Dichloroketene1

[4591-28-0]  · C2Cl2O  · Dichloroketene  · (MW 110.93)

(dichloroacetylating agent;2 undergoes cyclizations with numerous substrates3)

Solubility: sol ether, pentane, hexane.

Form Supplied in: not commercially available.

Preparative Methods: typically prepared in situ by dehalogenation of trichloroacetyl halides or dehydrohalogenation of dichloroacetyl halides. Elimination of dichloroacetyl chloride with Triethylamine affords the desired ketene,4 although material formed in this manner is of limited reactivity.5 Reduction of Trichloroacetyl Chloride with Zinc/Copper Couple activated with either Phosphorus Oxychloride6 or 1,1-Dimethoxyethane7 provides fully reactive dichloroketene. Recently, thermal activation of Zinc dust was used to generate dichloroketene.8

Handling, Storage, and Precautions: given the propensity of dichloroketene to dimerize or polymerize, the reagent must be made and used immediately. Polymeric material is obtained on heating or concentration of solutions of dichloroketene, and anhydrous conditions must be maintained.

Dichloroacetylation.

In his original preparation of dichloroketene, Brady formed the reagent in the presence of aniline to form the corresponding acetanilide (eq 1).2 Given the wealth of methods to perform this transformation, this is of limited synthetic utility.

Cyclizations.

The propensity of dichloroketene to undergo cycloaddition reactions with a variety of p-systems has rendered this reagent a powerful synthon.1,3 Treatment of dichloroketene with numerous alkenes such as 1-pentene causes a [2 + 2] cycloaddition to occur (eq 2).9 These cyclizations have been shown to occur in a syn fashion, as reaction of dichloroketene with cis- and trans-cyclooctene affords the corresponding cis and trans bicyclic products (eqs 3 and 4).10 The cycloadditions of dichloroketene are often sensitive to the method of preparation. For example, conjugated dienes react with dichloroketene in a [2 + 2] fashion to form cyclobutanones, but the ketene must be generated by the dehydrohalogenation of dichloroacetyl chloride, as Lewis acids promote the polymerization of most dienes (eq 5).11 In fact, the cyclization of acid sensitive alkenes such as vinyl ethers and styrene can only be realized with dichloroketene formed in this fashion.3a,9 Cyclizations with tri- and tetrasubstituted alkenes are also possible, although in this case the dichloroketene must be generated from activated zinc (eq 6).12 The cyclobutanones formed in this manner can undergo a vast array of transformations (see below).

Cyclization of dichloroketene with unsymmetrical alkenes typically occurs in a regiospecific fashion. For example, cyclization of 1-methylcyclohexene with dichloroketene gives a single product (eq 7).12 Exocyclic methylenes undergo facile conversion to the corresponding cyclobutanones, allowing easy access to spiro compounds (eq 8).13

Dichloroketene also reacts with carbonyls to generate 2-oxetanones.1,3 However, the method of preparation of the ketene is critical. Cyclohexanone, for example, is smoothly converted to the corresponding b-lactone on exposure to dichloroketene prepared via the activated zinc pathway (eq 9).14 It has been proposed that the zinc present in the reaction activates the ketone carbonyl toward cycloaddition.15 Dehydrohalogenation of dichloroacetyl chloride in the presence of acetone does not lead to useful product. However, dichloroketene generated in this fashion reacts readily with monosubstituted benzaldehydes (eq 10).16 The 3,3-dichloro-2-oxetanones formed in this fashion can be made to undergo thermolysis under elevated temperatures, resulting in the generation of dichlorostyrenes (eq 11).16 Cycloalkanones react with dichloroketene to form spirolactones (eq 12).17 Thermolysis leads to exocyclic dichloroalkenes, and Sodium-Ammonia reduction affords the exocyclic methylene (eq 13).17 This provides a useful complement to the methodology developed by Wittig and Tebbe. The chlorinated b-lactones formed via these cycloadditions are useful synthetic intermediates (see below).

Dichloroketene undergoes [2 + 2] cyclizations with numerous other unsaturated compounds. Imines, for example, serve as excellent cycloaddition partners, providing a rapid route to the synthesis of b-lactams (eq 14).18 Diimides also react readily with dichloroketene to form b-iminoazetidinones (eq 15).19 Addition of trichloroacetyl chloride to alkynes in the presence of activated zinc yields 2-cyclobutenones (eq 16).7 These reactions also occur in a regiospecific manner. Ethoxyacetylene adds to dichloroketene, and subsequent hydrolysis gives the vinylogous acid (eq 17).20 Cyclization of vinyl ethers with dichloroketene gives a single product, and chiral ethers have been used to generate optically pure cyclobutanones (eqs 18 and 19).21,22 a-Alkylidenecyclobutanones can be formed on cyclization of dichloroketene with allenes (eq 20).23

While [2 + 2] cyclizations are more common, dichloroketene does undergo [4 + 2] cycloaddition reactions in some cases. For example, b-dialkylamino-a,b-unsaturated enones add in an apparent [4 + 2] sense and, upon elimination of hydrogen chloride, furnish 2-pyrones (eq 21).24 Some imines are also substrates for this reaction, and 2-pyridones can be prepared (eq 22).25

Reaction of vinyl sulfoxides with dichloroketene gives a novel synthetic route to butyrolactones (eq 23).26 With the ready availability of optically pure sulfoxides, this provides an asymmetric source of g-lactones (eq 24).27 Allylic ethers and sulfides react with dichloroketene via a Claisen-type rearrangement to give esters, albeit in modest yields (eq 25).28 This method can be used as a novel entry into macrolide synthesis (eq 26).29

Reactions of Dichloroketene Adducts.

The cycloadduct of cyclopentadiene with dichloroketene can be hydrolyzed to furnish tropolone (eq 27).30 This is a fairly mild and general reaction, and a number of annulated tropolones can be formed in this fashion (eq 28).3,31

The reductive removal of one or both of the chlorine atoms of dichloroketene cycloadducts lends considerable flexibility to the synthetic utility of this reagent.3,4,32 Reduction of the cyclopentadiene addition product with Tri-n-butylstannane or Zinc-Acetic Acid gave the bicyclo[3.2.0]heptenone (eq 29).4 This compound can also be selectively reduced to give exclusively the endo-monochloro derivative (eq 30).33,34 The facile removal of both chlorine substituents renders dichloroketene as a synthetic equivalent of the parent ketene. Since dichloroketene is considerably more reactive than ketene and can be made from inexpensive starting materials, it is superior to ketene in most cases.1,3 In addition, many of the other adducts can also undergo dehalogenation, providing easy access to the b-lactones, b-lactams, and spiroalkanones (eq 31).35 In fact, these compounds are substrates for many of the same reactions known for the cyclobutanones.1,3,4

The dichlorocyclobutanones can easily be expanded or contracted, thereby providing a synthetic source of cyclopropanes or cyclopentanes. Reaction of diazomethane with the cycloadduct of cyclohexene and dichloroketene results in the formation of the corresponding cyclopentanone (eq 32).36 These can undergo several reactions, including dehalogenation (eq 33),36 reductive alkylation (eq 34),37 and conversion to cyclopentenes (eq 35).38,39

While these reactions are well precedented for the cyclopentanones, most are also amenable to the cyclobutanones.1,3,4 Ring contractions of a-chlorocycloalkanones via Favorskii rearrangements are well known.40 Direct exposure of dichloroketene cycloadducts to strong base, however, does not typically lead to ring contraction but rather to ring cleavage (eq 36).41 One method that has been developed to circumvent this shortcoming is the reduction of the carbonyl of the cyclobutanone followed by treatment with base, which causes ring contraction to the corresponding cyclopropane carbaldehyde (eq 37).42 Both endo- and exo-carbaldehydes can be made in this manner.43

An alternative method of ring expansion is via oxidation. Baeyer-Villiger oxidation of the cyclobutanone adducts supplies a synthetic route to cis-bicyclic lactones (eq 38).44 Ring expanded lactams can also be made, with migration of either of the alkyl substituents (eqs 39 and 40).45

The dichlorocyclobutanones can be converted into several other useful materials. Following reductive removal of the chlorines, Selenium(IV) Oxide generates the 1,2-cyclobutanediones (eq 41).46 Lithium-halogen exchange followed by acetylation of the enolate and Ruthenium(VIII) Oxide oxidation affords a one-pot conversion to vicinal dicarboxylic acids (eq 42).47 In tandem with the cycloaddition of dichloroketene, this provides a mild and general method for syn-vicinal dicarboxylations. In a similar fashion, the a-chloroenol acetates can be isolated (eq 43).48 Thermolysis of these compounds results in a retrocyclization reaction to give exclusively the (Z)-a-chloroenone (eq 44).48

Related Reagents.

Chlorosulfonyl Isocyanate; Diiodomethane-Zinc-Titanium(IV) Chloride; Trichloroacetyl Chloride; Zinc/Copper Couple.


1. For a general review of the chemistry of ketenes, see The Chemistry of Ketenes, Allenes and Related Compounds; Patai, Ed.; Wiley: New York, 1980.
2. Brady, W. T.; Liddell, H. G.; Vaughn, W. L. JOC 1966, 31, 626.
3. For extensive reviews on synthetic uses of halogenated ketenes, see (a) Brady, W. T. T 1981, 37, 2949. (b) Brady, W. T. S 1971, 415. For a recent review of ketenes, see Tidwell, T. T. ACR 1990, 23, 273.
4. Ghosez, L.; Montaigne, R.; Roussel, A.; Vanlierde, H.; Mollet, P. T 1971, 27, 615.
5. Hassner, A.; Fletcher, V. R.; Hamon, D. P. G. JACS 1971, 93, 264.
6. Krepski, L. R.; Hassner, A. JOC 1978, 43, 2879.
7. Danheiser, R. L.; Savariar, S.; Cha, D. D. OSC 1993, 8, 82.
8. Stenstrøm, Y. SC 1992, 22, 2801.
9. Brady, W. T.; Waters, O. H. JOC 1967, 32, 3703.
10. Montaigne, R.; Ghosez, L. AG(E) 1968, 7, 221.
11. Ghosez, L.; Montaigne, R.; Vanlierde, H.; Dumay, F. AG(E) 1968, 7, 643.
12. Bak, D. A.; Brady, W. T. JOC 1979, 44, 107.
13. Wiseman, J. R.; Chan, H.-F. JACS 1970, 92, 4749.
14. Brady, W. T.; Smith, L. JOC 1971, 36, 1637.
15. Brady, W. T.; Patel, A. D. JHC 1971, 8, 739.
16. Krabbenhoft, H. O. JOC 1978, 43, 1305.
17. Brady, W. T.; Patel, A. D. S 1972, 565.
18. (a) Duran, F.; Ghosez, L. TL 1970, 245. (b) Luttringer, J. P.; Streith, J. TL 1973, 4163.
19. Hull R. JCS(C) 1967, 1154.
20. Springer, J. P.; Clardy, J.; Cole, R. J.; Kirksey, J. W.; Hill, R. K.; Carlson, R. M.; Isidor, J. L. JACS 1974, 96, 2267.
21. Krepski, L. R.; Hassner, A. JOC 1978, 43, 3173.
22. Greene, A. E.; Charbonnier, F.; Luche, M.-J.; Moyano, A. JACS 1987, 109, 4752.
23. Brady, W. T.; Stockton, J. D.; Patel, A. D. JOC 1974, 39, 236.
24. (a) Mosti, L.; Schenone, P.; Menozzi, G. JHC 1978, 15, 181. (b) Bargagna, A.; Evangelisti, F.; Schenone, P. JHC 1979, 16, 93. (c) Mosti, L.; Schenone, P.; Menozzi, G. JHC 1979, 16, 913. (d) Bargagna, A.; Schenone, P.; Bondavalli, F.; Longobardi, M. JHC 1980, 17, 33. (e) Mosti, L.; Schenone, P.; Menozzi, G. JHC 1980, 17, 61.
25. Fitton, A. O.; Frost, J. R.; Houghton, P. G.; Suschitzky, H. JCS(P1) 1977, 1450.
26. Marino, J. P.; Neisser, M. JACS 1981, 103, 7687.
27. Marino, J. P.; Perez, A. D. JACS 1984, 106, 7643.
28. Malherbe, R.; Belluš, D. HCA 1978, 61, 3096.
29. Vedejs, E.; Buchanan, R. A. JOC 1984, 49, 1840.
30. (a) Minns, R. A. OSC 1988, 6, 1037. (b) Stevens, H. C.; Reich, D. A.; Brandt, D. R.; Fountain, K. R.; Gaughan, E. J. JACS 1965, 87, 5257.
31. Turner, R. W.; Seden, T. CC 1966, 399.
32. Ali, S. M.; Lee, T. V.; Roberts, S. M. S 1977, 155.
33. Brady, W. T.; Hoff, E. F., Jr.; Roe, R., Jr.; Parry, F. H., III JACS 1969, 91, 5679.
34. Rey, M.; Huber, U. A.; Dreiding, A. S. TL 1968, 3583.
35. (a) Brook, P. R.; Griffiths, J. G. CC 1970, 1344. (b) Brady, W. T.; Patel, A. D. JOC 1972, 37, 3536.
36. Greene, A. E.; Deprés, J.-P. JACS 1979, 101, 4003.
37. (a) Deprés, J.-P.; Greene, A. E. JOC 1980, 45, 2036. (b) Greene, A. E.; Luche, M.-J.; Deprés, J.-P. JACS 1983, 105, 2435.
38. Greene, A. E.; TL 1980, 21, 3059.
39. Kochi, J. K.; Singleton, D. M. JACS 1968, 90, 1582.
40. For a review of the Favorskii rearrangement, see Kende, A. S. OR 1960, 11, 261.
41. (a) Brook, P. R.; Duke, A. J. JCS(C) 1971, 1764. (b) Ghosez, L.; Montaigne, R.; Mollet, P. TL 1966, 135.
42. Brook, P. R. CC 1968, 565.
43. Brook, P. R.; Duke, A. J. JCS(P1) 1973, 1013.
44. Jeffs, P. W.; Molina, G.; Cass, M. W.; Cortese, N. A. JOC 1982, 47, 3871.
45. Jeffs, P. W.; Molina, G.; Cortese, N. A.; Hauck, P. R.; Wolfram, J. JOC 1982, 47, 3876.
46. Ried, W.; Bellinger, O. S 1982, 729.
47. Deprés, J.-P.; Greene, A. E. OSC 1993, 8, 377.
48. Deprés, J.-P.; Navarro, B.; Greene, A. E. T 1989, 45, 2989.

James W. Leahy

University of California, Berkeley, CA, USA



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