Palladium-catalyzed dehydroarylation of triarylmethanols and their coupling with unsaturated compounds accompanied by C-C bond cleavage

Article abstract of DOI:10.1021/jo049031t

Triarylmethanols are effectively dehydroarylated and reacted with some unsaturated compounds by using an appropriate palladium catalyst system such as Pd(OAc)₂-P(1-Nap)₃ (1-Nap = 1-naphthyl) to give the corresponding arenes and hydro

Full text of DOI:10.1021/jo049031t

SCHEME 1
P a lla d iu m -Ca ta lyzed Deh yd r oa r yla tion of
Tr ia r ylm eth a n ols a n d Th eir Cou p lin g w ith
Un sa tu r a ted Com p ou n d s Accom p a n ied by
C-C Bon d Clea va ge
Yoshito Terao, Michiyo Nomoto, Tetsuya Satoh,
Masahiro Miura,* and Masakatsu Nomura
SCHEME 2
SCHEME 3
Department of Applied Chemistry, Faculty of Engineering,
Osaka University, Suita, Osaka 565-0871, J apan
miura@chem.eng.osaka-u.ac.jp
Received J une 9, 2004
Abstr a ct: Triarylmethanols are effectively dehydroarylated
and reacted with some unsaturated compounds by using an
appropriate palladium catalyst system such as Pd(OAc)2-
P(1-Nap)3 (1-Nap ) 1-naphthyl) to give the corresponding
arenes and hydroarylation products, respectively, along with
diaryl ketones.
Transition metal catalyzed organic reactions involving
the cleavage of C-C single bonds have recently attracted
much attention.1 Although the cleavage is energetically
unfavorable, various unique catalytic transformations
including ring-expansion or ring-contraction, fragmenta-
tion, and coupling with another molecule can be realized
when appropriately designed. Among the most promising
strategies of C-C bond activation is to utilize the
proximate effect by coordination of a functional group in
a given substrate to the metal center of a catalyst. As
such an example, we recently reported that a number of
R,R-disubstituted arylmethanols react with aryl chlorides
and bromides to give biaryls via cleavage of the sp2-sp3
C-C bond (Scheme 1, path b),2 in which â-carbon
elimination in a Pd(II) alcoholate intermediate is involved
as the key step.3,4
phines, P(1-Nap)3 (1-Nap ) 1-naphthyl),5,6 triarylmetha-
nols selectively undergo dehydroarylation to give arenes
together with diaryl ketones (Scheme 2).
In this case, the aryl-aryl coupling hardly occurs even
in the presence of excess aryl halides. Thus, a new
mechanistic aspect appears to be involved in the catalytic
C-C cleavage. Furthermore, it has been revealed that
the hydroarylation of some unsaturated compounds oc-
curs by addition of them to the reaction system. These
new findings are reported herein.
As reported previously, treatment of triphenylmetha-
nol (1a ) with bromobenzene (2a ) (3 equiv) in the presence
of Pd(OAc)2-4PCy3 (5 mol %) and Cs2CO3 (3 equiv) as
catalyst and base, respectively, in refluxing o-xylene gave
biphenyl (3a ) and benzophenone (4) in good yields
(Scheme 3).
Using P(o-Tolyl)3 in place of PCy3 as ligand gave a
reduced yield of 3a , while 4 was formed in a quantitative
yield. The coupling product 3a was formed in only 16%
yield, when P(1-Nap)3 was employed. In the latter two
reactions, no other coupling products derived from 1a and
2a were observed, although a considerable amount of the
ligand phenylated was detected in the case of P(o-
Tolyl)3.2b Thus, it was conceived that dehydroarylation
to give benzene along with 4 predominantly took place,
especially when P(1-Nap)3 was used.
While this reaction occurs in competition with the
coupling via cleavage of the o-C-H bond (path a), it can
proceed selectively when a relatively bulky ligand such
as PCy3 (Cy ) cyclohexyl) is employed. In the course of
a further investigation into the reaction, it has been
found that using one of the most bulky aromatic phos-
(1) For reviews see: (a) Crabtree, R. H. Chem. Rev. 1985, 85, 245.
(b) Rybtchinski, B.; Milstein, D. Angew. Chem., Int. Ed. 1999, 38, 870.
(c) Murakami, M.; Ito, Y. Top. Organomet. Chem. 1999, 3, 97. (d) J un,
C.-H.; Moon, C. W.; Lee, D.-Y. Chem. Eur. J . 2002, 8, 2423. (e)
Perthuisot, C.; Edelbach, B. L.; Zubris, D. L.; Simhai, N.; Iverson, C.
N.; Mu¨ller, C.; Satoh, T.; J ones, W. D. J . Mol. Catal. A: Chem. 2002,
189, 157. (f) Catellani, M. Synlett 2003, 298.
(2) (a) Terao, Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J .
Am. Chem. Soc. 2001, 123, 10407. (b) Terao, Y.; Wakui, H.; Nomoto,
N.; Satoh, T.; Miura, M.; Nomura, M. J . Org. Chem. 2003, 68, 5236.
(3) Pd-catalyzed arylative coupling of alcohols via â-C elimination:
(a) Cyclobutanols: Matsumura, S.; Maeda, Y.; Nishimura, T.; Uemura,
S. J . Am. Chem. Soc. 2003, 125, 8862 and references therein. (b)
3-Allen-1-ols: Oh, C. H.; Yung, S. H.; Bang, S. Y.; Park, D. I. Org.
Lett. 2002, 4, 3325.
(4) Other Pd-catalyzed reactions involving â-C elimination via Pd-
(II) alcoholate: (a) Account; Nishimura, T.; Uemura, S. Synlett 2004,
201. (b) Harayama, H.; Kuroki, T.; Kimura, M.; Tanaka, S.; Tamaru,
Y. Angew. Chem., Int. Ed. Engl. 1997, 36, 2352. (c) Park S.-B.; Cha, J .
K. Org. Lett. 2000, 2, 147. (d) Okumoto, H.; J innai, T.; Shimizu, H.;
Harada, Y.; Mishima, H.; Suzuki, A. Synlett 2000, 629.
Consequently, the reaction of (1-naphthyl)diphenyl-
methanol (1b) was examined with P(1-Nap)3 as ligand
(Table 1). When 1b was treated with 2a (1.2 equiv),
(5) Bartik, T.; Himmler, T. J . Organomet. Chem. 1985, 293, 343.
(6) Application of P(1-Nap)3 in the palladium-catalyzed reaction of
organic halides: (a) Shaw, B. L.; Perera, S. D.; Staley, E. A. Chem.
Commun. 1998, 1361. (b) Goossen, L. J . Chem. Commun. 2001, 669.
(c) Ziegler, C. B., J r.; Heck R. F. J . Org. Chem. 1978, 43, 2941. (d)
Wagaw, S.; Rennels, R. A.; Buchwald, S. L. J . Am. Chem. Soc. 1997,
119, 8451. For the reaction of allyl compounds see: (e) Friess, B.; Cazes,
B.; Gore, J . Bull. Soc. Chim. Fr. 1992, 129, 273. (f) Ollivier, J .; Dorizon,
P.; Priras, P. P.; de Meijere, A.; Salau¨n, J . Inorg. Chim. Acta 1994,
222, 37. (g) Bienayme´ H. Tetrahedron Lett. 1994, 35, 7383.
10.1021/jo049031t CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/02/2004
6942
J . Org. Chem. 2004, 69, 6942-6944

TABLE 1. Rea ction of (1-Na p h th yl)Meth a n ols w ith or
w ith ou t Ar yl Br om id esa
TABLE 2. Deh yd r oa r yla tion of Tr ia r ylm eth a n ols 1d -j
% yieldb
bromide
(equiv)
time
(h)
entry
alcohol
3
7
1c
2
3
1b
1b
1b
1b
1b
1c
1c
2a (1.2)
2a (0.2)
3
3
36
2
2
24
24
6
0
88
98
98
94
0
4
2b (1)
2b (1)
0d
95
5e
6
90
94
7
2a (0.2)
0
a
Reaction conditions: [1]:[Pd(OAc)2]:[P(1-Nap)3] ) 0.5:0.05:0.1
(in mmol), [ArBr] ) [Cs2CO3], in refluxing o-xylene (2.5 mL) under
b
N2. GLC yield based on the amount of 1 used. Benzophenone (4)
was formed quantitatively in entries 1-5. c [1]:[Pd(OAc)2] ) 0.5:
d
0.025 (in mmol). Biphenyl (6%) was formed. e PCy3 was used in
place of P(1-Nap)3.
naphthalene (7) (88%) was produced along with 1-phen-
ylnaphthalene (3b) (6%) and 4 (>98%), indicating that
dehydroarylation occurred preferentially as expected
(entry 1).
Arene 7 was obtained exclusively with a reduced
amount of 2a (0.2 equiv) (entry 2). While the reaction
proceeded without addition of 2a and the base, a longer
reaction time was required to obtain a high yield of 7
(entry 3). In the reaction with 4-bromobiphenyl (2b) (1
equiv) in place of 2a , 1-(biphenyl-4-yl)naphthalene (3c)
was not detected and a minor amount of biphenyl (6%)
was formed (entry 4). This indicates that a part of the
bromide was reduced during the reaction. The role of aryl
bromides for the acceleration of dehydroarylation is
discussed later. In harmony with the results in Scheme
3, 3b was obtained selectively in good yield by using PCy3
in the reaction with 1b (entry 5). 2-(1-Naphthyl)-2-
propanol (1c) could also afford 7 by using P(1-Nap)3
(entries 6 and 7).
a
Condition A: [1]:[Pd(OAc)2]:[P(1-Nap)3]:[PhBr]:[Cs2CO3] ) 0.5:
0.05:0.1:0.1:0.1, in refluxing o-xylene (2.5 mL) under N2. Condition
B: [1]:[Pd(OAc)2]:[P(1-Nap)3]:[PhBr]:[Cs2CO3] ) 0.5:0.025:0.05:
b
0.05:0.05, in refluxing o-xylene (2.5 mL) under N2. GLC yield
based on the amount of 1 used. c Without addition of PhBr and
d
Cs2CO3. Naphthalene (7) was also formed quantitatively.
SCHEME 4
Various triarylmethanols 1d -j were also subjected to
the dehydroarylation. The results are summarized in
Table 2. As can be seen, the selectivity with respect to
which C-C bond is broken in each substrate is consistent
with that in the aryl-aryl coupling with use of PCy3 with
the exception of 1j.2b Thus, the aryl groups having an
ortho substituent in the alcohols are selectively elimi-
nated (entries 1 and 2). From 9-arylxanthen-9-ols 1h and
1i were produced only xanthone (12) (entries 5-7). The
reaction of 9-phenylfluoren-9-ol (1j) unexpectedly gave
fluorenone (13) as the single product. This contrasts with
the reaction with use of PCy3, in which ring-opening
aryl-aryl coupling took place.
reaction of B with 1 may give ArPd(II) alcoholate C,
which may lead to homocoupling of the aryl group.
However, the formation of biaryl was not detected or
negligible in each reaction. Thus, alcoholate C, if formed,
undergoes mainly protonolysis to give A before â-carbon
(7) P(1-Nap)3 may form
a palladacycle with Pd(II) species ac-
companied by cleavage of a peri C-H bond of the naphthyl groups.6a
The cyclization process is considered to be reversible under the present
conditions.
It seems to be reasonable to consider that the above
dehydroarylation procceds via â-carbon elimination in Pd-
(II) alcoholate intermediate A, which is formed by the
reaction of 1 with Pd(II) species in the medium, to give
ArPd(II) intermediate B (Scheme 4).7
(8) A reviewer has kindly suggested a possibility that intermediate
B reversibly reacts with the ketone moiety liberated to regenerate A.
Such a nucleophilic arylation of ketones with ArPd(II) species is known
to occur intramolecularly: (a) Quan, L. G.; Lamrani, M.; Yamamoto,
Y. J . Am. Chem. Soc. 2000, 122, 4827. (b) Sole´, D.; Vallverdu´, L.;
Solans, X.; Font-Bard´ıa, M.; Bonjoch, J . J . Am. Chem. Soc. 2003, 125,
1587. Thus, the selective formation of 13 as well as 12 under the
present conditions (Table 2) could be attributed to the reversibility.
This reacts with 1 to give arene with the regeneration
of A according to the reverse arrow.8 Alternatively, the
J . Org. Chem, Vol. 69, No. 20, 2004 6943

TABLE 3. Hyd r oa r yla tion of Un sa tu r a ted Com p ou n d s
14a -c w ith Alcoh ols 1a -c,h ,i,k ,l
elimination occurs to form Ar2Pd. Anyway, the steric
bulkiness of the ligand seems to make the protonolysis
of B and/or C to A favorable. Added aryl bromide appears
to oxidize adventitiously formed Pd(0) species to form
ArPd(II)Br (B, X ) Br), which then undergoes protonoly-
sis directly or via C (see entry 4 in Table 1).
It may be expected that intermediate B or C reacts
with unsaturated compounds, which allows hydroaryla-
tion of them via intermediate D. Thus, we next undertook
the hydroarylation. It was found that diphenylacetylene
(14a ) and 1-substituted 3-phenyl-2-propen-1-ones 14b
and 14c are suitable substrates for the reaction as
described below.
The reaction of 1a with 14a (1.5 equiv) under the
conditions employed for the dehydroarylation of aryl-
diphenylmethanols gave 1,1,2-triphenylethene (15) in
73% yield (Table 3, entry 1). (E)-1-(1-Naphthyl)-1,2-
diphenylethene (16) was produced in good yields by using
1b, 1c, and 1i. (entries 2-6). Especially, xanthenol 1i
afforded the best yield of 16 within 1.5 h with use of 5
mol % of Pd (entry 6). The exclusive formation of the (E)-
isomer is consistent with the mechanism shown in
Scheme 4. As expected, 9-(4-methoxyphenyl)- and 9-(4-
trifluoromethylphenyl)xanthen-9-ols (1k and 1l) afforded
the corresponding (E)-1-aryl-1,2-diphenylethenes (17 and
18) selectively (entries 9 and 10). While the reaction of
1k with 4-octyne gave a low yield of coupling product (ca.
15% by GC-MS), the alcohol efficiently reacted with
benzylideneacetophenone (14b) to afford the correspond-
ing conjugate addition product 19 (entry 11). Benzyli-
deneacetone (14c) could also be used, although the
product yield was moderate (entry 12). The reaction of
1i with 14b gave compound 21 in good yield (entry 13).
It should be noted that in the above hydroarylation
reactions, the contamination of phenyl group in bromide
2a was, if any, negligible. One of the possible reasons
for this is that ArPd(II)Br is relatively less reactive
toward 14 compared with the corresponding oxygen-
coordinated species under the conditions and preferen-
tially undergoes protonolysis. While further studies are
required to reveal the detailed mechanism, the consid-
eration may be partly supported by the fact that in the
reaction of 1h with 14a in the presence of 1-bromonaph-
thalene (1c) (Table 3, entry 8), the naphthyl group was
transformed to naphthalene and did not couple with 14a .
In summary, we have demonstrated that the pal-
ladium-catalyzed dehydroarylation of triarylmethanols
effectively occurs by using the bulky ligand P(1-Nap)3.
This reaction may be utilized as a method for the de-
protection of diaryl ketones, especially with an ortho-
substituted phenyl group as the sacrifice. It has also been
shown that the hydroarylation of some unsaturated com-
pounds with the alcohols is possible. While the hydroaryl-
ation of alkynes and R,â-unsaturated compounds under
palladium catalysis has been carried out with arylmetal
reagents and proton sources9-11 or aryl halides and
a
Condition A: [1]:[Pd(OAc)2]:[P(1-Nap)3]:[PhBr]:[Cs2CO3] ) 0.5:
0.05:0.1:0.1:0.1, in refluxing o-xylene (2.5 mL) under N2. Condition
B: [1]:[Pd(OAc)2]:[P(1-Nap)3]:[PhBr]:[Cs2CO3] ) 0.5:0.025:0.05:
0.05:0.05, in refluxing o-xylene (2.5 mL) under N2. GLC yield
b
based on the amount of 1 used. Value in parentheses is the yield
after chromatographic purification. c Without addition of PhBr and
d
Cs2CO3. 1-Bromonaphthalene was used in place of PhBr.
hydrogen sources,12 the present reaction represents the
first example of that involving â-carbon elimination.
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid from the Ministry of Education, Culture,
Sports, Science and Technology, J apan.
Su p p or tin g In for m a tion Ava ila ble: Standard experi-
mental procedure and characterization data of products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O049031T
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6944 J . Org. Chem., Vol. 69, No. 20, 2004