Cesium Carbonate (Cs₂CO₃)

Introduction

Cesium carbonate is a white hygroscopic powder that is readily soluble in water. It is produced by reacting cesium hydroxide with carbon dioxide [1] (Scheme 1).

Scheme 1 Preparation of cesium carbonate.

Many of the properties of cesium carbonate are due to the softness of the cesium cation. This softness makes cesium carbonate rather soluble in organic solvents such as alcohols, DMF and Et₂O. This has rendered cesium carbonate useful in palladium chemistry, which is often carried out in non-aqueous media where insolubility of inorganic bases can limit reactivity. Cs₂CO₃ has, for example, been used with good results in Heck, [2] [3] Suzuki [4] and Sonogashira [5] reactions.

Cesium carbonate has also received much attention for its use in O-alkylations, particularly of phenols. [6] [7] It has been postulated that O-alkylations of phenols using Cs₂CO₃ in non-aqueous solvents occurs via the ‘naked’ phenolate anion, which behaves as a strong nucleophile. Therefore, this methodology can even be applied to secondary halides, minimizing the usual unwanted side reactions such as elimination and decomposition.

Cesium carbonate has also found much use in solid supported synthesis, where solubility can be of importance. It has been reported that it not only promotes successful carbonylation of alcohols and carbamination of amines, but also suppresses common side reactions traditionally encountered with other protocols. [8]

In peptide chemistry, a very mild way to produce esters of amino-protected peptides is to treat the carboxylic acid with cesium carbonate followed by the addition of a ­halide in DMF. [9] An intramolecular version has been used to produce macrocyclic lactones. [10]

References

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• 5b Eckhardt M. Fu GC. J. Am. Chem. Soc.  2003,  125:  13642 
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• 7 Macor JE. Blank DH. Post RJ. Tetrahedron Lett.  1994,  35:  45 
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• 10 Buter J. Kellogg RM. J. Chem. Soc., Chem. Commun.  1980,  466 
• 11 Fujivara A. Kan T. Fukuyama T. Synlett  2000,  1667 
• 12 Walla P. Kappe CO. Chem. Commun.  2004,  564