Bridgehead positions nucleophilic substitution

Although the bridgehead positions of many polycyclic hydrocarbons have been found to be quite unreactive toward nucleophilic substitutions187), the 1-ada-mantyl cation may be generated with relative ease. Since the tertiary 1-ada-mantyl cation is considerably more stable than the secondary 2-cation, car-bonium ion substitution reactions strongly favor the bridgehead positions (see, however, below). 

Substituted bicycloalkyl halides are very unreactive toward nucleophilic substitution reactions. The low reactivity in S l reactions has been attributed to the fact that a planar configuration at the bridgehead carbon cannot be obtained without the introduction of considerable strain119. On the other hand, the S 2 reaction is precluded because a backside approach of the nucleophile cannot occur at a bridgehead position for a steric reason. The lack of reactivity of 1 -halobicycloalkanes toward nucleophiles by polar mechanisms makes them attractive substrates for the S l mechanism. 

In a manner similar to that of olefins, bicyclobutanes substituted by electron-withdrawing groups at the bridgehead position can undergo facile nucleophilic attacks. Studies of alkoxide-catalyzed additions of alcohols to bicyclobutanecarbonitrile (35, R = H) (equation 73) using crotononitrile as a reference olefin (equation 74), showed that the two substrates resemble one another very much in both their reactivity and activation parameters. ... 

An alternative substrate design, in which the alkene radical cation is substituted only at the internal position, forces the nucleophilic cyclization into the endocyclic mode, leading overall to bicyclic systems with a bridgehead nitrogen (Scheme 31) [139,140]. 

The nitro group does not necessarily have to be in the o- or -position of the benzene ring, nor is the presence of a nitro group a prerequisite for nucleophilic photosubstitution via the S l mechanism to occur. The meta-nitro analogue 35 with a tert-butyl group at Ca displays S l behaviour (with a series of nucleophiles)197 and so do the bridgehead halide 9-bromotriptycene (with phosphide and arsenide ions)32, compound 36 (with nitronate and azide ions)1, compound 37, X = Cl (with nitronate ions)199 and compound 38 (with azide ion)200. For compound 37, X = Br, SN2 substitution is competitive. 

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