Catalyst-Transfer Macrocyclization Protocol: Synthesis of π-Conjugated Azaparacyclophanes Made Easy.

Abstract

The present Protocol describes the application of the catalyst-transfer macrocyclization (CTM) reaction, focusing on the synthesis of aza[1_n]paracyclophanes (APCs). APCs are fully π-conjugated shape-persistent macrocycles with potential supramolecular chemistry and materials science applications. This method leverages the Pd-catalyzed Buchwald-Hartwig cross-coupling reaction to selectively form π-conjugated cyclic structures, a significant advancement due to its efficiency, versatility, and scalability. Overall, this Article highlights the following attributes of the CTM method: a) Efficiency and Yield: The CTM method works at mild temperatures (40 °C) and short reaction times (≥2 h), producing high yields of APCs (>75% macrocycles). It avoids the typical high-dilution conditions, making it more practical for large-scale applications. b) Versatility: The method allows the synthesis of APCs with diverse endocyclic and exocyclic functionalities and ring sizes (typically from 4- to 9-membered rings), expanding the chemical space for these compounds. This flexibility is crucial for tailoring APC properties for specific applications. c) Scalability and Reproducibility: Unlike many macrocyclization reactions, which require highly dilute conditions, CTM can perform under concentrated regimes (35-350 mM), making it more suitable for large-scale applications. d) Applications in Materials Science: APCs are noted for their potential in optoelectronic applications due to their π-conjugated structures, which are helpful in organic semiconductors, light-harvesting systems, and other advanced materials. This approach addresses the challenge of complicated multistep syntheses that have hindered the widespread integration of APCs into functional devices. A step-by-step guide to preparing exemplary APCs, including troubleshooting, is provided with photographic illustrations.