First total synthesis of the only known 2-isopropyliden-2H-benzofuran-3-

PERGOMET, J. L.; BRACCA, A. B. J.; KAUFMAN, T. S.; LARGHI, E. L.

RSC Advances

ROYAL SOC CHEMISTRY

Lugar: Londres; Año: 2017 vol. 7 p. 5242 - 5250

2046-2069

The first total synthesis of 5-(1-hydroxy-1-ethyl)-2-isopropyliden-2H-benzofuran-3-one, is reported in itsracemic and in one of its optically active [(S)-(¡V)] forms. This heterocycle, isolated from Verbesinaluetzelburgii, is the only known 2-isopropyliden-2H-benzofuran-3-one produced by species of Verbesina.The sequence took place in eight steps and 19% overall yield (up to 33% for the chiral form), from 4¡¦-10 hydroxyacetophenone. It entailed carbonyl group protection as the 1,3-dioxolane and a phenol orthoformylation, followed by a Williamson etherification with chloroacetone and an organocatalytic crossaldolization,to afford a 2-acetyl-2,3-dihydrobenzofuran-3-ol intermediate. The latter underwent a methylGrignard addition to the carbonyl moiety, followed by selective oxidation of the benzylic alcohol anddeptotection, resulting in a ?Ò-hydroxy diketone derivative. A MsCl-assisted dehydration of the tertiary15 alcohol, established the isopropylidene motif, whereas the syntheses culminated by chemical orenzymatic (carrot, celeriac) selective reductions of the exocyclic carbonyl group.