Solvent-Controlled Switchable C–H Alkenylation of 4-Aryl-1H-pyrrole-3-carboxylates: Application to the Total Synthesis of (±)-Rhazinilam

Abstract

A solvent-controlled switchable C-H alkenylation of 4-aryl-1H-pyrrole-3-carboxylates via a Pd(OAc)2 catalyzed oxidative Heck reaction was first realized. The corresponding C2 and C5 alkenylation products were obtained in good yields with high regioselectivities, respectively. The selective C5-alkenylation was successfully applied to the total synthesis of (±)-rhazinilam.

Pd-Catalyzed Intermolecular Dehydrogenative Heck Reactions of Five-Membered Heteroarenes

“…The regioselectivity of the alkenylation of 4-aryl-1H-pyrrole-3-carboxylates is highly dependent on the solvent (Scheme 5) [69,70]. In benzene, assisted chelation by the carboxylate would favor the formation of 6A (Scheme 6).…”

Synthesis of Natural Products and Pharmaceuticals via Catalytic CH Functionalization

“…In 2014, Lin, Yao, and coworkers also synthesized rhazinilam by palladiumcatalyzed C-H functionalization (Scheme 16.13b) [29]. In their synthesis, pyrrole 75, which is slightly different from Gaunt's intermediate 72, was used.…”

Site‐Selective Oxidative C4 Alkenylation of (NH)‐Pyrroles Bearing an Electron‐Withdrawing C2 Group

“…The palladium‐catalyzed oxidative alkenylation of N‐protected pyrroles can be achieved regioselectively at the C2 or C5 position ,. Despite their pharmaceutical relevance and utility in chemical synthesis, pyrroles containing a C3 alkenyl group have largely been synthesized by cross‐coupling reactions requiring prefunctionalized alkenes .…”