Cation-flow method

Figure 4.30 Electrochemical micro reactor, a diaphragm micro flow cell, applied to perform the cation flow method. Assembled device (left). Disassembled device showing the two compartments of the cell within the housings and the diaphragm (right) [67. ...

Concerning combinatorial operation, micro reactors can be operated in both a highly parallel a and fast serial manner. The latter approach has been realized for the cation flow method for C-C bond formation [66, 67]. 

Yoshida, J.-I., Cation Flow method a new approach to conventional and combinatorial organic syntheses using electrochemical micrqflow systems, J. Am. 

Cation Pool Method and Cation Flow 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 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... 

In the cation flow method an organic cation is generated continuously by low temperature electrolysis using an electrochemical microflow reactor. The cation thus generated is immediately allowed to react with a carbon nucleophile in the flow system. This method, in principle, enables the manipulation of highly reactive organic cations. 

A schematic diagram of the cation flow method for generating N-acyliminium ion 2 is shown in Fig. 5. A solution of carbamate 1 is introduced into the anodic compartment of electrochemical microflow cell, where oxidation takes place on the surface of a carbon fiber electrode. A solution of trifluoromethanesulfonic acid (TfOH) was introduced in the cathodic compartment, where protons are reduced to generate dihydrogen on the surface of a platinum electrode. A-Acyliminium ion 2 thus generated can be analyzed by an in-line FT-IR analyzer to evaluate the concentration of the cation. The solution of the cation is then allowed to react with a nucleophile such as allyltrimethylsilane in the flow system to obtain the desired product 3. 

Figure 5. Schematic diagram of the cation flow method.

An outstanding feature of the cation flow method is that the method enables continuous sequential combinatorial synthesis by simple flow switching as shown in Figure 6. In the first step, the cation flow generated from precursor A1 is allowed to react with nucleophile Bl. Then, the cation flow is allowed to react with the nucleophile B2. In the third step, the cation flow is allowed to react with nucleophile B3. Then, the precursor of the cation is switched to A2, and the cation flow generated from A2 is allowed to react with nucleophiles Bl, B2, and B3 sequentially. Then, the precursor of the cation is switched to A3, and the... 

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... 

Figure 4.3 Serial combinatorial synthesis based on the cation flow method. (a) Schematic diagram (b) example based on the reaction of N-acyliminium ion pools with carbon nucleophiles...

Figure 5.8 Electrochemical microflow reactor for the cation-flow method (a) outside (b) inside (anodic part). Copyright Wiley-VCH Verlag GmbH Co. KGaA. Reproduced with permission...

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