Palladium-catalyzed Cross-coupling Reactions Research Articles

Palladium-Catalyzed Negishi Cross-Coupling Reaction of Aryl Halides with (Difluoromethyl)zinc Reagent.

The palladium-catalyzed Negishi cross-coupling reaction of aryl iodides and bromides with (difluoromethyl)zinc reagent bearing a diamine such as TMEDA is achieved to provide the difluoromethylated aromatic compounds in good to excellent yields. The advantages of (difluoromethyl)zinc reagent are that (1) the derivatives, which possess different stability and reactivity, can be readily prepared via ligand screening and (2) transmetalation of a difluoromethyl group from the zinc reagent to palladium catalyst efficiently proceeds without an activator.

A two-dimension medium band gap conjugated polymer based on 5,10-bis(alkylthien-2-yl)dithieno[3,2-d:3′,2′-d′]benzo[1,2-b:4,5-b′]dithiophene: Synthesis and photovoltaic application

ABSTRACTA two-dimension medium band gap copolymer poly{5,10-bis(4,5-didecylthien-2-yl)dithieno[2,3-d:2′,3′-d′]benzo[1,2-b:4,5-b′]dithiophene-2,7-diyl-alt-2,5-di(3-octylthien-2-yl) thiophen-5,5′-diyl}, named as PDTBDT-T-3T, was prepared by the palladium-catalyzed Stille cross coupling reaction and characterized. The resulting polymer exhibits good solubility in common organic solvents, excellent thermal stability, and extensive light absorption from 300 nm to 650 nm with an optical band gap of 1.92 eV, the highest occupied molecular orbital (HOMO) level of −5.03 eV and the hole mobility up to 1.92 × 10−4 cm2·V−1·s−1. The power conversion efficiencies (PCEs) of 2.02%–3.19% have been achieved in the traditional PVCs for the copolymer. It should be noted that the PCEs of 4.2% for the inverted PVCs from the copolymer with PFN (poly[(9,9-bis(3′-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctyl- fluorene)]) as cathode modifying interlayer, were similar with the PCEs of 4.39% for the inverted PVCs from P3HT:PC71BM at the same condition. These results indicated that the copolymer could be used as potential candidate for P3HT.

Regioselective and Stepwise Syntheses of Functionalized BODIPY Dyes through Palladium-Catalyzed Cross-Coupling Reactions and Direct C-H Arylations.

Regioselective and stepwise syntheses of a series of functionalized BODIPY dyes through palladium-catalyzed cross-coupling reactions and direct C-H arylations have been developed. In particular, this method allows the straightforward synthesis of 2,6-dibromo-3,5-diarylBODIPYs and 2-bromo-3-arylBODIPYs from polybrominated BODIPYs. The X-ray structure of intermediates 5a-c indicated that the palladium was first inserted into the C-Br bonds at 3,5-positions of brominated BODIPYs. The resulting 2,6-dibromo-substituted BODIPYs are potential long wavelength photosensitizers which are not easily accessible using previous methods.

Sonogashira-Like Coupling Reactions with Phosphine–Gold(I) Alkynyl Complexes

Phosphine–gold(I) alkynyl complexes are stable compounds that can be subjected to palladium-catalyzed cross-coupling reactions. This article outlines the synthesis of such compounds and their ability to play the role as substrates in Sonogashira couplings is covered. This synthetic approach is particularly attractive when the related terminal alkynes are unstable. 1 Introduction 2 Phosphine–Gold(I) Alkynyl Complexes 3 Sonogashira-Like Couplings 4 Transmetalation Step – Mechanistic Insight 5 Acetylenic Scaffolding with Tetraethynylethene Derivatives 6 Conclusion

An efficient route to diverse 2H-pyrano[3,2-c]quinolin-5(6H)-ones via electrophilic cyclization reactions

Electrophilic cyclization of 4-((3-arylprop-2-yn-1-yl)oxy)quinolin-2(1H)-one derivatives with iodine leads to the formation of 2H-pyrano[3,2-c]quinolin-5(6H)-ones bearing an alkenyl iodide moiety in good to excellent yields under mild conditions. The resulting iodo-containing 2H-pyrano[3,2-c]quinolin-5(6H)-ones could be further elaborated via palladium-catalyzed cross-coupling reactions.

Structural Analogues of Selfotel.

A small library of phosphonopiperidylcarboxylic acids, analogues of NMDA antagonist selfotel (CGS 19755), was synthesized. First, the series of aromatic esters was obtained via a palladium-catalyzed cross-coupling reaction (Hirao coupling) of dialkyl phosphites with bromopyridinecarboxylates, followed by their hydrolysis. Then, hydrogenation of the resulting phosphonopyridylcarboxylic acids over PtO2 yielded the desired phosphonopiperidylcarboxylic acids. NMR studies indicated that the hydrogenation reaction proceeds predominantly by cis addition. Several compounds were obtained as monocrystal structures. Preliminary biological studies performed on cultures of neurons suggest that the obtained compounds possess promising activity toward NMDA receptors.

ChemInform Abstract: Palladium‐Catalyzed Chemo‐ and Regioselective Cross‐Coupling Reactions of 2,3‐Dichloronaphthalene‐1,4‐bistriflate.

AbstractThe Suzuki—Miyaura couplings of title substrate (I) provides tetra‐, di‐, and mono‐phenylnaphthalenes selectively.

Secondary Alkyl Groups in Palladium-Catalyzed Cross-Coupling Reactions

Important classes of cross-coupling reactions are those leading to the incorporation of secondary alkyl groups. While early work in cross-coupling focused mainly on primary alkyl groups, the past decade has seen significant advances in introducing secondary and tertiary groups. This review will focus on the advances made in recent years referencing landmark publications where necessary. Expansion of scope, ease of reaction setup, and mechanistic considerations will be stressed. Applications of methodologies towards complex scaffolds and natural products will be also be evaluated. 1 Introduction 2.1 Suzuki Coupling 2.2 Mizoroki–Heck Coupling 2.3 Stille Coupling 2.4 Sonagashira Coupling 2.5 Kumada Coupling 2.6 Negishi Coupling 2.7 Hiyama Coupling 2.8 Lithium Coupling 2.9 Titanium Coupling 2.10 C–H Activation 3 Conclusion

Synthesis of 4-substituted nipecotic acid derivatives and their evaluation as potential GABA uptake inhibitors

In this study, we disclose the design and synthesis of novel 4-susbtituted nipecotic acid derivatives as inhibitors of the GABA transporter mGAT1. Based on molecular modeling studies the compounds are assumed to adopt a binding pose similar to that of the potent mGAT1 inhibitor nipecotic acid. As substitution in 4-position should not cause an energetically unfavorable orientation of nipecotic acid as it is the case for N-substituted derivatives this is expected to lead to highly potent binders. For the synthesis of novel 4-substituted nipecotic acid derivatives a linear synthetic strategy was employed. As a key step, palladium catalyzed cross coupling reactions were used to attach the required biaryl moieties to the ω-position of the alkenyl- or alkynyl spacers of varying length in the 4-position of the nipecotic acid scaffold. The resulting amino acids were characterized with respect to their binding affinities and inhibitory potencies at mGAT1. Though the biological activities found were generally insignificant to poor, two compounds, one of which possesses a reasonable binding affinity for mGAT1, rac-57, the other a notable inhibitory potency at mGAT4, rac-84, both displaying a slight subtype selectivity for the individual transporters, could be identified.

A General Palladium-Catalyzed Hiyama Cross-Coupling Reaction of Aryl and Heteroaryl Chlorides.

A general palladium-catalyzed Hiyama cross-coupling reaction of aryl and heteroaryl chlorides with aryl and heteroaryl trialkoxysilanes by a Pd(OAc)2 /L2 catalytic system is presented. A newly developed water addition protocol can dramatically improve the product yields. The conjugation of the Pd/L2 system and the water addition protocol can efficiently catalyze a broad range of electron-rich, -neutral, -deficient, and sterically hindered aryl chlorides and heteroaryl chlorides with excellent yields within three hours and the catalyst loading can be down to 0.05 mol % Pd for the first time. Hiyama coupling of heteroaryl chlorides with heteroaryl silanes is also reported for the first time. The reaction can be easily scaled up 200 times (100 mmol) without any degasification and purification of reactants; this facilitates the practical application in routine synthesis.

Cyanotriflation gives versatile acrylonitriles

Chemists in Germany have added a new dimension to preparing acrylonitriles with the first method for adding both a cyano group and a triflate group to an alkyne (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b00869). Xi Wang and Armido Studer of the University of Münster took advantage of a known aryl(cyano)iodonium triflate reagent that other groups have used to transfer the cyano group or the triflate group. But until now, no one had devised a reaction system to add both groups to another molecule at once, in this case a range of alkynes and diynes. The Münster team’s syn addition proceeds with regio- and stereochemical control at up to gram scale via a radical mechanism mediated by an iron phenanthroline catalyst, leading to a host of triflate-modified acrylonitriles. The researchers found that the triflate provides a handle for further functionalizing the acrylonitriles via palladium-catalyzed cross-coupling reactions (example shown) to make

Heteroatom-substituted secondary phosphine oxides for Suzuki-Miyaura cross-coupling reactions

Several di-substituted diimines (3a–3f) and heteroatom-substituted unsaturated secondary phosphine oxides (HASPO, 6a–6f) were prepared and characterized. Compounds 6a–6f are regarded as pre-ligands because of their ability of tautomerization to heteroatom-substituted phosphinous acid (HAPA, 7a–7f). An unexpected 3e-coordinated palladium dibromide 8e was observed from the reaction of compound 6e with PdBr2. Molecular structures of pre-ligands 6a, 6c, and 6e, as well as palladium complexes 8e were determined by single crystal X-ray diffraction methods. When pre-ligand 6a was applied to palladium-catalyzed Suzuki-Miyaura cross-coupling reactions, satisfactory yields were obtained. Density functional theory were employed to examine the electronic properties of HASPO 6a–6f pre-ligands, their corresponding 1,3-di-N-substituted tautomers 7a–7f, and the saturated counterpart 7as of 7a. Compound 7a is the most effective and genuine ligand in Suzuki-Miyaura reaction that is confirmed by its higher-lying lone-pair (LP) molecular orbital (HOMO-1). The LP orbital of 7c–7f is lower-lying HOMO-5. For each 7c–7f, two conformational rotamers with minute energy difference were located. Hirshfeld charge and population analysis of 7c–7f were also calculated in order to comprehend the electronic properties for these two rotamers for each HAPAs. Besides, the steric effect of HAPAs was estimated in terms of the Percent Buried Volume (%Vbur). This model has shown that 7a has similar steric property to that of PCy3, which is an effective ligand in Suzuki-coupling reactions.

Design, Synthesis, and Validation of an Effective, Reusable Silicon-Based Transfer Agent for Room-Temperature Pd-Catalyzed Cross-Coupling Reactions of Aryl and Heteroaryl Chlorides with Readily Available Aryl Lithium Reagents

A reusable silicon-based transfer agent (1) has been designed, synthesized, and validated for effective room-temperature palladium-catalyzed cross-coupling reactions (CCRs) of aryl and heteroaryl chlorides with readily accessible aryl lithium reagents. The crystalline, bench-stable siloxane transfer agent (1) is easily prepared via a one-step protocol. Importantly, this "green" CCR protocol circumvents prefunctionalization, isolation of organometallic cross-coupling partners, and/or stoichiometric waste aside from LiCl. DFT calculations support a σ-bond metathesis mechanism during transmetalation and lead to insights on the importance of the CF3 groups.

ChemInform Abstract: Base‐Free Palladium‐Catalyzed Cross‐Coupling of Arylsulfonium Salts with Sodium Tetraarylborates.

Palladium-catalyzed cross-coupling reactions of arylsulfonium salts with sodium tetraarylborates were found to proceed smoothly without recourse to an additional base, providing a new, reliable route to biaryls from organosulfur compounds.

Palladium-catalyzed arylations in 4-pyrone systems: 2,6-diaryl-3,5-dibromo-4-pyrones and kojic acid

Palladium-catalyzed cross-coupling reactions of 2,6-diaryl-3,5-dibromo-4-pyrones with imidazole and benzimidazole in the presence of N,N′-dibutylbenzimidazol-2-ylidene as ligand resulted in the formation of the monosubstituted C- and N-arylated products. Kojic acid was also treated with some aryl halides at the same conditions, to afford C-6 arylated derivatives.

P-Bromoaryl- and ω-bromoalkyl-VA-PNBs: suitable starting materials for the functionalization of vinylic addition polynorbornenes via palladium-catalyzed cross-coupling reactions

New routes to functionalize the robust VA-polynorbornene skeleton by Pd-catalyzed cross-coupling reactions usep-bromoaryl- and ω-bromoalkyl-VA-PNBs as versatile starting materials.

Functionalization of pyridyl ketones using deprotolithiation-in situ zincation

Metallation of aryl ketones was achieved by using LiTMP in the presence of ZnCl2·TMEDA, as evidenced by subsequent interception with iodine or by palladium-catalysed cross-coupling reaction.

ChemInform Abstract: Synthesis of 2‐ and 6‐Thienylazulenes by Palladium‐Catalyzed Direct Arylation of 2‐ and 6‐Haloazulenes with Thiophene Derivatives.

Preparation of 2- and 6-thienylazulene derivatives was established by the palladium-catalyzed direct cross-coupling reaction of 2- and 6-haloazulenes with the corresponding thiophene derivatives in good yield. Several thienylazulene derivatives were also used in the reaction with 2-chloroazulene derivatives in the presence of the palladium-catalyst to afford the thiophene derivatives with two azulene functions in good yield.

Postsynthetic modification of peptoids via the Suzuki-Miyaura cross-coupling reaction.

We developed a new method for modifying the side chains of peptoids on a solid phase resin, employing the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction. Optimized conditions using Pd(PPh3 )4 and K2 CO3 in the presence of Buchwald's SPhos ligand provided a high conversion in the coupling reaction. The usefulness of this method was demonstrated by synthesis of a two pyrene-conjugated peptoid helix, which exhibited an interesting excimer formation.

Palladium-Catalyzed Cross-Coupling Reactions of Brominated Porphyrins with Functionalized Organomagnesium Reagents: Direct Preparation of Functional-Group-Bearing Free Base Porphyrins

Palladium-Catalyzed Cross-Coupling Reactions of Brominated Porphyrins with Functionalized Organomagnesium Reagents: Direct Preparation of Functional-Group-Bearing Free Base Porphyrins