Cross-coupling Methodology Research Articles

2,6‐Disubstituted Pyran‐4‐one and Thiopyran‐4‐one Inhibitors of DNA‐Dependent Protein Kinase (DNA‐PK).

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of tricarbonyl η 6- and η 5-[(3-thiophenyl)organo]chromium and -manganese complexes

The syntheses of tricarbonyl η 6-[(3-thiophenyl)arene]chromium 1a, 1b and η 5-[(3-thiophenyl)cyclohexadienyl]manganese complexes 2 are reported using a Stille cross-coupling methodology. A two-step strategy involving a Stille reaction– exo-hydride abstraction sequence allowed selective access to cationic tricarbonyl η 6-[(3-thiophenyl)arene]manganese complex 3. 1H-NMR data of these 3-thiophenylchromium and manganese complexes are presented as well as a comparison with the corresponding 2-thiophenyl-substituted derivatives described in the literature. The crystal structure determinations of 3-thiophenyl and 2-thiophenyl-η 6-(arene)Cr(CO) 3 complexes showing the conformations of the Cr(CO) 3 tripods are also reported.

2,6-disubstituted pyran-4-one and thiopyran-4-one inhibitors of DNA-Dependent protein kinase (DNA-PK).

6-aryl-2-morpholin-4-yl-4H-pyran-4-ones and 6-aryl-2-morpholin-4-yl-4H-thiopyran-4-ones were synthesised and evaluated as potential inhibitors of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). Several compounds in each series exhibited superior activity to the chromenone LY294002, and were of comparable potency to the benzochromenone NU7026 (IC(50)=0.23 microM). Importantly, members of both structural classes were found to be selective inhibitors of DNA-PK over related phosphatidylinositol 3-kinase-related kinase (PIKK) family members. A multiple-parallel synthesis approach, employing Suzuki cross-coupling methodology, was utilised to prepare libraries of thiopyran-4-ones with a range of aromatic groups at the 3'- and 4'-positions on the thiopyran-4-one 6-aryl ring. Screening of the libraries resulted in the identification of 6-aryl-2-morpholin-4-yl-4H-thiopyran-4-ones bearing naphthyl or benzo[b]thienyl substituents at the 4'-position, as potent DNA-PK inhibitors with IC(50) values in the 0.2-0.4 microM range.

Meso-tetraaryl cofacial bisporphyrins delivered by Suzuki cross-coupling.

The Suzuki cross-coupling methodology provides a facile synthetic approach for the modular preparation of meso-tetraaryl cofacial bisporphyrins anchored by xanthene and dibenzofuran. This synthetic method furnishes cofacial bisporphyrin templates with enhanced steric and electronic protection from mu-oxo formation and oxidative degradation. The ability of these platforms to support multielectron oxidation chemistry mediated by proton-coupled electron transfer (PCET) is demonstrated by their reactivity for the catalytic disproportionation of hydrogen peroxide to oxygen and water.

New pyrimidine- and fluorene-containing oligo(arylene)s: synthesis, crystal structures, optoelectronic properties and a theoretical study.

New pyrimidine containing oligo(arylene)s, notably the pyrimidine-fluorene hybrid systems 13-16, have been synthesised by Suzuki cross-coupling methodology. An efficient synthesis of the key reagent 9,9-dihexylfluorene-2,7-diboronic acid 10 from 2,7-dibromo-9,9-dihexylfluorene 9 is reported. Cross-coupling of 10 with two equivalents of 2-bromopyrimidine, 5-bromopyrimidine and 2,5-dibromopyrimidine gave 2,7-bis(2-pyrimidyl)-9,9-dihexylfluorene 13. 2,7-bis(5-pyrimidyl)-9,9-dihexylfluorene 14 and 2,7-bis(5-bromo-2-pyrimidyl)-9,9-dihexylfluorene 15 in 23-34% yields. A further two-fold Suzuki reaction of benzeneboronic acid with compound 15 gave 2,7-bis(5-phenyl-2-pyrimidyl)-9,9-dihexylfluorene 16 (35% yield). Ab initio calculations of the geometries and electronic structures at the Hartree Fock (HF) and density functional theory (DFT) levels of theory are reported for compounds 13, 14 and 16 (with ethyl substituents replacing hexyl) and for their dipyrazinyl and bistetraazenyl analogues, 17, 18, 20 and 21. The heterocyclic nitrogen atoms of 13 and 16 facilitate planarisation of the system, compared to 14, which is in agreement with X-ray structural data obtained for 5-bromo-2-phenylpyrimidine 6, 2,5-diphenylpyrimidine 7 and compound 15. Bistetrazenyl derivative 21 is calculated to be a fully planar system. The cyclic voltammogram (CV) of compound 16 in dichloromethane solution shows a quasi-reversible oxidation wave at E(1/2)0 = +1.36 V (vs. Ag/Ag+). Compound 13 is a poorer donor with an oxidation observed at Epa = +1.50 V which is in good agreement with the difference in the energies of their HOMO orbitals calculated at both HF and DFT levels of theory (0.11-0.12 eV). For compound 14 we were not able to measure an Eox potential which should lie at much more positive potentials. Compounds 15 and 16 are blue emitters in solution, with photoluminescence quantum yields (PLQY) of 25% and 85%, respectively. For thin films of 16 the PLQY is reduced to 21%. An OLED using compound 16 as the emissive layer has been fabricated in the configuration ITO/PEDOT/16/Ca/Al: blue-green light (lambda max 500 nm) most likely emanating primarily from excimer states is emitted at a high turn-on voltage.

Ortho-linked polyaryloxide ligands and their titanium complexes.

Ortho-linked polyphenols, quaterphenol L(OH)4, and moderately hindered terphenol PhL(OH)3 are developed as new multidentate polyaryloxide ligands for transition-metal chemistry. The polyphenols are synthesized using ortho-metalation and metal-catalyzed cross-coupling methodologies; the synthetic routes allow for facile electronic and steric modification of the basic ligand design. The Ti(IV) coordination chemistry of these ligands reveals a diverse collection of bridged structures: dimeric [Ti(mu-PhLO3)(OiPr)]2 (P2(1)/n, a = 12.2699(5) A, b = 11.7957(5) A, c = 21.238(1) A, beta = 94.551(1) degrees, Z = 2, T = 170(2) K), dimeric [Ti2(mu-PhLO3)2(mu-Cl)(Cl)(THF)] (P1, a = 11.212(1) A, b = 14.165(1) A, c = 22.447(2) A, alpha = 90.440(4) degrees, beta = 93.345(4) degrees, gamma = 111.164(4) degrees, Z = 2, T = 170(2) K), and trimeric [Ti3(mu,mu'-LO4)(mu-OiPr)2(OiPr)6] P2(1)/n, a = 11.1022(5) A, b = 18.7015(9) A, c = 24.409(1) A, beta = 95.369(2) degrees, Z = 4, T = 170(2) K). The reaction of TiCl3(THF)3 with [PhLO3]3- results in oxidation of Ti(III) to Ti(IV) and formation of the oxo dimer [Ti(PhLO3)(THF)]2(mu-O) (P1, a = 10.8649(6) A, b = 12.1882(7) A, c = 14.3349(9) A, alpha = 65.602(3) degrees, beta = 84.390(3) degrees, gamma = 86.582(3) degrees, Z = 1, T = 200(2) K); the oxo group presumably originates from the THF solvent. The titanium centers in these environments are either 5- or 6-coordinate, with distorted square pyramidal/trigonal bipyramidal and distorted octahedral geometries, respectively; the polyphenoxide chelate ligands are capable of bridging multiple oxophilic titanium sites.

Hypervalent siloxane derivatives. An alternative to Stille and Suzuki couplings

Abstract Siloxane methodology is extended to couplings with iodo- and bromoanilines, hindered arylbromides, and substituted siloxanes as substrates. Additionally, initial studies with 5-bromoindole and other heteroaromatics suggest that the siloxane-mediated cross coupling methodology will also be applicable in these systems.

Preparation of Novel 6-Substituted-4-Hydroxy-2H-Pyran-2-one-3-Carboxamides and Esters via Palladium-Catalyzed Cross-Coupling Methodology

Novel 6-substituted-4-hydroxy-2H-pyran-2-one-3-carboxamides and esters 1 were prepared in a 2-step procedure from known 7-chloro-2,2-dimethylpyrano[4,3-d]1,3-dioxin-4,5-dione 2. Palladium catalyzed cross coupling methodology was employed in the key transformation of 2 to 4. The strategy describes a significant improvement over known literature methods.

Synthesis of 4-Nitro-1-Pentynylbenzene: An Example of Transitional Metal-Mediated Cross-Coupling

A procedure for the preparation and purification of 4-nitro-1-pentynylbenzene is reported for use as an introductory organic laboratory exercise. Synthesis of the target compound exemplifies contemporary Pd-mediated cross-coupling methodologies. In this regard, several fundamental mechanistic aspects of catalytic organometallic chemistry are illustrated, including oxidative addition, transmetallation, and reductive elimination. Purification of the target compound via flash column chromatography exposes students to a central technique of modern synthetic methodology. Spectroscopic characterization of the target compound reinforces fundamental skills in 1H NMR, 13C NMR, and IR analysis and interpretation.

Highly conjugated, acetylenyl bridged porphyrins: new models for light-harvesting antenna systems.

A new class of porphyrin-based chromophore systems has been prepared from ethyne-elaborated porphyrin synthons through the use of metal-mediated cross-coupling methodologies. These systems feature porphyrin chromophores wired together through single ethynyl linkages. This type of topological connectivity affords exceptional electronic interactions between the chromophores which are manifest in their room temperature photophysics, optical spectroscopy, and electrochemistry; these spectroscopic signatures indicate that these species model many of the essential characteristics of biological light-harvesting antenna systems.

Combined directed metalation - cross coupling strategies. A regiospecific route to heteroring-annelated artho-naphthoquinones and a short synthesis of β-lapachone

A general combined metalation - cross coupling methodology ( Scheme 1) for the regiospecific construction of heteroring fused o-naphthoquinones 8 is described and its application to a short synthesis of the antimalarial/antitumor natural product β-lapachone ( 14) is demonstrated.

ChemInform Abstract: Integrated Aromatic Metalation. Cross Coupling Methodologies. A Concise Synthesis of the Azafluoranthene Alkaloid Imeluteine.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

Concise syntheses of the amaryllidaceae alkaloids ungerimine and hippadine via the suzuki aryl-aryl cross coupling reaction

Short syntheses of the betaine alkaloid ungerimine ( 1) and the lactam alkaloid hippadine ( 4) based on aryl boronic acid - aryl halide cross coupling methodology are described.