Lewis Acid Mediated N-aryl Nitrone Synthesis from Benzyl Alcohols

Abstract

A novel approach to access N-Aryl nitrones via copper catalyzed coupling of benzyl alcohols with nitrosobenzenes is described. The results of mechanistic studies are conflicting but suggest this reaction proceeds through either redox process or a nucleophilic nitroso hydrate intermediate formed in situ, which was previously unprecedented. The unique electronics of this process allow access to nitrones with excellent step and atom economy, which are otherwise difficult to make using conventional methods. In this work, a total of 22 nitrones have been made. 15 of which from pure starting materials with yields ranging from 26 - 89 % and another 7 from two step, one pot reactions where the nitrosobenzenes were made in situ from commercially available anilines and reacted in a subsequent step to produce the nitrone in 8 - 46 % yield. In addition to the nitrone forming reaction occurring in the second step of a two-step sequence, we have also shown that subsequent reactions can be done on newly formed nitrones in one pot. This was demonstrated with a newly synthesized nitrone and a donor-acceptor cyclopropane in a [3+3] annulation reaction forming the cycloadduct in 90% yield.