Triphenylphosphine-Hexachloroacetone

(Ph3P)

[603-35-0]  · C18H15P  · Triphenylphosphine-Hexachloroacetone  · (MW 262.30) (HCA)

[116-16-5]  · C3Cl6O  · Triphenylphosphine-Hexachloroacetone  · (MW 264.73)

(conversion of alcohols, particularly allylic alcohols, into chlorides with high regio- and stereoselectivity)

Physical Data: Ph3P: see Triphenylphosphine. Hexachloroacetone: mp -3 °C; bp 202 °C, 66 °C/6 mmHg; d 1.74 g cm-3.

Solubility: hexachloroacetone: slightly sol H2O; sol acetone, benzene, chloroform, ether.

Form Supplied in: hexachloroacetone: liquid, widely available.

Handling, Storage, and Precautions: hexachloroacetone: toxic, irritant.

General Discussion.

The conversion of allylic alcohols into chlorides (eq 1) presents difficulties not encountered with saturated compounds. A successful synthesis will be: (a) regiospecific (exclusive formation of either the a- or g-substituted product); (b) stereoselective or stereospecific (preservation of the b,g-double bond geometry when unrearranged product is formed; complete inversion or retention of configuration in the unrearranged product when the a-carbon is stereogenic); and (c) gentle (the conditions of the reaction, isolation, and workup should cause neither allylic rearrangement nor decomposition of the product).

There is, at present, no single method that meets all of these criteria for every type of allylic alcohol. Conventional reagents like SOCl2 and PCl3 have been used, but with mixed results.1 Some recently developed and frequently used methods are: (a) MeSO2Cl/LiCl/DMF/collidine;2a (b) RLi/HMPA, then TsCl, then LiCl/HMPA;2b and (c) N-chlorosuccinimide/Me2S/CH2Cl2.2c All of these are successful with primary substrates, but less so with secondary and tertiary allylic alcohols.1a,3 The combination Triphenylphosphine-Carbon Tetrachloride has had notable success, not only for transforming saturated alcohols into chlorides, but also for a variety of condensation reactions.4 Mechanistic studies5 have revealed that chloride formation succeeds even for alkyl groups that are prone to rearrange and that it proceeds with inversion of configuration at the alcohol center. The relative mildness of this system prompted Snyder6 to test it with allylic alcohols (eqs 2 and 3); crotyl alcohol (as an unspecified mixture of (E)- and (Z)-isomers) reacts without rearrangement, whereas 3-buten-2-ol proceeds regioselectively to an 89:11 mixture of products. One of the drawbacks to this procedure is that low molecular weight allylic chlorides have boiling points very close to those of carbon tetrachloride and its reaction product chloroform, thus making the isolation of product(s) difficult. It was principally for this reason that it was decided to replace CCl4 with a higher boiling source of Cl+; hexachloroacetone (HCA) was chosen, not only for its high boiling point, but also because the anionic intermediate after Cl+ removal would benefit from resonance stabilization.7

In fact, not only does the triphenylphosphine-hexachloroacetone system work admirably for a wide variety of allylic alcohols, but the conditions of the reaction and isolation are especially mild. Typically, a slight excess of solid Ph3P is added to an ice-cold solution of the allylic alcohol in hexachloroacetone solvent (although the order of mixing of the reagents appears to be unimportant); after about 10-15 minutes the solution is warmed to room temperature and the product flash-distilled (at about 1-3 mmHg), yielding the allylic chloride(s) in nearly quantitative yield, uncontaminated by Ph3P, HCA, or their reaction products. If desired, the reaction can be run with a stoichiometric quantity of hexachloroacetone in sulfolane; indeed, it is found that two chlorines (but not more) per HCA molecule can be used in this reaction. Saturated alcohols (1- and 2-butanol, neopentyl alcohol) give excellent yields of unrearranged chloride. The results shown in eqs 4-67b are typical of the behavior of a total of sixteen allylic alcohols. Primary alcohols give essentially 100% unrearranged chloride with total preservation of double bond stereochemistry. Secondary alcohols tend toward ca. 90/10 mixtures of unrearranged/rearranged product. When the a-carbon is stereogenic, the reaction proceeds with complete inversion of configuration. The method fails only for tertiary alcohols, which give significant amounts of rearranged chloride and elimination product.

The system Ph3P/HCA has also found use with cyclopropylcarbinyl alcohols.8a HCA can be replaced by hexabromoacetone in order to make allylic bromides.8b HCA, by itself, reacts with enamines,8c alcohols in DMF,8d tertiary amines,8e and miscellaneous nucleophiles.8f


1. (a) Magid, R. M. T 1980, 36, 1901. (b) DeWolfe, R. H.; Young, W. G. CRV 1956, 56, 753. (c) DeWolfe, R. H.; Young, W. G. In The Chemistry of Alkenes; Patai, S., Ed.; Interscience: New York, 1964; Chapter 10.
2. (a) Collington, E. W.; Meyers, A. I. JOC 1971, 36, 3044. (b) Stork, G.; Grieco, P. A.; Gregson, M. TL 1969, 1393. (c) Corey, E. J.; Kim, C. U.; Takeda, M. TL 1972, 4339.
3. (a) Czernecki, S.; Georgoulis, C. BSF 1975, 405. (b) Georgoulis, C.; Ville, G. BSF 1975, 607.
4. (a) Appel, R. AG(E) 1975, 14, 801. (b) Cadogan, J. I. G.; Mackie, R. K. CSR 1974, 3, 87.
5. (a) Weiss, R. G.; Snyder, E. I. CC 1968, 1358. (b) Weiss, R. G.; Snyder, E. I. JOC 1970, 35, 1627. (c) Weiss, R. G.; Snyder, E. I. JOC 1971, 36, 403. (d) Stephenson, B.; Solladié, G.; Mosher, H. S. JACS 1972, 94, 4184.
6. Snyder, E. I. JOC 1972, 37, 1466.
7. (a) Magid, R. M.; Fruchey, O. S. JACS 1979, 101, 2107. (b) Magid, R. M.; Fruchey, O. S.; Johnson, W. L.; Allen, T. G. JOC 1979, 44, 359. (c) Magid, R. M.; Talley, B. G.; Souther, S. K. JOC 1981, 46, 824.
8. (a) Hrubiec, R. T.; Smith, M. B. JOC 1984, 49, 431. (b) Oppolzer, W.; Mirza, S. HCA 1984, 67, 730. (c) Laskovics, F. M.; Schulman, E. M. JACS 1977, 99, 6672. (d) Freedlander, R. S.; Bryson, T. A.; Dunlap, R. B.; Schulman, E. M.; Lewis, C. A., Jr. JOC 1981, 46, 3519. (e) Talley, J. J. TL 1981, 22, 823. (f) Gold, V.; Johnston, G. J.; Wassef, W. N. JCS(P2) 1986, 471.

Ronald M. Magid

The University of Tennessee, Knoxville, TN, USA



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