Cycloalkenes transannular reactions

It is now almost 40 years since Cope and Prelog first described the phenomenon of transannulation reactions during their independent studies of electrophilic additions to medium ring cycloalkenes. - Since that time transannular reactions have been encountered in an enormous variety of carbo- and hete-ro-cyclic medium ring compounds having a wide array of differing functionalities. Indeed, the chemistry of these fascinating processes has now become part of the day-to-day armoury of the modem synthetic chemist. ... 

This chapter summarizes those transannular reactions in medium ring carbocycles which result in carbon-carbon bond formation via alkylation of carbon, in the presence of electrophilic reagents. It is therefore a logical extension of two other chapters in this volume, covering Friedel-Crafts Alkylations (Chapter 1.8), and Polyene Cyclizations (Chapter 1.9). The discussion of these processes is organized according to the size of the cycloalkene from which transannular cyclization is effected. 

Epoxide -> aliylic alcohol. Treatment of an oxirane with equimolar amounts of 1 and DBU in an aromatic solvent affords aliylic trimethylsilyl ethers in moderate yield. 2,2-Di-, tri-, and tetrasubstituted oxiranes, as well as oxides of cycloalkenes, react at 23° or below. 2,3-Di- and monosubstituted oxiranes do not react at this temperature these species react with 1 and DBU at 70-80° to give trimethylsilyl enol ethers. The reaction of epoxycyclooctane gives a product of transannular cyclization. In the case of epoxycyclohexane, the intermediate 2 has been isolated. 

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. 

One of the most common outcomes when an RCM reaction fails is the competing CM of the substrate to form linear or cychc dimers, or potentially ohgomers or even polymers. The competition between RCM and CM in the metathesis of dienes will depend on a number of factors, predominantly related to the structure of the target cycloalkene. The strain introduced (AH composed of angle strain, transannular strain, and torsional strain) will depend on the substitution pattern of the diene, while the loss of entropy (AS) will depend on the number of rotors frozen in the product that were otherwise free to rotate in the substrate. The formation of macrocycles will predominantly be influenced by AS, as rings greater than c. 12 members in size typically suffer relatively little strain. Macrocycle formation is not considered in detail here, but has been reviewed recently this section will focus on rings of 5-10 members. 

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