中国科学院上海有机化学研究所王晓明团队报道，以伯胺或水为杂原子源的铑-钯双催化[1 + 1 + 3]环化制备杂环。相关研究成果发表在2025年1月7日出版的《美国化学会杂志》。

化学生物学和药物研究中不断增长的需求要求开发新的合成方法，以便从简单的原料快速构建杂环库。在这种情况下，从原子和步骤经济的角度来看，在杂环骨架的组装中使用伯胺或H₂O，作为简单的N-或O-源是非常可取的。

该文中，研究人员描述了一种高效的重氮、烯丙基二乙酸酯和市售苯胺（或H₂O）的三组分反应，以获得结构多样的吡咯烷和四氢呋喃衍生物。这种正式的[1+1+3]环化反应具有高效、高产率和广泛的官能团相容性，使其成为几种重要生物活性分子（正式）合成的通用和稳健的平台。

机理研究表明，铑-钯双金属接力催化应在当前反应的连续步骤中发挥关键作用，包括碳烯顺序插入X-H键和双烯丙基取代，从而可以从这些简单的原料中建立分子复杂性。

附：英文原文

Title: Dirhodium–Palladium Dual-Catalyzed [1 + 1 + 3] Annulation to Heterocycles Using Primary Amines or H2O as the Heteroatom Sources

Author: Jie Xu, Gaoyin Wang, Kuiling Ding, Xiaoming Wang

Issue&Volume: January 7, 2025

Abstract: The ever-increasing demand in chemical biology and medicinal research requires the development of new synthetic methods for the rapid construction of libraries of heterocycles from simple raw materials. In this context, the utilization of primary amines or H2O as the simple N- or O-sources in the assembly of a heterocyclic ring skeleton is highly desirable from the viewpoint of atom- and step-economy. Herein, we describe a highly efficient three-component reaction of diazo, allylic diacetates, and commercially available anilines (or H2O) to access structurally diverse pyrrolidine and tetrahydrofuran derivatives. This formal [1 + 1 + 3] annulation reaction features high efficiency, good yields, and broad functional group compatibility, making it a versatile and robust platform for the (formal) synthesis of several important bioactive molecules. Mechanistic studies suggested that the dirhodium–palladium bimetallic relay catalysis should play a key role in the successive steps of the current reaction, including sequential carbene insertion into the X–H bond and double allylic substitutions, thus allowing for building up molecular complexity from these simple raw materials.

DOI: 10.1021/jacs.4c15161

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c15161