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

An unprecedented Cu-I-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).