Selective syntheses of aminocarbonyls by developing intermolecular nitrenoid transfer systems

Abstract

Nitrogen-containing molecules have experienced a major surge of interest as key structural scaffolds given the prevalence of these compounds in biorelevant compounds, marketed drugs and preclinical candidates. In this context, a growing emphasis has been placed on the selective introduction of amino functionalities of carbonyl compounds, since they provide an efficient platform to access value-added aminocarbonyl compounds. This dissertation describes the intermolecular α-amidation of 1,3-dicarbonyls by surpassing a variety of competing reactive sites. On the basis of frontier molecular orbital analysis, we are able to customized the iridium catalysis by modulating the electrophilic reactivity of putative iridium nitrenoid intermediate which displayed exquisite chemoselectivity as well as high catalytic efficiency. Also, we developed a highly efficient Rh-catalyzed ring-opening amidation of substituted cyclopropanols, which turned out to be serve as a unique three-carbon linchpin for the selective synthesis of β2-amino carbonyls, α-substituted β-amino scaffolds to outcompete the formation of β3-isomers. The observed high regioselectivity to discriminate two competitive C–C bonds are thoroughly rationalized by a series of computational techniques.