Gilman-Cason ketone synthesis

What is Gilman-Cason ketone synthesis?

Gilman first reported this reaction in 1936, and it was later studied extensively by Cason. This method, known as the Gilman-Cason ketone synthesis, involves the preparation of ketones from alkyl (or aryl) cadmium and acyl chloride or anhydride.

Gilman-Cason ketone synthesis - general reaction scheme
Gilman-Cason ketone synthesis

The cadmium reagent is typically prepared from a lithium derivative rather than a Grignard reagent, although aromatic Grignard reagents can form cadmium derivatives easily and yield good results for aromatic ketones. The reaction scope shows that n-butyl bromide is superior to n-butyl chloride, although it is much better than the corresponding iodide. Anhydride reactions are typically inferior to acid chloride reactions. The relative reactivity of acyl halides is in the order:

ArCOI > ArCOBr > ArCOCl > ArCOF

Cadmium chloride CdCl2 is at least as effective as cadmium bromide in preparing the cadmium reagents. Secondary or tertiary alkylcadmium reagents are too unstable to allow their effective use in synthesis, even at a temperature as low as 0 ºC. It was also reported that alkyl cadmium can dissociate and form an alkyl radical upon heating, resulting in coupling products.

The versatility of Gilman-Cason ketone synthesis allows for the synthesis of ketones containing multifunctional groups such as carbonyls and esters.

References

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