Triphenylphosphine-Carbon Tetrabromide1


[603-35-0]  · C18H15P  · Triphenylphosphine-Carbon Tetrabromide  · (MW 262.30) (CBr4)

[558-13-4]  · CBr4  · Triphenylphosphine-Carbon Tetrabromide  · (MW 331.61)

(reagent combination for the conversion of alcohols to bromides, aldehydes and ketones to dibromoalkenes, and terminal alkynes to 1-bromoalkynes; carboxyl activation)

Physical Data: Ph3P: mp 79-81 °C; bp 377 °C; d 1.0749 g cm-3. CBr4: mp 90-91 °C; bp 190 °C; d 3.273 g cm-3.

Solubility: sol MeCN, CH2Cl2, pyridine, DMF.

Preparative Method: the reactive species is generated in situ by reaction of Ph3P with CBr4.

Handling, Storage, and Precautions: Ph3P is an irritant; CBr4 is toxic and a cancer suspect agent. All solvents used must be carefully dried because the intermediates are all susceptible to hydrolysis. This reagent should be used in a fume hood.

Conversion of Alcohols to Alkyl Bromides.

The reaction of alcohols with Triphenylphosphine and Carbon Tetrabromide results in the formation of alkyl bromides. The conditions are sufficiently mild to allow for the efficient conversion of alcohols into the corresponding bromides. The uridine derivative (eq 1) is transformed into its bromide with Ph3P and CBr4.2

The geometry about the double bond of an allylic alcohol is usually not compromised (eq 2).3 Allylic rearrangement is also not commonly observed. Although ketones are known to react with this reagent combination, the reaction of an allylic alcohol has been selectively achieved in the presence of a ketone (eq 3).4

Regioselective bromination of primary alcohols in the presence of secondary alcohols is possible. These reactions are usually performed in pyridine as solvent. The reaction of the methyl glucopyranoside (eq 4) results in the selective formation of the primary bromide in 98% yield.5 An investigation of this reaction with a chiral deuterated neopentyl alcohol yielded a partially racemized bromide.6

Silyl ether protected alcohols (eq 5) have been converted directly into the corresponding bromides with Ph3P and CBr4. The reaction works best if 1.5 equiv of acetone are added.7 Tetrahydropyranyl ether protected alcohols have also been directly transformed into the bromides using this reagent combination. The reaction has been reported to proceed with inversion of configuration (eq 6).8 If unsaturation is appropriately placed within a tetrahydropyranyl (eq 7) or a methoxymethyl (eq 8) protected alcohol, cyclization occurs to afford tetrahydropyrans.9 The conversion of an alcohol to the bromide without complications with a methoxymethyl protected alcohol in the molecule is possible (eq 9).10

Amides from Carboxylic Acids.

N-Methoxy-N-methyl amides can be prepared from carboxylic acids and the amine hydrochlorides. In the case of an a-phenyl carboxylic acid (eq 10), the amide is formed in 71% yield and no racemization is detected.11

Dibromoalkenes from Aldehydes and Ketones.

Benzaldehyde is transformed into the dibromoalkene in 84% yield when treated with Ph3P and CBr4 (eq 11).12 An alternative procedure for the conversion of an aldehyde to the dibromoalkene uses Zinc dust in place of an excess of the phosphine. This allows the amount of Ph3P and CBr4 to be reduced to 2 equiv each as opposed to 4 equiv. This procedure gives comparable results to the original procedure. The dibromoalkenes can be reacted with n-Butyllithium to form the intermediate lithium acetylide. The acetylides can then be reacted with electrophiles such as H2O (eq 12) and CO2 (eq 13). This offers a convenient method for the formyl to ethynyl conversion.13

Ketones are converted to dibromomethylene derivatives. These intermediates can be transformed to isopropylidene compounds by reaction with Lithium Dimethylcuprate and Iodomethane (eq 14).14 No racemization was reported for the chain extension of the aldehyde derived from (S)-ethyl lactate under the reaction conditions (eq 15).15

b-Bromo Enones from 1,3-Diketones.

The reaction of Ph3P and CBr4 with a 1,3-diketone efficiently converts it to the b-bromo enone (eq 16).16

1-Bromoalkynes from Terminal Alkynes.

Terminal alkynes on reaction with Ph3P and CBr4 afford 1-bromoalkynes in high yield (eq 17).17

1. Castro, B. R. OR 1983, 29, 1.
2. Verheyden, J. P. H.; Moffatt, J. G. JOC 1972, 37, 2289.
3. Axelrod, E. H.; Milne, G. M.; van Tamelen, E. E. JACS 1970, 92, 2139.
4. Kang, S. H.; Hong, C. Y. TL 1987, 28, 675.
5. Kashem, A.; Anisuzzaman, M.; Whistler, R. L. CR 1978, 61, 511.
6. Weiss, R. G.; Snyder, E. I. JOC 1971, 36, 403.
7. Mattes, H.; Benezra, C. TL 1987, 28, 1697.
8. Wagner, A.; Heitz, M.-P.; Mioskowski, C. TL 1989, 30, 557.
9. Wagner, A.; Heitz, M.-P.; Mioskowski, C. TL 1989, 30, 1971.
10. Clinch, K.; Vasella, A.; Schauer, R. TL 1987, 28, 6425.
11. Einhorn, J.; Einhorn, C.; Luche, J.-L. SC 1990, 20, 1105.
12. Ramirez, F.; Desai, N. B.; McKelvie, N. JACS 1962, 84, 1745.
13. Corey, E. J.; Fuchs, P. L. TL 1972, 3769.
14. Posner, G. H.; Loomis, G. L.; Sawaya, H. S. TL 1975, 1373.
15. Mahler, H.; Braun, M. TL 1987, 28, 5145.
16. Gruber, L.; Tömösközi, I.; Radics, L. S 1975, 708.
17. Wagner, A.; Heitz, M.-P.; Mioskowski, C. TL 1990, 31, 3141.

Michael J. Taschner

The University of Akron, OH, USA

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