The Cation-pool Method

Tetrabutylammonium tetrafluoroborate (BU4NBF4) is usually used as a supporting electrolyte, and dichloromethane (CH2CI2) is suitable as the solvent because of its low viscosity at low temperatures. Trifluorometha-nesulfonic acid (CF3SO3H or TfOH) is added in the cathodic chamber to facilitate the reduction of protons in the cathodic process. It should be noted that both an anodic process and a cathodic process take place simultaneously in electrochemical reactions, and both processes should proceed smoothly to promote the overall reaction. 

After generation of a cation, a suitable nucleophile, such as an organic or organometallic compound, is added to the cation pool to accomplish a 

It is well known that oxidation of carbamates leads to the formation of N-acyliminium ions via dissociation of the C—H bond a to nitrogen. Electrochemical,metal-catalyzed,and chemical methods to accomplish this transformation have been reported in the literature. The transformation serves as a useful tool for organic synthesis, although only compounds of high oxidation potentials, such as methanol and cyanide ion, can be used as nucleophiles. It should be noted that N-acyliminium ions, which do not have a stabilizing group, had been considered to be only 

The following example illustrates how a cation pool of an N-acyliminium ion is generated and used for a subsequent reaction. Low-temperature electrolysis of pyrrolidine carbamate in BU4NBF4/CH2CI2 gives a solution of the corresponding N-acyliminium ion as a single species,as 

Alkoxycarbenium ions are widely utilized as reactive intermediates in 

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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. 

Figure 1. Schematic Diagram for the Cation Pool Method.

The W-acyliminium ion can be characterized by FTIR spectroscopy as well.9 The starting carbamate 1 exhibited an absorption at 1694 cm 1 due to the carbonyl stretching, while the V-acyliminium ion 2 generated by the cation pool method exhibited an absorption at 1814 cm 1. The higher wave number observed for the cation is consistent with the existence of a positive charge at the nitrogen atom adjacent to the carbonyl carbon. The shift to higher wave number is also supported by DFT (density functional theory) calculations. 

Af-Acyliminium ions are known to serve as electron-deficient 4n components and undergo [4+2] cycloaddition with alkenes and alkynes.15 The reaction has been utilized as a useftil method for the construction of heterocycles and acyclic amino alcohols. The reaction can be explained in terms of an inverse electron demand Diels-Alder type process that involves an electron-deficient hetero-diene with an electron-rich dienophile. Af-Acyliminium ions generated by the cation pool method were also found to undergo [4+2] cycloaddition reaction to give adduct 7 as shown in Scheme 7.16 The reaction with an aliphatic olefin seems to proceed by a concerted mechanism, whereas the reaction with styrene derivatives seems to proceed by a stepwise mechanism. In the latter case, significant amounts of polymeric products were obtained as byproducts. The formation of polymeric byproducts can be suppressed by micromixing. 

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. 

A typical example of the parallel synthesis based on the cation pool method is shown in Fig 4. A solution of a cation generated by low-temperature electrolysis is divided into several portions. To each portion, different nucleophiles are added to obtain products of different coupling combinations. 

Figure 4. Parallel combinatorial synthesis based on the cation pool" method.

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... 

Lewis acid-acetal complexes in NMR studies, but never detected alkoxycarbenium ions.29 The absence of alkoxycarbenium ions in the spectra, however, does not necessarily rule out their intermediacy in the reactions with nucleophiles. Therefore, it was imperative to accomplish the reactions of spectroscopically characterized, nonstabilized alkoxycarbenium ions with carbon nucleophiles. The cation pool method made it possible and opened a new chapter in the chemistry of alkoxycarbenium ions. 

The concept of electroauxiiiaiy is quite powerful to solve these problems. The pre-introduction of a silyl group as an electroauxiliary decreases the oxidation potential of dialkyl ethers by virtue of the orbital interaction. As a matter of fact, we demonstrated that the anodic oxidation of a-silyl ether took place smoothly in methanol.30 Selective dissociation of the C-Si bond occured and the methoxy group was introduced on the carbon to which the silyl group was attached. Therefore, a-silyl ethers seemed to serve as suitable precursors for alkoxycarbenium ions in the cation pool method. 

The alkoxycarbenium ions generated by the cation pool method react with various carbon nucleophiles such as substituted allylsilanes and enol silyl ethers to give the corresponding coupling products in good yields. It should be noted that the reactions of alkoxycarbenium ion pools with such nucleophiles are much faster than the Lewis acid promoted reactions of acetals with similar nucleophiles. A higher concentration of the cationic species in the cation pool method seems to be responsible. 

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... 

Recently, Yoshida and coworkers demonstrated that the cation pool method can be used to make available Ai-acyliminium ion intermediates for parallel synthesis approaches to molecular libraries [106]. In this work, the cation pool was split into separate flasks following the electrolysis reaction. Different nucleophiles were then added to each flask in order to form a series of products (Scheme 49). 

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