A simple one-step protocol for the olefination of vinylogous formamides

Vinylogous formamides--5-formyluracils and 4-formylpyrazoles-undergo smooth olefination in THF in the presence of indium metal (0.8 equiv) and BF₃·OEt₂ (1 equiv) and allyl bromide (1 equiv) to provide the respective diene-substituted heterocycles in a single step     

Tandem catalysis in ionic liquids: a recyclable catalytic synthesis of benzofuran derivatives

A convenient, recyclable catalytic synthesis of benzofuran-2-acetic esters 2 by sequential Pd(0)-catalyzed deallylation—Pd(II)-catalyzed carbonylative heterocyclization of 1-(2-allyloxyphenyl)-2-yn-1-ols 1 in ionic liquids is presented. Reactions were typically carried out in BmimBF₄ as the solvent at 100 °C and under 30 atm of CO, in the presence of catalytic amounts (1 mol %) of PdI₂ in conjunction with KI (1 equiv), PPh₃ (4 mol %), MeOH (28 equiv), and H₂O (2 equiv). The solvent-catalyst system could be recycled several times without appreciable loss of catalytic activity.     

Palladium catalyzed atom-efficient cross-coupling reactions of triarylbismuths with aryl bromides

Aryl bromides (3 equiv) were coupled efficiently with triarylbismuths (1 equiv) in an atom-efficient way using the Pd(OAc)₂/PPh₃ catalytic system in the presence of K₃PO₄ as base in DMF at 90 °C, providing excellent yields of the cross-coupled biaryls in short reaction times.     

Synthesis of α-aminonitriles under mild catalytic,metal-free conditions

α-Aminonitriles have been synthesized by a Strecker synthesis from aldehydes and ketones under mild catalytic, metal-free conditions. Aromatic aldehydes (1 equiv) were reacted with aromatic and 1° or 2° aliphatic amines (1 equiv) in EtOH containing 3 mol % of NH₄Cl to give high yields of α-aminonitriles. An alternative to adding NH₄Cl as a catalyst involved the use of excess TMSCN (1 equiv) and to promote the process. The reaction was also successful under microwave conditions using excess TMSCN with no solvent. Ketones similarly reacted with aromatic amines and excess TMSCN under conventional and microwave heating, but 30 mol % of added NH₄Cl was required for optimum conversion.     

Palladium-free zinc-mediated hydroamination of alkynes: efficient synthesis of indoles from 2-akynylaniline derivatives

Reaction of 2-phenylethynyl N-tosylanilide prepared by Pd-free procedure with ZnBr₂ (3 equiv) in refluxing toluene gave N-tosyl-2-phenylindole in 93% yield. Treatment of 2-phenylethynylaniline with ZnBr₂ (1 equiv) in refluxing toluene resulted in the formation of 2-phenylindole in 91% yield. Catalytic ZnBr₂ (0.05 equiv) effectively reacted with 2-alkynylanilines to afford 2-substituted indoles in high yields. Thus, complete Pd-free zinc catalyzed hydroamination of 2-alkynylanilines was achieved.     

An atom-efficient palladium-catalyzed cross-coupling reaction of triarylbismuths with acid chlorides: synthesis of diaryl and alkyl aryl ketones

The cross-coupling reaction of triarylbismuths with acid chlorides using a catalytic amount of PdCl₂/PPh₃ afforded the corresponding ketones in high yields. The reactions of aromatic and aliphatic acid chlorides occurred with atom efficiency, as 3 equiv of acid chlorides coupled effectively with 1 equiv of triarylbismuths to yield 3 equiv of the corresponding diaryl and alkyl aryl ketones.     

Iridium-catalyzed hydroboration of alkenes with pinacolborane

Hydroboration of terminal and internal alkenes with pinacolborane (1.2 equiv) was carried out at room temperature in the presence of an iridium(I) catalyst (3 mol%). Addition of dppm (2 equiv) to [Ir(cod)Cl]₂ gave the best catalyst for hydroboration of aliphatic terminal and internal alkenes at room temperature, resulting in addition of the boron atom to the terminal carbon of 1-alkenes with more than 99% selectivities. On the other hand, a complex prepared from dppe (2 equiv) and [Ir(cod)Cl]₂ resulted in the best yields for vinylarenes such as styrene. These complexes exhibited higher levels of catalyst activity and selectivity than those of corresponding rhodium complexes.     

gem-Difluoropropargylation of aldehydes using cat. In/Zn in aqueous media

Zn (0.9 equiv) in combination with catalytic amounts of In (0.1 equiv) and I₂ (0.1 equiv) was found to effect the reaction of several difluoropropargyl bromide derivatives with aldehydes to produce gem-difluorohomopropargyl alcohols in aqueous media under conditions suitable for large scale applications.     

Palladium(II) chloride/EDTA-catalyzed biaryl homo-coupling of aryl halides in aqueous medium in the presence of ascorbic acid

Both electron-deficient and electron-rich aryl bromides undergo biaryl homo-coupling in a basic aqueous-ethanolic medium in the presence of PdCl₂-EDTA (1:1 molar ratio, 3 mol %) as catalyst and ascorbic acid as reductant (1 mol equiv) in acceptable to good yields.     

Deprotonation of chloropyridines using lithium magnesates

4-Chloropyridine was deprotonated on treatment with 1/3 equiv of the highly coordinated magnesate Bu₃(TMP)MgLi₂ in THF at −10 °C, as evidenced by trapping with I₂. The use of Bu(TMP)₂MgLi in Et₂O allowed the reaction of 2-chloropyridine, giving the 3-functionalized derivative as the main product. Mixtures of 3- and 4-functionalized derivatives were obtained when 2,6-dichloropyridine was involved in the reaction. Performing the reaction on 3-chloropyridine with lithium magnesates in THF, either the 4,4′-dimer or the 4-iodo derivative was formed after quenching by I₂, the former using 1/3 equiv of Bu₂(TMP)MgLi and the latter using 1 equiv of (TMP)₃MgLi. Similar results were observed with 3,5-dichloropyridine, 2,5-dichloropyridine and 3-chloro-2-fluoropyridine. 1,2-Migration of the lithium arylmagnesate formed by deprotonation was proposed to justify the dimers formation.     

Sonogashira coupling with aqueous ammonia directed to the synthesis of azotolane derivatives

Sonogashira coupling with aqueous ammonia is tolerable for the reaction of aryl iodides or terminal alkynes bearing an azobenzene group. The reaction of (4-heptyloxyphenyl)ethyne with (4-heptyloxyphenyl)-(4-iodophenyl)diazene in the presence of 1 mol% of PdCl₂(PPh₃)₂, 2 mol% of CuI, and 2 equiv of 0.5 M aqueous ammonia gives the corresponding azotolane in 87% isolated yield after stirring at room temperature for 15 h.     

Ligand-free, atom-efficient Suzuki-Miyaura type cross-coupling reactions at room temperature

The atom-efficient cross-coupling reaction of sodium tetraarylborates with aryl iodides and bromides was reported. The reaction can be performed directly using a catalytic system composed of palladium chloride, sodium carbonate and methanol (PdCl₂/Na₂CO₃/MeOH) under heat-free conditions at room temperature in an open air conditions. The reactions carried out in an atom-efficient way as 4 equiv of aryl halides coupled effectively with 1 equiv of sodium tetraarylborates to furnish 4 equiv of the corresponding functionalized biaryls in good to excellent yields.     

4-(tert-Butyldimethylsilyloxy)benzylidene acetal: a novel benzylidene-type protecting group for 1,2-diols

A novel 1,2-diol-protecting group, p-silyloxybenzylidene group, has been developed. In addition to the stepwise deprotection conditions including desilylation and the subsequent acidic hydrolysis of the p-hydroxybenzylidene group in AcOH-THF-H₂O, we have established the one-pot deprotection under basic conditions [K₂CO₃ (5 equiv), NH₂OH·HCl (5 equiv), and CsF (1 equiv) in MeOH-H₂O].     

One-pot synthesis of 1,4-diarylsubstituted 1,3-diynes from the sequential coupling reactions of aryl iodides and propiolic acid

1,4-Disubstituted 1,3-dialkynes were obtained from the one-pot palladium/copper-catalyzed coupling reactions of aryl iodide and propiolic acid. The optimized catalytic system consisted of 5.0 mol % Pd(PPh₃)₂Cl₂, 10 mol % dppb, 10 mol % CuI, 2.4 equiv of DBU, and 1.2 equiv of K₂CO₃. The coupling reaction was carried out at 30 °C for 6 h and subsequently at 80 °C for 3 h.     

Synthesis and characterisation of titanium pyridine- and pyrimidine-thiolates and their application as precursors to titanium disulfide

The reaction of TiCl₄ with pyridine- and pyrimidine-thiol has been investigated. Reaction of TiCl₄ with 3 equiv. of 2-mercaptopyridine and 3 equiv. of tert-butylpyridine in toluene at room temperature resulted in the formation of the tris(pyridine-2-thiolate) complex [TiCl(SC₅H₄N)₃] (1). The related reaction between TiCl₄ with 3 equiv. of 2-mercaptopyrimidine and 3 equiv. of tert-butylpyridine in toluene at room temperature resulted in the isolation of the complex [TiCl(SC₄H₃N₂)₃] (2). Compound 2 has been characterised by X-ray crystallography. Low pressure CVD of 1 and 2 produced brown/gold films of TiS₂/TiO₂ on glass substrates at 550 and 600 °C.     

Microwave-assisted cycloadditions of 2-alkynylbenzonitriles with sodium azide: selective synthesis of tetrazolo[5,1-a]pyridines and 4,5-disubstituted-2H-1,2,3-triazoles

Under microwave irradiation (75 W), treatment of 2-alkynylbenzonitriles with 1.5 equiv of sodium azide in DMSO at 140 °C gave 4,5-disubstituted-2H-1,2,3-triazoles in 60-99% yields. Additionally, adding 8 equiv of ZnBr₂ and using 8 equiv of sodium azide in DMF at 100 °C lead to the formation of tetrazolo[5,1-a]isoquinolines up to 87% yield.     

Rhodium(I)/cationic 2,2′-bipyridyl-catalyzed [2+2+2] cycloaddition of α,ω-diynes with alkynes in water under air

A simply performed procedure for the [Rh(cod)Cl]₂/cationic 2,2′-bipyridyl system-catalyzed [2+2+2] cycloaddition of α,ω-diynes with terminal and internal alkynes was achieved in water under air at 60 °C. The reaction proceeded smoothly with 1 equiv α,ω-diynes and 3 equiv alkynes in the presence of 20 mol % KOH for 1 h or 9 h, resulting in the formation of tri- and tetra-substituted benzene derivatives in moderate to high yields. After separation of the organic products by extraction, the residual aqueous solution could be reused for further reactions until complete degradation of its catalytic activity.     

Highly enantioselective addition of linear alkyl alkynes to linear aldehydes

It is discovered that the use of biscyclohexylamine (Cy₂NH) as an additive can greatly enhance the enantioselectivity for the reaction of linear alkyl alkynes with linear aldehydes. The combination of (S)-BINOL (20 mol %), Cy₂NH (5 mol %), ZnEt₂ (2 equiv), and Ti(OⁱPr)₄ (0.5 equiv) catalyzes the reaction at room temperature in diethyl ether solution with 81-89% ee and 57-77% yield.     

Deprotonation of fluoro aromatics using lithium magnesates

3-Fluoropyridine was deprotonated on treatment with 1/3 equiv of Bu₃MgLi in THF at −10 °C. The lithium arylmagnesate formed was either trapped with electrophiles or involved in a palladium-catalyzed cross-coupling reaction with 2-bromopyridine. The use of a less nucleophilic lithium-magnesium-dialkylamide, (TMP)₃MgLi, allowed the reaction of 3-fluoroquinoline, giving the 2,2′-dimeric derivative. 2-Fluoropyridine and 2,6-difluoropyridine were deprotonated using 1/3 equiv of the highly coordinated magnesate Bu₄MgLi₂ in THF at −10 °C in the presence of a substoichiometric amount of 2,2,6,6-tetramethylpiperidine. 1,3-Difluorobenzene reacted similarly when treated with Bu₃MgLi; the reactivity of the base proved to be enhanced by the presence of TMEDA.     

Simultaneous reduction of nitro- to amino-group in the palladium-catalyzed Suzuki cross-coupling reaction

An efficient method for palladium-catalyzed Suzuki cross-coupling reaction with simultaneous reduction of nitro- to amino-group has been developed. This method allows nitro-substituted aryl halides to readily react with arylboronic acids, to afford aryl substituted aniline in low to excellent yields. The reaction was catalyzed by Pd(OAc)₂ (3 mol %) at 150 °C under atmospheric pressure in the presence of K₂CO₃ (3 equiv) in DMF/H₂O (5/1).