Ni-Catalyzed Electrochemical Decarboxylative C–C Couplings in Batch and Continuous Flow

Abstract

An electrochemically driven, nickel-catalyzed reductive coupling of N-hydroxyphthalimide esters with aryl halides is reported. The reaction proceeds under mild conditions in a divided electrochemical cell and employs a tertiary amine as the reductant. This decarboxylative C(sp3)–C(sp2) bond-forming transformation exhibits excellent substrate generality and functional group compatibility. An operationally simple continuous-flow version of this transformation using a commercial electrochemical flow reactor represents a robust and scalable synthesis of value added coupling process.

Mechanisms of Nickel-Catalyzed Cross-Coupling Reactions

“…Organic reductants [e.g., tetrakis(dimethylamino)ethylene (TDAE)] can provide strong reducing power but are more expensive [62]. Electrochemical reduction has also been demonstrated with tertiary amines as the sacrificial reductants [63]. The major challenge of reductive couplings is achieving selectivity for cross-coupling of different electrophiles over homocoupling [64].…”

“…Oxidative and reductive quenching of light-excited photoredox catalysts by electrophiles and nucleophiles, respectively, have broadened the scope of radical precursors to trifluoroborate salts, carboxylates, silicates, and dihydropyridines [91]. Alkyl halides [92] and phthalimides [63] are versatile radical precursors that can be activated electrocatalytically, photocatalytically, and by transition metals. Oxalates have found utility in both transition-metal and photocatalytic reactions [93].…”

Electrochemical strategies for C–H functionalization and C–N bond formation

“…Furthermore, the refinement and expansion of reaction engineering methods and wider commercial availability of electrochemical reactors provide a multifaceted and powerful toolbox for efficient generation of reactive intermediates from an ensemble of organic substrates. These include, among others, the development of dual catalytic platforms (Scheme 133), [1000][1001][1002][1003][1004][1005][1006][1007] paired electrolysis [1008][1009][1010][1011][1012] (Scheme 134) and electrochemical flow cells, [1013][1014][1015][1016][1017][1018][1019] which have contributed to advancing the field of electrosynthesis. Based on these unique features and the current renaissance in synthetic electrochemistry, it is anticipated that this field will soon be considered as a reliable and versatile platform by the broader scientific community for nontraditional bond construction in organic chemistry.…”

Enantioselective Electroreductive Coupling of Alkenyl and Benzyl Halides via Nickel Catalysis

“…10 Bio and coworkers reported an electrochemical reductive coupling of aryl iodides with alkyl N-hydroxyphthalimide (NHP) esters in a divided cell, both in batch and in flow, with Et 3 N as the terminal reductant. 11 Loren and coworkers reported an electroreductive decarboxylative coupling of carboxylate salts and aryl iodides, proceeding through in situ generation of NHP esters. 12 The photochemical and electrochemical methods reported to date all employ an excess of one of the electrophiles and form products that are either achiral or racemic -with the exception of the aforementioned auxiliary-based examples.…”