Macrocyclic ethers, synthesis

Macrocycles have been prepared by formation of macrocyclic imines as well as by using variations of the Williamson ether synthesis ". Typically, a diamine or dialdehyde is treated with its counterpart to yield the Schiff s base. The saturated macrocycle may then be obtained by simple reduction, using sodium borohydride, for example. The cyclization may be metal-ion templated. In the special case of the all-nitrogen macrd-cycle, 15, the condensation of diamine with glyoxal shown in Eq. (4.14), was unsuccess-ful ... 

Zhu and coworkers have developed SNAr-based macrocyclization via biaryl ether formation.4 The first example of SNAr-based macrocyclization for synthesis of model carboxylate-binding pocket C-O-D rings of vancomycin was reported in 1994 (Scheme 9.3).10... 

An early synthesis of [18]crown-6 (1) involved the cyclization of hydroxychloride (30) via a Williamson ether synthesis. The yield was 2%. In an adaptation of this approach ethylene oxide was oligomerized in the presence of an alkali cation template. By varying the cation template from lithium to sodium to potassium the major macrocyclic product changed from [12]crown-4 to [15]crown-5 to [18]crown-6, albeit only in about 10% yield (76CC295). 

I4 Gokel, G. W. Korzenioski, S. H., Macrocyclic Polyether Synthesis, Springer Berlin, (1982). 151 Gokel, G. W., Crown Ethers and Cryptands, Royal Society of Chemistry Cambridge, (1991). 

There has been growing interest in the synthetic macrocyclic molecular rjeceptors since Pedersen s pioneering work on crown ether synthesis Separate reports, dealing... 

To appreciate the wealth and diversity of crown ethers and their inclusion possibilities see for example Macrocyclic Poly ether Synthesis, G. W. Gokel and S. H. Korzeniowski, vol. 13 in Reactivity and structure concepts in organic chemistry, Springer-Verlag, Berlin, 1982. 

The principle of cyclopolymerization has been applied to the synthesis of macrocyclic ether-containing polymers which may simulate the properties of crown ethers. l,2-Bis(ethenyloxy)benzene (a 1,7-diene) and l,2-bis(2-ethenyloxyethoxy)benzene (a 1,13-diene) are typical of the monomers synthesized. Homopolymerization of the 1,7-diene via radical and cationic initiation led to cyclopolymers of different ring sizes homopolymerization of the 1,13-diene led to cyclic polymer only via cationic initiation. Both monomer types were copolymerized with maleic anhydride to yield predominantly alternating copolymers having macro-cyclic ether-containing rings in the polymer backbone. 

Asymmetric total synthesis of terpenoids possesing novel structure of macrocyclic ethers with two bibenzyl fragments 00YGK1167. 

Additional information on the synthesis of perfluorinated linear and macrocyclic ethers can be found in two review articles. 

Gokel, G.W. Dishong. D.M. Diamond, C.J. Lariat ethers. Synthesis and cation binding of macrocyclic polyethers possessing axially disposed secondary donor groups. J. Chem. Soc., Chem. Commun. 1980. (22), 1053-1054. 

Syntheses. The general method for preparing macrocyclic polyethers is the Williamson ether synthesis which involves nucleophilic displacement of halide ions from a dihaloalkane by the dianion derived from a diol (Scheme 1). 

Hetero-Crown Ethers—Synthesis and Metal-Binding Properties of Macrocyclic Ligands Bearing Group 16 (S, Se, Te) Donor Atoms... 

The simple macrocyclic ether 18 was synthesized as shown in Figure 16. Chain elongation of L-leucine via the Amdt-Eistort synthesis, followed by reduction, provided the basic 13-aminoalcohol building block. The ether linkage was formed by rhodium-catalyzed caibene insertion, and the phosphonate was introduced by an Arbusov reactkm on the bromoethyl derivative. Coupling to L-leucine and fomation of the macro-cyclic lactam proceeded as described above for the more rigid analog. 

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