[55700-44-2]  · C26H28FeNP  · (R)-N,N-Dimethyl-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethylamine  · (MW 441.37) (S)-(R)-PPFA


(effective chiral phosphine ligand1 for nickel- or palladium-catalyzed asymmetric cross coupling of organomagnesium or -zinc reagents with alkenyl bromides,2-4 and for palladium-catalyzed asymmetric hydrosilylation of 1,3-dienes5)

Alternate Name: (R)-(S)-PPFA.

Physical Data: mp 139 °C; [a]25D -361° (c 0.6, ethanol).1a

Purification: recrystallization from ethanol.1a

Handling, Storage, and Precautions: stable in air for years, but best kept sealed in a refrigerator.

Asymmetric Cross Coupling.

In the presence of a nickel catalyst, generated in situ from Nickel(II) Chloride and (R)-(S)-PPFA, secondary alkyl Grignard reagents, represented by 1-phenylethylmagnesium chloride, react with alkenyl halides to give optically active alkenes of up to 68% ee (eq 1). The isolated palladium complex, PdCl2[(R)-(S)-PPFA], can be also used for the cross coupling.2 Use of a zinc reagent in place of the Grignard reagent increases the enantioselectivity to 86% ee.3

The stereoselectivity obtained with the PPFA ligand is generally higher than that obtained with (2,3-O-Isopropylidene)-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane (DIOP) (7-16% ee), 1,2-bis(diphenylphosphino)propane (prophos) (0% ee), and 2,2-bis(diphenylphosphinomethyl)-1,1-binaphthyl (NAPHOS) (11% ee).

The asymmetric cross coupling with the chiral ferrocenylphosphine-palladium catalyst has been successfully applied to the synthesis of optically active allylsilanes (eq 2).4 The reaction of a-(trimethylsilyl)benzylmagnesium bromide with vinyl bromide and (E)-b-bromostyrene catalyzed by 0.5 mol % of PdCl2[(R)-(S)-PPFA] gives a quantitative yield of the corresponding allylsilanes of 95% ee. High enantioselectivity is also observed in the cross coupling of 1-(triethylsilyl)ethylmagnesium chloride with (E)-b-bromostyrene.

Asymmetric Hydrosilylation of Alkenes.

The palladium complex PdCl2[(R)-(S)-PPFA] catalyzes the asymmetric hydrosilylation of norbornene, styrene, and 1,3-dienes (eq 3).5 The hydrosilylation of 1-phenyl-1,3-butadiene with Trichlorosilane proceeds regioselectively in a 1,4-fashion to give (Z)-1-phenyl-1-silyl-2-butene of 64% ee.

Optically active ferrocenylbisphosphines, (R)-N,N-dimethyl-1-[(S)-1,2-bis(diphenylphosphino)ferrocenyl]ethylamine [(R)-(S)-BPPFA] and its derivatives, are efficient chiral bisphosphine ligands for rhodium-catalyzed asymmetric hydrogenation, palladium-catalyzed asymmetric allylic substitution reactions, and gold-catalyzed asymmetric aldol-type reactions of a-isocyano carboxylates.1,6

Synthesis of Chiral Phosphorane.

(S)-(R)-PPFA has been converted to an enantiomerically pure ferrocenylphosphonium salt (1) in two steps in 54% yield (eq 4). The chiral phosphorane (2), generated in situ from (1) by n-Butyllithium in THF, reacts with aldehydes in the presence of a Lewis acid, Diethylaluminum Ethoxide to give vinylation products (3) (eq 5) with variable enantiomeric excess (up to 70%).7

1. (a) 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. (b) Hayashi, T. PAC 1988, 60, 7.
2. (a) Hayashi, T.; Tajika, M.; Tamao, K.; Kumada, M. JACS 1976, 98, 3718. (b) Hayashi, T.; Konishi, M.; Fukushima, M.; Mise, T.; Kagotani, M.; Tajika, M.; Kumada, M. JACS 1982, 104, 180.
3. Hayashi, T.; Hagihara, T.; Katsuro, Y.; Kumada, M. BCJ 1983, 56, 363.
4. (a) Hayashi, T.; Konishi, M.; Ito, H.; Kumada, M. JACS 1982, 104, 3772. (b) Hayashi, T.; Konishi, M.; Okamoto, Y.; Kabeta, K.; Kumada, M. JOC 1986, 51, 3772.
5. (a) Hayashi, T.; Kabeta, K. TL 1985, 26, 3023. (b) Hayashi, T.; Matsumoto, Y.; Morikawa, I.; Ito, Y. TA 1990, 1, 151.
6. (a) Ojima, I. Catalytic Asymmetric Synthesis; VCH: New York, in press. (b) Togni, A.; Hayashi, T. Ferrocenes: From Catalysis to Materials Science; VCH: New York, 1994.
7. Iio, H.; Fujii, A.; Ishii, M.; Tokoroyama, T. CC 1991, 1390.

Tamio Hayashi

Hokkaido University, Sapporo, Japan

M. Mahmun Hossain & Anjan K. Saha

University of Wisconsin-Milwaukee, WI, USA

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