Stereoselective synthesis of octahydrocyclohepta[c]pyran-6(1H)-one scaffolds through a Prins/alkynylation/hydration sequence.

Aldehydes undergo a smooth coupling with (E/Z)-non-3-en-8-yn-1-ol in the presence of 10 mol% of CuX and BF3·OEt2 under mild conditions to produce a novel class of octahydrocyclohepta[c]pyran-6(1H)-one derivatives in good yields with excellent diastereoselectivity through a sequential Prins/alkynylation/hydration. This is the first report on the termination of Prins cyclization with a tethered alkyne.

Thia-prins bicyclization approach for the stereoselective synthesis of dithia- and azathia-bicycles.

A novel thia-Prins bicyclization approach has been developed for the first time for the synthesis of hexahydro-2H-thieno[3,2-c]thiopyran derivatives from the coupling of homoallylic mercaptans such as hex-3-ene-1,6-dithiol with various aldehydes using 10 mol % InBr3 in dichloromethane with high selectivity. In addition, the coupling of (E)-N-(6-mercaptohex-3-enyl)-4-methylbenzenesulfonamide with aldedydes affords the corresponding N-tosyloctahydrothiopyrano[4,3-b]pyrrole derivatives in good yields. This reaction is a stereoselective affording trans-fused product from E-homoallyllic mercaptan and cis-fused product from Z-homoallyllic mercaptan.

Total Synthesis of the Proposed Structure of Maltepolide C.

The first total synthesis of the proposed structure of cytotoxic macrolide maltepolide C has been achieved via an E-selective intramolecular Heck cyclization as a key step. Other key features of the synthesis are Z-selective Wittig olefination, Sharpless asymmetric dihydroxylation followed by Williamson-type cyclo-etherification, Brown asymmetric allylation, and Noyori reduction of an alkynone. Detailed NMR study confirms the structure and stereochemistry of the synthetic maltepolide C unambiguously. However, the deviation of the spectra of the synthetic maltepolide C from those of the natural maltepolide C indicates a possible error in the original structural assignment.