Electrochemical Deconstructive Methoxylation of Arylalcohols-A Synthetic and Mechanistic Investigation

Abstract

Herein, we report a mechanistic investigation of a recently developed electrochemical method for the deconstructive methoxylation of arylalcohols. A combination of synthetic, electroanalytical, and computational experiments have been performed to gain a deeper understanding of the reaction mechanism and the structural requirements for fragmentation to occur. It was found that 2-arylalcohols undergo anodic oxidation to form the corresponding aromatic radical cations, which fragment to form oxocarbenium ions and benzylic radical intermediates via mesolytic cleavage, with further anodic oxidation and trapping of the benzylic carbocation with methanol to generate the observed methyl ether products. It was also found that the electrochemical fragmentation of 2-arylalkanols is promoted by structural features that stabilize the oxocarbenium ions and/or benzylic radical intermediates formed upon mesolytic cleavage of the aromatic radical cations. With an enhanced understanding of the reaction mechanism and the structural features that promote fragmentation, it is anticipated that alternative electrosynthetic transformations will be developed that utilize this powerful, yet underdeveloped, mode of substrate activation.

Keywords: Deconstructive functionalization; Mechanistic studies; Organic electrochemistry.

Scheme 1

Context of this Investigation.

Scheme 2

Mechanisms considered for C−C bond cleavage.

Scheme 3

Spin density plot, synthetic, and cyclic voltammetry studies. RSM=recovered starting material. Yields as determined by ¹H NMR analysis of the crude reaction mixture with 1,3,5‐trimethylbenzene as the internal standard. Spin density visualisation performed using GaussView 6.

Scheme 4

Investigation into S_N1‐ and S_N2‐like mechanisms. All energies in kcal/mol. Transition states were visualised in CYLview 1.0b.

Scheme 5

Relative stabilities of possible radical and carbocation fragments. All energies in kcal/mol.

Scheme 6

Deconstructive methoxylation of 2‐arylalcohols.

Scheme 7

Alternative substrate studies. All energies in kcal/mol.

Scheme 8

Investigation using 1‐arylalcohol substrates. N.D.=Not Determined. All energies in kcal/mol.