Total Synthesis of (−)-Ascochlorin via a Cyclobutenone-Based Benzannulation Strategy

Abstract

The application of a convergent benzannulation strategy in an efficient synthesis of (-)-ascochlorin is described.

Intramolecular Diels–Alder Reactions of Cycloalkenones: Translation of High Endo Selectivity to Trans Junctions

“…The method of synthesis of such precursor substrates centered on reaction of a lithium derivative of the type 9 (R=H or Me) with the known 4-chloro-3-ethoxycyclobutenone 10 . 14 Following 1,2-addition and unraveling mediated by trifluoroacetic acid (TFAA) or trace BF 3 •OEt 2 , there was obtained the pre-IMDA substrate 12 , which could be reductively dechlorinated by the action of zinc in acetic acid, tertiary amine, and alcoholic solvent. 15 Two probe substrates 13 and 14 , prepared by this method, were to be studied in detail as to their performance in IMDA reactions (vide infra).…”

5.16 Cyclobutene Ring Opening Reactions

“…The synthesis of the sesquiterpene phenol (À)-ascochlorin was based on the [4 þ 2] annulation strategy (Scheme 120). 145 A solution of the cyclobutenone 312 and the alkoxyacetylene 313 was initially irradiated, and then briefly heated to complete conversion to the desired aromatic product. Intermolecular annulation of the cyclobutenone 314 with siloxyacetylene 315 afforded phenol 316, which was then desilylated and methylated (Scheme 121).…”

The Application of Cyclobutane Derivatives in Organic Synthesis

“…Thus, irradiation of the cyclobutenone 489 in toluene at room temperature triggered four-electron electrocyclic ring opening to give vinylketene 490, which combined with acetylene 491 in a regioselective [2+2]-cycloaddition to form 492. Further irradiation at refluxing temperature then induced a second four-electron electrocyclic ring opening reaction to generate dienylketene 493, which underwent a rapid 6π electrocyclization and tautomerization to afford the desired pentasubstituted benzene 494 219 .…”