6-endo- and 5-exo-digonal cyclizations of o-hydroxyphenyl ethynyl ketones: A key step for highly selective benzopyranone formation

The cyclization of o-hydroxyphenyl ethynyl ketones was examined from theoretical and experimental standpoints in order to develop efficient synthetic methods for the construction of 2-substituted pyranones possessing significant biological activities. Ab initio studies at HF/6-31G* level on the cyclization indicated that both 6-endo-digonal and 5-exo-digonal cyclizations giving benzopyranones and benzofuranones, respectively, were endothermic and reversible in aprotic media, and the irreversible protonation of the resulting anions would be critical for the products formation. We generated phenoxide ion under aprotic conditions in situ by desilylation of o-silyloxyphenyl ethynyl ketones with spray dried potassium fluoride and 18-crown-6 in anhydrous DMF. Under these conditions the cyclization of variety o-hydroxyphenyl ethynyl ketones proceeded smoothly to produce benzopyranone derivatives with exceedingly high selectivity. Theoretical and experimental results strongly suggested that the presence of a small amount of proton donor effecting the protonation of the resulting benzopyranone anion was essential for the high 6-endo-digonal selectivity. Copyright (C) 1996 Elsevier Science Ltd