(R)-(+)-Cyclohexyl(2-anisyl)methylphosphine1

(R)

[52885-02-6]  · C14H21OP  · (R)-(+)-Cyclohexyl(2-anisyl)methylphosphine  · (MW 236.29) (S)

[35144-03-7] (±)

[36293-81-9]

(ligand for transition metal catalyzed asymmetric hydrogenation of alkenes;2 reagent for asymmetric Wittig3 and Baylis-Hillman reactions4)

Alternate Name: (+)-CAMP.

Preparative Method: by hydrogenation (5% Rh/C) of optically pure (2-anisyl)phenylmethylphosphine oxide5 followed by reduction of the phosphine oxide with Trichlorosilane.2

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

Asymmetric Hydrogenation.

The synthesis of L-Dopa via asymmetric rhodium-catalyzed hydrogenation was reported using a catalyst prepared from rhodium(I) complexes and (+)-CAMP.2,6 Activation of the catalyst by pretreatment with 1 atm H2 was necessary. Hydrogenation at lower pressures (10 psi H2) gave the dihydrocinnamic acid in 90% yield and 88% ee (eq 1). Similar yields and enantioselectivities have been reported with related cinnamic acid derivatives which are capable of bifunctional binding to the rhodium catalyst.2 Bidentate diphosphine ligands generally lead to higher enantioselectivities in such reactions and are, therefore, employed in the commercial synthesis of L-Dopa.1

Wittig Reaction.

The intramolecular Wittig reaction of an ylide obtained from (+)-CAMP occurred with 77% ee to give the (S)-bicyclic diketone.3 Although a stoichiometric amount of the optically pure phosphine was required, the phosphine oxide (+)-CAMPO could be recycled. Enantiomeric excesses using CAMP were much higher than similar reactions which employed other chiral phosphines.

Baylis-Hillman Reaction.

Intramolecular cyclization of MeCO(CH2)2CH=CHCO2Et using (+)-CAMP produced the cyclopentene in 40% isolated yield.4 A 3:1 equilibrium mixture which favored the product cyclopentene was formed after 10 days at 25 °C. CAMP was found to be superior to other phosphines, such as PBu3. DABCO and other nitrogen bases were ineffective for the cyclization reaction. However, the enantioselectivity of the product using CAMP was only 14%.


1. Knowles, W. S. ACR 1983, 16, 106.
2. Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. CC 1972, 10.
3. Trost, B. M.; Curran, D. P. TL 1981, 22, 4929.
4. Roth, F.; Gygax, P.; Frater, G. TL 1992, 33, 1045.
5. Nauman, K.; Zon, G.; Mislow, K. JACS 1969, 91, 7012.
6. (a) Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. Adv. Chem. Ser. 1974, 132, 274. (b) Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. U.S. Patent 4 005 127, 1977.

Gregory T. Whiteker

Union Carbide Corporation, South Charleston, WV, USA



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