Selective synthesis of 5,6-disubstituted 3-methyl-2(2H)-pyranones and 6-substituted 3-methyl-2(2H)-pyranones, including fusalanipyrone and gibepyrone A

The 6-substituted 3-bromo-5-iodo-2(2H)-pyranones I [R = (Z)-MeC:CHMe, Bu, Ph], prepd. by iodolactonization of the corresponding 5-substituted (E)-2-bromo-2-en-4-ynoic acids (Z)-R1C≡CCH:CBrCO2H, were used as precursors to 5,6-disubstituted 3-methyl-2(2H)-pyranones II (R1 = Bu, R2 = 4-MeOC6H4; R1 = Ph, R2 = BuC≡C) (III) and 6-substituted 3-methyl-2(2H)-pyranones II [R1 = (Z)-, (E)-MeC:CHMe, Bu, R2 = H] (IV). The synthesis of compds. III involved two consecutive Stille-type reactions, whereas the approach followed to prep. compds. IV consisted of the selective redn. of the dihalogen derivs. I to the corresponding 6-substituted 3-bromo-2(2H)-pyranones, followed by a Pd/Cu-catalyzed reaction with tetramethyltin. However, this synthetic approach to compds. IV proved to be unsuitable for prepg. stereoisomerically pure fusalanipyrone II [R1 = (Z)-MeC:CHMe, R2 = H] (V), a natural product isolated from Fusarium solani. Nevertheless, V and gibepyrone A II [R1 = (E)-MeC:CHMe, R2 = H], which is a natural product isolated from Gibberella fujikuroi, could be synthesized in stereoisomerically pure form by reaction sequences involving iodolactonization of easily available (2Z,6Z)- and (2Z,6E)-2,6-dimethyl-2,6-octadien-4-ynoic acids, resp., followed by Pd-catalyzed triethylammonium formate redn. of the thus obtained 6-substituted 5-iodo-3-methyl-2(2H)-pyranones II [R1 = (Z)-MeC:CHMe, R2 = iodo; R1 = (E)-MeC:CHMe, R2 = iodo], resp.