Chiral Calix[3]pyrrole Derivatives: Synthesis, Racemization Kinetics, and Ring Expansion to Calix[9]- and Calix[12]pyrrole Analogues

Yuya Inaba; Jian Yang; Yu Kakibayashi; Tomoki Yoneda; Yuki Ide; Yuh Hijikata; Jenny Pirillo; Ranajit Saha; Jonathan L Sessler; Yasuhide Inokuma

doi:10.1002/anie.202301460

Chiral Calix[3]pyrrole Derivatives: Synthesis, Racemization Kinetics, and Ring Expansion to Calix[9]- and Calix[12]pyrrole Analogues

Angew Chem Int Ed Engl. 2023 Apr 3;62(15):e202301460. doi: 10.1002/anie.202301460. Epub 2023 Feb 28.

Authors

Affiliations

¹ Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita 13, Nishi 8, Kita-ku, Sapporo, Hokkaido, 060-8628, Japan.
² Department of Chemistry, The University of Texas at Austin, 105 East 24th Street, Stop A5300, Austin, TX 78712-1224, USA.
³ Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo, Hokkaido, 001-0021, Japan.

PMID: 36785520
DOI: 10.1002/anie.202301460

Abstract

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.

Keywords: Calixarenes; Chirality; Macrocycles; Racemization Kinetics; Ring Expansion.