Attempts Toward An Improved Synthesis of Aza-Dipyrrins

Abstract

Compounds built on the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (F-BODIPY) framework have a wide range of uses stemming from their highly tunable electronic properties. The versatility of this class of compound affords them applications as probes in biological systems ad as dyes. Aza-dipyrrins and respective boron compounds (aza-BODIPYs) are direct analogues of BODIPYs in which a carbon meso-atom is replaced with nitrogen. This change leads to a large red-shift in their absorption spectra making these compounds effective for applications such as biological imaging and photodynamic therapy (PDT). This thesis aims to develop new methodologies for the effective, eco-friendly and cost-effective synthesis of F-BODIPYs and aza-BODIPYs. Attempts to avert the challenges faced by the current synthesis of F-BODIPYs are described. These involve using only 1 equiv. of BF3•Et2O in a continuous flow operation. The design of alternative synthetic routes toward aza-dipyrrins is described, where the generation of unstable intermediates that render traditional methods inflexible are avoided. Details of preliminary experimentation to validate these methods are included, as are considerations for future development. Further attempts towards the synthesis of aza-dipyrrins are described. One new route takes advantage of the reductive power of tetravalent phosphorus reagents in C−N coupling. It also describes a new route towards the nitrosylation of pyrroles that is fast, effective and avoids the use of acidic conditions and can thus be potentially applied to less stable pyrroles.