Asymmetric Hydrogenation of In Situ Generated β,γ-Unsaturated Lactams

We present an efficient asymmetric hydrogenation of in situ generated unsaturated lactams catalyzed by N,P-iridium complexes. This strategy offers great advantages in terms of time, atom economy, and reduction of wastes. Moreover, this methodology would enable a one-pot synthesis of enantioenriched pyrrolidones and isoindolinones, which are common motifs in several natural and biologically active compounds. Mechanistic studies revealed the critical and cooperative roles of the acid, anhydride additive, and solvent in governing both reactivity and enantioselectivity. Hydrogenation of the isolated enamide and deuterium-labeling studies support the involvement of competing pathways and highlight the mechanistic advantages of the tandem protocol.