First total synthesis of the only known 2- isopropyliden-2H-benzofuran-3-one isolated from V. luetzelburgii

摘要

The first total synthesis of 5-(1-hydroxy-1-ethyl)-2-isopropyliden-2H-benzofuran-3-one, is reported in its\udracemic and in one of its optically active [(S)-( )] forms. This heterocycle, isolated from Verbesina\udluetzelburgii, is the only known 2-isopropyliden-2H-benzofuran-3-one produced by species of\udVerbesina. The sequence took place in eight steps and 19% overall yield (up to 33% for the chiral form),\udfrom 40-hydroxyacetophenone. It entailed carbonyl group protection as the 1,3-dioxolane and a phenol\udortho formylation, followed by a Williamson etherification with chloroacetone and an organocatalytic\udcross-aldolization, to afford a 2-acetyl-2,3-dihydrobenzofuran-3-ol intermediate. The latter underwent\uda methyl Grignard addition to the carbonyl moiety, followed by selective oxidation of the benzylic\udalcohol and deprotection, resulting in a b-hydroxy diketone derivative. A MsCl-assisted dehydration of\udthe tertiary alcohol, established the isopropylidene motif, whereas the syntheses culminated by chemical\udor enzymatic (carrot, celeriac) selective reductions of the exocyclic carbonyl group.