Regioselective Electrochemical Construction of Csp2−Csp2 Linkage at C5−C5’ Position of 2‐Oxindoles via an Intermolecular Anodic Dehydrogenative Coupling

• Published in: Chemistry : a European journal 2024-12, Vol.30 (70), p.e202403420-n/a
• Main Authors: Shaheeda, Saina, Sharma, Sulekha, Mandal, Nilangshu, Shyamal, Pranay, Datta, Ayan, Paul, Amit, Bisai, Alakesh
• Format: Article
• Language: English
• Subjects: 2-oxindole; C5−C5’ homo-dimer; Coupling; Dehydrogenation; Density functional theory; DFT; Dimerization; Electricity; Electro-dehydrogenative coupling; Electrochemistry; Electrolysis; Organic chemistry; Oxidants; Oxidizing agents; Reagents; Regioselectivity
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202403420

Applying electricity as a reagent in synthetic organic chemistry has attracted particular attention from synthetic chemists worldwide as an environmentally benign and cost‐effective technique. Herein, we report the construction of the Csp2−Csp2 linkage at the C5−C5’ position of 2‐oxindole utilizing electricity as the traceless oxidant in an anodic dehydrogenative homo‐coupling process. A variety of 3,3‐disubstituted‐2‐oxindoles were subjected to dimerization, achieving yields of up to 70 % through controlled potential electrolysis at an applied potential of 1.5 V versus Ag/Ag+ nonaqueous reference electrode. This electro‐synthetic approach facilitates the specific assembly of C5−C5’ (para‐para coupled) dimer of 3,3‐disubstituted‐2‐oxindole without the necessity of any external oxidants or additives and DFT (Density Functional Theory) calculations provided confirmation of this pronounced regioselectivity. Furthermore, validation through control experiments and voltammetric analyses substantiated the manifestation of radical‐radical coupling (or biradical pathway) for the dimerization process. A highly regioselective electrochemical homo‐coupling strategy was developed for the synthesis of C5−C5’ dimer of 3,3‐disubstituted‐2‐oxindole. Control experiments and cyclic voltammetry (CV) studies confirmed that C−C bond formation occurs via a radical‐radical dimerization process. Density Functional Theory (DFT) studies validated the reaction mechanism and the observed high regioselectivity. The reaction conditions are mild and compatible with a wide range of functional groups.