Previous experimental work identified 2-iodoanisole as the best precatalyst for the oxidative cyclization of N-alkenylamides into 2-oxazolines. Herein, we describe our investigation into the effect on reaction rate based on the structure of the iodoarene precatalyst. We also reveal the mechanism of the cyclisation based on DFT modelling and obtain a clear correlation between observed reaction rates and computationally derived activation energies for different iodoarenes. In addition, the rate-limiting step is shown to be the cyclization of the substrate which is zero order in the concentration of the iodoarene precatalyst. The rate of the cyclization is found to correlate with the ease of oxidation of the iodoarene, however the most easily oxidized iodoarenes generate iodine(III) species that decompose readily. Finally, loss of iodoarene from the cyclized intermediate can proceed by either ligand-coupling or SN2 displacement (reductive elimination), and this is shown to be substrate dependent.

f Enantiomeric excess = (I{[(R)-isomer] -[(S)-isomerl}I/{[(R)-isomerl + "59isomer]}) x 100.

367ChemInform Abstract (31 refs.).

Review: (144 refs.