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Chemistry
Defense: Noah Watkins- Catalytic selective aminofunctionalzation of 1, 3 dienes & aryl cyclopropanes enabled by copper catalysis
Thursday, July 10,
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Transition metal catalysis has emerged as an invaluable tool for the development of novel reaction systems. Transition metal catalyzed amination strategies are of the utmost importance due to the ubiquity of nitrogen in bioactive compounds of interest, ligands, and catalysts. Given the high degree of molecular complexity within the sought-after nitrogen-containing compounds, reactions that are able to install multiple functionalities in fewer steps are more useful. To this end, difunctionalization reactions have been researched using transition metal catalysis. The majority of the works already reported on transition metal catalyzed aminofunctionalization rely on alkenes as substrates. However, alkenes are generally limited to accessing 1,2-addition products.
Contrary to simple alkenes, 1,3-dienes offer access to a wide variety of isomeric products to deliver a range of aminated motifs based on regio-, site-, and geometric selectivity. Despite this, the subject of 1,3-diene 1,4-aminofunctionalizaiton remains underdeveloped and demands further study.
Based on this gap in the field, a copper-catalyzed 1,4-aminohydroxylation reaction has been developed using O-benzoylhydroxylamines as an electrophilic source of aliphatic amines. The transformation delivers exclusively 1,4-aminohydroxylated products by means of a carbonyl-assisted migration pathway, as confirmed by various mechanistic experiments. The reaction system is amenable to a wide variety of carbonyl-containing 1,3-diene substrates and has been successfully expanded to deliver exclusive 1,4-aminothiolated products from thioamide-containing 1,3-dienes.
Cyclopropanes represent another class of difunctionalization substrate that remains underdeveloped. The difunctionalization of cyclopropanes by ring-opening reactions serves as an access point to 1,3-functionalized motifs, a substitution pattern inaccessible by alkene or diene functionalization. Utilizing the unique reactivity of cyclopropanes for ring-opening difunctionalization, an enantioselective copper-catalyzed 1,3-aminoalkynylation of non-activated aryl cyclopropanes has been established.
Contrary to simple alkenes, 1,3-dienes offer access to a wide variety of isomeric products to deliver a range of aminated motifs based on regio-, site-, and geometric selectivity. Despite this, the subject of 1,3-diene 1,4-aminofunctionalizaiton remains underdeveloped and demands further study.
Based on this gap in the field, a copper-catalyzed 1,4-aminohydroxylation reaction has been developed using O-benzoylhydroxylamines as an electrophilic source of aliphatic amines. The transformation delivers exclusively 1,4-aminohydroxylated products by means of a carbonyl-assisted migration pathway, as confirmed by various mechanistic experiments. The reaction system is amenable to a wide variety of carbonyl-containing 1,3-diene substrates and has been successfully expanded to deliver exclusive 1,4-aminothiolated products from thioamide-containing 1,3-dienes.
Cyclopropanes represent another class of difunctionalization substrate that remains underdeveloped. The difunctionalization of cyclopropanes by ring-opening reactions serves as an access point to 1,3-functionalized motifs, a substitution pattern inaccessible by alkene or diene functionalization. Utilizing the unique reactivity of cyclopropanes for ring-opening difunctionalization, an enantioselective copper-catalyzed 1,3-aminoalkynylation of non-activated aryl cyclopropanes has been established.
