Reaction regioselectivity, proximity effects

Interestingly, in the reaction of 2-(3-chlorophenyl)-4,4-dimethyloxazoline with an alkyllithium [25], the deprotonation is chelation-controlled, but the addition of R" follows PAR. A reverse regioselectivity for alkylcuprate addition may well be explained by a complex-induced proximity effect which has been invoked to rationalize the alkyllithium additions. It is known that copper coordinates exceptionally well with amino and imino ligands. 

The likely reason for this change in regioselectivity lies in the spatial constraints imposed by the host structure by placing the dienophile in close proximity to the 1,4 positions of the diene. Similarly, substituted naphthalenes react with the same dienophile inside the cavity. This reaction is too slow to be observed in bulk solution but proceeds inside the host at 100 °C. Again, spatial preorganization inside the host s inner cavity is the likely reason for observing reactivity that is unknown from solution chemistry. This effect serves to overcome the entropic cost normally associated with reactions with the aromatic system of naphthalene. The same can be said for the photochemical [2-1-2] addition of substituted maleimide to a substimted naphthalene. 

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