Synthesis and Utilization of Nitroalkyne Equivalents in Batch and Continuous Flow

Angewandte Chemie 56(45),13999-14002, DOI: 10.1002/anie.201706157

We report a method for overcoming the low stability of nitroalkynes through the development of nitrated vinylsilyltriflate equivalents. Because of their instability, nitroalkynes have only rarely been utilized in synthesis. The reactivity of these silyltriflates, which are prepared in situ, is exemplified by dipolar cycloaddition reactions with nitrones to give highly substituted 4-nitro-4-isoxazolines in high yields. This approach has proven general for several different alkyl and aryl substituted alkynes. In order to minimize the accumulation of potentially hazardous reaction intermediates, we have also developed a continuous flow variant of this method that iscapable of carrying out the entire reaction sequence in a good yield and a short residence time.