Asymmetric Alkynylation/Lactamization Cascade: An Expeditious Entry to Enantiomerically Enriched Isoindolinones

An unprecedented CuI–pybox‐diPh‐catalyzed highly enantioselective (up to >99 % ee) alkynylation/lactamization cascade has been developed as a general catalytic system for the synthesis of diversely substituted isoindolinones of immense biological importance. The cascade effects one CC and two CN bond‐forming events in one reaction vessel under operationally simple, additive‐free reaction conditions in good to excellent yields. The methodology was further extended to the synthesis of tetrahydroisoquinoline scaffolds common to several biologically active natural products in a two‐step sequence with remarkable selectivity (up to 94 % ee). Simple and effective: A highly enantioselective domino alkynylation/lactamization involving the formation of one CC and two CN bonds was developed for the synthesis of diversely substituted isoindolinones (see scheme). The methodology was further extended to the synthesis of tetrahydroisoquinoline scaffolds found in a variety of biologically active natural products by a remarkably selective two‐step procedure (up to 94 % ee).