Catalytic, Atom-Economical Radical Arylation of Epoxides
Catalytic, Atom-Economical Radical Arylation of Epoxides
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DOI：
10.1002/anie.201200431
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Flowers, Robert A., II
中科院分区：
文献类型：
--
作者：
Gansaeuer, Andreas;Behlendorf, Maike;Flowers, Robert A., II
高效催化反应的发展是化学的核心方面之一，可以说是发明新的可持续工艺的最重要方面。[1]基于自由基的转化是用于催化循环中的最有吸引力的方法之一，这是由于自由基生成容易、高官能团耐受性和C13 C键形成的选择性。[2]在这里，我们提出了这样一个过程，一个原子经济的茂钛催化[3]分子内芳基化的环氧衍生的自由基。我们的方法利用了二茂钛（III）/（IV）氧化还原对进行可逆电子转移反应的固有能力。[4]这允许在催化循环中以单电子步骤实施氧化加成和还原消除。我们的方法的关键步骤被认为是质子耦合电子转移（PCET）。[5]它构成了关键的单电子还原消除，为自由基σ-络合物的有效rearomatization提供了驱动力，并否定了对基于自由基的链式过程或催化反应中所必需的牺牲共还原剂或氧化剂的需要。[6]这个问题在Minisci反应中至关重要，[7]对缺电子杂芳烃的自由基加成，通常需要化学计量的金属（Fe，Ag）盐和氧化剂（H2 O2或有机过氧化物）。最近，Heinrich等人报道了朝向更可持续的自由基芳基化的重大进展。[8]在这些反应中，芳基重氮盐用作自由基前体。尽管如此，必须以化学计量的量使用钛催化剂，以在相当酸性的介质（HCl水溶液）中产生自由基。我们的催化循环示于方案1中。它是由[Cp 2 TiCl]的单电子氧化加成到底物产生自由基中间体A引发的。在自由基移位步骤中，将自由基加成到侧链芳烃上产生关键的自由基σ络合物B。[Cp 2 TiCl]的单电子还原消除可以通过电子从芳烃B转移到二茂钛形成C来完成。随后质子转移到二茂钛（III）结合的烷氧基，得到产物和催化剂。因此，催化循环是完全原子经济的，并且不需要使用化学计量量的外部酸来质子化TiO 2-O键，或者不需要使用用于将B氧化成阳离子σ络合物的源（例如O2），并且原则上仅需要预催化剂[Cp 2 TiCl 2]的初始还原所需的金属粉末的量。[9]使用10摩尔%的3，在30分钟后在THF中实现1a向2a的完全转化，并以98%的产率分离（方案2）。该结果清楚地表明，外部氧化剂和酸都不是周转所必需的。锰仅需要用于产生活性催化剂，因为没有[Cp 2 TiCl 2]就不会发生反应。然而，催化剂负载量仍然相当高。为了克服这一限制，反应的影响
The development of efficient catalytic reactions is one of the central aspects of chemistry and arguably the most important for the invention of novel sustainable processes.[1] Radicalbased transformations are among the most attractive methods for use in catalytic cycles owing to the ease of radical generation, high functional group tolerance, and selectivity in CÀC bond formation.[2] Herein we present such a process, an atom-economical titanocene-catalyzed [3] intramolecular arylation of epoxide-derived radicals. Our approach exploits the innate capability of the titanocene (III)/(IV) redox couple to undergo reversible electron-transfer reactions.[4] This allows the implementation of both oxidative additions and reductive eliminations in single-electron steps into catalytic cycles. The key step of our method is presumed to be a proton-coupled electron transfer (PCET).[5] It constitutes the pivotal single-electron reductive elimination, provides the driving force for efficient rearomatization of the radical σ-complex, and negates the need for sacrificial co-reductants or oxidants necessary in radical-based chain processes or catalytic reactions.[6] This issue is critical in Minisci reactions,[7] radical additions to electron deficient heteroarenes, which often require stoichiometric amounts of metal (Fe, Ag) salts and oxidants (H2O2 or organic peroxides). More recently, significant progress towards more sustainable radical arylation has been reported by Heinrich et al.[8] In these reactions, aryl diazonium salts are employed as radical precursors. Nevertheless, titanium trichloride has to be employed in stoichiometric amounts for radical generation in rather acidic media (aqueous HCl). Our catalytic cycle is shown in Scheme 1. It is initiated by the single-electron oxidative addition of [Cp2TiCl] to the substrate generating radical intermediate A. Addition of the radical to the pendant arene produces the pivotal radical σcomplex B in the radical translocation step. The singleelectron reductive elimination of [Cp2TiCl] can be accomplished by an electron transfer from the arene B to the titanocene to form C. Subsequent proton transfer to the titanocene (III)-bound alkoxy group yields product and catalyst. As a consequence, the catalytic cycle is completely atomeconomical and does not require the use of stoichiometric amounts of an external acid for the protonation of a TiÀO bond, or a source (such as O2) for the oxidation of B to the cationic σ complex, and in principle requires only the amount of a metal powder necessary for the initial reduction of the precatalyst [Cp2TiCl2].[9]With 10 mol% 3, complete conversion of 1a to 2a was realized in refluxing THF after 30 min and was isolated in 98% yield (Scheme 2). This result clearly demonstrates that neither an external oxidant nor an acid are necessary for turnover. Manganese is only required for the generation of the active catalyst, as without [Cp2TiCl2] no reaction takes place. However, catalyst loading is still rather high. To overcome this limitation, the influence of the reaction