Mechanistic Aspects of the Ketene-Imine Cycloaddition Reactions

The [2+2]-cycloaddition reaction of imines with ketenes, also known as Staudinger reaction, is one of the most commonly employed synthetic entries to the β-lactam ring. Despite this, the detailed mechanism of this reaction has remained an open debate for many years. However, the application of theoretical methods has allowed a deeper understanding of many intricacies surrounding the Staudinger reaction. The experimental evidence and the theoretical studies carried out on the Staudinger reaction mechanism, using ab initio and Density-functional theory methods, are reviewed. Special emphasis is placed on the competition between the concerted and stepwise reaction pathways and the origin of the stereoselectivity of the reaction.