Catalytic Asymmetric Formal [3+2] Cycloaddition of 2‐Isocyanatomalonate Esters and Unsaturated Imines: Synthesis of Highly Substituted Chiral γ‐Lactams

Unlike their isocyano and isothiocyanato analogues, isocyanato esters remain almost unexplored as formal 1,3‐dipoles in asymmetric catalytic reactions. The first asymmetric formal [3+2] cycloaddition involving isocyanato esters and electrophilic alkenes is reported. Diisopropyl 2‐isocyanatomalonate reacts with α,β‐unsaturated N ‐( o ‐anisidyl) imines in the presence of a Mg(OTf) 2 –BOX complex to give highly substituted chiral pyrrolidinones featuring a conjugate exocyclic double bond with excellent yields and enantiomeric excesses up to 99 %. Several transformations of the resulting heterocycles, including the synthesis of a pyroglutamic acid derivative, have been carried out.