Cesium effect

Salvatore, R. N. Nagle, A. S. Jung, K. W. Cesium effect high chemoselectivity in direct... 

The Cesium Effect Syntheses of Medio- and Macrocyclic Compounds... 

The following contribution is intended to continue our earlier review [6] dealing with the then known cesium assisted ractions only some very important earlier cesium assisted reactions are described here for the sake of completeness After a short description of the properties of some cesium compounds used in this respect in organic synthesis, those reactions are discussed that have been published more recently and which proceed under the intermediate formation of organic cesium salts at oxygen, nitrogen or sulphur functions. Only those cyclization reactions are considered which allow a direct comparison of the yields obtained with cesium compounds or cesium metal. The description starts with reactions leading to the formation of C—C bonds and proceeds to the syntheses of ethers, lactones, amines and sulfides. The discussion ends with a summary of the attempts to explain the cesium effect . 

CesHDin Salts in Organic Chemistry and for the Cesium Effect ... 

A significant cesium effect was observed in reactions forming C—N bonds leading to macrobicyciic compounds. Lehn et al. [34] synthesized the nona-tosylaza macrobicycle 19 in a one step reaction by a threefold bond formation combining the two triply functionalized building blocks 17 and 18. The cryptand 19 was... 

A dramatic cesium effect was found by Weber in the case of the synthesis of the tetrabenzo crown ether 31, which is of interest for applications in ionselective electrodes [39]. The cyclization reactions starting from the cesium phenolate obtained from 29 and the tosylate 30 under high dilution conditions in DMF led to 31 in 37 % yield. This is a dramatic improvement of the formerly obtained yield of only 6 % in the system KOH/ -butanol/ethanol/DMF [40]. 

The investigation of thia crown ethers, e.g. trithiacyclononane (64, 9S3 ). wh< complexation properties towards transition metal cations were of interest [61,62], was complicated for a long time by the low yields obtained from the corresponding cyclization reactions [63]. The combined application of the cesium effect and of the high dilution principle [1] in the reaction of 1,2-dichloroethane and the dithiol 63 led to an increase of the yield of 64 from 4.1 % (tetraalkylammonimn methano-late as the base) [64] to 50% [65, 66]. 

Yield increases in a similar order of magnitude as in the synthesis of the lower homologues were achieved also in the preparation of hexathia[18]crown-6 ( 18S6 , 72) by the cesium effect . Cooper et al. [70] obtained 72 from the dithiol 70 and the dichloro compound 71 in a one-component dilution principle reaction [1] in a yield of 76% using a suspension of cesium carbonate in DMF. When the reaction was carried out under analogous conditions with potassium carbonate, 72 was isolated in a much lower yield of only 38% [70]. 

The highly strained oxathia[3.1]naphthalenocyclophane 84 was first synthesized by Duchene and Vogtle [80], who used the cesium effect in the cyclization of the bromide 83 with the reagent combination NaaS/CsjCOs in eth ol, yielding 84 in 5.4% yield. The sulfide 84 was desulfurized to the highly strained target molecule oxa[2.1]naphthalenophane 85. 

A significant cesium effect was also observed by Meurer and Vogtle [82] in the synthesis of the naphthalenophane 90 formed by reaction of the bis(bromo-methyl) compound 89 and 1,3-benzenedithiole. The cyclization carried out under dilution conditions [1] withCsOH in ethanol/benzene (10 1) produced the naphthalenophane 90 in 22% yield, whereas a change to the base NaOH decreased the yield to 7% [82]. 

The particular influence of cesium ions on the course of cyclization reactions which is proven by many comparison experiments with different metal cations has been called the cesium effect . As a rule, equimolar amounts of cesium compounds are used, which means that one cannot normally speak of a cesium catalysis. Nevertheless, a catalytic effect with respect to the cesium cation often cannot be excluded. 

Many attempts to interprete the cesium effect proceed from the special position of cesium in the periodic system of the elements and in the first main group Cesium forms the cation with the largest ionic radius and follows the Tl ion with respect to the largest polarizability (Table 10). 

More recent attempts to interprete the cesium effects suggest models of differential geometry [99]. So-called periodic ro-potential surfaces ( POPS ) and isopotential surfaces ( TFS , tangential eM OTrface ) of the cesimn ions as templates for organic molecules are proposed. According to these model considerations, an orientation of nonpolar molecular substructures at the zero-potential surface ( POPS ) and an orientation of polar substructures at the isopotential surface ( TFS ), take place, which should favour an intramolecular... 

Illuminati and Mandolini [101] explained the cesium effect from a physicochemical point of view solely in terms of ion pair effects. They introduced the term effective molarity ( EM ) to characterize the course of the cyclization reaction [101, 102], The effective molarity is definwi as the ratio of the velocity constants of the intramol mlar reaction (cyclization) Jind the intcrmolecular reaction (oligomerization) EM = kintra/ imer [mol/1]. EM therefore is the substrate concentration, at which the cyclization and oligomerization proceed with equal reaction rates. As a consequence, a concentration below the EM in the course of the reaction causes an intramolecular reaction path to be favored [102]. 

The starting materials are mostly crystalline and easily accessible in usually high yields (e.g., by application of the dilution principle [6] and/or the cesium effect [7]). 

Ostrowicky, A., Koepp, E., Vogtle, F. The Cesium Effect Syntheses of Medio- and Macrocyclic Compounds 161, 21-6S (1991). 

Another effect, called the cesium effect [843, 844], is also connected with the observation that salts of anions with large counterions are highly dissociated in dipolar aprotic solvents, and consequently more anion-reactive. For example, the higher solubility of cesium carbonate in dipolar aprotic solvents and the fact that this salt is far more dissociated than the corresponding Li+, Na" ", or K" " salts, makes this carbonate a superior base in organic synthesis. Amongst the alkali metal cations, the ionic radius of Cs+ r = 334 pm) is more than twice that of Li+ (r = 152 pm). 

Salvatore RN, Nagle AS, Jung KW (2002) Cesium effect high chemoselectivity in direct iV-atkylation of amines. J Org Chem 67 674-683... 

In this way compounds 62 and 63 required for the final cyclization were synthesized. This cyclization to the tube-shaped macropolycycle with four aromatic subunits was carried out using the cesium effect [60] and the dilution principle... 

Stereospecific conversion of peracetylated hexopyranosyl halides to 1-esters of complex carboxylic acids has been achieved in excellent yields by use of cesium salts cesium salts of amino acids), a method borrowed from peptide chemistry, the "cesium effect" ensuring a strictly 8 2... 

Inversion of Chiral Alcohols. One of the most common applications for cesium acetate is its use in the inversion of the stereochemistry of secondary alcohols that have been converted into better leaving groups. Once the acetate is substituted via a direct SN2-fike displacement, it can then be easily converted back to the alcohol. Some attribute the enhanced nucleophilicity of cesium acetate to a cesium effect. Previously, cesium propionate had been used with alkyl mesylates. The use of this reagent generally resulted in good yields and was preferred to other methods, but it could lead to complicated interpretation of resulting H NMR spectra, whereas an acetate product could be more easily carried forward into further synthetic modification. 

---