A Nickel-Catalyzed [2+2+1]-Cycloaddition Approach to Lactams

Significance

Reported is the synthesis of lactams 4/5 via the nickel-catalyzed [2+2+1] cyclo­addition of alkynes 1, isocyanates 2, and acrylates 3. Both alkyl and aryl alkynes are tolerated in the reaction. Unsymmetrical alkynes lead to a ­mixture of regioisomers, with the best selectivity obtained with sterically hindered substrates (R^² = i-Pr). ­Terminal alkynes failed to participate in the reaction. Aryl isocyanates bearing EDGs and EWGs performed equally well, although alkyl isocyanates were universally poor. More sterically demanding acrylates (R⁴ = Et, t-Bu) gave better regioselectivities, albeit with a decrease in yields. A mechanism is proposed without evidence.