1256169-41-1Relevant academic research and scientific papers
A simple, convenient, highly regioselective synthesis of isobenzofuran-1(3H)-ones (phthalides) as well as Maculalactone A & B, the Bioactive Butyrolactones
Joardar, Soumen,Chakravorty, Santanu,Das, Sakti P.
, p. 127 - 134 (2016/03/01)
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.
Negishi cross-coupling reaction catalyzed by an aliphatic, phosphine based pincer complex of palladium. biaryl formation via cationic pincer-type Pd IV intermediates
Gerber, Roman,Blacque, Olivier,Frech, Christian M.
experimental part, p. 8996 - 9003 (2011/10/31)
The aliphatic, phosphine-based pincer complex [(C10H 13-1,3-(CH2P(Cy2)2)Pd(Cl)] (1) is a highly active Negishi catalyst, enable to quantitatively couple various electronically activated, non-activated, deactivated, sterically hindered and functionalized aryl bromides with various diarylzinc reagents within short reaction times and low catalyst loadings. Experimental observations strongly indicate that a molecular mechanism is operative with initial chloride dissociation of 1 and formation of the cationic T-shaped 14e- complex [(C10H13-1,3-(CH2P(C6H 11)2)2)Pd]+ (B), which undergoes oxidative addition of an aryl bromide (Ar′Br) to yield the cationic, penta-coordinated aryl bromide pincer complexes of type [(C10H 13-1,3-(CH2P(Cy2)2)Pd(Br) (aryl′)]+ (C) with the metal center in the oxidation state of +IV and the aryl unit in cis position relative to the aliphatic pincer core. Subsequent transmetalation with Zn(aryl)2 result in the cationic diaryl pincer complexes of type [(C10H13-1,3-(CH 2P(Cy2)2)Pd(aryl)(aryl′)]+ (D), which reductively eliminate the coupling products, thereby regenerating the catalyst. The neutral square planar aryl pincer complex - a possible key intermediate in the catalytic cycle - was found to be reversibly formed in the reaction mixture but is not involved in the catalytic mechanism. Similarly, palladium nanoparticles as the catalytically active form of 1 could have been excluded. The Royal Society of Chemistry 2011.
[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
Bolliger, Jeanne L.,Frech, Christian M.
experimental part, p. 11072 - 11081 (2010/11/16)
[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.
