Nitrogenation of amides to nitriles via C–C and C–N bond cleavage

Amides are ubiquitous in organic chemistry. Compared to others carbonyl functional groups, the transformation of amide is relatively difficult and remains challenge due to the n(N) to π^*(C=O) conjugation leading to these planar bonds containing double-bond characters. In recent years, relaying on transition-metal catalyzed amide activation strategy attracted the interest of chemists. However, this deconstruction transformations of amides to other functional products are usually limited to twisted or electronic activation amides. Herein, we reported a general amide activation process enabled the inert C–C and C–N Bond cleavage resulting in the corresponding nitrile formation in good yields (up to 89% yield). Meanwhile, utilizing simple and readily available NaNO₂ as the nitrogen source, the shifts from inorganic salt to organic compounds was completed by this novel protocol. The compatibility of this methodology was demonstrated in late-stage modification of drugs and natural product derivatives.
Our approach provides a new sight in amide directly transformation through the deconstruction route. The great functional group tolerance makes this approach be of potential in complex compounds modification. The primary mechanism research proposed a unique conversion of NaNO₂ and amide which would indicate the different reactivity in organic synthesis. In conclusion, we anticipate that the present chemistry offers the novel insight and applicable pattern in amide transformation.