Progress in cycloaddition and α-functionalization reactions of isocyano esters

Isocyano esters bearing an acidic α-hydrogen are versatile building blocks in organic synthesis. They act as formal 1,3-dipoles in cycloadditions and as amino acid equivalents through functionalization of stabilized carbanions generated under mild deprotonation conditions. Recent advances have focused on catalytic enantioselective variants of these reactions. This account summarizes our group's contributions over the last decade, particularly in the development of enantioselective transformations of isocyano esters leading to products bearing tetrasubstituted stereogenic centers. Cooperative catalytic systems based on bifunctional squaramides and silver salts enabled efficient access to highly substituted oxazolines, spirocycles, fused heterocycles, and imidazolinones with excellent stereocontrol. Enantioselective Michael additions and electrophilic arylations of isocyanoacetates provided efficient access to α,α-disubstituted amino acid derivatives bearing quaternary stereocenters. Finally, newly designed vinylogous isocyano esters act as 1,3-dipoles in formal cycloadditions, enabling access to δ-amino acid derivatives.