Palladium-catalyzed cross-coupling reaction of alkenyl bromides with potassium alkyltrifluoroborates

The Suzuki-Miyaura-type cross-coupling reaction of potassium alkyltrifluoroborates with various alkenyl bromides in the presence of 10 mol % of PdCl₂(dppf)·CH₂Cl₂ and 3.0 equiv of Cs₂CO₃ in aqueous toluene at 80 °C provided the desired compounds in 63-95% yields. A variety of functional groups in the potassium alkyltrifluoroborates were tolerated under the basic conditions.     

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.     

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.     

Platinum(II)/europium(III)-catalyzed intramolecular hydroalkylation of 4-pentenyl β-dicarbonyl compounds

Reaction of 5,5-dimethyl-8-nonene-2,4-dione with a catalytic mixture of [PtCl₂(CH₂CH₂)]₂ (2) (1 mol %), and EuCl₃ (2 mol %) in dioxane that contained HCl (1.0 equiv) at 90 °C for 18 h led to the isolation of 2-acetyl-3,6,6-trimethyl-2-cyclohexanone in 85% yield. A number of 4-pentenyl β-dicarbonyl compounds underwent intramolecular hydroalkylation to form cyclohexanones in moderate to excellent yield.     

Microwave-assisted synthesis of 2-aminonicotinic acids by reacting 2-chloronicotinic acid with amines

2-(Methylamino)nicotinic acid was readily prepared in high yield by reacting 2-chloronicotinic acid with 40% aq MeNH₂ under microwave irradiation either at 120 °C for 2 h or at 140 °C for 1.5 h. Subsequently, we found that a range of 2-aminonicotinic acids could be obtained under microwave heating. The optimal reaction conditions involved the use of 3 equiv of amine, water as the solvent and heating at 200 °C for 2 h in the presence of diisopropylethylamine (3 equiv).     

Preparation of 2,2-difluoro-1-trialkylsilylethenylstannanes and their cross-coupling reactions

Reaction of 2 with bis(tributyltin) in the presence of 3 mol % Pd₂(dba)₃, 6 mol % XPhos, and 30 equiv of LiBr in wet and air bubbled THF at reflux for 8 h afforded the desired products 3 in 73–74% yields. The cross-coupling reaction of 3a with aryl iodides in the presence of 10 mol % Pd(PPh₃)₄ and 10 mol % CuI afforded the coupled products 4a–p in 47–90% yields. The coupling reaction of 3b with various alkynyl bromides having aryl-, alkyl, or trialkylsilyl group also afforded the corresponding 1,3-enynes 5a–g in 61–77% yields.     

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.     

Synthesis of new 3-arylindole-2-carboxylates using β,β-diaryldehydroamino acids as building blocks. Fluorescence studies

Several new methyl 3-arylindole-2-carboxylates were synthesized in high yields using a metal assisted [Pd(OAc)₂/Cu(OAc)₂, DMF, 130 °C] intramolecular C-N cyclization of β,β-diaryldehydroamino acids, developed by us, thus extending the scope of this reaction. The latter were obtained by a bis-Suzuki coupling of a β,β-dibromodehydroalanine with arylboronic acids bearing either electron-donating groups (EDGs) or electron-withdrawing groups (EWGs). We were able to establish general conditions for this coupling reaction [PdCl₂dppf·CH₂Cl₂ 1:1 (20 mol %), boronic acid (5 equiv), Cs₂CO₃ (1.4 equiv), THF/H₂O 1:1, 80 °C]. This strategy constitutes a novel, general and unprecedented approach to the synthesis of 3-arylindole-2-carboxylates. The fluorescence of the differently substituted indoles prepared was studied in several polar and non-polar solvents. In general the new indoles exhibit a solvent sensitive emission. The indoles with EDGs (OCH₃ and SCH₃) have reasonable fluorescence quantum yields in all solvents except in water. The indole with the cyano groups shows high fluorescent quantum yields in all solvents studied, despite the lower solvent sensitivity of its emission. The indole with the acetyl groups only exhibits reasonable fluorescence quantum yields in protic solvents. These studies show that the new 3-arylindole-2-carboxylates are good candidates to be used as fluorescent probes.     

π-Allyl palladium approach toward the diazabicyclo[3.2.1]octane core of the naphthyridinomycin alkaloids

A novel and efficient protocol for the synthesis of the 3,8-diazabicyclo[3.2.1]octane system found in the naphthyridinomycin, dnacin, and tetrazomine families of alkaloids is described. The key transformation involves an intramolecular palladium-catalyzed allylic alkylation. The cyclization proceeds smoothly under mild conditions (20 mol % Pd₂dba₃, 1.5 equiv DBU, 65 °C, THF, 20 min) to afford 3,8-diazabicyclo[3.2.1]octanes in excellent yields (94-98%).     

Iridium-catalyzed double incorporation reaction of N-benzylmaleimide to styrene via ortho-C-H bond activation, initiated by precoordination of the double bond of styrene to iridium

Reaction of styrene with N-benzylmaleimide in the presence of [IrCl(cod)]₂ (5 mol %) and bpy (10 mol %) in an autoclave (1 MPa of Ar) at 150 °C for 18 h stereoselectively led to the formation of a new cyclic product. The structure of the product suggests that a novel iridium-catalyzed double incorporation reaction takes place via a metallacyclopentane formed after ortho-C-H activation.     

Efficient approach to allylated quinolines via palladium-catalyzed cyclization–allylation of 1-azido-2-(2-propynyl) benzenes with allyl methyl carbonate

The palladium-catalyzed cyclization–allylation reaction of ortho-azido propynylbenzenes 1 and allyl methyl carbonate 2d gives the corresponding allylated quinolines in moderate to good yields. The reaction of 1-azido-2-(2-propynyl)benzene 1a proceeds smoothly with 10 mol % Pd(PPh₃)₄ and 5 equiv K₃PO₄ or NaOAc in DMF at 100 °C to afford 3,4-diallylquinoline 3a in 69% yield in the case of R² = H and 3-allylquinoline 4 in 67% yield in the case of R² ≠ H.     

Palladium-catalyzed homocoupling of aryl halides in the presence of fluoride

This report describes the fluoride-mediated homocoupling of aryl iodides and bromides catalyzed by palladium(0). This coupling protocol is tolerant of electron-donating and electron-withdrawing substitutents on the aryl halide, as well as ortho substitution. Optimum reaction conditions entail 10 mol% Pd(dba)₂, 3 equiv of tetrabutyl ammonium fluoride (TBAF) in DMF at 90 °C.     

Direct palladium-catalyzed C-3 alkynylation of indoles

The direct palladium-catalyzed coupling reaction of indoles with alkynyl bromides was described in this paper. In the presence of catalytic amount of PdCl₂(PPh₃)₂ and 2.0 equiv. NaOAc, the coupling reaction of indoles with alkynyl bromides proceeded smoothly at 50 °C to give the corresponding 3-alkynylindoles with high regioselectivity in good to excellent yields.     

Molybdenum oxide/bipyridine hybrid material {[MoO3(bipy)][MoO3(H2O)]}n as catalyst for the oxidation of secondary amines to nitrones

The inorganic-organic hybrid material {[MoO₃(bipy)][MoO₃(H₂O)]}_n (bipy = 2,2′-bipyridine) can be used as a water-tolerant catalyst for the oxidation of secondary amines under mild conditions using either urea hydrogen peroxide (UHP) or tert-butylhydroperoxide (TBHP) as the oxidant. Under optimized reaction conditions (2 mol % catalyst, 3-4 equiv TBHP, CH₂Cl₂ as the solvent, 40 °C), the corresponding nitrones were obtained with different efficiency depending on the nature of the cyclic or acyclic amine used.     

Efficient synthesis of trisubstituted alkenes in an aqueous-organic system using a versatile and recyclable Rh/m-TPPTC catalyst

We have found that the use of [Rh(cod)OH]₂ associated with the water-soluble ligand m-TPPTC was highly efficient for the Rh-catalyzed arylation of alkynes. Aryl and alkyl alkynes were transformed to alkenes using 3 mol % rhodium catalyst and 2.5 equiv of boronic acid at 100 °C in a biphasic water/toluene system in 80-99% yield. The reaction was found to be totally regioselective for alkyl arylalkynes and alkyl silylated alkynes. The Rh/m-TPPTC system was for the first time recycled with no loss of the activity and with excellent purity of the desired alkene.     

Copper-catalyzed decarboxylative coupling reactions for the synthesis of propargyl amines

When aryl alkynyl carboxylic acids were allowed to react with amines and aldehydes in CH₃CN at 80 °C in the presence of 10 mol % CuI, the desired propargyl amines were formed in good yields. This coupling reaction demonstrated to work across a broad range of reagents including functionalized aryl alkynyl carboxylic acids, aliphatic and aromatic aldehydes, and cyclic and acyclic amines.     

Cross coupling of 3-bromopyridine and sulfonamides (RNHSO2R·R = H, Me, alkyl; R = alkyl and aryl) catalyzed by CuI/1,3-di(pyridin-2-yl)propane-1,3-dione

N-(3-Pyridinyl)-substituted secondary and tertiary sulfonamides have been synthesized in good to excellent yields by the reaction of 3-bromopyridine with primary and secondary alkyl and aryl sulfonamides (MeSO₂NH₂, MeSO₂NHMe, TolSO₂NH₂, TolSO₂NHMe, 1,3-propanesultam, and 1,4-butanesultam), catalyzed by CuI (20 mol %) and 1,3-di(pyridin-2-yl)propane-1,3-dione (20 mol %) with K₂CO₃ (200 mol %) in DMF (0.17 M for ArBr) at 110-120 °C over 36-40 h. 2-Bromopyridine, 4-bromopyridine, and a wide variety of substituted phenyl bromides can also be successfully coupled with sulfonamides under these reaction conditions.     

Chromium-catalyzed pinacol coupling of benzaldehyde in water

The pinacol coupling of benzaldehyde (0.25 M or 1.25 M) in water was catalyzed by 5-25 mol % CrCl₂ in the presence of Zn-dust or Al-dust at 20 °C or 60 °C. In all cases at most 50% of the pinacol coupling product, 1,2-diphenyl-1,2-ethanediol, was obtained with the major product, benzyl alcohol, being formed by a competitive 2e⁻ reduction of the carbonyl. The dl- to meso-diastereoselectivity of the pinacol products ranged from 0.6:1 to nearly 1:1.     

Copper-catalyzed cross-coupling of aryl iodides and aryl acetylenes using microwave heating

An efficient copper-catalyzed cross-coupling of aryl iodides with aryl acetylenes under microwave irradiation is described. The reaction proceeds under microwave heating with 10 mol % CuI and 2 equiv Cs₂CO₃ in 43-87% yields.     

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.