Unique effect of coordination of an alkene moiety in products on Ruthenium-catalyzed chemoselective C-H alkenylation

Article abstract of DOI:10.1021/ol802819b

Ruthenium-catalyzed alkenylation of 2'-alkoxyacetophenones with alkenylboronates provides ortho C-H alkenylation products without sacrificing an ether functional group at the other ortho position. Both excellent chemoselectivity and high product yields ar

Full text of DOI:10.1021/ol802819b

ORGANIC
LETTERS
2009
Vol. 11, No. 4
855-858
Unique Effect of Coordination of an
Alkene Moiety in Products on
Ruthenium-Catalyzed Chemoselective
C-H Alkenylation
Satoshi Ueno,† Takuya Kochi,‡ Naoto Chatani,† and Fumitoshi Kakiuchi*,‡
Department of Chemistry, Faculty of Science and Technology, Keio UniVersity,
3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan, and Department
of Applied Chemistry, Faculty of Engineering, Osaka UniVersity, 2-1 Yamadaoka,
Suita, Osaka 565-0871, Japan
kakiuchi@chem.keio.ac.jp
Received December 7, 2008
ABSTRACT
Ruthenium-catalyzed alkenylation of 2′-alkoxyacetophenones with alkenylboronates provides ortho C-H alkenylation products without sacrificing
an ether functional group at the other ortho position. Both excellent chemoselectivity and high product yields are achieved with an aryloxo
ruthenium complex. The effective suppression of the C-O bond cleavage was attained by coordination of the alkenyl moiety in the C-H
alkenylation product to the ruthenium center.
Chelation-assisted transition-metal-catalyzed carbon-carbon
bond formation via cleavage of unreactive C-H bonds has
been an attractive research subject1 because excellent regi-
oselectivity can be achieved for a variety of transformations
such as alkylation,2 alkenylation,3 arylation,4,5 and acylation.6
These methods have also become powerful tools for regi-
oselective introduction of functional groups in modern
organic synthesis. Chelation-assisted control of regioselec-
tivity in catalytic reactions has not only been applied for
functionalization of C-H bonds but also for that of other
bonds including C-O and C-N bonds.7,8
However, chemoselective functionalization of C-H bonds
over those other cleavable bonds has not been a trivial task.
For example, the coupling reaction of 2′-methoxyacetophe-
none (1) with triethoxyvinylsilane catalyzed by RuH2-
(CO)(PPh3)3 (2) affords only 11% of the C-H/olefin
coupling product as a result of competing cleavage of the
C-O bond (eq 1),2d which is considered thermodynamically
easier to cleave than the C-H bond.7b
(2) (a) Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.;
Sonoda, M.; Chatani, N. Nature 1993, 366, 529. (b) Kakiuchi, F.; Sekine,
S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N.; Murai, S. Bull.
Chem. Soc. Jpn. 1995, 68, 62. (c) Harris, P. W. R.; Woodgate, P. D. J.
Organomet. Chem. 1997, 530, 211. (d) Sonoda, M.; Kakiuchi, F.; Chatani,
N.; Murai, S. Bull. Chem. Soc. Jpn. 1997, 70, 3117. (e) Lenges, C. P.;
Brookhart, M. J. Am. Chem. Soc. 1999, 121, 6616. (f) Thalji, R. K.; Ahrendt,
K. A.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2001, 123, 9692.
(g) Thalji, R. K.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2004,
126, 7192. (h) Jun, C.-H.; Moon, C. W.; Hong, J.-B.; Lim, S.-G.; Chung,
K.-Y.; Kim, Y.-H. Chem. Eur. J. 2002, 8, 485.
† Osaka University.
‡ Keio University.
(1) (a) Kakiuchi, R.; Murai, S. Top. Organomet. Chem. 1999, 3, 47. (b)
Miura, M.; Nomura, M. Top. Curr. Chem. 2002, 219, 211. (c) Ritleng, V.;
Sirlin, C.; Pfeffer, M. Chem. ReV. 2002, 102, 1731. (d) Kakiuchi, F.; Murai,
S. Acc. Chem. Res. 2002, 35, 826. (e) Labinger, J. A.; Bercaw, J. E. Nature
2002, 417, 507. (f) Kakiuchi, F.; Chatani, N. AdV. Synth. Catal. 2003, 345,
1077. (g) Kakiuchi, F.; Chatani, N. Top. Organomet. Chem. 2004, 11, 45.
(h) Godula, K.; Sames, D. Science 2006, 312, 67.
10.1021/ol802819b CCC: $40.75
Published on Web 01/22/2009
2009 American Chemical Society

Then the catalysts for the C-H alkenylation were screened
to improve both the chemoselectivity and the activity (Table
1).
Table 1. Screening of Catalysts for C-H Selective
Alkenylationa
In this communication, we report a highly C-H selective
alkenylation of o-alkoxyacetophenones such as 1 with
alkenylboronates using ruthenium catalysts. The unique effect
of an introduced alkenyl substituent in the product on the
chemoselectivity is also described.
Previously we reported RuH2(CO)(PPh3)3-catalyzed ary-
lation of o-alkoxyphenyl ketones with arylboronates via C-O
bond cleavage.7 When aryl ketone 1 was subjected to the
conditions with phenylboronic ester 3a, 2′,6′-diphenylac-
etophenone 6a was obtained in quantitative yield (Scheme
1) and no monophenylated products, 4a and 5a, were
a Reaction conditions: ketone 1 (0.5 mmol), ꢀ-styrylboronate 3c (0.6
mmol), pinacolone (0.5 mL), catalyst (0.02 mmol of Ru), reflux, 10 h.
Scheme 1. Coupling of 1 with Aryl- and Alkenylboronates
Initially, catalysts that have been used for C-H function-
alization were examined for this reaction. Although
Ru(CO)2(PPh3)3 exhibited excellent catalytic activity for
addition of C-H bonds to alkenes,2a,b the C-H alkenylation
product was obtained in low yield (entry 2 in Table 1). The
alkenylation using other known ruthenium catalysts also
resulted in poor yields or no product formation (entries 3-5).
However, when Ar-Ru-OAr′ complex 7, synthesized by
reaction of 1 with 2′-(4-methylphenoxy)pivalophenone,7b was
used as a catalyst for 10 h, C-H alkenylation product 4c
was obtained in 76% yield (entry 6). Catalyst 7 showed both
higher activity and higher chemoselectivity compared to
those of 2 (entry 1), and only a trace amount of 5c was
detected by GC/MS. Catalytic activities of rhodium com-
plexes2e,f were also examined, but the alkenylation reaction
did not take place (entries 7 and 8).
observed throughout the reaction. Thus, both C-H and
C-OMe bonds were phenylated efficiently under the reaction
conditions. In contrast to the phenylation, however, alkeny-
lation of 1 proceeds preferentially at C-H bonds to afford
monoalkenylated products. The reaction of 1 with 2-prope-
nylboronic ester 3b afforded monoalkenylation product 4b
in 58% yield. In this case, the corresponding C-O alkeny-
lation product 5b was formed only in 6% yield. The reaction
with ꢀ-styrylboronate 3c for 20 h also provided the corre-
sponding C-H alkenylation product 4c in 76% yield along
with 4% yield of 5c.
(4) Representative reviews, see: (a) Satoh, T.; Miura, M.; Nomura, M.
J. Organomet. Chem. 2002, 653, 161. (b) Catellani, M. Synlett 2003, 298.
(c) Campeau, L.-C.; Fagnou, K. Chem. Commun. 2006, 1253. (d) Daugulis,
O.; Zaitsev, V. G.; Shabashov, D.; Pham, Q. N.; Lazareva, A. Synlett 2006,
3382. (e) Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200. (g) Alberico, D.;
Scott, M. E.; Lautens, M. Chem. ReV. 2007, 174. (h) Ackermann, L. Synlett
2007, 507. (i) Pascual, S.; de Mendoza, P.; Echavarren, A. M. Org. Biomol.
Chem. 2007, 5, 2727.
(3) (a) Hong, P.; Cho, B. R.; Yamazaki, H. Chem. Lett. 1979, 339. (b)
Halbritter, G.; Knoch, F.; Wolski, A.; Kisch, H. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1603. (c) Kakiuchi, F.; Yamamoto, Y.; Chatani, N.; Murai,
S. Chem. Lett. 1995, 681. (d) Satoh, T.; Nishinaka, Y.; Miura, M.; Nomura,
M. Chem. Lett. 1999, 615. (e) Kakiuchi, F.; Uetsuhara, T.; Tanaka, Y.;
Chatani, N.; Murai, S. J. Mol. Catal. A: Chem. 2002, 182-183, 511. (f)
Lim, S.-G.; Lee, J. H.; Moon, C. W.; Hong, J.-B.; Jun, C.-H. Org. Lett.
2003, 5, 2759. (g) Tsukada, N.; Mitsuboshi, T.; Setoguchi, H.; Inoue, Y.
J. Am. Chem. Soc. 2003, 125, 12102. (h) Kuninobu, Y.; Tokunaga, Y.;
Kawata, A.; Takai, K. J. Am. Chem. Soc. 2006, 128, 202. (i) Ueno, S.;
Chatani, N.; Kakiuchi, F. J. Org. Chem. 2007, 72, 3600. (j) Matsuura, Y.;
Tamura, M.; Kochi, T.; Sato, M.; Chatani, N.; Kakiuchi, F. J. Am. Chem.
Soc. 2007, 129, 9858.
(5) (a) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.; Murai, S. J. Am. Chem.
Soc. 2003, 125, 1698. (b) Kakiuchi, F.; Matsuura, Y.; Kan, S.; Chatani, N.
J. Am. Chem. Soc. 2005, 127, 5936.
(6) (a) Moore, E. J.; Pretzer, W. R.; O’Connell, T. J.; Harris, J.;
LaBounty, L.; Chou, L.; Grimmer, S. C. J. Am. Chem. Soc. 1992, 114,
5888. (b) Chatani, N.; Fukuyama, T.; Kakiuchi, F.; Murai, S. J. Am. Chem.
Soc. 1996, 118, 493. (c) Imoto, S.; Uemura, T.; Kakiuchi, F.; Chatani, N.
Synlett 2007, 170.
(7) (a) Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani, N.; Murai, S. J. Am.
Chem. Soc. 2004, 126, 2706. (b) Ueno, S.; Mizushima, E.; Chatani, N.;
Kakiuchi, F. J. Am. Chem. Soc. 2006, 128, 16516.
(8) Ueno, S.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2007, 129,
6098.
856
Org. Lett., Vol. 11, No. 4, 2009

With catalyst 7 in hand, C-H selective alkenylation of
2′-alkoxyacetophenone with several alkenylboronates was
investigated to determine the generality of the reaction (Table
2).
and methoxy groups on the aryloxy group afforded the
products with 75% and 77% yields. On the other hand, in
the case of 2′-(4-fluorophenoxy)acetophenone, a longer
reaction period was required to attain a comparable yield
(entry 8). Introduction of bulkier substituents such as
isopropoxy and tert-butyldimethylsiloxy groups as the alkoxy
group on the substrate also retarded the reaction, but the
reaction for 20 h offered the desired C-H alkenylation
products in 91% and 75% yields, respectively.
Table 2. C-H Selective Alkenylation of
2′-Alkoxyacetophenones with Alkenylboronatesa
The sharp contrast in the product selectivity between
phenylation and alkenylation and the selective formation of
monoalkenylation products were also observed for the
reaction of acetophenone (8) (Scheme 2). As reported for
Scheme 2. Selective Monoalkenylation of Acetophenone
the ruthenium-catalyzed arylation, diphenylation product 6a
was obtained as a major product for the reaction of 8 with
3a.5b On the other hand, the reaction of 8 with 2-propenyl-
boronate 3b afforded the corresponding 1:1 coupling product
5b as a major product.3i
To investigate the origin of the product selectivity toward
monoalkenylated aryl ketones, a stoichiometric reaction of
ruthenium complex 2 with aryl ketones and alkenylboronate
3b was examined in an NMR tube (Scheme 3). To conduct
a Reaction conditions: aromatic ketone (0.5 mmol), alkenylboronate (0.6
mmol), pinacolone (0.5 mL), ruthenium complex 7 (0.02 mmol), reflux, 10
or 20 h. b B ) B(OCH2CMe2CH2O).
Scheme 3. Stoichiometric Reactions of Complex 9
The C-H alkenylation with various alkenylboronates
provides quite high yields of the desired products. It is
noteworthy that this alkenylation of alkoxyacetophenones
generally presents yields markedly higher than those of our
previously reported C-H alkenylation of aromatic ketones.3i
For example, the alkenylation of 1 with 2-propenylboronic
ester 3b offered desired product 4b in 88% yield (entry 1).
The reaction with 1-propenylboronate (3d, E:Z ) 39:61)
afforded propenylation product 4d in 82% yield with the E:Z
isomer ratio of 95:5 (entry 2). Use of R- and ꢀ-arylvinyl-
boronates is also effective for the alkenylation, and the
products were obtained in good yields (entries 3-5).
Aromatic ketones bearing aryloxy groups instead of methoxy
groups similarly reacted to give the corresponding C-H
alkenylation products, and electronically diverse substituents
(OMe, Me, and F groups) on the aryloxy group remained in
the coupling products (entries 6-8). The reactions of the
substrates with electron-donating substituents such as methyl
the reaction under mild reaction conditions, complex 2 was
converted to the activated ruthenium complex Ru(CO)(PPh3)3
(9) by reduction of 2 with trimethylvinylsilane.2b,9 A reaction
(9) A reaction of 2 with trimethylvinylsilane affords dehydrogenated
ruthenium complex, which shows high activity for C-H bond cleavage. See,
also ref 7b.
Org. Lett., Vol. 11, No. 4, 2009
857

of complex 9 with aryloxyacetophenone 10 at room tem-
perature resulted in complete conversion to hydrido complex
11, and apparently the ortho C-H bond of 10 was oxida-
tively added to the ruthenium. No Ar-Ru-OR type com-
plex, which should be formed by oxidative addition of the
C-O bond,7b was observed even after 2 days at room
temperature. Subsequently, 10 equiv of alkenylboronate 3b
was added to the resulting mixture, and heated at 80 °C.
The 31P NMR spectra of this reaction mixture indicated that
the alkenylation occurred, but most of complex 11 was
converted to ruthenium complex 12 bearing the product as
a ligand. When acetophenone (8) was used for a similar
NMR study without using pinacolone,10 the corresponding
complex bearing the monoalkenylation product (13) was
formed.
31P NMR spectrum of 13, two phosphine signals were
similarly observed at δ 46.2 and 46.6, and in the H NMR
spectrum, signals corresponding to the alkenyl hydrogens
1
of 13 appeared at δ -0.50 and 3.50. These signals on the
1
31P and H NMR spectra resemble those of the related 2′-
vinylacetophenone ruthenium complex 14, synthesized and
structurally characterized by Weber and co-workers.12 Re-
ported results of X-ray diffraction analysis performed on
complex 14 show that both the ketone carbonyl and the
alkene moieties coordinate to the ruthenium center. On the
basis of these NMR spectra, the alkene moieties in complex
12 and 13 are considered to coordinate to the ruthenium
center in a similar manner to 14.
The origin of the suppression of the second alkenylation
can be explained on the basis of the observations described
above. The π-acidic alkene moiety in the monoalkenylation
product coordinates to the metal as well as the carbonyl
oxygen in a bidentate fashion during the reaction. The
coordination places the C-O or C-H bond at the other ortho
position far from the metal center and prevents the bond
cleavage from occurring while the monoalkenylation product
is on the metal.
The structures of complexes 12 and 13 were characterized
1
by 31P and H NMR spectroscopy (Table 3). The 31P NMR
1
Table 3. 31P{1H} and H NMR Chemical Shifts of
Alkene-Coordinated Ruthenium Complexesa
In conclusion, we report that ruthenium-catalyzed alkeny-
lation of 2′-alkoxyacetophenones with alkenylboronates
provides ortho C-H alkenylation products without sacrific-
ing an ether functional group at the other ortho position.
Particularly, both excellent chemoselectivity and high product
yields are achieved with aryloxo complex 7. The unique
effect of the alkene moiety in the C-H alkenylation product
to suppress the second alkenylation by its coordination to
the metal center is also observed.
Acknowledgment. This work was supported, in part, by
a Grant-in-Aid for Scientific Research on Priority Areas
“Advanced Molecular Transformations of Carbon Resources”
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan and by The Science Research Promotion
Fund. S.U. acknowledges the Research Fellowship of J.S.P.S.
for Young Scientist and the Global COE Program “Global
Education and Research Center for Bio-Environmental
Chemistry” of Osaka University.
Supporting Information Available: General experimental
details and characterization data. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL802819B
a Multiplicities are in parentheses. b Only chemical shifts of vinyl
hydrogens are listed. c 1H NMR spectrum not measured due to the presence
of a large amount of pinacolone.
(10) In the absence of pinacolone, acetophenone (8) not only func-
tions as a substrate, but as a hydride acceptor. See ref 5b for further informa-
tion.
(11) 1H NMR signals of 12 were not fully assigned, because the presence
of an excess amount of pinacolone impeded the characterization.
(12) Lu, P.; Paulasaari, J.; Jin, K.; Bau, R.; Weber, W. P. Organome-
tallics 1998, 17, 584.
spectrum of 12 showed that the presence of two phosphine
ligands (δ 43.7 and 44.6) bound to the ruthenium.11 In the
858
Org. Lett., Vol. 11, No. 4, 2009