Bis(bicyclo[2.2.1]hepta-2,5-diene)rhodium Perchlorate-(R)-1-(S)-1,2-Bis(diphenylphosphino)ferrocenylethanol1

(1)

[60576-58-1]  · C14H16ClO4Rh  · Bis(bicyclo[2.2.1]hepta-2,5-diene)rhodium Perchlorate-(R)-1-(S)-1,2-Bis(diphenylphosphino)ferrocenylethanol  · (MW 386.64) (2)

[71049-99-5]  · C36H32FeOP2  · Bis(bicyclo[2.2.1]hepta-2,5-diene)rhodium Perchlorate-(R)-1-(S)-1,2-Bis(diphenylphosphino)ferrocenylethanol  · (MW 598.44)

(catalyst for asymmetric hydrogenation of functionalized carbonyl compounds2,3 and enol phosphinates4)

Alternate Name: (1): [Rh(nbd)2]ClO4; (2): (R)-(S)-BPPFOH.

Physical Data: (R)-(S)-BPPFOH: [a]25D -285° (c 0.5, CHCl3); mp 154-155 °C.

Solubility: [Rh(nbd)2]ClO4: sol CH2Cl2; insol THF, hexane.

Form Supplied in: [Rh(nbd)2]ClO4: rust-brown crystals containing 1 mol THF solvent of recrystallization.

Preparative Method: (R)-(S)-BPPFOH is prepared from optically resolved (R)-N,N-dimethyl-1-ferrocenylethylamine (3) as shown in eq 1.5 Dilithiation of (R)-(3) with n-Butyllithium followed by treatment with Chlorodiphenylphosphine affords (R)-(S)-BPPFA stereoselectively. It is treated with an excess of Acetic Anhydride at 100 °C to give (R)-(S)-BPPFOAc with retention of configuration. Finally, treatment with BuLi followed by hydrolysis affords (R)-(S)-BPPFOH in enantiomerically pure form.

Purification: (R)-(S)-BPPFOH: chromatography on alumina (EtOAc) followed by recrystallization from ethanol.

Handling, Storage, and Precautions: [Rh(nbd)2]ClO4: explosive when heated.

Asymmetric Hydrogenation of Functionalized Carbonyl Compounds.

(R)-(S)-BPPFOH is designed to have a secondary interaction with a carbonyl substrate through the hydroxy group on the side chain of the ferrocene ring. This additional interaction enables a substrate to coordinate to the metal center with preferential recognition of one prochiral face. In addition to the title combination reagent, [Rh(cod)2]ClO4 and (R)-(S)-BPPFOH and the isolated complex, [Rh{(R)-(S)-BPPFOH}(diene)]ClO4, will be considered together below.

A high optical yield is attained with [Rh{(R)-(S)-BPPFOH}(cod)]ClO4 in the hydrogenation of pyruvic acid to afford (R)-2-hydroxypropionic acid (eq 2).2 Addition of 1 equiv of Triethylamine is necessary to obtain optimal enantioselectivity. The beneficial effect of the hydroxy group on the side chain of the ferrocene ring is demonstrated by the fact that use of (R)-1-(S)-1,2-bis(diphenylphosphino)ferrocenylethyldimethylamine ((R)-(S)-BPPFA), which is analogous to (R)-(S)-BPPFOH but lacks the hydroxy group, gives a much inferior result. In the case of a simple ketone, e.g. acetophenone or methyl t-butyl ketone, the enantioselectivity is around 40-50% ee.

Hydrogenation of aminomethyl aryl ketone hydrochlorides is also catalyzed by [Rh{(R)-(S)-BPPFOH}(nbd)]ClO4 to give (R)-2-amino-1-arylethanol hydrochlorides in high ee in the presence of triethylamine (eq 3).3 3,4-Disubstitution on the aromatic ring by hydroxy or alkoxy groups affords higher selectivity. The principal sympathomimetic hormone, epinephrine, especially is produced in enantiometrically pure form from (N-methylamino)methyl 3,4-dihydroxyphenyl ketone hydrochloride.

Asymmetric Hydrogenation of Enol Phosphinates.

Catalytic asymmetric synthesis of secondary alkyl alcohols in up to 78% ee is accomplished by asymmetric hydrogenation of enol diphenylphosphinates followed by hydrolysis (eq 4).4 The highest enantioselectivity is obtained in the hydrogenation of 1-phenylvinyldiphenylphosphinate, though in the case of phosphinates derived from dialkyl ketones, selectivities are rather low. Substitution of the diphenylphosphinyl group for other phosphorus-containing functional groups lowers the stereoselectivity. Since enol phosphinates are easily prepared from prochiral ketones, this sequence provides an alternative method for the asymmetric hydrogenation of prochiral ketones.

Related Reagents.

Bis(bicyclo[2.2.1]hepta-2,5-diene)rhodium Perchlorate.


1. Harada, K.; Munegumi, T. COS 1991, 8, Chapter 1.6.
2. Hayashi, T.; Mise, T.; Kumada, M. TL 1976, 4351
3. Hayashi, T.; Katsumura, A.; Konishi, M.; Kumada, M. TL 1979, 425.
4. Hayashi, T.; Kanehira, K.; Kumada, M. TL 1981, 22, 4417.
5. Hayashi, T.; Mise, T.; Fukushima, M.; Kagotani, M.; Nagashima, N.; Hamada, Y.; Matsumoto, A.; Kawakami, S.; Konishi, M.; Yamamoto, K.; Kumada, M. BCJ 1980, 53, 1138.

Yoshihiko Ito & Michinori Suginome

Kyoto University, Japan



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