Hindered Aryl Bromides Research Articles

Highly Ordered Mesoporous Polymer‐Supported Phosphine as the Ligand for Organometallic Reaction: Suzuki‐Miyaura Cross‐Coupling of Aryl Chlorides at Room Temperature

AbstractWe prepared a highly ordered mesoporous polymer‐supported diarylphosphine ligand by simple substitution reaction. By utilizing this ligand, we successfully achieved the Suzuki‐Miyaura cross‐coupling of various aryl chlorides at room temperature with high yields. Also, we extended our investigation to the use of a macroporous polymer support in a similar way, which yielded effective Suzuki‐Miyaura cross‐coupling reactions of both aryl chlorides and hindered aryl bromides.

It Is Not All about the Ligands: Exploring the Hidden Potentials of tBu3P through Its Oxidative Addition Complex as the Precatalyst

A series of oxidative addition complexes with a general formula (tBu3P)Pd(Ar)X, as a class of precatalysts, were synthesized for challenging Suzuki–Miyaura coupling involving coupling partners, such as (i) sensitive polyfluorinated arylboronic acids or their corresponding boronic esters, (ii) sterically hindered electrophiles, and (iii) sterically hindered nucleophiles. A total of 89 examples are reported, of which 39 examples are in the Supporting Information. These precatalysts, in particular (tBu3P)Pd(4-CF3Ph)Br, were demonstrated to be powerful catalytic systems in general for cross coupling reactions in comparison to the in situ systems created by mixing tBu3P ligand with a palladium precursor. The precatalysts are also superior to the other monoligated systems, such as Buchwald’s biaryl based G3 or G4 palladacycles. In addition, the (tBu3P)Pd(4-CF3Ph)Br precatalyst is also highly effective for the second most popular coupling reaction, namely the Buchwald–Hartwig coupling. In this study, hindered and electron-deficient amines were coupled with hindered (hetero)aryl bromides and chlorides with 34 examples, of which 8 are in the Supporting Information. Interestingly, the results obtained for both C–C and C–N couplings were on par with or superior to that of the “state-of-the-art” catalysts containing Ad3P and Np3P ligands for the same or similar substrates, suggesting that it is not all about the ligands.

Carbonylative Suzuki-Miyaura couplings of sterically hindered aryl halides: synthesis of 2-aroylbenzoate derivatives.

We have developed a carbonylative approach to the synthesis of diversely substituted 2-aroylbenzoate esters featuring a new protocol for the carbonylative coupling of aryl bromides with boronic acids and a new strategy to favour carbonylative over non-carbonylative reactions. Two different synthetic pathways - (i) the alkoxycarbonylation of 2-bromo benzophenones and (ii) the carbonylative Suzuki-Miyaura coupling of 2-bromobenzoate esters - were evaluated. The latter approach provided a broader substrate tolerance, and thus was the preferred pathway. We observed that 2-substituted aryl bromides were challenging substrates for carbonylative chemistry favouring the non-carbonylative pathway. However, we found that carbonylative Suzuki-Miyaura couplings can be improved by slow addition of the boronic acid, suppressing the unwanted direct Suzuki coupling and, thus increasing the yield of the carbonylative reaction.

Palladium-Catalysed Amination of Hindered Aryl Halides with 9H-Carbazole

Palladium-catalysed Buchwald-Hartwig amination of ortho-substituted hindered aryl bromides or chlorides with 9H-carbazole has been investigated. In the amination of 1-bromo- or chloronaphthalene with 9H-carbazole, the combined use of Pd2(dba)3 as a Pd precursor, Buchwald ligands with two tert-butyl groups and LiOtBu or lithium hexamethyldisilazide as a base led to satisfactory yields. N,N’-Bis[2,6-bis(diphenylmethyl)-4-methoxyphenyl]imidazol-2-ylidene (IPr*OMe), which is a bulky N-heterocyclic carbene ligand, showed similar activity as Buchwald ligands with two tert-butyl groups. In contrast, only IPr*OMe provided satisfactory yields in the amination of 2-bromo-1,1′-biphenyl with 9H-carbazole. The amination of 2-bromo- or chlorotoluene and 1-(2-bromo- or chlorophenyl)naphthalene with 9H-carbazole proceeded smoothly when the IPr*OMe ligand was used.

Synthesis of Conformationally Constrained Esters and Amines by Pd-Catalyzed α-Arylation of Hindered Substrates

The α-arylation of sterically hindered silyl ketene acetals (SKAs) with sterically hindered aryl bromides occurs efficiently using Pd[P(t-Bu)3]2 as the optimal catalyst and ZnF2 as a promoter. Less sensitive P(t-Bu)3-based catalysts could be also employed but showed a lower activity. The reaction showed a broad scope with regard to both coupling partners, including heteroaryl bromides and cyclic SKAs. It also proved to be scalable to multigram quantities, which allowed us to further transform the ester group and to access conformationally constrained benzyl- and phenethylamines, highly sought-after building blocks for the synthesis of new agrochemicals.

ChemInform Abstract: Cooperative Catalysis by Palladium—Nickel Binary Nanocluster for Suzuki—Miyaura Reaction of ortho‐Heterocycle‐Tethered Sterically Hindered Aryl Bromides.

AbstractEfficient Suzuki—Miyaura cross‐coupling of benzoxazoles having an ortho‐bromoaryl substituent in the 2‐position is achieved using a binary PdCl2—NiCl2 catalyst.

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes.

The use of the congested aryl bromide 2-bromo-1,3-dichlorobenzene as coupling partner allows to modify the regioselectivity of the arylation of 3-substituted thiophene derivatives in favour of carbon C5. The coupling of this aryl bromide with a variety of 3-substituted thiophenes gave in all cases the desired 5-arylation products in moderate to good yields using only 0.5 mol % of a phosphine-free and air-stable palladium catalyst. Then, from these 5-arylthiophenes, a second palladium-catalysed C–H bond functionalization at C2 of the thiophene ring allows the synthesis of 2,5-diarylthiophenes with two different aryl units.

Cooperative Catalysis by Palladium–Nickel Binary Nanocluster for Suzuki–Miyaura Reaction of Ortho-Heterocycle-Tethered Sterically Hindered Aryl Bromides

The palladium-nickel binary nanocluster is reported as a new catalyst system for Suzuki-Miyaura cross-coupling of ortho-heterocycle-tethered sterically hindered aryl bromides. The inferior results obtained with the reported Pd/Ni salts/complexes or individual Pd/Ni nanoparticles as catalyst reveal the cooperative catalytic effect of the Pd and Ni nanoparticles in the Pd-Ni nanocluster. The broad substrate scope with respect to variation of the 2-arylbenzoxazole moiety and boronic acids, which offers a means for diversity generation and catalyst recyclability, marks a distinct advantage.

Palladium-catalysed direct cross-coupling of secondary alkyllithium reagents

Palladium-catalysed cross-coupling of secondary C(sp3) organometallic reagents has been a long-standing challenge in organic synthesis, due to the problems associated with undesired isomerisation or the formation of reduction products. Based on our recently developed catalytic C–C bond formation with organolithium reagents, herein we present a Pd-catalysed cross-coupling of secondary alkyllithium reagents with aryl and alkenyl bromides. The reaction proceeds at room temperature and on short timescales with high selectivity and yields. This methodology is also applicable to hindered aryl bromides, which are a major challenge in the field of metal catalysed cross-coupling reactions.

Desymmetrization of meso-2,5-diallylpyrrolidinyl ureas through asymmetric palladium-catalyzed carboamination: stereocontrolled synthesis of bicyclic ureas.

Desymmetrization of meso-2,5-diallylpyrrolidinyl ureas through asymmetric palladium-catalyzed carboamination: stereocontrolled synthesis of bicyclic ureas.

Phosphane‐Functionalized Cycloheptatrienyl–Cyclopentadienyl Titanium Sandwich Complexes: Phosphorus Ligands with an Integrated Reducing Agent for Palladium(0) Catalyst Generation

A picture of (non)innocence: Non-innocent and bulky phosphanes bearing a reducing cycloheptatrienyl–cyclopentadienyl titanium moiety swiftly convert PdII into Pd0 species at room temperature (see scheme). The resulting complex catalyzes the Suzuki–Miyaura coupling with fast conversion even of sterically hindered aryl bromides.

Trineopentylphosphine: A Conformationally Flexible Ligand for the Coupling of Sterically Demanding Substrates in the Buchwald–Hartwig Amination and Suzuki–Miyaura Reaction

Trineopentylphosphine (TNpP) in combination with palladium provides a highly effective catalyst for the Buchwald-Hartwig coupling of sterically demanding aryl bromides and chlorides with sterically hindered aniline derivatives. Excellent yields are obtained even when both substrates include 2,6-diisopropyl substituents. Notably, the reaction rate is inversely related to the steric demand of the substrates. X-ray crystallographic structures of Pd(TNpP)2, [Pd(4-t-Bu-C6H4)(TNpP)(μ-Br)]2, and [Pd(2-Me-C6H4)(TNpP)(μ-Br)]2 are reported. These structures suggest that the conformational flexibility of the TNpP ligand plays a key role in allowing the catalyst to couple hindered substrates. The Pd/TNpP system also shows good activity for the Suzuki coupling of hindered aryl bromides.

Anomalous Reactivity of Silylborane: Transition-Metal-Free Boryl Substitution of Aryl, Alkenyl, and Alkyl Halides with Silylborane/Alkoxy Base Systems

An unexpected borylation of organic halides with a silyborane in the presence of an alkoxy base has been observed. This formal nucleophilic boryl substitution can be applied to a broad range of substrates with high functional group compatibility. Even sterically hindered aryl bromides afforded the corresponding boryl compounds in high yields. Preliminary mechanistic studies indicated that this boryl substitution is promoted by neither transition-metal contamination nor a radical-mediated process.

Air-stable and highly efficient indenyl-derived phosphine ligand: Application to Buchwald–Hartwig amination reactions

2-Mesitylindenyl phosphine ligand (1) and [(2-mesitylindenyl)dicyclohexyl-phosphine]PdCl2 (2) have been synthesized and fully characterized by NMR and elemental analysis, as well as by X-ray crystallography for 2. A Highly active catalyst system derived from a palladium precatalyst and bulky 2-mesitylindenyl phosphine ligand (1) for the Buchwald–Hartwig amination reaction of aryl halides with primary and secondary amines has been developed. This method allows for the preparation of a wide variety of amines in moderate to excellent yields and displays a high level of activity for the coupling of aryl chlorides as well as hindered aryl bromides.

ChemInform Abstract: Chemoselective Suzuki Coupling of Diborylmethane for Facile Synthesis of Benzylboronates.

AbstractThe key is the use of an equimolar amount of KOH and diborylmethane (II).

The Suzuki Reaction in Aqueous Media Promoted by P, N Ligands

The synthesis and structure of palladium complexes of trisubstituted PTA derivatives, PTAR3, are described. Water-soluble phosphine ligands 1,3,5-triaza-7-phosphaadmantane (PTA), tris(aminomethyl)phosphine trihydrobromide, tri(aminomethyl) phosphine, 3,7-dimethyl-1,5,7-triaza-3-phosphabicyclo[3,3,1]nonane (RO-PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA), lithium 1,3,5-triaza-7-phosphaadamantane-6-carboxylate (PTA-CO2Li), 2,4,6-triphenyl-1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane, and 2,4,6-triphenyl-1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane were used as ligands for palladium catalyzed Suzuki reactions in aqueous media. RO-PTA in combination with palladium acetate or palladium chloride was the most active catalyst for Suzuki cross coupling of aryl bromides and phenylboronic acid at 80 °C in 1:1 water:acetonitrile. The activity of Pd(II) complexes of RO-PTA is comparable to PPh2(m-C6H4SO3Na) (TPPMS) and P(m-C6H4SO3Na)3 (TPPTS) and less active than tri(4,6-dimethyl-3-sulfonatophenyl)phosphine trisodium salt (TXPTS). Activated, deactivated, and sterically hindered aryl bromides were examined, with yields ranging from 50% to 90% in 6 h with 5% palladium precatalyst loading. X-ray crystal structures of (RO-PTA)PdCl2, (PTAR3)2PdCl2 (R = Ph, p-tert-butylC6H5), and PTAR3 (R = p-tert-butylC6H5) are reported.

Chemoselective Suzuki Coupling of Diborylmethane for Facile Synthesis of Benzylboronates

The chemoselective Pd-catalyzed Suzuki-Miyaura cross-coupling reaction using a diborylmethane is reported. The use of an equimolar amount of base with a diborylmethane realized chemoselective coupling for the synthesis of various benzylboronate derivatives. Sterically hindered aryl bromides can give products in moderate to excellent yields.

ChemInform Abstract: Efficient Monophosphorus Ligands for Palladium‐Catalyzed Miyaura Borylation.

AbstractSterically hindered aryl bromides and chlorides are converted with very low catalyst loadings using the new monophosphorus ligand (Ia) and Bedford′s Pd precursor (II).

Efficient Monophosphorus Ligands for Palladium-Catalyzed Miyaura Borylation

In combination with the Bedford Pd precursor, the new biaryl monophosphorus ligand 5 was efficient for palladium-catalyzed Miyaura borylation of sterically hindered aryl bromides at low catalyst loadings.

A Facile Route to Aryl Boronates: Room‐Temperature, Copper‐Catalyzed Borylation of Aryl Halides with Alkoxy Diboron Reagents

A simple but effective copper-catalyzed borylation of aryl halides, including electron-rich and sterically hindered aryl bromides, with alkoxy diboron reagents occurs under mild conditions (see scheme). Preliminary DFT studies of the mechanism suggest that sigma-bond metathesis between a copper-boryl intermediate and the aryl halide generates the aryl boronate product.