Chiral Calixpyrrole Derivatives: Synthesis, Racemization Kinetics, and Ring Expansion to Calix‐ and Calixpyrrole Analogues

Chiral pyrrolic macrocycles continue to attract interest. However, their molecular design remains challenging. Here, we report a calixpyrrole‐based chiral macrocyclic system, calix[1]furan[1]pyrrole[1]thiophene (1), synthesized from an oligoketone. Macrocycle 1 adopts a partial cone conformation in...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2023-04, Vol.62 (15)
Main Authors: Inaba, Yuya, Yang, Jian, Yu Kakibayashi, Yoneda, Tomoki, Ide, Yuki, Hijikata, Yuh, Pirillo, Jenny, Saha, Ranajit, Sessler, Jonathan L, Inokuma, Yasuhide
Format: Article
Language:English
Subjects:
Ammonium
Ammonium salts
Conformation
Enantiomers
Inversion
Methylation
Molecular dynamics
Racemization
Stereoselectivity
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Summary:Chiral pyrrolic macrocycles continue to attract interest. However, their molecular design remains challenging. Here, we report a calixpyrrole‐based chiral macrocyclic system, calix[1]furan[1]pyrrole[1]thiophene (1), synthesized from an oligoketone. Macrocycle 1 adopts a partial cone conformation in the solid state, and undergoes racemization via ring inversion. Molecular dynamics simulations revealed that inversion of the thiophene is the rate determining step. Pyrrole N‐methylation suppressed racemization and permitted chiral resolution. Enantioselective N‐methylation also occurred in the presence of a chiral ammonium salt, although the stereoselectivity is modest. A unique feature of 1 is that it acts as a useful synthetic precursor to yield several calix[n]furan[n]pyrrole[n]thiophene products (n=2–4), including a calix[12]pyrrole analogue that to our knowledge constitutes the largest calix[n]pyrrole‐like species to be structurally characterized.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202301460