Palladium on Carbon‐Catalyzed One‐Pot N‐Arylindole Synthesis: Intramolecular Aromatic Amination,Aromatization, and Intermolecular Aromatic Amination

Indole and indoline derivatives were selectively and temperature dependently synthesized via the intramolecular cross‐coupling reaction between the amino and aromatic bromine functionalities of 2‐bromophenethylamine derivatives in the presence of 10% palladium on carbon (Pd/C), 1,1′‐bis(diphenylphosphino)ferrocene (DPPF), and sodium tert‐butoxide (NaO‐t‐Bu) in mesitylene at 140 and 200 °C, respectively. The neutralization using acetic acid after formation of the indoline derivatives effectively promoted their aromatization, and the corresponding indole derivatives were obtained at 140 °C. Furthermore, various aryl groups were also introduced to the N‐1 position of the indole, pyrrole, and carbazole rings by their direct intramolecular arylation with aryl halides and a one‐pot protocol for N‐arylindole synthesis from 2‐bromophenethylamine was developed.

     

A General and Practical Palladium‐Catalyzed Direct α‐Arylation of Amides with Aryl Halides

An efficient system for the direct catalytic intermolecular α‐arylation of acetamide derivatives with aryl bromides and chlorides is presented. The palladium catalyst is supported by Kwong’s indole‐based phosphine ligand and provides monoarylated amides in up to 95% yield. Excellent chemoselectivities (>10:1) in the mono‐ and diarylation with aryl bromides were achieved by careful selection of bases, solvents, and stoichiometry. Under the coupling conditions, the weakly acidic α‐protons of amides (pK_a up to 35) were reversibly depotonated by lithium tert‐butoxide (LiO‐t‐Bu), sodium tert‐butoxide (NaO‐t‐Bu) or sodium bis(trimethylsilyl)amide [NaN(SiMe₃)₂].

     

Novel Palladium‐on‐Carbon/Diphenyl Sulfide Complex for Chemoselective Hydrogenation: Preparation,Characterization, and Application

A diphenyl sulfide immobilized on palladium‐on‐carbon system, Pd/C[Ph₂S], was developed to achieve the highly chemoselective hydrogenation of alkenes, acetylenes, azides, and nitro groups in the presence of aromatic ketones, halides, benzyl esters, and N‐Cbz protective groups. Instrumental analyses of the heterogeneous catalyst demonstrated that diphenyl sulfide was embedded on Pd/C via coordination of its sulfur atom to palladium metal or physical interaction with graphite layers of the activated carbon. The catalyst could be recovered and reused at least five times without any significant loss of the reactivity.     

Toward a Continuous‐Flow Synthesis of Boscalid®

A two‐step continuous‐flow protocol for the synthesis of 2‐amino‐4′‐chlorobiphenyl, a key intermediate for the industrial preparation of the fungicide Boscalid^® is described. Initial tetrakis(triphenylphosphine)palladium‐catalyzed high‐temperature Suzuki–Miyaura cross‐coupling of 1‐chloro‐2‐nitrobenzene with 4‐chlorophenylboronic acid in a microtubular flow reactor at 160 °C using the tert‐butanol/water/potassium tert‐butoxide solvent/base system provides 4′‐chloro‐2‐nitrobiphenyl in high yield. After in‐line scavenging of palladium metal with the aid of a thiourea‐based resin, subsequent heterogeneous catalytic hydrogenation is performed over platinum‐on‐charcoal in a dedicated continuous‐flow hydrogenation device. The overall two‐step homogeneous/heterogeneous catalytic process can be performed in a single operation providing the desired 2‐amino‐4′‐chlorobiphenyl in good overall yield and high selectivity.     

Oxime Palladacycle‐Catalyzed Suzuki–Miyaura Alkenylation of Aryl,Heteroaryl, Benzyl,and Allyl Chlorides under Microwave Irradiation Conditions

A simple new protocol for the palladium‐catalyzed Suzuki–Miyaura cross‐coupling of organic chlorides under microwave irradiation is presented. Deactivated aryl and heteroaryl chlorides are efficiently cross‐coupled with alkenylboronic acids and potassium alkenyltrifluoroborates using the 4,4′‐dichlorobenzophenone oxime‐derived palladacycle 1b as precatalyst in 0.1 to 0.5 mol% palladium loading, tris(tert‐butyl)phosphonium tetrafluoroborate {[HP(t‐Bu)₃]BF₄} as ligand, tetra‐n‐butylammonium hydroxide as cocatalyst, and potassium carbonate as base in N,N‐dimethylformamide at 130 °C under microwave irradiation conditions. Under these conditions, styrenes, stilbenes, and alkenylarenes are obtained in good to high yields, and with high regio‐ and diastereoselectivities in only 20 min. The reported protocol is also very efficient for the regioselective alkenylation of benzyl and allyl chlorides to afford allylarenes and 1,4‐dienes.     

Highly Active and Selective Semihydrogenation of Alkynes with the Palladium Nanoparticles‐Tetrabutylammonium Borohydride Catalyst System

Palladium nanoparticles are prepared from palladium(II) acetate and 2 equivalents of potassium tert‐butoxide in the presence of 4‐octyne. The palladium nanoparticles‐tetrabutylammonium borohydride system shows excellent catalytic activity and selectivity in the semihydrogenation of alkynes to the [(Z)‐]alkenes. The hydrogenation of 4‐octyne is conducted with the catalyst system at a substrate‐to‐palladium molar ratio of 10,000–200,000 under 8 atm of hydrogen to give (Z)‐4‐octene in>99% yield. Isomerization and over‐reduction of the Z‐alkene are very slow even after consumption of the alkyne.     

Palladium on Carbon‐Catalyzed Cross‐Coupling using Triarylbismuths

Simple and efficient protocols for the 10% palladium on carbon (Pd/C)‐catalyzed cross‐coupling reactions between triarylbismuths and aryl halides have been developed. A variety of iodo‐ and bromobenzenes possessing an electron‐withdrawing group on the aromatic nucleus were smoothly cross‐coupled in the presence of 10% Pd/C, sodium phosphate dodecahydrate (Na₃PO₄⋅12 H₂O) and 1,4‐diazabicyclo[2.2.2]octane (DABCO) in heated N‐methyl‐2‐pyrrolidone (NMP) as the solvent. For the arylations of iodobenzenes, the reactions effectively proceeded under the combined use of caesium fluoride (CsF) and 2,2′‐biquinoline. Furthermore, a ligand‐free 10% Pd/C‐catalyzed cross‐coupling reaction between the aryl iodides and triarylbismuths was also established by the addition of tetra‐n‐buthylammonium fluoride trihydrate (TBAF⋅3 H₂O) in which the palladium metals were hardly leached from the catalyst into the reaction media.     

Palladium‐Catalyzed N‐Arylation of N,N‐Dialkylhydrazines with Aryl Chlorides

N,N‐Dialkyl‐N′‐arylhydrazines have been prepared usually in high to excellent yields via the reaction of N,N‐dialkylhydrazines with aryl chlorides in the presence of Pd₂(dba)₃, Xphos and NaO‐t‐Bu in dioxane at 120 °C. With ortho‐substituted aryl chlorides best results have been obtained by using 2‐(2′,6′‐dimethoxybiphenyl)dicyclohexylphosphine (ligand d) as the ligand.     

Palladium‐Catalyzed,Highly Efficient,Regiocontrolled Arylation of Electron‐Rich Allylamines with Aryl Halides

The highly efficient and regioselective palladium‐catalyzed Heck coupling of aryl bromides with electron‐rich allylamine derivatives is described. It was found that the choice of solvent, olefin, ligand and additive had a fundamental influence on the regioselectivity and reactivity of the reaction. The combination of palladium acetate [Pd(OAc)₂] and 1,3‐bis(diphenylphosphino)propane (dppp) in ethylene glycol (EG) constitutes a highly effective catalyst system for internal arylation of N‐Boc‐allylamine (tert‐butyl methyl allyliminodicarbonate) with aryl bromides to give good to excellent regioselectivities, while the catalyst system consisting of Pd(OAc)₂, tetrabutylammonium bromide (TBAB) and 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) additive allows for a variety of aryl bromides to react efficiently with N,N‐(Boc)₂‐allylamine (di‐tert‐butyl allyliminodicarbonate) in water to exclusively afford the linear (E)‐allylamine products in high yields.     

Palladium‐Catalyzed Divergent Arylation with Triazolopyridines: One‐Pot Synthesis of 6‐Aryl‐2‐α‐styrylpyridines

We have developed a new strategy for palladium‐catalyzed arylation reactions with triazolopyridines, wherein two different chemical transformations (C‐3 vs. C‐7) are observed by differentiating the substrates using different bases. The reactive palladium carbenoids were directly generated from triazolopyridines and underwent denitrogenative arylations with aryl bromides. Intriguingly, when potassium carbonate was replaced with potassium tert‐butoxide, direct C H arylation occurred at the most acidic position (C‐7). Moreover, two different catalytic arylation events were successfully performed in a one‐pot sequence, providing a convenient access to 6‐aryl‐2‐α‐styrylpyridines.

     

Iron‐Catalyzed Mizoroki–Heck Cross‐Coupling Reaction with Styrenes

In the presence of iron(II) chloride (FeCl₂; 20 mol%) and potassium tert‐butoxide (t‐BuOK; 4 equiv.) in dimethyl sulfoxide (DMSO), aryl and heteroaryl iodides undergo stereoselective Mizoroki–Heck C C cross‐coupling reactions with styrenes at 60 °C giving the corresponding (E)‐alkenes. The best yields are obtained upon adding a ligand (80 mol%) such as proline or picolinic acid. Aryl bromides and pyridinyl bromides are also coupled with styrenes but in lower yields.     

Organocatalyzed Dynamic Kinetic Resolution

In the last decade, the first examples of organocatalyzed dynamic kinetic resolution (DKR) processes have been described, considerably expanding the synthetic scope of this powerful process which allows the resolution of racemic compounds with up to 100% yield. Today, a significant number of chiral organocatalysts are available that afford excellent levels of stereocontrol in various reactions evolving through DKR that could only previously be achieved using biocatalysts. The goal of the present review is to cover the works dealing with organocatalytic reactions evolving through DKR. This review is subdivided into four sections, according to the different types of organocatalysts employed in these reactions, such as Cinchona alkaloid catalysts, catalysts derived from amino acids, hydroxy acid catalysts, and miscellaneous organocatalysts. Abbreviations: Ac: acetyl; Ar: aryl; BINOL: 1,1′‐bi‐2‐naphthol; Bn: benzyl; Bu: butyl; c: cyclo; Cbz: benzyloxycarbonyl; CPME: cyclopentyl methyl ether; Cy: cyclohexyl; DABCO: 1,4‐diazabicyclo[2.2.2]octane; de: diastereomeric excess; DKR: dynamic kinetic resolution; DMF: dimethylformamide; Dmpe: 1,2‐bis(dimethylphosphino)‐ethane; DMSO: dimethyl sulfoxide; DYKAT: dynamic kinetic asymmetric transformation; ee: enantiomeric excess; Et: ethyl; Fmoc: 9‐fluorenylmethoxycarbonyl; Fu: furyl; Me: methyl; MTBE: methyl tert‐butyl ether; Naph: naphthyl; Pent: pentyl; Ph: phenyl; PMP: p‐methoxyphenyl; Pr: propyl; TBHP: tert‐butyl hydroperoxide; TEA: triethylamine; THF: tetrahydrofuran; Thio: thiophene; TMS: trimethylsilyl; Tol: tolyl.     

Catalytic syn‐Selective Direct Aldol Reactions of Benzophenone Glycine Imine with Aromatic,Heteroaromatic and Aliphatic Aldehydes

We have developed highly diastereoselective silver‐catalyzed direct aldol reactions of benzophenone glycine imines with aromatic, heteroaromatic and aliphatic aldehydes. Protection of the secondary alcohol in the aldol product in situ with di‐tert‐butyl dicarbonate was applied to effectively circumvent the retro‐aldol process resulting in improved yields of the aldol products. Only a catalytic amount of base, lithium tert‐butoxide, is required since tert‐butoxide is regenerated during the Boc protection. Computational studies support a stereochemical model in which the axially‐oriented nitrogen atom of the imino (Z)‐enolates coordinates the silver center in a boat conformation. The highly‐ordered transition states favor the formation of the syn aldol products due to the destabilizing interaction between the 1,3‐pseudoaxial alkoxyl group and the aldehyde substituent in the anti isomer.

     

Base‐Mediated Direct Arylation of Pyrrole Derivatives

It appears that transition metal catalysts are not necessary to perform the direct arylation of electron‐rich heterocycles with aryl iodides and bromides. Lithium tert‐butoxide in DMF promotes this reaction for a variety of N‐alkyl‐ and N‐arylpyrroles as well as for benzofuran and some other electron‐rich aromatic compounds and provides the desired products in moderate to high yields. In contrast to all previous reports on the Pd‐catalyzed direct arylation of indolizine, the reaction mediated by lithium tert‐butoxide proceeds selectively at position 5.     

Palladium(II)‐Catalyzed Direct ortho‐C?H Acylation of Anilides by Oxidative Cross‐Coupling with Aldehydes using tert‐Butyl Hydroperoxide as Oxidant

An efficient palladium‐catalyzed C H acylation with aldehydes using tert‐butyl hydroperoxide (TBHP) transforms various anilides into synthetically useful 2‐aminobenzophenone derivatives under mild conditions (40 °C, 3 h). The acylation reaction exhibits excellent regioselectivity and functional group tolerance, and simple aromatic aldehydes, functionalized aliphatic aldehydes and heteroaromatic aldehydes are effective coupling partners. The acylation reaction is probably initiated by a rate‐limiting electrophilic C H cyclopalladation (k_H/k_D=3.6; ρ⁺=−0.74) to form an arylpalladium complex, followed by acyl radical functionalization.     

Palladium‐Catalyzed Heck‐Type Reactions of Allylic Esters with Arylboronic Acids or Potassium Aryltrifluoroborates

A selective and general route to (E)‐1,3‐diaryl‐prop‐1‐enes and (E)‐3‐arylallyl acetates has been developed by palladium‐catalyzed Heck‐type reactions of allylic esters with arylboronic acids or potassium aryltrifluoroborates. The present method selectively proceeds including β‐OAc elimination or β‐H elimination on the basis of the boronic acids. Whereas a variety of allylic esters were reacted with arylboronic acids, palladium(II) acetate [Pd(OAc)₂], tetra(n‐butyl)ammonium chloride [(n‐Bu)₄NCl] and postassium dihydrogen phosphate (KH₂PO₄) to afford the corresponding diarylation products in moderate to good yields, treatment of allylic esters with potassium aryltrifluoroborates furnished the corresponding monoarylation products.     

Control of Polymer Composition in Pd‐Catalyzed CO/Olefin Terpolymerization Reactions

The CO/tert‐butylstyrene/ethylene terpolymerization catalyzed by Pd‐(N‐N′) complexes was studied. The results evidence that the olefin preferentially inserted in the terpolymer chain is strictly related to the nature of the nitrogen ligand, mainly to its steric constraints, and not to the kind of ligand. Indeed, slight variations in the backbone of the nitrogen ligands coordinated to palladium allow for the synthesis of terpolymers with a controlled composition.     

Effect of cross‐linker on morphology,catalytic activity,and recyclability of immobilized palladium chloride

Two kinds of immobilized palladium (Pd) catalysts were prepared by reversible addition fragmentation chain transfer polymerization of pyridine‐containing monomer followed by immobilizing palladium chloride (PdCl₂) on block copolymers. Namely, one of them includes the cross‐linking structure of maleic anhydride with 1,6‐diaminohexane (cross‐linker), polystyrene‐block‐poly(4‐(4‐vinylbenzyloxy)butylpicolinate‐alt‐maleic anhydride)‐Pd (PS‐b‐P(VBP‐alt‐MAn)‐Pd), and the other is its non‐cross‐linking counterpart, polystyrene‐block‐poly(4‐(4‐vinylbenzyloxy) butylpicolinate)‐Pd (PS‐b‐PVBP‐Pd). From transmission electron microscopy images, it could be observed that they both assembled into micelles in the selective solvents. The Pd of PS‐b‐P(VBP‐alt‐MAn)‐Pd located in the core of micelles, whereas the Pd of PS‐b‐PVBP‐Pd was on the shell of the micelles. The PS‐b‐P(VBP‐alt‐MAn)‐Pd can be continuously used for five times without any appreciable loss of activity in the aqueous Suzuki‐coupling reaction. However, the catalytic activities of the PS‐b‐PVBP‐Pd decreased sharply with the increase in the recycle times. Thus, this promising cross‐linking strategy not only greatly restrained the loss of Pd in the catalytic cycles, but also effectively maintained the immobilized Pd catalyst's high activity. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Potassium tert‐Butoxide‐Mediated Amine Acyl Exchange Reaction of N,N‐Disubstituted Formamides with Aromatic Carbonyl Derivatives via Sequential C?N Bond Cleavage/Formation: an Approach to Aromatic Amides

A novel potassium tert‐butoxide‐mediated amine acyl exchange of N,N‐disubstituted formamides with aromatic carbonyl derivatives in a sequential C N bond cleavage/formation process leading to aromatic amides is described. This methodology tolerates a wide range of aromatic carbonyl compounds, including aromatic aldehydes, acyl chlorides, unactivated esters, and acid anhydrides. The usage of inexpensive and readily available reagents, broad substrate scope, and the simple, mild (50 °C) and transition metal‐free conditions make this protocol very practical. In addition, a plausible reaction mechanism is proposed on the basis of experimental observations.

     

Alternating copolymerization and terpolymerization of vinyl‐substituted phenolic antioxidants with propene and carbon monoxide by a palladium(II)‐based catalyst: polyketones containing intramolecular stabilizers

The copolymerization and terpolymerization reactions of the vinyl‐substituted phenolic stabilizers, 6‐tert‐butyl‐2‐(1,1‐dimethylhept‐6‐enyl)‐4‐methylphenol, o‐allylphenol, 4‐methylstyrene‐2,6‐di‐tert‐butylphenol and 2,6‐di‐tert‐butyl‐4‐allylphenol, with propene and carbon monoxide, by using the solvent‐stabilized palladium(II ) phosphine complex [Pd(dppp)(NCCH₃)₂](BF₄)₂ (dppp, 1,3‐bis(diphenylphosphino)propane) as a catalyst precursor and methanol as a co‐catalyst, is described. The influence of functional α‐olefins/CO units, distributed statistically along the propene/carbon monoxide (P/CO) copolymer backbone, on the molecular weight, glass transition temperature (T_g), elastic behavior and stability of the high‐molecular‐weight P/CO copolymer has been investigated. Loss of both elasticity and transparency were observed upon incorporating o‐allylphenol as a termonomer. The terpolymers, which contain phenolic stabilizers, were shown to be more stable when compared to the stabilizer‐free polyketones. In contrast to the propene/carbon monoxide copolymer, no degradation was observed for the 2,6‐di‐tert‐butyl‐4‐allylphenol/P/CO terpolymer; instead, the molar masses increased. Copyright © 2004 Society of Chemical Industry