Pd-Catalyzed Oxidative Coupling of Enamides and Alkynes for Synthesis of Substituted Pyrroles

Abstract

A novel and efficient palladium(II)-catalyzed alkenyl C-H activation oxidative annulation of enamides with alkynes for the synthesis of substituted pyrroles has been developed. The reaction tolerates a wide range of functional groups and is a reliable method for the synthesis of triaryl-substituted pyrroles in high yields.

Amides as Weak Coordinating Groups in Proximal C–H Bond Activation

“…Later, Guan and coworkers reported Pd‐catalyzed oxidative coupling of enamides and alkynes for the synthesis of substituted pyrroles (Scheme a). [39a] Similarly, the research groups of Wang and Pawar independently reported oxidative annulations of enamides with alkynes under Ru II and Co III catalysis conditions, respectively (Scheme a). [39b], [39c] They also obtained the synthetically useful N–H pyrroles with use of an identical catalytic system by fine‐tuning the reaction conditions.…”

“…This protocol uses [RhCp*Cl 2 ] 2 as a catalyst and sluggishly reactive aminopyridines as starting materials (Scheme b). [39d] Later, the research group of Glorius reported a unique rhodium(III)‐catalyzed, hydrazine‐directed C–H activation protocol for the synthesis of indoles . This protocol avoids the usage of external oxidant because it employs facile cleavage of the N–N bond as an oxidant.…”

Directing group-assisted transition-metal-catalyzed vinylic C-H bond functionalization

“…In 2014, Guan et al [39] reported the synthesis of pyrroles through oxidative annulation of enamides with alkynes employing Pd(OAc) 2 and Xantphos as the catalyst and ligand, respectively (Scheme 30). The transformation showed high functional group tolerance towards both sides.…”

Dehydrogenative Heck Annelations of Internal Alkynes

“…52 The efficiency of this oxidative coupling was greatly improved in the presence of a biphosphine ligand, in particular Xantphos. The DHA also proceeded with aliphatic alkynes, methyl phenyl alkyne leading to the two regioisomers.…”