Transannular Addition of Nucleophiles

Transannular additions by nucleophiles tend to occur with the larger carbocy-cles due to their increased flexibility, or in polycyclic compounds where reactive centers are forced into close proximity. 

Large cyclic hemiacetals are also formed from the intramolecular alkylation of ketal radicals of lactones, as demonstrated by Eq. 56 [84]. 

Under Lewis acidic conditions, cyclic acetals such as 72a-b form oxonium ion intermediates which cyclize via an intramolecular Friedel-Crafts alkylation onto the tethered arene to form polycyclic benzylic ethers, Eq. 57 [85]. 

In electrophilic addition reactions, transannular participation by an oxirane to form an oxonium ion occurs in medium-ring cycloalkenes. Thomas first investigated this transannular addition in epoxide 73 [86]. Treatment with iodine gave iodinated bicyclic ethers 74 and 75, Eq. 58. 

Subsequently, Martin showed that treatment of epoxyketone 76 with iodine gave predominantly 77, as well as some 78, Eq. 59 [87a]. 

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