Scope and Mechanism of the Pd^II‐Catalyzed Arylation/Carboalkoxylation of Unactivated Olefins with Indoles

Abstract

Treatment of 1-methyl-2-(4-pentenyl)indole (5) with a catalytic amount of [PdCl2(MeCN)2] (2; 5 mol %) and a stoichiometric amount of CuCl2 (3 equiv) in methanol under CO (1 atm) at room temperature for 30 min gives methyl (9-methyl-2,3,4,9-tetrahydro-4-carbazolyl)acetate (6), which was isolated in 83% yield. A number of 2- and 3-alkenyl indoles undergo a similar palladium-catalyzed cyclization/carboalkoxylation to give the corresponding polycyclic indole derivatives in moderate to excellent yields with excellent regio- and diastereoselectivity. Under similar conditions, vinyl arenes undergo intermolecular arylation/carboalkoxylation with indoles to give 3-(1-aryl-2-carbomethoxyethyl) indoles in moderate yield with high regioselectivity. Stereochemical analyses of the palladium-catalyzed cyclization/carboalkoxylation of both 2- and 3-alkenyl indoles are in agreement with mechanisms involving outer-sphere attack of the indole on a palladium-olefin complex followed by alpha-migratory insertion of CO and methanolysis of the resulting acyl palladium intermediate. CuCl2 functions as the terminal oxidant in this palladium-catalyzed cyclization/carboalkoxylation of alkenyl indoles and also significantly increases the rate of reaction of 2 with the alkenyl indole to form the corresponding acyl palladium complex. Spectroscopic studies are in agreement with the intermediacy of a heterobimetallic Pd/Cu complex as the active catalyst in this reaction.

Electrophilic Activation of Alkenes by Platinum(II): So Much More Than a Slow Version of Palladium(II)

“…(30)]. [112] Although a palladiumcatalyzed analogue of this reaction has not been demonstrated, palladium-catalyzed oxidative cyclizations of alkenylindoles terminated either by b-elimination [24,113] or by methoxycarbonylation [114] have been reported. Interestingly, stereochemical studies into a palladium system support a mechanism that consists of an indole C À H bond activation, syn insertion of the olefin, and b-hydride elimination, [24] in contrast to the mechanism of olefin activation in the platinum system.…”

Palladium(II)-Catalyzed Alkene Functionalization via Nucleopalladation: Stereochemical Pathways and Enantioselective Catalytic Applications

“…63 These reactions proceed under one atmosphere of CO and with 3 equivalents of CuCl 2 . The CuCl 2 is proposed to act as the stoichiometric oxidant to regenerate Pd II from Pd 0 .…”

Total Syntheses of Bisdehydroneostemoninine and Bisdehydrostemoninine by Catalytic Carbonylative Spirolactonization

“…Cyclopropanol 8 could be derived from tricyclic lactone 7 via a sequence of α-ethylation and Kulinkovich reaction. To quickly access tricyclic lactone 7 , inspired by the pioneering work of Yang [14] and Widenhoefer, [15] we envisioned a palladium-catalyzed oxidative tandem cyclization and carbonylative lactonization to convert allylic alcohol 6 to tricyclic lactone 7 . Additionally, in the long term, we wish to use the pyrrole-containing bisdehydroneostemoninine ( 1a ) to access the related non-pyrrole-containing natural products (cf.…”