A tutorial on asymmetric electrocatalysis

Abstract

Electrochemistry has emerged as a powerful means to enable redox transformations in modern chemical synthesis. This tutorial review delves into the unique advantages of electrochemistry in the context of asymmetric catalysis. While electrochemistry has historically been used as a green and mild alternative for established enantioselective transformations, in recent years asymmetric electrocatalysis has been increasingly employed in the discovery of novel asymmetric methodologies based on reaction mechanisms unique to electrochemistry. This tutorial review first provides a brief tutorial introduction to electrosynthesis, then explores case studies on homogenous small molecule asymmetric electrocatalysis. Each case study serves to highlight a key advance in the field, starting with the historic electrification of known asymmetric transformations and culminating with modern methods relying on unique electrochemical mechanistic sequences. Finally, we highlight case studies in the emerging reasearch areas at the interface of asymmetric electrocatalysis with biocatalysis and heterogeneous catalysis.

Fig. 1

Brief introduction to electrochemistry in organic synthesis.

Fig. 2

(A) Chemical and electrochemical conditions for the Sharpless Dihydroxylation. (B) Scheme for the mediated anodic regeneration of Os^VIII.

Fig. 3

Ni catalysed reductive cross electrophile coupling. (A) Périchon first developed an electrochemical approach for XEC followed by a chemical route. (B) The asymmetric XEC from Reisman was first enabled by metal reductant and then electrochemistry.

Fig. 4

(A) Electrochemical electrophile generation for enamine coupling. (B) Electrochemical synthesis of bicyclic β-aminoketones. (C) TEMPO-mediated selective amine oxidation for enamine coupling.

Fig. 5

(A) Desymmetrization of meso-diols to produce enantioenriched lactones using a chiral peptide catalyst. (B) Electrochemical protocol for desymmetrization allowed for tolerance of alkenes. (C) Mechanism of oxoammonium mediated alcohol oxidation.

Fig. 6

(A) Mechanism of dual-electrocatalytic asymmetric cyanation. (B) The cyanophosphinoylation developed by Lin and coworkers using diphenylphosphine oxide as phosphine source, 3 mol% Cu(OTf)₂ as catalyst, conducted electrolysis with felt(+) | Pt(−) in TFE and DMF mixture at 0 °C at a constant current of 3 mA for 2 F/mol (upper); hydrocyanation from the Lin lab utilizing PhSiH₃ as hydride source, 0.5 mol% Co(salen) and 5 mol% Cu(OTf)₂ as catalyst, and with DMF as solvent to perform the electrolysis at 0 °C with a constant cell voltage of 2.3 V for 10 h, with carbon felt(+) | Pt(−) (middle); Liu used 5 mol% Cu(MeCN)₄BF₄ and 5 mol% anthraquinone as electrophotocatalyst, which was activated by a 420 nm LED to conduct the electrolysis with RVC(+) | Pt/Ti(−) in a mixture of acetonitrile and 1,2-dichloroethane at 2–3 mA depending on the substrate (lower). (C) Ligand design and stereochemical model for sBOX ligands.

Fig. 7

Electrochemically enabled Lewis acid catalysis supresses homocoupling.

Fig. 8

(A) Enzymatic cascade for the asymmetric reductive amination with molecular nitrogen. (B) Cyclic voltammograms supporting catalytic turnover of nitrogenase and diaphorase with methyl viologen radical. Reprinted (adapted) with permission from Chen et. al., J. Am. Chem. Soc., 2019, 141, 4963–4971. Copyright 2019 American Chemical Society (C) Reaction condition screening through constant potential electrolysis in the presence of varying pyruvate concentrations. (D). Electrocatalytic ATP regeneration.

Fig. 9

Chiral electrodes for asymmetric electrosynthesis. (A) Chiral environment created by polymer coating. (B) Organocatalysts entrapped on electrode. (C) Chiral cavity encoded on electrode, reproduced from S. Butcha et. al., Nat. Commun., 2021, 12, 1314.

Fig. 10

(A) Electrochemical diol desymmetrization with unmodified GF and SPIROXYL modified GF electrodes. (B) Kinetic resolution of 1-phenylethanol using SPIROXYL. (C). 1-phenylethanol enantiomers display different current responses in cyclic voltammograms of (6R,7S,10R)-SPIROXYL (0.1 mM) in NaClO₄/CH₃CN (0.1 M) and 2,6-lutidine (3.2 mM) in the presence of R-PE or S-PE (1.6 mM) at a scan rate of 25 mV/s. Reproduced with permission from Kashiwagi et. al., Chem. Pharm. Bull. (Tokyo), 1999, 47, 1051–1052. Copyright 1999 The Pharmaceutical Society of Japan.