Metal-catalyzed Cross-coupling Research Articles

Ni- and Fe-Catalyzed Cross-Coupling Reactions of Phenol Derivatives

This review describes our laboratory’s efforts to develop transition metal-catalyzed cross-couplings of several unconventional phenol-based electrophiles. Specifically, we highlight herein the following four key transformations: (a) nickel-catalyzed Suzuki–Miyaura couplings of aryl pivalates, carbamates, and sulfamates to construct sp2–sp2 C–C bonds; (b) iron-catalyzed Kumada couplings of aryl carbamates and sulfamates for the assembly of sp2–sp3 C–C bonds; (c) nickel-catalyzed amination reactions of carbamates and sulfamates to build aryl C–N bonds; and (d) nickel-catalyzed reductive cleavage reactions of aryl carbamates to achieve aryl deoxygenation and a rare method for cine substitution. We expect this review will enable the greater use of unconventional phenol-based cross-coupling electrophiles in industrial settings.

Attaching hexylbenzene and poly(9,9-dihexylfluorene) to brominated graphene via Suzuki coupling reaction

Halogenated organic compounds can represent a useful class of intermediates as they could act as precursors to a number of organometallic species and suitable substrates for metal-catalyzed cross coupling reactions. Here we present an interesting means of functionalizing graphene substrates based on a Suzuki coupling reaction. Firstly, brominated chemically converted graphene sheets were obtained by treating the graphene with ultrasonic assisted bromination. Next, the brominated graphene were modified via the formation of C–C bond between the brominated graphene and the employed aryl boronic. 4-Hexylphenyl boronic acid and 7-bromo-9,9-dihexyl-fluorene-2-ylboronic acids were chosen to show the utility of this reaction scheme in functionalizing graphene. The solubility and optical properties of the grafted material was improved dramatically by the modification. This will open a new interesting filed for the exploitation and application of graphene based materials.

Convenient preparation of (4-iodophenyl)aryliodonium salts

The (4-iodophenyl)aryliodonium salts bis(4-iodophenyl)iodonium, (4-iodophenyl)(4-methoxy-phenyl)iodonium and (4-iodophenyl)(2-thienyl)iodonium, each with three different anions, were prepared using 4-iodo-1-[hydroxy(tosyloxy)iodo]benzene. These are suitable precursor molecules for electrophilic radiofluorination and other 4-iodophenylation reactions, whose products can subsequently serve as reagents for transition metal catalysed cross coupling and other metal organic reactions.

Tetrathiafulvalene-based Cruciform Molecules

Abstract Molecules with two orthogonally oriented π-systems (cruciforms) have attracted interest by virtue of the different conjugation pathways that exist between the individual parts of the molecule. In particular, the possibility for changing the conjugation pathways by an external stimulus may provide controllable molecular switches for molecular electronics. Here we highlight our design and synthesis of cruciform molecules incorporating the redox-active unit tetrathiafulvalene (TTF) placed vertically to an oligo(phenyleneethynylene) (OPE) unit. These molecules have potential as redox-controlled wires (transistors) for molecular electronics. The OPE–TTF cruciforms are prepared by a combination of stepwise metal-catalyzed cross-coupling and Wittig reactions.

ChemInform Abstract: Pd‐, Ni‐, Fe‐, and Co‐Catalyzed Cross‐Couplings Using Functionalized Zn, Mg, Fe, and In Organometallics

AbstractReview: 95 refs.

Manipulating micellar environments for enhancing transition metal-catalyzed cross-couplings in water at room temperature.

The remarkable effects of added salts on the properties of aqueous micelles derived from the amphiphile PTS are described. Most notably, Heck reactions run in the presence of NaCl lead to couplings on aryl bromides in water at room temperature. Olefin cross- and ring-closing metathesis reactions run in the presence of small amounts of pH-lowering KHSO(4) are also accelerated, another phenomenon that does not apply to typical processes in organic media. These salt effects allow, in general, for synthetically valuable C-C bond-forming processes to be conducted under environmentally benign conditions. Recycling of the surfactant is also demonstrated.

TPGS-750-M: a second-generation amphiphile for metal-catalyzed cross-couplings in water at room temperature.

An environmentally benign surfactant (TPGS-750-M), a diester composed of racemic α-tocopherol, MPEG-750, and succinic acid, has been designed and readily prepared as an effective nanomicelle-forming species for general use in metal-catalyzed cross-coupling reactions in water. Several "name" reactions, including Heck, Suzuki-Miyaura, Sonogashira, and Negishi-like couplings, have been studied using this technology, as have aminations, C-H activations, and olefin metathesis reactions. Physical data in the form of DLS and cryo-TEM measurements suggest that particle size and shape are key elements in achieving high levels of conversion and, hence, good isolated yields of products. This new amphiphile will soon be commercially available.

ChemInform Abstract: Cross‐Coupling Reactions of Polyfluoroarenes via C—F Activation

AbstractReview: 97 refs.

Transition metal-catalyzed cross coupling with N-acyliminium ions derived from quinolines and isoquinolines

A Ni(0) catalyst facilitates efficient C–C bond formation between a wide range of π-neutral and π-deficient aryl boronic acids and N-acyliminium precursors derived from quinoline and isoquinoline. The reaction proceeds under mild conditions and is tolerant of common organic functional groups. In addition, a simple one-pot protocol amenable to the direct use of substituted quinolines is described. Consistent with preliminary data revealing a mild, organoboronate-mediated racemization of enantioenriched N-acyliminium precursors, initial results indicate that a chiral phosphoramidite-ligated nickel catalyst promotes enantioselective arylation of racemic substrate with no evidence of a kinetic resolution during catalysis.

Palladium-catalyzed synthesis of indoles via ammonia cross-coupling–alkyne cyclization

The synthesis of indoles via the metal-catalyzed cross-coupling of ammonia is reported for the first time; the developed protocol also allows for the unprecedented use of methylamine or hydrazine as coupling partners. These Pd/Josiphos-catalyzed reactions proceed under relatively mild conditions for a range of 2-alkynylbromoarenes.

ChemInform Abstract: Double Metal-Catalyzed Cross-Coupling Reactions of Alkenyl Sulfoximines with Diorganozinc Reagents: Stereoselective Synthesis of a Key Optically Active 3-Oxacarbacyclin Intermediate.

ChemInform Abstract: Double Metal-Catalyzed Cross-Coupling Reactions of Alkenyl Sulfoximines with Diorganozinc Reagents: Stereoselective Synthesis of a Key Optically Active 3-Oxacarbacyclin Intermediate.

ChemInform Abstract: Bio-organometallic Organosulfur Chemistry. Transition Metal-Catalyzed Cross-Coupling Using Coenzyme M or Thioglycolic Acid as the Leaving Group.

ChemInform Abstract: Bio-organometallic Organosulfur Chemistry. Transition Metal-Catalyzed Cross-Coupling Using Coenzyme M or Thioglycolic Acid as the Leaving Group.

Synthesis, characterization and theoretical studies of thiophene/phenylene derivatives as electroluminescent materials

Metal catalyzed cross coupling reaction have been employed to synthesize the four ring thiophene/phenylene compounds, 4,4′-bis(3-octylthienyl)biphenyl (OTBP) and 4,4′-bis(thienyl)biphenyl (BTBP). Compound OTBP crystallizes in the triclinic system with the phenyl rings almost coplanar and the dihedral angle of thiophene ring with the phenyl group is 37°. The molecule has an inversion center in the middle of the two phenyl groups. In the crystalline space the structure is stabilized by Van der Waals forces between the zig- zag carbon chains. The influence of the alkyl group on the geometry and coplanarity of the structures is discussed on the evidence of the spectroscopic results. These compounds have been fully characterized by 13C NMR, 1H NMR FT-IR, UV/visible spectroscopy. The results from fluorescence and X-ray crystallography structure analysis are reported. Ab-initio calculations of the ground state geometries of both molecules consider Hartree-Fock (HF) and Density Functional Theory (DFT) methodologies. In both cases, the 6-31G+(d, p) basis set was chosen and the B3LYP hybrid functional for correlation and exchange in the DFT calculations.

Intermolecular oxidative cross-coupling of arenes

Biaryls constitute an important subunit found in medicinal agents, functional materials, and natural products. While the Suzuki reaction and related processes currently represent the method of choice for the construction of arene-arene bonds, the direct-coupling of two unfunctionalized arenes mediated by the addition of an oxidant represents a powerful alternative strategy for biaryl synthesis. This tutorial review describes recent progress in this rapidly developing field, focusing on intermolecular examples of selective arene oxidation strategies and metal-catalyzed oxidative cross-coupling via C-H activation.

Cross coupling reactions of polyfluoroarenes via C–F activation

This Perspective provides an overview of transition metal-catalyzed cross coupling reactions of polyfluoroarenes. When appropriate, stoichiometric C-F activation and subsequent reaction are briefly covered.

Thiophene/Thieno[3,2-b]thiophene Co-oligomers: Fused-Ring Analogues of Sexithiophene

A series of six-ring oligothiophenes containing one to three degrees of ring fusion were assembled by a combination of metal-catalyzed Stille cross-coupling and oxidative homocoupling reactions. The effect of position and extent of ring fusion on the electronic properties was studied by UV-vis absorption and fluorescence spectroscopies, and these data were interpreted in the context of TD-DFT computational analysis. Within each set of regioisomers, a slight red shift is revealed in the onset of the UV-vis absorption spectra when the fused-ring unit is located nearer to the periphery of the oligomer, indicating a narrower HOMO-LUMO gap. Incorporation of the unit of ring fusion toward the interior of the oligomer results in a decrease in the longest wavelength emission maximum and a reduced Stokes shift, and is accompanied by an increase in fluorescence quantum yield.

Combined Directed Remote Metalation−Transition Metal Catalyzed Cross Coupling Strategies: The Total Synthesis of the Aglycones of the Gilvocarcins V, M, and E and Arnottin I

A key directed remote metalation (DreM)-carbamoyl migration strategy was applied in an efficient synthesis of the naturally occurring 6H-naphtho[1,2-b]benzopyran-6-one defucogilvocarcin V (1a, Scheme 11). The required biarylcarbamate 33d was best prepared by a high yielding Suzuki coupling reaction of 31a with the differentially protected trioxygenated naphthalene coupling partner 32d which was synthesized using a selective acylation of a juglone derivative. In the late stages of the synthesis, the triflate 39 served as the common intermediate to install the required C-8 vinyl group of 1a (Stille coupling) as well as the required substituents for the preparation of defucogilvocarcins M (1b) and E (1c). A variety of protecting group strategies were investigated and provided insight into which groups are preferred for the DreM-carbamoyl migration process. The strategic lessons learned from this total synthesis were applied in the successful total synthesis of the structurally similar natural product arnottin I (2).

ChemInform Abstract: Efficient Iridium‐Catalyzed C—H Functionalization/Silylation of Heteroarenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Nickel‐Catalyzed Negishi Cross‐Couplings of Secondary Nucleophiles with Secondary Propargylic Electrophiles at Room Temperature

In recent years, significant progress has been made in the development of metal-catalyzed cross-couplings of alkyl electrophiles.[1] A number of substantial challenges have not yet been met, including the coupling of sterically demanding partners. For example, we are not aware of reports of palladium- or nickel-catalyzed cross-couplings of secondary alkyl electrophiles with secondary organometallic nucleophiles.[2] Recognizing the importance of overcoming this limitation, we have recently turned our attention to addressing this deficiency. Due in part to the ease of synthesis and functional-group compatibility of alkylzinc reagents, we chose to focus our efforts on Negishi reactions.[3, 4, 5] In this communication, we describe the first nickel-based catalysts that achieve cross-couplings of secondary nucleophiles with secondary electrophiles [Eq. (1)]. (1) As part of our initial investigation, we explored the Negishi reaction illustrated in Table 1.[6] Unfortunately, none of the methods that have previously been reported for cross-couplings of secondary alkyl electrophiles with primary alkylzinc reagents furnishes the desired product in substantial yield (<20%).[7,8] By optimizing the various reaction parameters, we were able to develop a catalyst system that achieves this Negishi cross-coupling with good efficiency at room temperature (89% yield; Table 1, entry 1).[9] In the absence of NiCl2•glyme or terpyridine, essentially no carbon–carbon bond formation occurs (entries 2 or 3). If the bulky TIPS substituent is replaced with a smaller silyl or alkyl group, the yield of the cross-coupling decreases, due to the formation of a substantial amount of homocoupled electrophile (entries 4 and 5).[10] The other ligands, both bidentate and tridentate, that we have examined, are less useful than terpyridine (entries 6–8), as are solvents other than DMA (entries 9–11). Table 1 Negishi reactions of secondary nucleophiles with secondary propargylic electrophiles: Effect of reaction parameters. Our optimized method (NiCl2•glyme/terpyridine/DMA) can be applied to cross-couplings of a range of secondary propargylic bromides with secondary alkylzincs (Table 2). Esters, olefins (no E/Z isomerization), ethers, and carbamates are compatible with the reaction conditions.[11] Table 2 Room-temperature Negishi reactions of secondary nucleophiles with secondary propargylic electrophiles. Although our primary objective was to develop a method for secondary–secondary cross-couplings, we were also interested in exploring the versatility of this catalyst. We have determined that, without modification, NiCl2•glyme/terpyridine/DMA can also be applied to Negishi reactions of less-hindered coupling partners, e.g., primary alkylzinc reagents with secondary/primary propargylic bromides (Table 3). Cross-couplings proceed in very good yield in the presence of an unactivated primary alkyl chloride, an ether, and an ester.[12] Table 3 Negishi reactions of primary nucleophiles with secondary and primary propargylic electrophiles. If the alkyl group of the organozinc reagent is more hindered than cyclohexyl or isopropyl, the efficiency of NiCl2•glyme/terpyridine/DMA diminishes significantly (e.g., for entry 1 of Table 4: 20% yield). However, by replacing terpyridine with a related ligand, 2,6-bis(N-pyrazolyl)pyridine, and switching to THF as the solvent, the desired Negishi cross-coupling can be achieved in good yield (entry 1 of Table 4: 86% yield).[13,14] Functional groups such as alkynes, unactivated alkyl chlorides, and ethers are tolerated by this method (Table 4).[15] Table 4 Room-temperature Negishi reactions of secondary nucleophiles with secondary propargylic electrophiles. We have determined that our coupling conditions can be employed not only for propargylic bromides, but also for propargylic chlorides (also at room temperature; [Eq. (2) and Eq. (3)]. (2) (3) We have applied our method for secondary-secondary cross-couplings to the formal total synthesis of α-cembra-2,7,11-triene-4,6-diol (Scheme 1), a cembranoid diterpene with antitumor activity that has been synthesized by Marshall[16] and by Thomas.[17] We envisioned that the isopropyl substituent could be installed by a Negishi reaction of propargylic bromide 1, which can be generated from farnesyl acetate; indeed, using our Ni/terpyridine method, we were able to achieve the desired cross-coupling in 61% yield on a gram-scale. In preliminary studies, we have converted coupling product 2 into 14-membered macrocycle 3, which served as an intermediate in the Thomas synthesis of α-cembra-2,7,11-triene-4,6-diol.[17,18] Scheme 1 Application of a secondary-secondary Negishi cross-coupling in a formal total synthesis of α-2,7,11-cembranetriene-4,6-diol. In conclusion, we have developed the first method for secondary–secondary cross-couplings with a Group X catalyst, specifically a nickel-based system for coupling propargylic halides with alkylzinc reagents that proceeds under mild conditions (room temperature and no basic activators). Future efforts will focus on further expanding the scope of cross-coupling reactions of alkyl electrophiles.

Metal-Catalyzed Cross-Coupling Reactions for Ferrocene Functionalization: Recent Applications in Synthesis, Material Science and Asymmetric Catalysis

Recent examples on the functionalization of the ferrocene core by means of cross-coupling reactions are reported in this review. Several methods are discussed including Negishi, Suzuki and Stille couplings for ferrocene-aryl bond formation and Sonogashira reaction for ferrocene-alkyne coupling. The properties in material science and asymmetric catalysis of the prepared ferrocenyl compounds are briefly discussed.