Interrupted intramolecular [3 + 2] to 5-endo-dig cyclization: [3 + 2] cycloaddition of nitrile ylides of diazo esters: photo-induced solvent-free gem-diamination to synthesize α-amino-α-substituted α-amino esters†

Abstract

In this work, we transition the blue LED-induced intramolecular [3 + 2] cycloaddition of nitrile ylides, generated from singlet carbenes of diazo esters, towards an intermolecular [3 + 2] cycloaddition with substituted isocyanates. This photolytic reaction efficiently yields α-amino-α-aryl α-amino esters through gem-diamination of readily available diazo esters, using diverse organonitriles and isocyanates as amine sources. The resulting α,α-disubstituted α-amino acids (α-AAs) are known to exhibit enhanced properties compared to conventional amino acids. These reactions, employing nitriles as stoichiometric reagents, are easily scalable to multigram quantities. Control experiments, coupled with density functional theory calculations, provide detailed insight into the reaction mechanism.