Oxa-[3+3] Annulation of Resorcinols and Its Application in the Total Syntheses of Chromene Natural Products

Author:Wu Zuo

Supervisor:li cha de xiong richard phsungtang yu


Degree Year:2017





The formal oxa-[3+3] cycloaddition reaction has been investigated for several years in our laboratory.This formal cycloaddition involves condensation of α,β-unsaturated iminium salts with 1,3-dicarbonyl equivalents.These reactions consist of a Knoevenagel-type condensation followed by a reversible 6π-electron electrocyclic ring-closure.Based on our previous work,we developed an oxa-[3 + 3] annulation of vinyliminium salts with resorcinols as a 1,3-diketo equivalent,with which we completed the total syntheses of a series of chromene nature products.Our efforts are described as follows:(1)Firstly,We described here our efforts in developing an oxa-[3 + 3] annulation of vinyliminium salts with resorcinols as a 1,3-diketo equivalent.This annulation constitutes a powerful cascade of Knoevenagel condensation–oxa-electrocyclization to directly access chromenes.A series of attempts was made to demonstrate the synthetic utility of this new annulation in natural product syntheses.Ultimate total syntheses of(±)-rhododaurichromanic acid A and(±)-daurichromenic acid were achieved and featured an intramolecular Gassmantype cationic [2 + 2] cycloaddition.(2)Secondly,total syntheses of(±)-rhodonoids A,B,C12-epi-rhodonoid B,E and F are described here.A unified strategy employed in these syntheses is an intermolecular oxa-[3 + 3] annulation for accessing the chromene unit.A Fe(OTf)3 promoted diastereoselective cationic [2 + 2] cycloaddition and a photochemical [2 + 2] cycloaddition were featured to construct the cyclobutane core of(±)-rhodonoids A and B,C12-epi-rhodonoid B,E and F respectively.Fe(OTf)3 also leads to an interesting bridged tetracycle,which was unambiguously confirmed by single crystal X-ray analysis.(3)Finally,we describe the divergent,biosynthetically inspired syntheses of(±)-rhodonoids C,D,G and(±)-ranhuadujuanine B.The key steps of the syntheses include the chromene unit construction through a formal oxa-[3 + 3] annulation and a biomimetic acid-catalyzed ring cyclization.