Article pubs.acs.org/joc
Copper(II)-Mediated Chelation-Assisted Regioselective N‑Naphthylation of Indoles, Pyrazoles and Pyrrole through Dehydrogenative Cross-Coupling Sourav Pradhan, Pinaki Bhusan De, and Tharmalingam Punniyamurthy* Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati-781039, India S Supporting Information *
ABSTRACT: A copper-mediated picolinamide directed regioselective cross-coupling of naphthylamines with azoles is developed via C−H functionalization and C−N bond formation. The reaction of indoles leads to the formation of chiral C−N cross-coupled products with functional group tolerance. These reaction conditions can also be extended to the cross-coupling of pyrazole and pyrrole scaffolds.
■
■
INTRODUCTION
RESULTS AND DISCUSSION First, our optimization studies commenced using N-(naphthalen-1-yl)picolinamide 1a as a test substrate with indole 2a using different copper salts, additives, bases, and solvents (Table 1). Gratifyingly, the reaction proceeded selectively to furnish the cross-coupled 3a in 10% conversion when the substrates 1a and 2a were stirred with 20 mol % CuCl2, 25 mol % Ag2CO3, 2 equiv of NMO, and 2 equiv of K3PO4 at 140 °C in DMSO under air (entry 1). Subsequent screening of the copper sources led to an increase to 95% conversion using Cu(OAc)2, whereas CuBr2, CuO, and CuI gave inferior results (entry 2−5). In a set of additives studied, Ag2CO3, Ag2O, and AgOAc, the former furnished the best results (entries 5−7). Among the bases examined, K3PO4 was superior to Na2CO3, K2CO3, and Cs2CO3 (entries 8−10). DMSO was found to be the solvent of choice, whereas DMF and NMP produced a trace amount (entries 11− 12). In the absence of NMO, 3a was formed in
