One-Pot C–H Arylation/Lactamization Cascade Reaction of Free Benzylamines

An efficient method has been developed for the synthesis of seven-membered biaryl lactams involving Pd-catalyzed, native amine-directed, ortho-arylation of benzylamines followed by in situ lactamization. This cascade sequence is enabled by the use of 2-iodobenzoates, which facilitates C–H arylation from the free amine under conditions that typically require an improved directing group approach. This reaction is characterized by a broad substrate scope with good functional group tolerance. The need for an ester versus carboxylic acid-functionalized coupling partner is also explored, as is the potential for synthesizing eight-membered biaryl lactams. Various applications are also investigated, including access to the aza-brassinolide core.

本研究开发了一种高效合成七元联芳基内酰胺（seven-membered biaryl lactams）的方法，该方法涉及钯（Pd）催化、天然胺导向的苄胺邻位芳基化反应，随后进行原位内酰胺化。该串联反应可通过使用2-碘苯甲酸酯（2-iodobenzoates）实现，此类试剂能够在通常需要采用优化导向基团策略的反应条件下，促进游离胺参与的C-H芳基化（C-H arylation）反应。该反应具备宽泛的底物适用范围与优异的官能团耐受性。研究同时探讨了酯基与羧酸官能化偶联底物作为反应组分的适用性，以及合成八元联芳基内酰胺（eight-membered biaryl lactams）的可行性。此外还考察了该方法的多种应用场景，例如用于构建氮杂油菜素内酯（aza-brassinolide）核心结构。