714965-11-4

Upstream product

• 4433-11-8 3,4-dimethylbiphenyl 
• 4383-39-5 Propiolsaeure-(2-propinyl)ester 
• 536-74-3 phenylacetylene 
• 64169-34-2 5-bromophthalide 
• 1078-58-6 diphenylzinc 
• 1411945-85-1 C₈H₄O₂ 
• 71-43-2 benzene 
• 98-80-6 phenylboronic acid 
• 50-00-0 formaldehyd 
• 117926-67-7 5-phenyl-1,3-dihydro-isobenzofuran 
• 166386-69-2 5-bromo-2-benzofuran-1(3H)-one 

Relevant academic research and scientific papers

Rhodium-catalysed tetradehydro-Diels-Alder reactions of enediynes: Via a rhodium-stabilized cyclic allene

Efficient methods for the synthesis of fused-aromatic rings is a critical endeavour in the creation of new pharmaceuticals and materials. A direct method for preparing these systems is the tetradehydro-Diels-Alder reaction, however this is limited by the need for harsh reaction conditions. A potential, but underdeveloped, route to these systems is via transition metal-catalysed cycloaromatisation of ene-diynes. Herein, tethered unconjugated enediynes have been shown to undergo a facile room-temperature RhI-catalysed intramolecular tetradehydro-Diels-Alder reaction to produce highly substituted isobenzofurans, isoindolines and an indane. Furthermore, experimental and computational studies suggest a novel mechanism involving an unprecedented and complex RhI/RhIII/RhI/RhIII redox cycle involving the formation of an unusual strained 7-membered rhodacyclic allene intermediate and a RhIII-stabilized 6-membered ring allene complex.

Synthesis of 3-Unsubstituted Phthalides from Aryl Amides and Paraformaldehyde via Ruthenium(II)-Catalyzed C–H Activation

A straightforward and convenient route has been developed for the synthesis of 3-unsubstituted phthalide derivatives from aryl amides and paraformaldehyde by ruthenium(II)-catalyzed C–H activation. The reaction proceeds through tandem ortho-hydroxymethylation of aryl amide and subsequent intramolecular lactonization.

In Silico Fragment-Based Design Identifies Subfamily B1 Metallo-β-lactamase Inhibitors

Zinc ion-dependent β-lactamases (MBLs) catalyze the hydrolysis of almost all β-lactam antibiotics and resist the action of clinically available β-lactamase inhibitors. We report how application of in silico fragment-based molecular design employing thiol-

A simple, convenient, highly regioselective synthesis of isobenzofuran-1(3H)-ones (phthalides) as well as Maculalactone A & B, the Bioactive Butyrolactones

Bacground: Among the class of oxygen heterocycles, the benzoannulated lactone (3H-isobenzofuran-1-one or phthalide) moiety is found in many natural products. Phthalides possess a wide range of biological activity e.g. (-)-Hidrastine is active at the human opioid receptor known as CCR5, while fuscinarin interferes with HIV entry into cells. Phthalides also represent an important structural subunit in numerous natural products that exhibit a wide range of biological activities, such as antispasmodic, antifungal, vasodilators, and coronary artery dilators. Except their biological activities, phthalides are also versatile starting material for the synthesis of various important organic compounds, including the key intermediates in the synthesis of functionalized naphthalenes and anthracenes, which in turn are used as synthons for tricyclic and tetra cyclic aromatic natural products. The present communication describes a simple but efficient and expedient one pot strategy for the synthesis of phthalides. Methods: Diethyl phthalate was considered initially for the cyclization strategy using different metal hydrides at variable temperatures. The reaction was carried out at-30°C with 2.5 equivalent of DIBAL-H, the phthalide was obtained in ~68% yield along with minor amount of alcohol (~10%) and the unreacted starting material (~12%). In the reaction protocol, other solvents such as tetrahydrofuran, diethyl ether, and chlorobenzene were found to be effective in cyclization at-30°C. But yield of the phthalide was observed to be less compare to CH2Cl2. Further decrease of the reaction temperature up to-78°C showed no effect on the yield of cyclized product. Use of 3 equivalent of DIBAL-H dramatically decreases the yield of the cyclized product (30%) and increased the amount of reduced product (60%). Results: The promising outcome of the above observations encouraged us to study the general scope and limitations of this protocol for the reduction of different substituted phthalides. It was found that diethyl esters of nitro-, bromo-, 4'-methyl-biphenyl-, 3'-methyl-biphenyl-, 2'-methyl-biphenyl-, biphenyl-, 4-pyrazin-2-yl-, and 4-(4-methyl-Thiazol-5-yl)-substituted phthalic acids readily underwent reduction with DIBAL-H to afford the corresponding phthalides in moderate to good yields. Conclusion: We developed a simple, convenient, one step protocol for the synthesis of isobenzofuran-1(3H)-ones (phthalides) from phthalate esters in moderate to good yields. We have also demonstrated a short and effective route to prepare two bioactive butyrolactones, viz., maculalactone A & B. In our opinion, the present approach is general in nature and could be useful to design diverse butyrolactone skeletons.

Facile construction of pyrrolo[1,2-: B] isoquinolin-10(5 H)-ones via a redox-amination-aromatization-Friedel-Crafts acylation cascade reaction and discovery of novel topoisomerase inhibitors

An efficient redox-amination-aromatization-Friedel-Crafts acylation cascade process from trans-4-hydroxyproline and 2-formylbenzoic acids has been developed for the synthesis of pyrrolo[1,2-b]isoquinolin-10(5H)-ones. Compound 3h was identified as a new potent dual topoisomerase I/II inhibitor.

Hydroarylation of arynes catalyzed by silver for biaryl synthesis

A new biaryl synthesis via silver-catalyzed hydroarylation of arynes from acyclic building blocks with unactivated arenes in intra- and intermolecular manners has been developed. The previously observed Diels-Alder reactions of arynes with arene were not observed under the current silver-catalyzed conditions. Deuterium scrambling and DFT calculations suggest a stepwise electrophilic aromatic substitution mechanism through the formation of a Wheland-type intermediate followed by a water-catalyzed proton transfer in the final step of the hydroarylation.

Negishi cross-coupling reactions catalyzed by an aminophosphine-based nickel system: A reliable and general applicable reaction protocol for the high-yielding synthesis of biaryls

Treatment of NMP solutions of NiCl2 with 1,1′,1″- (phosphanetriyl)tripiperidine (≈2.05 equiv), dissolved in THF, in air at 25°C forms a highly active catalytic system for the cross-coupling of a large variety of electronically activated, non-activated, deactivated, and ortho-substituted, heterocyclic, and functionalized aryl bromides and aryl chlorides with diarylzinc reagents. Very high levels of conversion and yields were obtained within 2 h at 60°C in the presence of only 0.1 mol% of catalyst (based on nickel) and thus at catalyst loadings far lower than typically reported for nickel-catalyzed versions of the Negishi reaction. Various aryl halides-which may contain trifluoromethyl groups, fluorides, or other functional groups such as acetals, ketones, ethers, esters, lactones, amides, imines, anilines, alkenes, pyridines, quinolines, and pyrimidines-were successfully converted into the corresponding biaryls. Electronic and steric variations are tolerated in both reaction partners. Experimental observations indicate that a molecular (NiI/NiIII) mechanism is operative.

[Pd(Cl)2(P(NC5H10)(C6H 11)2)2] - A highly effective and extremely versatile palladium-based negishi catalyst that efficiently and reliably operates at low catalyst loadings

[Pd(Cl)2(P(NC5H10)-(C6H 11)2]2] (1) has been prepared in quantitative yield by reacting commercially available [Pd(cod)(Cl)2] (cod = cyclooctadiene) with readily prepared 1-(dicyclohexylphosphanyl)piperidine in toluene under N2 within a few minutes at room temperature. Complex 1 has proved to be an excellent Negishi catalyst, capable of quantitatively coupling a wide variety of electronically activated, non-activated, deactivated, sterically hindered, heterocyclic, and functionalized aryl bromides with various (also heterocyclic) arylzinc reagents, typically within a few minutes at 100°C in the presence of just 0.01 mol% of catalyst. Aryl bromides containing nitro, nitrile, ether, ester, hydroxy, carbonyl, and carboxyl groups, as well as acetais, lactones, amides, anilines, alkenes, carboxylic acids, acetic acids, and pyridines and pyrimidines, have been successfully used as coupling partners. Furthermore, electronic and steric variations are tolerated in both reaction partners. Experimental observations strongly indicate that a molecular mechanism is operative.

The 1,3-diaminobenzene-derived aminophosphine palladium pincer complex {C6H3[NHP(piperidinyl)2]2Pd(Cl)} - A highly active Suzuki-Miyaura catalyst with excellent functional group tolerance

The rapidly prepared 1,3-diaminobenzenederived aminophosphine pincer complex {C6H3 [NHP(piperidinyl)2] 2Pd(Cl)} (1) is an effective Suzuki catalyst with excellent functional group tolerance. Side-product formations, such as homocoupling, debromation or protodeboration have only rarely been detected and if so, were in all cases below the 5% level. The presented reaction protocol is universally applicable. Experimental observations indicate that palladium nanoparticles are the catalytically active form of 1.