A Preparative Route Investigation of N-Heterocyclic Phosphine Catalysts and their Application Towards the Synthesis of Colchinoid Analogues

Abstract

A growing field in chemistry is the reduction of small molecules employing main group element catalysts. A recent advance has been the use of N-heterocyclic phosphines (NHPs) in the reduction of imines to produce secondary amines. NHPs can also perform conjugate reductions of electron poor alkenes.1 (-)-Colchicine is a natural product of biological interest due to its antimitotic properties. Current synthetic methods require expensive and toxic transition metal catalysts to generate colchinoids.2 The second chapter explores an alternative route towards the total synthesis of (-)-colchicine analogues by utilizing NHPs instead of traditional metal catalysis. A chemoselective conjugate reduction mediated by NHPs allows the expedient assembly of a precursor to a cyclization reaction. The next chapter provides a unique synthetic route towards the synthesis of previously inaccessible NHP moieties and preliminary exploration of their reactivity that aims to simplify current synthetic techniques by proposing an efficient one-pot synthesis.