Cyclization reactions in confined space

Cyclization of chain substrates into ring products is an important reaction in organic synthesis. The ease of this process is measured by the Effective Molarity, which indicates that some rings (5, 6 and 7-membered ones) are especially facile to close, while others (>8 membered) are far more challenging. Confinement of the cyclization inside the nanometric cavity of capsules, coordination cages or porous materials can greatly facilitate the reaction via preorganization of the reagents and stabilization of the transition states, also offering the chance to alter the innate selectivity of the reaction. Moreover, the use of chiral cavities enables control over cyclization stereoselectivity. Eventually, pre-organization of the substrate chain inside the cavity can facilitate the closure of medium and large rings, a longstanding goal in organic synthesis. This review analyzes examples of the use of nanoconfinement to improve cyclization reactions, control their selectivity and close challenging rings. © 2023 Elsevier Ltd