Ar-Rh(III) pivalate complexes assembled in situ from the reaction of [RhCl(coe)2]2 (coe = cis-cyclooctene), [p-(CF3)C6H4]3P, and CsOPiv effectively catalyzed the direct C-arylation of free (NH)-indoles and (NH)-pyrroles in good yields and with high regioselectivity. The reaction displayed excellent functional group compatibility and low moisture sensitivity. Kinetics studies support a mechanism involving phosphine displacement by indole in complex 2 (resting state of the catalyst), followed by a rate-limiting C-H bond metalation.
The new air-stable PdCl2[PR2(Ph-R')]2 complexes, readily prepared from commercial reagents, exhibit unique efficiency as catalysts for the Suzuki-Miyaura coupling reactions of a variety of heteroatom-substituted heteroaryl chlorides with a diverse range of aryl/heteroaryl boronic acids. The coupling reactions catalyzed by the new complexes exhibit high product yields (88-99%) and high catalyst turnover numbers (up to 10,000 TON).
This paper describes a phosphine-free palladium-catalyzed method for direct C-arylation of free (N-H)-indoles and pyrroles with iodo-and bromoarene donors. Employing commercially available materials, this new and operationally simple procedure provides a rapid entry to a wide range of Carylated (N-H)-indoles including derivatives of tryptamine. In the course of this study, a profound halide effect was uncovered, affecting both the efficiency and regioselectivity of indole arylation.Many natural products and pharmaceuticals contain C-arylated azole core structures. Although palladium-catalyzed cross-coupling reactions provide an efficient entry to these compounds, such protocols require the preparation of functionalized heteroarenes (e.g., boronates and halides). 1 For this reason, considerable effort has been directed toward the development of Carylation reactions of azole and related heteroarenes via direct C-H bond functionalization of the parent heteroarenes. 2 Despite significant progress in this area, C-arylation of free (N-H)-indoles and pyrroles with haloarene donors remains an unsolved problem. One approach relies on the protection of the amine functionality prior to the palladium-catalyzed arylation step, either by formation of azole magnesium3 , 4 or azole zinc salts,5 or by installing the SEM protecting group [SEM = 2-(trimethylsilyl)-ethoxymethyl].6 Direct C-arylation of free indoles and pyrroles has recently been described with a rhodium catalyst and a mild base. 7 However, this system did not tolerate hindered substrates containing a substituent in the 3-position of indole or in the 2-position of the haloarene donor. [8][9][10] As part of our continuing efforts in the broad area of C-H bond functionalization, 11 we herein describe the development of a simple phosphine-free palladium catalytic system for the direct C-arylation of free indoles and pyrroles. This protocol not only obviates the protection of the N-H function, but also accommodates both ortho-substituted aryl donors and 3-substituted indoles, including tryptamine derivatives. On a strategic level, this method (as well as other catalytic C-H functionalization reactions) provides new approaches to complex heteroarenes, advantages of which are particulalry apparent in the context of preparation of a series of compounds, wherein established multistep methods become inefficient. 11 We have previously reported a catalytic system [Pd(OAc) with free (N-H)-indoles, closer examination revealed that the efficiency could be improved by increasing the substrate concentration. Specifically, the yield was nearly tripled, from 6% to 16% of 2-phenylindole, when the indole concentration was increased from 1.25 to 5.0 M (Table 1, entries 1 and 2). In addition to this concentration effect, we also found that phosphine ligands inhibited the reaction. 12 A representative collection of phosphine and carbene ligands, frequently used in arylation coupling chemistry, was examined (Table 1, entries 3-7). While the presence of the IPr carbene ligand had ...
Reaction of 5,5-dimethyl-8-nonene-2,4-dione catalyzed by PdCl2(CH3CN)2 (5 mol %) in the presence of CuCl2 (2.5 equiv) at room temperature for 3 h formed 2-acetyl-3,6,6-trimethyl-2-cyclohexenone in 96% isolated yield. Palladium-catalyzed intramolecular oxidative alkylation tolerated a range of substitution and was applicable to the synthesis of spirobicyclic compounds and to the cyclization of zeta-alkenyl beta-keto esters.
A new synthetic strategy that turns styrene-type olefins into excellent substrates for Rh-catalyzed asymmetric hydrogenation by installing a 2'-hydroxyl substituent is described. This methodology accommodates trisubstituted olefinic substrates in various E/Z mixtures, leading to valuable benzylic chiral compounds including (R)-tolterodine. It is also demonstrated that the 2'-hydroxyl groups could be readily removed in high yield without loss of ee from the products. Thus, this technology represents an attractive alternative to the Ir(P-N) catalyst system for the asymmetric hydrogenation of unfunctionalized olefins.
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