Stereoselective synthesis of trifluoro- and monofluoro-analogues of frontalin and evaluation of their biological activity

The stereoselective synthesis of both enantiomers of trifluoro frontalin (- )-(15,5R)- and (+)-(1R,5S)-8, as well as of diastereomeric monofluoro front alines (-)-(1R,2R,5R)-18 and (-)-(1R,2S,5R)-20, analogues of the bioactive component of the aggregation pheromone of the Scolytidae insect family, has been accomplished starting from (-)-(1R)- and (+)-(1S)-menthyl (S)-toluene -4-sulfinate as a source of chirality and methyl trifluoroacetate or fluoro acetate, respectively, as sources of fluorine. The C-1 stereocenters were i nstalled via stereoselective epoxidation of beta -sulfinyl ketones 2 and 13 with diazomethane. The bicyclic core was obtained by totally stereocontrol led and chemoselective tandem Wacker oxidation/intramolecular ketalization of the intermediate unsatured sulfinyl diols 5, 15, and 19. Axially fluorin ated (-)-20 elicited a strong electroantennographic response in laboratory tests on females of Dendroctonus micans, whereas equatorially fluorinated ( -)-18 and the trifluoroanalogue (-)-8 showed modest responses. Field trials using (-)-20 were not indicative owing to the locally scarce population of D. micans, but it showed some attractiveness for other Coleoptera families .