Exploiting continuous processing for challenging diazo transfer and telescoped copper-catalyzed asymmetric transformations
Crowley, Daniel C.
Brouder, Thomas A.
Kearney, Aoife M.
Collins, Stuart G.
Maguire, Anita R.
American Chemical Society
Generation and use of triflyl azide in flow enables efficient synthesis of a range of α-diazocarbonyl compounds, including α-diazoketones, α-diazoamides, and an α-diazosulfonyl ester, via both Regitz-type diazo transfer and deacylative/debenzoylative diazo-transfer processes with excellent yields and offers versatility in the solvent employed, in addition to addressing the hazards associated with handling of this highly reactive sulfonyl azide. Telescoping the generation of triflyl azide and diazo-transfer process with highly enantioselective copper-mediated intramolecular aromatic addition and C–H insertion processes demonstrates that the reaction stream containing the α-diazocarbonyl compound can be obtained in sufficient purity to pass directly over the immobilized copper bis(oxazoline) catalyst without detrimentally impacting the catalyst enantioselectivity.
Triflyl azide , Regitz-type diazo transfer , Deacylative/debenzoylative diazo transfer , α-diazocarbonyl compounds , α-diazoketones , α-diazoamides , α-diazosulfonyl ester
Crowley, D. C., Brouder, T. A., Kearney, A. M., Lynch, D., Ford, A., Collins, S. G. and Maguire, A. R. (2021) 'Exploiting continuous processing for challenging diazo transfer and telescoped copper-catalyzed asymmetric transformations', Journal of Organic Chemistry. doi: 10.1021/acs.joc.1c01310