although many chiral ligands have been successfully applied
for asymmetric hydrogenation of the parent itaconic acid or
Table 1. Asymmetric Hydrogenation of â-Substituted Itaconic
Acid Derivatives with the Rh-TangPhos Catalyst
5
its methyl ester, there are only a few successful results for
6
hydrogenation of â-substituted itaconic acid derivatives. The
best catalytic system to date is the Rh-Et-DuPhos catalyst,
which has shown great ee values for both â-alkyl and â-aryl
7
itaconic acids. We applied TangPhos as the ligand for
hydrogenation of dimethyl itaconate (Scheme 1). The initial
entrya
R1
R2b
ee (%)c
1
2
3
4
5
6
7
8
9
H
H
99
96
95
97
97
>99
99
99
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH(CH3)2
Ph
p-MeO-Ph
p-Me-Ph
p-Cl-Ph
m-Cl-Ph
1-naphthyl
2-naphthyl
Scheme 1. Asymmetric Hydrogenation of Dimethyl Itaconate
99
a
The hydrogenations were carried out at room temperature in THF under
0 psi of hydrogen pressure with [Rh(TangPhos)(nbd)]SbF6 (0.5 mol %)
2
reaction was carried out at room temperature under 20 psi
of H pressure with 0.5 mol % of [Rh(TangPhos)nbd]SbF
2 6
as the catalyst precursor. When methanol was used as the
reaction solvent, the hydrogenation product (S)-dimethyl
as the catalyst precursor. All reactions proceeded completely. The absolute
configurations of the products were determined as S by comparing the optical
rotations with reported values bMost substrates (except entry 1) were
7
c
employed as crude E/Z mixtures ranging from 2/1 to >10/1.
The ee
values were determined by chiral HPLC (Chiralcel OD-H) or chiral GC
(chiralselect 1000) after conversion of the hydrogenation products into their
dimethyl esters.
2-methylsuccinate was obtained in 98% ee and in quantitative
yield. Further screening of the reaction solvent showed that
THF was a better solvent in terms of the enantioselectivity
(
99% ee in THF). We thus used THF as the solvent to test
the catalytic efficiency of the Rh-TangPhos system for this
reaction. When 0.02 mol % [Rh(TangPhos)nbd]SbF (2
as the catalyst precursor. As shown in Table 1, a variety of
E/Z isomeric mixtures of â-alkyl and â-aryl itaconic acid
derivatives provide excellent ee values with complete
conversions. No major electronic effect was observed in
hydrogenation of â-aryl itaconic acid derivatives, since all
electronic-rich and electronic-poor substrates gave excellent
ee values (entries 4-6). Two naphthyl derivatives also
provided extremely high ee values (entries 8 and 9). It is
noteworthy that these ee values are comparable to those
6
µmoL) was used as the catalyst precursor, the hydrogenation
of dimethyl itaconate (10 mmol) proceeded smoothly to give
the product in complete conversion (5000 TON) and in 99%
ee (Scheme 1).
We then applied the Rh-TangPhos catalyst to hydrogena-
tion of various â-substituted itaconic acid derivatives (Table
1
). The substrates were prepared from dimethyl succinate
7
7,8
obtained with the Rh-Et-DuPhos system.
and aldehydes via Stobbe condensation. The obtained E/Z
isomeric mixtures of the substrates were directly used for
hydrogenation. The hydrogenations were conducted at room
Asymmetric hydrogenation of enol acetates may serve as
an alternative to direct hydrogenation of ketones since the
chiral acetate products can be easily transformed into chiral
temperature in THF with 0.5 mol % Rh(TangPhos)nbd]SbF
6
9
10
alcohols. Several efficient chiral Rh or Ru catalysts have
been reported for this type of substrate. For example,
asymmetric hydrogenation of electron-poor enol actates
(
3) (a)Tang, W.; Zhang, X. Angew. Chem., Int. Ed. Engl. 2002, 41, 1612.
b) Tang, W.; Zhang, X. Org. Lett. 2002, 4, 4159.
4) (a) Morimoto, T.; Chiba, M.; Achiwa, K. Tetrahedron Lett. 1990,
1, 261. (b) Heitsch, H.; Henning, R.; Kleemann, H.-W.; Linz, W.; Nickel,
(
(
9
c
9e
bearing carboxylic ester or phosphonate groups has been
successfully realized by the Rh-DuPhos system. High enan-
tioselectivities were also obtained for some acylic enol
acetates bearing a vinylic or acetylenic substituent.9b Up to
3
W.-U.; Ruppert, D.; Urbach, H.; Wagner, A. J. Med. Chem. 1993, 36, 2788.
5) (a) Ojima, I.; Kogure, T.; Achiwa, K. Chem. Lett. 1978, 567. (b)
Ojima, I.; Kogure, T. Chem. Lett. 1978, 1145. (c) Achiwa, K. Tetrahedron
Lett. 1978, 1475. (d) Christofel, W. C.; Vineyard, B. D. J. Am. Chem. Soc.
(
1
979, 101, 4406. (e) Kawano, H.; Ishii, Y.; Ikariya, T.; Saburi, M.;
Yoshikawa, S.; Uchida, Y.; Kumamoto, N. Tetrahedron Lett. 1987, 28, 1905.
f) Takahashi, H.; Achiwa, K. Chem. Lett. 1987, 1921. (g) Takahashi, H.;
9
9% ee values have been reported in hydrogenation of cyclic
9d
(
aromatic enol acetates with a Rh-PennPhos catalyst.
Yamamoto, N.; Takeda, H.; Achiwa, K. Chem. Lett. 1989, 559. (h) Inoguchi,
K.; Morimoto, T.; Achiwa, K. J. Organomet. Chem. 1989, 370, C9. (i)
Chiba, T.; Miyashita, A.; Nohira, H.; Takaya Tetrahedron Lett. 1991, 32,
However, for acyclic aromatic enol acetates, only modest to
good ee values have been reported (Rh-DuPhos: up to 91%
9
a
9d
4
1
745. (j) Kuwano, R.; Sawamura, M.; Ito, Y. Tetrahedron: Asymmetry
995, 6, 2521. (k) Berens, U.; Burk, M. J.; Gerlach, A.; Hems, W. Angew.
ee; Rh-PennPhos: up to 85% ee: Ru--BINAP: 73%
10a
ee ). We applied the Rh-TangPhos catalyst for asymmetric
Chem., Int. Ed. 2000, 39, 1981. (l) Gridnev, I.; Yamanoi, Y.; Higashi, N.;
Tsuruta, H.; Yasutake, M.; Imamoto, T. AdV. Synth. Catal. 2001, 343, 118.
(
6) (a) Morimoto, T.; Chiba, M.; Achiwa, K. Tetrahedron lett. 1989,
(9) (a) Burk, M. J. J. Am. Chem. Soc. 1991, 113, 8518. (b) Boaz, N. W.
Tetrahedron Lett. 1998, 39, 5505. (c) Burk, M. J.; Karlberg, C. S.; Pizzano,
A. J. Am. Chem. Soc. 1998, 120, 4345. (d) Jiang, Q.; Xiao, D.; Zhang, Z.;
Cao, P.; Zhang, X. Angew. Chem., Int. Ed. 1999, 38, 516. (e) Burk, M. J.;
Stammers, T. A.; Straub, J. A. Org. Lett. 1999, 1, 387. (f) Li, W.; Zhang,
Z.; Xiao, D.; Zhang, X. J. Org. Chem. 2000, 65, 3489.
(10) (a) Ohta, T.; Miyake, T.; Seido, N.; Kumobayashi, H.; Takaya, H.
J. Org. Chem. 1995, 60, 357. (b) Kuroki, Y.; Asada, D.; Sakamaki, Y.;
Iseki, K. Tetrahedron Lett. 2000, 41, 4603.
3
1
4
0, 735. (b) Morimoto, T.; Chiba, M.; Achiwa, K. Chem. Pharm. Bull.
993, 41, 1149. (c) Morimoto, T.; Chiba, M.; Achiwa, K. Tetrahedron 1993,
9, 1793. (d) Jendralla, H.; Henning, R.; Seuring, B.; Herchen, J.;
Kulitzscher, B.; Wunner, J. Synlett 1993, 155. (e) Jendralla, H. Synthesis
994, 494.
7) Burk, M. J.; Bienewald, F.; Harris, M.; Zanotti-Gerosa, A. Angew.
Chem., Int. Ed. 1998, 37, 1931.
8) Johnson, W. S.; Daub, G. H. Org. React. (N.Y.) 1951, 6, 1-73.
1
(
(
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Org. Lett., Vol. 5, No. 2, 2003