Crown ethers as catalysts

There are two other approaches to enhancing reactivity in nucleophilic substitutions by exploiting solvation effects on reactivity the use of crown ethers as catalysts and the utilization of phase transfer conditions. The crown ethers are a family of cyclic polyethers, three examples of which are shown below. 

Several other high inductions have been reported by using crown ethers as catalysts (Scheme 10.8). The Toke group has used a chiral crown 11 (Chart 10.2), which incorporates a glucose unit, for the addition of 2-nitropropane to a chalcone (Scheme 10.8) [38], Several other effective chiral crowns (12-17, Chart 10.2 and Scheme 10.8) are noted [24e,39-42,48b]. An interesting study of the Michael addition under both solvent-free (0% ee) and liquid-liquid conditions (up to 70% ee) was reported by Diez-Barra and co-workers, who also addressed the question of free -OH quats (28, 58% ee) verses O-benzyl quats (30, 46% ee) [43]. 

Scheme 7. Use of crown ether as catalyst in the Michael reaction.

A high complexation constant between the ligand and the salt in the organic phase, together with a high partition ratio for the complexed crown ether in the organic phase, are both prerequisites to the successful use of crown ethers as catalysts in aqueous-organic biphasic systems [38,39]. 

Scheme 5.4 Enantioselective Michael reaction of ethyl glycinate benzophenone imine with several enones using chiral crown ethers as catalysts.

Two conditions should be satisfied to allow the use of crown ethers as catalysts under PTC conditions i) a favourable partition ratio of complexed crown... 

Nordlander, J. E., and Catalano, D., Crown ether as catalyst of N-alkylation reactions, Tetrahedron Lett., 1978, 4987. 

All four commonly occurring halide ions (fluoride [1-5], chloride [5—11], bromide [5, 8-10], and iodide [5, 7-9, 10, 12-15] have been phase-transferred and in the process, quaternary ions [1, 6-8, 10, 12-15], crowns [2, 4, 8, 9, 13], cryptates [3, 13] and resins [5] have all been utilized. Most of the processes reported are essentially Finkelstein reactions [16]. In a typical phase transfer of fluoride utilizing crown ether as catalyst, an acetonitrile solution of benzyl bromide is stirred with a catalytic amount of 18-crown-6 and solid potassium fluoride. The product, benzyl fluoride (see Eq. 9.1), is isolated in quantitative yield [2]. 

Crown ethers as catalysts of fluoride-anion-mediated reactions in peptide synthesis. Part 1. Protection of tryptophan by benzyloxycarbonyl and 2,4-dichlorobenzyloxy-carbonylgroups. Y. S. Klausner and M. Chorev, J. C. S. Perkin I, 627 (1977)... 

The nature of the activity of crown ethers and the advantages of the use of crown ethers as catalysts in chemical reactions make it applicable for polymer synthesis. 

With the discovery of the crowns and related species, it was inevitable that a search would begin for simpler and simpler relatives which might be useful in similar applications. Perhaps these compounds would be easier and more economical to prepare and ultimately, of course, better in one respect or another than the molecules which inspired the research. In particular, the collateral developments of crown ether chemistry and phase transfer catalysis fostered an interest in utilizing the readily available polyethylene glycol mono- or dimethyl ethers as catalysts for such reactions. Although there is considerable literature in this area, much of it relates to the use of simple polyethylene glycols in phase transfer processes. Since our main concern in this monograph is with novel structures, we will discuss these simple examples further only briefly, below. 

The unique ability of crown ethers to form stable complexes with various cations has been used to advantage in such diverse processes as isotope separations (Jepson and De Witt, 1976), the transport of ions through artificial and natural membranes (Tosteson, 1968) and the construction of ion-selective electrodes (Ryba and Petranek, 1973). On account of their lipophilic exterior, crown ether complexes are often soluble even in apolar solvents. This property has been successfully exploited in liquid-liquid and solid-liquid phase-transfer reactions. Extensive reviews deal with the synthetic aspects of the use of crown ethers as phase-transfer catalysts (Gokel and Dupont Durst, 1976 Liotta, 1978 Weber and Gokel, 1977 Starks and Liotta, 1978). Several studies have been devoted to the identification of the factors affecting the formation and stability of crown-ether complexes, and many aspects of this subject have been discussed in reviews (Christensen et al., 1971, 1974 Pedersen and Frensdorf, 1972 Izatt et al., 1973 Kappenstein, 1974). 

The cocatalytic effects of pinacol in the phase transfer catalysis (PTC) of dihalocarbene additions to alkenes were noted by Dehmlow and co-workers who showed that pinacol accelerates the PTC deprotonation of substrates up to pKa 27.7 Dehmlow also studied the effects of various crown ethers as phase transfer catalysts in the addition of dibromocarbene to allylic bromides.8 In Dehmlow s study, elevated temperature (40°C) and dibenzo-18-crown-6 did not give the highest ratio of addition/substitution to allyl bromide. However, the submitters use of pinacol,... 

Breccia, P., Cacciapaglia, R.. Mandolini. L. and Scorsini, C. (1998) Alkaline-earth metal complexes of thiol pendant crown ethers as turnover catalysts of ester cleavage. J. Chem. Soc., Perkin Trans., 2, 1257. 

Crown Ethers as Chiral Phase-Transfer Catalysts 163... 

The use of chiral crown ethers as asymmetric phase-transfer catalysts is largely due to the studies of Bako and Toke [6], as discussed below. Interestingly, chiral crown ethers have not been widely used for the synthesis of amino acid derivatives, but have been shown to be effective catalysts for asymmetric Michael additions of nitro-alkane enolates, for Darzens condensations, and for asymmetric epoxidations of a,P-unsaturated carbonyl compounds. 

Landini D, Montanar F, Pirisi FM (1974) Crown ethers as phase-transfer catalysts in 2-phase reactions. J Chem Soc Chem Commun 879-880... 

One of the major developments in organic chemistry during the past 15 years has been the application of phase-transfer catalysis to synthesis. These reactions are often effected in an aqueous base-organic two-phase system with an ammonium or phosphonium salt or crown ether as the catalyst. Crown ethers have also been of great utility as catalysts for solid-liquid phase-transfer processes. Some of the more attractive fea-... 

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