Copper-catalyzed homocoupling of ketoxime carboxylates for synthesis of symmetrical pyrroles

Abstract

A novel and efficient copper-catalyzed homocoupling of ketoxime carboxylates has been developed for the synthesis of symmetrical pyrroles. This reaction tolerates a wide range of functional groups and provides a synthetically useful process to synthesize valuable symmetrical pyrroles under mild conditions.

Synthesis of Highly Substituted Pyridines through Copper‐Catalyzed Condensation of Oximes and α,β‐Unsaturated Imines

“…In contrast, the reaction using parent chalcone 2 a ′′ afforded only a trace amount of 3 aa (entry 9). Note that the reaction of 2 a ′, when performed using a large excess (>2 equiv) of 1 a , was accompanied by homocoupling of 1 a to produce 2,5‐diphenyl‐3,4‐dimethylpyrrole as a byproduct, while this homocoupling was not observed at all in the optimized reaction systems (entries 1 and 8).…”

“…Besides the ionic pathway for the C−C bond formation, we cannot exclude an alternative pathway involving α‐imino radical C ′, which could be formed through homolytic N−Cu cleavage of C . Note that the radical C ′ and its dimerization were proposed for the copper‐catalyzed pyrrole‐forming homocoupling reaction of oxime acetate . Addition of C ′ to 2 and reduction/protonation of the resulting radical D ′ with Cu I /H + would eventually lead to the same pyridine product.…”

Recent developments in the group-1B-metal-catalyzed synthesis of pyrroles

“…This method tolerates a wide range of functionality (Scheme 10a). 15 Remarkably, they also achieved CuBrcatalyzed anti-Baldwin 5-endo-trig cyclization of ketoxime carboxylates for the synthesis of 2-arylpyrroles (Scheme 10b). 16 The reaction shows good functional group toleration and is an efficient protocol for rapid synthesis of valuable 2arylpyrroles under mild conditions.…”

Cu‐Catalyzed Heterocycle Synthesis

“…The reaction proceeded through C-H and N-H bond functionalization of enamides Cu/O 2 system [22]. They also developed an efficient CuBr-catalyzed homocoupling of ketoxime carboxylates for the synthesis of symmetrical pyrroles [23] …”