Direct Preparation of Organocadmium Compounds from Highly Reactive Cadmium Metal Powder

Synthesis of Ketones from Alkyl Halides by Cd* Mediated Coupling with Acyl Halides

E. R. Burkhardt & R. D. Rieke
J. Org. Chem. 50, 416-417 (1985)

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Summary

Highly reactive cadmium metal powders and a cadmium-lithium alloy were prepared and were used to prepare organocadmium reagents directly from organic halides.

The transmetalation reaction of an organomagnesium or organolithium reagent with cadmium halides is a well-known standard preparation method for organocadmium reagents.1

It has been reported that an organocadmium reagent can be prepared directly from cadmium metal and alkyl halides.2 However, the reaction was limited to ethyl iodide. Using the general reduction approach which we reported earlier, highly reactive cadmium metal powders as well as a cadmium-lithium alloy can be readily prepared.3 This metal is highly reactive toward a variety of organic halides. The organocadmium reagents formed undergo the well-known reaction with acid chlorides4 to form ketones in high yields.

Three general methods can be used to prepare the metal powders:

  1. Lithium naphthalide is first prepared in glyme or THF at room temperature and then transferred via cannula into a second flask containing cadmium chloride.5 The mixture is stirred for 30 min at room temperature to produce a black slurry. After standing for 6-12 h, the black powders settle, leaving a clear solution above the metal. The solvent can be removed via a cannula at this point and the metal washed with fresh dry solvent to remove naphthalene and lithium salts. A different solvent may be added at this point.
  2.  
  3. This approach allows the preparation of the highly reactive cadmium powders in hydrocarbon rather than ethereal solvents and produces a more highly reactive cadmium than method A.6 Lithium naphthalide is prepared by sonicating lithium, naphthalene, and N,N,N,N-tetramethylethylenediamine in toluene for 8-12h.7 The deep purple solution is then transferred via cannula onto cadmium chloride, and the resulting mixture is stirred for 30 min, yielding a black slurry which slowly settles on standing.
  4.  
  5. The following approach represents a new convenient method of producing the cadmium lithium alloy Cd3Li.
    In this method, lithium (28.94 mmol), cadmium chloride (12.39 mmol), and a catalytic amount of naphthalene are added to glyme or THF (20 mL) and the mixture is refluxed until the lithium disappears, approximately 3-4 h.8 The resulting black slurry contains the known alloy Cd3Li. The alloy Cd3Li has been previously prepared by melting lithium and cadmium together in an inert atmosphere. However, there have been no reports of any attempts to use this alloy synthetically.
    Treatment of the alloy with one equivalent of I2 to leach out the majority of the lithium produces a very reactive cadmium metal powder. This metal will react with alkyl and aryl halides, yielding organocadmium reagents.
Table III
Ketones from Acid Chlorides
RX RCOCl Ketone Yield
Me(CH2)4Br MeCOClMeCO(CH2)4Me80%
PhCH2BrMeCOClPhCH2COMe40%
PhCH2BrPhCOClPhCH2COCH2Ph88%

The high reactivity of the cadmium metal powders the direct oxidative insertion to a variety of organic halides is readily apparent, reacting with benzyl bromides in under 3h at room temp and in 18 h in refluxing THF with iodobenzene. This highly reactive metal powder reacts selectively with the benzyl bromide of o-bromobenzyl bromide, giving an organocadmium which yields o-bromotoluene upon quenching with acid. The organocadmium reagent produced adds to allyl bromide to give the cross-coupled product in high yield. α-Bromo-p-tolunitrile reacts with cadmium metal powder at 0°C, giving an organocadmium reagent which can react with allyl bromide or an acyl chloride to give products with the cyano group intact.

The organocadmium reagents can be used in the standard ketone synthesis from acid chlorides.10 However, when highly reactive cadmium is used, a variety of new functional groups can be present in the organocadmium reagent. Table III summarizes some of these results.


References

  1. Gilman, H.; Nelson, J. F. Rec. Trav. Chim. Pays-Bas 55, 518 (1936); Cason, J. Chem. Rev. 40, 15 (1947)
  2. Klabunde, K. J.; Murdock, T. O. J. Org. Chem. 41, 1076 (1976)
  3. Rieke, R. D.; Li, P. T.; Bums, T. P.; Uhm, S. T. J. Org. Chem. 46, 4323 (1981)
    Rieke, R. D.; Hudnall, P. M. J. Am. Chem. Soc. 94, 7178 (1972)
  4. Cason, J. Chem. Rev. 40, 15 (1947); Shirley, D. A. Organic Reactions, Vol. 8, 28 (1954)
  5. Method A: Li (36.84 mmol) and naphthalene (38.58 mmol) in 30 mL of glyme or THF is stirred 4 h under argon. The green lithium naphthalide is transferred via cannula into the CdCl2 (16.01 mmol) and stirred 30 min. The black cadmium powders settle from the colorless solution in 6-12 h.
  6. Method B: Li (9.993 mmol), naphthalene (11.833 mmol), and TMEDA (11.512 mmol) in 25 mL of toluene is sonciated for 8-12 h under argon.7 The deep purple lithium naphthalide is transferred via cannula into the CdCl2 (4.9820 mmol) and stirred 30-60 min. The black cadmium powders settle from the colorless solution in 6-12 h.
  7. Fujita, T.; Watanaba, S.; Suga, K.; Sugahara, K.; Tsuchimoto, K. Chem. Ind. (London), 4, 167 (1983)
  8. Method C: Li (28.94 mmol), CdCl2 (12.39 mmol), and naphthalene (2.88 mmol) are stirred in 30 mL of refluxing glyme or THF. The reduction is complete when the lithium piece is consumed.
  9. Van der Merel, C.; Vinke, G. J. B.; Hennephof, J.; van der Lugt, W. J. Phys. Chem. Solids 43, 1013 (1982)
  10. General reaction procedure: Iodine (7.416 mmol) in glyme was added to the cadmium-lithium alloy (14.79 mmol of CdCl2 reduced). Benzyl bromide (12.6 mmol) was dripped into the black slurry over 30 min. The glyme was stripped off in vacuo and 15 mL of benzene added. Benzoyl chloride (12.1 mmol) was added and stirred 20h at room temperature. The yield by GLC was 88% benzyl phenyl ketone and 9% bibenzyl. Cadmium powders generated by Method A5 are used without treatment with iodine.