Copper-Catalyzed 1,2-Aminocarbonation of Unactivated Alkenes Utilizing O-Benzoylhydroxylamines

Abstract

Alkene difunctionalization is a powerful synthetic method that introduces two distinct functional groups simultaneously, which can transform simple alkenes feedstock into richly functionalized valuable skeletons. With the well-known importance of nitrogen containing molecules in organic synthesis, pharmaceuticals, and materials, great efforts have been devoted to developing alkene amination functionalization strategies, including diamination, aminooxygenation and aminohalogenation. Despite extensive progress in this area, the aminocarbonation of alkenes remains underdeveloped. Moreover, the ubiquity of carbon–carbon and carbon–nitrogen bonds in nature makes it highly desirable to develop efficient methods for concurrent formation of these two valuable bonds. In this dissertation, novel copper-catalyzed 1,2-aminocarbonation strategies have been established using O-benzoylhydroxylamines as an electron-rich amine radical precursor and oxidant. (1) First, 1,2-aminoheteroarylation via heteroaryl group migration was developed, which can furnish diverse heteroarylethylamine core. Distinctive from previous migratory strategies requiring a hydroxyl moiety as a starting material, this method is widely effective on alcohol-, amide-, and even ether-containing alkenes. This reaction was also proved to be a viable strategy for the synthesis of cyclic ketone systems. (2) Furthermore, the development of Minisci-type 1,2-aminoheteroarylation is in progress based on the discovery that a carbon-centered radical intermediate generated by addition of O-benzoylhydroxylamine to alkenes can couple with an electron-deficient aromatic moiety to easily synthesize azaheteroarene-fused cyclic skeleton. (3) Finally, a copper-catalyzed aminocyanation of alkenes was achieved through distal cyano migration using O-benzoylhydroxylamines and N-fluorobenzenesulfonimides as a rapid approach to generate diverse β-amino and β-sulfonimido nitriles, demonstrating the wide utility of this amine-initiated migration strategy as a general aminocarbonation synthetic tool.