Synthesis of a Bulky and Electron-Rich
Derivative of SEGPhos and Its Application
in Ru-Catalyzed Enantioselective
Hydrogenation of â-Ketoesters
†
‡
†
†
Xiaobing Wan, Yanhui Sun, Yunfei Luo, Dao Li, and
Zhaoguo Zhang*,†
State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry,
Shanghai 200032, China, and Department of Chemistry,
Nanjing University, Nanjing 210093, China
Received September 1, 2004
2
FIGURE 1. Some atropisomeric C -symmetric biaryl ligands.
preparable, finely tunable, easily handled, cheap yet
efficient ligands is still a challenging issue.
Herein, we report the synthesis and resolution of a
bulky and electron-rich derivative of SEGPhos (Scheme
1
) and its application in Ru-catalyzed asymmetric hy-
drogenation reaction. The synthetic route was concise and
straightforward: Grignard reagent of 5-bromo-benzo[1,3]-
The synthesis and resolution of a bulky and electron-rich
derivative of SEGPhos and its application in Ru-catalyzed
asymmetric hydrogenation reaction of â-ketoesters are
reported. Up to 99.5% ee was achieved. Under solvent-free
reaction conditions, acetoacetates could be reduced with good
enantioselectivity and high efficiency; a TON of 20 000 was
obtained within 3.5 h. The results obtained were comparable
to those when SEGPhos was applied.
dioxole (1) was slowly added to a solution of PCl
3
in dry
THF, followed by oxidation with H to provide (2).
2
O
2
Treatment of (2) with 1.2 equiv of LDA at -15 °C for 4 h
and oxidative coupling with anhydrous ferric chloride
afforded 3 in moderate yield (42.1%). Optical resolution
of 3 was performed by employing (-)-2,3-dibenzoyl
tartaric acid ((-)-DBTA) as a resolving agent in i-PrOH.
At last, a steric and electron-rich biaryl ligand (4) was
Transition metal-catalyzed enantioselective hydrogen-
ation has been established as one of the most efficient
strategies for the synthesis of optically pure molecules,
in which the reasonable design of chiral ligands is the
key issue for obtaining high activity and selectivity.
Over the past 30 years, thousands of chiral ligands have
been synthesized to effect a variety of catalytic asym-
(
4) (a) Schmid, R.; Cereghetti, M.; Heiser, B.; Sch o¨ nholzer, P.;
Hansen, H.-J. Helv. Chim. Acta 1988, 71, 897. (b) Schmid, R.; Foricher,
J.; Cereghetti, M.; Sch o¨ nholzer, P. Helv. Chim. Acta 1991, 74, 370. (c)
Schmid, R.; Broger, E. A.; Cereghetti, M.; Crameri, Y.; Foricher, J.;
Lalonde, M.; M u¨ ller, R. K.; Scalone, M.; Schoettel, G.; Zutter, U. Pure.
Appl. Chem. 1996, 68, 131.
1
,2
(
5) Zhang, Z.; Qian, H.; Longmire, J.; Zhang, X. J. Org. Chem. 2000,
5, 6223.
6) (a) Pai, C.-C.; Lin, C.-W.; Lin, C.-C.; Chen, C.-C.; Chan, A. S. C.;
6
(
metric hydrogenation processes in both academic re-
Wong, W.-K. J. Am. Chem. Soc. 2000, 122, 11513. (b) Wu, J.; Chen,
H.; Kwok, W.; Guo, R.; Zhou, Z.; Yeung, C.; Chan, A. S. C. J. Org.
Chem. 2002, 67, 7908. (c) Wu, J.; Chen, H.; Kwok, W.-H.; Lam, K.-H.;
Zhou, Z.-Y.; Yeung, C.-H.; Chan, A. S. C. Tetrahedron Lett. 2002, 43,
1539.
search and industrial production.1,2 Many atropisomeric
3
C
2
-symmetric biaryl biphosphines such as BINAP, BI-
PHEMP, MeO-BIPHEP, TunePhos,5 P-Phos,6 SEG-
Phos, Diflurophos, and other important biaryl phos-
phine ligands (Figure 1) have been developed in the past
4
4
7
8
(7) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura,
T.; Kumobayashi, H. Adv. Synth. Catal. 2001, 343, 264.
9
(
8) Jeulin, S.; Duprat de Paule, S.; Ratovelomanana-Vidal, V.; Gen eˆ t,
2
0 years. Although tremendous success has been achieved
J.-P.; Champion, N.; Dellis, P. Angew. Chem., Int. Ed. 2004, 43, 320.
9) (a) Yamamoto, N.; Masano, M.; Toshiaki, M.; Achiwa, K. Chem.
(
in catalytic asymmetric hydrogenation, developing easily
Pharm. Bull. 1991, 39, 1085. (b) Zhang, X.; Mashima, K.; Koyano, K.;
Sayo, N.; Kumobayashi, H.; Akutagawa, S.; Takaya, H. J. Chem. Soc.,
Perkin Trans. 1 1994, 16, 2039. (c) Enev, V.; Ewers, Ch. L. J.; Harre,
M.; Nickisch, K.; Mohr, J. T. J. Org. Chem. 1997, 62, 7092. (d) Gelpke,
A. E. S.; Kooijman, H.; Spek, A. L.; Hiemstra, H. Chem. Eur. J. 1999,
5, 2472. (e) Henschke, J. P.; Burk, M. J.; Malan, C. G.; Herzberg, D.;
Peterson, J. A.; Wildsmith, A. J.; Cobley, C. J.; Casy, G. Adv. Synth.
Catal. 2003, 345, 300. (f) Hu, A.; Ngo, H. L.; Lin, W. Angew. Chem.,
Int. Ed. 2004, 43, 2501. (g) Pai, C.-C.; Li, Y.-M.; Zhou, Z.-Y.; Chan, A.
S. C. Tetrahedron Lett. 2002, 43, 2789. (h) Qiu, L.; Qi, J.; Pai, C.-C.;
Chan, S.; Zhou, Z.; Choi, M. C. K.; Chan, A. S. C. Org. Lett. 2002, 4,
4599. (i) Duprat de Paule, S.; Jeulin, S.; Ratovelomanana-Vidal, V.;
Gen eˆ t, J.-P.; Champion, N.; Dellis, P. Tetrahedron Lett. 2003, 44, 823.
(j) Gen eˆ t, J.-P. Acc. Chem. Res. 2003, 36, 908. (k) Sun, Y.; Wan, X.;
Guo, M.; Wang, D.; Dong, X.; Pan, Y.; Zhang, Z. Tetrahedron:
Asymmetry 2004, 15, 2185.
†
Shanghai Institute of Organic Chemistry.
‡
Nanjing University.
(
1) (a) Noyori, R. Angew. Chem., Int. Ed. 2002, 41, 2008, and
references therein. (b) Knowles, W. S. Adv. Synth. Catal. 2003, 345,
. (c) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley:
3
New York, 1994. (d) Ojima, I. Catalytic Asymmetric Synthesis, 2nd ed.;
Wiley: New York, 2000. (e) Brown, J. M. In Comprehensive Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
Berlin, 1999.
(2) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029.
(3) (a) Miyashita, A.; Yasuda, H.; Takaya, H.; Toriumi, K.; Ito, T.;
Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932. (b) Noyori,
R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345. (c) Noyori, R. Chem.
Soc. Rev. 1989, 18, 187.
10.1021/jo048466d CCC: $30.25 © 2005 American Chemical Society
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J. Org. Chem. 2005, 70, 1070-1072
Published on Web 01/05/2005