Nucleophilic and Electrophilic Attack on Cycloalkenes

2 Bicyclic alkenes. Bicyclic systems like the alkenes 5.188 and 5.189 are well known to be attacked from the exo direction,600 601 on the less hindered convex face of the bicyclic system. Similarly high levels of stereocontrol are found for nucleophilic attack on bicyclic systems, as in the reduction of the ketone 5.190, in which the preference for exo attack overwhelms the steric hindrance offered by the adjacent methyl group.602 Bicyclic systems, especially like these with a zero bridge, are often used in synthesis to give reliably high levels of stereocontrol, with the penalty that there may be many steps needed to open them up to reveal a target structure. 

However, there are anomalies, where a steric effect is clearly not enough to explain the observed stereoselectivity. The steric argument, although commonly invoked, is weak for norbomene 5.191 and for the bicycloocta[2.2.2]diene 5.192, but the selectivity for exo attack in the former and endo in the latter is 

More convincingly, the steric argument is nearly nonexistent for the diene 5.193, but it shows high levels of diastereoselectivity in Diels-Alder reactions, with attack in the endo direction, which is, if anything, the more hindered.605 

However, pyramidalisation is not the whole story, for there are alkenes known to be pyramidalised in one direction, which nevertheless react in another,608 and we shall come to further anomalies in using only pyramidalisation when we come to discuss Se2 reactions in Section 5.2.3.4. 

3 Electrophilic Attack on Open-chain Double Bonds with Diastereotopic Faces 

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