2,6-Bis[(S)-4-isopropyloxazolin-2-yl](pyridine)rhodium Trichloride1


[119038-51-6]  · C17H23Cl3N3O2Rh  · 2,6-Bis[(S)-4-isopropyloxazolin-2-yl](pyridine)rhodium Trichloride  · (MW 510.65) (Pybox-(S,S)-ip)

[118949-61-4]  · C17H23N3O2  · 2,6-Bis[(S)-4-isopropyloxazolin-2-yl]pyridine  · (MW 301.39)

(highly enantioselective catalyst for hydrosilylative reduction of methyl ketones in combination with Ph2SiH2 and AgBF45,6)

Alternate Name: [Pybox-(S,S)-ip]RhCl3.

Physical Data: [Pybox-(S,S)-ip]RhCl3: mp 279 °C (dec); [a]20D = +543° (c 1.09, CH2Cl2); Pybox-(S,S)-ip: white solid, mp 152-153 °C, [a]26D = -116.8° (c 1.0, CH2Cl2).6

Solubility: sol CH2Cl2, CHCl3, and alcohols; slightly sol THF and ethyl acetate; insol diethyl ether, benzene, and H2O.

Form Supplied in: orange solid; synthesized with RhCl3(H2O)3 and Pybox-(S,S)-ip in ethanol at reflux for 3 h. The crude solid was purified by silica gel column chromatography with ethyl acetate and methanol as eluents; TLC Rf = 0.45 (ethyl acetate/methanol = 5:1, Merck Art 5715). Drying: although the rhodium compound is nonhygroscopic, it contains some quantity of water or solvents after the purification by chromatography. It should be dried under vacuum (< ca. 1 Torr) for 1 day at 20-60 °C before use.

Handling, Storage, and Precautions: stable in air and moisture.

Enantioselective Reduction of Ketones.

Hydrosilylation of ketones with chiral metal catalysts and hydrosilanes followed by hydrolysis provides optically active secondary alcohols from ketones. Most of the enantioselective hydrosilylations of ketones have been carried out with rhodium catalysts and chiral phosphine ligands. These systems give a middle range of enantioselectivities, especially with diphenylsilane and 1-naphthylsilane.2 In the 1980s, many splendid results of more than 90% ee were reported with rhodium catalysts of chiral nitrogen-containing ligands such as pyridinethiazolidine3 and pyridineoxazoline-t-Bu,4,5 which are easily accessible from readily available, optically active amino acids and amino alcohols.

The 2,6-bis(oxazolinyl)pyridine ligand [Pybox-(S,S)-ip] was also developed as a chiral adjuvant for the asymmetric hydrosilylation of ketones. The Pybox ligand can be synthesized in large scale as a white crystalline solid by condensation of (S)-valinol and pyridine-2,6-dicarboxylic acid.6 Heating of the ethanol solution of Pybox-(S,S)-ip and Rhodium(III) Chloride trihydrate gave the stable complex [Pybox-(S,S)-ip]RhCl3 in 70% yield. Diphenylsilane and the catalytic amount of the Pybox-rhodium(III) complex with the aid of Silver(I) Tetrafluoroborate reduced aromatic and aliphatic methyl ketones in THF solution at -5 to 25 °C. After hydrolysis of the product silyl ethers in acidic methanol at 0 °C, optically active secondary alcohols were obtained in high yields and high enantioselectivities, e.g. from acetophenone to 1-phenylethanol in 91% yield and 94% ee (S) (eq 1; Table 1).6

The stereoselectivity of the reduction of 4-t-butylcyclohexanone has been shown to give high proportions (>90%) of the cis (equatorial) alcohol in hydrogenations with heterogeneous rhodium catalysts or in transfer hydrogenations with homogeneous rhodium or iridium catalysts.7 However, the Pybox-rhodium catalyst gave a ratio of 67:33 of the trans/cis alcohol,8 similar to that obtained with the Wilkinson catalyst (eq 2).9 Despite the low axial/equatorial selectivity, the enantioselectivities of the reduction of 2-phenyl- and 2-methoxycarbonylmethylcyclohexanone were extremely high (eqs 3 and 4).8 Chalcone was also reduced to the allylic alcohol in 71% ee (eq 5).6

In place of diphenylsilane, 1,2-bis(dimethylsilyl)ethane was applied to the reduction of several ketones by the combination of the Pybox-rhodium complex and Silver(I) Trifluoromethanesulfonate to give the corresponding silyl enol ether exclusively (eq 6).10

Chiral 4-substituted Pybox derivatives (1) were synthesized as chiral adjuvants to study remote electronic effects of the substituents in the asymmetric hydrosilylation.11 The 4-Cl-Pybox-(S,S)-ip-Rh catalyst afforded the highest result (80% ee (S)) for the reduction of 2-octanone to 2-octanol in 88% yield.

1. (a) Brunner, H.; Nishiyama, H.; Itoh, K. Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993, Chapter 6. (b) Bolm, C. AG(E) 1991, 30, 542.
2. (a) Ojima, I.; Clos, N.; Bastos, C. T 1989, 45, 6901. (b) Ojima, I. The Chemistry of Organic Silicon Compounds, Part 2; Patai, S.; Rappoport, Z., Ed.; Wiley: New York, 1989; pp 1479-1526. (c) Brunner, H. S 1988, 645. (d) Ojima, I.; Hirai, K. Asymmetric Synthesis; Morrison, J. D., Ed.; Academic: Orlando, Fl, 1985; Vol. 5, Chapter 4, pp 103-146.
3. (a) Brunner, H.; Riepl, G.; Weitzer, H. AG(E) 1983, 22, 331. (b) Brunner, H.; Becker, R.; Riepl, G. OM 1984, 3, 1354. (c) Brunner, H.; Kürzinger, A. JOM 1988, 346, 413.
4. Brunner, H.; Obermann, U. CB 1989, 122, 499.
5. Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.; Kondo, M.; Itoh, K. OM 1989, 8, 846.
6. Nishiyama, H.; Kondo, M.; Nakamura, T.; Itoh, K. OM 1991, 10, 500.
7. (a) Henbest, H. B.; Mitchell, T. R. B. JCS(C) 1970, 785. (b) Kaspar, J.; Spogliarich, R.; Graziani, M. JOM 1982, 231, 71. (c) Felföldi, K.; Kapocsi, I.; Bartók, M. JOM 1984, 277, 439. (d) Bennett, M. A.; Mitchell, T. R. B. JOM 1985, 295, 223. (e) Smith, T. A.; Maitlis, P. M. JOM 1985, 289, 385.
8. Nishiyama, H.; Park, S.-B.; Itoh, K. TA 1992, 3, 1029.
9. (a) Ishiyama, J.; Senda, Y.; Shinoda, I.; Imaizumi, S. BCJ 1979, 52, 2353. (b) Semmelhack, M. F.; Misra, R. N. JOC 1982, 47, 2469.
10. Nagashima, H.; Ueda, T.; Nishiyama, H.; Itoh, K. CL 1993, 347.
11. Nishiyama, H.; Yamaguchi, S.; Kondo, M.; Itoh, K. JOC 1992, 57, 4306.

Hisao Nishiyama

Toyohashi University of Technology, Japan

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