Copper(II)-catalyzed aminohydroxylation of olefins with N-sulfonyl oxaziridines

The Yoon laboratory is interested in the development of new oxidation reactions that employ oxaziridines as the terminal oxidant. We report herein that copper(II) salts efficiently catalyze the aminohydroxylation of olefins with N-sulfonyl oxaziridines. In this atom economic process, all atoms of the oxaziridine are incorporated into the final product, generating an amino alcohol that is fully protected as a 1,3-oxazolane. A variety of electron rich and electron poor styrenes are excellent substrates for this aminohydroxylation reaction. This new reactivity represents a rare example in which oxygen transfer is not the favored reaction of an N-sulfonyl oxaziridine. In addition, the ability to use cheap, readily available and environmentally benign copper(II) salts to effect this oxyamination reaction makes it a highly attractive alternative the osmium-catalyzed Sharpless aminohydroxylation reaction.;The complete regiocontrol obtained in the reaction of styrenes can be explained by a two step mechanism involving a stabilized radical intermediate. Thus, olefins bearing functional groups capable of stabilizing the build up of spin density are efficient substrates for this reaction, including styrenes, vinyl ethers, allyl silanes, and 1,3-dienes. In the case of the non-symmetrical 1,3-dienes, good to excellent olefin selectivity is obtained, which can be rationalized by consideration of the stability of the electron-deficient allylic radical intermediate. The olefins containing products resulting from mono-aminohydroxylation of 1,3-dienes are excellent substrates for further synthetic manipulations.;We also report development of a rapid and scalable synthesis of highly enantioenriched 1,2-amino alcohols by oxaziridine-mediated aminohydroxylation of styrenes with chiral copper(II) bis(oxazoline) complexes. In our asymmetric variant of the aminohydroxylation reaction, selectivities up to 83% ee have been obtained with a variety of styrenic substrates. Furthermore, acid hydrolysis of the aminal products generates highly crystalline N-sulfonyl amino alcohols that can easily be recrystallized to enantiopurity.