Coupling Of Bromides Research Articles

Nickel-mediated reductive coupling of neopentyl bromides with activated alkenes at room temperature and its synthetic application

Reductive coupling of sterically hindered neopentyl bromides with activated alkenes mediated by the in situ generated Ni(0) complexes along with some feedstock is achieved in good yield under the mild conditions. This practically useful method of C(sp3)−C(sp3) bond formation provides a complementary approach to the traditional conjugate addition of preformed organometallic reagents to electrophilic olefins, which often requires cryogenic temperature and rigorous exclusion of air and moisture. The robust application of this reductive coupling reaction was demonstrated in a formal synthesis of stereodivergent (−)-copacamphor and (−)-ylangocamphor, which are valuable intermediates for a class of tricyclo[5.3.0.03,8]decane sesquiterpenes. Moreover, this convenient protocol resulted in a facile access to the homolog of Corey aldehyde en route to prostaglandins, implying the possible involvement of radical-like species.

Copper-Catalyzed Trifluoromethylation of Alkyl Bromides

Copper oxidative addition into organohalides is a challenging two-electron process. In contrast, formal oxidative addition of copper to Csp2 carbon-bromine bonds can be accomplished by employing latent silyl radicals under photoredox conditions. This novel paradigm for copper oxidative addition has now been applied to a Cu-catalyzed cross-coupling of Csp3-bromides. Specifically, a copper/photoredox dual catalytic system for the coupling of alkyl bromides with trifluoromethyl groups is presented. This operationally simple and robust protocol successfully converts a variety of alkyl, allyl, benzyl, and heterobenzyl bromides into the corresponding alkyl trifluoromethanes.

Synthesis of novel and room temperature-operable palladium complexes on graphene oxide: An efficient recyclable catalyst for Suzuki-Miyaura coupling reactions

Novel palladium complexes composed of palladium and a conjugated ligand (imine–aldehyde) were immobilized on graphene oxide. The developed catalyst was characterized by XPS, and TEM. The novel catalyst was proven to be highly efficient for the Suzuki-Miyaura coupling reaction of aryl halides (Br, Cl) with arylboronic acids under mild conditions with a low amount of catalyst (0.1 mol%). In particular, excellent yields could be also obtained at room temperature within 1 h for monosubstituted aryl bromide coupling. Furthermore, the novel catalyst could be reused at least ten times without significant loss of its catalytic activities.

Synthesis of Pyridinothienogermoles as Unsymmetrically Condensed Germoles

Pyridinothienogermoles (PyTGs) were prepared by the reaction of dilithiopyridylthiophene with dichlorodi(n-octyl)germane and dichlorodiphenylgermane, and their electronic states were investigated by optical measurements and density functional theory (DFT) calculations. Bromination of trimethylsilyl-substituted PyTG with N-bromosuccinimide gave PyTG bromide, and palladium-catalyzed Stille coupling reactions of bromide with diphenyl[(trimethylstannyl)phenyl]amine and N-[(trimethylstannyl)phenyl]carbazole provided donor–acceptor compounds with pyridine as the acceptor and triphenylamine or phenylcarbazole as the donor. These compounds showed clear solvatochromic properties in the photoluminescence (PL) spectra. Bi(pyridinothienogermole) was prepared by the Stille coupling of DPyG bromide and trimethylstannyl-substituted DPyG. The Lewis basicity of the pyridine ring made it possible to use these DPyG derivatives as ligands for complex formation. Protonation and complex formation of the PyTG pyridine unit with...

Coupling of bromide and on-line mechanical modified fly ash for mercury removal at a 1000 MW coal-fired power plant

Modified fly ash is a potential competitive sorbent for flue gas mercury remove in coal-fired power plant. The adsorption characteristics of coal fly ash under different temperature and modification methods were studied. On-line modified fly ash as a sorbent for mercury removal at a coal-fired power plant was carried out. The results of laboratory show that the adsorption performance of a coupled bromide and mechanical modified fly ash was better than that of inherent fly ash and mechanical modified fly ash. Furthermore, it was found that high temperatures are more favorable for mercury adsorption. In a demonstration at a full-scale 1000 MW coal-fired power plant unit, injection of the bromide and mechanical modified fly ash resulted in a decrease of the total concentration of mercury emissions at the stack. Additionally, a decrease in Hg2+ from the SCR to the ESP was found. When injected modified fly ash, the final emission concentration of mercury at the unit outlet reached 1.15 μg/m3, with a mercury emission reduction efficiency of 56.1%.

Cross-Electrophile Csp 3–Csp 3 Coupling of Aliphatic Bromides

Cross-Electrophile Csp 3–Csp 3 Coupling of Aliphatic Bromides

Visible light promoted coupling of alkynyl bromides and Hantzsch esters for the synthesis of internal alkynes.

A metal-free visible light promoted C(sp3)-C(sp) coupling reaction of alkynyl bromides and Hantzsch esters was developed, giving internal alkynes with primary, secondary, tertiary alkyl or other functional groups in good to high yields.

Synthesis of novel morpholine, thiomorpholine and N-substituted piperazine coupled 2-(thiophen-2-yl)dihydroquinolines as potent inhibitors of Mycobacterium tuberculosis

A series of novel morpholine, thiomorpholine and N-substituted piperazine coupled 2-(thiophen-2-yl)dihydroquinolines 7a–p was designed and synthesized from 2-acetyl thiophene in six step reaction sequence involving modified Bohlmann-Rahtz and Vilsmeier-Haack-Arnold reactions as key transformations. 2-(Thiophen-2-yl)dihydroquinoline was formylated and subsequently chlorinated using DMF-POCl3. The resulting aldehyde was reduced to give an alcohol and then converted to bromide using PBr3. Further coupling of bromide with morpholine, thiomorpholine and N-substituted piperazines resulted in the desired quinolines 7a-p in very good yields. All the new derivatives 7a–p were characterized by their NMR and mass spectral analysis. In vitro screening of new compounds for antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), resulted in two derivatives 7f and 7p as most potent antitubercular agents (MIC:1.56 μg/mL) with lower cytotoxicity profiles.

Ruthenium‐Catalyzed C–H Bond Heteroarylation of Triazoles Enabled by a Deconvolution Strategy

Reaction optimization for C–H bond functionalization reactions with transition‐metal catalysts is traditionally based on long and tedious screening of multiple conditions. In this contribution we have applied a deconvolution strategy to identify reaction conditions suitable for the C–H bond heteroarylation of 1,2,3‐triazoles with a ruthenium catalyst by performing only 18 experiments with mixtures of reagents instead of the theoretically 576 experiments that should have been considered individually. The activation and functionalization takes place at the ortho position of the phenyl ring attached to the 1,2,3‐triazole directing group as confirmed by X‐ray crystallographic studies. The bis‐ vs. mono‐heteroarylation was controlled by tuning the stoichiometry of the reagents. Such methodology was also applicable to aryl bromide coupling partners bearing ortho and meta substituents.

Direct arylation of strong aliphatic C-H bonds.

Despite the widespread success of transition-metal-catalysed cross-coupling methodologies, considerable limitations still exist in reactions at sp3-hybridized carbon atoms, with most approaches relying on prefunctionalized alkylmetal or bromide coupling partners1,2. Although the use of native functional groups (for example, carboxylic acids, alkenes and alcohols) has improved the overall efficiency of such transformations by expanding the range of potential feedstocks3-5, the direct functionalization of carbon-hydrogen (C-H) bonds-the most abundant moiety in organic molecules-represents a more ideal approach to molecular construction. In recent years, an impressive range of reactions that form C(sp3)-heteroatom bonds from strong C-H bonds has been reported6,7. Additionally, valuable technologies have been developed for the formation of carbon-carbon bonds from the corresponding C(sp3)-H bonds via substrate-directed transition-metal C-H insertion8, undirected C-H insertion by captodative rhodium carbenoid complexes9, or hydrogen atom transfer from weak, hydridic C-H bonds by electrophilic open-shell species10-14. Despite these advances, a mild and general platform for the coupling of strong, neutral C(sp3)-H bonds with aryl electrophiles has not been realized. Here we describe a protocol for the direct C(sp3) arylation of a diverse set of aliphatic, C-H bond-containing organic frameworks through the combination of light-driven, polyoxometalate-facilitated hydrogen atom transfer and nickel catalysis. This dual-catalytic manifold enables the generation of carbon-centred radicals from strong, neutral C-H bonds, which thereafter act as nucleophiles in nickel-mediated cross-coupling with aryl bromides to afford C(sp3)-C(sp2) cross-coupled products. This technology enables unprecedented, single-step access to a broad array of complex, medicinally relevant molecules directly from natural products and chemical feedstocks through functionalization at sites that are unreactive under traditional methods.

Indium-Mediated Allylation of Carbonyl Compounds in Ionic Liquids: Effect of Salts in Ionic Liquids.

The In-mediated allylation of carbonyl compounds can be performed in various types of solvents including ionic liquids. However, we have found that in [bmim][BF4] (where bmim = 1-butyl-3-methylimidazolium), the In-mediated coupling of crotyl bromide with benzaldehyde gives a complex mixture, and some additives, such as halides and amines, are crucial for the successful conversion to the corresponding γ-adduct. Instead, the addition of alcohols or water promotes the formation of the α-adduct. An asymmetric induction with up to 62% enantiomeric excess (ee) was observed employing cinchonidine as an additive in a binary solvent consisting of an ionic liquid and dichloromethane.

Multimetallic Ni- and Pd-Catalyzed Cross-Electrophile Coupling To Form Highly Substituted 1,3-Dienes.

The synthesis of highly substituted 1,3-dienes from the coupling of vinyl bromides with vinyl triflates is reported for the first time. The coupling is catalyzed by a combination of (5,5'-bis(trifluoromethyl)-2,2'-bipyridine)NiBr2 and (1,3-bis(diphenylphosphino)propane)PdCl2 in the presence of a zinc reductant. This method affords tetra- and penta-substituted 1,3-dienes that would otherwise be difficult to access and tolerates electron-rich and -poor substituents, heterocycles, an aryl bromide, and a pinacol boronate ester. Mechanistically, the reaction appears to proceed by an unusual zinc-mediated transfer of a vinyl group between the nickel and palladium centers.

Synthesis of quinolinyl-based pincer copper(ii) complexes: an efficient catalyst system for Kumada coupling of alkyl chlorides and bromides with alkyl Grignard reagents.

Quinolinamide-based pincer copper(ii) complexes, κN,κN,κN-{C9H6N-(μ-N)-C(O)CH2NEt2}CuX [(QNNNEt2)CuX (X = Cl, 2; X = Br, 3; X = OAc, 4)], were synthesized by the reaction of ligand (QNNNEt2)-H (1) with CuX2 (X = Cl, Br or OAc) in the presence of Et3N. The reaction of (QNNNEt2)-H with CuX (X = Cl, Br or OAc) also afforded the Cu(ii) complexes 2, 3 and 4, respectively, instead of the expected Cu(i) pincer complexes. The formation of Cu(ii) complexes from Cu(i) precursors most likely occurred via the disproportionation reaction of Cu(i) into Cu(0) and Cu(ii). A cationic complex [(QNNNEt2)Cu(CH3CN)]OTf (5) was synthesized by the treatment of neutral complex 2 with AgOTf. On the other hand, the reaction of (QNNNEt2)-H (1) with [Cu(MeCN)4]ClO4 produced cationic Cu(i) complex, [(QNN(H)NEt2)Cu(CH3CN)]ClO4 (6), in good yield. All complexes 2-5 were characterized by elemental analysis and HRMS measurements. Furthermore, the molecular structures of 2, 3 and 4 were elucidated by X-ray crystallography. Complex 4 crystallizes in a dimeric and catemeric pattern. The cationic complex 5 was found to be an efficient catalyst for the Kumada coupling reaction of diverse nonactivated alkyl chlorides and bromides with alkyl magnesium chloride under mild reaction conditions.

Copper powder-catalyzed coupling and cyclization of 1-bromoallyl bromides with amidine hydrochlorides leading to pyrimidines

ABSTRACT1-Bromoallyl bromides are coupled and cyclized with amidine hydrochlorides in DMF at 130 °C in the presence of a catalytic amount of copper powder along with K3PO4 to give pyrimidines in moderate to good yields.

Mechanism and Applications of the Photoredox Catalytic Coupling of Benzyl Bromides

The photoredox catalytic coupling of halomethyl arenes to bibenzyl derivatives has been demonstrated. The catalytic protocol employed the Hantzsch ester, potassium phosphate, and a photoactive cyclometalated IrIII complex catalyst. A photochemical quantum yield as high as 20 % was obtained. The catalytic mechanism was investigated in detail by performing photophysical and electrochemical measurements, as well as by quantum chemical calculations. The results suggest that two-electron mediation might be responsible for the improved photon economy. The reaction protocol was compatible with halomethyl arenes that contain a variety of functional groups. Finally, the synthetic utility of our protocol was demonstrated by the preparation of a natural dihydrostilbenoid, brittonin A.

Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process.

Benzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron-transfer (SET) process for radical reactions. Representative recent progress includes α-carbon benzylation of ketones and aldehydes via photoredox catalysis. Here we disclose the generation of (nitro)benzyl radicals via N-heterocyclic carbene (NHC) catalysis under reductive conditions. The radical intermediates generated via NHC catalysis undergo formal 1,2-addition with ketones to eventually afford tertiary alcohol products. The overall process constitutes a formal polarity-inversion of benzyl bromide, allowing a direct coupling of two initially electrophilic carbons. Our study provides a new carbene-catalysed reaction mode that should enable unconventional transformation of (nitro)benzyl bromides under mild organocatalytic conditions.

A Luminescent Zirconium(IV) Complex as a Molecular Photosensitizer for Visible Light Photoredox Catalysis

Titanium and zirconium complexes carrying two 2,6-bis(pyrrolyl)pyridine ligands have been synthesized and characterized. The neutral complexes Ti(MePDP)2 and Zr(MePDP)2 (MePDP = 2,6-bis(5-methyl-3-phenyl-1H-pyrrol-2-yl)pyridine) show intense ligand-to-metal charge-transfer bands in the visible region and undergo multiple reversible redox events under highly reducing conditions. Zr(MePDP)2 exhibits photoluminescent behavior and its excited state can be quenched by mild reductants to generate a powerful electron transfer reagent with a ground state potential of -2.16 V vs Fc+/0. This reactivity was utilized to facilitate dehalogenation reactions, the reduction of electron-poor olefins, and the reductive coupling of benzyl bromide via photoredox catalysis. In these reactions, the earth-abundant metal complex Zr(MePDP)2 acts as a substitute for the precious metal photosensitizer [Ru(bpy)3]2+.

ChemInform Abstract: Synthesis of Allenamides by Copper‐Catalyzed Coupling of Propargylic Bromides and Nitrogen Nucleophiles.

AbstractThe title reaction affords a broad spectrum of the desired target compounds under mild conditions A) or B).

Silicon-Carbon Bond Formation via Nickel-Catalyzed Cross-Coupling of Silicon Nucleophiles with Unactivated Secondary and Tertiary Alkyl Electrophiles.

A wide array of cross-coupling methods for the formation of C-C bonds from unactivated alkyl electrophiles have been described in recent years. In contrast, progress in the development of methods for the construction of C-heteroatom bonds has lagged; for example, there have been no reports of metal-catalyzed cross-couplings of unactivated secondary or tertiary alkyl halides with silicon nucleophiles to form C-Si bonds. In this study, we address this challenge, establishing that a simple, commercially available nickel catalyst (NiBr2·diglyme) can achieve couplings of alkyl bromides with nucleophilic silicon reagents under unusually mild conditions (e.g., -20 °C); especially noteworthy is our ability to employ unactivated tertiary alkyl halides as electrophilic coupling partners, which is still relatively uncommon in the field of cross-coupling chemistry. Stereochemical, relative reactivity, and radical-trap studies are consistent with a homolytic pathway for C-X bond cleavage.

ChemInform Abstract: Copper‐Catalyzed Tandem Ullmann Type C—N Coupling and Dehydrative Cyclization: Synthesis of Imidazo[1,2‐c]quinazolines.

AbstractAn efficient one‐pot procedure is elaborated for the preparation of imidazo[1,2‐c]quinazolines (III) by an Ullmann‐type C—N coupling of bromides (I) with formamide followed by intramolecular dehydrative cyclization.