Diversity‐Oriented Synthesis of [2.2]Paracyclophane‐derived Fused Imidazo[1,2‐a]heterocycles by Groebke‐Blackburn‐Bienaymé Reaction: Accessing Cyclophanyl Imidazole Ligands Library

• Published in: Chemistry : a European journal Vol. 28; no. 3; pp. e202103511 - n/a
• Main Authors: Stahlberger, Mareen, Schwarz, Noah, Zippel, Christoph, Hohmann, Jens, Nieger, Martin, Hassan, Zahid, Bräse, Stefan
• Format: Journal Article
• Language: English
• Published: Germany John Wiley and Sons Inc 13.01.2022
• Subjects: [2.2]Paracyclophane; Cyanides; Cyclization; Fused-imidazoles; Groebke-Blackburn-Bienaymé (GBB) reaction; Imidazoles; Isocyanide Chemistry; Ligands; Multicomponent reactions; Groebke-Blackburn-Bienaymé (GBB) reaction; Isocyanide Chemistry; Multicomponent reactions; [2.2]Paracyclophane; Fused-imidazoles
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202103511

This report describes the synthesis of a [2.2]paracyclophane‐derived annulated 3‐amino‐imidazole ligand library through a Groebke‐Blackburn‐Bienaymé three‐component reaction (GBB‐3CR) approach employing formyl‐cyclophanes in combination with diverse aliphatic and aromatic isocyanides and heteroaromatic amidines. The GBB‐3CR process gives access to skeletally‐diverse cyclophanyl imidazole ligands, namely 3‐amino‐imidazo[1,2‐a]pyridines and imidazo[1,2‐a]pyrazines. Additionally, a one‐pot protocol for the GBB‐3CR by an in situ generation of cyclophanyl isocyanide is demonstrated. The products were analyzed by detailed spectroscopic techniques, and the cyclophanyl imidazo[1,2‐a]pyridine was confirmed unambiguously by single‐crystal X‐Ray crystallography. The cyclophanyl imidazole ligands can be readily transformed to showcase their useful utility in preparing N,C‐palladacycles through regioselective ortho‐palladation. Diversified Groebke‐Blackburn‐Bienaymé Approach: Diversity‐oriented synthesis of cyclophanyl‐derived fused imidazo[1,2‐a]heterocycles by one‐pot Groebke‐Blackburn‐Bienaymé (GBB) three‐component reaction employing formyl‐cyclophane components in combination with various aliphatic and aromatic isocyanides and different heteroaromatic amidines is described. Additionally, a one‐pot protocol for the GBB 3CR process by an in‐situ generation of cyclophanyl isocyanide is demonstrated. The cyclophanyl imidazole ligands can be readily transformed to showcase their useful utility in preparing N,C palladacycles via regioselective ortho‐palladation.