The transformation and utilization of amides are significant in organic synthesis and drug discovery. Here we demonstrate a divergent alkynylative difunctionalization of amides in a single transformation. In this reaction, amides react with an organometallic nucleophile to form a tetrahedral intermediate. By altering the N-substitution or the acyl group, the tetrahedral intermediate species selectively undergoes C–O or C–N cleavage with a concomitant capture by an alkynyl nucleophile generated in situ. This process enables the selective introduction of two different functional groups into the amide molecular architecture, producing valuable propargyl amine and propargyl alcohol products. The selectivity between deoxygenation and deamination process has been further elucidated by DFT calculations. Overall, this reaction successfully transforms the traditional mode of nucleophilic acyl addition to amides to a divergent C–O/C–N cleavage. The particularly wide substrate scope, including late-stage modification of bioactive molecules, demonstrates its potential broad applications in organic synthesis.

酰胺的转化和利用在有机合成和药物发现中具有重要意义。在这里，我们展示了酰胺在一次转化中的发散炔基化二官能化。在该反应中，酰胺与有机金属亲核试剂反应形成四面体中间体。通过改变 N-取代或酰基，四面体中间体选择性地经历 C-O 或 C-N 切割，同时被原位产生的炔基亲核试剂捕获。该工艺能够将两种不同的官能团选择性地引入酰胺分子结构中，从而产生有价值的炔丙胺和炔丙醇产品。DFT 计算进一步阐明了脱氧和脱氨过程之间的选择性。总体而言，该反应成功地将亲核酰基加成酰胺的传统模式转变为不同的 C-O/C-N 切割。特别广泛的底物范围，包括生物活性分子的后期修饰，证明了它在有机合成中的潜在广泛应用。