Kuai Chang-Sheng, Wang Yuanrui, Yang Ting, 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.
J Am Chem Soc. 2025 Mar 5;147(9):7950-7964. doi: 10.1021/jacs.5c00032. Epub 2025 Feb 19.
Efficiently constructing structurally diverse and complex organic molecules through selective catalytic functionalization is a central goal in synthetic chemistry, yet achieving precise control over multiple reactive centers in multisite substrates remains a formidable challenge. Building on foundational advances in single- and dual-selective transformations, we report a multimodal strategy for the selective carbonylation of 1,3-enynes, a versatile class of multisite substrates. Through meticulous fine-tuning of the catalytic conditions, our approach enables five distinct regio- and stereoselective carbonylative transformations, including direct functionalization (1,2- and 2,1-hydroaminocarbonylation) and tandem cyclization pathways (2,4-, 1,3-, and 2,3-carbonylation). Furthermore, mechanistic studies suggested that multidimensional precise regulation enables the seamless relay of up to three tandem reactions (hydroaminocarbonylation-hydroamination-transamination) with exceptional accuracy. This unified platform not only establishes a robust framework for tackling the enduring challenges of selectivity control in multisite substrates but also broadens the chemical space accessible through 1,3-enyne transformations, exemplifying atom- and step-economic principles and paving the way for transformative advancements in drug discovery, materials science, and beyond.
通过选择性催化官能团化高效构建结构多样且复杂的有机分子是合成化学的核心目标，然而，对多位点底物中的多个反应中心实现精确控制仍然是一项艰巨的挑战。基于单选择性和双选择性转化的基础进展，我们报道了一种用于1,3-烯炔（一类通用的多位点底物）选择性羰基化的多模式策略。通过对催化条件进行细致微调，我们的方法能够实现五种不同的区域和立体选择性羰基化转化，包括直接官能团化（1,2-和2,1-氢胺羰基化）和串联环化途径（2,4-、1,3-和2,3-羰基化）。此外，机理研究表明，多维精确调控能够以极高的精度实现多达三个串联反应（氢胺羰基化-氢胺化-转氨作用）的无缝接力。这个统一的平台不仅为应对多位点底物选择性控制这一长期挑战建立了一个强大的框架，还拓宽了通过1,3-烯炔转化可进入的化学空间，体现了原子经济性和步骤经济性原则，并为药物发现、材料科学及其他领域的变革性进展铺平了道路。
