Copper bis(oxazolines) as catalysts for stereoselective aziridination of styrenes with N-tosyloxycarbamates

A Cu(I)-catalyzed asymmetric aziridination of styrenes with a chiral N-tosyloxycarbamate has been developed. Double stereodifferentiation was observed and both the N-tosyloxycarbamate substituent and the bis(oxazoline) ligand have a significant effect on the yields and diastereoselectivities. The best results for the aziridination were obtained with electron-deficient styrenes. Subsequent ring-opening reactions of styrene-derived aziridines at the benzylic position were observed with various oxygen and nitrogen nucleophiles under Lewis acid catalysis affording the corresponding products with complete inversion of stereochemistry. The strategy was used to synthesize the β-blocker, (R)-nifenalol.