Convenient approach to an advanced intermediate toward the naturally occurring, bioactive 6-substituted 5-hydroxy-4-aryl-1H-quinolin-2-ones

SEBASTIÁN O. SIMONETTI; TEODORO S. KAUFMAN; ENRIQUE L. LARGHI

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2016 vol. 14 p. 2625 - 2636

1477-0520

The 5-hydroxy-4-aryl-3,4-dihydro-1H-quinolin-2-ones are a small family of natural products, isolated from fungal strains of Penicillium and Aspergillus. Most of its members, which are insecticides and antihelmintics, carry an isoprenoid C-6 side chain. The synthesis of a 6-propenyl-substituted advanced intermediate for the total synthesis of these natural products is disclosed. This was achieved through the stereoselective construction of a β,β-diarylacrylate derivative from 6-nitro salicylaldehyde, using a Wittig olefination and a Heck-Matsuda arylation, followed by a selective Fe0-mediated reductive cyclization. Installation of the 6-propenyl side chain was performed by 5-O-allylation of the heterocycle, followed by Claisen rearrangement and conjugative migration of the allyl double bond, as key steps. The Grubbs II-catalyzed olefin cross metathesis of the 6-allyl moiety with 2-methylbut-2-ene to afford a precursor of peniprequinolone, is also reported.