Anodic Substitution Reaction of Cyclic Carbamates in Stable Nanoemulsion Solution Using a Flow Microreactor
Authors: Mikami Rio , Nakamura Yuto , Atobe Mahito 
Published: December 2020

Carbocations are important reactive intermediates in organic synthesis. Although a variety of reactions involving carbocations have been developed so far, nucleophilic reactions between chemically and electrochemically generated carbocations and nucleophiles have been widely utilized in organic synthesis1. Since carbocations are usually unstable intermediates, the oxidative generation of carbocations often has to be conducted in the presence of nucleophiles so that the nucleophile can trap the carbocation immediately as it is generated. However, the oxidation potentials of the nucleophiles are usually lower than those of the corresponding organic substrates, and therefore the presence of nucleophiles would prevent oxidation of organic substrates. In this regard, introduction of an electro-auxiliary into substrates2and the “cation pool” method3have been developed, but thesenecessarily include multi-step reactions.
In order to overcome this problem, we developed a novel electrolytic system for anodic substitution reactions using acoustic emulsification in our previous work4. In this system, the substrate is predominantly oxidized to give corresponding carbocation intermediate because the acoustically emulsified nucleophile phase which is insoluble in an electrolytic medium is electro-inactive.
In this work, we have tried to improve further the current efficiency of this reaction system by using a flow microreactor which offers advantages such as large specific interfacial area and precise control of reaction time. Moreover, the emulsion electrolytic solution was prepared by sequential ultrasonic irradiations in order to stabilize the emulsion droplets before the electrolysis in a flow microreactor5.
We chose an anodic substitution reaction of N-(methoxycarbonyl) pyrrolidine (oxidation potential E
ox = 1.91 V vs. Ag/AgCl) as a substrate with allyltrimethylsilane (oxidation potential E
ox = 1.75 V vs. Ag/AgCl) as a nucleophile for the model reaction (Scheme). We prepared a stable two-phase emulsified solution composed of ionic liquid [EMIM] [BF4] phase containing the substrate and nucleophile phase by sequential ultrasonication with 1.6 MHz treatment after 20 kHz ultrasonication. This solution was introduced into an electrolytic flow microreactor using a syringe pump, and then galvanostatically electrolyzed (Figure).
Especially in this work, we have investigated the effect of four parameters (nucleophile amount, electrode distance, flow rate and current density) on the current efficiency of desired product and determined the best electrolysis condition in a flow microreactor. As a result, it was confirmed that the current efficiency (38％) was much higher compared with that obtained by the use of a batch type reactor (13%).
References
1) Moeller, K. D. Tetrahedron, 2000,56, 9527.
2) Yoshida, J.; Sugawara, M. et. al. J. Org. Chem.
1998, 63, 5950.
3) Yoshida, J.; Suga, S. et. al. J. Am. Chem. Soc.
1999, 121, 9546.
4) Asami, R.; Fuchigami, T.; Atobe, M. Chem. Commun. 2008, 244.
5) Nakabayashi, K.; Atobe, M. et. al. Chem. Commun.
2011. 47. 5765

Figure 1