Palladium-catalyzed reaction of 2-hydroxy-2-methylpropiophenone with aryl bromides: A unique multiple arylation via successive C-C and C-H bond cleavages

Article abstract of DOI:10.1021/ja0477874

2-Hydroxy-2-methylpropiophenone undergoes a unique multiple arylation via C-C and C-H bond cleavages upon treatment with excess aryl bromides in the presence of a palladium catalyst to give 1,1,2,2-tetraarylethanes and 4,4-diaryl-1-phenylisochroman-3-ones. Copyright

Full text of DOI:10.1021/ja0477874

Published on Web 06/25/2004
Palladium-Catalyzed Reaction of 2-Hydroxy-2-methylpropiophenone with Aryl
Bromides: A Unique Multiple Arylation via Successive C-C and C-H Bond
Cleavages
Hiroyuki Wakui, Satoshi Kawasaki, Tetsuya Satoh, Masahiro Miura,* and Masakatsu Nomura
Department of Applied Chemistry, Faculty of Engineering, Osaka UniVersity, Suita, Osaka 565-0871, Japan
Received April 17, 2004; E-mail: miura@chem.eng.osaka-u.ac.jp
Transition metal-catalyzed organic reactions via cleavage of
Scheme 1
Scheme 2
1
2
C-H and C-C bonds have recently attracted much attention from
atom-economic and chemoselective points of view, and various
catalytic processes involving different modes to activate the
relatively inert bonds have been developed. We reported that
phenols, aromatic ketones, and benzamides undergo regioselective
aromatic arylation via C-H bond cleavage upon treatment with
aryl halides in the presence of palladium catalysts.3 Coordination
of the functional groups to arylpalladium(II) intermediates is the
key to the reaction. The arylation of tert-benzyl alcohols was found
to occur not only via C-H bond cleavage but also via C-C bond
cleavage (Scheme 1), and the systematic studies of factors affecting
the reaction revealed that the C-C bond cleavage predominates
a-d
4,5
by using an appropriate ligand such as PCy
new findings that a structurally related substrate to the alcohols,
-hydroxy-2-methylpropiophenone (1), undergoes unexpected suc-
3
.
We now report our
2
cessive multiple arylation via C-C and C-H bond cleavages upon
3
treatment with excess bromobenzenes (Scheme 2), which appears
Table 1. Reaction of 2-Hydroxy-2-methylpropiophenone (1) with
Aryl Bromides (2)a
to proceed through an intriguing catalytic sequence.
% yieldb
When ketone 1 (0.5 mmol) was treated with bromobenzene (2a)
(
2.5 mmol) in the presence of Pd(OAc)
mmol), and Cs CO (2.5 mmol) in refluxing o-xylene for 20 h,
,1,2,2-tetraphenylethane (3a) was formed in 62% yield (calculated
2 3
(0.025 mmol), PPh (0.15
entry
bromide
ligand
PPh3
P(t-Bu)3
P(p-tolyl)3
PCy3
P(t-Bu)3
P(t-Bu)3
P(t-Bu)3
time (h)
3
4
2
3
1
2
3
4
5
6
7
2a
2a
2b
2b
2b
2c
2d
20
6
12
6
6
6
62
>98 (79)
74
78
>98 (73)
c
1
13 (9)
as 2 × [3a]/[1a], see below) as the single major product (Scheme
c
c
2
2
and entry 1 in Table 1). Use of p-bromotoluene (2b) in place of
a gave 1,1,2,2-tetra(p-tolyl)ethane (3b) (74%) (entry 3), suggesting
45 (33)
(40)
d
(80)
(71)
that the four aryl groups come from the bromide. In this case, P(p-
tolyl) was used as ligand for preventing the contamination of the
phenyl group in PPh
not only 3b was formed in a quantitative yield, but also another
structurally attractive compound, that is, 1-phenyl-4,4-di(p-tolyl)-
6
3
6
a
3
. It was of interest that with P(t-Bu)
3
as ligand
2 2 3
Reaction conditions: [1]:[2]:[Pd(OAc) ]:[ligand]:[Cs CO ] ) 0.5:2.5:
b
0.025:0.15:2.5 (in mmol), in refluxing o-xylene under N2. GLC yield
based on amount of 1a used. Value in parentheses indicates yield after
purification. c Not detected. d Detected (ca. 5%) by GC-MS.
7
-methylisochroman-3-one (4b), was produced in substantial yield
entry 5). Similarly, the reaction with p-bromoanisole (2c) gave
ethane 3c and isochromanone 4c (entry 6). Using 2a and p-
bromofluorobenzene (2d) in the presence of P(t-Bu) , ethanes 3a
(
Scheme 3
3
and 3d were formed in good yields as expected, but the yields of
the corresponding isochromanones were low (entries 2 and 7). The
yield of 4a could not be improved with an increased amount of 2a
(3.5 mmol), while that of 3a was quantitative. The structure of 4a
was verified by X-ray analysis (see Supporting Information). It is
noted that no products via the reaction similar to Scheme 1 were
detected in these reactions.
It seems reasonable to consider that the initial R-ketol rearrange-
ment is catalyzed by ArPd(II) species, which is followed by the
first arylation (Scheme 4). It should be described that the reaction
of 1-benzoyl-1-hydroxycyclohexane (9) with 2b under the same
conditions used for the reactions in Scheme 2 gave compound 10,
which is a monoarylation product at the 2-position of 9, in 59%
To rationalize the formation of tetraarylethanes 3 and isochro-
manones 4, we assumed the sequence illustrated in Scheme 3. The
first step involves the R-ketol rearrangement of 1 to 5, that is 1,2-
methyl-migration.7 The successive catalytic R,R-diarylation of
1f,8
ketone 5 to give 6 takes place in a usual manner. The reverse
R-ketol rearrangement of 6 occurs to give ketol 7. The diarylmethyl
moiety in 7 dimerizes to give 3 accompanied by formation of
diketone 8, and the triarylation of 8 leads to 4.
9
yield as a sterically stable, single isomer (Scheme 5). This implies
that 10 is formed by R-ketol rearrangement to 11 and R-arylation
to 12,7 which may occur as in Scheme 4. The product appears to
b,c
8658
9
J. AM. CHEM. SOC. 2004, 126, 8658-8659
10.1021/ja0477874 CCC: $27.50 © 2004 American Chemical Society

C O MMU N I C A T I O N S
Scheme 4
Scheme 5
In summary, we have described a unique reaction for the effective
production of 1,1,2,2-tetraarylethanes by a 2:4 coupling under
palladium catalysis that involves C-C bond cleavages. An interest-
ing arylative cyclization involving C-H bond cleavage to give
substituted isochroman-3-ones has also been shown. These unprec-
edented reactions seem to provide useful information for designing
new catalytic cycles that occur via C-C and C-H cleavages.
Acknowledgment. This work was supported by a Grant-in-Aid
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
Supporting Information Available: Standard experimental pro-
cedures and characterization data for new compounds: This material
is available free of charge via the Internet at http://www.pubs.acs.org.
References
Scheme 6
(
1) For reviews, see: (a) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997,
97, 2879-2932. (b) Kakiuchi, F.; Murai, S. Top. Organomet. Chem. 1999,
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3
(
d) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826-834. (e)
Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. ReV. 2002, 102, 1731-1769.
(
f) Miura, M.; Nomura, M. Top. Curr. Chem. 2002, 219, 211-241. (g)
Kakiuchi, F.; Chatani, N. AdV, Synth. Catal. 2003, 345, 1077-1101.
2) For reviews, see: (a) Crabtree, R. H. Chem. ReV. 1985, 85, 245-269. (b)
Rybtchinski, B.; Milstein, D. Angew. Chem., Int. Ed. 1999, 38, 870-
(
8
1
2
83. (c) Murakami, M.; Ito, Y., Top. Organomet. Chem. 1999, 3, 97-
29. (d) Jun, C.-H.; Moon, C. W.; Lee, D.-Y. Chem. Eur. J. 2002, 8,
422-2428. (e) Catellani. M. Synlett 2003, 298-313.
(
3) (a) Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1740-1742. (b) Kawamura, Y.; Satoh, T.; Miura,
M.; Nomura, M. Chem. Lett. 1999, 961-962. (c) Terao, Y.; Kametani,
Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. Tetrahedron 2001, 57,
Scheme 7
5
967-5974. (d) Okazawa, T.; Satoh, T.; Miura, M.; Nomura, M. J. Am.
Chem. Soc. 2002, 124, 5286-5287. (e) Dyker, G.; Heiermann, J.; Miura,
M.; Inoh, J.; Pivsa-Art, S.; Satoh, T.; Nomura, M. Chem. Eur. J. 2000, 6,
3426-3433.
(
4) (a) Terao, Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J. Am. Chem.
Soc. 2001, 123, 10407-10408. (b) Terao, Y.; Wakui, H.; Nomoto, N.;
Satoh, T.; Miura, M.; Nomura, M. J. Org. Chem. 2003, 68, 5236-5243.
5) Palladium-catalyzed arylative coupling of alcohols via â-carbon elimina-
tion. Cyclobutanols: Matsumura, S.; Maeda, Y.; Nishimura, T.; Uemura,
S. J. Am. Chem. Soc. 2003, 125, 8662-8669. 3-Allen-1-ols: Oh, C. H.;
Yung, S. H.; Bang, S. Y.; Park, D. I. Org. Lett. 2002, 4, 3325-3327.
(
be relatively less reactive under the conditions, so that there is very
little further arylation. 1-Hydroxy-1,1,3-triphenyl-2-propanone (13),10
which is a model substrate of mono-arylation product of 5, was
also treated with 2b. As expected, 1,2-diphenyl-1,2-di(p-tolyl)ethane
(6) (a) Goodson, F. E.; Wallow, T. I.; Novak, B. M. J. Am. Chem. Soc. 1997,
119, 12441-12453. (b) Grushin, V. V. Organometallics 2000, 19, 1888-
1900.
(7) (a) Brunner, H.; St o¨ hr, F. Eur. J. Org. Chem. 2000, 2777-2786 and
references therein. R-Ketol rearrangement of 1-benzoyl-1-cycloalkanols:
(
b) Brunner, H.; Kagan, H. B.; Kreutzer, G. Tetrahedron Assymetry 2001,
(14) was obtained in quantitative yield as a mixture of two possible
1
2, 497-499. (c) Elphimoff-Felkins, I.; Tchoubar, B. Compt. Rend. 1953,
2
36, 1978-1980.
diastereomers (ca. 3:2) together with benzil (15) (Scheme 6). These
compounds may be formed via intermediary products 16 and 17
as in Scheme 3. As a relevant reaction to the transformation of 17
to 14 and 15 as well as that of 7 to 3 and 8, Ru-catalyzed
dimerization of diphenylmethanol to give 3a has been reported.11
In the present reaction, a diarylmethylpalladium(II) species, which
is formed via â-carbon elimination of the corresponding palladium-
(8) For a review, see: Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003,
36, 234-245.
(9) Two-dimensional NMR analysis indicated that it has a cis arrangement.
MOPAC PM-3 caluculation suggested the coumpound is more stable than
its trans isomer by 1.9 kcal/mol.
(10) Kohler, E. P.; Barnes, R. P. J. Am. Chem. Soc. 1934, 56, 211-214. The
NMR spectra indicated that it contained an isomer, 2-hydroxy-1,2,3-
triphenyl-1-propanone (20%), which is not a matter in this case.
(11) Peri-Bar, I.; Buchman, O.; Blum, J. Tetrahedron Lett. 1977, 1443-1446.
(12) In the present case, aryl bromide may act as oxidant.
possible sequences is as follows:
3
c,4b
12
One of the
(II) alcoholate, seems to participate.
It was also confirmed that treatment of diketone 8 with 2b
afforded isochromanone 4b in 46% yield (Scheme 7). Although
the precise mechanism for the cyclization accompanied by C-H
bond cleavage along with lactonization is not clear at the present
stage, it seems to involve an electrophilic character since the
reactions with 2b and 2c, each of which has an electron-donating
substituent, afforded relatively good yields of 4, while in the case
(
13) A palladium enolate may be involved as the key intermediate. One of the
possible sequences is as follows:
1
3
of 2d, nonproductive consumption of 8 predominated.
Thus, the reactions in Schemes 5-7 seem to be satisfactorily in
harmony with our hypothesis shown in Scheme 3, although further
studies are required to establish the details.
JA0477874
J. AM. CHEM. SOC.
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VOL. 126, NO. 28, 2004 8659