Oxidative coupling of arenes using molybdenum(V) reagents

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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.