Electrochemical Reduction of Ethyl 2-(2-(Bromomethyl)Phenoxy)Acetate at Carbon Cathodes in DMF Affected By the Presence of Oxygen
Authors: Ji Chang , Simon Tamir , Vasquez Antonio , Kelcher Austin , Olivares Jacob 
Published: May 2020

Many cyclic and bicyclic compounds have been synthesized by electrochemical means via direct reduction of various organic halides involving carbanion intermediates. For example, electrochemical cyclization of allylic α,ω-dibromides was accomplished for the synthesis of cycloalkadienes1 while reduction of dimethyl α,α′-dibromoalkanedioates at platinum cathodes in DMF could produce dimethyl 1,2-cylcoalkanedicarboxylates in relatively high yields.2 More interestingly, electrolyses of o-trichloroacetylanilides in acetonitrile at selected cathodic potentials would lead to different bicyclic products, depending upon the substituents on the imine group.3 Recently, our group studied the reduction of methyl 2-bromomethylbenzoate at carbon cathodes in DMF and found that the corresponding benzylic anions could be formed, which would undergo intramolecular cyclization in the presence of water to generate phthalide.4 Nevertheless, electrochemical methods are limited for the synthesis of heterocyclic compounds by direct reduction of organic halides, mostly due to the low product yields. Some haloalkenes can also be reduced to radicals to form different cyclic compounds.5,6 However, these processes often require various metal catalysts.

In this study, we examined the electrochemical reduction of ethyl 2-(2-(bromomethyl)phenoxy)acetate at carbon cathodes in dry DMF containing TMABF4 as the electrolyte. It was expected that the direct two-electron reduction of the substrate will cause the cleavage of carbon−bromine bond to give the corresponding carbanion, which may undergo nucleophilic attack on the carbonyl and the addition-elimination reaction could lead to the formation of a bicyclic product (chroman-3-one, 1, Scheme 1). On the contrary to this prediction, controlled-potential electrolyses of the substrate under argon generated a different bicyclic compound (ethyl 2,3-dihydro-1-benzofuran-2-carboxylate, 2) in a yield of approximately 20%, in addition to ethyl (2-methylphenoxy)acetate as the major product. Interestingly, in the presence of oxygen, the reduction of substrate would produce ethyl benzofuran-2-carboxylate (3) in a much higher yield of > 40%. Experimental evidences were shown that the reduction of oxygen played a significant role in the intramolecular cyclization initiated by electrogenerated bases. A possible reaction mechanism (Scheme 2) has been proposed accordingly and further discussed.

References

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2. M. Tokuda, A. Hayashi, and H. Suginome, Bull. Chem. Soc. Jpn., 64, 2590 (1991).

3. P. Molina, C. Conesa, and M. D. Velasco, Tetrahedron
Lett., 34, 175 (1993).

4. C. R. Allen, D. K. Brown, J. L. Potts, and C. Ji, J. Electrochem. Soc., 160, G3069 (2013).

5. D. M. Fang, D. G. Peters, and M. S. Mubarak, J. Electrochem. Soc., 148, E464 (2001).

6. E. Duñach, A. P. Esteves, M. J. Medeiros, D. Pletcher, and S. Olivero, J. Electroanal. Chem., 566, 39 (2004).

Figure 1