Sequential Suzuki Coupling Research Articles

Synthesis of Fused-Ring Derivatives Containing Bifluorenylidene Units via Pd-Catalyzed Tandem Multistep Suzuki Coupling/Heck Cyclization Reaction.

A series of bifluorenylidene derivatives has been facilely synthesized via a palladium-catalyzed tandem multistep Suzuki cross-coupling and Heck cyclization in one pot. The tandem reaction involves two sequential Suzuki couplings and a subsequent Heck cyclization. The target products are obtained in good yields up to 94%. Even in an extended conjugated substrate, the anticipated products can be prepared.

Synthesis of Isoquinolones by Sequential Suzuki Coupling of 2-Halobenzonitriles with Vinyl Boronate Followed by Cyclization.

A novel, facile, and expeditious two-step synthesis of 3,4-unsubstituted isoquinolin-1(2H)-ones from a Suzuki cross-coupling between 2-halobenzonitriles and commercially available vinyl boronates followed by platinum-catalyzed nitrile hydrolysis and cyclization is described.

Synthetic Studies toward Bazzanin K: Regioselective and Chemoselective Three-Component Suzuki Coupling.

The terphenyl substructure of the chiral cyclophane natural product bazzanin K was constructed. The key step involved sequential Suzuki couplings of a nonsymmetric dibromobenzene, which can be performed as a two-step process or as a one-pot three-component coupling. The key step represented a regioselective coupling of a dibromobenzene, as well as a chemoselective coupling of phenyl bromides in the presence of phenyl chlorides. Terphenyl intermediates displayed atropdiastereoisomerism, and they were converted to a single phenanthrene target by way of ring-closing metathesis.

Tailored Synthesis of N -Substituted peri-Xanthenoxanthene Diimide (PXXDI) and Monoimide (PXXMI) Scaffolds.

The tailored synthesis of homo (A2) and hetero (AB) N-substituted peri-xanthenoxanthene diimides (PXXDIs) and peri-functionalized PXX monoimides (PXXMIs) from 3-hydroxy naphthalic anhydride is described. As A2-type PXXDIs could be synthesized in one step, AB-type PXXDIs and PXXMIs were prepared through a modular approach capitalizing on sequential Suzuki coupling, imidation, and Pummerer reactions with very high yields. In view of their potential applications as organic semiconductors, self-organization studies were performed through liquid deposition on surfaces, depicting the formation of islands, needles, and rods.

Selective Preparation of C 2v -Symmetric Hexaphenylbenzene Derivatives through Sequential Suzuki Coupling

We have developed effective reaction conditions for the ­Suzuki cross-coupling of chlorinated hexaphenylbenzene derivatives. A chloro group on a hexaphenylbenzene framework exhibits a low reactivity to Suzuki cross-coupling, and only nickel catalysts bearing alkyl-substituted phosphine ligands achieved the coupling. With this as a key step, we succeeded in the selective preparation of a C 2v -symmetric hexaphenylbenzene derivative containing two kinds of aryl group.

Unexpected Alkene Isomerization during Iterative Cross-Coupling To Form Hindered, Electron-Deficient Trienes.

An iterative cross-coupling approach to conjugated trienes was explored as part of a planned stereoselective synthesis of bicyclic terpenes. Using a bifunctional bromoboronate building block, sequential Suzuki coupling reactions were employed to provide a conjugated trienone target containing a tetrasubstituted alkene. During the final cross-coupling step, an unexpected alkene isomerization was observed to give less hindered trans products. Examination of different substrates determined that conjugation to a ketone withdrawing group was responsible for isomerization, rather than steric hindrance of the tetrasubstituted alkene.

A Sequential Suzuki Coupling Approach to Unsymmetrical Aryl s‐Triazines from Cyanuric Chloride

AbstractA practical approach has been developed for efficient synthesis of unsymmetrical aryl s‐triazines via highly selective sequential Suzuki coupling of cyanuric chloride (2,4,6‐trichlorotriazine) with aryl or vinyl boronic or diarylborinic acids catalysed by 0.1–0.5 mol% Pd(PPh3)2Cl2 under mild conditions. The second and third Suzuki couplings for unsymmetrically trisubstituted aryl s‐triazines could be more practically conducted in one‐pot procedure. An electron‐withdrawing conjugate group at phenyl ring of arylboronic acids was unexpectedly found to completely block the coupling while steric hindrance from an ortho electron‐donating substituent could be overcome.magnified image

Effective one-pot synthesis of (E)-poly(vinyl arylenes) via trans-borylation/Suzuki coupling protocol

Abstract A new stereoselective method for the synthesis of (E)-poly(vinylarenes) on the basis of the Ru-H catalyzed trans-borylation reaction and sequential Suzuki coupling is described. Two different strategies of Pd-catalyzed polycondensation leading to unsaturated organic macromolecular compounds are discussed. Development of a one-pot procedure reduces costs and time, needed for the separation of intermediates, the amount of organic solvents used for purification and therefore has a positive influence on the process sustainability.

One-pot Synthesis and Antitumor Activity of Unsymmetrical Terphenyls.

In this paper a simple and efficient method for the unsymmetrical terphenyls via sequential one-pot Suzuki coupling reactions using Pd(OAc)2 without isolation of the intermediate is described. The prepared terphenyls were found to possess potent anticancer properties against a panel of cancer cells which includes A549, HeLa, MCF7, DU145, HT29 and BxPC-3. Structural similarity with combretastatin A4, these terphenyls disrupted the tubulin polymerization in vitro and destabilized the microtubules in cells. Flow cytometry studies indicated growth arrest of cells in the G2/M phase of the cell cycle corresponding to antimitotic action. Furthermore, compound 4c showed potent anti-mitotic activity even in zebrafish model and could likely be a potential therapeutic compound as it is active both in in vitro and in vivo.

Improved and scalable synthesis of building blocks for the modular synthesis of teraryl-based alpha-helix mimetics

The modular synthesis of teraryl-based alpha-helix mimetics can be accomplished by sequential Suzuki-couplings of arylboronic acid building blocks with 4-iodophenyltriflate core-fragments. We report about new synthetic accesses to core fragments featuring the side chains of Leu, Lys, Cys, Glu, Gln, Ser, and Thr starting from simple phenol precursors.

Synthesis and optical properties of the isomeric pyrimidine and carbazole derivatives: Effects of polar substituents and linking topology

A series of nonlinear oligoarylenes with a pyrimidine unit as central core and carbazole containing aryl branches in positions 2, 4 and 4, 6 of the pyrimidine ring were successfully synthesized by sequential Suzuki coupling of the corresponding 2,4- or 4,6-dichloropyrimidines. Optical properties of the compounds were thoroughly investigated in the media of different polarity. Owing to pronounced electron-accepting properties of pyrimidine core, the compounds with donating carbazole groups showed expressed intramolecular charge transfer (ICT) character of the excited states, which was proved by solvatochromic dynamics and supported by DFT calculations. ICT resulted in the dramatic enhancement of excited state lifetime (up to 5 times) with increased solvent polarity. The competition of constantly decreasing radiative and nonradiative relaxation rates resulted in non-monotonous variation of fluorescence quantum yield from 24% to 74%. The tailoring of fluorescence quantum yield of the pyrimidine derivatives via altering linking topology and polarity of the substituents is discussed.

ChemInform Abstract: Synthesis and Biological Evaluation of Substituted 2‐Anilino‐7H‐pyrrolopyrimidines as PDK1 Inhibitors.

AbstractTitle compounds (V) are synthesized via sequential Suzuki coupling of dichloro‐pyrrolopyrimidine (I) with boronate (II) followed by Buchwald—Hartwig cross‐coupling with various customized anilines (IV).

Diarylpyridazines through Sequential Regioselective Suzuki Coupling

Diarylpyridazines through Sequential Regioselective Suzuki Coupling

One-pot Synthesis of Dibenzyls and 3-Arylpropionic Acids Catalyzed by Linear Polystyrene-Stabilized Palladium Oxide Nanoparticles in Water

Wat-er transformation! Linear, polystyrene-stabilized PdO nanoparticles (PS-PDONPs) are active catalysts for one-pot, multistep reactions in water. The one-pot synthesis of dibenzyls by sequential Suzuki coupling of β-bromostyrene with arylboronic acid and subsequent hydrogenation was achieved. The catalyst was recycled without significant loss of activity. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

From discrete monomeric complexes to hydrogen-bonded dimeric assemblies based on sterically encumbered square planar palladium(ii) ONN-pincers

The 2-(3-biphenyl-2-ol)-6-iminepyridines, 2-(3-C12H8-2-OH)-6-(CH=NAr)C5H3N (Ar = 2,6-i-Pr2C6H3 (L1a-H), 2,4,6-Me3C6H2 (L1b-H)), have been prepared in high yield via sequential Suzuki coupling, deprotection and condensation reactions from 2-methoxybiphenyl-3-ylboronic acid and 2-bromo-6-formylpyridine. Treatment of L1-H with Pd(OAc)2 or (MeCN)2PdCl2 results in deprotonation of L1-H to afford the discrete square planar ONN-chelates, [{2-(3-C12H8-2-O)-6-(CHNAr)C5H3N}Pd(OAc)] (Ar = 2,6-i-Pr2C6H3 (1a), 2,4,6-Me3C6H2 (1b)) and [{2-(3-C12H8-2-O)-6-(CH=NAr)C5H3N}PdCl] (Ar = 2,6-i-Pr2C6H3 (2a), 2,4,6-Me3C6H2 (2b)), in good yield, respectively; conversion of 1 to 2 using aqueous sodium chloride has been demonstrated. Selective reduction of the imino unit in L1-H with LiAlH4 proceeds smoothly to yield the 2-(3-biphenyl-2-ol)-6-(methylamine)pyridines, 2-(3-C12H8-2-OH)-6-(CH2-NHAr)C5H3N (Ar = 2,6-i-Pr2C6H3 (L2a-H), 2,4,6-Me3C6H2 (L2b-H)), which on reaction with Pd(OAc)2 give [{2-(3-C12H8-2-O)-6-(CH2-NHAr)C5H3N}Pd(OAc)] (Ar = 2,6-i-Pr2C6H3 (3a), 2,4,6-Me3C6H2 (3b)). Depending on the temperature of the reaction, the oxidised aldimine products 1a or 1b can also be observed as a competitive side-product during the formation of 3a or 3b. Similarly, ketimine-containing, [{2-(3-C12H8-2-O)-6-(CMe=N(2,6-i-Pr2C6H3))C5H3N}Pd(OAc)] (5), can be detected during the preparation of chiral [{2-(3-C12H8-2-O)-6-(CMeH-NH(2,6-i-Pr2C6H3))C5H3N}Pd(OAc)] (4) from 2-(3-C12H8-2-OH)-6-(CH2-NH(2,6-i-Pr2C6H3))C5H3N (L3-H) and Pd(OAc)2. Complexes 3a, 3b and 4 all exist as dimeric species in the solid state in which two anti-aligned square planar monomers are held together by two intermolecular NH(amine)···O(phenolate) interactions resulting in palladium–palladium separations of between 3.141–3.284 Å. The structurally related chloride-containing dimeric assemblies, [{2-(3-C12H8-2-O)-6-(CH2-NHAr)C5H3N)}PdCl] (Ar = 2,6-i-Pr2C6H3 (6a), 2,4,6-Me3C6H2 (6b)), can also be isolated on treatment of 3 with aqueous sodium chloride or by reaction of L3-H with (MeCN)2PdCl2. Single crystal X-ray diffraction studies have been performed on L1a-H, L3-H, 1a, 1b, 2a, 2b, 3a, 3b, 4, 6a and 6b.

A crystalline D-π-A organic small molecule with naphtho[1,2-b:5,6-b′]dithiophene-core for solution processed organic solar cells

In this work, we have designed and synthesized a new naphtho[1,2-b:5,6-b′]dithiophene-containing enlarged π-conjugated donor–acceptor (D–A) small molecule, NDT(TTz)2, for use in solution-processed organic photovoltaics. NDT(TTz)2, which contains a thiophene-bridged naphtho[1,2-b:5,6-b′]dithiophene as the central fused core and triphenylamine-flanked thiophene thiazolothiazole as a spacer, was synthesized via sequential Suzuki and Stille coupling reactions. The thermal, physiochemical, and electrochemical properties of NDT(TTz)2 have been evaluated by differential scanning calorimetry, thermogravimetry, UV–Vis spectroscopy, photoluminescence spectroscopy, X-ray diffraction, and cyclic voltammetry. As desired for photovoltaic applications, NDT(TTz)2 possesses good solubility, thermal stability, and a well-ordered, π–π stacked, crystallinity. The optical band gap and HOMO level of NDT(TTz)2 were determined to be 2.0eV and −5.23eV, respectively. In addition to organic thin film transistor studies, application of NDT(TTz)2 to preliminary photovoltaic devices has also been investigated by fabricating solution-processed bulk heterojunction solar cells together with PC71BM in a typical layered device structure, ITO/PEDOT:PSS/NDT(TTz)2:PC71BM/LiF/Al. Without extensive optimization of the device, NDT(TTz)2 in these devices shows a maximum power conversion efficiency of 1.44% under AM 1.5 illumination at a 100mW/cm2 intensity.

Photophysical and Electrochemical Properties of Thiophene‐Based 2‐Arylpyridines

AbstractTwo families of thiophene‐based 2‐arylpyridines, in which aryl is phenyl and 2,4‐difluorophenyl, have been developed. The pyridine ring of the new compounds is substituted at the 4‐position with π‐conjugated electron‐rich and electron‐poor thiophene‐based fragments to tune the optical and energetic properties. The high‐yielding synthetic access, which consists of two sequential Suzuki coupling reactions, the first of which is completely regioselective, is of wide applicability and allows access to a large variety of derivatives. The absorption/emission and redox features, as well as the HOMO and LUMO energy levels, have been investigated; the results show that the optical and electronic properties can be tuned over a broad range. The diversity of the characteristics may be effectively exploited by using the thiophene‐substituted 2‐arylpyridines as ligands in cyclometalated sensitizers for dye‐sensitized solar cells and other optoelectronic applications.

Synthesis and Pharmacological Evaluation of N-(3-(1H-Indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a Potent Antimitotic Agent

The synthesis and optimization of a series of orally bioavailable 1-(1H-indol-4-yl)-3,5-disubstituted benzene analogues as antimitotic agents are described. A functionalized dibromobenzene intermediate was used as a key scaffold, which when modified by sequential Suzuki coupling and Buchwald-Hartwig amination provided a flexible entry to 1,3,5-trisubstituted phenyl compounds. A 1H-indol-4-yl moiety at the 1-position was determined to be a critical feature for optimal potency. The compounds have been shown to induce cell cycle arrest at the G2/M phase and demonstrate efficacy in both cell viability and cell proliferation assays. The primary site of action for these agents is revealed by their colchicine competitive inhibition of tubulin polymerization, and a computational model has been developed for the association of these compounds to tubulin. An optimized lead LP-261 significantly inhibits growth of a human non-small-cell lung tumor (NCI-H522) in a mouse xenograft model.

ChemInform Abstract: One‐Pot Double Suzuki Couplings of Dichloropyrimidines.

AbstractReaction conditions are developed for a sequential Suzuki coupling of substrate (I) with 2 different arylboronic acids which allow the synthesis of diarylated pyrimidines in a one‐pot manner.

Palladium-catalyzed one-pot Suzuki coupling followed by arylpalladium addition to aldehyde: a convenient route to fluoren-9-one derivatives

Various fluoren-9-one derivatives were prepared efficiently by a one-pot reaction involving sequential Suzuki coupling of 2-bromophenyl boronic acid with 2-bromocarboxaldehyde followed by intramolecular arylpalladium addition to aldehyde.