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

Date

2017

Authors

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

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Abstract

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.

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Subject

cycloaddition
nitrogen-containing molecules
zinc
hydrogen atom transfer
C-H functionalization
radical

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