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Enantioselective Phase-Transfer-Catalyzed Synthesis of Spirocyclic Azetidine Oxindoles.

ABSTRACT: Spiro-3,2'-azetidine oxindoles combine two independently important pharmacophores in an understudied spirocyclic motif that is attractive for medicinal chemistry. Here, the enantioselective synthesis of these structures is achieved in up to 2:98 er through intramolecular C-C bond formation, involving activation of the substrate with a novel SF₅-containing chiral cation phase-transfer (PT) catalyst. The products are readily elaborated/deprotected to afford medicinally relevant enantioenriched compounds. Control experiments suggest an interfacial PT mechanism, whereby catalytic asymmetric induction is achieved through the activation of the chloride leaving group.

SUBMITTER: Boddy AJ

PROVIDER: S-EPMC10949229 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Enantioselective Phase-Transfer-Catalyzed Synthesis of Spirocyclic Azetidine Oxindoles.

Boddy Alexander J AJ Sahay Aditya K AK Rivers Emma L EL White Andrew J P AJP Spivey Alan C AC Bull James A JA

Organic letters 20240306 10

Spiro-3,2'-azetidine oxindoles combine two independently important pharmacophores in an understudied spirocyclic motif that is attractive for medicinal chemistry. Here, the enantioselective synthesis of these structures is achieved in up to 2:98 er through intramolecular C-C bond formation, involving activation of the substrate with a novel SF<sub>5</sub>-containing chiral cation phase-transfer (PT) catalyst. The products are readily elaborated/deprotected to afford medicinally relevant enantioe ...[more]

PMID: 38447584

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