzuki–Miyaura
reactions of 1,4-bis(trifluoromethylsulfonyl-oxy)-9H-fluo-
ren-9-one. These reactions provide a convenient access to a
variety of 1,4-diarylated 9H-fluoren-9-ones. The reactions
showed a very good regioselectivity in favor of the 1-posi-
tion. Palladium-catalyzed cross-coupling reactions of poly-
halogenated substrates and of bis(triflates) usually proceed
in favor of the sterically less hindered and electronically
more deficient position. The first attack of palladium(0)-
catalyzed cross-coupling reactions generally occurs at the
electronically more deficient and sterically less hindered
position.22 Position 1 of bis(triflate) 2 is sterically more hin-
Entry
3
Ar
3,4-(MeO)2C6H3
Yield of 4 (%)a
1
2
3
4
5
6
7
3a
3b
3c
3d
3f
4a 97
4b 98
4c 97
4d 98
4f 98
4-MeOC6H4
4-MeC6H4
Ph
4-HOC6H4
5-F-2-MeOC6H3
4-F3CC6H4
3g
3h
4g 86b
4h 87
a Yield of isolated products.
b DMF was used as solvent.
The Suzuki–Miyaura reaction of 2 with one equivalent
of arylboronic acids 3a–h gave 1-aryl-4-(trifluoromethane-
sulfonyloxy)-9H-fluoren-9-ones 5a–h in 66–92% yield
(Scheme 3,Table 2).17,18 The reactions proceeded by regiose-
lective attack onto the 1-position. During the optimization,
it proved to be important to perform the reaction at lower
temperature (60 °C) with lower catalyst amount as com-
pared to the synthesis of 1,4-diarylated-9H-fluoren-9-ones.
Repeatedly, both electron-rich and electron-poor arylbo-
ronic acids afforded the corresponding compounds in good
yields. The structure of 5b was independently confirmed by
X-ray crystal-structure analyses19 (Figure 3) and by 2D-
NMR measurements.
O
O
Ar
Ar
Ar1B(OH)2
3a–g
i
Ar1
6a–g
TfO
5
Scheme 4 Synthesis of 6a–g. Reagents and conditions: i) 5 (1.0 equiv),
3a–g (1.2 equiv), Pd(PPh3)4 (5 mol%), K3PO4 (2.0 equiv), 1,4-dioxane,
100 °C, 12 h.
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Table 3 Synthesis of Compounds 6a–g
Entry
5
3
Ar
Ar1
4-MeOC6H4
Yield of 6 (%)a
1
2
3
4
5
6
7
5g
5g
5b
5e
5a
5d
5c
3b
3c
3a
3b
3f
5-F-2-MeOC6H3
5-F-2-MeOC6H3
4-MeOC6H4
3-CH2=CHC6H4
3,4-(MeO)2C6H3
Ph
6a 99
6b 99
6c 97
6d 42
6e 94
6f 99
4-MeC6H4
3,4-(MeO)2C6H3
4-MeOC6H4
4-HOC6H4
3a
3g
3,4-(MeO)2C6H3
5-F-2-MeOC6H3
4-MeC6H4
6g 96b
a Yield of isolated products.
b DMF was used as solvent.
catalyst by the carbonyl group might play a role. The selec-
tivity can be explained by the highly electron-deficient na-
ture of the 1-position of the 9H-fluoren-9-one moiety (due
to the electron-withdrawing effect of the carbonyl group).
O
OTf
electronically more deficient
1
2
3
sterically less hindered
4
TfO
2
Figure 3 Possible explanation for the regioselectivity of the reactions
of bis(triflate) 2
Acknowledgement
Financial support from the Hungarian Scientific Research Fund –
OTKA (grant number PD 106244) is gratefully acknowledged. Finan-
cial support by the Alexander von Humboldt foundation (Institute
Partnership Program Debrecen-Rostock) is gratefully acknowledged.
Financial support by the European Social Fund (EFRE program) is also
acknowledged.
References and Notes
(1) Campo, M. A.; Larock, R. C. J. Org. Chem. 2002, 67, 5616; and ref-
erences cited therein.
(2) Perry, P. J.; Read, M. A.; Davies, R. T.; Gowan, S. M.; Reszka, A. P.;
Wood, A. A.; Kelland, L. R.; Neidle, S. J. Med. Chem. 1999, 42,
2679.
(3) (a) Gould, S. J.; Melville, C. R.; Cone, M. C.; Chen, J.; Carney, J. R.
J. Org. Chem. 1997, 62, 320. (b) Mal, D.; Hazra, N. K. Tetrahedron
Lett. 1996, 37, 2641; and references cited therein. (c) Cragoe, E.
J.; Marangos, P. J.; Weimann, T. R. US 6251898 BI, 2001.
(4) (a) Galasso, V.; Pichierri, F. J. Phys. Chem. A 2009, 113, 2534.
(b) Saikawa, Y.; Hashimoto, K.; Nakata, M.; Yoshihira, M.; Nagai,
K.; Ida, M.; Komiya, T. Nature (London, U.K.) 2004, 429, 363.
(c) Hashimoto, K.; Saikawa, Y.; Nakata, M. Pure Appl. Chem.
2007, 79, 507. (d) Saikawa, Y.; Moriya, K.; Hashimoto, K.;
Nakata, M. Tetrahedron Lett. 2006, 47, 2535.
Figure 2 ORTEP plot for compound 5b19
dered compared to position 4, because of the neighbour-
hood of the carbonyl group (Figure 3). Therefore, the site-
selective formation of 5a–h and 6a–g can be interpreted by
electronic reasons. In addition, chelation of the palladium
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 75–79

78
M. Sonneck et al.
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(5) (a) Fuchibe, K.; Akiyama, T. J. J. Am. Chem. Soc. 2006, 128, 1434.
(b) Morgan, L. R.; Thangaraj, K.; LeBlanc, B.; Rodgers, A.;
Wolford, L. T.; Hooper, C. L.; Fan, D.; Jursic, B. S. J. Med. Chem.
2003, 46, 4552. (c) Pan, H.-L.; Fletcher, T. L. J. Med. Chem. 1965,
8, 491. (d) Miller, E. C. Cancer Res. 1978, 38, 1479. (e) Robillard,
B.; Lhomme, M. F.; Lhomme, J. Tetrahedron Lett. 1985, 26, 2659.
(f) Fletcher, T. L.; Namkung, M. J.; Pan, H. L. J. Med. Chem. 1967,
10, 936. (g) Doisy, R.; Tang, M. S. Biochemistry 1995, 34, 4358.
(6) (a) Petry, P. J.; Read, M. A.; Davies, R. T.; Gowan, S. M.; Reszka, A.
P.; Wood, A. A.; Kelland, L. R.; Neidle, S. J. Med. Chem. 1999, 42,
2679. (b) Han, Y.; Bisello, A.; Nakamoto, C.; Rosenblatt, M.;
Chorev, M. J. Pept. Res. 2000, 55, 230. (c) Greenlee, M. L.; Laub, J.
B.; Rouen, G. P.; Dininno, F.; Hammond, M. L.; Huber, J. L.;
Sundelof, J. G.; Hammond, G. G. Bioorg. Med. Chem. Lett. 1999, 9,
322. (d) Tierney, M. T.; Grinstaff, M. W. J. Org. Chem. 2000, 65,
5355.
(7) (a) Gould, S. J.; Melville, C. R.; Cone, M. C.; Chen, J.; Carney, J. R.
J. Org. Chem. 1997, 62, 320. (b) Koyama, H.; Kamikawa, T. Tetra-
hedron Lett. 1997, 38, 3973.
(8) Burke, S. M.; Joullie, M. M. Synth. Commun. 1976, 6, 371.
(9) (a) Andrews, E. R.; Fleming, R. W.; Grisar, J. M.; Khim, J. C.;
Wentstrup, D. L.; Mayer, D. J. J. Med. Chem. 1974, 17, 882.
(b) Burke, H. M.; Joullie, M. M. J. Med. Chem. 1978, 21, 1084.
(10) Goel, A.; Chaurasia, S.; Dixit, M.; Kumar, V.; Parakash, S.; Jena,
B.; Verma, J. K.; Jain, M.; Anand, R. S.; Manoharan, S. Org. Lett.
2009, 11, 1289; and references cited therein.
(11) Reim, S.; Lau, M.; Adeel, M.; Hussain, I.; Yawer, M. A.; Riahi, A.;
Ahmed, Z.; Fischer, C.; Reinke, H.; Langer, P. Synthesis 2009, 445.
(12) For reviews of cross-coupling reactions of polyhalogenated het-
erocycles, 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.
(13) For Suzuki–Miyaura reactions of bis(triflates) from our labora-
tory, see, for example: (a) Methyl 2,5-dihydroxybenzoate:
Nawaz, M.; Ibad, M. F.; Abid, O.-U.-R.; Khera, R. A.; Villinger, A.;
Langer, P. Synlett 2010, 150. (b) Alizarin: Mahal, A.; Villinger, A.;
Langer, P. Synlett 2010, 1085 3,4. (c) Dihydroxybenzophenone:
Nawaz, M.; Khera, R. A.; Malik, I.; Ibad, M. F.; Abid, O.-U. R.;
Villinger, A.; Langer, P. Synlett 2010, 979. (d) Phenyl 1,4-dihy-
droxynaphthoate: Abid, O.-U.-R.; Ibad, M. F.; Nawaz, M.; Ali, A.;
Sher, M.; Rama, N. H.; Villinger, A.; Langer, P. Tetrahedron Lett.
2010, 51, 1541. (e) 5,10-Dihydroxy-11H-benzo[b]fluoren-11-
one: Ali, A.; Hussain, M. A.; Villinger, A.; Langer, P. Synlett 2010,
3031.
(C), 136.09 (CH), 133.49 (C), 131.48 (CH), 129.39 (C), 127.62
(CH), 125.70, 124.5, 124.38 (C), 118.85 (q, JF,C = 321.00 Hz, CF3),
118.66 (q, JF,C = 321.00 Hz, CF3). 19F NMR (282 MHz, CDCl3): δ =
–73.02 (CF3), –73.17 (CF3). IR (ATR): ν = 3104.6 (w), 3089 (w),
2921 (w), 2849 (w), 1726 (s), 1427 (s), 1224 (s), 1207 (s), 1166
(m), 1134 (s), 1104 (m), 905 (s), 886 (s), 845 (s), 812 (m), 803
(s), 762 (m), 754 (s), 598 (s) cm–1. MS (EI, 70eV): m/z = 476 (52)
[M+], 343 (13), 279 (100), 251 (49), 223 (35), 185 (14), 154 (16),
128 (33), 100 (12), 69 (43). HRMS (EI): m/z calcd for C15H6F6O7S2
[M+]: 475.94536; found: 475.94491. Anal. Calcd for C15H6F6O7S2
(476.32): C, 37.82; H, 1.27. Found: C, 37.92; H, 1.08.
(15) General Procedure for the Synthesis of 4a–h
In a pressure tube 2 (0,315 mmol), K3PO4 (3.0 equiv), Pd(PPh3)4
(6.0 mol%), and arylboronic acid (2.4 equiv) were mixed with
dry 1,4-dioxane, degassed with argon und stirred for 12 h at
100 °C. After cooling to r.t. the solution was filtered through
Celite, washed with CH2Cl2, and the filtrate was concentrated by
reduced pressure. The residue was purified by column chroma-
tography to receive the bis-substituted fluorenone 4a–h in good
yields.
(16) 1,4-Bis-(3,4-dimethoxyphenyl)-9H-fluoren-9-one (4a)
Starting with 2 (150 mg, 0.315 mmol), 3a (138 mg, 0.756 mmol,
2.4 equiv), Pd(PPh3)4 (22 mg, 0.018 mmol, 6 mol%), K3PO4 (200
mg, 0.945 mmol, 3.0 equiv), and 1,4-dioxane (5 mL). After puri-
fication by column chromatography (silica gel; heptane–EtOAc,
1:1) 4a was isolated as an orange solid (138 mg, 97%); mp 192–
194 °C. 1H NMR (300 MHz, CDCl3): δ = 7.62–7.58 (m, 1 H, ArH),
7.34 (d, J = 7.9 Hz, 1 H, ArH), 7.23 (d, J = 7.9 Hz, 1 H, ArH), 7.21–
7.17 (m, 2 H, ArH), 7.15–7.11 (m, 2 H, ArH), 7.02 (s, 2 H, ArH),
6.97 (d, J = 9.2 Hz, 2 H, ArH), 6.81–6.75 (m, 1 H, ArH), 4.00 (s,
3 H, OCH3), 3.95 (s, 3 H, OCH3), 3.94 (s, 3 H, OCH3), 3.89 (s, 3 H,
OCH3). 13C NMR (75 MHz, CDCl3): δ = 193.09 (CO), 149.35,
149.18, 149.11, 148.43, 143.72, 142.41, 141.17, 136.87 (C),
136.41 (CH), 134.80 (C), 134.20 (CH), 132.29 (C), 131.35 (CH),
130.18 (C), 128.85, 124.03, 123.30, 121.88, 121.20, 113.09,
112.26, 111.57, 110.82 (CH), 56.15, 5615 (OCH3), 56.06, 56.06
(OCH3). IR (ATR): ν = 3008 (w), 2955 (w), 2933 (w), 2905 (w),
2838 (w), 2627 (w), 2577 (w), 1701 (m), 1519 (m), 1441 (s),
1251 (s), 1222 (s), 1146 (s), 1020 (s), 746 (s) cm–1. MS (EI,
70 eV): m/z = 452 (100) [M+], 437 (9), 263 (4); 250 (4), 226 (5),
132 (4). HRMS (ESI-TOF/MS): m/z calcd for C29H24O5 [M + H]+:
453.16965; found: 453.16995; m/z calcd for C29H24O5 [M + Na]+:
475.15159; found: 475.15191.
(17) General Procedure for the Synthesis of 5a–h
(14) Synthesis of 9-Oxo-9H-fluorene-1,4-diaryl-bis(trifluoro-
methanesulfonate) (2)
In a pressure tube 2 (0.525 mmol), K3PO4 (2.0 equiv), Pd(PPh3)4
(3.0 mol%), and arylboronic acid (1.2 equiv) were mixed with
dry 1,4-dioxane, degassed with argon und stirred for 12 h at
60 °C. After cooling to r.t., the solution was filtered through
Celite, washed with CH2Cl2, and the filtrate was concentrated by
reduced pressure. The residue was purified by column chroma-
tography to receive the monosubstituted fluorenone 5a–h in
good yields.
To a CH2Cl2 solution (150 mL) of 1 (1.8 g, 8.543 mmol) was
added dry pyridine (10 mL), and the solution was cooled to
–78 °C under argon atmosphere. Then Tf2O (5.785 g, 20.503
mmol, 2.4 equiv) was added dropwise to the solution and
stirred for 20 h at r.t. After removal of the solvent with reduced
pressure H2O (100 mL) was added to the resulting oil, and the
precipitate was filtered off and recrystallized with hot heptane.
After cooling to r.t., the precipitated pure product 2 was filtered
and washed with heptane. To obtain the residual product, the
heptane was concentrated under vacuum, and the product 2
was isolated by column chromatography (silica gel; heptane–
EtOAc, 3:1) as a yellow fluffy solid (3.318 g, 82%); mp 131–
(18) 1-(4′-Hydroxyphenyl)-9-oxo-9H-fluoren-4-yl-trifluorometh-
anesulfonate (5f)
Starting with 2 (150 mg, 0.315 mmol), 3f (53 mg, 0.378 mmol,
1.2 equiv), Pd(PPh3)4 (11 mg, 0.009 mmol, 3 mol%), K3PO4 (134
mg,0.63 mmol, 2.0 equiv), and 1,4-dioxane (9 mL). After purifi-
cation by column chromatography (silica gel; heptane–EtOAc,
6:1) 5f was isolated as deep yellow solid (112 mg, 86%); mp
194–196 °C. 1H NMR (300 MHz, DMSO): δ = 9.75 (s, 1 H, OH),
7.80–7.69 (m, 2 H, ArH), 7.64 (t, J = 7.2 Hz, 2 H, ArH), 7.51 (t, J =
7.2 Hz, 1 H, ArH), 7.40 (m, 3 H, ArH), 6.83 (d, J = 8.6 Hz, 2 H,
ArH). 13C NMR (63 MHz, CDCl3): δ = 190.03 (CO), 158.21, 142.34,
1
3
133 °C. H NMR (300 MHz, CDCl3): δ = 7.88 (d, J = 7.6 Hz, 1 H,
ArH), 7.78 (d, 3J = 7.4 Hz, 1 H, ArH), 7.64 (dt, 3J = 7.6 Hz, 4J = 1.2
Hz, 1 H, ArH), 7.53 (d, 3J = 9.1 Hz, 1 H, ArH), 7.48 (dt, 3J = 7.5 Hz,
4J = 0.9 Hz, 1 H, ArH), 7.21 (d, 3J = 9.1 Hz, 1 H, ArH). 13C NMR (75
MHz, CDCl3): δ = 187.40 (CO), 144.29, 143.06, 139.32, 138.13
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M. Sonneck et al.
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141.91, 138.63, 135.74 (C), 135.49, 134.00 (CH), 133.54, 133.58
(C), 130.81, 130.81, 130.68, 127.34 (CH), 126.01 (C), 124.47,
123.03 (CH), 118.06 (q, JF,C = 320.70 Hz, CF3), 114.73, 114.73
(CH). 19F NMR (282 MHz, CDCl3): δ = –73.13 (CF3). IR (ATR): ν =
3320 (w), 3019 (w), 2920 (w), 2850 (w), 1699 (m), 1422 (s),
1205 (s), 1137 (s), 825 (s), 608 (s), 585 (s), 567 (s), 547 (m), 527
(s) cm–1. MS (EI, 70eV): m/z = 420 (28) [M+], 287 (100), 259 (22),
231 (7), 202 (22), 176 (4), 150 (2), 101 (5), 69 (8). HRMS (EI):
m/z calcd for C20H11F3O5S1 [M+]: 420.02738; found: 420.02764.
Anal. Calcd for C20H11F3O5S (420.36): C, 57.15; H, 2.64. Found: C,
57.23; H, 2.52.
(21) 1-(5′-Fluoro-2′-methoxyphenyl)-4-(4′′-methoxyphenyl)-9H-
fluoren-9-one (6a)
Starting with 5g (75 mg, 0.166 mmol), 3b (30 mg, 0.199 mmol,
1.2 equiv), Pd(PPh3)4 (9 mg, 0.008 mmol, 5 mol%), K3PO4 (67 mg,
0.315 mmol, 2.0 equiv), and 1,4-dioxane (3 mL). After purifica-
tion by column chromatography (silica gel; heptane–EtOAc, 4:1)
6a was isolated as a deep yellow solid (67 mg, 99%); mp 193–
195 °C. 1H NMR (300 MHz, CDCl3): δ = 7.58–7.52 (m, 1 H, ArH),
7.45–7.39 (m, 2 H, ArH), 7.34 (d, J = 7.9 Hz, 1 H, ArH), 7.20–7.14
(m, 3 H, ArH), 7.13–7.03 (m, 3 H, ArH), 7.01 (dd, J = 8.7, 3.1 Hz,
1 H, ArH), 6.93 (dd, J = 9.0, 4.4 Hz, 1 H, ArH), 6.84–6.78 (m, 1 H,
ArH), 3.92 (OCH3), 3.74 (OCH3). 13C NMR (75 MHz, CDCl3): δ =
(19) CCDC-1416855 contains all crystallographic details of this pub-
2
lication
and
is
available
free
of
charge
at
192.72 (CO), 159.71 (OCH3), 156.92 (d, JF,C = 238.5 Hz, CF),
4
www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered
from the following address: Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB21EZ, UK; fax:
+44(1223)336033; or deposit@ccdc.cam.ac.uk.
153.52 (d, J = 2.0 Hz, COCH3), 144.11, 137.45 (C), 136.57 (CH),
4
135.42 (d, JF,C = 3.1 Hz, CH), 134.72 (C), 134.16 (CH), 131.95,
131.61 (C), 131.25, 130.22, 130.22 (CH), 128.68 (d, J = 6.6 Hz,
2
CH), 123.94, 123.24 (CH), 117.23 (d, JF,C = 23.7 Hz, CH), 115.33
(20) General Procedure for the Synthesis of 6a–g
(d, 2JF,C = 22.6 Hz, CH), 114,29 (CH), 111.67 (d, 3JF,C = 8.2 Hz, CH),
56.33 (OCH3), 55.52 (OCH3). 19F NMR (282 MHz, CDCl3): δ =
–124.53 (CF). IR (ATR): ν = 3392 (w), 3068 (w), 3000 (w), 2957
(w), 2945 (w), 2914 (w), 2835 (w), 1704 (s), 1483 (s), 1469 (s),
1175 (s), 1026 (s), 940 (s), 764 (s) cm–1. MS (EI, 70eV): m/z = 410
(35) [M+], 379 (100), 294 (6), 190 (8), 153 (5). HRMS (EI): m/z
calcd for C27H19F1O3 [M+]: 410.13127; found: 410.13077.
In a pressure tube 5a–e,g, K3PO4 (2.0 equiv), Pd(PPh3)4 (5.0
mol%), and arylboronic acid (1.2 equiv) were mixed with dry
1,4-dioxane, degassed with argon and stirred for 12 h at 100 °C.
After cooling to r.t. the solution was filtered through Celite,
washed with CH2Cl2, and the filtrate was concentrated by
reduced pressure. The residue was purified by column chroma-
tography to receive the cross-substituted fluorenone 6a–g in
good yields.
(22) Handy, S. T.; Zhang, Y. Chem. Commun. 2006, 299.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 75–79