The Scaffold-assisted Diastereoselective Synthesis of small αα Calix[4]pyrrole Building Blocks via Strapped Calix[4]pyrroles & A Robust Analytical Tool for the Notoriously Difficult Separation of "Two Wall" sp3 Calix[4]pyrrole Diastereomers

The new methodology for the diastereoselective synthesis of αα "two-wall" calix[4]pyrroles with aliphatic walls ("αα sp 3 C[4]Ps") offers a unique access to these elusive building blocks. Their conventional synthesis by acid-condensation of dipyrromethanes with acetone lacks stereocontrol and the formed αα and αβ diastereomers are commonly inseparable by chromatography. In this study, a robust chromatography method for "two-wall" sp 3 C[4]Ps was developed for the analysis of C[4]P diastereomeric mixtures. To circumvent the difficult, labour and material intensive diastereoseparations entirely, we developed a modular "scaffold-assisted" synthesis that utilises a catechol-based dicarboxylic acid tether "Henkel" and different dipyrromethanes for the convergent preparation of strapped C[4]Ps on the g-scale. Cleavage of the strap produces the desired αα C[4]P building blocks diastereoselectively. This approach offers a platform for the diastereoselective synthesis of various αα C[4]Ps due to the simplicity, inexpensiveness and scalability to the multi 100 g scale of the "Henkel" synthesis. Both, αα C[4]Ps with aromatic and aliphatic "walls" are easily obtained by the method in good to excellent yields. The obtained αα C[4]Ps are versatile building blocks for C[4]P-based supramolecular architectures and smart materials. Their structures are discussed based on XRD analysis. The small αα sp 3 C[4]P offers flexible walls and a synthetic handle close to the C[4]P core, while the αα sp 2 C[4]P features electron-poor aromatic walls. To aid future investigations, diverse post-modification methods for the C[4]Ps and their precursor dipyrromethanes were developed.