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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Stereocontrolled syntheses of the nemorensic acids using 6-diazoheptane-2,5-dione in carbonyl ylide cycloadditions
David M Hodgson1, Frédéric Le Strat, Thomas D Avery
1Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, United Kingdom. david.hodgson@chem.ox.ac.uk
Abstract:
Levulinic acid-derived 6-diazoheptane-2,5-dione (9) serves as a common precursor in a formal synthesis of frontalin 19, and in syntheses of cis-nemorensic acid 1, 4-hydroxy-cis-nemorensic acid 2, 3-hydroxy-cis-nemorensic acid 3, and nemorensic acid 4. The key step in these syntheses is the Rh(2)(OAc)(4)-catalyzed tandem carbonyl ylide formation-intermolecular 1,3-dipolar cycloadditions of diazodione 9 with formaldehyde, alkynes or allene, which occur with high regioselectivity. Subsequent oxidative cleavage of the ring originally derived from the cyclic carbonyl ylide intermediate provides a straightforward access to polysubstituted tetrahydrofurans, and in particular an efficient entry to the nemorensic acids. Enantioselective cycloadditions with diazodione 9, using chiral rhodium catalysts, gave cycloadducts in up to 51% ee.
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