Development of directed carbonylative ring expansions of aminocyclopropanes

• Main Author: Shaw, Megan H.
• Published: University of Bristol 2015
• Subjects: 547
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.683460

A novel catalysis platform has been developed that provides facile access to complex N-heterocyclic scaffolds via the generation and trapping of amino-substituted rhodacyclopentanones. A directing group-based strategy was employed that enabled regioselective generation of the desired rhodacyclopentanone intermediates from readily accessible substituted amino cyclopropane precursors. Incorporation of this strategy into a multicomponent protocol resulted in the development of (3+1 +2) cycloadditions between aminocyclopropanes, CO and tethered alkynes to deliver N-heterobicyclic enones. Studies exploring the reactivity of different Rh(I)-catalyst systems enabled expansion of the scope to highly diastereoselective (3+ 1 +2) carbonylative cycloadditions involving tethered alkenes. In this system, a novel strategy for achieving diastereocontrol was developed that relies upon reversible C-C bond activation and allows the synthesis of 'Sp3 -rich' chiral scaffolds. Integration of the n-unsaturated component with the directing group provided a new synthetic approach to azocane ring systems from acryloyl-substituted aminocyclopropanes. Studies towards the total synthesis of phantasmidine have been conducted and a synthetic route to the substrate required for the key catalysis step was established. In relation, the carbonylative ring expansion methodology was examined with the aim of developing an enantioselective route to aminocyclobutanones, however, at present, these studies have been unsuccessful.