Photooxygenation of 2-(gamma-hydroxyalkyl)furans followed by dehydration affords, in one synthetic operation and in high yield, gamma-spiroketal gamma-lactones. This newly developed technology was successfully applied to the synthesis of three different epimers of pyrenolide D, as well as to the first synthesis of the anticancer natural product crassalactone D and its C4-epimer.

[reaction: see text] A versatile and general method for the biomimetic construction of [5,5,5]- and [6,5,6]-bis-spiroketals, starting from easily accessible furan nuclei, by means of a powerful one-pot singlet oxygen-mediated cascade sequence is reported.

Singlet oxygen (1O2) proves to be a powerful tool in mediating the one-pot synthesis of a salinomycin-type [6,6,5]-bis-spiroketal unit starting from a suitably substituted furan nucleus.

[structure: see text]. An unusual regioselectivity pattern for the ortho lithiation of 3-aryl and 3-styryl furans has been uncovered wherein lithiation occurs preferentially at the sterically encumbered 2-position. The results are attributed, at least in part, to stabilization of the intermediate furyl anion by through-space donation of pi-electron density from the substituent appended at the 3-position to the lithium cation. This ortho lithiation reaction may be applied as a useful synthetic tool for accessing 2,3-disubstituted furans.

2005 Furan derivatives R 0060Regioselective ortho-Lithiation of 3-Aryl and 3-Styryl Furans. -The reaction is studied for a variety of substituted furans. Silylation occurs preferentially at the sterically encumbered 2-position for aryl, benzyl and conjugated derivatives, while the reverse regioselectivity is observed for unconjugated substrates (XIV). Electron-donating groups decrease the selectivity. -(TOFI, M.; GEORGIOU, T.; MONTAGNON, T.; VASSILIKOGIANNAKIS*, G.; Org. Lett. 7 (2005) 15, 3347-3350; Dep. Chem., Univ. Crete, GR-71409 Iraklion, Crete, Greece; Eng.) -R. Steudel 48-115