Chemoenzymatic and Enantiomeric Switching Regimes Enabling the Synthesis of Homochiral Cyclohexa-2,5-dienones Incorporating All-Carbon Quaternary Centers.

Abstract

The enantiomerically pure, bromobenzene-derived metabolite 5 has been transformed into enone 20 using a reaction sequence involving Suzuki-Miyaura cross-coupling and Eschenmoser-Claisen rearrangement processes. Treatment of compound 20 with lithium hydroxide results in an acetonide fragmentation reaction that delivers the 4,4-disubstituted cyclohexa-2,5-dienone 21, reductive de-oxygenation of which leads to congener 22. A closely related sequence of reactions can be used to convert the same homochiral starting material 5 into compound ent-22.