Ruthenium-catalyzed 1,4-addition of organoboronic acids to α,β-unsaturated ketones

Article abstract of DOI:10.1246/cl.2008.724

A ruthenium-catalyzed 1,4-addition of organoboronic acids to α,β-unsaturated ketones has been developed. The use of 2-(di-tert-butylphosphino)biphenyl as the ligand in combination with [RuCl ₂(p-cymene)]₂ complex catalyzes these reactions to selectively give 1,4-adducts in good yield by effectively suppressing Heck-type and reduced products. Copyright

Full text of DOI:10.1246/cl.2008.724

724
Chemistry Letters Vol.37, No.7 (2008)
Ruthenium-catalyzed 1,4-Addition of Organoboronic Acids to ꢀ,ꢁ-Unsaturated Ketones
Ryo Shintaniꢀ and Tamio Hayashiꢀ
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502
(Received April 25, 2008; CL-080431; E-mail: shintani@kuchem.kyoto-u.ac.jp, thayashi@kuchem.kyoto-u.ac.jp)
A ruthenium-catalyzed 1,4-addition of organoboronic acids
Table 1. Ruthenium-catalyzed 1,4-addition of phenylboronic
acid (2a) to 1-phenyl-2-buten-1-one (1a)
to ꢀ,ꢁ-unsaturated ketones has been developed. The use of
2-(di-tert-butylphosphino)biphenyl as the ligand in combination
with [RuCl2(p-cymene)]2 complex catalyzes these reactions
to selectively give 1,4-adducts in good yield by effectively
suppressing Heck-type and reduced products.
O
Catalyst
(5 mol % Ru)
Me
Ph
Ph
O
Ph
O
O
1a
+
KOH (1.0 equiv)
Dioxane/H2O
(100/1)
Me
Ph Me
Ph Me
Ph
PhB(OH)2
2a (4.0 equiv)
3aa
4
5
90 °C, 24 h
Yield/%a
3aa
1,4-Addition of readily available and easy-to-handle carbon
nucleophlies such as organoboronic acids to electron-deficient
alkenes is a useful method for efficient construction of carbon–
carbon bonds. Traditionally, copper complexes have been typi-
cally employed as catalysts for 1,4-addition reactions,1 particu-
larly of alkyl nucleophiles such as alkylmagnesium halides,2
dialkylzincs,3 and trialkylaluminums.4 Within the context of
the addition of organoboronic acids, rhodium complexes have
been most widely used as effective catalysts since the first report
by Miyaura et al. in 1997,5 and its asymmetric variants have
also been successfully developed in the past decade.6 In addition
to rhodium complexes, palladium7 and nickel8 complexes have
also exhibited catalytic activity in the 1,4-addition reactions of
organoboronic acids and/or their derivatives. In contrast, the
use of other transition metals for these useful carbon–carbon
bond-forming reactions has been scarcely explored. In this
context, herein we describe the development of a ruthenium-cat-
alyzed 1,4-addition of organoboronic acids to ꢀ,ꢁ-unsaturated
ketones (eq 1).9
Entry
Catalyst
4
5
1
2
3
4
5
6
7
RuCl2(PPh3)3
[RuCpꢀCl]4
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2/dppf
[RuCl2(p-cymene)]2/PPh3
[RuCl2(p-cymene)]2/PCy3
4
14
2
5
6
5
38 16 20
17
5
4
22 17 18
34 12 11
[RuCl2(p-cymene)]2/P(t-Bu)2(2-PhC6H4) 70
6
7
aDetermined by H NMR against internal standard (MeNO2).
1
[Ru]
X
PhB(OH)2
O
[Ru]
H
[Ru] Ph
H2O
[Ru]
Ph
1a
3aa
−
X
Me
Ph
A
β
-H elimination
[RuCl2(p-cymene)]2
(5 mol % Ru)
P(t-Bu)2(2-PhC6H4) (5 mol %)
4
+
O
R
O
O
[Ru]
+ RB(OH)2
(4.0 equiv)
(1)
KOH (1.0 equiv)
Dioxane/H2O (100/1)
90 °C, 24 h
R1
R2
[Ru]
H
H2O
R1
R2
Ph
1a
5
up to 83% yield
−
[Ru]
X
H
Me
B
H
We started the study by employing 1-phenyl-2-buten-1-one
(1a) as a model substrate and conducted reactions with
phenylboronic acid (2a) in the presence of 5 mol % of several
readily available ruthenium(II) complexes in aqueous dioxane
at 90 ꢁC. Among those examined (Table 1, Entries 1–3),
[RuCl2(p-cymene)]2 showed the highest catalytic activity, but
it gave a mixture of 1,4-adduct 3aa (38%), Heck-type product
4 (16%), and reduced product 5 (20%) rather nonselectively.
The formation of these products can be rationalized by the path-
ways proposed in Scheme 1. Thus, phenylruthenium species,
generated by transmetalation of phenyl group from boron to
ruthenium,9 adds to enone 1a in a 1,4-fashion to give intermedi-
ate A. Protonolysis of A gives 1,4-adduct 3aa, whereas ꢁ-hy-
dride elimination of A produces Heck-type product 4 along with
a ruthenium hydride. Hydroruthenation of this species to another
molecule of 1a, followed by protonolysis, leads to reduced
product 5. To improve the selectivity toward the formation of
1,4-adduct 3aa by suppressing the undesired ꢁ-hydride elimina-
tion of A, we decided to conduct the reaction in the presence of
added phosphine ligands. The use of bisphosphine ligands such
Scheme 1. Proposed reaction pathways for the formation of
3aa, 4, and 5.
as dppf did improve the selectivity toward 3aa over 4/5 to some
extent, but the overall reactivity became significantly lower
(Entry 4). Common tertiary monophosphines such as triphenyl-
phosphine and tricyclohexylphosphine did not show much
influence on reactivity or selectivity (Entries 5 and 6). In
contrast, the use of 2-(di-tert-butylphosphino)biphenyl10 led to
the formation of 3aa in 70% yield by effectively minimizing
the formation of 4 and 5 (Entry 7).
Under the conditions using [RuCl2(p-cymene)]2/2-(di-tert-
butylphosphino)biphenyl as the catalyst, several ꢀ,ꢁ-unsaturat-
ed acyclic ketones can be used for 1,4-addition of phenylboronic
acid to give the corresponding products in 60–80% yield
(Table 2, Entries 1–4). For cyclic ketones such as 2-cyclopent-
en-1-one, the reaction proceeded better without using 2-
(di-tert-butylphosphino)biphenyl (Entry 5). With regard to the
nucleophilic component, several aryl- as well as alkenylboronic
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.7 (2008)
725
Table 2. Ruthenium-catalyzed 1,4-addition of organoboronic
acids 2 to ꢀ,ꢁ-unsaturated ketones 1: scope
compound 7 as a sole product in 61% yield (eq 2). This result
markedly contrasts to that obtained with [RhCl(cod)]2 as a cata-
lyst where one-to-two adduct 8 {R = 2,3-endo,endo-bis(ben-
zyloxymethyl)bicyclo[2.2.1]hept-5-exo-yl} becomes the major
product (71% yield) due to a facile 1,4-rhodium migration.11
In summary, we have developed a ruthenium-catalyzed
1,4-addition of organoboronic acids to ꢀ,ꢁ-unsaturated ketones.
The use of 2-(di-tert-butylphosphino)biphenyl as the ligand
in combination with [RuCl2(p-cymene)]2 complex effectively
catalyzes these reactions, selectively giving 1,4-adducts over
Heck-type and reduced products.12 Future studies will explore
further improvement of the reaction conditions and expansion of
the substrate scope as well as the development of an asymmetric
variant.
[RuCl2(p-cymene)]2
(5 mol % Ru)
O
R
O
P(t-Bu)2(2-PhC6H4) (5 mol %)
+
RB(OH)2
KOH (1.0 equiv)
Dioxane/H2O (100/1)
90 °C, 24 h
R1
R2
R1
R2
1
2 (4.0 equiv)
3
2a: R = Ph
2b: R = 4-MeOC6H4
2c: R = 4-ClC6H4
2d: R = 3-MeC6H4
2e: R = (E)-CH=CHPh
Entry
1
1
O
2
Product
Yield/%a
71
Ph
O
1a
1b
3aa
3ba
2a
Me
Me
Ph
Et
Me
Me
Ph
Et
O
Ph
Ph
Ph
O
O
2
3
4
2a
2a
2a
74
80
60
O
O
Support has been provided in part by a Grant-in-Aid for
Scientific Research, the Ministry of Education, Culture, Sports,
Science and Technology, Japan (the Global COE Program ‘‘In-
tegrated Materials Science’’ on Kyoto University).
1c
3ca
n-Pr
Me
n-Pr
Ph
Me
O
O
1d
3da
Ph
Ph
Ph
O
References and Notes
1
5b
2a
2b
62
82
1e
3ea
´
For reviews, see: a) F. Lopez, A. J. Minnaard, B. L. Feringa, Acc.
Chem. Res. 2007, 40, 179. b) A. Alexakis, C. Benhaim, Eur. J. Org.
Chem. 2002, 3221. c) J. Christoffers, G. Koripelly, A. Rosiak, M.
Ph
OMe
Rossle, Synthesis 2007, 1279.
¨
For recent progress, see: a) D. Martin, S. Kehrli, M. d’Augustin,
2
3cb
3cc
6
1c
H. Clavier, M. Mauduit, A. Alexakis, J. Am. Chem. Soc. 2006, 128,
´
O
8416. b) S. R. Harutyunyan, F. Lopez, W. R. Browne, A. Correa,
n-Pr
Me
Me
D. Pen˜a, R. Badorrey, A. Meetsma, A. J. Minnaard, B. L. Feringa,
J. Am. Chem. Soc. 2006, 128, 9103. c) S.-Y. Wang, S.-J. Ji, T.-P.
Loh, J. Am. Chem. Soc. 2007, 129, 276.
Cl
3
For recent progress, see: a) H. Clavier, L. Coutable, J.-C. Guillemin,
M. Mauduit, Tetrahedron: Asymmetry 2005, 16, 921. b) F. Valleix,
K. Nagai, T. Soeta, M. Kuriyama, K. Yamada, K. Tomioka, Tetra-
hedron 2005, 61, 7420. c) A. Hajra, N. Yoshikai, E. Nakamura, Org.
Lett. 2006, 8, 4153. d) M. Pineschi, F. D. Moro, V. D. Bussolo, F.
Macchia, Adv. Synth. Catal. 2006, 348, 301. e) K. Lee, M. K. Brown,
A. W. Hird, A. H. Hoveyda, J. Am. Chem. Soc. 2006, 128, 7182. f) K.
Li, A. Alexakis, Chem.—Eur. J. 2007, 13, 3765.
7
1c
2c
79
O
n-Pr
Me
3cd
3ce
8
9
1c
1c
2d
2e
83
O
O
n-Pr
Ph
Me
Me
4
M. Vuagnoux-d’Augustin, A. Alexakis, Chem.—Eur. J. 2007, 13,
9647.
62c
5
6
M. Sakai, H. Hayashi, N. Miyaura, Organometallics 1997, 16, 4229.
For reviews, see: a) T. Hayashi, K. Yamasaki, Chem. Rev. 2003, 103,
2829. b) K. Fagnou, M. Lautens, Chem. Rev. 2003, 103, 169. c) C.
Bolm, J. P. Hildebrand, K. Mun˜iz, N. Hermanns, Angew. Chem., Int.
Ed. 2001, 40, 3284.
n-Pr
aIsolated yield. bThe reaction was conducted in the absence
of P(t-Bu)2(2-PhC6H4) using 3.5 equiv of PhB(OH)2 and
c
1.5 equiv of KOH in dioxane/H2O (27/1). Containing 6% of
olefin isomer 3ce0.
7
a) C. S. Cho, S. Motofusa, K. Ohe, S. Uemura, S. C. Shim, J. Org.
Chem. 1995, 60, 883. b) T. Nishikata, Y. Yamamoto, N. Miyaura,
Angew. Chem., Int. Ed. 2003, 42, 2768. c) F. Gini, B. Hessen, A. J.
Minnaard, Org. Lett. 2005, 7, 5309. d) X. Lu, S. Lin, J. Org. Chem.
2005, 70, 9651. e) T. Yamamoto, M. Iizuka, T. Ohta, Y. Ito, Chem.
Lett. 2006, 35, 198. f) P. He, Y. Lu, C.-G. Dong, Q.-S. Hu, Org. Lett.
2007, 9, 343. g) H. Horiguchi, H. Tsurugi, T. Satoh, M. Miura, J. Org.
Chem. 2008, 73, 1590.
Ph
O
n-Pr
Me
3ce'
acids can be employed to give the 1,4-adducts in good yield
(up to 83% yield; Entries 6–9).
8
9
a) E. Shirakawa, Y. Yasuhara, T. Hayashi, Chem. Lett. 2006, 35, 768.
See also: b) K. Hirano, H. Yorimitsu, K. Oshima, Org. Lett. 2007,
9, 1541.
Ruthenium-catalyzed oxidative Heck-type reaction of acrylates with
arylboronic acids has been reported: a) E. J. Farrington, J. M. Brown,
C. F. J. Barnard, E. Rowsell, Angew. Chem., Int. Ed. 2002, 41, 169.
b) E. J. Farrington, C. F. J. Barnard, E. Rowsell, J. M. Brown, Adv.
Synth. Catal. 2005, 347, 185.
Catalyst
(5 mol % M)
R
2a (4.0 equiv)
OBn
OBn
OBn
OBn
+
(2)
KOH (1.0 equiv)
Dioxane/H2O (100/1)
90 °C, 20 h
Ph
R
6
7 (Ph−R)
8
[RuCl2(p-cymene)]2
61% yield
6% yield
0% yield
10 A. Aranyos, D. W. Old, A. Kiyomori, J. P. Wolfe, J. P. Sadighi, S. L.
Buchwald, J. Am. Chem. Soc. 1999, 121, 4369.
[RhCl(cod)]2
71% yield
11 K. Oguma, M. Miura, T. Satoh, M. Nomura, J. Am. Chem. Soc.
2000, 122, 10464.
12 Supporting Information is available electronically on the CSJ-Journal
Web site, http://www.csj.jp/journals/chem-lett/.
It is worth noting that [RuCl2(p-cymene)]2 catalyst is also
effective for hydroarylation of norbornene derivatives. Thus,
compound 6 undergoes hydrophenylation smoothly to give
Published on the web (Advance View) June 7, 2008; doi:10.1246/cl.2008.724