Asymmetric Lewis Acid Catalyzed Electrochemical Alkylation

Abstract

Lewis‐acid catalysis and electrochemistry represent two powerful fields that have found widespread application in organic chemistry. Reported herein is an asymmetric electrosynthesis in combination with a chiral Ni catalyst leading to an intermolecular alkylation reaction in good yields with excellent enantioselectivities (up to 97 % ee). Mechanistic studies suggest that the Lewis‐acid‐bound radical intermediate from a single‐electron anodic oxidation selectively reacts with the benzylic radical species to generate the desired adducts.

Catalytic Asymmetric Electrochemical α‐Arylation of Cyclic β‐Ketocarbonyls with Anodic Benzyne Intermediates

“…Though the diastereoselectivity was low in these cases, both diasteroisomers were obtained with high enantioselectivity, indicating the arylation step is under strict catalytic control. The reaction worked well with cyclopentanone and in these cases the chiral primary amine catalyst 3 f was found to give better enantioselectivity (entries [8][9][10][11][12][13][14]. A free ketoamide could also be accommodated to afford the a-arylated adduct 4 ar (33 % yield, 84 % ee, entry 17).…”

“…[5] Anodic oxidation could be employed to in situ generate stabilized electrophilic species such as imine or iminium ion intermediates, in asymmetric aminocatalytic processes, as reported by the groups of Jørgensen [6] and Luo, [7] respectively. Recently, the groups of Meggers, [8] Guo, [9] and Lin [10] have also developed asymmetric catalysis with anodically generated free radical species. Despite these advances, the potential of asymmetric electrochemical catalysis remains largely unexplored.…”

Electrosynthesis 2.0 in 1,1,1,3,3,3‐Hexafluoroisopropanol/Amine Mixtures

“…Inspired by the benzyl-aryl coupling via HFIP ethers by Waldvogel et al, the Guo group developed an outstanding asymmetric nickel-catalyzed electrochemical alkylation. [39] Asymmetric induction is achieved through the radical-radical coupling of a chiral Ni(II) complex chelated radical with an electrochemically formed benzylic radical. The resulting alkylation products could be isolated in yields up to 85 % (22) and enantiomeric excess up to 97 % (23) (Scheme 6).…”

“…[35] Many more seminal applications of this powerful combination have been recently published and will be discussed within this review. [36][37][38][39][40]…”

Evolution of High‐Valent Nickela‐Electrocatalyzed C−H Activation: From Cross(‐Electrophile)‐Couplings to Electrooxidative C−H Transformations

“…In 2019, nickel-catalyzed electrochemical asymmetricC (sp 3 )ÀH functionalization was reported by Guo (Scheme 7). [52] Thus, an enantioselective a-benzylation of 2-acyl imidazoles 14 was realized with p-methylphenol derivatives 15 as the benzylation reagents under electrochemical conditions. The combination of Ni(OAc) 2 and ac hiral diamine ligand L3 served as at ypical Lewis-acid to deliver the benzylationp roducts 16 a-16 i in good yields and enantioselectivities.T he tailored design of substrates 14 called for a-aryl substituents at the ketones to enhancei ts acidity (pK aCÀH % 15-18 in DMSO) and activated toluene derivatives 15 with ab ond dissociation energy (BDE CÀH ) of % 80 kcal mol À1 )t og uarantee high efficacy.…”