Ag(I)-catalyzed Michael additions of β-ketoesters to nitroalkenes in water: Remarkable effect of water as a reaction medium on reaction rates

Article abstract of DOI:10.1055/s-2006-939709

AgOTf-PPh₃ complex-catalyzed Michael additions of β-ketoesters to nitroalkenes in water were performed. The system promotes the reaction efficiently only in water, and interestingly the reaction does not proceed well in organic solvents. In add

Full text of DOI:10.1055/s-2006-939709

1
410
LETTER
Ag(I)-Catalyzed Michael Additions of b-Ketoesters to Nitroalkenes in Water:
Remarkable Effect of Water as a Reaction Medium on Reaction Rates
M
S
ichael
A
ddit
e
ions in
W
a
i
Graduate School of Pharmaceutical Sciences, The University of Tokyo, The HFRE Division, ERATO, Japan Science and Technology
Agency (JST), Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax +81(3)56840634; E-mail: skobayas@mol.f.u-tokyo.ac.jp
Received 4 February 2006
Table 1 Effect of Catalysts
Abstract: AgOTf–PPh complex-catalyzed Michael additions of
3
O
O
Ph
b-ketoesters to nitroalkenes in water were performed. The system
promotes the reaction efficiently only in water, and interestingly the
reaction does not proceed well in organic solvents. In addition, this
reaction system could be applied to catalytic asymmetric synthesis
in water.
catalyst
NO2
NO2
+
Ph
COOt-Bu
H2O, r.t., 24 h
COOt-Bu
(1.5 equiv)
dra
Yield (%)b
Key words: water, silver, Michael additions, solvent effects, asym-
Entry
Catalyst
metric synthesis
1
2
3
AgOTf (10 mol%)
–
0
13
90
PPh (20 mol%)
79: 21
80: 20
3
The use of water as a reaction medium has received con-
siderable attention in organic synthesis due to its advan-
tages in terms of economy and from environmental and
safety standpoints. In addition, reactions in water may
offer different reactivity and selectivity compared with
those in common organic solvents due to the unique
AgOTf (10 mol%) +
PPh (20 mol%)
3
1
4
AgOTf (10 mol%) +
–
0
P(C H -m-SO Na) (20 mol%)
6
4
3
3
a
1
Determined by H NMR analysis.
Isolated yield.
2
b
physical and chemical properties of the solvent. In the
course of our investigations into developing efficient
organic reactions in aqueous media, we have exploited
several carbon–carbon bond-forming reactions catalyzed P(C H -m-SO Na) complex was tested as a catalyst, and
6
4
3
3
by water-compatible metal catalysts, and some of them it was found that no reaction took place (entry 4). These
have been applied to catalytic asymmetric reactions.3 results suggest that the catalyst should be hydrophobic for
However, examples of catalytic asymmetric reactions in efficient reaction to take place, probably because hydro-
4
pure water are still limited. Herein we report AgOTf– phobic catalysts come into contact most easily with
PPh complex-catalyzed Michael additions of b-keto- hydrophobic substrates in water.
3
5
esters to nitroalkenes that proceed in pure water without
Next, we examined the effect of solvents in the reaction
the need for any additives. A remarkable point is that the
system (Table 2). Intriguingly, the reaction in CH Cl and
2
2
catalyst system promotes the reaction efficiently only in
water, but does not work well in organic solvents. More-
over, this system can be conveniently applied to catalytic
asymmetric synthesis by the use of chiral phosphine
ligands.
THF proceeded very slowly and gave the product only in
Table 2 Effect of Solvents
AgOTf (10 mol%)
O
O
Ph
PPh3 (20 mol%)
NO2
NO2
+
Initially, we examined the AgOTf-catalyzed Michael
Ph
COOt-Bu
r.t., 24 h
6
,7
COOt-Bu
addition of cyclopentanone-2-carboxylic acid tert-butyl
ester to nitrostyrene in water (Table 1). Interestingly, Ag-
OTf that was soluble in water did not catalyze the reaction
and only starting materials were recovered (entry 1).
(1.5 equiv)
dra
Yield (%)b
Entry
Solvent
CH Cl
1
2
3
4
82:18
76:24
83:17
78:22
80:20
9
3
However, when PPh was added to the system, the reac-
2
2
3
tion proceeded smoothly to give the desired product in ex-
THF
cellent yield (entry 3). It is noted that PPh itself promoted
3
THF–H O (1:1)
10
5
the reaction sluggishly (entry 2). This result clearly
2
indicated that the AgOTf–PPh complex was the real cat-
3
No solvent
alyst (entry 3). Furthermore, the water-soluble AgOTf–
5
H O
90
2
SYNLETT 2006, No. 9, pp 1410–1412
Advanced online publication: 26.04.2006
DOI: 10.1055/s-2006-939709; Art ID: U01606ST
0
1.
0
6.
2
0
0
6
a
1
Determined by H NMR analysis.
Isolated yield.
b
©
Georg Thieme Verlag Stuttgart · New York

LETTER
% and 3% yields, respectively (entries 1, 2). The reac-
Michael Additions in Water
1411
9
R1
O
O
O
tions in THF–H O and no-solvent conditions gave poor
results (entries 3, 4). It is noteworthy that this reaction was
promoted effectively only in pure water (entry 5).
NO2
COOR4
2
R2
COOMe
R3 COOR4
3
4
1
2
(R = t-Bu)
(R = Me)
4
With these interesting observations in hand, we then in-
vestigated the substrate generality of the reaction system.
As shown in Table 3, the reactions of nitroalkenes having
aromatic, heteroaromatic, and alkyl groups gave the
corresponding products in good yields. Additionally, it
was found that a range of b-ketoesters could be employed
as nucleophiles in the reaction, leading to the formation of
O
COOMe
O
O
O
O
Ot-Bu
Ph
OEt
4
5
6
Figure 1
8
the desired products in good yields.
Significantly, the present reaction system was trans-
AgOTf (10 mol%)
R1
O
O
9
(R)-Tol-BINAP
(7.5 mol%)
formed into an asymmetric version by switching the
NO2
+
R1
COOt-Bu
NO2
1
0
phosphine ligand to (R)-Tol-BINAP. As shown in
COOt-Bu
H2O, 4 °C, 96 h
Scheme 1, the Michael addition products were obtained
(1.5 equiv)
1
1
R1 = Ph: 71% yield, dr 77:23, 78% ee (major)
R1 = 2-thienyl: 63% yield, dr 74:26, 77% ee (major)
with good enantioselectivities.
The assumed catalytic cycle of the present reaction system
is shown in Scheme 2. Although the remarkable effect of
water on reaction rates is not clear at this stage, a plausible
mechanism may be put forward. In the formation of metal
enolate B, TfOH is generated and in the case of a normal
organic solvent system, the reaction mixture is homo-
geneous and the reverse reaction from B to A may be fast.
However, in a water system, the reaction mixture is
heterogeneous and metal enolate B and TfOH occupy
PAr2
PAr2
(
(
R)-Tol-BINAP
Ar = 4-MeC6H4)
Scheme 1
Table 3 Michael Additions of b-Ketoesters to Nitroalkenes in
separate phases due to the difference in their hydropho-
bicity. As a result, metal enolate B does not come into
contact with TfOH, and the reverse reaction from B to A
is suppressed. Metal enolate B and nitrostyrene would
thus combine in high concentration and the Michael addi-
tion step (B to C in Scheme 2) may proceed smoothly.
Water
AgOTf (10 mol%)
O
O
O
R1
PPh3 (20 mol%)
H2O, r.t.
NO2
NO2
R1
+
R2
OR4
R2
R3
1.5 equiv)
R3 COOR4
(
Entry R1
b-Keto- Time (h) dra
ester
Yield (%)b
O
COOt-Bu
TfOH
Ag
+
1
2
3
4
5
6
7
8
9
0
1
Ph
2-Furyl
1
1
1
2
2
2
3
3
4
5
6
24
24
24
24
48
48
3
80:20c
90
86
90
80
76
90
99
89
66
71
86
Ot-Bu
P
P
P
81:19c
O
Ag
OTf
2-Thienyl
Ph
81:19c
84:16c
P
A
O
B
O
Ph
NO2
83:17c
COOt-Bu
4-MeOC H4
NO2
6
Ph
TfOH
C
t-BuO
O
88:12c
P
P
Ph
4-NO C H
2
6
4
NO2
Ag
Ph
59:41
62:38
89:11c
66:34
67:33
O
Cyclohexyl
8
Scheme 2
Ph
Ph
Ph
96
48
24
In summary, we have developed AgOTf–PPh -catalyzed
3
1
1
Michael additions of b-ketoesters to nitroalkenes in water.
The present system promotes the reaction efficiently only
in water. Moreover, this reaction system could be applied
to catalytic asymmetric synthesis in water. Further inves-
tigations fully to elucidate the mechanism as well as the
application of the methodology to other reactions of this
system are in progress.
a
b
c
1
Determined by H NMR analysis.
Isolated yield.
Relative configuration of the major isomer was shown in below
b,c
(
Figure 1).9
Synlett 2006, No. 9, 1410–1412 © Thieme Stuttgart · New York

1
412
S. Shirakawa, S. Kobayashi
LETTER
Typical Experimental Procedures
Entry 1 of Table 3: AgOTf (0.020 mmol) and PPh (0.040 mmol)
(3) (a) Manabe, K.; Kobayashi, S. Chem. Eur. J. 2002, 8, 4095.
(b) Kobayashi, S.; Manabe, K. Acc. Chem. Res. 2002, 35,
209.
3
were added to H O (2.0 mL) and the mixture was stirred for 15 min
2
at r.t. Cyclopentanone-2-carboxylic acid tert-butyl ester (0.30
mmol) and nitrostyrene (0.20 mmol) were added to the reaction so-
lution. The reaction mixture was stirred for 24 h at r.t., and then
CH Cl (5.0 mL) and H O (5.0 mL) were added. The mixture was
(4) For recent examples of catalytic asymmetric reactions in
water, see: (a) Hamada, T.; Manabe, K.; Kobayashi, S.
Chem. Eur. J. 2006, 12, 1205. (b) Mase, N.; Nakai, Y.;
Ohara, N.; Yoda, H.; Takabe, K.; Tanaka, F.; Barbas, C. F.
III J. Am. Chem. Soc. 2006, 128, 734. (c) Hayashi, Y.;
Sumiya, T.; Takahashi, J.; Gotoh, H.; Urushima, T.; Shoji,
M. Angew. Chem. Int. Ed. 2006, 45, 958. (d) Azoulay, S.;
Manabe, K.; Kobayashi, S. Org. Lett. 2005, 7, 4593.
(e) Hamada, T.; Manabe, K.; Kobayashi, S. J. Am. Chem.
Soc. 2004, 126, 7768.
2
2
2
1
2
extracted with CH Cl (2 × 5.0 mL) and the organic phase was
2
2
concentrated. Purification of the crude product by flash chromatog-
raphy (neutral silica gel, hexane–EtOAc = 15:1) provided the de-
sired product.
1
Scheme 1 (R = Ph): AgOTf (0.020 mmol) and (R)-Tol-BINAP
(0.015 mmol) were dissolved in THF (1.0 mL) and the mixture was
(
5) For reviews of nitroalkenes in organic synthesis, see:
a) Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org.
stirred for 15 min at r.t. The solvent was evaporated and the residue
was dried in vacuo for 30 min. To the resulting white solid was add-
(
Chem. 2002, 1877. (b) Barrett, A. G. M.; Graboski, G. G.
Chem. Rev. 1986, 86, 751.
ed H O (2.0 mL) and the mixture was cooled to 4 °C. Cyclopen-
2
tanone-2-carboxylic acid tert-butyl ester (0.30 mmol) and
nitrostyrene (0.20 mmol) were added to the reaction solution and
the mixture was stirred for 96 h at 4 °C. Isolation of the product was
performed in a manner similar to that described above. IR (neat):
(
6) For Michael additions of b-ketoesters to MVK in water, see:
(
a) Ding, R.; Katebzadeh, K.; Roman, L.; Bergquist, K.-E.;
Lindström, U. M. J. Org. Chem. 2006, 71, 352.
b) Kobayashi, S.; Kakumoto, K.; Mori, Y.; Manabe, K. Isr.
(
2
977, 2930, 1746, 1722, 1554, 1454, 1373, 1250, 1146, 844, 704
–
1
1
J. Chem. 2001, 41, 247. (c) Mori, Y.; Kakumoto, K.;
Manabe, K.; Kobayashi, S. Tetrahedron Lett. 2000, 41,
cm . H NMR (600 MHz, CDCl ): d = 7.17–7.32 (m, 5 H), 5.33
3
(
dd, J = 13.1, 11.3 Hz, 0.23 H), 5.16 (dd, J = 13.0, 3.5 Hz, 0.77 H),
.98 (dd, J = 13.0, 11.3 Hz, 0.77 H), 4.84 (dd, J = 13.1, 3.4 Hz, 0.23
H), 4.13 (dd, J = 11.3, 3.4 Hz, 0.23 H), 4.04 (dd, J = 11.3, 3.5 Hz,
3107. (d) Keller, E.; Feringa, B. L. Tetrahedron Lett. 1996,
4
37, 1879. (e) Hamashima, Y.; Hotta, D.; Umebayashi, N.;
Tsuchiya, Y.; Suzuki, T.; Sodeoka, M. Adv. Synth. Catal.
2005, 347, 1576.
0
1
2
1
3
.77 H), 2.24–2.42 (m, 2 H), 1.77–1.99 (m, 4 H), 1.46 (s, 2.07 H),
1
3
.45 (s, 6.93 H) ppm. C NMR (150 MHz, CDCl ): d = 215.9,
3
(
7) For AgOTf-catalyzed reactions in water or aqueous media,
see: (a) Loncaric, C.; Manabe, K.; Kobayashi, S. Adv. Synth.
Catal. 2003, 345, 475. (b) Loh, T.-P.; Zhou, J.-R.
Tetrahedron Lett. 2000, 41, 5261; see also ref. 6b.
8) The appearance of organic materials in the reaction mixture
12.7, 170.3, 168.4, 135.7, 135.6, 129.4, 129.2, 128.9, 128.7, 128.3,
28.1, 83.5, 83.3, 77.2, 76.6, 63.0, 62.8, 47.3, 46.3, 39.5, 37.8, 33.6,
+
1.5, 27.78, 27.76, 19.6, 19.4 ppm. HRMS (FAB ): m/z calcd for
+
+
C H NO : 334.1649 [M + H] ; found: 334.1660 [M + H] . HPLC
1
8
24
5
(
Chiralcel OD-H columun (hexane–i-PrOH = 150:1, 1.0 mL/min,
54 nm) t (major diastereomer, 78% ee) = 24.9 min (major enanti-
(solid, liquid, droplets, etc.) depends on the substrate
2
R
species.
omer), 29.5 min (minor enantiomer); t (minor diastereomer, 61%
R
(9) (a) Evans, D. A.; Seidel, D. J. Am. Chem. Soc. 2005, 127,
ee) = 17.7 min (major enantiomer), 20.1 min (minor enantiomer).
9958. (b) Okino, T.; Hoashi, Y.; Furukawa, T.; Xu, X.;
Takemoto, Y. J. Am. Chem. Soc. 2005, 127, 119. (c) Li, H.;
Wang, Y.; Tang, L.; Wu, F.; Liu, X.; Guo, C.; Foxman, B.
M.; Deng, L. Angew. Chem. Int. Ed. 2005, 44, 105.
Acknowledgment
This work was partially supported by a Grant-in-Aid for Scientific
Research from the Japan Society of the Promotion of Science
(
d) Watanabe, M.; Ikagawa, A.; Wang, H.; Murata, K.;
Ikariya, T. J. Am. Chem. Soc. 2004, 126, 11148. (e) Barnes,
D. M.; Ji, J.; Fickes, M. G.; Fitzgerald, M. A.; King, S. A.;
Morton, H. E.; Plagge, F. A.; Preskill, M.; Wagaw, S. H.;
Wittenberger, S. J.; Zhang, J. J. Am. Chem. Soc. 2002, 124,
(JSPS). S.S. thanks the JSPS for a post-doctoral research fel-
lowship.
13097.
References and Notes
(
10) For selected examples of AgOTf–BINAP-catalyzed
asymmetric reactions, see: (a) Momiyama, N.; Yamamoto,
H. J. Am. Chem. Soc. 2004, 126, 5360. (b) Yanagisawa, A.;
Nakashima, H.; Ishiba, A.; Yamamoto, H. J. Am. Chem. Soc.
(
1) (a) Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous
Media; Wiley: New York, 1997. (b) Organic Synthesis in
Water; Grieco, P. A., Ed.; Blackie Academic and
1996, 118, 4723. (c) Yanagisawa, A.; Yamamoto, H. J.
Professional: London, 1998. (c) Li, C.-J. Chem. Rev. 2005,
Synth. Org. Chem. Jpn. 2005, 63, 888.
105, 3095. (d) Li, C.-J. Chem. Rev. 1993, 93, 2023.
(11) Various Ag/(R)-Tol-BINAP ratios were tested, and the ratio
in Scheme 1 gave better results.
(
2) (a) Lindström, U. M.; Andersson, F. Angew. Chem. Int. Ed.
2006, 45, 548. (b) Pirrung, M. C. Chem. Eur. J. 2006, 12,
(
12) Extraction solvents other than CH Cl (ex. EtOAc) can also
1312. (c) Li, C.-J.; Chen, L. Chem. Soc. Rev. 2006, 35, 68.
2
2
be used.
(
1
d) Otto, S.; Engberts, J. B. F. N. Org. Biomol. Chem. 2003,
, 2809. (e) Breslow, R. Acc. Chem. Res. 1991, 24, 159.
Synlett 2006, No. 9, 1410–1412 © Thieme Stuttgart · New York