Total synthesis of (±)-9-deoxygoniopypyrone. Application of the iodocyclofunctionalization reaction of bold α-allenic alcohol derivatives

Abstract

The synthesis of ( ±)-9-deoxygoniopypyrone (1) from the α-allenic alcohol 5 is described. Iodocyclofunctionaliztion of the N-tosyl carbamate derivative of 5 using I2and Ag2CO3provided, in a highly diastereoselective and regioselective fashion, the vinyl iodo syn-vicinal diol 4. Two routes were explored in order to introduce the third stereogenic centre in the molecule. Reductive deiodination of the vinyl iodide and diastereoselective epoxidation of the derived acetonide14 using mCPBA provided a mixture of epoxides 15 and 16 (2:1) in which the desired threo 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 alcohol. The major silyl ether erythro diastereomer 24 was converted to the desired epoxide 15 by mesylation (MsCl, Et3N) and epoxide formation (TBAF) with inversion of stereochemistry. The minor threo diastereomer 23 was also converted to the desired epoxide 15 (TBAF; ArSO2Cl; NaOMe). Epoxide opening was effected with lithium acetylide and the resulting alkyne 27 was carbonylated (MeLi, ClCO2Me) to afford the α , β-acetylenic ester 28. Semi hydrogenation over Lindlar's catalyst followed by protecting- group removal under acidic conditions provided ( ±)-8-epigoniodiol 30. Finally, conversion of 30 to ( ±)-9-deoxygoniopypyrone 1 was effected under basic conditions (DBU).Key words: ( ±)-9-deoxygoniopypyrone, α-allenic alcohol, iodocyclofunctionalization, syn-diol.