Cascade ring expansion reactions for the synthesis of medium-sized rings and macrocycles

TY - JOUR

T1 - Cascade ring expansion reactions for the synthesis of medium-sized rings and macrocycles

AU - Wootton, Jack M

AU - Tam, Jerry K F

AU - Unsworth, William P

N1 - © The Royal Society of Chemistry 2024

PY - 2024/4/18

Y1 - 2024/4/18

N2 - This Feature Article discusses recent advances in the development of cascade ring expansion reactions for the synthesis of medium-sized rings and macrocycles. Cascade ring expansion reactions have much potential for use in the synthesis of biologically important medium-sized rings and macrocycles, most notably as they don't require high dilution conditions, which are commonly used in established end-to-end macrocyclisation methods. Operation by cascade ring expansion method can allow large ring products to be accessed via rearrangements that proceed exclusively by normal-sized ring cyclisation steps. Ensuring that there is adequate thermodynamic driving force for ring expansion is a key challenge when designing such methods, especially for the expansion of normal-sized rings into medium-sized rings. This Article is predominantly focused on methods developed in our own laboratory, with selected works by other groups also discussed. Thermodynamic considerations, mechanism, reaction design, route planning and future perspective for this field are all covered.

AB - This Feature Article discusses recent advances in the development of cascade ring expansion reactions for the synthesis of medium-sized rings and macrocycles. Cascade ring expansion reactions have much potential for use in the synthesis of biologically important medium-sized rings and macrocycles, most notably as they don't require high dilution conditions, which are commonly used in established end-to-end macrocyclisation methods. Operation by cascade ring expansion method can allow large ring products to be accessed via rearrangements that proceed exclusively by normal-sized ring cyclisation steps. Ensuring that there is adequate thermodynamic driving force for ring expansion is a key challenge when designing such methods, especially for the expansion of normal-sized rings into medium-sized rings. This Article is predominantly focused on methods developed in our own laboratory, with selected works by other groups also discussed. Thermodynamic considerations, mechanism, reaction design, route planning and future perspective for this field are all covered.

U2 - 10.1039/d4cc01303d

DO - 10.1039/d4cc01303d

M3 - Review article

C2 - 38655659

SN - 1359-7345

JO - Chemical communications

JF - Chemical communications

ER -