Rodríguez Laura G, Serra Aina, Bonjoch Josep, Bradshaw Ben
Laboratori de Química Orgànica, Facultat de Farmàcia, IBUB, Universitat de Barcelona 08028 Spain
Chem Sci. 2025 Jul 23. doi: 10.1039/d5sc04274g.
The development of general methods for radical bond formation remains a central goal in organic synthesis, particularly those that enable diverse transformations from simple, abundant starting materials. Here, we report a unified approach that merges carboxylic acid activation with metal-catalyzed hydrogen atom transfer (MHAT) to enable the generation and selective functionalization of open-shell intermediates under a single catalytic system. Key to this strategy is the design of a redox-active ester bearing an internal alkene "trigger" that undergoes regioselective MHAT using Fe(acac) and phenylsilane, leading to decarboxylative radical formation under mild conditions. This platform supports the synthesis of a wide array of products C-C, C-heteroatom, and C-H bond-forming processes, accessed solely by varying the radical acceptor. Notably, it enables the formation of linear coupling products-previously inaccessible under conventional MHAT conditions- access to primary radical intermediates. We anticipate that this conceptually distinct mode of activation will find applications in modular synthesis, late-stage functionalization, and the generation of medicinally relevant analogs.
自由基键形成通用方法的开发仍然是有机合成的核心目标，特别是那些能够从简单、丰富的起始原料实现多样转化的方法。在此，我们报道了一种统一的方法，该方法将羧酸活化与金属催化的氢原子转移（MHAT）相结合，以在单一催化体系下实现开壳中间体的生成和选择性官能化。该策略的关键在于设计一种带有内部烯烃“触发基团”的氧化还原活性酯，它能使用Fe(acac)和苯基硅烷进行区域选择性的MHAT，从而在温和条件下导致脱羧自由基的形成。这个平台支持多种产物的合成——碳 - 碳、碳 - 杂原子和碳 - 氢键形成过程，只需改变自由基受体即可实现。值得注意的是，它能够形成线性偶联产物——这在传统的MHAT条件下是无法实现的——从而获得伯自由基中间体。我们预计这种概念上独特的活化模式将在模块化合成、后期官能化以及药用相关类似物的生成中得到应用。
