Ring expansion and ring contraction

In the course of an organic synthesis, a chemist often needs to form a new or alter an existing ring. Ring expansion and ring contraction reactions refer to a set of reactions which can lead to the expansion or contraction of an existing ring, often making it possible to access structures that would be difficult if not impossible to synthesise with single cyclization reactions.

Ring expansions are valuable because they allow access to larger systems that are difficult to synthesize through a single cyclization due to the slow rate of formation (seven member and larger rings). Classifying ring expansions by the mechanism of expansion and the atom(s) added allows one to see the similarities between different expansions methods and different incorporated atoms. The broadest classification comes by the mechanism of expansion. The rings can be expanded by attack of the ring onto an outside group already appended to the ring (a migration/insertion), opening of a bicycle to a single larger ring, or coupling a ring closing with an expansion. These expansions can be further broken down by what type of atom they incorporate (a carbon or a heteroatom) into the expanded ring.

Carbon insertions are tremendously useful reactions which introduce an additional carbon atom into the ring. These reactions are used in the synthesis of many drugs and natural products. These can proceed through any of the mechanisms listed below.

These reactions have the general features of having an exocyclic leaving group on a carbon adjacent to the ring and an electron donating group on the ring capable of initiating a migration of an endocyclic bond.

A common migration introduction of carbon is a pinacol rearrangement. While this reaction refers specifically to a vicinal dihydroxide rearrangement, there are other pinacol type rearrangements that proceed through the same general mechanism such as the Tiffeneau-Demjanov rearrangement. These "semipinacol rearrangements occur under milder conditions and are thus preferable in complex syntheses. These reactions are useful beyond simply expanding a ring because the exocyclic group attacked may also have other functionality appended to it besides the leaving group. The group to which the endocyclic bond migrates can also be selectively added to the ring based on the functionality already present, for example 1,2 addition into a cyclic ketone.

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