Cathodic Cross-Coupling Reaction of Aromatic Compounds Though SET Pathway Towards a Novel Biphenyl Synthesis
Authors: Qu Yang , Tateno Hiroyuki , Atobe Mahito 
Published: February 2020

Biaryls are considered as one of the useful organic compounds in the industry and medical fields. Owing to its perfect widely usefulness, the more convenient and efficient synthesis method of biphenyl compounds has attracted considerable interest in recent years. For the synthesis of biphenyl compounds, the cross-coupling reaction is one of the most efficient method. However, in general, it requires to use of expensive and harmful transition metal catalysts.1In addition, the harsh reaction temperature and the long reaction time are usually required.

 The global chemistry community has been addressing future-oriented research, innovation, and development towards environmentally-benign systems, processes, and products for the sustainable development of society. Under the consideration of these, electrooganic synthesis has turned out to be an attractive alternative to conventional methods, because it makes oxidation and reduction of organic compounds with no aid of redox reagents. Recently, the cross-coupling reactions via electrochemical process have been reported for the synthesis of biaryls. However, most of previous studies on electrochemical cross-coupling reactions based on the anodic oxidation process, and to our knowledge, cathodic cross-coupling reaction toward a biphenyl synthesis has been very limited so far.2

 Herein, we wish to report a novel cross-coupling reaction system based on electrochemical reduction of aryl halides without the use of transition metal catalysts. In the system, activation of aryl halides is accomplished by single electron transfer (SET) pathway as a key step, as shown in Scheme 1. By using this system, we successfully carried out that cathodic cross-coupling reactions between aryl halides and arenes in mild condition.

 The cathodic cross-coupling reaction was carried out in H-type divided cell. The catholyte was consist of 4-iodotoluene (0.09 M, 0.9 mmol), benzonitrile (2.7 M, 27 mmol), NaOt-Bu (0.18 M, 1.8 mmol), and tetrabutylammonium tetrafluoroborate (0.1 M, 1 mmol) in dimethylformamide (10 ml). The anolyte was consist of tetrabutylammonium tetrafluoroborate (0.1 M, 1 mmol) in dimethylformamide (10 ml). Pt electrodes (1.0 × 1.0 cm2) were used as working and counter electrodes. All experiments were performed at constant current method (20 mA cm-2) by passing through 1.0 F mol-1of electricity.

 In this work, the cathodic cross-coupling reaction between 4-iodotoluene and benzonitrile was employed as a model process (Scheme 2). The reaction was successfully achieved to provide corresponding coupling products with a moderate yield (38%).

 In addition, we performed cathodic cross-coupling reaction using other aryl halides and arenes to check the generality of this C,C bond forming reaction (Table 1). As shown in Entry 2, when anisole was used as an arene, the yield was improved. On the other hand, as shown in Entries 3 and 4, the introduction of electron-withdrawing groups on aryl halides also improved their reactivities, and the use of 1-chloro-4-iodobenzene led to provide the corresponding cross-coupling product with 55% yield.

Figure 1