Parallel solution-phase syntheses of functionalised bicyclo[2.2.2]octanes: generation of a library using orchestrated multi-step sequences of polymer-supported reagents and sequesterants

Abstract

An array of bicyclo[2.2.2]octane derivatives was prepared in high yield using an orchestrated multi-step sequence of polymer-supported reagents and sequestering agents, without any chromatographic purification steps. Nine intermediate libraries were synthesised, with the final library possessing five sites of diversity. Key steps included an efficient tandem Michael addition reaction of acrylates with cyclohexenones and a subsequent reductive amination reaction.