TOTAL SYNTHESIS OF (+ -)-9-DEOXYGONIOPYPYRONE - APPLICATION OF THE IODOCYCLOFUNCTIONALIZATION REACTION OF ALPHA-ALLENIC ALCOHOL DERIVATIVES/

The synthesis of (+/-)-9-deoxygoniopypyrone (1) from the alpha-allenic alcohol 5 is described. Iodocyclofunctionalization of the N-tosyl car bamate derivative of 5 using I-2 and Ag2CO3 provided, in a highly dias tereoselective and regioselective fashion, the vinyl iodo syn-vicinal diol 4. Two routes were explored in order to introduce the third stere ogenic centre in the molecule. Reductive deiodination of the vinyl iod ide and diastereoselective epoxidation of the derived acetonide 14 usi ng mCPBA provided a mixture of epoxides 15 and 16 (2:1) in which the d esired three diastereomer predominated. Alternatively, dihydroxylation of acetonide 14 (OsO4, NMO) yielded a mixture of diols 21 and 22 (2:3 ) which were separated after monosilylation (TBDMSCl) of the primary a lcohol, The major silyl ether erythro diastereomer 24 was converted to the desired epoxide 15 by mesylation (MsCl, Et3N) and epoxide formati on (TBAF) with inversion of stereochemistry, The minor three diastereo mer 23 was also converted to the desired epoxide 15 (TBAF; ArSO2Cl; Na OMe). Epoxide opening was effected with lithium acetylide and the resu lting alkyne 27 was carbonylated (MeLi, ClCO2Me) to afford the alpha,b eta-acetylenic ester 28. Semi hydrogenation over Lindlar's catalyst fo llowed by protecting-group removal under acidic conditions provided (/-)-8-epigoniodiol 30. Finally, conversion of 30 to (+/-)-9-deoxygonio pypyrone 1 was effected under basic conditions (DBU).