Strain‐Induced Ring Expansion Reactions of Calix[3]pyrrole‐Related Macrocycles

• Published in: Chemistry : a European journal 2022-03, Vol.28 (17), p.e202200056-n/a
• Main Authors: Inaba, Yuya, Kakibayashi, Yu, Ide, Yuki, Pirillo, Jenny, Hijikata, Yuh, Yoneda, Tomoki, Inokuma, Yasuhide
• Format: Article
• Language: English
• Subjects: calixarenes; Calixarenes - chemistry; macrocycles; porphyrinoids; Pyrroles - chemistry; reaction mechanisms; strained molecules
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202200056

The recent discovery of calix[3]pyrrole, a porphyrinogen‐like tripyrrolic macrocycle, has provided an unprecedented strain‐induced ring expansion reaction into calix[6]pyrrole. Here, we synthesized calix[n]furan[3‐n]pyrrole (n=1∼3) macrocycles to investigate the reaction scope and mechanism of the ring expansion. Single crystal X‐ray analysis and theoretical calculations revealed that macrocyclic ring strain increases as the number of inner NH sites increases. While calix[1]furan[2]pyrrole exhibited almost quantitative conversion into calix[2]furan[4]pyrrole within 5 minutes, less‐strained calix[2]furan[1]pyrrole and calix[3]furan were inert. However, N‐methylation of calix[2]furan[1]pyrrole induced a ring‐expansion reaction that enabled the isolation of a linear reaction intermediate. The mechanism analysis revealed that the ring expansion consists of regioselective ring cleavage and subsequent cyclodimerization. This reaction was further utilized for synthesis of calix[6]‐type macrocycles. Growing rings: Calix[n]furan[3‐n]pyrroles (n=0∼3) were synthesized from cyclicoligoketone precursors to investigate strain‐induced macrocyclic ring expansion reactions. As the number of inner NH sites increases, the macrocyclic ring strain increased. Detailed mechanism analysis revealed that calix[6]pyrrole type larger macrocycles were formed through regioselective cleavage and subsequent cyclodimerization of linear intermediates.