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

Abstract

The 6-substituted 3-bromo-5-iodo-2(2H)-pyranones 11, prepared by iodolactonization of the corresponding 5-substituted (E)-2-bromo-2-en-4-ynoic acids 10, were used as precursors to 5,6-disubstituted 3-methyl-2(2H)-pyranones 8 and 6-substituted 3-methyl-2(2H)-pyranones 7. The synthesis of compounds 8 involved two consecutive Stille-type reactions, whereas the approach followed to prepare compounds 7 consisted of the selective reduction of the dihalogen derivatives 11 to the corresponding 6-substituted 3-bromo-2(2H)-pyranones 12, followed by a Pd/Cu-catalysed reaction with tetramethyltin. However, this synthetic approach to compounds 7 proved to be unsuitable for preparing stereoisomerically pure fusalanipyrone (7a), a natural product isolated from Fusarium solani. Nevertheless, 7a and gibepyrone A (7b), 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 (16a) and (16b), respectively, followed by Pd-catalysed triethylammonium formate reduction of the thus obtained 6-substituted 5-iodo-3-methyl-2(2H)-pyranones 17a and 17b, respectively. © Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.