ADVANCES IN THE DIRECTED ORTHO METALATION, SUZUKI-MIYAURA CROSS COUPLING, AND RING-OPENING REACTIONS OF INDAZOLES. SYNTHESIS OF LUMINESCENT ACRIDINE AND NOVEL INDAZOLE-BASED OXAZABORINES
Organic Synthesis , Metalation Chemistry , Cross-Coupling Chemistry , Borylation Chemistry , Heterocyclic Chemistry
The Directed ortho Metalation (DoM) reaction is a ubiquitous tool in the synthesis of polyfunctionalized aromatic and heteroaromatic molecules. Its regioselective nature endowed by the virtue of directed metalation groups (DMGs) coupled with its compatibility alongside many other well-established reactions, has led DoM into the modern age of synthetic organic chemistry. Chapter one of this thesis begins with a brief review of traditional approaches for the carbon and nitrogen functionalization of indazoles and the reactivity challenges faced therein. This is followed by a comprehensive review of current C-7 substitution strategies and their limitations. It then describes our developments in the regioselective C-7 functionalization of N-1 carbamoylated indazoles using DoM. A variety of electrophiles were well-tolerated, where the metalation / cross-coupling ‘fusion’ is illustrated using DoM-derived halides. We then coupled these methods with the traditionally undesirable ring-opening of 1H-indazoles towards the synthesis of 6-substituted N-(2-cyanophenyl)ureas, molecules difficult to access by conventional means. Chapter two begins with a brief introduction on the broad applications of indazoles in materials science, followed by a detailed analysis of the key electronic / structural properties of luminescent indazoles. The discussion then shifts to a short review of historical approaches and modern developments in the preparation of N,O-ligand chelated boron(III) complexes - oxazaborines. We then highlight the challenges we faced in synthesis of luminescent indazole-based azaborines, which we circumvented using a key structural modification. Our advances in the synthesis of highly luminescent acridine and novel indazole-based boron(III) complexes are detailed herein. To the best of our knowledge, these are the first oxazaborines of indazole reported in the scope of the current literature.