Abstract

Our daily lives depend heavily on industrial chemicals; however, this process often results in a greater level of pollution and toxic contamination. It is of extreme importance to chemists to reduce these damaging substances and develop more environmentally friendly processes. In order to address these challenges, we applied concepts of green chemistry to our research on heteroaromatic synthesis using catalysis and flow chemistry. Multi-arylated and arylated pyrroles are important structural motifs for a number of industries, including medicinal chemistry and organic semiconductors. Asymmetric, multi-arylated pyrroles are typically prepared by either cyclization or cross-coupling reactions catalyzed by transition metals. This latter approach has the advantage of facilitating access to compound libraries by allowing for late-stage functionalization. It is, however, quite common for these traditional cross-couplings to involve a stoichiometric amount of organometallic reagent, resulting in heavy organometallic waste, while the reaction time and sensitivity to air or moisture can make these processes impractical. We have developed cross-coupling methodologies to enable regioselective arylation of pyrroles through the use of carboxylic acid and ester functional groups. Aside from being greener than most other existing methodologies, this approach is also remarkably easily accessible. First, to increase the appeal of our protocols for industrial applications, they need to be adapted to new synthetic and greener technologies. Continuous-flow is a powerful technique that is carried out using microtubes and small benchtop reactors. There are advantages to it over other methods commonly used for organic synthesis. In this research project, we employed flow chemistry technique to improve the decarboxylative cross-coupling methodology developed by our group. Second, an expanded route utilizing Buchwald coupling, saponification, decarboxylative cross-coupling and C-H arylation was developed in order to access 1,2,5-triarylated pyrroles. Lastly, a double decarboxylative cross-coupling was employed towards the synthesis of bispyrrole pyridine oligomers achieving high yields. Future work will include the functionalization of the pyrrole moiety to extend the oligomer to 5 units.