Cyclopropyltriphenylphosphonium Bromide

[14114-05-7]  · C21H20BrP  · Cyclopropyltriphenylphosphonium Bromide  · (MW 383.27)

(phosphonium salt used to generate phosphorane;1 behaves as an electrophile and generates an ylide by ring opening if reacted with a nucleophile;2 starting material for other functionalized phosphonium salts3)

Physical Data: mp 183-185 °C (commercial suppliers), mp 189-190 °C when recrystallized from EtOAc.4

Solubility: normally used in THF, DME, or DMF, although solubility is reported to be poor.1b

Form Supplied in: cream-colored or white powder or crystalline solid, available from various suppliers.

Analysis of Reagent Purity: proton and heteronuclear NMR and IR data have been reported.5

Handling, Storage, and Precautions: cyclopropyltriphenylphosphonium bromide exhibits long-term stability and should be protected from moisture in a well-sealed vial. Present data suggest potential skin irritation if contacted and inhalation of the dust may be irritating to the respiratory system.

Ylide Generation: Cyclopropylidenetriphenylphosphorane.

A significant application of cyclopropyltriphenylphosphonium bromide involves the generation of cyclopropylidenetriphenylphosphorane1a (for reactions involving this ylide, see Cyclopropylidenetriphenylphosphorane). Ylide generation generally involves an aprotic solvent like THF6 or DME7 and n-Butyllithium as a base. Alkene generation under these reaction conditions often results in poor yields. Subsequent investigations have suggested that the use of a phase transfer catalyst in cooperation with Sodium Hydride in THF results in a substantial improvement in yield (Table 1 and eq 1).1b NaH in DMSO and Sodium Hexamethyldisilazide in Et2O have also been utilized in ylide formation.8 Additional work suggests that an alternate synthetic approach involving 3-bromopropyltriphenylphosphonium bromide and 2 equiv of base (NaH in DME) generates cyclopropyltriphenylphosphonium bromide in situ and results in equivalent or better yields of alkene product.9

Cyclopropyltriphenylphosphonium Bromide as an Electrophile.

The phosphonium moiety can stabilize a negative charge on the adjacent carbon atom as an ylide. This stabilization manifests itself as an intrinsic electrophilicity at the remaining two carbon atoms of the cyclopropyl ring. The anion of salicylaldehyde reacts with cyclopropyltriphenylphosphonium bromide at 160 °C to yield a mixture of two products and 75% recovered starting material (eq 2),4 presumably through a nucleophilic opening of the cyclopropyl ring.

A synthesis of pyrrolizidines provides another application of cyclopropyltriphenylphosphonium bromide as an electrophile. Succinimide anion opens the cyclopropyl ring and the ylide generated cyclizes to yield the bicyclic product after hydrolysis (eq 3).2 Cyclopropyltriphenylphosphonium bromide can be reduced by Lithium Aluminum Hydride to yield cyclopropyldiphenylphosphine.4

Investigations have generated two analogs of cyclopropyltriphenylphosphonium bromide designed to improve the yield of cyclopropyl ring opening by nucleophiles. 1-(Ethoxycarbonyl)cyclopropyltriphenylphosphonium tetrafluoroborate (1) undergoes facile cyclopropyl ring opening by b-keto ester carbanions (eq 4), salicylaldehyde anion (eq 5), and pyrrole-2-carbaldehyde anion (eq 6).3a

1-(Phenylthio)cyclopropyltriphenylphosphonium tetrafluoroborate experiences facile cyclopropyl ring opening by b-keto ester carbanions and the subsequent ylide is sufficiently reactive to generate a vinyl sulfide with the ketone moiety.3b Acid-catalyzed hydrolysis results in cyclopentanone products in 75-80% yield.

1. (a) Schweizer, E. E.; Thompson, J. G. CC 1966, 666. (b) Stafford, J. A.; McMurry, J. E. TL 1988, 29, 2531.
2. Flitsch, W.; Hampel, K. LA 1988, 387.
3. (a) Fuchs, P. L. JACS 1974, 96, 1607. (b) Marino, J. P.; Landick, R. C. TL 1975, 4531.
4. Schweizer, E. E.; Berninger, C. J.; Thompson, J. G. JOC 1968, 33, 336.
5. (a) Albright, T. A.; Freeman, W. J.; Schweizer, E. E. JACS 1975, 97, 2942. (b) Baldwin, J. E.; Peavy, R. E. JOC 1971, 36, 1441.
6. Norden, W.; Sander, V.; Weyerstahl, P. CB 1983, 116, 3097.
7. Eitel, M.; Pindur, U. S 1989, 364.
8. Zefirov, N. S.; Averina, N. V.; Boganov, A. M.; Laryukova, M. V.; Rashchupkina, Z. A.; Terent'ev, P. B.; Sharbatyan, P. A. ZOR 1981, 17, 1450. (JOU 1981, 17, 1291).
9. (a) Sisido, K.; Utimoto, K. TL 1966, 3267. (b) Utimoto, K.; Tamura, M.; Sisido, K. T 1973, 29, 1169. For additional examples of 3-bromopropyltriphenylphosphonium bromide as the ylide source, see: (c) Salaün, J.; Bennani, F.; Compain, J.-C.; Fadel, A.; Ollivier, J. JOC 1980, 21, 4129. (d) Bertrand, M.; Leandri, G.; Meou, A. T 1981, 37, 1703. (e) Schmidbaur, H.; Schier, A.; Milewski-Mahrla, B.; Schubert, U. CB 1982, 115, 722. (f) Lasne, M.-C.; Ripoll, J.-L. BSF(2) 1981, 2, 340. For an example utilizing the less hydroscopic cyclopropyltriphenylphosphonium tetrafluoroborate, see: (g) Marino, J. P.; Ferro, M. P. JOC 1981, 46, 1828.

Edward J. Adams

E. I. DuPont de Nemours, Newark, DE, USA

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