N-tert-Butyl-N-chlorocyanamide: a new reagent for the efficient preparation of gem-chloronitroso compounds

A new reagent for the efficient preparation of gem-chloronitroso compounds has been developed. The reaction of ketoximes with N-tert-butyl-N-chlorocyanamide takes place instantaneously in carbon tetrachloride at room temperature with excellent yields under mild conditions.     

Synthesis of methyl (5Z,8Z,10E,12E,14Z)-eicosapentaenoate

The first total synthesis of methyl (5Z,8Z,10E,12E,14Z)-eicosapentaenoate has been achieved in seven steps and in 16% overall yield. The synthesis confirmed the assigned structure of this polyunsaturated natural product.     

Synthesis of modified Weinreb amides: N-tert-butoxy-N-methylamides as effective acylating agents

An efficient preparation of N-methyl-O-tert-butylhydroxylamine hydrochloride has been settled, which allowed the synthesis of modified Weinreb amides. Nucleophilic addition of organolithium and Grignard reagents on these N-tert-butoxy-N-methylamides afforded efficiently the corresponding ketones and reduction with DIBAL furnished the corresponding aldehydes in good yields up to 97%.     

Interaction of 3,5-di-tert-butyl-o-benzoquinone with secondary amines—a pathway to new sterically hindered N,N-disubstituted o-aminophenols

The interaction of 3,5-di-tert-butyl-o-benzoquinone with secondary amines has been studied. The synthetic procedure was developed in order to synthesize a series of new N,N-disubstituted o-aminophenols. The interaction of 3,5-di-tert-butyl-o-benzoquinone with dimethylamine leads to 2-(N,N-dimethylamino)-4,6-di-tert-butyl-phenol, which is oxidized in the reaction medium by the parent 3,5-di-tert-butyl-o-benzoquinone forming spirocompound 4,5′,6,7′-tetra-tert-butyl-3′-methyl-3′H-spiro[1,3-benzodioxol-2,2′-[1,3]benzoxazole].     

Diastereoselective synthesis of homo-N,O-nucleosides

A new class of homo-N,O-nucleosides has been designed, based on the 1,3-dipolar cycloaddition of C-substituted nitrones with allyl nucleobases. The N-methyl-C-ethoxycarbonyl nitrone 1, and the C-α-silyloxymethyl-N-methyl nitrone 7 have been exploited: the stereochemical features of the obtained nucleosides are dependent on the nature of the dipole. The results obtained with DFT calculations fully agree with the experimental results and successfully reproduce the experimentally observed reversal of endo/exo selectivity for nitrones 1 and 7.     

Catalytic photocarboxylation of 1,1-diphenylethylene with N,N,N′,N′-tetramethylbenzidine and carbon dioxide

Photocarboxylation of 1,1-diphenylethylene with N,N,N′,N′-tetramethylbenzidine (TMB) in MeCN under bubbling of CO₂ proceeded with high catalytic efficiency, giving 3,3-diphenylacrylic acid (DPA) and 3-hydroxy-3,3-diphenylpropionic acid (20). The turnover number (TON=(DPA+20)/TMB) reached 17. Similarly, 1-phenyl-1-cyclohexene yielded cis-2-acetamido-2-phenylcyclohexanecarboxylic acid with TON 5.9. As compared with related N,N-dimethylaniline derivatives, TMB is more resistant to photodecomposition, has the much larger absorbance in the S₀→S₁ transition, and has the lower quenching efficiency by CO₂. Probably these factors are partly responsible for the high TON observed for TMB.     

Convenient method for the synthesis of C-phosphorylated N-arylformamidines

C-Phosphorylated (P^V) arylformamidines have been prepared by the reaction of N-arylamidotrichloromethyl derivatives of phosphorus, thiophosphorus, and selenophosphorus acids with secondary amines. Dependence of the reaction on the nature of chalcogene, electronic and steric factors has been studied. By reduction of N-arylformamidinophosphonoselenides the corresponding C-phosphorylated (P^III) arylformamidines have been synthesized.     

Stereoselective synthesis of protected (2S,3S)-N-methyl-5-hydroxyisoleucine, a component of halipeptins

The stereocontrolled synthesis of the protected (2S,3S)-N-methyl-5-hydroxyisoleucine, a component of halipeptins A and B with potent anti-inflammatory activity, has been achieved. The key steps include (i) installation of a double bond to bicyclic lactam 4 using N-tert-butyl phenylsulfinimidoyl chloride, (ii) highly exo-selective Michael reaction with lithium dimethylcuprate in the presence of chlorotrimethylsilane, and (iii) Ru-catalyzed oxidative deprotection of N,O-benzylidene acetal to the acid anhydride.     

Pd/C mediated synthesis of 2-substituted benzo[b]furans/nitrobenzo[b]furans in water

An efficient synthesis of 2-alkyl/aryl substituted benzo[b]furans/nitrobenzo[b]furans in water has been accomplished via Pd/C catalyzed reaction of o-iodophenols with terminal alkynes in the presence of PPh₃, CuI and prolinol. This method can tolerate a variety of functional groups present in the alkynes as well as base labile nitro group in the o-iodophenols. The protocol does not require the use of a phase transfer catalyst or water-soluble phosphine ligands and is free from the use of any organic co-solvent.     

Synthesis and evaluation of N6-substituted azide- and alkyne-bearing N-mustard analogs of S-adenosyl-l-methionine

The synthesis of a family of N-mustard analogs of S-adenosyl-l-methionine (SAM) containing azides and alkynes at the N6-position of the adenosine base has been accomplished from commercially available inosine. Further biochemical analysis of these analogs indicates successful modification of pUC19 plasmid DNA in an enzyme-dependent fashion with DNA methyltransferases M.TaqI and M.HhaI.     

Vinylogous N,N-dimethylaminomethylenation of 3-[(1-substituted)ethylidene]-oxindoles with N,N-dimethylformamide dimethylacetal

An efficient stereoselective synthesis of various 3-(3-dimethylaminoprop-2-enylidene)oxindoles has been disclosed. The compounds were synthesized via a vinylogous N,N-dimethylaminomethylenation at the γ-position of 3-[(1-substituted)ethylidene]oxindoles with DMF-DMA.     

Suzuki-Miyaura monocouplings of p-dibromobiphenyl and substituted p-dibromo(penta-p-phenylenes)

The mono/bis ratio for the Suzuki-Miyaura cross coupling of p-dibromobiphenyl and p-dibromo(penta-p-phenylenes) with arylboronic acids and esters has been studied. The coupling reaction is demonstrated to be highly selective for monoarylation when the substrate is a p-dibromooligoarene, while selective biarylation is obtained for p-diiodoterphenyl. The mono/bis coupling-ratio for these compounds was highly sensitive to the nature of the halogen involved, however steric hindrance or electronic characteristics of the boronic derivative did not affect the selectivity of the reaction. The reaction yields observed were higher at room temperature and when arylboronic pinacol esters were used. These reactions also offer a useful method for the preparation of asymmetrically substituted terphenyls and hexa-p-phenylenes, giving good yields.     

Synthesis of polylactide using a zinc complex containing (S)-N-ethyl-N-phenyl-2-pyrrolidinemethanamine

The reaction between ZnCl₂ and (S)-N-ethyl-N-phenyl-2-pyrrolidinemethanamine (S-EPP) as a chiral ligand affords [ZnCl₂(S-EPP)], whose structure has been determined by X-ray crystallography. [ZnEt₂(S-EPP)] has demonstrated high activity toward the polymerization of rac-lactide with a maximum turnover frequency (TOF) of 121. Despite the intended stereocontrol by employing a chiral ligand, however, the observed heterotacticity was limited to under 0.6. The MWDs of the PLAs were found to be modulated by changing the solvent or controlling the concentration of the monomer in the solution. The glass transition temperature (T_g) was critically dependent on the MW within the narrow MWD regime, but the dependence became significantly shallow when the MWD was broadened.     

DFT study of the reaction sites of N,N′-substituted p-phenylenediamine antioxidants

The geometry of N,N′-diphenyl-p-phenylenediamine (DPPD), N-phenyl-N′-(1′-methylbenzyl)-p-phenylenediamine (SPPD), N-phenyl-N′-(1,3-dimethyl-butyl)-p-phenylenediamine (6PPD), N-phenyl-N′-isopropyl-p-phenylenediamine (IPPD), and N-(1-methyl-1-phenylethyl)-N′-phenyl-p-phenylenediamine (CPPD) as well as of their dehydrogenation products has been optimized at B3LYP/6-31G^∗ level of theory. Our results support the idea of formation of stable ketimine Ph-NC structures (instead of quinonediimine structures) during consecutive dehydrogenation of SPPD, 6PPD, and IPPD antioxidants despite the formation of tertiary carbon-centered radicals in the first dehydrogenation step is energetically preferred for SPPD only.     

Palladium(II) complexes with S-benzyl dithiocarbazate and S-benzyl-N-isopropylidenedithiocarbazate: Synthesis,spectroscopic properties and X-ray crystal structures

Two new palladium(II) bis(NS) chelates, bis(S-benzyl dithiocarbazato)palladium(II) (1) and bis(S-benzyl-N-isopropylidenedithiocarbazato)palladium(II) (2), have been prepared and characterized using single-crystal X-ray diffraction and spectroscopic (electronic, IR and NMR) techniques. Complex 1 has a perfectly square planar trans configuration (point group C_i), while complex 2 has a distorted square planar cis configuration.     

Studies of some hydrogenated thiazolo[2,3-a]isoquinoline S-oxides

Several hydrogenated thiazolo[2,3-a]isoquinolinone S-oxides have been prepared and their stereochemistry established on the basis of spectral data analysis combined with X-ray crystallography. A reversible syn/anti isomerization of diastereomeric sulfoxides has been postulated to occur via a 10b proton abstraction.     

One-pot synthesis of 12H-benzo[b]xanthen-12-ones and naphtha[2,3-b]furans from non-naphthalene substrates

An efficient one-pot synthesis of 12H-benzo[b]xanthen-12-ones via an oxidant initiated and base promoted tandem reaction of 2-(4-(2-haloaryl)-4-hydroxybut-1-ynyl)benzaldehydes has been developed. By using similar strategy, a one-pot synthesis of naphtha[2,3-b]furans from the cascade reaction of 2-(4-hydroxy-but-1-ynyl)benzaldehydes with 2-bromoacetonitrile or α-bromocarbonyl compounds has also been achieved.     

Palladium-catalyzed cross-coupling reaction of aryldioxaborolane with 2-bromo-N,N-dimethylacetamide

A Suzuki-type cross-coupling of aryldioxaborolane with 2-bromo-N,N-dimethylacetamide in the presence of a catalytic amount of tricyclohexylphosphine as the ligand and hydroquinone as the free-radical scavenger has been demonstrated as a convenient and simple way for the synthesis of α-arylacetamide.     

Rapid differentiation of Panax ginseng and Panax quinquefolius by matrix-assisted laser desorption/ionization mass spectrometry

A matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)-based method has been developed for rapid differentiation between Panax ginseng and Panax quinquefolius, two herbal medicines with similar chemical and physical properties but different therapeutic effects. This method required only a small quantity of samples, and the herbal medicines were analyzed by MALDI-MS either after a brief extraction step, or directly on the powder form or small pieces of raw samples. The acquired MALDI-MS spectra showed different patterns of ginsenosides and small chemical molecules between P. ginseng and P. quinquefolius, thus allowing unambiguous differentiation between the two Panax species based on the specific ions, intensity ratios of characteristic ions or principal component analysis. The approach could also be used to differentiate red ginseng or P. quinquefolius adulterated with P. ginseng from pure P. ginseng and pure Panax quinquefolium. The intensity ratios of characteristic ions in the MALDI-MS spectra showed high reproducibility and enabled quantitative determination of ginsenosides in the herbal samples and percentage of P. quinquefolius in the adulterated binary mixture. The method is simple, rapid, robust, and can be extended for analysis of other herbal medicines.