Synthesis of Secondary Amines via Self-Limiting Alkylation of N - Aminopyridinium Salts

Synthesis of Secondary Amines via Self-Limiting Alkylation of N - Aminopyridinium Salts

Partial amine alkylation to prepare secondary amines is challenging due to the enhanced N-nucleophilicity that accompanies alkylation. Here we introduce N -aminopyridinium salts as ammonia surrogates for the synthesis of secondary amines via self-limiting alkylation chemistry. A one-pot protocol based on N -aminopyridinium arylation followed by N -alkylation and in situ depyridylation provides access to aryl alkyl amines. The method is compatible with complex molecular settings and overcomes classical challenges in selective amine alkylation by accomplishing alkylation via transient pyridinium ylide intermediates. These findings both establish N -aminopyridinium salts as ammonia synthons and provide a new disconnection for the construction of structurally complex secondary amines.

由于烷基化过程中氮亲核性增强，部分胺烷基化制备仲胺具有挑战性。在此，我们引入N -氨基吡啶鎓盐作为氨替代物，通过自限性烷基化化学合成仲胺。一种基于N -氨基吡啶鎓芳基化，接着进行N -烷基化和原位脱吡啶基的一锅法方案可用于制备芳基烷基胺。该方法适用于复杂的分子环境，并且通过瞬态吡啶叶立德中间体实现烷基化，克服了选择性胺烷基化的传统难题。这些发现既确立了N -氨基吡啶鎓盐作为氨合成子的地位，又为构建结构复杂的仲胺提供了一种新的切断策略。