Synthesis of fluoren-9-ones by the palladium-catalyzed cyclocarbonylation of o-halobiaryls

Article abstract of DOI:10.1021/jo020140m

The synthesis of various substituted fluoren-9-ones has been accomplished by the palladium-catalyzed cyclocarbonylation of o-halobiaryls. The cyclocarbonylation of 4′-substituted 2-iodobiphenyls produces very high yields of 2-substituted fluoren-9-ones bearing either electron-donating or electron-withdrawing substituents. 3′-Substituted 2-iodobiphenyls afford 3-substituted fluoren-9-ones in excellent yields with good regioselectivity. This chemistry has been successfully extended to polycyclic fluorenones and fluorenones containing fused isoquinoline, indole, pyrrole, thiophene, benzothiophene, and benzofuran rings.

Full text of DOI:10.1021/jo020140m

Syn th esis of F lu or en -9-on es by th e P a lla d iu m -Ca ta lyzed
Cycloca r bon yla tion of o-Ha lobia r yls
Marino A. Campo and Richard C. Larock*
Department of Chemistry, Iowa State University, Ames, Iowa 50011
larock@iastate.edu
Received February 28, 2002
The synthesis of various substituted fluoren-9-ones has been accomplished by the palladium-
catalyzed cyclocarbonylation of o-halobiaryls. The cyclocarbonylation of 4′-substituted 2-iodobiphe-
nyls produces very high yields of 2-substituted fluoren-9-ones bearing either electron-donating or
electron-withdrawing substituents. 3′-Substituted 2-iodobiphenyls afford 3-substituted fluoren-9-
ones in excellent yields with good regioselectivity. This chemistry has been successfully extended
to polycyclic fluorenones and fluorenones containing fused isoquinoline, indole, pyrrole, thiophene,
benzothiophene, and benzofuran rings.
In tr od u ction
Resu lts a n d Discu ssion
To develop an optimum set of reaction conditions, we
first studied the palladium-catalyzed cyclocarbonylation
of commercially available 2-iodobiphenyl (1) to fluoren-
Fluoren-9-ones are of considerable interest because of
1
their important biomedical applications and their use
2
as key synthetic intermediates. The most useful syn-
9
-one (2) as our model system. All of the optimization
theses of fluorenones include Friedel-Crafts ring closures
3
reactions have been carried out using 0.25 mmol of
2-iodobiphenyl (1) in DMF (6 mL) at 110 °C for 7 h under
1 atm of carbon monoxide. It is evident from the results
listed in Table 1 that the base added and the ligand
present on palladium are critical elements in this reac-
tion. For instance, the use of chelating ligands, such as
of biarylcarboxylic acids and derivatives, intramolecular
4
[
4 + 2] cycloaddition reactions of conjugated enynes,
5
oxidation of fluorenes, and remote metalation of 2-bi-
phenylcarboxamides or 2-biphenyloxazolines.6 Fluo-
renones have also been synthesized by the palladium-
catalyzed cyclization of o-iodobenzophenones.7
1
,2-bis(diphenylphosphino)ethane (dppe), 1,1′-bis(diphe-
Our interest in fluoren-9-ones has led to the develop-
ment of a novel palladium-catalyzed cyclocarbonylation
of o-halobiaryls, which provides a highly efficient and
direct route to the fluoren-9-one skeleton, as well as other
nylphosphino)ferrocene (dppf), and 1,10-phenanthroline
gave poor yields of the desired fluoren-9-one (2) (entries
1
-3). Monodentate phosphine ligands have a major effect
8
on the yield of the cyclocarbonylation reaction. Use of the
electron-deficient ligands tris(p-fluorophenyl)phosphine
and tris(p-chlorophenyl)phosphine gave low yields of
fluoren-9-one (33% and 37%, respectively), while the more
electron-rich triphenylphosphine produced a 58% yield
related cyclic aromatic ketones (eq 1). Herein, we report
the full details of this new fluorenone synthesis.
(entries 4-6). Following this electronic trend, we ob-
served that the bulky, electron-rich ligand tricyclohexy-
lphosphine was by far the most effective ligand, produc-
ing a quantitative yield of the desired compound 2 (entry
7). Finally, we explored the effect of different bases on
the yield of fluoren-9-one and found that replacing the
(
1) (a) Tierney, M. T.; Grinstaff, M. W. J . Org. Chem. 2000, 65, 5355.
(
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. Biorg. Med. Chem. Lett. 1999, 9, 3225. (d) 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. (e) J ones, W. D.; Ciske,
F. L.; Dinerstein, R. J .; Diekema, K, A. U.S. Patent No. 6,004, 959,
unusual cesium pivalate (CsPiv) base with NaOAc or Cs
2
-
CO was detrimental to the reaction (entries 8 and 9),
3
the yield dropping from 100% to 92% and 82%, respec-
tively. The use of organic bases, such as pyridine and
diisopropylethylamine, gave negligible yields of fluoren-
1
999.
2) (a) Koyama, H.; Kamikawa, T. Tetrahedron Lett. 1997, 38, 3973.
b) Carney, J . R. J . Org. Chem. 1997, 62, 320.
3) (a) Olah, G. A.; Mathew, T.; Farnia, M.; Prakash, S. Synlett 1999,
067. (b) Yu, Z.; Velasco, D. Tetrahedron Lett. 1999, 40, 3229.
4) (a) Danheiser, R. L.; Gould, A. E.; Pradilla, R. F.; Helgason, A.
L. J . Org. Chem. 1994, 59, 5514.
5) (a) Hashemi, M.; Beni, Y. J . Chem. Res., Synop. 1999, 434. (b)
Nikalje, M.; Sudalai, A. Tetrahedron 1999, 55, 5903.
6) (a) Ciske, F.; J ones, W. D., J r. Synthesis 1998, 1195. (b) Wang,
W.; Snieckus, V. J . Org. Chem. 1992, 57, 424.
(
9
-one (entries 10 and 11).
(
(
The results of this optimization study have led to the
development of a standard set of reaction conditions
1
(
(
(7) (a) Qabaja, G.; J ones, G. B. Tetrahedron Lett. 2000, 41, 5317.
(b) Kozikowski, A. P.; Ma, D. Tetrahedron Lett. 1991, 32, 3317.
(8) For a preliminary communication, see: Campo, M. A.; Larock,
R. C. Org. Lett. 2000, 2, 3675.
(
1
0.1021/jo020140m CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/04/2002
5
616
J . Org. Chem. 2002, 67, 5616-5620

Synthesis of Fluoren-9-ones
TABLE 1. P a lla d iu m -Ca ta lyzed Cycloca r bon yla tion of 2-Iod obip h en yl (1)a
entry
base
Pd catal
ligand (mol %)
time (h)
% isolated yield of 2
1
2
3
4
5
6
7
8
9
CsPivb
CsPiv
CsPiv
CsPiv
CsPiv
CsPiv
CsPiv
NaOAc
Cs2CO3
pyridine
(i-Pr)2NEt
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PCy3)2
Pd(PCy3)2
Pd(Pcy3)2
Pd(PCy3)2
Pd(PCy3)2
dppe (5)
dppf (5)
1,10-phenanthroline (5)
(p-FC6H4)3P (10)
(p-ClC6H4)3P (10)
Ph3P (10)
d
d
d
d
d
7
7
7
7
7
7
7
7
7
46
25
<5
33
37
58 (38 )
100
92
c
84
<5
<5
1
1
0
1
24
24
a
All reactions were run with 0.25 mmol of 2-iodobiphenyl (1), 2 equiv of base, 5 mol % of Pd catalyst, and 5 or 10 mol % of an appropriate
ligand in 6 mL of DMF at 110 °C for 7 h under 1 atm of CO. CsPiv ) cesium pivalate. c The amount of DMF solvent was reduced from
mL to 1 mL. The palladium catalyst contains 10 mol % of tricyclohexylphosphine, so no further ligand was added to the reaction
b
d
6
mixture.
TABLE 2. Syn th esis of F lu or en -9-on es by th e P d -Ca ta lyzed Cycloca r bon yla tion of o-Ha lobia r ylsa
a
All reactions were carried out under the optimal conditions described in the text. b The product ratio was determined by 1H NMR
c
d
spectroscopic analysis. To keep the equivalents of aryl halide consistent, we employed 0.125 mmol of aryl dibromide 26. The reaction
period was extended to 14 h. A 42% yield of compound 47 was recovered at the end of the reaction.
e
employing 1 atm of carbon monoxide, 1 equiv of the aryl
halide (0.25 mmol), 5 mol % of commercially available
Pd(PCy ) , and 2 equiv of anhydrous cesium pivalate in
3 2
DMF (6 mL) at 110 °C for 7 h. This procedure has been
applied to a wide range of aryl halides (Table 2). 2-Io-
dobiphenyl produced fluoren-9-one in a quantitative yield
titative yield (entry 1). However, (biphenyl-2-yl)trifluo-
romethanesulfonate failed to afford the desired product.
The utility of this reaction for the synthesis of 2-sub-
stituted fluoren-9-ones was assessed by studying the
cyclocarbonylation of readily prepared9 4′-substituted
2-iodobiphenyls (entries 2-6). As indicated, the reaction
works well, tolerating both electron-donating and electron-
withdrawing substituents.
(entry 2). Under these reaction conditions, 2-bromobi-
phenyl was also converted to fluoren-9-one (2) in a quan-
J . Org. Chem, Vol. 67, No. 16, 2002 5617

Campo and Larock
We have also addressed the question of regiochemistry
in the cyclocarbonylation of 3′-substituted 2-iodobiphe-
nyls9 (entries 7 and 8). The cyclocarbonylation of the
electron-rich 2-iodo-3′-methylbiphenyl (12) and the elec-
tron-poor 3-(2-iodophenyl)benzaldehyde (15) afforded
similar 9:1 regiochemical mixtures in excellent yields. In
both cases, the predominant isomer arises from ring
closure distal to the substituent. These experimental
results seem to indicate that there is only a weak
electronic effect during the cyclization process, and that
a more important steric effect favors the less hindered
isomers 13 and 16.
[2,1-d]furan-10-one (29) (entry 14). On the other hand,
the cyclocarbonylation of 3-(2-iodophenyl)benzofuran (30),
in which ring closure takes place onto the electron-rich
benzofuran ring, produced the desired benz[b]indeno[1,2-
d]furan-6-one (31) in 81% yield (entry 15). In these
benzofuran-containing systems, cyclocarbonylation oc-
curred onto the more reactive benzofuran moiety of the
biaryl (entry 15) but failed to do so onto the less electron-
rich phenyl ring of the biaryl (entry 14). Similar electronic
effects were observed with o-halobiaryls containing either
benzothiophene or thiophene rings. For instance, 3-iodo-
2-phenylbenzothiophene19 (32) produced a 67% yield of
10-oxo-10H-benz[b]indeno[1,2-d]thiophene (33) (entry
16), while 3-(2-bromophenyl)thiophene21 (34) produced an
86% yield of indeno[2,1-d]thiophen-8-one22 (35) with
excellent C-2 regioselectivity (entry 17). It is noteworthy
that switching from the oxygen heterocycle of entry 14
to the sulfur analogue of entry 16 resulted in a substan-
tial increase in yield. In like manner, the pyrrole deriva-
tive N-(2-iodophenyl)pyrrole (36) gave a 96% yield of
pyrrolo[1,2-a]indol-9-one23 (37) (entry 18).
2
0
This cyclocarbonylation does not appear to be signifi-
cantly affected by the presence of substituents ortho to
the halo group. For example, the palladium-catalyzed
reaction of 2-iodo-3-methoxybiphenyl10 (18) produced
1
-methoxyfluoren-9-one (19) in 99% yield (entry 9).
Interestingly, this palladium-catalyzed transformation
can be readily employed on biaryl systems containing
either polycyclic or heterocyclic rings. Thus, treatment
of 9-iodo-10-phenylphenanthrene (20) with carbon mon-
oxide under our standard reaction conditions produced
indene[1,2-l]phenanthren-13-one11 (21) in 98% yield.
The yield of the palladium-catalyzed cyclocarbonylation
of o-halobiaryls containing an indole was dependent not
only on electronic effects but also on the nature of the
protecting group on the indole nitrogen. To illustrate,
1
2
Similarly, 2-bromo-1-phenylnaphthalene (22) produced
a 96% yield of benzo[c]flouren-7-one13 (23) (entry 11).
Furthermore, cyclocarbonylation of the nitrogen-contain-
2
-iodo-3-phenyl-1H-indole (38) and 3-iodo-2-phenyl-1H-
1
4
ing heterocycle 4-iodo-3-phenylisoquinoline (24) pro-
duced 11-oxoindeno[1,2-c]isoquinoline15 (25) in a 95%
yield (entry 12).
24
indole (42), both of which have unprotected nitrogens,
failed to give the desired indenoindolones under the
standard reaction conditions (entries 19 and 21). How-
ever, the N-methyl-substituted indole analogues 2-iodo-
This palladium reaction was also effective for the
double cyclocarbonylation of 2,2′′′-dibromo-p-quaterphe-
nyl16 (26) (entry 13). Under the standard reaction condi-
tions, but 14 h reaction time, substrate 26 produced the
desired [2,2′]bifluorenyl-9,9′-dione17 (27) in 87% yield.
So far, we have demonstrated the utility of this
chemistry by preparing a variety of fluorenones in high
yields with good regioselectivity from o-halobiaryls con-
taining six-membered ring aromatics, such as benzene,
naphthalene, phenanthrene, etc. (Table 2, entries 1-13).
We next turned our attention to applying this palladium
methodology to o-halobiaryls in which one of the aromatic
rings is a five-membered ring heterocycle, such as a
benzofuran, a benzothiophene, a thiophene, a pyrrole, or
an indole (entries 14-24). We began by studying the
electronic effects of the carboannulation of o-iodobiaryls
containing a benzofuran. When 3-iodo-2-phenylbenzofu-
ran18 (28) was subjected to the standard reaction condi-
tions, it failed to give any of the desired benz[b]indeno-
1
-methyl-3-phenylindole (40) and 3-iodo-1-methyl-2-
phenylindole (44) produced the desired 5-methyl-5H-
25
indeno[2,1-b]indol-6-one (41) and 5-methyl-5H-indeno-
26
[
1,2-b]indol-10-one (45) in 49% and 21% yields, respec-
tively (entries 20 and 22). In an attempt to increase the
yield of indeno[1,2-b]indol-10-one, 3-iodo-2-phenyl-1-(4-
toluenesulfonyl)indole (46) was prepared and subse-
quently cyclocarbonylated under our standard reaction
27
conditions to produce 5H-indeno[1,2-b]indol-10-one (43)
in a 45% yield (entry 23). It is worth emphasizing that
compound 46 led to the cyclocarbonylated product 43 in
which the sulfonamide functionality had been removed
under the relatively mild reaction conditions employed.
This unusual deprotection was also observed in the
cyclocarbonylation of 3-(2-bromophenyl)-1-(4-toluene-
sulfonyl)indole (47), which led to 5H-indeno[2,1-b]indol-
6
-one (39) in 55% yield (entry 24). Furthermore, 42% of
the 3-(2-bromophenyl)-1-(4-toluenesulfonyl)indole (47)
was recovered at the end of the reaction, which seems to
(
9) These starting materials were prepared using the procedure of
the following: Hart, H.; Harada, K.; Du, C. J . Org. Chem. 1985, 50,
104.
10) This starting material was prepared using the procedure of the
following: Huisgen, R.; Rist, H. Liebigs Ann. Chem. 1955, 594, 137.
11) (a) Sprinzak, Y. J . Am. Chem. Soc. 1958, 80, 5449. (b) Horspool,
3
(18) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F.; Moro, L. Synlett
1999, 9, 1432.
(19) This starting material was prepared using the procedure of the
following: Larock, R. C.; Harrison, L. W. J . Am. Chem. Soc. 1984, 106,
4218.
(20) Sauter, F.; Dzerovicz, A. Monatsh. Chem. 1969, 100, 913.
(21) Martelli, G.; Spagnolo, P.; Tiecco, M. J . Chem. Soc. B 1968, 901.
(22) MacDowell, D. W. H.; Patrick, T. B. J . Org. Chem. 1967, 32,
2441.
(
(
W. M. J . Chem. Soc. C 1971, 400. (c) Pandey, B.; Mahajan, M. P.;
Tikare, R. K.; Muneer, M.; Rath, N. P.; Kamat, P. V.; George, M. V.
Res. Chem. Intermed. 1991, 15, 271.
(
12) Wittig, G.; Hellwinkel, D. Chem. Ber. 1964, 97, 769.
(13) (a) Fu, J .; Zhao, B.; Sharp, M. J .; Snieckus, V. J . Org. Chem.
1
991, 56, 1683. (b) Harvey, R. G.; Abu-shqara, E.; Yang, C. J . Org.
Chem. 1992, 57, 6313.
14) This aryl iodide was prepared by the procedure of the follow-
ing: Huang, Q.; Hunter, J . A.; Larock, R. C. Org. Lett. 2001, 3, 2973.
15) (a) Wawzonec, S.; Stowell, J . K.; Karll, R. E. J . Org. Chem. 1966,
1, 1004. (b) Dusemund, J .; Kroeger, E. Arch. Pharm. 1987, 320, 617.
(23) (a) Mazzola, V. J .; Bernady, K. F.; Franck, R. W. J . Org. Chem.
1967, 32, 486. (b) Flitsch, W.; Kappenberg, F.; Schmitt, H. Chem. Ber.
1978, 111, 2407.
(24) This substrate was prepared by the procedure of the following:
Bocchi, V.; Palla, G. Synthesis 1982, 1096.
(25) (a) Kozikowski, A. P.; Ma, D. Tetrahedron Lett. 1991, 32, 3317.
(b) Borsche, W.; Klein, A. Liebigs Ann. Chem. 1941, 548, 64.
(26) Itahara, T.; Sakakibara, T. Synthesis 1978, 607.
(27) Eisch, J . J .; Abraham, T. Tetrahedron Lett. 1976, 1647.
(
(
3
(
16) Fujioka, Y. Bull. Chem. Soc. J pn. 1984, 57, 3494.
17) Barnett, M. D.; Daub, G. H.; Hayes, N.; Ott, D. G. J . Am. Chem.
(
Soc. 1959, 81, 4583.
5
618 J . Org. Chem., Vol. 67, No. 16, 2002

Synthesis of Fluoren-9-ones
SCHEME 1
to the acylpalladium to generate a Pd(IV) intermediate
path 1)29 or electrophilic palladation (path 2) and
30
(
subsequent elimination of HI to generate intermediate
B, and (4) reductive elimination of the ketone with
simultaneous regeneration of the Pd(0) catalyst (Scheme
1
).
Con clu sion
The palladium-catalyzed cyclocarbonylation of o-halo-
biaryls provides a short, straightforward route to a
variety of substituted fluoren-9-ones under mild reaction
conditions and short reaction times. Our success in
extending this reaction to other biaryl systems, as well
as vinylic halides, indicates its potential for the synthesis
of a wide variety of carbocyclic and heterocyclic aromatic
ketones.
indicate that removal of the sulfonamide functionality
occurs during or after the cyclocarbonylation reaction and
not before.
Exp er im en ta l Section
In summary, the synthesis of fluorenones have been
accomplished in excellent yields with good regioselectivity
by the cyclocarbonylation of o-halobiaryls containing only
six-membered ring aromatics (Table 2, entries 1-13).
Similarly, this palladium-catalyzed reaction can also be
used to prepare more strained fluorenones containing two
fused five-membered rings (Table 2, entries 14-24). In
the latter reactions, the yield of fluorenone is strongly
dependent on electronic effects. This fact can be rational-
ized in terms of the ring strain of the palladium inter-
mediates (see Scheme 1) leading to such fluorenones. The
transformation is more favorable if cyclization occurs onto
an electron-rich system, such as a benzofuran [81% yield
Gen er a l P r oced u r es. All 1H and 13C spectra were recorded
at 300 and 75.5 MHz or 400 and 100 MHz, respectively. Thin-
layer chromatography was performed using commercially
prepared 60-mesh silica gel plates (Whatman K6F), and
visualization was effected with short wavelength UV light (254
nm) and a basic KMnO
4
solution [3 g of KMnO
4
2
+ 20 g of K -
CO + 5 mL of NaOH (5%) + 300 mL of H
3
2
O]. All melting
points are uncorrected. High-resolution mass spectra were
recorded on a Kratos MS50TC double-focusing magnetic sector
mass spectrometer using EI at 70 eV.
Rea gen ts. All reagents were used directly as obtained
commercially unless otherwise noted. Anhydrous forms of
THF, DMF, diethyl ether, ethyl acetate, and hexanes were
purchased from Fisher Scientific Co. 2-Iodobiphenyl (1), 2-io-
dothioanisole, and thiophene-3-boronic acid were obtained from
Lancaster Synthesis Ltd. 2-Iodoaniline, 1,2,2-triphenyl-1-
bromoethene (48), 2-bromobiphenyl (3), 1-bromo-2-iodoben-
zene, 4-bromotoluene, 3-bromotoluene, 2-fluoroanisole, 4-bro-
moanisole, 2,5-dihydro-2,5-dimethoxyfuran, 2-bromophenyl-
boronic acid, 4,4′-diiodobiphenyl, phenyllithium, phenylacety-
lene, cesium carbonate, cesium fluoride, pivalic acid, and
triethylamine were obtained from Aldrich Chemical Co., Inc.
Bis(tricyclohexylphosphine)palladium(0) was purchased from
Strem Chemicals, Inc. Cesium pivalate was prepared according
(
[
entry 15)], a thiophene [86% yield (entry 17)], a pyrrole
96% yield (entry 18)], or an indole [97% yield based on
percent conversion (entry 24)] versus cyclization onto a
relatively unreactive phenyl group [0-67% yields (entries
1
4, 16, and 19-23)].
Finally, this chemistry can also be applied to vinylic
halides. For instance, the cyclocarbonylation of com-
mercially available 1,2,2-triphenyl-1-bromoethene (48)
led to 2,3-diphenyl-1-indenone (49) in 81% yield (eq 2).
Furthermore, 5-iodo-6-phenyl-dibenz[b,f]oxepine28 (50)
produced indeno[5,6]dibenz-[b,f]oxepin-14-one in 80%
yield (eq 3).
8
to the procedure of Larock and Campo. Compounds 1-7, 10-
5, 32, and 33 have been previously reported.8
2
Syn th esis of o-Ha lobia r yls. The following procedures are
representative of those used to prepare the o-halobiaryls:
3-(2-Br om op h en yl)th iop h en e (34). This aryl bromide was
prepared by a selective Suzuki-Miyaura cross-coupling reac-
tion as follows. 1-Bromo-2-iodobenzene (0.2829 g, 1.0 mmol),
We propose a possible reaction mechanism for this
palladium-catalyzed synthesis of fluorenones involving
(
1) oxidative addition of the aryl halide to Pd(0), (2) CO
insertion to generate the acylpalladium intermediate A,
3) either oxidative addition of the neighboring aryl C-H
(
29) Gretz, E.; Oliver, T. F.; Sen, A. J . Am. Chem. Soc. 1987, 109,
109.
30) (a) Catellani, M.; Chiusoli, G. P. J . Organomet. Chem. 1992,
(
8
(
(
28) Kitamura, T.; Takachi, H.; Taniguchi, K.; Taniguchi, H. J .
425, 151. (b) Stock, L. M.; Tse, Kwok-tuen; Vorvick, L. J .; Walstrum,
S. A. J . Org. Chem. 1981, 46, 1757.
Chem. Soc., Perkin Trans. 1 1992, 1969.
J . Org. Chem, Vol. 67, No. 16, 2002 5619

Campo and Larock
thiophene-3-boronic acid (0.140 g, 1.1 mmol), cesium fluoride
0.304 g, 2 mmol), Pd(dba) (0.0288 g, 0.05 mmol), and
triphenylphosphine (0.026 g, 0.1 mmol) in DME (5 mL) were
stirred under Ar at 90 °C for 6 h. The reaction mixture was
diluted with diethyl ether (50 mL) and washed with brine (30
(MgSO
4
) and filtered, and the solvent was removed under
(
2
reduced pressure. The residue was purified by column chro-
matography on a silica gel column.
F lu or en -9-on e (2). The reaction mixture was chromato-
graphed using 7:1 hexanes/ethyl acetate to afford 45.1 mg
mL). The organic layer was dried (MgSO
the solvent was removed under reduced pressure. The residue
was purified by column chromatography using hexanes to
4
) and filtered, and
(100%) of the indicated compound as a yellow solid: mp 82-
1
83 °C. This compound was identified by comparing the
H
1
3
NMR and C NMR spectra and melting point with an
authentic sample obtained from Aldrich Chemical Co., Inc.
Characterization of all other fluorenones prepared in this
study can be found in the Supporting Information.
afford 0.210 g (88%) of the desired compound 34 as a clear oil:
1
H NMR (CDCl
3
) δ 7.17 (td, J ) 7.6, 0.4 Hz, 1H), 7.28-7.40
13
(
1
m, 5H), 7.65 (d, J ) 8.0 Hz, 1H); C NMR (CDCl ) δ 122.6,
24.0, 124.8, 127.4, 128.7, 129.0, 131.3, 133.4, 137.6, 141.1;
3
-1
IR (CH
2
Cl
2
) 3112, 3048, 1468 cm ; HRMS m/z 237.9455 (calcd
Ack n ow led gm en t. We thank the donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, for partial support of this re-
search and Kawaken Fine Chemicals Co., Ltd., and
J ohnson Matthey Inc. for the donation of Pd(OAc)2 and
PPh3.
for C10
7
H BrS, m/z 237.9452).
The characterization of all other o-halobiaryls prepared in
this study can be found in the Supporting Information.
Gen er a l P r oced u r e for th e P d -Ca ta lyzed Cycloca r bo-
n yla tion of o-Ha lobia r yls. DMF (6 mL), Pd(PCy
3 2
) (8.4 mg,
0
.0125 mmol), anhydrous cesium pivalate (0.117 g, 0.5 mmol),
and the o-halobiaryl (0.25 mmol) were stirred under an Ar
atmosphere at room temperature for 5 min. The mixture was
flushed with CO and fitted with a CO filled balloon. The
reaction mixture was heated to 110 °C with vigorous stirring
for 7 or 14 h. The reaction mixture was then cooled to room
temperature, diluted with diethyl ether (35 mL), and washed
with brine (30 mL). The aqueous layer was reextracted with
diethyl ether (15 mL). The organic layers were combined, dried
Su p p or tin g In for m a tion Ava ila ble: Preparation and
characterization data for compounds 8, 9, 26-28, 30, 31, 35-
7, and 49-51 and copies of 1H and C NMR spectra for
13
4
compounds 8, 9, 26, 27, 30, 31, 34, 36, 38-41, 44, 46, 47, and
5
1. This material is available free of charge via the Internet
at http://pubs.acs.org.
J O020140M
5
620 J . Org. Chem., Vol. 67, No. 16, 2002