School of Chemistry and Chemical Engineering, South China University of Technology , Guangzhou 510640, People's Republic of China.
Acc Chem Res. 2014 Aug 19;47(8):2483-504. doi: 10.1021/ar5001499. Epub 2014 Jul 2.
Inspired by the need for green and sustainable chemistry, modern synthetic chemists have been seeking general and practical ways to construct complex molecules while maximizing atom economy and minimizing synthetic steps. Over the past few decades, considerable progress has been made to fulfill these goals by taking advantage of transition metal catalysis and chemical reagents with diverse and tunable reactivities. In recent years, haloalkynes have emerged as powerful and versatile building blocks in a variety of synthetic transformations, which can be generally conceived as a dual functionalized molecules, and different reaction intermediates, such as σ-acetylene-metal, π-acetylene-metal, and halovinylidene-metal complexes, can be achieved and undergo further transformations. Additionally, the halogen moieties can be retained during the reaction processes, which makes the subsequent structural modifications and tandem carbon-carbon or carbon-heteroatom bond formations possible. As a consequence, impressive effort has been devoted to this attractive area, and some elegant work has been done over the past several years. This Account highlights some of the recent progress on the development of efficient and practical synthetic methods involving haloalkyne reagents in our laboratory and in others around the world, which showcase the synthetic power of haloalkynes for rapid assembly of complex molecular structures. The focus is primarily on reaction development with haloalkynes, such as cross-coupling reactions, nucleophilic additions, and cycloaddition reactions. The designed approaches, as well as serendipitous observations, will be discussed with special emphasis placed on the mechanistic aspects and the synthetic utilities of the obtained products. These transformations can lead directly to heteroatom-containing products and introduce structural complexity rapidly, thus providing new strategies and quick access to a wide range of functionalized products including many synthetically useful conjugated cyclic and acyclic structures that have potential applications in natural product synthesis, materials science, and drug discovery. Importantly, most of these protocols allow multiple bond-forming events to occur in a single operation, thereby offering opportunities to advance chemical synthesis and address the increasing demands for economical and sustainable synthetic methods. We anticipate that a deep understanding of the properties of haloalkyne reagents and the underlying working mechanism can lead to the development of novel catalytic systems to answer the unsolved challenges in haloalkyne chemistry, which, in turn, may be also instructive for other research areas. We hope this Account will help to provide a guideline for researchers who are interested in this fertile area.
受绿色和可持续化学的需求的启发，现代合成化学家一直在寻找通用且实用的方法来构建复杂分子，同时最大限度地提高原子经济性并减少合成步骤。在过去的几十年中，通过利用过渡金属催化和具有多种可调反应性的化学试剂，已经在实现这些目标方面取得了相当大的进展。近年来，卤代炔烃已成为各种合成转化中的强大而多功能的构建块，通常可以被视为双官能化分子，并且可以实现不同的反应中间体，例如 σ-炔基金属、π-炔基金属和卤代烯基金属配合物，并进一步转化。此外，卤素部分可以在反应过程中保留下来，这使得随后的结构修饰和串联碳-碳或碳-杂原子键形成成为可能。因此，人们为此领域投入了大量的努力，并且在过去的几年中已经完成了一些出色的工作。本综述重点介绍了我们实验室和世界各地的其他实验室在开发涉及卤代炔试剂的高效实用合成方法方面的一些最新进展，这些进展展示了卤代炔在快速组装复杂分子结构方面的合成能力。重点主要放在与卤代炔的反应开发上，例如交叉偶联反应、亲核加成反应和环加成反应。设计的方法以及偶然的观察结果将进行讨论，特别强调了反应的机理方面和获得产物的合成实用性。这些转化可以直接得到含杂原子的产物，并快速引入结构复杂性，从而提供了新的策略和快速获得广泛的功能化产物的途径，包括许多在天然产物合成、材料科学和药物发现中具有潜在应用的合成有用的共轭环状和非环状结构。重要的是，这些方案中的大多数允许在单个操作中发生多个键形成事件，从而为推进化学合成和满足对经济可持续合成方法的日益增长的需求提供了机会。我们预计，对卤代炔试剂性质和潜在工作机制的深入了解将导致开发新型催化体系来解决卤代炔化学中的未解决挑战，这反过来也可能对其他研究领域有启示。我们希望本综述能为对这一富有成果的领域感兴趣的研究人员提供一个指导。
