Repository logo

Synthesis of nitrogen-containing molecules by zinc-catalyzed [4+2] cycloaddition and photoredox-catalyzed C-H functionalization




Chu, John Chun Kit, author
Rovis, Tomislav, advisor
Kennan, Alan, committee member
Prieto, Amy, committee member
Kanatous, Shane, committee member

Journal Title

Journal ISSN

Volume Title


This work first describes an enantioselective Zn-catalyzed [4+2] cycloaddition of 1-azadienes and nitro-alkenes for the synthesis of medicinally valuable piperidines. The detrimental coordination of 1-azadienes to the Zn catalysts undermines the stereochemical control of the reaction. Fortunately, a novel bisoxazoline ligand limits this undesired coordination and delivers high stereoselectivity. Mechanistic studies suggest the reaction proceeds via a stepwise mechanism in which aza-Michael addition is followed by cyclization. This proposed mechanism also explains the successful cycloaddition between two electron-deficient reaction partners. Secondly, amide-directed carbon-carbon bond formation at unactivated sp3 C-H bonds has been achieved using photoredox catalysis. The reaction features a hydrogen atom abstraction from the C-H bond to a nitrogen radical generated from the amidyl N-H bond, leading to formation of a carbon-centered radical. Trapping of the resulting alkyl radical with an electrophilic alkene gives the desired C-C bond formation. Experimental evidence supports the generation of the nitrogen radical through a stepwise deprotonation/oxidation event in a closed catalytic cycle. The potential to incorporate other functionalities in the C-H bonds, as well as g functionalization of carbonyl compounds, is disclosed.


Rights Access


nitrogen-containing molecules
hydrogen atom transfer
C-H functionalization


Associated Publications