Tandem olefin migration-aldol condensation in water with an amphiphilic resin-supported ruthenium complex

Article abstract of DOI:10.1055/s-0030-1259689

A catalytic tandem olefin migration-aldol condensation process with allylic carbinols and aryl aldehydes was performed with 0.5 mol% of an amphiphilic polystyrene-poly(ethylene glycol) (PS-PEG) resin supported phosphine-ruthenium complex in water as a single reaction medium under heterogeneous conditions to give the corresponding aldols with syn selectivity. Inverse stereoselectivity (anti selectivity) was observed when the reaction was carried out in the presence of KO Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1259689

LETTER
787
Tandem Olefin Migration–Aldol Condensation in Water with an Amphiphilic
Resin-Supported Ruthenium Complex
Tandem
O
lefin Mi
o
gration–Aldo
h
l
C
ondensat
e
ion in Wate
i
r
Oe,1 Yasuhiro Uozumi*
Institute for Molecular Science (IMS), Higashiyama 5-1, Myodaiji, Okazaki 444-8787, Japan
Fax +81(564)595574; E-mail: uo@ims.ac.jp
Received 15 December 2010
Abstract: A catalytic tandem olefin migration–aldol condensation
process with allylic carbinols and aryl aldehydes was performed
O
C
Ph
P
Ru
PS
O
O
N
H
Ru
Cl
n
Cl
with 0.5 mol% of an amphiphilic polystyrene-poly(ethylene glycol)
(PS-PEG) resin supported phosphine–ruthenium complex in water
as a single reaction medium under heterogeneous conditions to give
the corresponding aldols with syn selectivity. Inverse stereoselec-
tivity (anti selectivity) was observed when the reaction was carried
out in the presence of K2CO3.
Ph
PS-PEG-PPh2-Cp*RuCl2 (1)
Cl
Ru
in H2O, 60 °C, 9 h
CCl3
Key words: tandem reaction, aldol condensation, aqueous media,
polymer support, ruthenium catalyst
+ CCl4
S/C = 2,000, in H2O; TOF = 1445 h–1 (at initial 15 min)
Aqueous and heterogeneous switching of a given organic
transformation has been rapidly gaining in importance for
its ability to provide safe and green-chemical processes.2,3
In 1997, we published our first report on the development
of heterogeneous aquacatalytic reactions by the use of am-
phiphilic polystyrene-poly(ethylene glycol) (PS-PEG)4,5
resin supports, in which we described very early examples
of catalytic organic transformations in water without any
organic media with immobilized heterogeneous palladi-
um complexes. Since then we have developed a variety of
PS-PEG resin supported transition-metal catalysts to
achieve various catalytic transformations in water under
heterogeneous conditions. As part of our continuing effort
to demonstrate the wide utility of this heterogeneous
aquacatalytic system, we have now developed PS-PEG
resin supported ruthenium complexes6,7 which were found
to promote the Kharasch reaction efficiently in water
without any radical initiator (Scheme 1). Li’s recent find-
ing that a ruthenium complex catalyzes the formation of
aldol products from allyl alcohols via the tandem olefin
migration–aldol condensation under aqueous conditions
(Scheme 2),8,9 prompted us to examine the tandem aldol
formation process in water under heterogeneous condi-
tions using the PS-PEG resin supported CpRu(phosphine)
complex. Herein we wish to report our preliminary results
on the catalytic tandem olefin migration–aldol condensa-
tion process, which is promoted by the ruthenium com-
plex anchored onto the amphiphilic PS-PEG resin
supported triarylphosphine in water under heterogeneous
conditions to give the corresponding aldol products.
Scheme 1 Amphiphilic polymeric Ru-catalyzed Kharasch reaction
in water
OH
O
O
O
[Ru]
[Ru]
3
+
H
2
3
O
OH
OH
+
syn-4
anti-4
Scheme 2 Ru-catalyzed tandem olefin migration–aldol condensation
First, the reaction of benzaldehyde (3) and 3-buten-2-ol
(2) was carried out in neat water in the presence of various
PS-PEG resin supported transition-metal complexes,
where PS-PEG-phosphine-RuCl2Cp* (1) was found to
catalyze the tandem olefin migration–aldol condensation
process smoothly at 45 °C (Scheme 3). Thus, a mixture of
2 (2.0–3.0 equiv), 3, and 0.5 mol% Ru of PS-PEG-phos-
phine-RuCl2Cp* (1) was agitated in water at 45 °C for 2
hours. The reaction mixture was filtered, and the resin
beads were rinsed with a small portion of hot water, and
the combined aqueous filtrates were freeze-dried in vac-
uo. The diastereomeric (syn/anti) ratio of the resulting al-
dol 4 was determined by 1H NMR spectroscopic analysis
of the crude material to be 82:18, and the chemical yield
was determined via chromatographic isolation of the syn/
anti mixture of 4 to be 74%. The tandem aldol formation
with PS-PEG-phosphine-RuCl2(p-cymene) (5), PS-PEG-
phosphine-RhCl(CO)2 (6), or PS-PEG-phosphine-
PdCl(h3-C3H5) (7) afforded <3% of 4 even at 100 °C (in
SYNLETT 2011, No. 6, pp 0787–0790
x
x.
x
x.
2
0
1
1
Advanced online publication: 25.02.2011
DOI: 10.1055/s-0030-1259689; Art ID: D32210ST
© Georg Thieme Verlag Stuttgart · New York

788
Y. Oe, Y. Uozumi
LETTER
OH
O
O
OH
Table 1 Catalytic Tandem Olefin Migration–Aldol Condensation
in Water with PS-PEG-phosphine-RuCl2Cp* (1)a
[cat]
+
H
in H2O
Ru
1
O
OH
OH
O
2
3
syn/anti-4
(0.5 mol% Ru)
R1
R1
H
+
in H2O
45 °C, 2 h
O
C
Ph
P
R2
R2
PS
O
O
N
H
M
4, 8–12
n
2a,b
a: R1 = Me
3A–E
Ph
E: R2 = Br
A: R2 = H
C: R2 = OMe
D: R2 = Cl
PS-PEG-phosphine–M complex
b: R1 = C5H11
B: R2 = Me
Entry 2/3
Productb
Yield (%)c
(syn/anti)d
45 °C, 2 h
74% (syn/anti = 82:18)
–M =
Ru
Cl
1
Cl
Cl
O
OH
1
2
3
2a/3A
4
8
9
74 (82:18)
45 (74:26)
67 (79:21)
45 °C, 2 h, <3%
100 °C, 2 h, <3%
–M =
–M =
5
6
Ru
Cl
O
OH
2b/3A
2a/3B
n-C5H11
45 °C, 2 h, <3%
100 °C, 2 h, <3%
RhCl(CO)2
O
OH
OH
45 °C, 2 h, <3%
100 °C, 2 h, <3%
PdCl(η3-C3H5)
–M =
7
Scheme 3
O
O
O
4
5
6
2a/3C
2a/3D
2a/3E
10
11
12
61 (75:25)
52 (81:19)
64 (81:19)
refluxing water) under otherwise similar conditions
(Scheme 3).
OMe
Cl
It is noteworthy that the catalytic performance of the poly-
meric complex PS-PEG-phosphine-RuCl2Cp* (1) in wa-
ter was much higher than that reported for RuCl2(PPh3)3
in aqueous reaction media. Thus, 0.5 mol% Ru of the
polymeric catalyst 1 promoted the tandem olefin migra-
tion–aldol condensation in water at 45 °C within 2 hours,
whereas the reaction with 3 mol% of RuCl2(PPh3)3 re-
quired 110 °C (5–10 h) under aqueous conditions (e.g.,
H2O–toluene = 4:1). The inefficiency of the aqueous reac-
tion system using RuCl2(PPh3)3 is presumably attributable
to the heterogeneity of the reaction mixture. In the present
reaction system using PS-PEG-phosphine-RuCl2Cp* (1)
in water, the organic substrates 2 and 3 should automati-
cally diffuse into the PS-PEG matrix, because of their
hydrophobicity, to afford highly self-concentrated condi-
tions, where the condensation reaction would proceed ef-
ficiently to decrease the molar concentration of the
reaction matrix.
OH
OH
Br
a All reactions were carried out in H2O at 45 °C for 2 h with 0.5 mol%
Ru of 1. The ratio of 2 (mol)/3 (mol)/Ru (mol)/H2O
(L) = 2.0:1.0:0.005:1.0.
b The structure of the major diastereomer is depicted.
c Isolated yield.
d Determined by 1H NMR.
respectively, where the syn isomers were obtained with
75–81% selectivity.
During the screening of the catalytic conditions, inversion
of diastereoselectivity was observed when the reaction
was carried out in the presence of potassium carbonate
(Table 2). Thus, when the reaction of benzaldehyde (3)
and 3-buten-2-ol (2) was carried out in the presence of 20
mol% of K2CO3 under otherwise similar conditions, the
aldol product 4 was obtained in 79% yield with a syn/anti
diastereoselectivity of 26:74 (Table 2, entry 1).
Table 1 summarizes the representative results of the tan-
dem olefin migration–aldol condensation process with
various allylic alcohols and benzaldehydes catalyzed by
PS-PEG-phosphine-RuCl2Cp* (1) in water under hetero-
geneous conditions, where the structures of the major di-
astereomeric isomer are depicted. Pentyl vinyl carbinol
(2b) reacted with benzaldehyde (3) to give a 45% yield of
the aldol 8 (syn/anti = 74:26). Reactions of 2a with ben-
zaldehydes bearing methyl, methoxy, chloro, and bromo
substituents at their 4-positions 3B–E afforded the corre-
sponding aldols 9–12 in 67%, 61%, 52%, and 64% yield,
A similar anti-selective trend was observed in the reac-
tions with combinations of the substrates 2b/3A, 2a/3B,
2a/3C, 2a/3D, and 2a/3E where the corresponding aldols
8–12 were obtained in 48–98% yield with 67–81% anti-
Synlett 2011, No. 6, 787–790 © Thieme Stuttgart · New York

LETTER
Tandem Olefin Migration–Aldol Condensation in Water
789
anti-4 as the major isomer with 77% and 70% diastereo-
selectivity, respectively (Table 2, entries 5 and 6), though
the isolated chemical yield of 4 was slightly lower. A re-
cycling experiment was examined for the reaction of 2a
with 4-bromobenzaldehyde (3E). Thus, after the 1st cata-
lytic use of the PS-PEG resin-supported Ru complex 1
(12; 78% yield, syn/anti = 33:67; entry 9), the catalyst
beads were collected by simple filtration, rinsed with wa-
ter and EtOAc, dried in vacuo, and subjected to the second
catalytic use (entry 10). The reaction of 2a and 3E with
the recycled catalyst beads gave 81% isolated yield of 12
with 63% of the anti selectivity under similar conditions.
Though loss of the catalytic activity was observed in the
subsequent recycle experiment affording 38% yield of 12
(entry 11), the anti selectivity was retained almost intact
(syn/anti = 32:68). When the aldol 9 (syn/anti = 70:30)
was exposed to the anti-selective catalytic conditions
(Table 2, footnote a), 9% of retro-aldol product 3B was
obtained but no significant epimerization giving anti-9
was observed. The aldol condensation of 2-butanone and
3B did not take place under the catalytic conditions
(Scheme 4). Thus, neither a-carbonyl epimerization nor a
retro-aldol–aldol sequence could explain the anti-selec-
tive aldol formation. Though the reaction mechanism is as
yet unclear, inversion of the diastereoselectivity by the
simple additive should enhance its practical utility.
Table 2 Catalytic Tandem Olefin Migration–Aldol Condensation
in Aqueous K2CO3 with PS-PEG-phosphine-RuCl2Cp* (1)a
Ru
1
OH
O
O
OH
(0.5 mol% Ru)
R1
H
+
R1
in H2O
K2CO3
45 °C, 2 h
R2
R2
2a,b
3A–E
4, 8–12
a: R1 = Me
A: R2 = H
C: R2 = OMe
D: R2 = Cl
E: R2 = Br
b: R1 = C5H11
B: R2 = Me
Entry 2/3
Productb
Yield (%)c
(syn/anti)d
O
OH
1
2
3
2a/3A
4
79 (26:74)
O
OH
2b/3Ae
2a/3B
8
9
75 (19:81)
78 (26:74)
n-C5H11
O
OH
4
5
6
without Ru complex 1
Na2CO3 was used
K3PO4 was used
9
9
9
no reaction
69 (23:77)
52 (30:70)
Ru
1
O
OH
(0.5 mol% Ru)
9 (syn/anti = 60:40)
+ 3B (9%)
O
O
O
OH
in H2O
K2CO3
7
2a/3C
2a/3D
2a/3E
10
11
12
48 (27:73)
98 (33:67)
92 (33:67)
45 °C, 2 h
9 (syn/anti = 70:30)
OMe
Cl
OH
OH
Ru
1
8
9
O
(0.5 mol% Ru)
no reaction
+
3B
in H2O
K2CO3
45 °C, 2 h
Scheme 4
Br
10f
11f
recycle experiment
recycle experiment
12
12
81 (37:63)
38 (32:68)
In summary, the catalytic tandem olefin migration–aldol
condensation of allylic alcohols and aldehydes has been
achieved in water with an amphiphilic polymer-supported
ruthenium complex to give the corresponding aldol prod-
ucts. The polymeric complex exhibited high catalytic per-
formance even at 45 °C with 0.5 mol% of ruthenium. A
detailed mechanistic study and further catalytic applica-
tions of 1 are currently under investigation in our lab and
will be reported in due course.
a All reactions were carried out in H2O at 45–55 °C for 2 h with 0.5
mol% Ru of 1. The ratio of 2 (mol)/3 (mol)/Ru (mol)/K2CO3 (mol)/
H2O (L) = 2.0:1.0:0.005:0.2:5.0, unless otherwise noted.
b The structure of the major diastereomer is depicted.
c Isolated yield.
d Determined by 1H NMR.
e Ratio of 2b/3A = 1.5:1.0.
f Entries 10 and 11 were performed with catalyst beads recovered
from entries 9 and 10, respectively.
Experimental: PS-PEG Resin Supported Ruthenium Complex
(1)
A reactor was charged with PS-PEG-PPh2 (340 mg), Cp*RuCl2 (35
mg), and CH2Cl2 (10 mL). The reaction mixture was shaken on a
wrist action shaker at 25 °C for 5 h. The solvent was removed by fil-
selectivity (Table 2, entries 2, 3, 7–9). The aldol reaction
did not occur without the polymeric Ru complex 1 even in
the presence of K2CO3 (Table 2, entry 4). The reactions
with Na2CO3 and K3PO4 instead of K2CO3 provided the
Synlett 2011, No. 6, 787–790 © Thieme Stuttgart · New York

790
Y. Oe, Y. Uozumi
LETTER
(4) (a) Bayer, E.; Rapp, W. In Chemistry of Peptides and
tration, and the collected beads were washed with CH2Cl2 (5 × 5
mL) and dried under reduced pressure overnight to give PS-PEG-
PPh2-Cp*RuCl2 (1) as reddish beads (0.23 mmol Ru/g, 0.24 mmol
P/g).
Proteins, Vol. 3; Voelter, W.; Bayer, E.; Ovchinikov, Y. A.;
Iwanov, V. T., Eds.; Walter de Gruter: Berlin, 1986, 3.
(b) Rapp, W. In Combinatorial Peptide and Nonpeptide
Libraries; Jung G., VCH: Weinheim, 1996, 425.
General Procedure for Isomerization–Aldol Condensation Re-
action of Benzaldehyde and 3-Buten-2-ol with the Polymeric 1
in Water
(5) For studies on polymer-supported transition-metal-complex
catalysts from the author’s group, see for allylic
substitution: (a) Uozumi, Y.; Danjo, H.; Hayashi, T.
Tetrahedron Lett. 1997, 38, 3557. (b) Danjo, H.; Tanaka,
D.; Hayashi, T.; Uozumi, Y. Tetrahedron 1999, 55, 14341.
Cross-coupling: (c) Uozumi, Y.; Danjo, H.; Hayashi, T.
J. Org. Chem. 1999, 64, 3384. Carbonylation reaction:
(d) Uozumi, Y.; Watanabe, T. J. Org. Chem. 1999, 64,
6921. Suzuki–Miyaura coupling: (e) Uozumi, Y.; Nakai, Y.
Org. Lett. 2002, 4, 2997. Heck reaction: (f) Uozumi, Y.;
Kimura, T. Synlett 2002, 2045. Asymmetric alkylation:
(g) Uozumi, Y.; Shibatomi, K. J. Am. Chem. Soc. 2001, 123,
2919. Asymmetric amination: (h) Uozumi, Y.; Tanaka, H.;
Shibatomi, K. Org. Lett. 2004, 6, 281. Asymmetric
catalysis: (i) Hocke, H.; Uozumi, Y. Synlett 2002, 2049. Rh
catalysis: (j) Uozumi, Y.; Nakazono, M. Adv. Synth. Catal.
2002, 344, 274. Asymmetric catalysis: (k) Hocke, H.;
Uozumi, Y. Tetrahedron 2003, 59, 619. (l) Hocke, H.;
Uozumi, Y. Tetrahedron 2004, 60, 9297. Asymmetric
cycloisomerization: (m) Nakai, Y.; Uozumi, Y. Org. Lett.
2005, 7, 291. Cross-coupling: (n) Uozumi, Y.; Kikuchi, M.
Synlett 2005, 1775. Asymmetric etherification: (o) Uozumi,
Y.; Kimura, M. Tetrahedron: Asymmetry 2006, 17, 161.
Asymmetric alkylation: (p) Kobayashi, Y.; Tanaka, D.;
Danjo, H.; Uozumi, Y. Adv. Synth. Catal. 2006, 348, 1561.
Allylic azidation: (q) Uozumi, Y.; Suzuka, T.; Kawade, R.;
Takenaka, H. Synlett 2006, 2109. Nitromethylation:
(r) Uozumi, Y.; Suzuka, T. J. Org. Chem. 2006, 71, 8644.
Allylic sulfonylation: (s) Uozumi, Y.; Suzuka, T. Synthesis
2008, 1960. Asymmetric desymmetrization: (t)Uozumi,Y.;
Takenaka, H.; Suzuka, T. Synlett 2008, 1557. Asymmetric
Suzuki coupling: (u) Uozumi, Y.; Matsuura, Y.; Arakawa,
T.; Yamada, Y. M. A. Angew. Chem. Int. Ed. 2009, 48,
2708. Pt-catalyzed oxidation: (v) Yamada, Y. M. A.;
Arakawa, T.; Hocke, H.; Uozumi, Y. Chem. Asian J. 2009,
4, 1092. Sonogahsira coupling: (w) Suzuka, T.; Okada, Y.;
Ooshiro, K.; Uozumi, Y. Tetrahedron 2010, 66, 1064.
Buchwald–Hartwig reaction: (x) Hirai, Y.; Uozumi, Y.
Chem. Commun. 2010, 46, 1103. (y) Hirai, Y.; Uozumi, Y.
Chem. Asian J. 2010, 5, 1788.
A typical procedure is given for the reaction with benzaldehyde
(3A) and 3-buten-2-ol (2a) in H2O (Table 1, entry 1). A mixture of
PS-PEG-PPh2-Cp*RuCl2 (1, 11 mg, 0.0025 mmol Ru), 3-buten-2-
ol (2a, 72 mg, 1.0 mmol), benzaldehyde (3A, 53 mg, 0.5 mmol), and
H2O (2.5 mL) was shaken at 45 °C for 2 h under nitrogen atmo-
sphere. The reaction mixture was filtered, and the resin was rinsed
three times with 5 mL of hot H2O or supercritical CO2 (flow extrac-
tion system). The crude product was purified by silica gel column
chromatography to give a diastereomeric (syn/anti = 82:18) mixture
of 4 (66 mg, 74% yield). The ratio of the diastereomers was deter-
mined by 1H NMR analysis.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
We thank Ms. Aya Tazawa for her technical assistance. This work
was supported by the CREST program, which is sponsored by the
JST. We also acknowledge the JSPS (Grant-in-Aid for Scientific
Research #20655035; Grant-in-Aid for Scientific Research on Inno-
vative Area #2105) for partial financial support of this work.
References and Notes
(1) Present address: Graduate School Division of Engineering,
Doshisha University; yoe@mail.doshisha.ac.jp.
(2) For reviews on aqueous switching of organic
transformations, see: (a) Li, C.-J.; Chan, T.-H. Organic
Reactions in Aqueous Media; Wiley-VCH: New York,
1997. (b) Grieco, P. A. Organic Synthesis in Water; Kluwer
Academic Publishers: Dordrecht, 1997. (c) Herrmann, W.
A.; Kohlpaintner, C. W. Angew. Chem., Int. Ed. Engl. 1993,
32, 1524. (d) Lindström, U. M. Chem. Rev. 2002, 102,
2751. (e) Commentary: Uozumi, Y. Synlett 2010, 1988.
(3) For reviews on heterogeneous switching of organic
transformations, see: (a) Bailey, D. C.; Langer, S. H. Chem.
Rev. 1981, 81, 109. (b) Shuttleworth, S. J.; Allin, S. M.;
Sharma, P. K. Synthesis 1997, 1217. (c) Shuttleworth, S. J.;
Allin, S. M.; Wilson, R. D.; Nasturica, D. Synthesis 2000,
1035. (d) Dörwald, F. Z. Organic Synthesis on Solid Phase;
Wiley-VCH: Weinheim, 2000. (e) Leadbeater, N. E.;
Marco, M. Chem. Rev. 2002, 102, 3217. (f) Ley, S. V.;
Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.;
Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.;
Taylor, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3815.
(g) McNamara, C. A.; Dixon, M. J.; Bradley, M. Chem. Rev.
2002, 102, 3275. (h) Chiral Catalyst Immobilization and
Recycling; De Vos, D. E.; Vankelecom, I. F. J.; Jacobs,
P. A., Eds.; Wiley-VCH: Weinheim, 2000. (i) Fan, Q.-H.;
Li, Y.-M.; Chan, A. S. C. Chem. Rev. 2002, 102, 3385.
(j) Uozumi, Y. Top. Curr. Chem. 2004, 242, 77. (k) Guino,
M.; Hii, K. K. M. Chem. Soc. Rev. 2007, 36, 608. (l) Wang,
Z.; Chen, G.; Ding, K. Chem. Rev. 2009, 109, 322. (m) Lu,
J.; Toy, P. H. Chem. Rev. 2009, 109, 815.
(6) Kharasch reaction: Oe, Y.; Uozumi, Y. Adv. Synth. Catal.
2008, 350, 1771.
(7) For examples of amphiphilic polymer-supported ruthenium
complexes, see: (a) Kayaki, Y.; Shimokawatoko, Y.;
Ikariya, T. Adv. Synth. Catal. 2003, 345, 175. (b) Judkins,
C. M. G.; Knights, K. A.; Johnson, B. F. G.; De Miguel,
Y. R.; Raja, R.; Thomas, J. M. Chem. Commun. 2001, 2624.
(8) In water: (a) Wang, M.; Li, C. J. Tetrahedron Lett. 2002, 43,
3589. In ionic liquid: (b) Yang, X.-F.; Wang, M.; Varma,
R. S.; Li, C.-J. Org. Lett. 2003, 5, 657. In aqueous organic
media: (c) Wang, M.; Yang, X.-F.; Li, C.-J. Eur. J. Org.
Chem. 2003, 998. (d) Yang, X.-F.; Wang, M.; Varma, R. S.;
Li, C.-J. J. Mol. Catal. A: Chem. 2004, 214, 147.
(9) Rh catalysis: (a) Gazzard, L. J.; Motherwell, W. B.;
Sandham, D. A. J. Chem. Soc., Perkin Trans. 1 1999, 979.
Fe: (b) Crévisy, N.; Wietrich, M.; Le Boulaire, V.; Uma, R.;
Grée, R. Tetrahedron Lett. 2001, 42, 395. (c) Uma, R.;
Gouault, N.; Crévisy, N.; Grée, R. Tetrahedron Lett. 2003,
43, 6187. Ni: (d) Cuperly, D.; Crévisy, N.; Grée, R. Synlett
2004, 93. (e) Cuperly, D.; Petrignet, J.; Crévisy, N.; Grée, R.
Chem. Eur. J. 2006, 12, 3261.
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