Intermolecular synthons

Syntheses of alkenes with three or four bulky substituents cannot be achieved with an ylide or by a direct coupling reaction. Sterical hindrance of substituents presumably does not allow the direct contact of polar or radical carbon synthons in the transition state. A generally applicable principle formulated by A. Eschenmoser indicates a possible solution to this problem //an intermolecular reaction is complex or slow, it is advisable to change the educt in such a way. that the critical bond formation can occur intramolecularly (A. Eschenmoser, 1970). 

In the synthesis of molecules without functional groups the application of the usual polar synthetic reactions may be cumbersome, since the final elimination of hetero atoms can be difficult. Two solutions for this problem have been given in the previous sections, namely alkylation with nucleophilic carbanions and alkenylation with ylides. Another direct approach is to combine radical synthons in a non-polar reaction. Carbon radicals are. however, inherently short-lived and tend to undergo complex secondary reactions. Escheirmoser s principle (p. 34f) again provides a way out. If one connects both carbon atoms via a metal atom which (i) forms and stabilizes the carbon radicals and (ii) can be easily eliminated, the intermolecular reaction is made intramolecular, and good yields may be obtained. 

Paraphrasing Corey s historic definition of synthon [203], Desiraju defined a supramolecular synthon as a structural unit within a supermolecule that can be formed or assembled by known or conceivable synthetic operations involving intermolecular interactions [204], The robustness of the XB has allowed several supramolecular synthons based on this interaction to be identified and some examples have been presented in this chapter. 

Bicycloheptanones formed by intermolecular cycloaddition of 2-cyclo-pentenones to olefins, as in (4.53) 465), are valuable synthons in organic chemistry 454a). 

Interactions can be combined by a designed placement of functional groups in the molecular skeleton to generate supramolecular synthons, which are defined as structural units within supermolecules that can be formed and/or assembled by known or conceivable synthetic operations involving intermolecular interactions (Desiraju, 1995). In other words supramolecular synthons are spatial arrangements of intermolecular interactions. 

Carbenoid sources other than those derived from diazo precursors for catalytic cyclopropanation reactions are currently limited. Inter- and intramolecular catalytic cyclopropanation using iodonium ylide have been reported. Simple olefins react with iodonium ylides of the type shown in equations 83 and 84, catalysed by copper catalysts, to give cyclopropane adducts in moderate yield127 128. In contrast to the intermolecular cyclopropanation, intramolecular cyclopropanation using iodonium ylides affords high yields of products (equations 85 and 86). The key intermediate 88 for the 3,5-cyclovitamin D ring A synthon 89 was prepared in 80% yield as a diastereomeric mixture (70 30) via intramolecular cyclopropanation from iodonium ylide 87 (equation 87)1 0. 

Whereas the intermolecular Heck reaction is limited to unhindered alkenes, the intramolecular version permits the participation of even hindered substituted alkenes, and many cyclic compounds can be prepared by the intramolecular Heck reaction [37]. The stereospecific synthesis of an A ring synthon of la-hydroxyvitamin D has been carried out. Cyclization of the (7T)-alkene 88 gives the (fT)-exo-diene 90, and the (Z)-alkene 91 affords the (Z)-exo-diene 92 [38]. These reactions are stereospecific, and can be understood by cis carbopalladation to form 89 and the. sun-elimination mechanism. 

Recently, we have been investigating the chemistry of a series of racemic diquinoline compounds that form lattice inclusion hosts. The solid-state structures of these involve only rather weak intermolecular attractions. A number of these hosts assemble by means of centrosymmetric supramolecular synthons, and therefore their enantiomer separation is limited in the solid state. 

Pyridinium salts can also be used as synthons in crystal engineering, with the electron-deficient Jt-system interacting with electron-rich aromatic systems. Whether the interactions are either intermolecular or intramolecular is determined by the substituents on the pyridinium ring, as demonstrated by the bispyridinium salts 133 <2003EJO4528> and the pyridinium-appended calixarenes 134 <2006TL181>. 

Wuest has demonstrated that the pyridone moiety also generates a hydrogen-bonded supramolecular synthon that is suitable for building extended arrays.67 Remarkably, methanetetra(6-phenylethynyl-2-pyridone) exhibits a diamondoid network, sevenfold interpenetration and cavities large enough to enclathrate butyric or valeric acid.27 Wuest introduced the concept of tectons to describe molecules that inherently possess the molecular structure and intermolecular recognition features to predictably self-assemble into crystalline networks. He followed this study with several other examples of diamondoid networks sustained by the pyridone moiety 27c d... 

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