Pd-catalyzed chemo-selective mono-arylations and bis-arylations of functionalized 4-chlorocoumarins with triarylbismuths as threefold arylating reagents

Cross-coupling reactions of differently substituted 4-chlorocoumarins were studied under palladium catalysis using triarylbismuths as threefold arylating reagents. The high reactivity of 4-chlorocoumarins was demonstrated delivering mono- and bis-arylation products in a chemo-selective manner. The reaction conditions employed are simple, robust and the threefold coupling reactivity of triarylbismuth reagents was witnessed with good to high yields in 2–4 h conditions. The utility of the methodology was explored in the synthesis of a few natural occurring neoflavones (3.27–3.30). In addition, the 4-arylcoumarin 3.1 product is a useful precursor for the preparation of (R)-tolterodine.     

1,2,3-Triazol-5-ylidene-palladium complex catalyzed Mizoroki-Heck and Sonogashira coupling reactions

The bis-1,4-dimesityl-1,2,3-triazol-5-ylidene-palladium complex (1a) successfully catalyzes the Mizoroki-Heck and Sonogashira coupling reactions with aryl bromides to give the corresponding alkenes and alkynes, respectively, in good to excellent yields. In the Mizoroki-Heck reaction, electron-rich, electron-poor, and functionalized aryl bromides and alkenes are tolerated, while the substrates are limited to electron-poor aryl halides in the Sonogashira coupling reaction. The palladium complex also catalyzes cross-coupling reactions with aryl chlorides to give higher yields of products than does the bis-IMes-Pd complex analogue (2), under specific conditions.     

Hydrogen peroxide mediated formation of heteroaryl ethers from pyridotriazol-1-yloxy heterocycles and arylboronic acids

Pyridotriazol-1-yloxypyrimidine 3 reacts with arylboronic acids under palladium-free, Cs₂CO₃, (0.8%) H₂O₂, and DME conditions to produce heteroaryl ethers 4-16 in good yields comparable to the oxidative palladium-catalyzed reaction. The yields of aryl ethers 17-19 from quinazoline 2 with (0.8%) H₂O₂ were modest. Hydrogen peroxide is superior to dioxygen as an oxidant in these reactions.     

Pd(II) polymeric compounds directed by intermolecular C–H⋯X–C interactions (X = F,Cl): Suzuki–Miyaura cross-coupling catalytic activity by a novel N4-type saturated Pd complex

New palladium polymeric compounds containing novel tetradentate halogen-substituted 6Me₂bpX²⁻ ligands (6Me₂bpX²⁻ = 1,2-bis(6-methylpyridine-2-carboxamide) halobenzene dianion, X = F for 4, Cl for 5) were constructed by non-classical C–H?X–C interactions, and the novel catalyst 5 was used to carry out Suzuki coupling reactions with aryl iodides and aryl boronic acids under mild conditions.     

Palladium-catalysed Heck reaction on 1,2-dien-1-ols: a stereoselective synthesis of α-arylated α,β-unsaturated aldehydes

A new methodology for preparing α-arylated α,β-unsaturated aldehydes is reported. The starting materials are all commercially available alkyn-1-ols (1a-c) that have been easily isomerised to the corresponding allenes (2a-c). The key step is the Heck coupling of the 1,2-dien-1-ols with a series of iodo- and bromoarene. The products have been synthesised in good yields, and the reactions were carried out under very mild conditions.     

Synthesis of novel fluorescent 3-aryl- and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines by Suzuki cross-coupling reactions

Two series of compounds, 3-aryl- (series A, compounds 2a-j) and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines (series B, compounds 3a-j) have been synthesized by Suzuki cross-coupling reactions, with a triazolopyridine halide and an aryl or heteroaryl boronic acid in moderate to good yields. All compounds obtained are fluorescents, the quantum yields, particularly those of compounds 3f-j, are very high.     

Sodium dithionite initiated addition of 1-bromo-1-chloro-2,2,2-trifluoroethane to allylaromatics: Facile synthesis of conjugated dienes substituted with terminal CF3 group

Sodium dithionite effectively promotes the addition of 1-bromo-1-chloro-2,2,2-trifluoroethane to the terminal double bond of allylbenzenes 1. The reactions proceeded in MeCN/H₂O to give a 3:1 mole ratio of diastereoisomers of 1-(2-bromo-4-chloro-5,5,5-trifluoropentyl)benzenes 2 as the main products together with small amounts of its reductive debromination products 3. Total yields of 2 and 3 were dependent on the nature of the aromatic ring substituents in 1. Treatment of adducts 2 with DBU in refluxing hexanes resulted in double dehydrohalogenation affording, in good yields, conjugated dienes 4 (1,1,1-trifluoro-5-phenyl-2,4-pentadienes) terminated with the CF₃ group at the one end and the phenyl group at the opposite end. These dienes were found to be sufficiently reactive to undergo Diels-Alder condensation with active dienophiles to give trifluoromethylated carbocycles. The reactions of CF₃CHClBr with allylheterocycles were less successful and lead to low yields of mixtures of hardly separable compounds or to polymeric resins.     

Synthesis of 4-(2-arylvinyl)-8-hydroxyquinolines via anhydrous Heck coupling reaction and the PL properties of their Al complexes

Anhydrous Heck coupling between 2 and eight different arylvinyl compounds using 3 mol % of PdCl₂/2PPh₃ catalyst system occurs selectively at position-4 of 2 affording 4-(2-arylvinyl)-8-tosyloxyquinolines 3 in good to high yields. The tosyloxy protecting group showed high stability under anhydrous coupling conditions. Deprotection of the resulting 4-arylvinyl-8-tosyloxyquinolines produced 4-(2-arylvinyl)-8-hydroxyquinolines 4 in high yields. The aluminium complexes of the resulting 8-hydroxyquinolines have been synthesized and their photoluminescence (PL) properties have been studied. One of the complexes with a 2,4,6-trimethoxystyryl substituent at position-4 of the quinolate shows higher relative PL quantum yield than the other complexes due to the minimization of the cis-trans photoisomerization in solution.     

Palladium-catalyzed cross-coupling reaction of allyl acetates with pinacol aryl- and vinylboronates

Pinacol boronates 2 couple efficiently with allyl acetates 1 in the presence of a palladium catalyst prepared in situ from PdCl₂ and TFP to give the coupled products 3 in moderate to good yields under mild conditions.     

Practical method for synthesis of 2,3-disubstituted indole derivatives promoted by β-(benzotriazol-1-yl)allylic O-stannyl ketyl radicals

Treatment of β-aryl-β-(benzotriazol-1-yl)-α-primary alkyl (or aryl)-α,β-unsaturated ketones 1 with n-Bu₃SnH (4 equiv) in a catalytic amount of AIBN in PhH at reflux afforded 3-alkyl (or aryl)-2-arylindoles 8 in good yields. However, when tert-butyl group is bonded at α-position, 3-acyl (or aroyl)-2-arylindoles 9 were obtained as major products along with phenanthridines 5 as minor products.     

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.     

PPh3-catalyzed ylide cyclization for the controllable synthesis of benzobicyclo[4.3.0] compounds: base effects and scope

A catalytic intramolecular ylide annulation for the controllable construction of benzobicyclo[4.3.0] ring systems with three continuous stereogenic centers is developed in a single manipulation. In the presence of 20 mol % of triphenylphosphine, the reactions of compounds 1a-1f afford benzobicyclo[4.3.0] compounds 3 and 4 as major products, respectively, with excellent diastereoselectivities in good to excellent yields, depending on the base used. In addition, 2-methyl α,β-unsaturated esters 2a-2c also work well to give the corresponding benzobicyclo[4.3.0] compounds with one quaternary carbon center with high diastereoselectivities in good yields under the same conditions.     

Studies directed toward the synthesis of protein-bound GPI anchor

Mannobioside-linked phosphoethanolamine 10, a prototype model of the GPI anchor, was synthesized via glycosidation of the monosaccharide donor and acceptor, and subsequent phosphorylation. In order to test the reactivity of the amino group involved in 10 against the activated amino acid esters, 10 was reacted with N-protected amino acid pentafluorophenyl esters in the presence of HOBt. The reactions gave the aminoacylated products in moderate yields. When Fmoc-Ser-OPfp 12 and Fmoc-Cys(SBu^t)-OPfp 14 were reacted with 10, byproducts 19, 20 and 21 derived from N- and O-acylation were produced. In contrast, reactions of 10 and N-protected amino acid thioesters were promoted with AgNO₃, HOSu, and DIEA to afford the coupling products without the undesired O-acylation. Peptidylation of 10 with the synthesized oligopeptide thioesters 24 and 27 was also successful under the segment coupling conditions of the peptide thioester method as well as those of the native chemical ligation.     

An inexpensive and highly stable ligand 1,4-bis(2-hydroxy-3,5-di-tert-butylbenzyl)piperazine for Mizoroki-Heck and room temperature Suzuki-Miyaura cross-coupling reactions

A bulky, inexpensive and simple bidentate ligand 1,4-bis(2-hydroxy-3,5-di-tert-butylbenzyl)piperazine (1) has been synthesized and characterized. The palladium catalyst was formed by combination of 1 with [Cl₂Pd(COD)] in a ratio of 1:1, tested in the Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions. Coupling of a variety of aryl bromides with phenylboronic acid using methanol as solvent at room temperature, or at 60 °C, gave generally high yields of coupled products. Coupling of aryl chlorides with organoboron reagent at 110 °C in DMF afforded good yields of biaryls under aerobic conditions. This non-phosphorus, air and moisture stable catalyst also displays good activity for Mizoroki-Heck coupling reaction in methanol at 60 °C with various aryl chlorides and bromides.     

Enantiocontrolled synthesis of the epoxycyclohexenone moieties of scyphostatin, a potent and specific inhibitor of neutral sphingomyelinase

The epoxycyclohexenone moieties 2 and 3b of scyphostatin (1), a potent and specific inhibitor of neutral sphingomyelinase, were synthesized in enantiomerically pure forms starting from (−)-quinic acid (11). The synthetic method features (i) the preparation of the olefin masked enones 25 and 29, the precursors for the key aldol-type coupling reaction, (ii) the efficient and stereocontrolled aldol-type coupling reactions between 25 (or 29) and benzaldehyde (8) and Garner's aldehyde analogue 9 to deliver alcohols 23 and 24, respectively, both of which possess the requisite asymmetric quaternary carbon center at the C6 position, and (iii) the stereospecific S_N2-type epoxide ring formation of the mesylates 35 and 47 under mild basic conditions to produce the targeted compounds 2 and 3b, respectively.     

Stilbene like carbazole dimer-based electroluminescent materials

Two carbazole dimers (1 and 10) were synthesized from 9-ethyl-9H-carbazole-3-carbaldehyde and 6-bromo-9-ethyl-9H-carbazole-3-carbaldehyde by McMurry C-C coupling reaction. Palladium(0)-catalyzed C-N coupling reactions of 10 and various diarylamines result in the formation of stable carbazole derivatives in good yields. These compounds are fluorescent in blue to yellow region with moderate to good quantum yields. Also, they are thermally stable and capable of hole-transporting due to the presence of the carbazole moieties. The electroluminescent devices fabricated using 1, 2, and 3 as hole-transporters/emitters with a bilayer structure ITO/Cpd/TPBI or Alq₃/LiF/Al (Cpd=1, 2, and 3) exhibit good performance (e.g., η_ext=1.0-2.1%; η_p=0.9-1.9 lm/W; η_c=2.4-4.8 cd/A at a current density of 100 mA/cm²).     

Di-t-butyl(ferrocenylmethyl)phosphine: air-stability, structural characterization, coordination chemistry, and application to palladium-catalyzed cross-coupling reactions

Di-t-butyl(ferrocenylmethyl)phosphine (1) has been isolated and structurally characterized. This ligand was found to be reasonably air stable as a solid and it has been shown to possess electron donating ability similar to that of tri-i-propylphosphine. A palladium catalyst bearing this ligand performed room temperature Suzuki-Miyaura coupling reactions with aryl bromides. Modest Heck coupling reactivity with aryl bromides was also observed at 100 °C. Complexation of 1 with Pd₂(dba)₃ led to formation of (1)₂Pd⁰. Addition of 4-bromoanisole to solutions containing both 1 and Pd₂(dba)₃ led to formation of an oxidative addition product when 1:Pd ratios were ?1. With a 2:1 ratio of 1:Pd, monophosphine complex formation and oxidative addition were significantly inhibited.     

Highly stereoselective synthesis of novel trans-thiophenylene-silylene-vinylene-arylene molecular and macromolecular compounds

Novel stereoregular molecular compounds 8-13 containing thiophenylene-silylene-vinylene-phenylene units have been synthesised via highly effective silylative coupling of styrene and 1,4-divinylbenzene (7) with respective vinylsilylthiophenes (3, 4) and bis(vinylsilyl)thiophenes (5, 6) catalyzed by RuHClCO(PCy₃)₂. Respective copolymers (14, 15) were produced via silylative copolycondensation of 5 and 6 with 7. All products were isolated and characterised by NMR, MS, HRMS and two of them 10 and 11 by X-ray method. Catalytic study as well as stoichiometric reactions of Ru-H (1) with 2-(vinylsilyl)thiophene (3) and Ru-Si (16) with styrene confirmed the mechanism of the silylative coupling olefins with vinylsilicon compounds.     

Highly efficient synthesis of extended triptycenes via Diels-Alder cycloaddition in water under microwave radiation

Microwave-irradiated Diels-Alder reactions of anthracene and endoxides (6a-g) in water afforded the cycloadducts (8a-g) with high efficiencies. The extended triptycenes (2a-g) were readily obtained by dehydration of 8a-g in a mixture of AcOH and Ac₂O with good overall yields.     

Study on the reactions of fluoroalkanesulfonyl azides with indole derivatives

The reactions of fluoroalkanesulfonyl azides 1 with different indole derivatives have been studied in detail. Treatment of 1 with equimolar amount of 1,3-dimethylindole 3 in 1,4-dioxane at room temperature afforded 2-(1,3-dimethyl-1,3-dihydro-indolinylidene) fluoroalkanesulfonylimines 5 in moderate to good yields. However, under the same reaction conditions, in the case of 1 with 1,2-dimethylindole 4, the corresponding 2-fluoroalkanesulfonyl (1,2-dimethyl-1H-indol-3-yl)-amide 6 was obtained in moderate yields. In addition, the reactions of 1 and indole 7 gave different products under different conditions. Possible mechanisms of these reactions were proposed.