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

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

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Año: 2017

1477-0520

Theconcise and efficient total syntheses of the naturally-occurring coumarinderivatives gerberinol I, and the pterophyllins 2 and 4, from 5-methyl-4-hydroxycoumarinas a common precursor employing different Casnati-Skattebøl reactionconditions, are reported. The synthesis of the key intermediate coumarin wasachieved by the organocatalytic condensation of acetylacetone andcrotonaldehyde followed by a LiCl-assisted cyclization, CuCl2-promotedaromatization and a final Et2CO3-mediated cyclization. A Casnati-Skattebølformylation under high-temperature conditions afforded gerberinol I, whereasmilder 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 tofurnish pterophyllin 4. Wittig methylenation of the latter conveniently affordedpterophyllin 2.