The Promise and Challenge of Iron-Catalyzed Cross Coupling
The Promise and Challenge of Iron-Catalyzed Cross Coupling
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DOI：
10.1002/chin.200906265
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发表时间：
2009-02
期刊：
影响因子：
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通讯作者：
B. Sherry;A. Fuerstner
中科院分区：
文献类型：
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作者：
B. Sherry;A. Fuerstner
过渡金属催化剂，特别是那些来源于第VIII族−X金属的催化剂，通过合适的亲核试剂与有机亲电伙伴反应，显示出显著的效率，可以形成碳−碳和碳−杂原子键。在元素周期表的这一子集中，钯和镍的络合物提供了最广泛的用途，同时还提供了对所谓的“交叉偶联反应”的最深刻的机理洞察。过去30年致力于钯和镍催化剂的巨大努力，在某种程度上掩盖了这一领域中替代金属络合物的报道。由于交叉偶联反应已经发展成为现代合成化学的重要支撑，对替代催化剂的研究也重新活跃起来。当当代合成化学家回顾交叉偶联的起源以获得灵感时，铁盐对格氏试剂与有机亲电试剂的反应性的影响被充分记录下来，作为替代催化剂开发的肥沃土壤。铁具有更适合碱金属或碱土金属的实际好处，同时显示出d-块元素的独特反应性。因此，寻找广泛适用于交叉偶联的铁催化剂是现代合成有机化学中一个日益重要的目标。本文描述了铁催化交叉偶联从Kochi工作开始到现在的演变。特别强调了反应性和合成应用，包括从酰基、烯基、芳基和烷基卤化物/假卤化物交叉偶联中选择的例子。典型的反应伙伴是格氏试剂，尽管在某些情况下也使用了有机锰、铜和锌的衍生物。这种铁催化的过程即使在低温下也会非常迅速地发生，因此具有广泛的官能团相容性。此外，还介绍了碳−杂原子键形成的最新进展，以及与原位生成和结构定义的低价铁催化剂的一般反应活性相关的研究。铁催化交叉偶联的制备方面是令人鼓舞的，但将这些过程归类于特征反应流形的倾向还为时过早，因为机理研究进展相对缓慢。一种典型的交叉偶联方案采用Fe(+2)或Fe(+3)预催化剂，其被有机金属亲核试剂原位还原。30多年后，所产生的活性成分(S)的性质，用高知最初的术语来说，仍然是最好的描述，即“可溶性铁的还原形式”。尽管我们目前的知识存在巨大的差距，但已经形成了三种不同的机制，主要基于经验证据：一种“典型的”交叉偶联过程，一种以有机铁中间体的烷基化取代易位作用为关键步骤的多种机制，以及一种依赖于亲核络合物形成的建议。猜测和猜测比比皆是，但铁催化的交叉偶联反应中的催化循环究竟是什么，仍然是一个极具挑战性的悬而未决的问题。
Transition metal catalysts, particularly those derived from the group VIII−X metals, display remarkable efficiency for the formation of carbon−carbon and carbon−heteroatom bonds through the reactions of suitable nucleophiles with organic electrophilic partners. Within this subset of the periodic table, palladium and nickel complexes offer the broadest utility, while additionally providing the deepest mechanistic insight into thus-termed “cross-coupling reactions”. The mammoth effort devoted to palladium and nickel catalysts over the past 30 years has somewhat obscured reports of alternative metal complexes in this arena. As cross-coupling reactions have evolved into a critical support for modern synthetic chemistry, the search for alternative catalysts has been taken up with renewed vigor.When the current generation of synthetic chemists reflects back to the origins of cross coupling for inspiration, the well-documented effect of iron salts on the reactivity of Grignard reagents with organic electrophiles surfaces as a fertile ground for alternative catalyst development. Iron possesses the practical benefits more befitting an alkali or alkaline earth metal, while displaying the unique reactivity of a d-block element. Therefore the search for broadly applicable iron catalysts for cross coupling is an increasingly important goal in modern synthetic organic chemistry.This Account describes the evolution of iron-catalyzed cross coupling from its inception in the work of Kochi to the present. Specific emphasis is placed on reactivity and synthetic applications, with selected examples from acyl-, alkenyl-, aryl-, and alkyl halide/pseudohalide cross coupling included. The typical reaction partners are Grignard reagents, though organomanganese, -copper, and -zinc derivatives have also been used in certain cases. Such iron-catalyzed processes occur very rapidly even at low temperature and therefore are distinguished by broad functional group compatibility. Furthermore, recent advances in carbon−heteroatom bond formation and studies relevant to the general reactivity of in situ generated and structurally defined “low-valent” iron catalysts are presented.The preparative aspects of iron-catalyzed cross coupling are encouraging, but the inclination to classify these processes within the characteristic reaction manifold is premature, as mechanistic studies have evolved at a comparatively slow pace. A typical protocol for cross coupling employs an Fe(+2) or Fe(+3) precatalyst, which is reduced in situ by the organometallic nucleophile. The nature of the resulting active component(s) is still best described, more than 30 years later, in Kochi’s original terms as a “reduced form of soluble iron”. Despite huge gaps in our current knowledge, three distinct mechanisms have been formulated, largely based on empirical evidence: a “canonical” cross-coupling process, a manifold wherein alkylation of an organoiron intermediate replaces transmetalation as a key step, and finally a proposal reliant on the formation of nucleophilic ate complexes. Conjecture and speculation abound, but precisely what constitutes the catalytic cycle in iron-catalyzed cross coupling remains an extremely challenging unanswered question.