Medium rings, transannular interactions

A large number of cyclic acetylenes have been synthesized to investigate the proximity interactions between two triple bonds or between a triple bond and other unsaturated systems. Such transannular proximity interactions have been observed in some cyclic acetylenes of medium ring size. However, no appreciable evidence of the interaction was detected in the electronic spectra of diacctylenes 1 2 - and 3... 

The most difficult rings to close are those that are of medium size (8-11) because torsional and transannular interactions destabilize the transition state. 

TransannUlar interaction Literally cross-ring interactions. Non-bonded interaction between ligands attached to nonadjacent atoms in a ring, for example in a cyclohexane boat or in medium-sized rings. 

Infrared and ultraviolet spectroscopies, introduced in the chemistry of natural products about three decades later, provided the first evidence to support this idea [8, 9]. The discovery of similar modification of reactivity of amino and keto groups across a nine-membered ring of vomicine [10], a strychnine congener [11], pointed to the generality of such transannular interactions in medium-size rings. This then became the topic of systematic and extensive investigations by Leonard and coworkers [12]. 

Shemyakin and co-workers44-47 have shown that the cyclopeptide 80, when heated in inert solvents, undergoes transannular amide-amide interaction with conversion via the azacyclol 81 into 2,3,4,6,7,8-hexa-hydropyrrolol l,2-a pyrimidin-4-one (82) [Eq. (23). This appears to be a general reaction of medium ring cyclopeptides. 

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