Wang Yuanrui, Qi Xin, Bao Zhi-Peng, Wu Xiao-Feng
Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences Dalian Liaoning 116023 China
University of Chinese Academy of Sciences Beijing 100049 China.
Chem Sci. 2025 Apr 25. doi: 10.1039/d5sc02418h.
In radical carbonylation chemistry, orderly and sequential construction of C-C and C-N bonds with CO can effectively approach amide units and quickly incorporate a wide range of functional groups. However, this procedure remains underdeveloped for the synthesis of β-lactams. In general, especially for four-membered rings, end-to-end annulation is a thermodynamically unfavorable process compared to [2 + 2] cycloaddition. Here we developed a photoinduced radical relay carbonylative annulation (RRCA) strategy in which the key β-amino acyl radical intermediates exhibit superior capability of cyclization. This unique and underrated property is crucial in the process of successfully overcoming the tension of four-membered annulation for the synthesis of β-lactams. Mild conditions and wide substrate compatibility indicate the value of this method in the field of new drug discovery with special therapeutic effects. Particularly, embedding the amine group of the amino acid into the β-lactam skeleton further illustrates the utility of this methodology enabling late-stage modification of bioactive molecules.
在自由基羰基化化学中，与一氧化碳有序且连续地构建碳 - 碳键和碳 - 氮键能够有效地合成酰胺单元，并能快速引入多种官能团。然而，该方法在β - 内酰胺的合成中仍未得到充分发展。一般来说，特别是对于四元环，与[2 + 2]环加成反应相比，端对端环化是一个热力学不利的过程。在此，我们开发了一种光诱导自由基接力羰基化环化（RRCA）策略，其中关键的β - 氨基酰基自由基中间体表现出卓越的环化能力。这种独特且被低估的性质对于成功克服合成β - 内酰胺时四元环化的张力过程至关重要。温和的条件和广泛的底物兼容性表明了该方法在具有特殊治疗效果的新药发现领域的价值。特别地，将氨基酸的氨基嵌入β - 内酰胺骨架进一步说明了该方法在生物活性分子后期修饰方面的实用性。
