The copper(I)-mediated reaction of nitrones with terminal acetylenes, known as the Kinugasa reaction, represents an attractive method of direct formation of the β-lactam ring. The reaction can be performed in many ways. Diastereoselective versions, including cyclic chiral nitrones or chiral acetylenes and open-chain nitrones, are the most attractive. An alternative method yielding β-lactams with high stereoselectivity, in which nitrones are used, is their 1,3-dipolar cycloaddition to unsaturated lactones. After N- O bond cleavage, cycloadducts can be easily transformed into β-lactams via an intramolecular acylation of the nitrogen atom. Both methodologies are demonstrated in the synthesis of carbapenems (Thienamycin and 4AA azetidinone), monobactams (Carumonam) and Ezetimibe, a powerful cholesterol absorption inhibitor.
Application of nitrones in the stereoselective synthesis of important β-lactam compounds
