Green and scalable procedure for extremely fast ligandless Suzuki–Miyaura cross-coupling reactions in aqueous IPA using solid-supported Pd in continuous flow

An environmentally friendly continuous-flow protocol for the Suzuki coupling of boronic acids and aryl halides under ligand-free conditions using solid-supported Pd is presented. The process described herein uses very simple reaction conditions and equipment setup and can be readily scaled up to provide multigram quantities of products containing low levels of residual Pd.     

High-intensity ultrasound and microwave, alone or combined, promote Pd/C-catalyzed aryl-aryl couplings

Pd-catalyzed homo- and cross-couplings of boronic acids and aryl halides were successfully carried out both in aqueous media under high-intensity ultrasound (US) and in DME under microwave (MW). Heterogeneous catalysis with Pd/C was employed, avoiding phosphine ligands and phase-transfer catalysts. In a trial series involving 15 different iodo- and bromoaryls and 7 boronic acids, both energy sources drastically reduced reaction times affording biaryls in acceptable to good yields. With palladium(II) acetate as catalyst, electron-deficient aryl chlorides also reacted, affording a few biaryls in acceptable yields. Ullmann-type zinc-mediated homocoupling of iodo- and bromoaryls in the presence of Pd/C under CO₂ atmosphere was achieved in aqueous media under US, though not under MW. Suzuki homo- and cross-couplings were also carried out in a new reactor developed in our laboratory, featuring combined US and MW irradiation, further improving a green synthetic method.     

Cost-effective bio-derived mesoporous carbon nanoparticles-supported palladium catalyst for nitroarene reduction and Suzuki–Miyaura coupling by microwave approach

A new heterogeneous catalyst was synthesized by immobilizing Pd on areca nut kernel-derived carbon nanospheres (CNSs). The CNSs, without any further activation processes, accommodated 3% of Pd on their surface. The new Pd/CNS material was used for the reduction of nitroarenes and Suzuki–Miyaura coupling of bromoarenes with aryl boronic acids. The reactions were conducted under microwave irradiation at 160 °C using 12 mol% of Pd/CNS (0.36% actual Pd content). The reduction of nitroarenes into their respective amino compounds was achieved in 10–20 min (conversion up to 100%); by contrast, the Suzuki–Miyaura reactions yielded up to 98% at 150 °C with 10 mol% of Pd/CNS catalyst. The products were identified using gas chromatography and nuclear magnetic resonance spectroscopy. The catalyst was isolated from reaction mixture and reused without any significant loss in the activity. Thus, the present work introduces one-pot-derived porous CNSs as efficient catalytic support to Pd, establishing an alternative to existing Pd/C in terms of cost and efficiency.     

Palladium-catalyzed tandem reaction of yne-propargylic carbonates with boronic acids: a simple method for the synthesis of fused aromatic rings through allene-mediated electrocyclization

The palladium-catalyzed tandem reactions of yne-propargylic carbonates with aryl boronic acids, 2-furyl boronic acid, and 2-thiopheneboronic acid, followed by 6pi-electrocyclization to give fused ring aromatic products such as naphthalene, benzofuran, and benzothiophene derivatives are realized. Screening of the reaction conditions revealed that the combination of [Pd(PPh3)4] in THF gave the best results in terms of reactivity and product yields in the reaction of yne-propargylic carbonates with phenylboronic acid. The reaction is sensitive toward steric hindrance when substituted phenylboronic acids are employed. However, when we take 2-furyl boronic acid as the organometallic reagent, most substrates perform very well to give benzofuran derivatives. In addition, 2-thiopheneboronic acid is also a very effective coupling reagent to give bezothiophenes in high yields. A mechanism is proposed that involves the formation of an allenylpalladium complex from Pd0 and propargylic carbonate, followed by insertion of an intramolecular triple bond and the Suzuki coupling reaction, and then electrocyclization.     

Polymer-assisted solution-phase (PASP) Suzuki couplings employing an anthracene-tagged palladium catalyst

A general method for polymer-assisted solution-phase (PASP) Suzuki reactions employing a combination of anthracene-tagged palladium catalyst and anthracene-tagged boronic acid with a polymer-supported carbonate base is reported. The anthracene-tagged catalyst allows for the easy removal of the Pd catalyst along with the dissociated phosphine ligand and phosphine oxide byproducts by sequestration through a chemoselective Diels-Alder reaction with a maleimide resin. The polymer-supported carbonate base facilitates the removal of excess boronic acid and the borane-containing byproducts present at the end of the coupling reaction. The Suzuki coupling reaction can be efficiently conducted by using combinations of the anthracene-tagged Pd catalyst, polymer-supported carbonate base, and anthracene-tagged boronic acid to yield the desired product in high purity and yield without the use of chromatography.     

Pd(0)‐Catalyzed Cu(I)‐Thiophene‐2‐carboxylate‐mediated Cross‐Coupling of Heteroaromatic Thioethers and Boronic Acids—First Liebeskind–Srogl Reaction in Water

The first example of a Liebeskind–Srogl cross‐coupling reaction in water as sole reaction solvent is reported. 2‐(Methylthio)pyridine and 2‐(methylthio)benzothiazole were reacted in the presence of a Pd(0) catalyst and copper(I) thiophene‐2‐carboxylate with a series of arylboronic acids. These cross coupling reactions in water proceeded well with electron‐rich boronic acids and gave comparable yields to literature examples using organic solvents. Electron‐poor boronic acids gave somewhat lower yields in aqueous medium.     

Alkyne Aminopalladation/Heck and Suzuki Cascades: An Approach to Tetrasubstituted Enamines

Alkyne aminopalladation reactions starting from tosylamides are reported. The emerging vinylic Pd species are converted either in an intramolecular Heck reaction with olefinic units or in an intermolecular Suzuki reaction by using boronic acids exhibiting broad functional group tolerance. Tetra(hetero)substituted tosylated enamines are obtained in a simple one-pot process.     

Palladium on carbon as a precatalyst for the Suzuki-Miyuara cross-coupling of aryl chlorides

Palladium on carbon is used as a precatalyst for Suzuki-Miyaura reaction of aryl chlorides and aryl boronic acids. An efficient catalyst system is obtained that allows the reaction of substrates that are difficult to couple under ligand free conditions. This includes electron rich and sterically hindered aryl chlorides as well as electron deficient and sterically hindered boronic acids. We have discovered that the amount of ligand needed to catalyze these reactions can be significantly decreased by incorporating an incubation period. This study also provides valuable insight into the mechanism of the Pd/C-catalyzed Suzuki-Miyaura cross-coupling. For example, mercury poisoning studies provide evidence that the active catalytic species is homogeneous. However, catalyst reuse and low metal contamination indicate that this system retains many of the advantages of a heterogeneous catalyst. From these results, a catalytic cycle is proposed.     

Mizoroki-Heck type reaction of organoboron reagents with alkenes and alkynes. A Pd(II)-catalyzed pathway with Cu(OAc)2 as an oxidant

[reaction: see text]. In contrast to the Pd(0)-catalyzed mechanism by Uemura, Mizoroki-Heck type reaction of boronic acids is found to proceed under a Pd(II)-mediated pathway using a catalytic amount of Pd(OAc)2 in the presence of Cu(OAc)2 as an oxidant. Treatment of a variety of alkenes with boronic acids, boronates, and sodium tetraphenylborate furnishes beta-arylated and alkenylated products in good to excellent yields. The reactions with norbornene, norbornadiene, and diphenylacetylene are also performed to give 1:2 or 2:1 coupling products.     

Suzuki-Miyaura cross-coupling reaction catalyzed by Pd/MgLa mixed oxide

A new, reusable Pd/MgLa mixed oxide catalyst has been applied successfully in the Suzuki-Miyaura carbon-carbon cross-coupling reaction of aryl halides as well as benzylic bromide with boronic acids in ethanol. The catalyst is air stable, can be stored and handled under an ambient atmosphere and after the reaction it can be recovered by simple filtration and reused without significant loss of activity.     

Oxidative cross-coupling of allyl(trimethyl)silanes with aryl boronic acids by palladium catalysis

The first oxidative cross-coupling of allylsilanes with aryl boronic acids has been developed by palladium catalysis. The reaction between β-substituted allyl(trimethyl)silanes and a wide range of aryl boronic acids afforded allylarenes in moderate to good yields and excellent selectivity. On the basis of experimental results and literature reports, it was suggested that the reaction might start from transmetalation of aryl boronic acid with AgOAc followed by transmetalation with Pd(II) to give an arylpalladium acetate complex as a key intermediate. This intermediate underwent either electrophilic addition/desilylation or transmetalation with allylsilane and subsequent reductive elimination to give the final product.     

An expeditious aqueous Suzuki-Miyaura method for the arylation of bromophenols

The development of a novel Suzuki-Miyaura method has been achieved to allow the efficient arylation of bromophenols. A range of functionality is tolerated with regard to the boronic acid coupling partner and the reaction exhibits complete chemoselectivity for the C_aryl-Br bond versus the C_aryl-Cl bond in the aryl halide input. The experimental protocol features a short reaction time of 15 min, utilizes inexpensive Pd/C as a catalyst, and is conducted with water as the solvent.     

Heterogeneous Pd/C-catalyzed ligand-free, room-temperature Suzuki-Miyaura coupling reactions in aqueous media

A mild and efficient ligand-free Suzuki-Miyaura coupling reaction catalyzed by heterogeneous Pd/C was developed. Aryl bromides and triflates undergo the cross-coupling with aryl boronic acids in excellent yields without the presence of any additives in aqueous media at room temperature. Aryl vinyl boronic acids are also applicable to this coupling reaction and provide the trans-stilbene derivatives in high yields. The application of wet-type Pd/C to the coupling reaction was achieved without any loss of activity under aerobic conditions, and the reuse of Pd/C is feasible for a fifth run without significant loss of activity. Inductively coupled plasma (ICP) mass-spectrometric analysis of the filtrate from the reaction mixture of 4-bromonitrobenzene with phenylboronic acid demonstrated that the palladium metal hardly leached into the solution within the limits of the detector (<1 ppm), thus suggesting that the present Suzuki-Miyaura reaction proceeded by heterogeneous catalysis.     

Palladium-catalyzed Suzuki cross-coupling of 2-haloselenophenes: synthesis of 2-arylselenophenes, 2,5-diarylselenophenes, and 2-arylselenophenyl ketones

We present herein our results on the Suzuki coupling reaction of 2-haloselenophenes with boronic acids catalyzed by palladium salt and describe a new route established to prepare 2-arylselenophenes and 2,5-diarylselenophenes in good yields. The reaction proceeded cleanly under mild conditions and was performed with aryl boronic acids bearing electron-withdrawing, electron-donating, and neutral substituents, in the presence of Pd(OAc)2, K2CO3/H2O in DME. In addition, by this protocol unsymmetrical aryl ketones were also obtained from 2-iodoselenophene and boronic acids via a carbonylative process.     

Combining enabling techniques in organic synthesis: solid-phase-assisted catalysis under microwave conditions using a stable Pd(II)-precatalyst

The catalytic activity of a 2-pyridinealdoxime-based Pd(II)-complex covalently anchored via the oxime moiety to a glass/polymer composite material was evaluated in Suzuki-Miyaura cross-coupling reactions of aryl and heteroaryl halides, including arylchlorides, with aryl and heteroaryl boronic acids both under thermal as well as microwave irradiating conditions in water. The stability and reusability of this Pd-precatalyst is part of the present study.     

Synthesis of novel cyclic α-amino acid derivatives via a one-pot sequential Petasis reaction/palladium catalysed process

A novel one pot Petasis reaction/palladium catalysed process is described involving 2-iodo/bromo benzylamine, ethyl glyoxalate and aryl/heteroaryl boronic acids. The in situ generated carbinolamine/imine undergoes the Petasis reaction to afford 2 which reacts with carbon monoxide or allene (1 atm) in the presence of Pd(0) to generate acyl palladium or π-allyl palladium species which are intercepted intramolecularly by the proximal secondary amine to afford isoindolone/4-methylene-3,4-dihydroisoquinoline α-amino acid derivatives in good yield.     

Simple amine/Pd(OAc)(2)-catalyzed suzuki coupling reactions of aryl bromides under mild aerobic conditions

A new palladium catalyst (DAPCy) made from Pd(OAc)(2) and commercially available, inexpensive dicyclohexylamine has been developed for the Suzuki coupling reaction of aryl bromides with boronic acids to give the coupling products in good to high yields. The air-stable catalyst was characterized and well-defined by X-ray crystallography. A catalytic system involving DAPCy in dioxane demonstrates a temperature-dependent reactivity toward aryl bromides with different electronic substituents, and selectively couples electron-deficient aryl bromides with boronic acids over electron-rich ones at room temperature. Another catalytic system employing DAPCy in EtOH provides a general and convenient method to prepare biaryls from aryl bromides and boronic acids with a broad range of functional groups at room temperature and under aerobic conditions.     

Leaching from Heterogeneous Heck Catalysts: A Computational Approach

ＩｎｔｒｏｄｕｃｔｉｏｎＴｈｅＨｅｃｋｒｅａｃｔｉｏｎｉｓｔｈｅＣ—ＣｃｏｕｐｌｉｎｇｏｆａｎａｒｙｌｈａｌｉｄｅｗｉｔｈａｎａｌｋｅｎｅｖｉａａＰｄｂａｓｅｄｃａｔａｌｙｓｔ[1] ,ａｎｄｉｓａｔｒｅｍｅｎｄｏｕｓｌｙｖｅｒｓａｔｉｌｅｓｙｓｔｅｍａｃｃｏｍｍｏｄａｔｉｎｇｍａｎｙｄｉｆｆｅｒｅｎｔｓｕｂｓｔｒａｔｅｓａｓｗｅｌｌａｓｃａｔａｌｙｓｔｓ .Ａｃｏｍ ｐｒｅｈｅｎｓｉｖｅｒｅｖｉｅｗａｒｔｉｃｌｅｈａｓｒｅｃｅｎｔｌｙｂｅｅｎｐｕｂｌｉｓｈｅｄ ,ｗｈｉｃｈｎｉｃｅｌｙｉｌｌｕｓｔｒａｔ…     

乙二醇中钯催化无配体的室温Suzuki反应

报道了一种在室温下醋酸钯催化乙二醇中无外加配体的Suzuki反应体系.以K3PO4·7H2O为碱,在该体系中可高效进行芳基溴代物和芳基硼酸的Suzuki交叉偶联反应,具有反应条件温和、无需惰性气体保护等特点.在n(ArBr)=0.5mmol,n(ArB(OH)2)=0.75mmol,x(Pd(OAc)2)=0.5mol%,n(K3PO4·7H2O)=1.0mmol,v(乙二醇)=2ml的优化条件下,4-溴苯甲醚和苯硼酸反应20min,分离收率即达95%.     

Catalytic properties of several supported Pd(II) complexes for Suzuki coupling reactions

Pd(II) complexes with N-ligands were synthesized and tested for Suzuki coupling reaction. These complexes were also heterogenized on silica. The resulting site-isolated catalysts showed a high catalytic activity. The most stable complex was supported N-(propyl)ethylenediamine, which did not display any notable leaching. The effects of reaction conditions and the nature of the boronic acid derivative on the conversion of the starting compounds were studied.