5-exo Radical Cyclization onto 3-Alkoxyketimino-1,6-anhydromannopyranoses. Efficient Preparation of Synthetic Intermediates for (−)-Tetrodotoxin

Abstract

Ketoxime ethers at C3 of 1,6-anhydro-beta-D-mannopyranose derivatives were found to be useful 5-exo radical traps of alkyl and vinyl radicals generated at a chain tethered to the C2 hydroxyl group, allowing advanced synthetic intermediates for (-)-tetrodotoxin to be prepared from D-mannose in good overall yield.

Enantioselective Total Synthesis of the Highly Oxygenated 1,10‐seco‐Eudesmanolides Eriolanin and Eriolangin

“…The final stage of the synthesis was initiated with a chemoselective oxidation35 of triol 28 to give hydroxy γ‐lactone 29 (Scheme ). After protection of the secondary hydroxy group, a one‐step α‐methylenation of lactone 30 succeeded with sodium hydride and paraformaldehyde,36 and following desilylation, lactone 31 was isolated in good overall yield. Preparation2 of methacrylate 32 as well as detritylation to give 1 proceeded uneventfully and delivered (−)‐eriolanin, which proved to be identical to the natural product by comparison of optical rotation data 37.…”

The Chemical Synthesis of Tetrodoxin: An Ongoing Quest

“…Access to 214 was secured from 211 , recognized as a deacetylated O -methyl oxime derivative of 200 , by formation of a 2-iodoacetal from the free alcohol, cyclization with Bu 3 SnH/AIBN, protection, and Jones oxidation [56,57]. …”

Regiocontrolled and Stereoselective Syntheses of Tetrahydrophthalazine Derivatives using Radical Cyclizations

“…This radicalc yclization is not only an unprecedenteda pproachfor the syntheses of phthalazine derivatives, but also involvesa nu nderexplored 6-endo cyclization onto aC =Nb ond. Althoughm any synthetic studies have examined radical cyclizations onto C=NÀRc ontaining functionalg roups,s uch as oximes, [10] imines, [11] and hydrazones, [12] most of them have fo-cused on the exo-cyclizations. [13] There are no examples of 6endo cyclizationso ntoo ximes,a nd the only 6-endo hydrazone cyclization was demonstrated by our group in am ethod that featured cyclization of av inyl radicalw ith ah ydrazone to afford at ransient tetrahydropyradazine radical.…”