Stereocontrolled syntheses of the nemorensic acids using 6-diazoheptane-2,5-dione in carbonyl ylide cycloadditions.
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.
Hodgson
David M
DM
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, United Kingdom. david.hodgson@chem.ox.ac.uk
Le Strat
Frédéric
F
Avery
Thomas D
TD
Donohue
Andrew C
AC
Brückl
Tobias
T
D001391:Azo Compounds / Q000737:chemistry*; D003500:Cyclization; D005663:Furans / Q000138:chemical synthesis*; D006536:Heptanes / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008968:Molecular Conformation; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis*; D013237:Stereoisomerism
D001391:Azo Compounds; D005663:Furans; D006536:Heptanes; D007659:Ketones; D011763:Pyrrolizidine Alkaloids; C458241:nemorensic acid