A concise asymmetric synthesis has been developed to prepare idasanutlin, a 
small molecule MDM2 antagonist. Idasanutlin is currently being investigated as a 
potential treatment for various solid tumors and hematologic malignancies. The 
highly congested pyrrolidine core, containing four contiguous stereocenters, was 
constructed via a Cu(I)/(R)-BINAP catalyzed [3+2]-cycloaddition reaction. This 
optimized copper(<small>I</small>)-catalyzed process has been used to produce 
more than 1500 kg of idasanutlin. The manufacturing process will be described, 
highlighting the exceptionally selective and consistent 
cycloaddition/isomerization/hydrolysis sequence. The excellent yields, short 
cycle times and reduction in waste streams result in a sustainable production 
process with low environmental impact.