[74839-84-2]  · C28H28P2  · 2,3-Bis(diphenylphosphino)butane  · (MW 426.48) (2S,3S)


(ligand for asymmetric hydrogenation of alkenes2 and b-keto esters;3 allylic alkylation;4 hydroarylation5)

Alternate Name: (R,R)-CHIRAPHOS.

Physical Data: mp 107-109 °C; [a]20D +195° (c = 1.5, CHCl3).

Form Supplied in: white solid; widely available.

Handling, Storage, and Precautions: is indefinitely stable in air in the solid state. Solutions of CHIRAPHOS are readily oxidized to the phosphine oxide and should be handled under N2 or Ar.2

Asymmetric Hydrogenation.

CHIRAPHOS has been employed in the enantioselective hydrogenation of a variety of unsaturated functional groups. The asymmetric hydrogenation of cinnamic acid derivatives has been extensively studied due to its relevance to the commercial synthesis of amino acids, such as L-Dopa.1 Hydrogenation of (Z)-a-benzoylaminocinnamic acid is catalyzed in quantitative yield and 98% ee by a cationic rhodium complex prepared from [Rh(cod)2](ClO4) and (S,S)-CHIRAPHOS (eq 1).2 Asymmetric hydrogenations have also been performed using racemic CHIRAPHOS which has been resolved in situ by a substrate-induced kinetic resolution.6 When racemic CHIRAPHOS (2 equiv) was reacted with complex (1) (R = (-)-menthyl), (S,S)-CHIRAPHOS selectively coordinated to Ir. This resulting (S,S)-CHIRAPHOS-Ir complex is catalytically inactive for alkene hydrogenation under typical conditions. In the presence of this Ir complex the remaining uncoordinated (R,R)-CHIRAPHOS is then utilized for rhodium-catalyzed hydrogenation of methyl (Z)-a-acetylaminocinnamate (eq 2). The enantiomeric excess using this route is identical to that observed with authentic (R,R)-CHIRAPHOS.

Rhodium and ruthenium complexes of CHIRAPHOS are also useful for the asymmetric hydrogenation of b-keto esters. Dynamic kinetic resolution of racemic 2-acylamino-3-oxobutyrates was performed by hydrogenation using ((S,S)-CHIRAPHOS)RuBr2 (eq 3).3 The product yields and enantiomeric excesses were dependent upon solvent, ligand, and the ratio of substrate to catalyst. Under optimum conditions a 97:3 mixture of syn and anti b-hydroxy esters was formed, which was converted to D-threonine (85% ee) and D-allothreonine (99% ee) by hydrolysis and reaction with propylene oxide.

Allylic Alkylation.

The palladium-catalyzed asymmetric alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl sodiomalonate produces (2) in 86% yield and 90% ee (eq 4).4 CHIRAPHOS was found to give higher enantioselectivity than both 2,2-Bis(diphenylphosphino)-1,1-binaphthyl (BINAP) and (+)-trans-(2S,3S)-Bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene (NORPHOS). Alkylation using other malonic acid derivatives gave similar optical yields. The product enantiomeric excess was reported to be greatly dependent upon the method of catalyst preparation.

Alkene Hydroarylation.

The enantioselective addition of aryl iodides to norbornene has been reported using a palladium(II) complex of (S,S)-CHIRAPHOS. The reaction of norbornadiene with 4-methoxyiodobenzene proceeded with 30% ee (eq 5).5 Enantioselectivities were dependent upon phosphine structure (see (+)-trans-(2S,3S)-Bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene).

1. Ojima, I.; Clos, N.; Bastos, C. T 1989, 45, 6901.
2. Fryzuk, M. D.; Bosnich, B. JACS 1977, 99, 6262.
3. Genet, J. P.; Pinel, C.; Mallart, S.; Juge, S.; Thorimbert, S.; Laffitte, J. A. TA 1991, 2, 555.
4. Yamaguchi, M.; Shima, T.; Yamagishi, T.; Hida, M. TA 1991, 2, 663.
5. Brunner, H.; Kramler, K. S 1991, 12, 1121.
6. Alcock, N. W.; Brown, J. M.; Maddox, P. J. CC 1986, 1532.

Gregory T. Whiteker

Union Carbide Corporation, South Charleston, WV, USA

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