Total syntheses of gerberinol I and the pterophyllins 2 and 4 using the Casnati-Skattebøl reaction under different conditions

PERGOMET, JORGELINA LEONOR; BRACCA, ANDREA B.J.; KAUFMAN, TEODORO S

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Año: 2017

1477-0520

The concise and efficient total syntheses of the naturally‐occurring coumarin derivatives gerberinol I, and the pterophyllins 2 and 4, from 5‐methyl‐4‐hydroxycoumarin as a common precursor employing different Casnati‐Skattebøl reaction conditions, are reported. The synthesis of the key intermediate coumarin was achieved by the organocatalyticcondensation of acetylacetone and crotonaldehyde followed by a LiCl‐assisted cyclization, CuCl2‐promoted aromatization and a final Et2CO3‐mediated cyclization. A Casnati‐Skattebøl formylation under high‐temperature conditions afforded gerberinol I, whereas milder conditions resulted in an unstable 3‐formyl‐4‐hydroxycoumarin derivative, which was subjected to a basic alumina‐mediated one pot O‐alkylation with chloroacetone and intramolecular aldolization to furnish pterophyllin 4. Wittig methylenation of the latter conveniently afforded pterophyllin 2.