NUCLEOPHILIC ATTACK ON RING HETEROATOMS

Electrophilic attack on ring heteroatoms ties up an electron pair (which may have been engaged in resonance in the parent species) and confers positive charge on the system, thereby inviting nucleophilic attack or elimination reactions to follow. In small systems the primary product is usually quite unstable. Nucleophilic attack on protonated or Lewis acid-coordinated species will be treated below (Section 5.2.7), because it is not always clear whether such reactions are preceded by an electrophilic step (e.g. protonation) or not. 

Nucleophilic Attack on Ring Atoms Adjacent to Heteroatom or Conjugated with 428... 

Nucleophilic attack on ring atoms adjacent to a heteroatom or conjugated with a... 

We solved the problem by using a three-membered ring (epoxide) for (2) and an a-halo carbonyl compound for (3) two apparently different devices which in fact rely on the same principle. The atoms marked + in (2) and (3) are easily made nucleophilic —by enolisation (i) for example—and the common principle is to use a preliminary nucleophilic attack on a heteroatom to reverse the natural polarity of the atom from nucleophilic to electrophilic. Halogenation (i, E = Br) of a ketone provides a reagent for (3) and epoxidation... 

Onium ions of small and large heterocyclics are usually produced by electrophilic attack on a heteroatom. In three- and four-membered rings nucleophilic attack on an adjacent carbon follows immediately, in most cases, and ring opening stabilizes the molecule. In large rings the onium ion behaves as would its acyclic analog, except where aromaticity or transannular reactions come into play (each with its electronic and steric pre-conditions). A wide diversity of reactions is observed. 

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