[1079-66-9]  · C12H10ClP  · Chlorodiphenylphosphine  · (MW 220.64)

(mild reagent for the halogenation of alcohols,1 conversion of vicinal diols to alkenes,2 transformation of sulfoxides to thioesters,3 and formation of phosphines4)

Physical Data: bp 320 °C; d 1.229 g cm-3.

Form Supplied in: light-yellow liquid; widely available.

Handling, Storage, and Precautions: handle only in a chemical fume hood, wear respirator, chemical-resistant gloves, and safety goggles; do not breathe vapor, and avoid contact with eyes or skin. The compound is a corrosive lachrymator. It reacts violently with water to generate hydrogen chloride gas. It may be fatal if inhaled. See the material safety data sheet for first aid procedures.

Halogenation Reagent.

Primary and secondary alcohols can be converted to iodides and bromides in excellent yields employing chlorodiphenylphosphine, Imidazole, and the appropriate halogen.1 This reagent system is superior to most phosphorus-based reagents, which require the removal of triphenylphosphine and its oxide, because the phosphorus byproducts can be removed by basic aqueous extraction. Imidazole serves to neutralize the liberated halogen acids, enhances the reactivity, and can be washed away from the toluene phase during the extraction. Primary alcohols react at room temperature in less than 10 min (eq 1). Secondary alcohols require elevated temperatures and longer reaction times (eq 2). Competitive chlorination does not arise from the chloride anion generated during the reaction.

Alkenes from Vicinal Diols.

The same reagent system can be employed to convert vicinal diols to alkenes (eqs 3 and 4).2 This single step procedure is more efficient than methods that require transformation of the diols to activated groups, such as disulfonates or cyclic thiocarbonates, which are subsequently converted into alkenes. The reaction proceeds through a vicinal iododiphenylphosphinate which can sometimes be isolated.

Thioesters from Sulfoxides.

Chlorodiphenylphosphine has been utilized to convert sulfoxides into thioesters (eq 5).3 a-Lithio sulfoxides react with chlorodiphenylphosphine to provide a-sulfinylphosphines, which are rearranged by iodine to a-sulfenylphosphine oxides. Horner-Bestmann oxygenation gives the thioesters in good yields. This transformation has also been applied to cyclic sulfoxides to provide thiolactones (eq 6).5

Phosphine and Phosphine Oxide Formation.

Chlorodiphenylphosphine has been electrochemically coupled with organic halides to generate phosphines.4 It also reacts with anions to give alkyl- or arylphosphines which can be oxidized to phosphine oxides. This method has been used to form a bifunctional molecule capable of serving as a phase transfer catalyst and transition metal ligand (eq 7).6

1,3-Dienylphosphines, bifunctional transition metal ligands, have been generated employing chlorodiphenylphosphine by two different routes. The first one involves hydrozirconation of conjugated enynes, followed by reaction with chlorodiphenylphosphine, to provide the dienylphosphines (eq 8).7 In the other process, an in situ generated methylenephosphine phosphonate anion is alkylated with an a,b-enal to give the dienylphosphine (eq 9).8 The second procedure is more versatile, because a,b-unsaturated aldehydes are more readily available than the corresponding enynes.

Ketones have been converted to vinylphosphine oxides (eq 10).9 This process requires the conversion of the ketone to the trisylhydrazone. Subsequent formation of the vinyl carbanion, trapping with chlorodiphenylphosphine, and oxidation yields the vinylphosphine oxides.

b-Ketophosphine oxides can be prepared from enolates by trapping with chlorodiphenylphosphine, followed by oxidation.10 This sequence has also been applied to enolates generated from a Michael addition (eq 11).

a-Functionalized phosphine oxides are versatile reagents for the formation of enol ethers, enamines, and vinyl sulfides via Horner-Wittig reactions.11 a-Alkoxyphosphine oxides can be prepared by reaction of acetals with chlorodiphenylphosphine (eq 12). Ketene acetals can be generated from carbonyl compounds via the Horner-Wittig reaction with a,a-dialkoxyphosphine oxides made in a similar fashion to that of the previous equation from orthoesters and chlorodiphenylphosphine.12 a-Aminophosphine oxides can be formed by reaction between chlorodiphenylphosphine and aminals in an analogous fashion.13

Propargylic alcohols react with chlorodiphenylphosphine to form phosphinite esters which subsequently undergo [2,3]-sigmatropic shifts to give allenylphosphine oxides.14 This transformation has been coupled with an intramolecular Diels-Alder reaction to give vinylphosphine oxides (eq 13).

Other Applications.

Aldoximes and ketoximes react with chlorodiphenylphosphine to produce phosphinyloximes which undergo rearrangement to phosphinylimines.15 This class of compounds can be reduced to provide protected amines, combined with organometallic reagents to give new amine derivatives, treated with hydrogen cyanide to yield a-aminonitriles, or reacted with diethyl phosphite to produce a-aminophosphonates (eq 14)

Lithium diphenylphosphide (Ph2PLi) can be prepared from chlorodiphenylphosphine and lithium metal.16 This is a versatile reagent for the dehydroxylation of a-hydroxy ketones and inversion of alkenes via epoxides.17

Chlorodiphenylphosphine can be oxidized with oxygen to form chlorodiphenylphosphine oxide.18 This reagent can be utilized for the activation of carboxylic acids and protection of amines (see RC098-).

Chlorodiphenylphosphine has been utilized as a reducing agent for diselenides and pyridine N-oxides.19

1. Classon, B.; Liu, Z.; Samuelsson, B. JOC 1988, 53, 6126.
2. Liu, Z.; Classon, B.; Samuelsson, B. JOC 1990, 55, 4273.
3. Vedejs, E.; Mastalerz, H.; Meier, G. P.; Powell, D. W. JOC 1981, 46, 5253.
4. Folest, J. C.; Nedelec, J. Y.; Perichon, J. TL 1987, 28, 1885.
5. (a) Vedejs, E.; Buchanan, R. A.; Conrad, P.; Meier, G. P.; Mullins, M. J.; Watanabe, Y. JACS 1987, 109, 5878. (b) Vedejs, E.; Buchanan, R. A.; Conrad, P. C.; Meier, G. P.; Mullins, M. J.; Schaffhausen, J. G.; Schwartz, C. E. JACS 1989, 111, 8421. (c) Vedejs, E.; Buchanan, R. A.; Watanabe, Y. JACS 1989, 111, 8430.
6. Okano, T.; Iwahara, M.; Suzuki, T.; Konishi, H.; Kiji, J. CL 1986, 1467.
7. Fryzuk, M. D.; Bates, G. S.; Stone, C. JOC 1988, 53, 4425.
8. Teulade, M.-P.; Savignac, P. TL 1989, 30, 6327.
9. Mislankar, D. G.; Mugrage, B.; Darling, S. D. TL 1981, 22, 4619.
10. Mikolajczyk, M.; Kielbasinski, P.; Wieczorek, M. W.; Blaszczyk, J.; Kolbe, A. JOC 1990, 55, 1198.
11. Maleki, M.; Miller, A.; Lever, O. W., Jr. TL 1981, 22, 365.
12. van Schaik, T. A. M.; Henzen, A. V.; van der Gen, A. TL 1983, 24, 1303.
13. (a) Broekhof, N. L. J. M.; Jonkers, F. L.; van der Gen, A. TL 1979, 2433. (b) Broekhof, N. L. J. M.; Jonkers, F. L.; van der Gen, A. TL 1980, 21, 2671. (c) Bakker, B. H.; Tjin A-Lim, D. S.; van der Gen, A. TL 1984, 25, 4259. (d) Oleksyszyn, J. S 1981, 444.
14. Curtin, M. L.; Okamura, W. H. JOC 1990, 55, 5278.
15. (a) Krzyzanowska, B.; Stec, W. J. S 1978, 521. (b) Hutchins, R. O.; Rutledge, M. C. TL 1987, 28, 5619.
16. Mena, P. L.; Pilet, O.; Djerassi, C. JOC 1984, 49, 3260.
17. (a) Leone-Bay, A. JOC 1986, 51, 2378. (b) Vedejs, E.; Snoble, K. A. J.; Fuchs, P. L. JOC 1973, 38, 1178.
18. Tyssee, D. A.; Bausher, L. P.; Haake, P. JACS 1973, 95, 8066.
19. Sakakibara, M.; Toru, T.; Imai, T.; Watanabe, Y.; Ueno, Y. BCJ 1992, 65, 1291.

David N. Deaton

Glaxo Research Institute, Research Triangle Park, NC, USA

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