Total syntheses of gerberinol I and the pterophyllins 2 and 4 using the Casnati-Skattebøl reaction under different conditionsElectronic supplementary information (ESI) available: NMR spectra of the intermediates and final products and spectral data tables of the natural and synthetic pterophyllins 2 and 4. See DOI: 10.1039/c7ob01471f

• Main Authors: Pergomet, Jorgelina L, Bracca, Andrea B. J, Kaufman, Teodoro S
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c7ob01471f

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 organocatalytic condensation of acetylacetone and crotonaldehyde followed by a LiCl-assisted cyclization, CuCl 2 -promoted aromatization and a final Et 2 CO 3 -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 . The total syntheses of the title compounds were achieved from a single coumarin precursor, taking advantage of the temperature-dependent divergent outcomes of the Casnati-Skattebøl reaction.