Department of Material Chemistry, Faculty of Science, Xi’an Jiaotong University, PR China.
Acc Chem Res. 2011 Feb 15;44(2):111-22. doi: 10.1021/ar100109m. Epub 2010 Oct 28.
Many groups have explored the scope of the palladium-based cyclization of propargylic compounds since Tsuji's first report in 1985. Through the proper positioning of an internal nucleophilic center and the judicious selection of an appropriate external nucleophile, the synthetic chemist can effectively assert control over the course of the reaction and its products. However, initial investigations were very limited: only heterocyclic compounds were originally synthesized. We have found the palladium-catalyzed cyclization of propargylic compounds to be a very efficient method for producing both carbocyclic and heterocyclic compounds. In this Account, we discuss the cyclization reactions of functionalized propargylic compounds with a variety of nucleophiles that we have developed over the past few years. We also review similar reactions reported by other groups. We focus here on the cyclization of functionalized propargylic compounds containing a carbon nucleophilic center that is in close proximity to the propargylic moiety. We conducted a detailed investigation of their cyclizations with carbon nucleophiles, with nitrogen nucleophiles, with oxygen nucleophiles, and without nucleophiles. We have developed several efficient and useful methods for the synthesis of indenes, naphthalenes, polycycles, and spirocyclic compounds. All of these reactions proceed satisfactorily under very mild conditions; high regio- and stereoselectivity have been observed as well. In the course of our studies, we provided the first demonstration of a novel tandem C-H activation/bis-cyclization reaction of propargylic compounds with terminal alkynes. In addition, we used external nucleophiles to investigate the cyclization of functionalized propargylic compounds that bear an unsaturated carbon-carbon or carbon-heteroatom bond. We presented the first report of the use of external nucleophiles to initiate a novel cyclization of functionalized propargylic compounds containing an electrophile. This revelation provided a fresh perspective through the discovery of a new type of domino cyclization of propargylic compounds. Metal-catalyzed cyclization of propargylic compounds can provide indenes, cyclopentanones, cyclic carbonates, benzofurans, and a range of other cyclic molecules. A thorough understanding of the mechanisms involved in this class of reaction affords exceptional synthetic control, as shown here by our development of efficient procedures and reagents for palladium-catalyzed propargylic cyclizations.
自 1985 年 Tsuji 首次报道以来，许多小组已经探索了钯催化炔丙基化合物环化的范围。通过适当定位内部亲核中心和明智选择合适的外部亲核试剂，合成化学家可以有效地控制反应过程及其产物。然而，最初的研究非常有限：最初只合成了杂环化合物。我们发现钯催化炔丙基化合物的环化是一种非常有效的方法，可以生成碳环和杂环化合物。在本报告中，我们讨论了过去几年中我们开发的各种亲核试剂对功能化炔丙基化合物的环化反应。我们还回顾了其他小组报道的类似反应。我们在这里重点介绍了含有靠近炔丙基部分的碳亲核中心的功能化炔丙基化合物的环化反应。我们详细研究了它们与碳亲核试剂、氮亲核试剂、氧亲核试剂和无亲核试剂的环化反应。我们已经开发了几种用于合成茚、萘、多环和螺环化合物的有效且有用的方法。所有这些反应都在非常温和的条件下顺利进行；观察到高区域和立体选择性。在我们的研究过程中，我们首次证明了末端炔烃与炔丙基化合物的新型串联 C-H 活化/双环化反应。此外，我们还使用外部亲核试剂研究了带有不饱和碳-碳或碳-杂原子键的功能化炔丙基化合物的环化反应。我们首次报道了使用外部亲核试剂引发含亲电试剂的功能化炔丙基化合物的新型环化反应。这一发现通过发现炔丙基化合物的新型多米诺环化反应提供了一个新的视角。金属催化的炔丙基化合物环化可以提供茚、环戊酮、环状碳酸酯、苯并呋喃和一系列其他环状分子。对这类反应机制的透彻理解提供了卓越的合成控制，正如我们开发用于钯催化炔丙基环化的有效程序和试剂所证明的那样。
