Halide Substrates Research Articles

An Efficient and Selective Pd-catalyzed Dehalogenation Reaction

During the research on the Pd-catalyzed intramolecular cyclization reaction via C-H activation, the dehalogenation of 3-halo-2(5H)-furanones is unexpectedly discovered. Under the optimized conditions without any special anaerobic and anhydrous treatments, using N,N-diisopropylethylamine (DIPEA) simultaneously as hydrogen source and base, the reactions of 27 substrates with less Pd catalyst (5 mol% Pd(PPh3)4) usually give higher yields (70-99%, mostly over 82%). Especially for 3-halo-2(5H)-furanone substrates simultaneously containing aryl halide structure, this kind of Pd-catalyzed dehalogenation has good selectivity. After the selectivity is explained via the substrate theoretical calculation, a possible reaction mechanism of the Pd-catalyzed dehalogenation is proposed. These novel investigations provide an efficient, simple, practical and selective Pd-catalyzed dehalogenation method for the non-aromatic halide substrates with many different functional groups.

Organocatalysis approach to trifluoromethylation with fluoroform

The organic base methodology exploits an access to generate the “trifluoromethyl anion” for carbonyl, ester, acid halide, epoxide, deuterium donor, and carbon dioxide substrates to afford the trifluoromethylation products with good overall efficiency even in organocatalysis conditions. The NMR analysis of the mixture of fluoroform and P4-base shows no change thereof. However, on addition of electrophiles, the trifluoromethylation products were obtained efficiently.

Rapid oxidation of organic halides with N-methylmorpholine N-oxide in an ionic liquid under microwave irradiation

A simple and rapid method for the conversion of organic halides into carbonyl derivatives is developed via microwave-assisted oxidation with N-methylmorpholine N-oxide in an ionic liquid. A variety of halide substrates are oxidized to the corresponding products in good to excellent yields in short reaction times. The ionic liquid is recovered and reused in several reaction cycles without any significant loss in activity.

DFT and ab-initio study on the mechanism of the gas-phase elimination kinetics of 1-chloro-3-methylbut-2-ene and 3-chloro-3-methylbut-1-ene and their isomerization

The mechanisms of the gas-phase elimination kinetics of 1-chloro-3-methylbut-2-ene and 3-chloro-3-methylbut-1-ene and their interconversion have been examined at MP2 and DFT levels of theory. These halide substrates yield isoprene and hydrogen chloride. The results MPW1PW91 calculations agree with the experimental kinetic parameters showing the elimination reaction occurs at greater rate for 1-chloro-3-methylbut-2-ene than that for the 3-chloro-3-methylbut-1-ene isomer. The mechanism for the molecular elimination of 1-chloro-3-methylbut-2-ene suggests proceeding through an uncommon six-membered cyclic transition state for alkyl halides in the gas phase, while 3-chloro-3-methylbut-1-ene eliminates through the usual four-membered cyclic transition state. The elongation and subsequent polarization of the C-Cl bond, in the direction of C^{δ+}…Cl^{δ-}, is rate determining step of these reactions. The isomerization of 1-chloro-3-methylbut-2-ene and 3-chloro-3-methylbut-1-ene was additionally studied. The 1-chloro-3-methylbut-2-ene converts to 3-chloro-3-methylbut-1-ene easier than the reverse reaction. This means that 1-chloro-3-methylbut-2-ene was found thermodynamically more stable than 3-chloro-3-methylbut-1-ene.

Synthesis of enantiomerically enriched imidazolidin-2-ones through asymmetric palladium-catalyzed alkene carboamination reactions.

Positive water effect: A catalyst composed of [Pd(2)(dba)(3)] (dba=dibenzylideneacetone) and (S)-Siphos-PE is effective for the enantioselective coupling of N-allyl ureas with aryl bromides to afford 4-substituted imidazolidin-2-ones. Added water leads to significantly improved enantioselectivities with electron-poor aryl halide substrates. It is suggested that the C-C bond-forming reductive elimination is the enantiodetermining step in these reactions.

ChemInform Abstract: Cross‐Coupling Reactions Catalyzed by Iron Group Metals and N‐Heterocyclic Carbenes via Nonconventional Reaction Mechanisms

AbstractReview: ca. 100 refs.

The role of magnetic nanoparticles (MNP) as reducing agents in an MNP-supported Pd–catalyst for the reductive homocoupling of aryl halides

A palladium pincer catalyst grafted onto the surface of magnetic nanoparticles (MNPs) has been developed. This material effectively catalyzes the reductive homocoupling of various aryl halide substrates, with the MNP support acting as the reducing agent. The catalyst can be recycled up to five times in the absence of additional reducing agent to give almost quantitative yields of biaryl homocoupling products. After the reducing power of the MNP has been depleted, the supported Pd complex remains an effective catalyst for Suzuki–Miyaura cross-coupling.

Nucleophilic Aryl Fluorination and Aryl Halide Exchange Mediated by a CuI/CuIII Catalytic Cycle

Copper-catalyzed halide exchange reactions under very mild reaction conditions are described for the first time using a family of model aryl halide substrates. All combinations of halide exchange (I, Br, Cl, F) are observed using catalytic amounts of Cu(I). Strikingly, quantitative fluorination of aryl-X substrates is also achieved catalytically at room temperature, using common F(-) sources, via the intermediacy of aryl-Cu(III)-X species. Experimental and computational data support a redox Cu(I)/Cu(III) catalytic cycle involving aryl-X oxidative addition at the Cu(I) center, followed by halide exchange and reductive elimination steps. Additionally, defluorination of the aryl-F model system can be also achieved with Cu(I) at room temperature operating under a Cu(I)/Cu(III) redox pair.

Synthesis of Chiral Benzoxa(thia)zepine and Pyridoxazepine Derivatives Using Palladium‐Catalyzed Intramolecular Aryl Amination Reaction

AbstractA palladium‐catalyzed method employing different bulky biaryl phosphanes as ligands has been developed for the intramolecular amination of aryl bromides and iodides. A variety of aryl halide substrates have been aminated through the intramolecular pathway in good yield using different sugar‐derived amines to give furo‐benzoxa(thia)zepine and pyridoxazepine derivatives. The method is capable of furnishing chiral, enantiopure benzoxa(thia)zepines and pyridoxazepines of significant biological importance.

Living nanocatalyst for effective synthesis of symmetrical biaryls

A convenient procedure is described for the synthesis of symmetrical biaryls via Ullmann coupling reaction catalyzed by palladium nanoparticles stabilized in a polymer matrix. A wide range of aryl halide substrates is transformed into corresponding symmetrical biaryls at a mild reaction condition. Living nature of the nanocatalysts is revealed by in situ recycling methodology and transmission electron microscopy (TEM). Calculation based on density functional theory (DFT) was performed to have better insight on mechanistic cycle and the result was supported by experimental evidence. Preliminary investigation also reveals that these PdNPs act as efficient catalyst in Heck and copper free Sonogashira reactions.

Cross-Coupling Reactions Catalyzed by Iron Group Metals and <i>N</i>-Heterocyclic Carbenes via Nonconventional Reaction Mechanisms

New cross-coupling reactions catalyzed by iron or iron group metals (IGMs), consisting of Fe, Co, and Ni with N-heterocyclic carbenes (NHCs), are described in this report. Highly selective biaryl cross-coupling reactions between aryl halides and aryl Grignard reagents were achieved by using a combination of fluoride salts of IGMs and NHCs. In the course of the study, an unexpected alkenylative cross-coupling between alkyl aryl sulfides and aryl Grignard reagents was found, in which a typical Ni/NHC catalyst displayed unprecedented reactivity toward sulfide substrates. Theoretical studies suggest that the biaryl coupling and the alkenylative coupling reactions proceed via two nonconventional mechanisms, which are substantially different from the widely-accepted cross-coupling mechanism: In the biaryl cross-coupling, treatment of the catalyst mixtures of IGM fluorides and NHCs with an excess amount of the aryl Grignard reagent results in the generation of organometalate complexes, [Ar1MIIF2]MgBr (M=Fe, Co, and Ni). These organometalate species undergo oxidative addition of aryl halide substrates to form intermediates in a high oxidation state (most likely a+IV state) possessing two different aryl groups, Ar1Ar2MIVF2. The heteroleptic diaryl organometallic intermediates collapse easily to afford unsymmetrical biaryls in a highly selective manner. On the other hand, the alkenylative coupling reaction using a Ni/NHC catalyst involves formation of a low-oxidation-state Ni(0)-thioaldehyde complex, which is transformed to an alkenylnickel species via α-deprotonation of the thioaldehyde and subsequent C-S bond cleavage of the resulting enethiolate intermediate. The alkenylnickel species undergoes transmetalation with an aryl Grignard reagent to form alkenyl/aryl coupling products via reductive elimination. The present cross-coupling reactions catalyzed by IGMs with NHC ligands provide highly selective Csp2-Csp2 coupling methods for the synthesis of unsymmetrical biaryls and styrene derivatives, offering an opportunity to gain new mechanistic insights into IGM-catalyzed cross-coupling reactions.

Intermediates of the PTC carbonylation of benzyl halides by cobalt carbonyls, II

The structures of intermediates in the PTC carbonylation of two fluorinated benzyl halide substrates were studied. X-ray crystal and molecular structure of 2- and 3-fluorobenzylcobalt tricarbonyl triphenylphosphine derivatives was determined. The supposed influence of structural parameters on the reactivity is discussed.

Synthesis of Purine Derivatives as Scaffolds for a Diversity of Biological Activities

The purine ring is undoubtedly among the most ubiquitous of all the heterocyclic compounds. This arises not only from the universal occurrence of adenine and guanine in DNA and RNA and of additional modified derivatives in the various tRNAs but also from the subsidiary uses of the ring system in a great number of biochemical systems. The development of new methods for metal-mediated coupling with aryl or heteroaryl halide substrates has expanded the range of synthetically accessible arylpurine derivatives. Aryl boronic acids have proved to be extremely available reagents for metal-mediated C-C and C-N coupling reactions. Coupling reactions resulting in C-C bond formation are catalyzed by palladium and nickel catalysts at positions C2, C6 and C8. The reactivity at C6 position has been demonstrated using fluoro-, chloro-, bromo-, iodo-, sulfanyl, sulfonyl, sulfonyloxy- and azole-substrates. The ease of obtaining the activated purine substrates is an important factor when selecting appropriate coupling conditions. Copper-mediated N-arylations occur at positions N7 and N9. These methods are also applicable using solid-supported purine substrates and provide convenient access to structurally unique derivatives with applications in drug discovery. Continuing advances in this field can be expected to result through improved mechanistic understanding and the development of new catalysts and ligands. Keywords: Alkyl-purine derivatives, aryl-purine derivatives, cross-coupling, ferrocene-modified purines, fluorinated compounds, microwave, nucleosides, solid-phase synthesis, antiparasitic agents, cyclin-dependent kinase inhibitors, 5-alkylamino-4-amino-6-arylthiopyrimidine, cyclohexyl nucleosides, 9-Phenyl-9H-purin-6-amines, 5-amino-1-phenyl-1H-imidazole-4-carbonitriles, methyl ethyl ketone, perfluoroalkylation reaction, Tetrabutylammonium triphenyldifluorosilicate, imidazolium-carbene ligand, Phosphonated azaheterocycles, C6-phosphonated purine nucleosides, 2-Amino-6-(1,2,4-triazol-4-yl)purine, Disubstituted Purines, tetrabutylammonium nitrate, trifluoroacetic anhydride, 2,6-Dichloropurine, tributyltin chloride, trimethylsilyl chloride, hexamethyldisilazane, anhydrous acetonitrile, 1,2-dichloroethane, dihydrodiazepinopurine, Mycobacterium avium, N,N-dimethylacetamide, TETRASUBSTITUTED PURINES, diaminopyrimidine

Copper(I) Iodide Polyphosphine Adducts at Low Loading for Sonogashira Alkynylation of Demanding Halide Substrates: Ligand Exchange Study between Copper and Palladium

The prestabilization of copper iodide with a multidentate ferrocenyl phosphine ligand promotes the palladium-catalyzed cross-coupling of demanding halides with phenylacetylene in a selective way. Novel CuI-triphosphine adducts are described in the solid state and in solution. Their use allowed the introduction of the copper iodide cocatalyst in unprecedented low amounts (0.4 to 0.1 mol %) in systems also employing low amounts of “ligand-free” [PdII(η3-allyl)Cl]2 precursor (0.2 to 0.05 mol %). The scope of substrates is reported, and electronically or sterically deactivated bromides were efficiently coupled. Concerning aryl chlorides, electron-poor activated substrates were also coupled using this innovative low-metal-content catalytic system. Some rarely tackled mechanistic aspects are discussed herein. In particular, the transfer of ligand from copper to palladium monitored by NMR was found to be different depending on the polyphosphine ligand. The inhibition of diyne formation was also an interesting fe...

Palladium‐Catalyzed Intramolecular Aryl Amination Reaction: An Expeditious Approach to the Synthesis of Chiral Benzodiazocine Derivatives

AbstractA palladium‐catalyzed method for intramolecular amination of aryl bromides and iodides has been developed employing different bulky biaryl phosphanes as ligands and toluene as solvent. A variety of electron‐rich aryl halide substrates have been aminated by the intramolecular pathway in good yield using different sugar‐derived amines as well as benzylamine. The method is capable of furnishing benzodiazocines in chiral form besides dibenzodiazocine derivatives of potential biological interest.

Theoretical calculations on the mechanisms of the gas phase elimination kinetics of chlorocyclohexane, 3-chlorocyclohexene and 4-chlorocyclohexene

The kinetics of the thermal decomposition of the title compounds in the gas phase have been studied at the B3LYP/6-31G(d,p), B3LYP/6-31++G(d,p), MPW91PW91/6-31G(d,p), MPW91PW91/6-31++G(d,p), PBEPBE/6-31G(d,p), and PBEPBE/6-31++G(d,p) levels of theory. These halide substrates produce the corresponding cyclohexadiene and hydrogen chloride. The DFT calculations suggest a non-synchronous four-membered cyclic transition state type of mechanism. The elongation and subsequent polarization of the C–Cl bond, in the direction of C δ+…Cl δ−, is rate determining step in these elimination reactions. Differences in reactivity in these substrates are discussed in terms of the transition state structure and electron distribution.

N , N ′ -dimethylperylene-3,4,9,10-bis(dicarboximide) on alkali halide (001) surfaces

The growth of N,N′-dimethylperylene-3,4,9,10-bis(dicarboximide) (DiMe-PTCDI) on KBr(001) and NaCl(001) surfaces has been studied. Experimental results have been achieved using frequency modulation atomic force microscopy at room temperature under ultrahigh vacuum conditions. On both substrates, DiMe-PTCDI forms molecular wires with a width of 10nm, typically, and a length of up to 600nm at low coverages. All wires grow along either the [110] direction (or [11¯0] direction, respectively) of the alkali halide (001) substrates. There is no wetting layer of molecules: atomic resolution of the substrates can be achieved between the wires. The wires are mobile on KBr but substantially more stable on NaCl. A p(2×2) superstructure in a brickwall arrangement on the ionic crystal surfaces is proposed based on electrostatic considerations. Calculations and Monte Carlo simulations using empirical potentials reveal possible growth mechanisms for molecules within the first layer for both substrates, also showing a significantly higher binding energy for NaCl(001). For KBr, the p(2×2) superstructure is confirmed by the simulations; for NaCl, a less dense, incommensurate superstructure is predicted.

Epitaxial Orientation of Dimethylglyoximatoplatinum(II) on Various Substrates

Thin films of bis(dimethylglyoximato)platinum(II) (Pt(dmg)2) with one-dimensional metal chains were fabricated by vacuum deposition on four alkali halide, graphite, and molybdenite substrates. The epitaxy of the films was characterized by transmission electron microscopy and atomic force microscopy. One-dimensional metal chains of Pt(dmg)2 stood perpendicular to the substrate surfaces, with the exception of the NaCl substrate. The epitaxial orientation of Pt(dmg)2 was thought to be primarily governed by lattice-matching between the deposited material and substrate surface. However, when the electrostatic interactions were taken into consideration, experimental orientations were more adequately explained.

Cascade Palladium-Catalyzed Alkenyl Aminocarbonylation/ Intramolecular Aryl Amidation: An Annulative Synthesis of 2-Quinolones

Palladium-catalyzed intermolecular aminocarbonylation/intramolecular amidation cascade sequences can be used to convert a range of 2-(2-haloalkenyl)aryl halide substrates efficiently and selectively to the corresponding 2-quinolones. Delaying the introduction of the CO atmosphere allows an amination/carbonylation sequence and the preparation of an isoquinolone.

Tandem copper-catalysed aryl and alkenyl amination reactions: the synthesis of N-functionalised indoles

A Cu-diamine complex effectively catalyses tandem C-N bond formation on 2-(2-haloalkenyl)-aryl halide substrates, to deliver a series of N-functionalised indoles. Anilines, amides and carbamates are all effective coupling partners under the developed conditions.