Macrocyclic synthesis

Intramolecular condensation of phosphonate carbanions with carbonyl groups carried out under conditions of high dilution have been utilized in macrocycle syntheses. Entries 7 and 8 show macrocyclizations involving the Wadsworth-Emmons reaction. Entries 9 to 11 illustrate the construction of new double bonds in the course of a multistage synthesis. The LiCl/amine conditions are used in Entries 9 and 10. 

A normal priority in both direct and template procedures is to maximize yields of the required product by choosing strategies which inhibit competing linear polymerization and other reactions. Unless special circumstances obtain, polymeric materials are often the major product when macrocyclic syntheses are attempted in the absence of appropriate conditions. 

Scheme 8.3 Macrocycle syntheses with aikene metathesis allenylidene-ruthenium catalyst la.

Dziomko and coworkers have utilized the nucleophilic aromatic substitution of aryl amines to chloropyrazoles or chloropyridines in the template step of their macrocycle syntheses.174 175 The nature of the template process is unclear and it could simply be thermodynamic. However, a kinetic effect is a distinct possibility and would require attack of a coordinated aryl amine (Scheme 52). 

In view of the widespread use of tertiary phosphines in coordination chemistry, it is somewhat surprising that phosphorus-containing macrocycles have not evoked more interest. In part this is undoubtedly due to experimental difficulties. The synthesis of P macrocycles is doubly difficult, since the usual difficulties and hazards of phosphorus(III) chemistry are compounded by the complexities and low yields of multistage heterocyclic macrocyclic syntheses. Because of these difficulties, the development of synthetic methods has been slow. Mann s survey73 of the heterocyclic derivatives of P, As, Sb and Bi did not mention phosphorus macrocycles and recent textbooks74,75 give them only cursory mention. 

The synthetic methods can be conveniently divided into those based on conventional (classical) macrocyclic syntheses and those based on template methods. The schools of Ciampolini and Kybe were early, and are still major, contributors to this field. 

As in most synthetic schemes, there are advantages and disadvantages to these in situ macrocycle syntheses. The advantages include increased yields by virtue of the elimination or reduction of side reactions and macrocyclic product control by steric influence of the metal ion. The disadvantages include the fact that the steric requirements of the metal ion may preclude formation of the desired macrocyclic product and the occasional inability to remove the metal ion from the resulting complex due to the inherent instablity of the free ligand. 

D. Zhao, J.S. Moore, Shape-Persistent Arylene Ethylene Macrocycles Syntheses and Supramolecular Chemistry , Chem. Commun., 807 (2003)... 

Many macrocycle syntheses yield products with alkyl or aryl C-substituents, or with fused 2,6-pyridiyl, o-phenylene, or 1,2-cyclohexdiyl rings. Template-style syntheses (see Section 1.20.3) are often substituent-sensitive, and yield products with particular substituent patterns. The (3-enone/ (diamineH+) method for preparing cyclic amines (Section 1.20.2) introduces a variety of substituents on the six-membered chelate rings of cyclam, but only 3-methyl and 3,10-dimethyl substituents on the five-membered rings. Cyclams with a variety of methyl and 1,2-cyclohexdiyl substituents on the five-membered chelate rings have been prepared and structurally characterized.71... 

Hexen-l-yn-3-one, 1-methoxy spiroanellation with, 74 Hexonamides, TV-alkyl- aqueous suspensions various micellar aggregates, 352-353 L-Hexoses total synthesis, 264-265 2-Hexulosides by redox glycosylation , 272 High-dilution methods macrocycle syntheses by, 145-146, 240-241, 329, 338 Hindrance, steric. See Steric hindrance Hippuric acid See Glycine, iV-bcnzoyl-HMDS. See Silanamine,. .. 

It is by now well established that all lanthanide (III) ions, as well as the yttrium(III) and uranyl ions, are effective templates for the synthesis of macrocyclic complexes the scarcity of information on similar systems involving 5f-block elements other than uranium appears to be due to lack of investigation rather than to any intrinsic failure of these elements to function as templates in macrocyclic syntheses. 

Fig. 1 First macrocycle synthesized in 1912 by the high dilution method.

Zhao, D. Moore, J. S. Shape-persistent arylene ethynylene macrocycles syntheses and supramolecular chemistry. Chem. Commun. 2003, 807-818. 

EIGURE 8.2 Depsipeptide-like macrocycles synthesized through a multicomponent P-3CR. 

A number of macrocyclic syntheses which are effected by transition metal reagents have been described. Suggest an organometallic reagent or metal complex which could bring about the following conversions ... 

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