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Catalytic atroposelective dynamic kinetic resolutions and kinetic resolutions towards 3-arylquinolines via S_NAr.

ABSTRACT: Herein we report the catalytic atroposelective syntheses of pharmaceutically relevant 3-arylquinolines via the nucleophilic aromatic substitution (S_NAr) of thiophenols into 3-aryl-2-fluoroquinolines mediated by catalytic amounts of Cinchona alkaloid-derived ureas. These reactions displayed a spectrum of dynamic kinetic resolution (DKR) and kinetic resolution (KR) characters depending upon the stereochemical stability of the starting material. Low barrier substrates proceeded via DKR while higher barrier substrates proceeded via KR. On the other hand, substrates with intermediate stabilities displayed hallmarks of both DKR and KR. Finally, we also show that we can functionalize the atropisomerically enriched quinolines into pharmaceutically privileged scaffolds with minimal observed racemization.

SUBMITTER: Cardenas MM

PROVIDER: S-EPMC9799074 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Catalytic atroposelective dynamic kinetic resolutions and kinetic resolutions towards 3-arylquinolines via SNAr.

Cardenas Mariel M MM Saputra Mirza A MA Gordon Deane A DA Sanchez Andrea N AN Yamamoto Nobuyuki N Gustafson Jeffrey L JL

Chemical communications (Cambridge, England) 20210930 78

Herein we report the catalytic atroposelective syntheses of pharmaceutically relevant 3-arylquinolines via the nucleophilic aromatic substitution (SNAr) of thiophenols into 3-aryl-2-fluoroquinolines mediated by catalytic amounts of Cinchona alkaloid-derived ureas. These reactions displayed a spectrum of dynamic kinetic resolution (DKR) and kinetic resolution (KR) characters depending upon the stereochemical stability of the starting material. Low barrier substrates proceeded <i ...[more]

PMID: 34515276

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