TEMPO-Enabled Electrochemical Enantioselective Oxidative Coupling of Secondary Acyclic Amines with Ketones

Abstract

An electrochemical asymmetric coupling of secondary acyclic amines with ketones via a Shono-type oxidation has been described, affording the corresponding amino acid derivatives with good to excellent diastereoselectivity and enantioselectivity. The addition of an N-oxyl radical as a redox mediator could selectively oxidize the substrate rather than the product, although their oxidation potential difference is subtle (about 13 mV). This electrochemical transformation proceeds in the absence of stoichiometric additives, including metals, oxidants, and electrolytes, which gives it good functional group compatibility. Mechanistic studies suggest that proton-mediated racemization of the product is prevented by the reduction of protons at the cathode.

Merging the Non‐Natural Catalytic Activity of Lipase and Electrosynthesis: Asymmetric Oxidative Cross‐Coupling of Secondary Amines with Ketones

“…Based on the above experiments and literature, [33–38, 43–47] a possible mechanism was proposed (Figure 3). The reaction initiates with ACT oxidation at the anode to give ACT + .…”

“…Meanwhile, by‐product 4 formed from the oxidative self‐coupling of 1 a was isolated in 54 % yield. Since redox mediators can facilitate the oxidation process under milder reaction conditions at lower electrode potentials, [38] mediator screening was performed (Supporting Information, Tables S1 and S2). The results showed that the addition of 4‐acetamido‐2,2,6,6‐tetramethyl‐1‐piperidineoxy (ACT) could significantly inhibit the generation of 4 and improved the yield of 3 a to 52 %.…”

Asymmetric oxidative Mannich reactions promoted by photocatalysis and electrochemistry

“…The last example of this review comes from the research group of Mei (Scheme 25). 39 They reported an electrochemical oxidative asymmetric Mannich reaction of glycine esters with cyclic ketones, which was unprecedented. TEMPO was employed as a redox mediator in this study, effectively avoiding the excessive oxidation of the products.…”

The Utility of Oxoammonium Species in Organic Synthesis: Beyond Alcohol Oxidation

“…116 In 2021, Mei reported an electrochemical enantioselective Shono-type oxidative coupling of N-arylglycines with ketones using TEMPO as a mediator and β-proline as an organocatalyst. 117 Some cyclic amines can also be employed as the substrate (Scheme 16). Liu et al reported the diastereoselective oxidative alkynylation/allylation of 2-substituted tetrahydropyridines to give 2,6-disubstituted tetrahydropyridines.…”