Study and Development of Synthetic Methodology Towards Pyrrolic Frameworks

Abstract

This thesis focuses on the study and development of synthetic methodology towards pyrrolic frameworks. Three projects are discussed: the development of open-air conditions for the synthesis of F-BODIPYs, mechanistic studies in the synthesis of symmetrical dipyrrins, and the development of new reactions for the synthesis of sulfur-bridged pyrroles. The atmospheric effects of water on the synthesis of F-BODIPYs were explored. A methodology was developed for the high-yielding synthesis of F-BODIPYs involving non-anhydrous reagents and requiring no precautions to exclude moisture. This simple and robust strategy requires the addition of two aliquots of NEt3 and BF3OEt2. The ratio and amounts of NEt3 and BF3OEt2 used in each aliquot are critical to success (6 equivalents of NEt3 and 9 equivalents of BF3OEt2 per each aliquot). Most important is that the protocol can be completed using air-dried bench-top apparatus, without the need to either purchase anhydrous solvents or achieve and maintain anhydrous solvents and conditions. The synthesis of symmetric α-free meso-H-dipyrrin hydrobromides from 5-unsubstituted 2-formylpyrroles (2-formyl-5-H-pyrroles) was investigated and it was found that the self-condensation produces regioisomeric dipyrrins through adoption of two mechanistic pathways. Through a systematic study involving variously substituted and isotopically labelled 2-formyl-5-H-pyrroles, evidence was provided to suggest that not only does there exist two mechanistic pathways, but that the steric bulk of the substituent adjacent to the 5-unsubstituted position influences which pathway dominates. There are few synthetic routes to preparing sulfur-bridged dipyrrolyl sulfides, most of which require use of sulfur dichloride, a restricted chemical unavailable within Canada. Towards the preparation of sulfur-bridged di-, tri-, and tetrapyrroles, the first example of electrophilic aromatic substitution of pyrrole using thionyl chloride to produce dipyrrolyl sulfides was developed. The use of thionyl chloride results in an interesting auto-reduction of the sulfoxide centre to produce a sulfide-bridged dipyrrole. The new synthesis was investigated and a mechanism for the auto-reduction reaction was proposed.