Diphenyl(vinyl)phosphine Oxide1

[2096-78-8]  · C14H13OP  · Diphenyl(vinyl)phosphine Oxide  · (MW 228.24)

(Horner-Wittig2 reagent for the preparation of allylic amines; undergoes a variety of cycloaddition3 and conjugate addition reactions4)

Physical Data: mp 115-117 °C; bp 180-210 °C/1 mmHg.

Solubility: sol THF, CH2Cl2, toluene; insol H2O.

Preparative Methods: can be prepared (eq 1) by four methods: (a) dehydrohalogenation of a haloethyldiphenylphosphine oxide,5,6 (b) reaction of diphenylphosphinic chloride and vinylmagnesium bromide,7 (c) palladium-catalyzed coupling of vinyl bromide and diphenylphosphine oxide,8 (d) oxidation of commercially available diphenyl(vinyl)phosphine.9

Handling, Storage, and Precautions: the toxicological properties of the reagent are unknown; however, by analogy with other Michael acceptors it should be assumed to be toxic. While radical polymerization is sluggish, diphenyl(vinyl)phosphine oxide readily undergoes anionic polymerization in the presence of Grignard reagents.5

Conjugate Additions.

Diphenyl(vinyl)phosphine oxide readily undergoes conjugate addition with carbon,4 nitrogen,4,10,11 oxygen,4,12 and sulfur4,13 nucleophiles. Of particular interest is the addition of chiral amines (eq 2)11 and alcohols (eq 3),12 which provide precursors of chiral phosphines, potentially useful ligands for various transition metal catalyzed processes.

Alkylation of the pyrrolidine enamine of cyclohexanone, followed by a Baeyer-Villiger oxidation and acyl transfer, leads to a two-carbon ring expansion (eq 4).14

Horner-Wittig Reactions.

Simple amines such as Morpholine, Piperidine, and Pyrrolidine add to the vinylphosphine oxide to furnish adducts11 which can be used in the regio and stereospecific Horner-Wittig synthesis of allylic tertiary amines (eq 5).2 The anions, generated with n-Butyllithium in THF at 0 °C, react with aldehydes and ketones (including enolizable ones) at -78 °C to give isolable b-hydroxyphosphine oxides. Completion of the Horner-Wittig reaction (Sodium Hydride, DMF, 30 °C) gives allylamines in high yield. In the cases where R1 &neq; R2 the diastereoisomeric b-hydroxyphosphine oxides can be separated by chromatography or fractional crystallization. Stereospecific syn elimination of Ph2PO2- then enables isolation of both the (Z)- and (E)-alkenes. In contrast, the conventional Wittig reaction often gives inseparable mixtures of geometric isomers.

Cycloaddition Reactions.

Diphenyl(vinyl)phosphine oxide undergoes 1,3-dipolar cycloaddition reactions with a variety of nitrones, giving mixtures of regioisomeric isoxazolidines.3 The regiochemistry of the cycloaddition is very sensitive to minor structural changes in the nitrone (eqs 6-8). The chemistry has been extended to chiral nitrones.15

Lewis acid catalyzed Diels-Alder reactions with Cyclopentadiene giving predominantly endo selectivity have been described (eq 9).16

1. Maryanoff, B. E.; Reitz, A. B. CRV 1989, 89, 863.
2. (a) Cavalla, D.; Warren, S. TL 1982, 23, 4505. (b) Cavalla, D.; Cruse, W. B.; Warren, S. JCS(P1) 1987, 1883.
3. Brandi, A.; Cicchi, S.; Goti, A.; Pietrusiewicz, K. M.; Wisniewski, W. T 1990, 46, 7093 and references therein.
4. Brandi, A.; Cicchi, S.; Goti, A.; Pietrusiewicz, K. M. TL 1991, 32, 3265 and references therein.
5. Welch, F. J.; Paxton, H. J. J. Polym. Sci. (A) 1965, 3, 3427.
6. (a) Rabinowitz, R.; Pellon, J. JOC 1961, 26, 4623. (b) Postle, S. R.; Whitham, G. H. JCS(P1) 1977, 2084.
7. Collins, D. J.; Rowley, L. E.; Swan, J. M. AJC 1974, 27, 841.
8. Xu, Y.; Xia, J.; Guo, H. S 1986, 691.
9. Berlin, K. D.; Butler, G. B. JOC 1961, 26, 2537.
10. Märkl, G.; Merkl, B. TL 1981, 22, 4459.
11. Collins, D. J.; Mollard, S.-A.; Rose, N.; Swan, J. M. AJC 1974, 27, 2365.
12. Märkl, G.; Merkl, B. TL 1981, 22, 4463.
13. Horner, L.; Lindel, H. PS 1984, 20, 161.
14. Wallace, P.; Warren, S. JCS(P1) 1992, 3169.
15. Brandi, A.; Cicchi, S.; Goti, A.; Pietrusiewicz, K. M. TA 1991, 2, 1063.
16. Maffei, M.; Buono, G. NJC 1988, 12, 923.

Chris J. Wallis

Glaxo Research & Development, Ware, UK

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