Interception and Synthetic Application of Diradical and Diene Forms of Dual‐Nature Azabicyclic o‐Quinodimethanes Generated by 6π‐Azaelectrocyclization

• Published in: Angewandte Chemie Vol. 136; no. 41
• Main Authors: Shankar, Majji, Lee, Daniel J., Inaththappulige, Supuni I. N. Hewa, Acharya, Ayush, Yennawar, Hemant P., Giri, Ramesh
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 07.10.2024
• Subjects: 6π-Azaelectrocyclization; [4+2] Cycloaddition; Alkenes; Alkylamines; Amines; Bridged Azabicycles; Chemical synthesis; Cycloaddition; Dimerization; Diradicals; Imines; Interception; o-Quinodimethanes; Organic compounds; Tetrahydroisoquinoline
• DOI: 10.1002/ange.202409613
• ISSN: 0044-8249

We demonstrate that 2‐alkenylarylaldimines and ketimines undergo thermal 6π‐azaelectrocyclization to generate a wide range of azabicyclic o‐quinodimethanes (o‐QDMs). These o‐QDMs exist as a hybrid of a diene and a benzylic diradical. The diradical nature was confirmed by their ability to undergo dimerization and react with H‐atom donor, 2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) and O2. In addition, the interception of the diradicaloid o‐QDMs by H‐atom transfer was used to synthesize five tetrahydroisoquinoline alkaloids and related bioactive molecules. The diene form can undergo [4+2] cycloaddition reactions with different dienophiles to generate bridged azabicycles in high endo:exo selectivity. The azabicyclic o‐QDMs can be generated for [4+2] cycloaddition from a wide range of electronically and sterically varied 2‐alkenylarylimines, including mono, di, tri and tetrasubstituted alkenes, and imines derived from arylamine, alkylamine (1°, 2°, 3°), benzylamine, benzylsulfonamide and Boc‐amine. 2‐Alkenylarylimines have been shown to undergo 6π‐azaelectrocyclization thermally to generate azabicyclic o‐quinodimethanes. These o‐quinodimethanes show dual nature as a cyclic diene and a benzylic diradical. The interception of the diradicaloid o‐quinodimethanes by H‐atom transfer enabled the synthesis of five tetrahydroisoquinoline alkaloids. The cyclic dienes were intercepted by [4+2] cycloaddition to generate bridgehead azabicycles.