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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Easy access to a cyclic key intermediate for the synthesis of trisporic acids and related compounds
José A González-Delgado1, Gustavo Escobar1, Jesús F Arteaga2
1Department of Organic Chemistry and Institute of Biotechnology, University of Granada, Avda Fuentenueva s/n, 18071 Granada, Spain.
Abstract:
The synthesis of a cyclohexane skeleton possessing different oxygenated functional groups at C-3, C-8 and C-9, and a D1,6-double bond has been accomplished in 10 steps with an overall 17% yield. This compound is a key intermediate for access to a wide range of compounds of the bioactive trisporoid family. The synthetic sequence consists of the preparation of a properly functionalized epoxygeraniol derivative, and its subsequent stereoselective cyclization mediated by Ti(III). This last step implies a domino process that starts with a homolytic epoxide opening followed by a radical cyclization and regioselective elimination. This concerted process gives access to the cyclohexane moiety with stereochemical control of five of its six carbon atoms.
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