(1R,5R,6R)-Spiro[4.4]nonane-1,6-diyl Diphenylphosphinous acid Ester (R-SpirOP)

[197159-86-7]  · C33H34O2P2  · (MW 524.578)

(spirocyclic phosphinite ligand used as a rhodium catalyst in the asymmetric hydrogenation of prochiral olefins)

Physical Data: mp 96-96.5 °C; [a]D -43.2 (c 0.104, CHCl3).

Solubility: soluble in alcohol, ether, and most organic solvents.

Analysis of Reagent Purity: 1H NMR (400 MHz, CDCl3) d 1.33 (m, 2H), 1.65-1.82 (m, 10H), 4.53 (d, J = 5.3 Hz, 2H), 7.10-7.52 (m, 20H). 13C NMR (100 MHz, CDCl3) d 20.9,32.5 (d, 3JP-C =  7.9 Hz), 33.1, 63.2, 87.3 (d,2JP-C = 18.9 Hz), 128.5 (d, 3JP-C =  6.9 Hz), 128.7, 128.8 (d, 3JP-C = 8.8 Hz), 129.6, 130.0 (d, 2JP-C = 21.8 Hz), 130.9 (d, 2JP-C = 23.4 Hz), 143.4 (d, 1JP-C =  12.0 Hz), 145.2 (d, 1JP-C = 21.8 Hz). 31P NMR (160 MHz, CDCl3) d 102.8. IR (KBr), 3060, 2968, 2907, 2868, 1486, 1440, 1348, 1104, 1006, 940, 742, 703 cm-1. Analytically calculated for C33H34O2P2: C, 75.57; H, 6.48; P, 11.83. Found: C, 75.23; H, 6.41; P, 11.71. MS: m/z 524 (M+).

Preparative Methods: (-)-(1R,5R,6R)-(cis,cis)-spiro[4.4]nona-ne-1,6-diol1 (78 mg, 0.50 mmol), 4-N,N-dimethylaminopyridi-ne (12.4 mg, 0.10 mmol), and triethylamine (101.9 mg, 1.00 mmol) in THF (3 mL) were charged to a 10 mL Schlenk flask under a nitrogen atmosphere. This flask was cooled in an ice-cooled water bath. A solution of chlorodiphenylphosphine (0.18 mL, 1.0 mmol) in THF (1 mL) was added dropwise to the above solution, the ice-water bath was removed and the mixture was stirred at room temperature for 8 h. The solution was filtered to remove the solid triethylamine hydrochloride. THF was removed in vacuo and the residue was dissolved in approximately 10 mL of anhydrous diethyl ether with heating. After cooling in a refrigerator, white needle shaped crystals were obtained (218 mg, 83%).

Handling, Storage, and Precautions: R-SpirOP is obtained as a white solid that is stable in air but decomposes gradually in alcoholic solution. To help prevent oxidation, storage under a nitrogen atmosphere is recommended. The stability of R-SpirOP has been tested in methanol solution through a 31P NMR study. Observable decomposition occurred in 2 h and complete decomposition in 24 h.

Hydrogenation of Amidoacrylic Acids2

When a cationic rhodium catalyst containing R-SpirOP is used in the asymmetric hydrogenation of 2-acetamidoacrylic acid at ambient temperature and under 1 atm of H2 in methanol, the desired 2-acetamidopropio-nic acid is obtained in > 99.9% ee. Under similar conditions, the asymmetric hydrogenation of the methyl ester of 2-acetamidoacr-ylic acid gave 100% conversion to the corresponding hydrogenation product in 99.0% ee (1).

Further studies for the hydrogenation of other prochiral amidoacrylic acids confirmed that the high enantioselectivity of the catalyst is quite general. Several (Z)-2-acetamido-3-arylacrylic acids were hydrogenated with this catalyst and in all cases the desired products were found to have ee values of over 97%. More detailed data are summarized in 1.

The enantioselectivities of Rh(R-SpirOP)+ in the asymmetric hydrogenation of the methyl esters of (Z)-2-acetamido-3-arylacr-ylic acids were also found to be very high (2).

In addition to the high enantioselectivity, the rate of the hydrogenation using Rh(R-SpirOP)+ catalyst is also very fast. When a substrate/catalyst ratio of 10 000 was used and when the reaction was carried out at ambient temperature under 200 psi H2, > 99.9% conversion of 2-acetamidoacrylic acid to 2-acetamidopropionic acid (96.8% ee) was observed in 1 h. The detailed results are shown in 3.

Hydrogenation of Enol Esters

In addition to the high activity and excellent enantioselectivity being obtained in the asymmetric hydrogenation of amidoacrylic acid substrates, the cationic complex Rh(R-SpirOP)+ afforded excellent ee in the hydrogenation of enol esters (2). The best result was derived from the hydrogenation of enol esters in acetone at 0 °C and under 1 atm of H2 for 1 h.

Hydrogenation of Enamides3

Except for the asymmetric hydrogenation of specific cyclic enamides with Ru(BINAP) catalyst which shows high enantioselectivity,4 the successful enantioselective hydrogenation of simple a-substituted enamides has been relatively rare.5 The Ru(R-SpirOP)+ catalyst was found to be effective in the asymmetric hydrogenation of a series of a-substituted enamides (4). The best result (97.4% ee) was achieved in the hydrogenation of N-acetyl-a-(2-furanyl)ethena-mine (entry 7 of 4). The high enantioselectivity (97.4% ee) and the fast hydrogenation rate (10 min, 100% conversion compares favorably with the Rh-Me-DuPHOS system (96.1% ee, 15 h, 100% conversion).6

Hydrogenation of Itaconic Acid

Compared to the hydrogenation of amidoacylic acids, enols, and enamides, the Rh(R-SpirOP)+ catalyzed hydrogenation of itaconic acid was less successful. After optimizing the hydrogenation conditions, 76.8% ee of the corresponding product was obtained in isopropanol at ambient temperature under 100 psi H2 for 2 h (3).


1. Chan, A. S. C.; Lin, C. C.; Sun, J.; Hu, W.; Li, Z.; Pan, W.; Mi, A.; Jiang, Y.; Huang, T.-M.; Yang, T.-K.; Chen, J.-H.; Wang, Y.; Lee, G.-H., Tetrahedron: Asymmetry 1995, 6, 2953, and references therein.
2. Chan, A. S. C.; Hu, W.; Pai, C.-C.; Lau, C.-P.; Jiang, Y.; Mi, A.; Yan, M.; Sun, J.; Lou, R.; Deng, J., J. Am. Chem. Soc. 1997, 119, 9570.
3. Hu, W.; Yan, M.; Lau, C.-P.; Yang, S. M.; Chan, A. S. C., Tetrahedron Lett. 1999, 40, 973.
4. (a) Noyori, R.; Ohta, M.; Hsiao, Y.; Kitamura, M.; Ohta, T.; Takaya, H., J. Am. Chem. Soc. 1986, 108, 7117. (b) Kitamura, M.; Hsiao, T.; Noyori, R.; Takaya, H., Tetrahedron Lett. 1987, 28, 4829. (c) Heiser, B.; Broger, E. A.; Crameri, Y., Tetrahedron: Asymmetry 1991, 2, 51. (d) Tschaen, D. M.; Abramson, L.; Cai, D.; Desmond, R.; Dolling, U.-H.; Frey, L.; Karady, S.; Shi, Y.-J.; Verhoeven, T. R., J. Org. Chem. 1995, 60, 4324.
5. Zhang, F.-Y.; Pai, C.-C.; Chan, A. S. C., J. Am. Chem. Soc. 1998, 120, 5808.
6. Burk, M. J.; Wang, Y. M.; Lee, J. R., J. Am. Chem. Soc. 1996, 118, 5142.

Wai Him Kwok, Wen Hao Hu & Albert S. C. Chan

The Hong Kong Polytechnic University, Hong Kong



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