Strained carbocycles as gateways to polycyclic molecular scaffolds and natural products targets

Abstract

Cyclopropanes and cyclobutanes, when activated with donor and acceptor groups, provide facile access to a plethora of interesting chemical scaffolds. Importantly, D-A cyclopropanes and cyclobutanes undergo efficient reactivity under mild Lewis acid conditions. This reactivity can be carried out in a modular fashion allowing for broad substrate scope enabling access to wider chemical space. In this thesis, D-A cyclopropanes and cyclobutanes were systematically used as chemical precursors to a variety of natural product-like scaffolds. Firstly, novel interrupted formal homo-Nazarov cyclizations were investigated and provided concise entry into α-arylated cyclohexenols, α-allylated cyclohexenols, and hexahydrobenzofurans. In a different pursuit, formal [5+2] cycloadditions, presumably occurring via D-A cyclobutane intermediates, afforded efficient, high-yielding and diastereoselective access to azepino[1,2-a]indoles and cyclohepta[b]indoles, two important backbones in the indole alkaloid family of natural products (Figure 6.1). Finally, homo-Nazarov-inspired cyclizations of strategically-chosen D-A cyclopropanes were successfully employed in the synthesis of hydropyrido[1,2-a]indoles (under continuous flow conditions) as well the dihydrodibenzo[b,d]furan core (featured in natural product propolisbenzofuran B).