Efficient, Functional Group‐Tolerant, and Catalyst‐Free Nitrile Formation from Aldehydes

The development of efficient methods for nitrile syntheses is a challenge due to the current reliance on toxic cyanide sources, metal catalysts and their associated waste products, and harsh conditions that limit functional group compatibility. Here, we show a metal- and complex reagent-free strategy for the conversion of aldehydes to nitriles through carbamoylaldoxime intermediates. Therefore, we synthesize aldoximes from several aldehydes using hydroxylamine, which in turn are reacted with dimethylcarbamoyl chloride (DMCC) to afford N,N-dimethylcarbamoyloximes. Subsequent heating cleanly produces the desired nitriles as well as volatile CO₂ and HNMe₂ through a pericyclic syn elimination. This approach relies on widely available commercial chemicals, proceeds with broad functional group tolerance, and minimizes the need for extensive purification of the nitrile product.