CuH-Catalyzed Olefin Functionalization: From Hydroamination to Carbonyl Addition.
CuH-Catalyzed Olefin Functionalization: From Hydroamination to Carbonyl Addition.
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DOI：
10.1021/acs.accounts.0c00164
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发表时间：
2020-06-16
影响因子：
18.3
通讯作者：
Buchwald SL
中科院分区：
文献类型：
--
作者：
Liu RY;Buchwald SL
在有机合成中，配体修饰的铜(I)氢化物(CuH)络合物已成为公认的选择性还原试剂和催化剂，特别是对Michael受体和羰基化合物。最近，我们的团队和其他人发现，这些氢化物络合物与相对未活化和电子未极化的烯烃发生迁移插入(氢铜化)，产生烷基铜中间体，可用于锻造各种有用的键。由此产生的形式氢化功能化反应已经形成了CuH催化研究的复兴基础。这篇文章记录了这个概念在我们的研究组中的发展，强调了它在不对称氢胺化的背景下的起源，进化到更一般的C-X成键反应，以及在将烯烃衍生的亲核试剂加到羰基衍生物中的应用。氢胺化反应是将烯烃正式插入到胺的N-H键上的过程，由于它有可能将广泛存在的烯烃和炔烃转化为有价值的复合胺，因此具有重要的学术和工业意义。我们开发了一种催化对映体选择性氢胺化反应的极性反转策略，依赖于烯烃与CuH反应生成手性有机铜中间体，并被亲电胺试剂截留。通过改变辅助配体、亲胺和反应条件，这种方法的范围已经扩展到包括许多类型的烯烃，包括具有挑战性的内烯烃。此外，胺试剂的范围已扩大到能够合成伯胺、仲胺和叔胺以及酰胺、N-烷基化杂环和苯胺。所有这些反应都表现出很高的区域和立体选择性，并且由于条件温和，对杂环和极性官能团具有极好的耐受性。虽然从烯烃生成烷基铜物种最初是为了解决氢胺化问题，但我们很快发现，这些中间体可以与出人意料的广泛的亲电试剂反应，包括烷基卤化物、硅试剂、芳基钯物种、杂环和羰基衍生物。烯烃作为亲核中间体前体的一般能力已被证明在羰基加成反应中特别有利，因为它克服了传统有机金属试剂的许多缺点。由于不需要在单独的操作中预先生成亲核试剂，CuH催化的烯烃类亲核试剂加成反应具有更好的步骤经济性、增强的官能团耐受性以及催化剂控制区域和立体选择性的潜力。在此基础上，丙二烯、丁二烯和苯乙烯等原料烯烃已被用作酮、亚胺和醛的不对称烷基化试剂。
In organic synthesis, ligand-modified copper(I) hydride (CuH) complexes have become well-known reagents and catalysts for selective reduction, particularly toward Michael acceptors and carbonyl compounds. Recently, our group and others have found that these hydride complexes undergo migratory insertion (hydrocupration) with relatively unactivated and electronically unpolarized olefins, producing alkylcopper intermediates that can be leveraged to forge a variety of useful bonds. The resulting formal hydrofunctionalization reactions have formed the basis for a resurgence of research in CuH catalysis. This Account chronicles the development of this concept in our research group, highlighting its origin in the context of asymmetric hydroamination, evolution to more general C–X bond-forming reactions, and applications in the addition of olefin-derived nucleophiles to carbonyl derivatives. Hydroamination, the formal insertion of an olefin into the N–H bond of an amine, is a process of significant academic and industrial interest, due to its potential to transform widely available alkenes and alkynes into valuable complex amines. We developed a polarity-reversed strategy for catalytic enantioselective hydroamination relying on the reaction of olefins with CuH to generate chiral organocopper intermediates, which are intercepted by electrophilic amine reagents. By engineering the auxiliary ligand, amine electrophile, and reaction conditions, the scope of this method has since been extended to include many types of olefins, including challenging internal olefins. Further, the scope of amine reagents has been expanded to enable the synthesis of primary, secondary, and tertiary amines, as well as amides, N-alkylated heterocycles, and anilines. All of these reactions exhibit high regio- and stereoselectivity and, due to the mild conditions required, excellent tolerance for heterocycles and polar functional groups. Though the generation of alkylcopper species from olefins was originally devised as a means to solve the hydroamination problem, we soon found that these intermediates could react efficiently with an unexpectedly broad range of electrophiles, including alkyl halides, silicon reagents, arylpalladium species, heterocycles, and carbonyl derivatives. The general ability of olefins to function as precursors for nucleophilic intermediates has proved particularly advantageous in carbonyl addition reactions because it overcomes many of the disadvantages associated with traditional organometallic reagents. By removing the need for pre-generation of the nucleophile in a separate operation, CuH-catalyzed addition reactions of olefin-derived nucleophiles feature improved step economy, enhanced functional-group tolerance, and the potential for catalyst control over regio- and stereoselectivity. Following this paradigm, feedstock olefins such as allene, butadiene, and styrene have been employed as reagents for asymmetric alkylation of ketones, imines, and aldehydes.
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影响因子：
15
作者：
Gribble MW Jr;Guo S;Buchwald SL
通讯作者：
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影响因子：
18.3
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通讯作者：
Buchwald, SL
影响因子：
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