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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Tandem Suzuki Coupling/Intramolecular Oxetane Ring Opening to Form Polycyclic Ring Systems
Lindsey G DeRatt1, Edward C Lawson1, Kiran Kumar1
1Discovery Chemistry, Janssen Pharmaceutical Research and Development, 1400 McKean Road, Spring House, Pennsylvania 19477, United States.
Abstract:
A tandem one-pot reaction featuring a cross-coupling followed by an intramolecular oxetane ring opening by mild nucleophiles is reported. The overall transformation comprises a carbon-carbon bond formation along with a carbon-heteroatom bond construction providing diverse multicyclic ring systems with a pendant hydroxymethyl handle for further elaboration. This approach constitutes a convergent method for rapid access to various scaffolds. Furthermore, a comparison of computed low-energy conformers is presented to rationalize instances in which cyclization was not observed.
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Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.