Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita 13, Nishi 8, Kita-ku, Sapporo, Hokkaido, 060-8628, Japan.
Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo, Hokkaido, 001-0021, Japan.
Chemistry. 2022 Mar 22;28(17):e202200056. doi: 10.1002/chem.202200056. Epub 2022 Feb 25.
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.
最近发现了杯[3]吡咯，一种类似于卟啉原的三吡咯大环，它提供了一种前所未有的应变诱导的环扩张反应，生成杯[6]吡咯。在这里，我们合成了杯[n]呋喃[3-n]吡咯（n=1∼3）大环，以研究环扩张的反应范围和机制。单晶 X 射线分析和理论计算表明，随着内环 NH 位数量的增加，大环环应变增加。虽然杯[1]呋喃[2]吡咯在 5 分钟内几乎定量转化为杯[2]呋喃[4]吡咯，但应变较小的杯[2]呋喃[1]吡咯和杯[3]呋喃则没有反应活性。然而，杯[2]呋喃[1]吡咯的 N-甲基化诱导了环扩张反应，从而能够分离出线性反应中间体。机理分析表明，环扩张由区域选择性的环断裂和随后的环二聚反应组成。该反应进一步用于合成杯[6]型大环。
