In Situ Alkyl Radical Recycling-Driven Decoupled Electrophotochemical Deamination

Abstract

Molecular electrophotocatalysis has emerged as a powerful strategy for the development of sustainable synthetic protocols. With the proof-of-concept, we exploited a versatile electrophotocatalytic deaminative alkylation approach. Mechanistic investigation indicated that in situ recycling of the alkyl radicals was the key point. Notably, ligand modification and late-stage functionalization of pharmaceuticals were also established, highlighting its feasibility in practical utilization.

Contemporary photoelectrochemical strategies and reactions in organic synthesis

“…In 2022, Chen, Liu, and Li collaborated to report an electro-photocatalysis promote alkyl radical cycling in situ for the alkylation of heteroarenes (Scheme 28(I)). 56 Using a reticulated vitreous carbon electrode at a potential of −1.4 V ( vs. Fc/Fc + ) and blue LEDs irradiation, heteroarene and Katritzky salts were alkylated under the photoelectrochemical conditions in the presence of catalytic Ru(bpy) 3 Cl 2 ·6H 2 O to obtain heteroarene alkylation products 10 . The reaction exhibits a surprisingly wide range of substrate suitability, including a wide variety of cycloalkanes, heterocyclic alkanes, straight chain alkanes and heteroarenes, and can also be used for ligand modification and late functionalization of bioactive scaffolds, which will have great potential for applications in the fields of pharmaceuticals, natural products and materials science.…”

Late‐Stage Functionalisation of Pyridine‐Containing Bioactive Molecules: Recent Strategies and Perspectives

“…Finally, using carboxylic acid 34 as the radical precursor, the merging of photocatalysis with electrochemistry has also enabled selective ortho ‐functionalisation, as reported for chlorantraniliprole 33 , an insecticide of the ryanoid classes (Scheme 11). [32] Electrophotochemical methods also enabled deaminative alkylation of pyridine‐containing drugs using Katritzky salts as radical precursors (see section 6 for Loratadine) [33] …”

Electrocatalytic synthesis: an environmentally benign alternative for radical-mediated aryl/alkenyl C(sp2)–C(sp3) cross-coupling reactions

“…In 2022, Chen et al employed primary amine derivatives ( pyridin-1-ium salts/Katritzky salts) as alkyl radical donors to realize the radical-mediated C(sp 2 )-C(sp 3 ) cross-coupling of N-heteroarenes by merging electrocatalysis and photocatalysis (Scheme 11). 29 Considering the electron-deficient nature of Katritzky salts, N-heteroarenes, and the cross-coupled products, the selective reduction of Katritzky salts is a critical step for orderly transformation. To circumvent the occurrence of undesired cathodic reduction events, constant-potential electrolysis (CPE) was selected to accurately control the reaction potential.…”