Liang Yu-Feng, Bilal Muhammad, Tang Le-Yu, Wang Tian-Zhang, Guan Yu-Qiu, Cheng Zengrui, Zhu Minghui, Wei Jialiang, Jiao Ning
School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Chem Rev. 2023 Nov 22;123(22):12313-12370. doi: 10.1021/acs.chemrev.3c00219. Epub 2023 Nov 9.
Late-stage functionalization (LSF) introduces functional group or structural modification at the final stage of the synthesis of natural products, drugs, and complex compounds. It is anticipated that late-stage functionalization would improve drug discovery's effectiveness and efficiency and hasten the creation of various chemical libraries. Consequently, late-stage functionalization of natural products is a productive technique to produce natural product derivatives, which significantly impacts chemical biology and drug development. Carbon-carbon bonds make up the fundamental framework of organic molecules. Compared with the carbon-carbon bond construction, the carbon-carbon bond activation can directly enable molecular editing (deletion, insertion, or modification of atoms or groups of atoms) and provide a more efficient and accurate synthetic strategy. However, the efficient and selective activation of unstrained carbon-carbon bonds is still one of the most challenging projects in organic synthesis. This review encompasses the strategies employed in recent years for carbon-carbon bond cleavage by explicitly focusing on their applicability in late-stage functionalization. This review expands the current discourse on carbon-carbon bond cleavage in late-stage functionalization reactions by providing a comprehensive overview of the selective cleavage of various types of carbon-carbon bonds. This includes C-C(sp), C-C(sp), and C-C(sp) single bonds; carbon-carbon double bonds; and carbon-carbon triple bonds, with a focus on catalysis by transition metals or organocatalysts. Additionally, specific topics, such as ring-opening processes involving carbon-carbon bond cleavage in three-, four-, five-, and six-membered rings, are discussed, and exemplar applications of these techniques are showcased in the context of complex bioactive molecules or drug discovery. This review aims to shed light on recent advancements in the field and propose potential avenues for future research in the realm of late-stage carbon-carbon bond functionalization.
后期官能团化（LSF）是在天然产物、药物和复杂化合物合成的最后阶段引入官能团或进行结构修饰。预计后期官能团化将提高药物发现的有效性和效率，并加速各种化学文库的创建。因此，天然产物的后期官能团化是生产天然产物衍生物的一种有效技术，对化学生物学和药物开发具有重大影响。碳 - 碳键构成了有机分子的基本框架。与碳 - 碳键构建相比，碳 - 碳键活化能够直接实现分子编辑（原子或原子团的删除、插入或修饰），并提供更高效、准确的合成策略。然而，无张力碳 - 碳键的高效选择性活化仍然是有机合成中最具挑战性的课题之一。本综述涵盖了近年来用于碳 - 碳键裂解的策略，特别关注它们在后期官能团化中的适用性。本综述通过全面概述各种类型碳 - 碳键的选择性裂解，扩展了当前关于后期官能团化反应中碳 - 碳键裂解的论述。这包括C - C(sp)、C - C(sp²)和C - C(sp³)单键；碳 - 碳双键；以及碳 - 碳三键，重点关注过渡金属或有机催化剂的催化作用。此外，还讨论了特定主题，如涉及三、四、五和六元环中碳 - 碳键裂解的开环过程，并在复杂生物活性分子或药物发现的背景下展示了这些技术的典型应用。本综述旨在阐明该领域的最新进展，并为后期碳 - 碳键官能团化领域的未来研究提出潜在途径。
