“…Various approaches have been taken to develop methodologies which circumvent this issue, including the use of masked nitrile transfer reagents, 9,15 biocatalysis 10,11 and continuous flow chemistry. [12][13][14][15] To date, none have been as attractive and robust as the van Leusen reaction, which was first reported in 1977, and is frequently used in the total synthesis of medicinal compounds. [16][17][18][19] The reaction relies on ketones reacting with TosMIC ( p-tosylmethyl isocyanide), 20 a nitrile transfer reagent, which prevents the inadvertent release of cyanide side products via a mechanistic sequence involving ring formation and subsequent ring-opening.…”