Cyanomethyldiphenylphosphine Oxide

[23040-22-4]  · C14H12NOP  · Cyanomethyldiphenylphosphine Oxide  · (MW 243.23)

(Horner-Wittig reagent for formation of a,b-unsaturated nitriles1; reaction with nitrones to form aziridines or enamines2)

Solubility: sol THF and DMF.

Preparative Methods: reaction of Ethyl Diphenylphosphinite3 with Chloroacetonitrile;4 reaction of Ph2P(O)CH2CO2H with urea in acetic anhydride.5

Handling, Storage, and Precautions: hazards unknown.

a,b-Unsaturated Nitriles.

Use of cyanomethyldiphenylphosphine oxide (1) in a Horner-Wittig reaction for the formation of a,b-unsaturated nitriles provides, stereoselectively, the (E) isomer (&egt;90%) with aromatic aldehydes and ca. 75% (E) with isobutanal in very good chemical yields (eq 1). The reactions are run in either THF or DMF with Potassium t-Butoxide as the base at rt. Use of THF provides greater chemical yields and improved stereoselectivity over DMF or Lithium t-Butoxide in THF. The potassium diphenylphosphinate byproduct is water soluble and easily removed from the reaction mixture.

Reaction of the anion of (1) with acetophenone provides the (E) isomer in a 94:6 ratio in 82% yield. Condensation with cinnamaldehyde provides a 90:10 ratio (E:Z) (70:30 E:Z with analogous phosphonate). Use of (1) generally provides greater stereoselectivity for the (E) isomer than other methods for the formation of a,b-unsaturated nitriles.1

Of the other methods available, the Doebner condensation6 of aldehydes with cyanoacetic acid leads to mixtures of (E) and (Z) isomers.7 The Wittig alkenation with Cyanomethylenetriphenylphosphorane,8 usually in refluxing benzene, yields a predominance of the (E) isomer and triphenylphosphine oxide as a byproduct. In alkenation employing the Horner-Emmons reagents, Diethyl Cyanomethylphosphonate,9 in THF at rt, the (E) isomer predominates (&egt;70%) with aromatic aldehydes and little or no selectivity is seen with aliphatic aldehydes.

Reaction with Nitrones.2

Reaction of the anion of (1) with 3,4-dihydroisoquinoline N-oxide (2) (eq 2) and 5,5-dimethyl-D1-pyrroline N-oxide (5) (eq 3) can result in the formation of either aziridine or enamine products. The product distribution is markedly different employing (1) as opposed to diethyl cyanomethylphosphonate. This is thought to be due to the ability of the phenyl groups of (1) to better stabilize the build up of negative charge on phosphorus in the putative oxazaphospholidine intermediate, thereby decreasing the amount of fragmentation to the aziridine.


1. (a) Loupy, A.; Sogadji, K.; Seyden-Penne, J. S 1977, 126. (b) Etemad-Moghadam, G.; Seyden-Penne, J. SC 1984, 14, 565.
2. Zbaida, S.; Breuer, E. T 1978, 34, 1241.
3. Rabinowitz, R.; Pellon, J. JOC 1961, 26, 4623.
4. Regitz, M.; Anschütz, W. CB 1969, 102, 2216.
5. Frolovskii, V. A., Studnev, Yu. N.; Rozantsev, G. G. JGU 1992, 62, 784.
6. Jones, G. OR 1967, 15, 204.
7. Fairhurst, J.; Horwell, D. C.; Timms, G. H. TL 1975, 3843.
8. Schiemenz, G. P.; Engelhard, H. CB 1961, 94, 578; Trippett, S.; Walker, D. M. JCS 1961, 1266.
9. Deschamps, B.; Lefebvre, G.; Redjal, A.; Seyden-Penne, J. T 1973, 29, 2437.

Brian E. Marron

Glaxo Research Institute, Research Triangle Park, NC, USA



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