Asymmetric Synthesis of Nidulalin A and Nidulaxanthone A: Selective Carbonyl Desaturation Using an Oxoammonium Salt

Abstract

To expedite the synthesis of nidulalin A and study the proposed dimerization, we developed methodology involving the use of allyl triflate for chromone ester activation, followed by vinylogous addition, to rapidly forge the nidulalin A scaffold in a four-step sequence which also features ketone desaturation using Bobbitt's oxoammonium salt. An asymmetric synthesis of nidulalin A was achieved using acylative kinetic resolution (AKR) of chiral, racemic 2H-nidulalin A. Dimerization of enantioenriched nidulalin A to nidulaxanthone A was achieved using solvent-free, thermolytic conditions. Computational studies have been conducted to probe both the oxoammonium-mediated desaturation and (4 + 2) dimerization events.

Triple-Dearomative Photocycloaddition: A Strategy to Construct Caged Molecular Frameworks

“…Nidulalin A 1 and nidulaxanthone A 2 (Figure ) belong to the dihydroxanthone natural product family. We have recently reported total syntheses of 1 and 2 involving use of allyl triflate for chromone ester activation followed by vinylogous addition to access the nidulalin A scaffold in a four-step sequence, which also employs ketone desaturation using Bobbitt’s oxoammonium salt . An initial approach to target monomer 1 involved use of chromone ester 3 as a substrate for Diels–Alder cycloaddition with furan to produce the intended cycloadduct 4 (Figure ) followed by base-mediated carbon–oxygen bond cleavage to dienone 5 and subsequent demethylation.…”