Understanding the Reactivity of Enol Ether Radical Cation: Investigation of Electrochemical [2 + 2] Cycloaddition Reactions

Electrochemical process has proven to be powerful tool to form carbon-carbon bond and has widely used to construct various carbon skeletons. Especially, the electrochemical carbon-carbon bond forming reactions have demonstrated to afford complicated ring systems effectively, including naturally occurring compounds. For example, enol ether radical cations are readily produced in anodic oxidations of enol ethers and provide versatile reactive intermediates. This reaction is synthetically intriguing due to the umpolung process that polarity of nucleophilic enol ethers is reversed to give enol ether radical cations which function as electrophilic species.

  We have developed the electrochemical reactions in lithium perchlorate/nitromethane (LPC/NM) electrolyte solution, which exhibits a remarkable accelerating property as a Lewis acid catalyst and stabilize carbocation intermediates. The feature of LPC/NM allows facile synthesis of biologically relevant compounds, such as dihydrobenzofuran derivatives¹ and azanucleoside derivatives.² In LPC/NM, unactivated olefins can serve as efficient nucleophiles to trap anodically generated cationic species. In this context, we also have developed electrochemical [2 + 2] cycloaddition reactions between enol ethers and unactivated olefins, affording cyclobutane products(Scheme 1).³ The reaction was initiated by anodic oxidation of enol ether (1) and thus generated enol ether radical cation (2) was trapped by unactivated olefin nucleophile to give transient cyclobutyl radical cation (3). In order for successful cyclobutane formation, electron rich aromatic ring was required as an electron donor to form relatively long lived aromatic ring radical cation (4), which was finally reduced by cathode or starting enol ether, affording neutral cycloadduct (5) (Scheme 2).

Although our previous work have focused on the use of enol ether (1) for electrochemical [2 + 2] cycloaddition reactions, the reactivity of enol ether radical cation (2) still remains unclear. To investigate the reactivity of such enol ether radical cations, we designed and synthesized several types of new substrates and then subjected them to the electrochemical [2 + 2] cycloaddition reactions(Scheme 3). Synthetic and mechanistic details would be discussed in the presentation.

Reference

(1) Kim, S.; Hirose, K.; Uematsu, J.; Mikami, Y.; Chiba,K. Chem.–Eur. J. 2012, 18, 6284–6288.

(2) Kim, S.; Shoji, T.; Kitano, Y.; Chiba, K. Chem. Commun. 2013, 49, 6525–6527.

(3) (a) Yamaguchi, Y.; Okada, Y.; Chiba, K. J. Org. Chem., 2013, 78, 2626–2638. (b) Yamaguchi, Y.; Okada, Y.; Chiba, K. Electrochemistry 2013, 81, 331–333 and references therein.