Photo-induced coupling of tertiary amines with Ugi-derived dehydroalanines as a practical device in the synthesis to 2,4-diaminobutyric acid derivatives

An Ir-mediated photocatalytic coupling of tertiary amines with Ugi-dehydroalanines was developed as an entry to medicinally important 2,4-diaminobutyric acid derivatives. In the process the 2,4-diaminobutyric acid framework is assembled directly embedded into a peptoide structure, via the construction of the C₃(sp³)–C₄(sp³) bond, through a CH functionalization. The photocatalyzed oxidation of the tertiary amine produce a free radical intermediate which reacts with the double bond present in the dehydroalanines. The complete protocol comprises an Ugi 4-CR followed by an elimination reaction and the photo-induced coupling. Using this strategy, 15 new diversely substituted unnatural α,γ-diamino acids peptide derivatives were prepared in low to good yields.     

A highly divergent Pictet-Spengler approach for pyrrolo[1,2-a]quinoxalines from aryl amine using 1,2-dinitrobenzene as an oxidant

A convenient Pictet-Splengler approach for the synthesis of substituted pyrrolo[1,2-a]quinoxalines from aryl amine and 1-(2-aminoaryl)-pyrrole has been developed. This is the first domino protocol involving formation of benzaldehyde as an intermediate from benzyl amines and benzyl alcohols using 1,2-DNB as an oxidant, followed by its endo cyclization with 1-(2-aminophenyl)-pyrrole to furnish the pyrrolo[1,2-a]quinoxalines. Notably, this procedure exhibits good functional group tolerance as well as good to moderate yield of pyrrolo[1,2-a]quinoxaline.     

Novel coupling reaction between sulfonyl azide and N,N,N',N'-tetramethylthiourea

The synthesis of sulfonylguanidines from N,N,N',N'-tetramethylthiourea and sulfonyl azides is described. This method serves as an alternative route for generating sulfonylguanidines via the use of stable starting materials.     

Asymmetric catalyzed intramolecular aza-Michael reaction mediated by quinine-derived primary amines

An intramolecular organocatalytic enantioselective aza-Michael reaction of carbamates, sulfonamides and acetamides to a,b-unsaturated ketones was developed. This process is promoted by 9-amino-9-deoxy-epi-quinine and diphenyl hydrogen phosphate to afford a straightforward and expeditious synthesis of several synthetically useful five-and six-membered heterocycles with excellent enantioselectivity(92%–97.5% ee) and very good yields(up to 99%).     

Annulation chemistry based on tandem Michael addition-enamine formation – An improved method for the preparation of 1-substituted-2,3,5,6,7,8-hexahydroquinolin-4(1H)-ones

The reaction of 2-(but-2-enoyl)cyclohexan-1-one 2 with primary amines affords 1-substituted-2,3,5,6,7,8-hexahydroquinolin-4(1H)-ones through a tandem Michael addition/enamine formation reaction sequence at room temperature in high yields. Reaction times are greatly reduced (4–24 h vs. 1–2 h; reflux versus room temperature) when powdered 4 Å sieves are used.     

Nitrobutadienes as powerful benzannulating agents: An unprecedented easy access to rare nitroindoles

We report herein an original protocol to the indole nucleus, which could contribute to significantly expand the synthetic access to a heterocyclic moiety of undeniable paramount importance. The protocol consists in the construction of the benzene ring onto a pyrrole (benzannulation) starting from 2,3-dinitro-1,3-butadienes. This appealing, metal-free process characterized by high atom economy and mild reaction conditions allows to synthesize indoles possessing nitro group(s) on the benzene ring: a result which cannot be likewise easily obtained by exploiting most common pathways such as functionalization of a preformed indole or heteroannulation of a suitable benzene derivative. From a mechanistic point of view, a stepwise, ionic process is suggested by the identification of a pivot dihydroindole intermediate whose interception facilitates some selectivity in the preparation of different nitroindoles.     

Computational and cyclic voltammetry studies of high effective-molarity assisted reversible reductions of [4]- and [5]heli-viologens: Potential building blocks for new materials

Computational and cyclic voltammetry studies have been used to explore electrochemical reductions of three helically chiral homologues, 2²⁺, 3²⁺, and 4²⁺, of methyl viologen. Thermochemical-electrochemical cycles are used as frameworks to describe the reversible redox properties of these helically chiral viologens as novel reversible four-sided ECEC (Electron-transfer Chemical-reaction Electron-transfer Chemical-reaction) processes.     

Palladium(II) acetate‐catalyzed reduction of imines to the corresponding amines by triethylsilane

Reduction of a variety of imine compounds with triethylsilane in the presence of catalytic amounts of palladium(II) acetate in ethanol resulted in the formation of the corresponding amines in excellent yields after short reaction times. Copyright © 2013 John Wiley & Sons, Ltd.     

Vanadium-catalyzed oxidative Strecker reaction: α-C–H cyanation of para-methoxyphenyl (PMP)-protected primary amines

We describe an oxidative Strecker reaction that allows for direct cyanation of para-methoxyphenyl (PMP)-protected primary amines. A vanadium(V) complex was used as the catalyst and TBHP as the oxidant. The cyanation occurs at the α-C position bearing either an alkyl or an aromatic group. This method provides a direct access to α-aminonitrile from amines with one-carbon extension.     

Synthesis of ferrocene annulated trifluoromethylated heterocycles with crispine and lamellarin skeletons

Ferrocene analogues of pyrrolo[2,1-a]isoquinoline alkaloids, 2-(trifluoromethyl)-5,6-dihydroferroceno[g]indolizine and 6-(trifluoromethyl)-8,9-dihydro-6H-chromeno[4,3-b]ferroceno[g]indolizines, were obtained in 44–65% yield via the Grob reaction between 1-nitro-1-(2,2,2-trifluoroethylidene)alkanes or 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1-alkyl-3,4-dihydroferroceno[c]pyridines in 2-propanol at reflux.     

Catalytic enantioselective Michael addition of deconjugated butyrolactams to maleimides

The first catalytic enantioselective Michael addition of deconjugated butyrolactams to N-arylmaleimides is developed with the help of a bifunctional tertiary aminosquaramide catalyst. Unlike the widely explored and structurally related vinylogous nucleophile – deconjugated butenolides, deconjugated butyrolactams are found to be exclusively α-selective. The resulting highly substituted and densely functionalized products, bearing contiguous all-carbon quaternary and tertiary stereocenters, are formed in good yields with moderate diastereoselectivity and good to excellent enantioselectivity (up to 99:1 er).     

Synthesis of water-soluble phenylazosalicylaldehyde analogues and their application to capillary electrophoretic determination of primary amines

Several primary amines are known to be endogenous substances, and they are to be detected at very low concentration level. Novel water-soluble azo dyes as precolumn derivatizing reagents were synthesized for the analysis of primary amines with strong visible-light absorption by CZE. A coupling reaction was used to introduce a sulfophenylazo group to salicylaldehyde or 1-hydroxy-2-naphthaldehyde to extend the conjugation and to improve the solubility in water of the derivatizing reagents, as well as the target compounds of the reaction products with the primary amines. Two azo dyes of 5-(4-sulfophenylazo)salicylaldehyde sodium salt (AZO1) and 4-(4-sulfophenylazo)-1-hydroxy-2-naphthaldehyde sodium salt (AZO2) were synthesized. Separation of eight kinds of n-alkylamines was performed by CZE after the derivatization with AZO1 or AZO2. The addition of Brij 35 to the running electrolyte and to the sample solutions was necessary to improve the solubility and the resolution among the analytes. Both reagents, AZO1 and AZO2, were compared with each other in terms of the reaction time of derivatization, the detection sensitivity and the total analysis time. The derivatization process using AZO2 was applied to the determination of four biogenic amines, histamine, tyramine, cadaverine and putrescine, and LODs at around micromolar level were achieved for the four amines.     

Indium(III)-catalyzed intramolecular addition of silyl enolates to alkynes

In the presence of water and a catalytic amount of InBr₃, intramolecular trans-addition of silyl enolates derived from ketones and an aldehyde to alkynes proceeded smoothly to give 4 to 7-membered carbocycles bearing an acyl group. When carboxylic anhydrides were used as electrophiles instead of water, the cyclized products could be functionalized with an additional acyl group.     

Dinickel catalyzed carbonylation reactions using metal carbonyl reagents as CO sources

Dinickel complexes promote stoichiometric Pauson–Khand reactions of enynes and CO (g). However, catalytic turnover is precluded by the strong binding of CO to the Ni₂ active site. This article describes the use of M(CO)_x reagents as stoichiometric CO precursors in Ni₂-catalyzed carbonylation reactions. As part of these studies, well-defined heterotrinuclear Ni₂Fe, Ni₂Co, and Ni₂Mn carbonyl clusters are synthesized using the [NDI]Ni₂ platform as a template (NDI = naphthyridine–diimine).     

Hantzsch-like three-component synthesis of tetracyclic 10b-azachrysenes: Unambiguous structural elucidation using X-ray crystallography and 2D-HMBC spectroscopy

Herein, we report the first synthesis of 10b-azachrysenes via the Hantzsch-like reaction of aldehydes with 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile and dimedone in the presence of acetic acid. The regioselectivity was established using X-ray crystallography and 2D-HMBC spectroscopy.     

An expeditious entry to rare tetrahydroimidazo[1,5-c]pyrrolo[1,2-a]pyrimidin-7(8H)-ones: A single-step gateway synthesis of glochidine congeners

A single-step gateway synthesis of glochidine and its congeners that possess the rare uncommon tetrahydroimidazo[1,5-c]pyrrolo[1,2-a]pyrimidine core was developed employing histamine and readily available γ-ketoesters. Key features of the developed reaction involve tandem three C–N bonds formation and concomitant annulation of two rings in one pot to access this unique and complex tricyclic structure. Exploration of the unknown bioactivity of these compounds revealed that they elicit antiproliferative activity comparable to the anticancer drug imatinib against 6 cancer cell lines.     

Water-soluble polymer anchored peroxotitanates as environmentally clean and recyclable catalysts for mild and selective oxidation of sulfides with H2O2 in water

Anchoring of peroxotitanium (pTi) species to linear water-soluble acrylic acid based polymers, poly(sodium acrylate) (PA) and poly(sodium methacrylate) (PMA) led to the successful synthesis of a pair of new, water-tolerant and recyclable catalysts of the type [Ti₂(O₂)₂O₂(OH)₂]^4-—L (L = PA or PMA), highly effective in chemoselective sulfoxidation of organic sulfides with 30% H₂O₂ in aqueous medium at ambient temperature. The catalytic protocol is high yielding (TOF up to 11,280 h^?1), operationally simple as well as environmentally clean and safe, being free from halide, or any other toxic auxiliaries. The catalysts are sufficiently stable to afford easy recyclability for at least 10 consecutive reaction cycles of sulfoxidation with consistent activity selectivity profile. Oxidation of dibenzothiophene (DBT) to respective high purity sulfoxide or sulfone could also be accomplished using the same catalysts by variation of reaction conditions.     

Convenient synthesis of 2-(het)arylpyrrolidines via stable 1-pyrrolinium salts

The efficient method for the synthesis of 2-(het)aryl-substituted pyrrolidines possessing exocyclic carbon-carbon double bond via the Mannich-type reaction of stable 3-arylidene-1-pyrrolinium salts with different heterocyclic C-nucleophiles is proposed.     

Diastereoselective heterocyclization of geminal bromo-fluoro arylcyclopropanes by nitrosonium tetrafluoroborate: Access to 4-fluorinated isoxazolines and isoxazoles

A series of 5-aryl-4-bromo-4-fluoroisoxazolines was synthesized via nitrosation of 2-aryl-1-bromo-1-fluorocyclopropanes with NOBF₄. It was shown that the E-isomers of the cyclopropanes react highly regio- and diastereoselectively leading exclusively to the E-isomers of the isoxazolines. The obtained 5-aryl-4-bromo-4-fluoroisoxazolines were transformed selectively into the corresponding 5-aryl-4-fluoro- or 5-aryl-4-bromoisoxazoles in good yields in the reaction with Lewis acids.     

Development of standard operation procedures for the manufacture of n-octadecyl bonded silicas as packing material in certified reference columns for reversed-phase liquid chromatography

The development of standard operation procedures for the manufacture of a n-octadecyl bonded spherical silica packing from partially condensed tetraethoxysilane as silica source is described. The synthesis comprises five intermediate products and six synthesis steps which were examined according to their reproducibility and robustness. The results led to the optimisation of the manufacturing process for a n-octadecyl bonded silica. Correlations were drawn between the dynamic viscosity of the poly(ethoxy)siloxane (PES), the synthesis parameters, the resulting pore structural properties and particle size distribution of the silicas. Validated procedures were developed to manufacture spherical porous ultra-pure silicas with a specific surface area of 350 m2 g(-1) +/- 5% R.S.D., a specific pore volume of 1.0 ml (-1) +/- 3.7% R.S.D., an average pore diameter of 12.0 nm +/- 0.5% R.S.D. and an average particle diameter of 5 microm. Results are presented on trial batches and the final master batch which were both used as packing materials in reversed-phase liquid chromatography (RP-LC) columns. The latter columns were certified and accepted as an HPLC column as reference material (BCR-722) by the European Commission, Institute for Reference Materials and Measurements (IRMM), Geel, Belgium.