Organic cations pool” method

In the cation pool method organic cations are generated by electrochemical oxidation and are accumulated in a solution. In the next step, a suitable nucleophile is added to the thus-generated solution of the cation. In the cation flow method organic cations are generated by electrochemical oxidation using a microflow cell. The cation thus generated is allowed to react with a nucleophile in the flow system. 

Before discussing the concepts of the cation pool method and the cation flow method, let us briefly touch on generation methods of organic cations. 

The cation pool method is based on the irreversible oxidative generation of organic cations. In the first step, the cation precursor is oxidized via an electrochemical method. An organic cation thus generated is accumulated in the solution in the absence of a nucleophile that we want to introduce onto the cationic carbon. Counter anions which are normally considered to be very weak nucleophiles are used to avoid the nucleophilic attack on the cationic center. In order to avoid thermal decomposition of the cation, electrolysis should be carried out at low temperatures such as -78 °C. After electrolysis is complete, the nucleophile is then added to obtain the desired product. The use of a carbon nucleophile results the direct carbon-carbon bond formation. 

Carbocations, carbon radicals, and carbanions are important reactive carbon intermediates in organic chemistry and their interconversions could be effected, in principle, by redox processes. With the cation pool method at hand, we next examined the redox-mediated interconversions of such reactive carbon species. 

The cation pool method serves as a powerful tool for parallel combinatorial synthesis.25 Required for successful combinatorial synthesis are reactions of high generality to couple any desired combination of molecules we want. The cation pool method seems to be suitable for this purpose, because organic cations generated by this method are usually so highly reactive as to couple with a wide range of nucleophiles. 

The cation pool method enables easy manipulation of organic cation intermediates to achieve reactions with various nucleophiles, but its applicability strongly depends on the stability of the cation that is generated and accumulated. In order to solve this problem, the cation flow method using a microflow electrochemical system has been developed.9,27... 

The cation pool method and the cation flow method, which are based on low temperature electrochemical oxidation, have opened up a new chapter in the chemistry of organic cations, which have been considered to be difficult to manipulate in normal reaction media. The indirect cation pool method, which... 

The electrochemical method is also effective for the oxidation of heteroatom compounds. For example, oxidation of carbamates using a microflow electrochemical cell leads to the formation of N-acyliminium ion, which is allowed to react with various carbon nucleophiles such as allylsilanes in the flow system (Figure 7.5). This is a microflow version of the cation pool method, in which highly reactive organic cations are generated and accumulated in the absence of nucleophile and are allowed to react with nucleophiles in the next step [36-47]. The microflow version is called the cation flow method [48, 49]. The cation flow method can be applied, in principle, to more reactive and unstable organic cations, which are difficult to accumulate in a macro-scale batch system. 

The distannane mediated organic radical addition to A -acyliminium ions [13], and the benzylic radical addition to A/ -acyliminium ions which proceeds via radical/cation/radical cation chain mechanism [14] show that the cation pool can be utilized as good nucleophilic radical acceptors because of their strong electrophilic character. Iterative molecular assembly based on the cation pool method lead to the efficient formation of dendritic molecules [15]. The manipulation of the cation pool in the microflow system realized an efficient... 

However, the use of low-temperature electrochemical oxidation allows generation and storage of organic cations such as Af-acyliminium ions in a normal reaction medium such as dichloromethane in the absence of a nucleophile. This method is called the cation pool method (Fig. 7.4) [5-7]. 

The organic cations generated and accumulated by the cation pool method can be observed by nuclear magnetic resonance (NMR) spectroscopy or infrared spectroscopy (IR). A solution can contain organic cations at concentrations of 0.1-0.05 M. An iV-acyliminium ion generated by the cation pool method can be used for the Friedel-Crafts alkylation reaction of aromatic compounds. 

Yoshida J, SugaS (2002) Basic concepts of cation pool and catirai flow methods and their applications in conventional and combinatorial organic synthesis. Chem Eur J 8 2650-2658... 

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