Novel applications of convertible isonitriles for the synthesis of mono and bicyclic γ-lactams via a UDC strategy

Abstract

This communication reveals a novel application of the so-called convertible isonitriles for the solution/solid phase generation of γ-lactam analogues. Use of tethered N-BOC aldehydes in the Ugi multi-component reaction (MCR), followed by BOC removal and base treatment (a ‘3-step, 1-pot procedure’) affords γ-lactams in good yield. The UDC (Ugi/De-BOC/Cyclize) strategy, coupled with a convertible isonitrile, is now feasible from all three substitution sites of the Ugi product. A conceptually novel approach, combining a bi-functional precursor with a post-condensation modification to give fused lactam-ketopiperazines, is also revealed.