Electro‐Organocatalysis: Enantioselective α‐Alkylation of Aldehydes

Abstract

The asymmetric organocatalyzed α‐alkylation of aldehydes via a cationic radical enamine intermediate was performed under environmentally benign electro‐oxidation conditions without the use of chemical oxidants. To promote the desired α‐alkylation reaction of aldehydes, various aldehydes with xanthene or cycloheptatriene groups were exposed to electro‐organocatalytic conditions to afford optically active α‐substituted aldehydes (α‐alkylated aldehydes) in good yield. A reaction mechanism involving the cationic radical enamine was proposed based on the cyclic voltammetry (CV) results, DFT calculations, and control experiments.

Contributions of organic electrosynthesis to green chemistry

“…The authors propose on the basis of cyclovoltammetry and DFT calculations the coupling of a xanthene radical with an enamine cation radical, both are generated at the anode (Scheme 34) [63]. The combination of electrochemistry and asymmetric organocatalysis is demonstrated in a further example by a direct intermolecular a-arylation of aldehydes with aniline leading to a meta-alkylation; this selectivity cannot be achieved by a Friedel-Crafts reaction.…”

“…Anodic substitution of benzylic C-H bonds 1 [45,62].Scheme 34. Organocatalyzed anodic a-alkylation of aldehydes with xanthene[63].…”

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

“…Analogously, Jang also reported a method for α -alkylation of xanthene and cycloheptatriene through anodic enamine oxidation (Figure 32A, bottom). 492 …”

Aromatic Cations from Oxidative Carbon–Hydrogen Bond Cleavage in Bimolecular Carbon–Carbon Bond Forming Reactions

“…Indeed numerous examples of bimolecular reactions that proceed through oxidative carbon–hydrogen bond cleavage have been reported. The challenges of preparing cations that have a sufficient lifetime to engage in bimolecular reactions dictates that these transformations employ readily-oxidized substrates such as electron-rich alkenes, 4 isochromans and related alkoxybenzyl ethers, 5 xanthenes, 6 and amines, with tetrahydroisoquinolines being particularly common. 7 …”