Rhodium-catalyzed ring opening of benzocyclobutenols with site-selectivity complementary to thermal ring opening

Article abstract of DOI:10.1021/ja309013a

A rhodium catalyst induced ring opening of benzocyclobutenols with selective cleavage of the C(sp²)-C(sp³) bond adjacent to the hydroxyl group. The site-selectivity markedly contrasted with that of their thermal ring-opening reaction. The rhodium-catalyzed ring opening led to the development of a new alkyne insertion reaction constructing a dihydronaphthalene framework.

Full text of DOI:10.1021/ja309013a

Communication
pubs.acs.org/JACS
Rhodium-Catalyzed Ring Opening of Benzocyclobutenols with Site-
Selectivity Complementary to Thermal Ring Opening
Naoki Ishida, Shota Sawano, Yusuke Masuda, and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Katsura, Kyoto 615-8510, Japan
S
* Supporting Information
a
Table 1. Ring Opening of 1a
ABSTRACT: A rhodium catalyst induced ring opening of
benzocyclobutenols with selective cleavage of the C(sp2)−
C(sp3) bond adjacent to the hydroxyl group. The site-
selectivity markedly contrasted with that of their thermal
ring-opening reaction. The rhodium-catalyzed ring open-
ing led to the development of a new alkyne insertion
reaction constructing a dihydronaphthalene framework.
b
yields/%
entry
conditions
2a
3a
1
2
3
4
toluene, 100 °C
NaOH aq, dioxane, rt
86
87
0
0
arbon−carbon single bonds are thermodynamically stable
Cand kinetically inert in general. Nevertheless, transition
metal catalysis in organic synthesis has made a significant
progress so that a number of unique synthetic reactions in
which a carbon−carbon single bond is cleaved in preference to
other seemingly more reactive functional groups have emerged
in the past decade.1
c
hν, benzene, rt
30
14
0
5 mol % of Rh(acac)(CH2CH2)2
10 mol % of P(t-Bu)3, toluene, 100 °C
2.5 mol % of [Rh(OH)(cod)]2, toluene, 100 °C
2.5 mol % of [Rh(OH)(cod)]2, dioxane, 100 °C
2.5 mol % of [Rh(OH)(cod)]2,
12 mol % of IPr, toluene, 100 °C
74
5
6
7
0
20
80
89
74
0
Cyclobutenes undergo thermal and photochemical ring-
opening reactions with cleavage of the C(sp3)−C(sp3) bond to
form 1,3-dienes.2 An oxy substituent, in particular an anionic
one, accelerates the ring-opening reaction and directs its own
rotational direction (torquoselectivity).3 Analogously, benzocy-
clobutenols undergo ring opening with cleavage of the C(sp3)−
C(sp3) bond, which we refer as the “distal” bond (Scheme 1).
Heating,4 photo irradiation,5 and treatment with a base6−8
induce their ring opening to furnish reactive o-quinodi-
methanes,9 which subsequently engage in [4 + 2] cycloaddition
with dienophiles.10 This type of [4 + 2] cycloaddition has
served for the synthesis of natural products11 and functional
materials.12 On the other hand, we previously reported a
rhodium-catalyzed addition reaction of phenylboronic acid
onto 6-chlorobenzocyclobutenone.13 The resulting rhodium
tert-benzocyclobutenolate intermediate underwent ring opening
with preferential cleavage of the “proximal” bond rather than
the distal bond. This preliminary finding led us to examine
rhodium catalysts for ring opening of benzocyclobutenols in
detail. Herein, we report a rhodium-catalyzed ring-opening
a
Benzocyclobutenol 1a (0.20 mmol), solvent (1.0 mL). See
b
c
Supporting Information for details. Isolated yields. NMR yield.
Scheme 2. Plausible Mechanism
reaction of benzocyclobutenols, which is characterized by the
site-selectivity complementary to those of the conventional
ring-opening reactions, that is, by exclusive cleavage of the
proximal C(sp2)−C(sp3) bond.14 A new alkyne insertion
reaction was also developed based on this unique ring opening
(Scheme 1).15
Initially, ring opening of 1a was examined under various
reaction conditions (Table 1). Simple heating of 1a in toluene
at 100 °C selectively gave 2a in 86% yield (entry 1). Addition of
a base accelerated the ring-opening reaction, which occurred
even at room temperature to produce only 2a again (entry 2).
Irradiation with UV light (254 nm) also afforded 2a albeit in
30% yield along with a number of unidentified byproducts
(entry 3). On the other hand, when 1a was heated at 100 °C in
Scheme 1. Ring Opening of Benzocyclobutenols
Received: September 11, 2012
Published: October 9, 2012
© 2012 American Chemical Society
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dx.doi.org/10.1021/ja309013a | J. Am. Chem. Soc. 2012, 134, 17502−17504

Journal of the American Chemical Society
Communication
a
Scheme 3. Rhodium-Catalyzed Reaction of 2a with 3-Hexyne
(4a)
Table 2. Insertion of Alkynes into Benzocyclobutenols
toluene in the presence of Rh(acac)(CH2CH2)2 (5 mol %) and
P(t-Bu)3 (10 mol %),13 a mixture of 2a and 3a was formed with
the latter predominating by 84:16 (entry 4). Remarkably, 3a
was exclusively obtained in 89% yield when [Rh(OH)(cod)]2
(2.5 mol %) was used in toluene in the absence of any
additional ligand (entry 5). No 2-methylbenzophenone (2a)
was detected in the reaction mixture even by GC analysis. The
product selectivity was also subject to a solvent and an additive.
The reaction in dioxane under otherwise identical conditions
afforded a mixture of 2a and 3a with a ratio of 21:79 (entry 6).
Only 2a was formed upon addition of the 1,3-bis(2,6-
diisopropylphenyl)imidazol-2-ylidene (IPr) to [Rh(OH)-
(cod)]2 (entry 7).
Thus, it proved possible to completely shift the site of ring
opening from the distal C(sp3)−C(sp3) bond to the proximal
C(sp2)−C(sp3) bond. We propose the following mechanistic
explanation (Scheme 2). Initially, rhodium hydroxide deprot-
onates 1a to form rhodium(I) benzocyclobutenolate A. It is
assumed that the arene moiety intramolecularly coordinates to
the rhodium center in an η2 fashion, as is the case with
Rh(PEt3)2(OCPh3).16 This coordination would assist the
migration of the sp2 carbon onto the rhodium in preference
to the sp3 carbon migration, thereby releasing the structural
strain and forming a carbonyl group. The superior π-accepting
character of the 1,5-cyclooctadiene ligand would facilitate the
η2-binding of the arene moiety. The generated arylrhodium
species B undergoes protonation with 1a to form the benzyl
phenyl ketone (3a) together with regeneration of the rhodium
alkoxide A. On the other hand, the ionic character of the
rhodium benzocyclobutenolate is augmented in dioxane to
partially cause anion-induced thermal ring opening. The
strongly binding IPr ligand would occupy the fourth binding
site of rhodium of A to discourage the η2-coordination of the
arene, thus suppressing the formation of 3a.
Next, we examined an alkyne insertion reaction by carrying
out the rhodium-catalyzed ring opening of 1a in the presence of
3-hexyne (Scheme 3). The reaction mixture containing 3-
hexyne was heated in toluene at 100 °C for 4 h, and subsequent
chromatographic isolation furnished dihydronaphthalene 5a in
85% yield. Mechanistically, the ring-opened arylrhodium(I)
intermediate B undergoes not protonation but 1,2-addition
across the carbon−carbon triple bond. The resulting
alkenylrhodium(I) C adds back onto the carbonyl group in a
6-exo mode. Alkoxyrhodium(I) D is then protonated with 1a to
give dihydronaphthalene 5a with regeneration of rhodium
benzocyclobutenolate A. Overall, the alkyne 4a is inserted into
the proximal C(sp2)−C(sp3) bond of 1a, producing a formal [4
+ 2] cycloadduct with site-selectivity which is different from
that available via o-quinodimethane intermediates.9,10
a
Reaction conditions: benzocyclobutenol 1 (0.20 mmol), alkyne 4
(1.1 equiv), [Rh(OH)cod]2 (2.5 mol %), toluene (1.0 mL), 100 °C, 4
h. Isolated yields. Regioisomeric ratios in parentheses.
b
The six-membered ring forming reaction proceeded
successfully with various combinations of benzocyclobutenols
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dx.doi.org/10.1021/ja309013a | J. Am. Chem. Soc. 2012, 134, 17502−17504

Journal of the American Chemical Society
Communication
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol.
5, pp 999−1035.
1 and alkynes 4 to demonstrate the generality of the unique
site-selectivity of insertion (Table 2). Even the ortho-substituted
derivative 1d showed the same site-selectivity to give
dihydronaphthalene 5d in 79% yield (entry 3). The presence
of electron-donating methoxy and -withdrawing trifluoromethyl
groups on the benzene ring scarcely affected the reaction
(entries 4 and 5). A chloro group remained intact (entry 6).
High regioselectivities were observed with unsymmetrical
alkynes bearing one aryl or vinyl substituent (entries 8 and
9), which was located at the β-position (next to the hydroxyl
group) of the resulting dihydronaphthalene skeleton. On the
other hand, the unsymmetrical dialkyl-substituted alkyne 4e
gave a mixture of regioisomers with the ratio of 75:25 (entry
10). The regioselectivities observed with these unsymmetrical
alkynes were similar to those of intermolecular 1,2-addition of
o-carbonyl-substituted arylrhodium species onto alkynes.17 An
unprotected hydroxyl group and a pyridine moiety were
allowed in the alkynes (entries 11 and 12). Insertion of terminal
alkynes such as phenylethyne failed due to rapid self-
oligomerization.
(4) (a) Kitaura, Y.; Matsuura, T. Tetrahedron 1971, 27, 1597.
(b) Arnold, B. J.; Sammes, P. G.; Wallace, T. W. J. Chem. Soc., Perkin
Trans. 1 1974, 409.
(5) Caubere, P.; Derozier, N.; Loubinoux, B. Bull. Soc. Chim. Fr.
1971, 302.
(6) Cava, M. P.; Muth, K. J. Am. Chem. Soc. 1960, 82, 652.
(7) For proximal cleavage of benzocyclobutenols possessing an
anion-stabilizing group at the 6-position, see: (a) Stevens, R. V.;
Bisacchi, G. S. J. Org. Chem. 1982, 47, 2396. (b) Gokhale, A.; Schiess,
P. Helv. Chim. Acta 1998, 81, 251.
(8) For proximal cleavage of benzocyclobutenols coordinating to
chromium(0) in an η6-fashion, see: Brands, M.; Wey, H. G.;
Butenschon, H. J. Chem. Soc., Chem. Commun. 1991, 1541.
̈
(9) For reviews on o-quinodimethanes, see: (a) Oppolzer, W.
Synthesis 1978, 793. (b) Charlton, J. L.; Alauddin, M. M. Tetrahedron
1987, 43, 2873. (c) Segura, J. L.; Martín, N. Chem. Rev. 1999, 99,
3199.
(10) (a) Arnold, B. J.; Sammes, P. G. J. Chem. Soc., Chem. Commun.
1972, 30. (b) Arnold, B. J.; Sammes, P. G.; Wallace, T. W. J. Chem.
Soc., Perkin Trans. 1 1974, 415. (c) Choy, W.; Yang, H. J. Org. Chem.
1988, 53, 5796. See also ref 9.
(11) (a) Kametani, T.; Katoh, Y.; Fukumoto, K. J. Chem. Soc., Perkin
Trans 1 1974, 1712. (b) Fitzgerald, J. J.; Michael, F. E.; Olofson, R. A.
Tetrahedron Lett. 1994, 35, 9191. (c) Kraus, G. A.; Zhao, G. Synlett
1995, 541. (d) Takemura, I.; Imura, K.; Matsumoto, T.; Suzuki, K.
Org. Lett. 2004, 6, 2503.
In conclusion, we have demonstrated that [Rh(OH)(cod)]2
induces ring opening of benzocyclobutenols with site-selective
cleavage of the proximal C(sp2)−C(sp3) bond. The site-
selectivity is complementary to that of the conventional ring-
opening reactions. A new alkyne insertion reaction constructing
a dihydronaphthalene framework was developed based upon
the unique ring opening.
(12) (a) Tomioka, H.; Ichihashi, M.; Yamamoto, K. Tetrahedron Lett.
1995, 36, 5371. (b) Zhang, X.; Foote, C. S. J. Org. Chem. 1994, 59,
5235.
ASSOCIATED CONTENT
* Supporting Information
(13) Matsuda, T.; Makino, M.; Murakami, M. Bull. Chem. Soc. Jpn.
2005, 78, 1528.
■
S
(14) The proximal C(sp2)−C(sp3) bond of benzocyclobutenols was
cleaved also in the palladium-catalyzed reaction of benzocyclobutenols
with bromobenzenes: Chtchemelinine, A.; Rosa, D.; Orellana, A. J.
Org. Chem. 2011, 76, 9157.
Experimental procedures and spectral data for new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(15) Intramolecular alkene insertion into a proximal C(sp2)−C(sp2)
bond of benzocyclobutenones has been recently reported: Xu, T.;
Dong, G. Angew. Chem., Int. Ed. 2012, 51, 7567.
AUTHOR INFORMATION
Corresponding Author
murakami@sbchem.kyoto-u.ac.jp
■
(16) (a) Zhao, P.; Incarvito, C. D.; Hartwig, J. F. J. Am. Chem. Soc.
2006, 128, 3124. For rhodium-catalyzed reactions of tert-alcohols
through β-aryl eliminations, see: (b) Nishimura, T.; Katoh, T.;
Hayashi, T. Angew. Chem., Int. Ed. 2007, 46, 4937. (c) Uto, T.;
Shimizu, M.; Ueura, K.; Tsurugi, H.; Satoh, T.; Miura, M. J. Org. Chem.
2008, 73, 298. (d) Seiser, T.; Cathomen, G.; Cramer, N. Synlett 2010,
1699.
(17) (a) Shintani, R.; Okamoto, K.; Hayashi, T. Chem. Lett. 2005, 34,
1294. (b) Matsuda, T.; Makino, M.; Murakami, M. Chem. Lett. 2005,
34, 1416.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported in part by a Grant-in-Aid for Scientific
Research on Innovative Areas “Molecular Activation Directed
toward Straightforward Synthesis” and Grant-in-Aid for
Scientific Research (B) from MEXT and The Asahi Glass
Foundation.
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