A Stereoselective, Multicomponent Catalytic Carbonylative Approach to a New Class of α,β-Unsaturated γ-Lactam Derivatives
Raffaella Mancuso, Ida Ziccarelli, Matteo Brindisi, Cosimo Altomare, Luca Frattaruolo, Aurelia Falcicchio, Nicola Della Ca’, Anna Rita Cappello, Bartolo Gabriele
Abstract
We report a stereoselective, multicomponent catalytic carbonylative approach to a new class of α,β-unsaturated γ-lactam derivatives with potential biological activity, that are, alkyl (Z)-2-(2-oxopyrrolidin-3-ylidene)acetates. Our method is based on the catalytic assembly of readily available building blocks, namely, homopropargylic amines, carbon monoxide, an alcohol, and oxygen (from air). These simple substrates are efficiently activated in ordered sequence under the action of a very simple catalytic system, consisting of PdI2 in conjunction with KI to give the γ-lactam products in 47–85% yields. Carbonylation reactions are carried out at 100 °C for 2–5 h under 40 atm of a 4:1 mixture of CO‒air, with 0.5–5 mol% of PdI2 and 5–50 mol% of KI.