Regioselective alkenylation of aromatic ketones with alkenylboronates using a RuH2(CO)(PPh3)3 catalyst via carbon - Hydrogen bond cleavage

Article abstract of DOI:10.1021/jo070182g

(Chemical Equation Presented) The ruthenium-catalyzed alkenylation of C-H bonds with alkenylboronates has been explored for a series of aromatic ketones. The coupling reaction of pivalophenone (1) with 2-isopropenyl-5,5-dimethyl[1,3, 2]dioxaborinane (2) g

Full text of DOI:10.1021/jo070182g

ruthenium-catalyzed ortho selective arylation of arylpyridines
with arylstannanes.6a We subsequently reported the RuH2(CO)-
(PPh3)3-catalyzed arylation of aromatic ketones with aryl-
boronates.7a,b To explore the synthetic utility of our protocol of
C-H/organoboronate coupling to a variety of organoboronates,
we examined the ruthenium-catalyzed alkylation of aromatic
ketones using alkenylboronates. We wish to report a new aspect
of the regioselective alkenylation of aromatic ketones with
alkenylboronates via cleavage of C-H bonds using RuH2(CO)-
(PPh3)3 as a catalyst.
Regioselective Alkenylation of Aromatic Ketones
with Alkenylboronates Using a RuH2(CO)(PPh3)3
Catalyst via Carbon-Hydrogen Bond Cleavage
Satoshi Ueno,‡ Naoto Chatani,‡ and Fumitoshi Kakiuchi*,†
Department of Chemistry, Faculty of Science and Technology,
Keio UniVersity, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama
223-8522, Japan, and Department of Applied Chemistry,
Faculty of Engineering, Osaka UniVersity, Suita,
Osaka 565-0871, Japan
In our previous studies, which focused on the ruthenium-
catalyzed arylation of aromatic ketones with arylboronates (Ar-
B(OR)2), the use of the acceptor of the H-B(OR)2 species was
found to be essential for attaining high yields in the coupling
reaction. To this end, we discovered that pinacolone can function
as an efficient acceptor of the HB(OR)2 species. As a result of
this finding, pinacolone was used as a solvent in this study.
kakiuchi@chem.keio.ac.jp
ReceiVed February 1, 2007
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The ruthenium-catalyzed alkenylation of C-H bonds with
alkenylboronates has been explored for a series of aromatic
ketones. The coupling reaction of pivalophenone (1) with
2-isopropenyl-5,5-dimethyl[1,3,2]dioxaborinane (2) gave the
corresponding isopropenylation product in 73% yield. In the
case of the reaction of a sterically congested alkenylboronate,
such as 2-methylpropenylboronate (8), the yield was de-
creased slightly. When â-styrylboronates were used, the
corresponding coupling products were obtained in good
yields. The reaction of acetophenone with R-styrylboronate
afforded the corresponding 1:1 coupling product, exclusively.
In recent years, considerable attention has been directed
toward the selective functionalization of unreactive carbon-
hydrogen bonds with the aid of a transition metal catalyst.1 To
date, several types of transformations of C-H bonds have been
reported. Among these, C-C bond formations such as alkyla-
tion,2 alkenylation,3 acylation,4 and arylation5-7 have widely
been studied. In these reactions, three types of protocols have
been published. The first is the addition of C-H bonds to C-C
multiple bonds;2-4 the second involves coupling with organo-
halides;5 and the third involves coupling using organometallic
compounds.6,7 The former two protocols have been the subject
of extensive investigations. The third has great potential as a
synthetic tool, but this is still at a primitive stage of development.
Only two types of coupling reagents have appeared in the
literature.6,7 For example, Oi and co-workers reported the
† Keio University.
‡ Osaka University.
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J. A.; Bercaw, J. E. Nature 2002, 417, 507-514. (e) Miura, M.; Nomura,
M. In Cross-Coupling Reactions; Springer: Berlin, 2002; pp 211-241. (f)
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Kakiuchi, F.; Chatani, S. In Topics in Organometallic Chemistry; Bruneau,
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(b) Chen, X.; Li, J.-J.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem.
Soc. 2006, 128, 78-79.
(7) (a) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.; Murai, S. J. Am. Chem.
Soc. 2003, 125, 1698-1699. (b) Kakiuchi, F.; Matsuura, Y.; Kan, S.;
Chatani, N. J. Am. Chem. Soc. 2005, 127, 5936-5945. (c) Park, Y. J.; Jo,
E-A.; Jun, C.-H. Chem. Commun. 2005, 1185-1187. (d) Chen, X.; Goodhue,
C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128, 12634-12635. (e) Pastine,
S. J.; Gribkov, D. V.; Sames, D. J. Am. Chem. Soc. 2006, 128, 14220-
14221.
10.1021/jo070182g CCC: $37.00 © 2007 American Chemical Society
Published on Web 04/04/2007
3600
J. Org. Chem. 2007, 72, 3600-3602

TABLE 1. Ruthenium-Catalyzed Alkenylation of Pivalophenone
the addition of the C-H bond to the C-C double bond in 2, in
the case of the reaction using isopropenyltrimethylsilane, where
the addition of the C-H bond across the C-C double bonds
gave the corresponding alkylation product exclusively.2b,d
Several alkenylboronates can be applied to the present new
alkenylation reaction. The results for the reaction using 1 are
listed in Table 1. The reaction with 1-propenylboronate (6),
which was used as a mixture of E- and Z-isomers (E:Z ) 39:
61), afforded the coupling product 7 in 58% yield as a single
isomer (entry 1). To obtain information concerning the reaction
pathway of the stereochemical isomerization of the double bond,
the following two control experiments were conducted. When
a pinacolone solution of 6 was refluxed in the absence of
ruthenium catalyst 3, no change in the stereochemistry of 6 was
observed even after 20 h. In the second experiment, a solution
of 6 was heated at 60 °C for 5 min in the presence of catalyst
3. In this case, the Z-isomer of 6 was completely converted to
the corresponding E-isomer. Thus, the ruthenium catalyst also
participated in the isomerization of the stereochemistry of the
alkenylboronate 6. The reaction of 2-butenylboronate (E:Z )
18:82) gave a mixture of E- and Z-isomers in the ratio of 65:35
(entry 2). Several styrylboronates having electron-donating or
-withdrawing groups can also be used in this coupling reaction
(runs 3-6). In these cases, (E)-â-styryl derivatives were obtained
as a sole product. Oi and co-workers reported that the alkenyl-
ation of aryloxazolines with (E)-â-styrylbromide using [RuCl2-
(η6-C6H6)]2 catalyst provided a mixture of stereo- and regio-
isomers via â-hydride elimination from the styryl-ruthenium
intermediate.6 Interestingly, however, in our case, no isomer-
ization of the stereo- and regiochemistry was observed, although
the reaction proceeded through a similar styryl-ruthenium
intermediate. From these results, we propose that C-C bond
formation, that is, the reductive elimination step, is faster than
the â-hydride elimination from the styryl-ruthenium intermedi-
ate. In the case of a sterically congested alkenylboronate, such
as 2-methyl-1-propenylboronate 8, the product yield was
decreased to 37% (entry 7). When the coupling reaction of 1 (2
equiv) with 8 (1 equiv) was carried out in refluxing toluene, 9
was obtained in 70% yield (0.7 mmol) based on 8 (entry 8). In
this case, 1 functioned also as an acceptor of the H-B(OR)2
species. These results suggest that the choice of the acceptor of
the H-B(OR)2 species and the steric congestion of the alkenyl-
boronate affect the yields of the alkenylation products. Presently,
it is not certain why 1 has high activity as an acceptor of the
H-B(OR)2 species, and the reason of the different activity
between 1 and 4 as the acceptor must await further study.
(1) with Alkenylboronates via C-H Bond Cleavagea
a Reaction conditions: pivalophenone (1) (1 mmol), alkenylboronate (1.2
mmol), RuH2(CO)(PPh3)3 (3) (0.02 mmol), pinacolone (0.5 mL), reflux,
20 h. b Isolated yield. c The values in parentheses are the yields at 5 mol %
catalyst loading. d Alkenylboronate (1.5 mmol) was used. e Reaction condi-
tions: 1 (2 mmol), 8 (1 mmol), 3 (0.02 mmol), toluene (0.5 mL), reflux,
3 h. f Based on 8.
The reaction of pivalophenone (1) with 2-isopropenyl-5,5-
dimethyl[1,3,2]dioxaborinane (2) was initially examined using
RuH2(CO)(PPh3)3 (3) as a catalyst in refluxing pinacolone 4
(eq 1). The expected propenylation reaction occurred ortho to
the pivaloyl group to give product 5 in 73% yield. In the case
of the C-H/acetylene coupling (addition of C-H bonds to
acetylenes), only internal acetylenes can be used as the substrate
because terminal acetylenes are prone to dimerize under these
reaction conditions, and as a result, alkenylation products, such
as 5, cannot be obtained. Thus, the present alkenylation of
aromatic ketones using alkenylboronates provides a comple-
mentary protocol to C-H/acetylene coupling.
Alkenylboronate 2 has two different reaction sites. One is
the C-B bond, and the other is the C-C double bond. In the
case of the reaction of eq 1, the alkenylation product was formed
via C-H/C-B coupling. This coupling mode contracts with
Reactions of p-methoxy- and p-fluoropivalophenones pro-
vided the corresponding coupling products in 64 and 59% yields,
J. Org. Chem, Vol. 72, No. 9, 2007 3601

1268 w, 1185 w, 963 s, 946 w, 752 w; MS m/z (% relative intensity)
202 (M+, 10), 146 (12), 145 (100), 117 (65), 116 (11), 115 (47),
91 (20), 57 (12), 51 (12). Anal. Calcd for C14H18O: C, 83.12; H,
8.97%. Found: C, 82.84; H, 8.83%.
respectively (eq 2). A higher reaction temperature (140 °C)
improved the yields, slightly, to 73 and 68%, respectively. The
coupling reaction of acetophenone with R-styrylboronate pro-
vided the monoalkenylation product as the sole product (eq 3).
In summary, our results concerning the ruthenium-catalyzed
coupling of aromatic ketones with alkenylboronates are pre-
sented herein. Several alkenylboronates can be used in this
coupling reaction. The electronic nature of the substituent on
the benzene ring in styrylboronates did not substantially affect
the reactivity. In these cases, C-C bond formation took place
between the ortho C-H bonds in aromatic ketones and the C-B
bonds in the alkenylboronates.
2,2-Dimethyl-1-(2-styrylphenyl)propan-1-one. Following the
general procedure above, the crude product was purified by
chromatography on basic aluminum oxide (hexane/EtOAc ) 10:
1
1): mp 70-72 °C; Rf ) 0.42 (hexane/EtOAc ) 5:1); H NMR
(CDCl3) δ 1.24 (s, 9H, C(CH3)3), 6.94 (d, J ) 16.2 Hz, 1H, dCH),
7.03 (d, J ) 16.2 Hz, 1H, CHd), 7.14 (d, J ) 6.8 Hz, 1H, ArH),
7.22-7.46 (m, 7H, ArH), 7.69 (d, J ) 6.8 Hz, 1H, ArH); 13C NMR
(CDCl3) δ 27.39, 45.29, 124.87, 125.58, 125.67, 126.51, 126.57,
127.86, 128.62, 128.67, 130.97, 133.70, 136.83, 140.34, 215.18;
IR (KBr, cm-1) 2964 w, 2868 w, 1685 s, 1496 m, 1478 w, 1461
w, 1449 w, 1363 w, 1271 w, 1195 w, 1184 w, 963 s, 945 w, 767
s, 749 w, 734 w, 694 m, 681 w, 669 w, 655 w, 531 w; MS m/z (%
relative intensity) 264 (M+, 11), 208 (16), 207 (100), 179 (28),
178 (46), 57 (16), 51 (12). Anal. Calcd for C19H20O: C, 86.32; H,
7.63%. Found: C, 86.17; H, 7.62%.
Experimental Section
General Procedure. The apparatus used, which consisted of a
10 mL two-necked flask equipped with a reflux condenser and a
magnetic stirring bar, was flame-dried and then cooled to room
temperature under a flow of nitrogen. RuH2(CO)(PPh3)3 (0.02
mmol), pinacolone (0.5 mL), aromatic ketones (1.0 mmol), and
alkenylboronates (1.2 mmol) were placed in the flask. The resulting
mixture was refluxed under a nitrogen atmosphere. The progress
of the reaction was monitored by a GC analysis, and the product
was isolated and purified by alumina (Merck, aluminum oxide 90
active basic (0.063-0.200 mm)) and/or silica gel (Merck, silica
gel 60 (230-400 mesh ASTM)) column chromatography. Further
purification of the product was preformed by GPC.
Acknowledgment. This work was supported, in part, by a
Grant-in-Aid for Scientific Research on Priority Areas “Ad-
vanced Molecular Transformations of Carbon Resources” from
the Ministry of Education, Culture, Sports, Science and Tech-
nology, Japan. F.K. thanks Tokuyama Science Foundation and
The Science Research Promotion Fund of The Promotion and
Mutual Aid Corporation for Private Schools of Japan, and S.U.
acknowledges Research Fellowships of J.S.P.S. for Young
Scientist.
2,2-Dimethyl-1-(2-propenylphenyl)propan-1-one. Following
the general procedure above, the crude product was purified by
chromatography on basic aluminum oxide (hexane/EtOAc ) 10:
Supporting Information Available: General experimental
procedures and characterization data (1H NMR, 13C NMR, IR, Rf,
mp, GC-MS analyses, elemental analyses) for all compounds and
1
1): Rf ) 0.44 (hexane/EtOAc ) 5:1); bp 125 °C/1.0 mmHg; H
NMR (CDCl3) δ 1.22 (s, 9H, C(CH3)3), 1.83-1.86 (m, 3H,
dCCH3), 6.08-6.21 (m, 1H, dCHCH3), 6.25 (d, J ) 16.2 Hz,
1H, CdCHAr), 7.06-7.33 (m, 3H, ArH), 7.49 (d, J ) 7.8 Hz, 1H,
ArH); 13C NMR (CDCl3) δ 18.79, 27.33, 45.17, 124.61, 125.59,
125.77, 128.33, 128.42, 128.47, 134.31, 139.49, 215.22; IR (KBr,
cm-1) 2966 w, 1690 s, 1481 m, 1461 w, 1446 w, 1394 w, 1365 w,
1
copies of H NMR and 13C NMR for all new compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
JO070182G
3602 J. Org. Chem., Vol. 72, No. 9, 2007