Enantioselective Radical Dearomative Conjugate Amination Enabled by Co(II)-Based Metalloradical Catalysis

基于Co(II)金属自由基催化的对映选择性自由基脱芳构化共轭胺化反应

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Abstract

Delocalized radical systems present a challenging yet appealing ground to test the control of multiple selectivity in organic synthesis. Despite some recent advancements, the issue of regioselectivity in delocalized radical system has largely centered on allylic radicals. To explore larger delocalized radical systems, we report the catalytic generation of extensively delocalized 4-vinylphenoxyl radicals and their involvement as key intermediates in regioselective radical C-N bond formation. Guided by the mechanistic principles of metalloradical catalysis, we develop a Co(II)-based enantioselective radical system for dearomative 1,7-conjugate amination of readily available 4-vinylphenols with aryl azides. This can afford valuable chiral α-tertiary amino acid derivatives in high yields with excellent enantioselectivities for the newly-created tetrasubstituted stereocenters. Unlike prior systems, this amination involves hydrogen-atom abstraction from O-H bonds. As demonstrated with 1,6-conjugate addition with various nucleophiles, the resulting α-tertiary amino acid derivatives, which bear additional para-quinone methide (p-QM) functionality, may find useful synthetic applications.

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