Arylation Of Indoles Research Articles

Regioselective direct arylation of indoles on the benzenoid moiety.

Recent advances in transition metal-catalyzed selective C-H functionalization of indoles have garnered tremendous attention. Great efforts have been devoted to C2 and C3 arylation because of the inherent reactivity of the pyrrole ring. Until recently, elegant methods have been developed to enable selective direct arylation on the benzenoid moiety at C4, C5, C6, and C7. This review highlights the contributions made in benzenoid direct arylation of indoles and presents their potential in organic synthesis.

Ruthenium(II)-Catalyzed Direct C-H Arylation of Indoles with Arylsilanes in Water.

The ruthenium(II)-catalyzed, heteroatom-directed C-H arylation of indoles with arylsilanes in water has been developed. The method represents the first example of a ruthenium(II)-catalyzed oxidative C-H arylation in water/aqueous media as a sustainable solvent for C-H functionalization. The reaction enables the synthesis of a wide range of indoles with exquisite selectivity for arylation at the C-2 position. Preliminary mechanistic studies indicate reversibility of the C-H ruthenation step under the developed reaction conditions.

Mechanism and selectivity of rhodium‐catalyzed CH bond arylation of indoles

AbstractDensity functional theory calculations are used to study the reaction mechanism and origins of C2‐selectivity in a rhodium‐catalyzed arylation of indole. It is shown that the reaction is catalyzed by an anionic Rh(III)‐intermediate that activates the substrate through a concerted‐metalation deprotonation. Dissociation of pivalic acid and subsequent reductive elimination generate the arylated indole product. Oxidative addition of the aryl iodide and a subsequent ligand exchange regenerates the active catalytic species. The origin of the regioselectivity is found to be the more favorable interaction between the 2‐indolyl fragment and the metal center compared to the 3‐indolyl fragment. Moreover, the better interaction of the pivalate ligands with the substrate in the transition state for the activation of C2H compared to the transition state for the C3H activation further favors the C2‐selectivity.

Organocatalytic asymmetric arylation of indoles enabled by azo groups.

Arylation is a fundamental reaction that can be mostly fulfilled by electrophilic aromatic substitution and transition-metal-catalysed aryl functionalization. Although the azo group has been used as a directing group for many transformations via transition-metal-catalysed aryl carbon-hydrogen (C-H) bond activation, there remain significant unmet challenges in organocatalytic arylation. Here, we show that the azo group can effectively act as both a directing and activating group for organocatalytic asymmetric arylation of indoles via formal nucleophilic aromatic substitution of azobenzene derivatives. Thus, a wide range of axially chiral arylindoles have been achieved in good yields with excellent enantioselectivities by utilizing chiral phosphoric acid as catalyst. Furthermore, highly enantioenriched pyrroloindoles bearing two contiguous quaternary chiral centres have also been obtained via a cascade enantioselective formal nucleophilic aromatic substitution-cyclization process. This strategy should be useful in other related research fields and will open new avenues for organocatalytic asymmetric aryl functionalization.

Highly Enantioselective Friedel–Crafts Reactions of Indoles with Isatins Catalyzed by Chiral Imidodiphosphoric Acids

AbstractA highly enantioselective Friedel–Crafts arylation of indoles with isatins catalyzed by H8‐1,1’‐bi‐2‐naphthol (BINOL) imidodiphosphoric acids is reported here. This reaction proceeds smoothly under mild conditions and afford a range of 3‐hydroxy‐3‐indolyloxindoles with high yields (<92 %) and excellent enantioselectivities (<99 % ee). To the best of our knowledge, this is the first example in which the highly enantioselective arylation of indoles with isatins has been catalyzed by a Brønsted acid.

Hydrothermal Synthesis of CuFe2O4 Magnetic Nanoparticles as Active and Robust Catalyst for N‐arylation of Indole and Imidazole with Aryl Halide

AbstractSpinel ferrite magnetic nanoparticles are superior to the conventional catalysts. Here we report the synthesis of different types of spinel ferrite nanoparticles, MFe2O4 (M= Cu, Mn, Mg, Co, Ni), by a hydrothermal method. The prepared spinel ferrite nanoparticles were used for the N‐arylation reaction of indole with iodobenzene. Among these CuFe2O4 nanoparticles exhibited the best activity and selectivity for N‐arylation under ligand free condition. The prepared spinel ferrite microspheres were well characterised by using various characterization techniques such as TEM, XRD, XPS, SEM, EDXA, FT‐IR, N2 adsorption desorption measurements and TGA. The effect of various parameters were studied such as solvent, base, speed of agitation, mole ratio, catalyst loading and temperature in the reaction of indole with iodobenzene. Best conversion and yield were achieved at 110 °C and 1×10‐3 g/cm3 catalyst loading. Notably, CuFe2O4 magnetic nanoparticles were completely recovered and could be reused six times without any noticeable loss of activity. Reaction mechanism and kinetics are also presented.

Regiocontrolled Direct C−H Arylation of Indoles at the C4 and C5 Positions

An effective and practical strategy has been established for the direct and site-selective arylation of indoles at the C4 and C5 positions with the aid of a readily accessible, cheap, and removable pivaloyl directing group at the C3 position. This transformation shows good functional-group tolerance and could serve as a powerful synthetic tool for the synthesis of medicinally relevant compounds. This method and those developed in previous research together enable the regiocontrolled direct arylation of indole at each C-H bond without prefunctionalization of the reactive sites.

Regiocontrolled Direct C−H Arylation of Indoles at the C4 and C5 Positions

AbstractAn effective and practical strategy has been established for the direct and site‐selective arylation of indoles at the C4 and C5 positions with the aid of a readily accessible, cheap, and removable pivaloyl directing group at the C3 position. This transformation shows good functional‐group tolerance and could serve as a powerful synthetic tool for the synthesis of medicinally relevant compounds. This method and those developed in previous research together enable the regiocontrolled direct arylation of indole at each C−H bond without prefunctionalization of the reactive sites.

Pyridylmethylamine–Palladium Catalytic Systems: A Selective Alternative in the C−H Arylation of Indole

AbstractA highly efficient pyridylmethylamine‐Pd alternative catalytic system for the C−H arylation of indole was explored. Variously substituted aryl groups were regio‐ and chemoselectively installed at the indole nucleus by using barium hydroxide as the base. The method was found to be efficient even in the presence of hindered coupling partners and Pd‐reactive bonds.

Cobalt(II)-Catalyzed Oxidative C-H Arylation of Indoles and Boronic Acids.

Co(II)-catalyzed C-H C2 selective arylation of indoles with boronic acids through monodentate chelation assistance has been achieved for the first time. The unique features of this methodology include mild reaction conditions, highly C2 regioselectivity, and employment of a Grignard reagent-free catalytic system. A wide range of substrates, including unreactive arenes, are well tolerated, which enables the construction of the coupling products efficiently. This new strategy provides an alternative and versatile approach to construct biaryls using inexpensive cobalt catalyst.

Easy access to 3-indolyl 1,1,2,2-ethanetetracarboxylates from malonates and indoles catalyzed by Pd(OAc)2

A novel dehydrodimerization of malonates with indoles has been developed, providing simple and rapid access to 3-indolyl tetramethyl 1,1,2,2-ethanetetracarboxylates. Pd(OAc)2-catalyzed ‘one pot’ C(sp2)–C(sp3) and C(sp3)–C(sp3) cross-dehydrogenative-couplings of malonates with a variety of 2-aryl indoles were involved. The titled compounds were obtained in high yields with good functional group tolerance.

ChemInform Abstract: Metal‐Free, C—H Arylation of Indole and Its Derivatives with Aryl Diazonium Salts by Visible‐Light Photoredox Catalysis.

AbstractA novel, general, efficient and environmentally benign synthesis 3‐arylindoles is developed.

Cu-Catalyzed Direct C6-Arylation of Indoles.

The first example of direct and site-selective arylation of indoles at the C6 position has been reported. The key to this high regioselectivity is the appropriate choice of the N-P(O)(t)Bu2 directing group and the use of diaryliodonium triflate salts as the coupling partners in the presence of catalytic CuO. The protocol is distinguished by mild reaction system that avoids ligand and additives, exhibiting wide scope of indole and arene coupling components without compromising its efficiency and scalability, thus representing a significant advancement in the implementation of regioselective direct arylation of indoles.

ChemInform Abstract: Palladium‐Catalyzed C—H Arylation of Indoles at the C7 Position.

AbstractKey to the regioselectivity is the choice of the phosphinoyl directing group and a pyridine‐type ligand in the presence of Pd(OAc)2 as catalyst.

ChemInform Abstract: Palladium‐Catalyzed Direct Arylation of Indoles with Arylsulfonyl Hydrazides.

A novel method to synthesise 2-arylindoles is demonstrated via direct arylation of indoles with arylsulfonyl hydrazides. Under the optimized reaction conditions, the reaction well tolerates a wide variety of functional groups to afford structurally diverse 2-arylindoles in good to excellent yields at 70 °C.

Metal-free, C–H arylation of indole and its derivatives with aryl diazonium salts by visible-light photoredox catalysis

In this Letter, we present the Rhodamine B catalyzed direct C–H arylation of indole with aryl diazonium salts. This method only requires green light and room temperature.

Direct Arylation of Indoles by Using Mesoporous Solid-Supported Palladium

Direct Arylation of Indoles by Using Mesoporous Solid-Supported Palladium

Palladium-Catalyzed C-H Arylation of Indoles at the C7 Position.

In the past decade, direct C-H arylation of indoles has been developed with high selectivity at the C2 and C3 positions via transition-metal-catalyzed cross-coupling reactions. Here we show that C-H activation can be directed to the C7 position with high selectivity in Pd-catalyzed coupling of indoles with arylboronic acids. The key to this high regioselectivity is the appropriate choice of a phosphinoyl directing group and a pyridine-type ligand in the presence of Pd(OAc)2 catalyst. This previously elusive transformation should provide insight for the design of other cross-couplings as well.

ChemInform Abstract: 3‐Naphthylindole Construction by Rhodium(II)‐Catalyzed Regioselective Direct Arylation of Indoles with 1‐Diazonaphthalen‐2‐(1H)‐ones.

AbstractThe Rh‐catalyzed arylation of indoles (I) with 1‐diazonaphthalenones (II) affords a series of 3‐naphthylindoles (III) in high yields.

Palladium-catalyzed direct arylation of indoles with arylsulfonyl hydrazides.

A novel method to synthesise 2-arylindoles is demonstrated via direct arylation of indoles with arylsulfonyl hydrazides. Under the optimized reaction conditions, the reaction well tolerates a wide variety of functional groups to afford structurally diverse 2-arylindoles in good to excellent yields at 70 °C.