Nickel-Catalyzed Stereoselective Coupling Reactions of Benzylic and Alkyl Alcohol Derivatives.
Nickel-Catalyzed Stereoselective Coupling Reactions of Benzylic and Alkyl Alcohol Derivatives.
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苄醇和烷基醇衍生物的镍催化立体选择性偶联反应
DOI：
10.1021/acs.accounts.3c00547
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发表时间：
2023-11-21
影响因子：
18.3
通讯作者：
Jarvo, Elizabeth R.
中科院分区：
文献类型：
--
作者：
Herbert, Claire A.;Jarvo, Elizabeth R.
烷基醇衍生物的镍催化反应利用了天然产物、药剂和合成中间体中羟基的高度普遍性，以提供获得富含C（sp3）的框架的途径。本报告介绍了我们实验室发展的立体定向和立体会聚的C-C键形成反应，采用C（sp3）-O和C（sp3）-N亲电试剂。在开发新转化的背景下，我们还定义了镍催化剂的基本特性。第一部分详细介绍了我们小组开发的镍催化交叉偶联反应，该反应取决于稳定的π-苄基中间体的立体选择性形成。无环和环状醚、酯、氨基甲酸酯、内酯和磺酰胺经历Kumada-、Suzuki-和Negishi-型偶联反应以产生具有高保真立体化学信息的对映体富集产物。我们描述扩展到包括开环反应的饱和杂环，以提供高非对映异构体比例的无环1，3-片段。我们还介绍了我们的立体定向镍催化交叉亲电偶联反应的进展。束缚的C-O和C-X亲电试剂被证明在构建各种碳环框架方面卓有成效。本文报道了新戊酸苄酯与溴代芳烃的分子内交叉亲电偶联反应，合成了茚满和四氢萘。我们发现，4-卤代四氢吡喃和4-卤代哌啶容易进行立体特异性环收缩，得到取代的环丙烷。机理研究与闭壳中间体、Ni（0）/Ni（II）循环和关键有机镍中间体形成环丙烷的分子内SN 2型反应一致。建立更复杂的级联反应，我们已经证明，2-炔基哌啶将MeMgI在一个二碳官能化的炔，以提供高度取代的乙烯基环丙烷。在第二部分中，我们介绍了我们的发展，立体收敛反应的烷基醇衍生物。为了扩大分子内XEC反应的实用性，我们试图采用未活化的烷基亲电试剂。具体地，二甲磺酸烷基酯参与分子内XEC反应以形成烷基环丙烷。与我们以前的工作相比，这些反应通过开壳层中间体进行，有利于反式环丙烷的立体收敛形成。对映选择性Aldol反应可用于合成1，3-二醇，提供对映体富集的环丙烷在高ee. Experimental和计算的证据表明，MeMgI介导的烷基碘原位形成。偶联反应起始于在仲烷基碘上夺取卤素原子。然后烷基Ni（II）络合物通过立体特异性SN 2型环闭合进行以形成环丙烷。为了增加由二甲磺酸烷基酯合成环丙烷中官能团的相容性，我们开发了由药用类似物制备的1，3-二甲磺酸酯的锌介导的反应。在具有挑战性的镍催化的分子内交叉亲电偶联中，我们也能够表明，邻位碳环可以在类似的条件下制备，以高产率提供邻位环戊基-环丙基基序。在第三部分中，我们讨论了我们最近的研究结果的作用，配体的身份在催化剂的选择性立体与立体烧蚀机制的氧化加成。我们展示了多变量控制机制，其中底物和配体的选择一起工作，以促进开壳或闭壳中间体。在4-卤代四氢吡喃的发散反应中，我们观察到在C（sp3）-O中心或C（sp3）-Cl中心的反应具有不同的配体偏好。这些发现是我们实验室继续研究的来源。
Nickel-catalyzed reactions of alkyl alcohol derivatives leverage the high prevalence of hydroxyl groups in natural products, medicinal agents, and synthetic intermediates to provide access to C(sp3)-rich frameworks. This Account describes our laboratory’s development of stereospecific and stereoconvergent C–C bond forming reactions employing C(sp3)–O and C(sp3)–N electrophiles. In the context of development of new transformations, we also define fundamental characteristics of the nickel catalysts. Part I details the nickel-catalyzed cross-coupling reactions developed by our group which hinges on stereospecific formation of stable π-benzyl intermediates. Acyclic and cyclic ethers, esters, carbamates, lactones, and sulfonamides undergo Kumada-, Suzuki-, and Negishi-type coupling reactions to produce enantioenriched products with high fidelity of stereochemical information. We describe extension to include ring-opening reactions of saturated heterocycles to afford acyclic 1,3-fragments in high diastereomeric ratios. We also describe our advances in stereospecific nickel-catalyzed cross-electrophile coupling reactions. Tethered C–O and C–X electrophiles proved fruitful for construction of a variety of carbocyclic frameworks. We report an intramolecular cross-electrophile coupling of benzylic pivalates with aryl bromides for the synthesis of indanes and tetralins. We found that 4-halotetrahydropyrans and 4-halopiperidines readily undergo stereospecific ring contraction to afford substituted cyclopropanes. Mechanistic investigations are consistent with closed-shell intermediates, a Ni(0)/Ni(II) cycle, and an intramolecular SN2-type reaction of a key organonickel intermediate to form the cyclopropane. Building toward more complex cascade reactions, we have demonstrated that 2-alkynyl piperidines incorporate MeMgI in a dicarbofunctionalization of the alkyne to afford highly substituted vinyl cyclopropanes. In Part II we present our development of stereoconvergent reactions of alkyl alcohol derivatives. In order to expand the utility of the intramolecular XEC reaction, we sought to employ unactivated alkyl electrophiles. Specifically, alkyl dimesylates engage in intramolecular XEC reactions to form alkyl cyclopropanes. In contrast to our previous work, these reactions proceed through open-shell intermediates and favor stereoconvergent formation of the trans-cyclopropane. Enantioselective aldol reactions can be employed in syntheses of 1,3-diols which furnish enantioenriched cyclopropanes in high ee. Experimental and computational evidence reveals that MeMgI mediates formation of alkyl iodides in situ. The coupling reaction initiates with halogen atom abstraction at the secondary alkyl iodide. The alkyl Ni(II) complex then proceeds through a stereospecific SN2-type ring closure to form cyclopropane. In an effort to increase functional group compatibility in the synthesis of cyclopropanes from alkyl dimesylates we developed a zinc-mediated reaction of 1,3-dimesylates prepared from medicinal analogues. In challenging nickel-catalyzed intramolecular cross-electrophile coupling we were also able to show that vicinal carbocycles can be prepared under similar conditions, affording vicinal cyclopentyl-cyclopropyl motifs in high yield. In Part III we discuss our recent findings on the role of ligand identity in catalyst selectivity for stereospecific vs stereoablative mechanisms for oxidative addition. We demonstrate multivariable control of mechanism, where the choice of substrate and ligand work together to promote open- or closed-shell intermediates. In divergent reactions of 4-halotetrahydropyrans we observe distinct ligand preference for reactions at the C(sp3)–O center or the C(sp3)–Cl center. These findings are the source of continued investigations in our laboratory.
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影响因子：
2.8
作者：
Greaves ME;Ronson TO;Maseras F;Nelson DJ
通讯作者：
Nelson DJ
DOI：
10.1002/chem.202000215
发表时间：
2020-03-09
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Dawson DD;Oswald VF;Borovik AS;Jarvo ER
通讯作者：
Jarvo ER
影响因子：
15
作者：
Diccianni, Justin B.;Katigbak, Joseph;Diao, Tianning
通讯作者：
Diao, Tianning
影响因子：
15
作者：
Estrada, Jesus G.;Williams, Wendy L.;Doyle, Abigail G.
通讯作者：
Doyle, Abigail G.
影响因子：
5.1
作者：
Ertl, Peter;Schuhmann, Tim
通讯作者：
Schuhmann, Tim