Notable and obvious ketene substituent-dependent effect of temperature on the stereoselectivity in the Staudinger reaction.

A notable and obvious ketene substituent-dependent effect of temperature on the stereoselectivity in the Staudinger reaction was observed. Most Staudinger reactions show concave Eyring plots characterized by two lines with an inversion point, following the principle of isoinversion. Their cis-selectivities decrease with increasing temperature. Reactions involving intramolecular p-pi and pi-pi interactions between the ketene substituents and imine C-substituents reveal protruding, S-shaped or straight-line Eyring plots. Their cis-selectivities increase with increasing temperature in a certain temperature region because such interactions enhance the cis-selectivity. Staudinger reactions involving cyclic imines with different ketenes clearly indicate that the temperature-dependent stereoselectivity is caused by the different rate increases of the direct ring closure, which are affected by the p-pi and pi-pi interactions between ketene substituents and imine C-substituents if they exist, and the isomerization of the zwitterionic intermediates generated from ketenes and imines during the change in the reaction temperature, not by the competition of the imine exo and endo attacks to the ketenes. Our results also indicate that nonlinear Eyring plots do not always reveal a change of the stereoselectivity-determining step. Thus, one should use them carefully to determine any changes in the stereoselectivity-determining step during the change in the reaction temperature.