Ring‐Expansion Reactions in the Synthesis of Macrocycles and Medium‐Sized Rings

Functionalised macrocycles and medium‐sized rings have applications in a number of scientific fields, ranging from medicinal chemistry and supramolecular chemistry, to catalysis and nanotechnology. However, their value in these areas can be undermined by a simple, but important limitation: large ring systems are very often difficult to make. Traditional end‐to‐end cyclisation reactions of long linear precursors are typically unpredictable and impractical processes, mainly due to unfavourable enthalpic and entropic factors. Most published methods to make large rings focus on minimising the damage inflicted by performing the difficult cyclisation step; in contrast, ring‐expansion reactions enable it to be avoided altogether. In this Review article, it is highlighted how “growing” rings from existing cyclic systems via ring expansion can expedite the efficient, practical and scalable synthesis of macrocycles and medium‐sized rings.