Stereoselective Radical Cascade Cyclizations via Co(II)-Based Metalloradical Catalysis

Abstract

This dissertation will present three projects focusing on the development of stereoselective radical cascade reactions via metalloradical catalysis (MRC) using Co(II) D2-symmetric chiral amidoporphyrins [Co(D2-Por*)] as the catalyst. The first project demonstrated the feasibility of applying MRC for asymmetric radical cascade processes by achieving an enantioselective radical bicyclization of 1,6-enynes with diazo compounds, which constructed multi-substituted cyclopropane-fused tetrahydrofurans bearing three contiguous stereogenic centers and one trisubstituted alkene. Detailed mechanistic studies including EPR studies and DFT calculation unveiled a radical-based stepwise mechanism. The synthetic utility of this reaction was demonstrated by a series of diastereoselective transformations of the bicyclic products. In the second project, this strategy was expanded to the application of Co(II)-based MRC to catalyze radical cascade reactions involving hydrogen-atom abstraction (HAA) process. A broad array of homopropargyl ethers reacted with diazo compounds to generate enantiomerically enriched ɑ,β-disubstituted tetrahydrofurans in good yields with high diastereoselectivities and enantioselectivities. The third project explored the utilization of the established strategy to accomplish more challenging bicyclization of 1,6,8-dienynes for the construction of cycloheptadiene-fused tetrahydrofurans in regio- and diastereoselective fashions. Such 5,7-fused ring system has been widely found in natural products and bioactive species.