Phosphine-Catalyzed [4+1] Cycloadditions of Allenes with Methyl Ketimines, Enamines, and a Primary Amine

Unprecedented phosphine-catalyzed [4+1] cycloadditions of allenyl imides have been discovered using various N-based substrates including methyl ketimines, enamines, and a primary amine. These transformations provide a one-pot access to cyclopentenoyl enamines and imines, or (chiral) gamma-lactams through two geminal C-C bond or two C-N bond formations, respectively. Several P-based key intermediates including a 1,4-(bis)electrophilic alpha,beta-unsaturated ketenyl phosphonium species have been detected by P-31 NMR and HRMS analyses, which shed light on the postulated catalytic cycle. The synthetic utility of this new chemistry has been demonstrated through a gram-scaling up of the catalytic reaction as well as regioselective hydrogenation and double condensation to form cyclopentanoyl enamines and fused pyrazole building blocks, respectively.