Notes on the directed aldol synthesis and reduction of some compounds related to cycloheximide

Abstract

Several N-phenylcycloheximide analogues were prepared by TiCl4-promoted aldol condensation between trimethylsilyl enol ethers of cyclic ketones and (N-phenylglutarimide)-β-acetaldehyde. Favored stereoisomers were isolated in several instances and identified from nuclear magnetic resonance data. Only for the analogue from 4-tert-butylcyclohexanone was it possible to obtain both erythro and threo isomers. Catalytic reduction of the β-hydroxyketone system overPtO2 gave dihydrocycloheximide analogues possessing an axial ring hydroxyl group. Reduction in glacial HOAc was noted as promoting fission of the glutarimide ring with formation of lactone amides and, in several instances, concomitant reduction of the phenyl ring to a cyclohexyl group.