(+)-trans-(2S,3S)-Bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene1

(+)

[71042-54-1]  · C31H28P2  · (+)-trans-(2S,3S)-Bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene  · (MW 462.51) (-)

[71042-55-1] (±)

[76740-45-9]

(ligand for transition metal catalyzed asymmetric hydrogenation of alkenes,2 a-keto esters,3 imines,4 and b-keto esters;5 homo-Diels-Alder reactions;6 hydroarylation7)

Alternate Name: (+)-NORPHOS.

Physical Data: mp 129-130 °C; [a]20D = +45° (c = 1.0, CHCl3).

Preparative Method: trans-(2S,3S)-bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene (R,R-NORPHOS) has been prepared by reduction (Trichlorosilane) of the phosphine oxide, which was resolved with (-)-dibenzoyltartaric acid.2

Handling, Storage, and Precautions: NORPHOS is readily oxidized to the phosphine oxide and should be handled under N2 or Ar. Use in a fume hood.

Asymmetric Hydrogenation.

Numerous optically active phosphines have been utilized for enantioselective hydrogenations of prochiral substrates.1 In particular, transition metal complexes of (+)-NORPHOS have found particularly widespread use in asymmetric hydrogenations of a variety of unsaturated functional groups. Rhodium catalysts, prepared in situ from the reaction of [Rh(diene)Cl]2 complexes and (+)-NORPHOS, have been reported for use in asymmetric hydrogenations.2 The use of 80% Formic Acid as an alternative to hydrogen gas for catalytic alkene hydrogenations has been described.8 Reduction of the bicyclo[2.2.1]hept-5-ene backbone of (+)-NORPHOS rapidly occurs under catalytic hydrogenation conditions to give the reduced diphosphine which is the actual ligand involved in catalysis (eq 1).9 Asymmetric hydrogenation of (Z)-a-acetylaminocinnamic acid using a Rh complex of (+)-NORPHOS gave (S)-PhCH2CH(NHAc)CO2H in quantitative yield and 92% ee (eq 2).2 Similarly, hydrogenation of (Z)-a-acetylamino-2-butenoic acid occurred with 91.4% ee.10 An additional example of the asymmetric hydrogenation of a-acetylaminoacrylic esters was reported in a synthesis of phosphinothricin in 91% ee (eq 3).11 High enantiomeric excesses for alkene hydrogenation with (+)-NORPHOS are limited to a-acetylaminoacrylates which are capable of forming a chelate structure involving rhodium, the alkenic double bond, and the acetylamino functional group.

Rhodium complexes of (+)-NORPHOS have also been used for enantioselective hydrogenation of carbon-oxygen and carbon-nitrogen double bonds. Hydrogenation of PhCH2CH2COCO2Et with a catalyst prepared from Bis(bicyclo[2.2.1]hepta-2,5-diene)dichlorodirhodium and (+)-NORPHOS gave a quantitative yield of PhCH2CH2CH(OH)CO2Et with 96% ee (eq 4).3 Kinetic resolutions of racemic b-keto esters have been performed using asymmetric hydrogenation in the synthesis of (+)- and (-)-threonine.5 Enantioselective hydrogenation of imines using a Rh complex of (+)-NORPHOS has been reported. Hydrogenation of ArN=C(Me)CH2OMe occurred with 61% ee (eq 5).4 The product enantioselectivity using NORPHOS was comparable to that observed using other diphosphine ligands.

Homo-Diels-Alder Reactions.

The enantioselective synthesis of deltacyclenes from norbornadiene and monosubstituted alkynes has been catalyzed by a cobalt catalyst prepared from Tris(acetylacetonato)cobalt-Diethylaluminum Chloride-NORPHOS. 4-Phenyldeltacyclene was obtained in quantitative yield with >98% ee (eq 6).6

Asymmetric Alkene Hydroarylation.

The enantioselective addition of aryl iodides to norbornene has been reported using a palladium(II) complex of (+)-NORPHOS.7 The reaction of norbornadiene with 4-methoxyiodobenzene proceeded with 40.6% ee (eq 7).


1. Ojima, I.; Clos, N.; Bastos, C. T 1989, 45, 6901.
2. Brunner, H.; Pieronczyk, W. AG 1979, 91, 655.
3. Spindler, F.; Pittelkow, U.; Blaser, H. U. Chirality 1991, 4, 370.
4. Cullen, W. R.; Fryzuk, M. D.; James, B. R.; Kutney, J. P.; Kang, G. J.; Herb, G.; Thorburn, I. S.; Spogliarich, R. J. Mol. Catal. 1990, 62, 243.
5. Genet, J. P.; Pinel, C.; Mallart, S.; Juge, S.; Thorimbert, S.; Laffitte, J. A. TA 1991, 2, 555.
6. Brunner, H.; Prester, F. JOM 1991, 414, 401.
7. Brunner, H.; Kramler, K. S 1991, 12, 1121.
8. Brunner, H.; Kunz, M. CB 1986, 119, 2868.
9. Kyba, E. P.; Davis, R. E.; Juri, P. N.; Shirley, K. R. IC 1981, 20, 3616.
10. Brunner, H.; Knott, A.; Kunz, M.; Thalhammer, E. JOM 1986, 308, 55.
11. Zeiss, H. J. JOC 1991, 56, 1783.

Gregory T. Whiteker

Union Carbide Corporation, South Charleston, WV, USA



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