Oxidative coupling of arenes using molybdenum(V) reagents

芳烃的脱氢偶联反应近年来受到越来越多的关注。使用MoCl5可以实现高产量的这些转换。然而，氯化的底物或产物通常被视为副产物。此外，这种氧化偶联的反应机制仍有不同的讨论，其中提出了自由基阳离子或正碳途径作为机制基础。在这个合作项目中，将讨论以下主题：1)阐明Mo(V)试剂的底物范围和可获得的产品类别。2) C- C与相关Mo(V)试剂偶联的潜在自由基型中间体将被确定，3)新的Mo(V)试剂将被开发，能够抑制氯化作用，提供多米诺骨牌序列，并用于电化学/电催化。通过建立创新的多米诺氧化途径，Mo(V)介导的偶联将扩展到广泛的衬底和各种产品类别。芳基在苯基位置的偶联和随后被亲核试剂捕获，可以快速获得杂蒽、硫杂蒽和吖啶酮衍生物。吡啶n-氧化物与芳烃的氧化偶联使用MoX5，然后由共形成的Mo（IV）进行原位脱氧，将产生一个通用的一锅方案，以获得生物碱，如-碳碱。最具挑战性的是交叉偶联反应。在这里，我们将通过一个额外的刘易斯酸的配位来控制所需的途径，这使得最富电子的耦合组分不容易发生初始氧化步骤。这个概念在一定程度上允许氧化势和亲核性解耦，为交叉偶联反应提供了一种通用的方法。为了理解反应途径，并以合理和有效的方式优化这些途径，对机理的了解将是至关重要的。因此，通过带电标签分子的ESI-MS实验来检测潜在的自由基性质的反应中间体是可行的。这允许检测中性自由基。这些实验将通过在DFT水平上计算耦合反应的中间体和过渡态来支持。为了优化这两方面的反应性和选择性，开发较少甚至不含氯基配体的Mo(V)试剂是必不可少的。这一部分将在一个相关的项目中讨论。此外，除了最近报道的配合物Mo2Cl6(hfip)4外，还设想制备具有稳定的氟化烷氧基配体的MoV配合物。如果能成功地合成无卤化物的Mo(V)烷氧配合物，例如用取代法从氟配合物或用氧化法从Mo2(hfip)6合成的Mo(V)烷氧配合物，那么用MoV作为介质的电化学C、C偶联应该是长期可行的。

Dehydrogenative coupling reactions of arenes have recently experienced increasing attention. Employing MoCl5 enables these conversions in high yield. However, often chlorinated substrates or products are observed as by-products. Moreover, the reaction mechanism of this oxidative coupling is still subject of divergent discussions, wherein a radical cationic or carbenium pathway is proposed as mechanistic rationale. Within this collaborative project the following topics will be addressed : 1) the scope of substrates and accessible product classes by Mo(V) reagents will be elucidated. 2) potential radical-type intermediates of the C,C-coupling with involved Mo(V) reagents will be identified, and 3) novel Mo(V) reagents will be developed, being capable to suppress chlorination, providing access to domino sequences, and to electrochemically/electrocatalytically uses. The Mo(V)-mediated coupling will be extended to a broad scope of substrates and a variety of product classes by establishing innovative domino-oxidation pathways. The coupling of aryls in benzylic position and subsequent trapping by nucleophiles will give quick access to xanthene, thioxanthene, and acridone derivatives. Oxidative coupling of pyridine N-oxides with arenes using MoX5 followed by an in-situ deoxygenation by the co-formed Mo(IV) will result in a versatile one-pot protocol to alkaloids like beta-carbolines. Most challenging will be the cross-coupling reaction. Herein, we will control the desired pathway by coordination of an additional Lewis acid which makes the most electron rich coupling component less prone to the initial oxidation step. The concept will allow a decoupling of oxidation potential from nucleophilicity to some extent, providing a general approach to cross-coupling reactions. For an understanding of the reaction pathways, and to optimize these in a rationale and efficient way, the knowledge of the mechanism will be crucial. Consequently, the detection of potential reactive intermediates of radical nature is envisioned by ESI-MS experiments of charged tag molecules. This allows the detection of neutral radical species. These experiments will be supported by calculations of intermediates and transition states of the coupling reaction on a DFT level. To optimize both, reactivity and selectivity the development of Mo(V) reagents with less or even no chlorido ligands is essential. This section will be treated in an associated project. In addition, to the recently reported complex Mo2Cl6(hfip)4 the preparation of further MoV complexes with stable fluorinated alkoxido ligands is envisaged. If the synthesis of halide-free Mo(V) alkoxido complexes, e.g. from fluorido complexes by substitution or from Mo2(hfip)6 by oxidation, is successful, an electrochemical C,C coupling using MoV as mediator should be feasible on a long term.