Development of novel Ni-catalyzed reductive coupling reactions of aziridines

Identifier:  TDX:4425

Handle: https://hdl.handle.net/20.500.11797/TDX4425

Authors:  Zimin, Dmitry

Abstract:
Beta-functionalized amines are highly valuable chemicals and are widely used in the chemical industry. New methodologies for their synthesis are highly demanded. In the past decade, the area of transition metal-catalyzed cross-coupling transformations using aziridines as a substrate to access beta-functionalized amines has attracted significant attention. Initial methodologies were designed based on pioneering studies of Hillhouse and Wolfe who successfully isolated and characterized potential reaction intermediates – so-called azametallacyclobutanes. Since that moment numerous elegant protocols were published describing cross-coupling transformations of aziridines. In the group of Prof. Ruben Martin we saw the potential to access beta-amino acids and homoallylamines from aziridines upon coupling them with carbon dioxide or simple alkynes. Thus the development of these transformations became a goal of the Doctoral Thesis. To the best of our knowledge such transformations were unknown in the literature. The goal was achieved and Ni-catalyzed reductive carboxylation and hydroalkenylation methodologies have been developed. Before mentioned transformations were optimized through a systematic and rational screening of reaction conditions. Their synthetic applicability was studied on the broad scope of starting materials, demonstrating reaction limitations. In addition, the mechanism of developed transformations was studied and the key part of catalytic cycle was proposed. Based on this proposal, a new Ni-catalyzed electrophile cross-coupling transformation was designed. To conclude, the present Doctoral Thesis contribute significantly to the area of transition metal-catalyzed cross-coupling transformations of aziridine and developed methodologies will find application in the synthesis of beta-functionalized amines, specifically beta-amino acids and homoallylamines.