Functionalization of dihydrodipyridopyrazines involving palladium-catalyzed coupling reactions

Various 4-substituted dihydrodipyridopyrazines were synthesized by palladium-mediated cross-coupling reactions. Starting from the corresponding 4-iodo or 4-bromo derivatives, the incorporation of aryl, vinyl, alkynyl and methoxycarbonyl groups is described.     

Boehmite@tryptophan‐Pd nanoparticles: A new catalyst for C–C bond formation

A boehmite@tryptophan‐Pd nanoparticulate catalyst was prepared by a simple, fast and convenient route. The nanomaterial was characterized using various techniques and employed as a thermally stable catalyst for Heck, Stille and Suzuki cross‐coupling reactions. Optimized conditions for these reactions are described. The catalyst could be isolated, post‐reaction, by simple filtration and recycled for several consecutive cycles without a notable change in its activity.     

Biochar as heterogeneous support for immobilization of Pd as efficient and reusable biocatalyst in C–C coupling reactions

Biochar is a stable and carbon‐rich solid which has a high density of carbonyl, hydroxyl and carboxylic acid functional groups on its surface. In this work, the surface of biochar nanoparticles (BNPs) was modified with 3‐choloropropyltrimtoxysilane and further 2‐(thiophen‐2‐yl)‐1H‐benzo[d]imidazole was anchored on its surface. Then, palladium nanoparticles were fabricated on the surface of the modified BNPs and further the catalytic application was studied as recyclable biocatalyst in carbon–carbon coupling reactions such as Suzuki–Miyaura and Heck–Mizoroki cross‐coupling reactions. The structure of the catalyst was characterized using scanning electron microscopy, transmission electron microscopy, energy‐dispersive X‐ray spectroscopy, thermogravimetric analysis, X‐ray diffraction and atomic absorption spectroscopy. The catalyst can be reused several times without a decrease in its catalytic efficiency. In addition to the several advantages reported, application of biochar as catalyst support for the first time is a major novelty of the present work.     

Pillared salicylaldehyde derivatives as building blocks for the design of cofacial salen-type ligands

The syntheses of pillared salicylaldehyde derivatives on a naphthalene block are reported. These compounds can be considered as building blocks for the elaboration of cofacial salen-typed ligands. The X-ray structure of a dinuclear manganese(III) complex is described, supporting our strategy to build topologically controlled multinuclear metal complexes.     

1,3,2,4-Diazadiphosphetidines as new P-N ligands for palladium-catalyzed Heck reaction in water

1,3,2,4-Diazadiphosphetidine-based phosphazane class have been used as a new generation of heterogeneous bidentate P(III) ligands containing nitrogen for base-free Pd(II) catalyzed C-C bond formation through Heck coupling reaction of aryl iodides, bromides and chlorides in water with styrene, n-butyl acrylate, 1-octene, and cyclohexene. The reactions occur heterogeneously in water and homogenously or partially heterogeneously in appropriate organic solvents. The ligand together with its Pd(0) complex is easily separated by filtration and reused for several runs.     

1,3-Dicarbonyl compounds as phosphine-free ligands for Pd-catalyzed Heck and Suzuki reactions

Some 1,3-dicarbonyl compounds (such as pentane-2,4-dione and 3-oxo-N-phenylbutanamide) were found to constitute highly efficient, yet low-priced and phosphine-free ligands for the Pd-catalyzed Heck and Suzuki reactions of aryl bromides and iodides with very high turnover numbers (ca. 103-104).     

Palladacycles bearing pendant benzamidinate ligands as catalysts for the Suzuki and Heck coupling reactions

Three pendant benzamidines [Ph-C(NC₆H₅)-{NH(CH₂)₂NMe₂}] (1), [Ph-C(NC₆H₅)-{NH(CH₂Py)}] (2) and [Ph-C(NC₆H₅)-{NH(o-C₆H₄)(oxazoline)}] (3) are described. Reactions of 1, 2 or 3 with one molar equivalent of Pd(OAc)₂ in THF give the palladacyclic complexes [Ph-C{-NH(η¹-C₆H₄)}{N(CH₂)₂NMe₂}]Pd(OAc) (4), [Ph-C{-NH(η¹-C₆H₄)}{N (CH₂Py)}]Pd(OAc) (5) and [Ph-C{-NH(η¹-C₆H₄)}{N(o-C₆H₄)(oxazoline)}]Pd(OAc) (6), respectively. Treatment of 4, 5 or 6 with excess of LiCl in chloroform affords [Ph-C{-NH(η¹-C₆H₄)}{N(CH₂)₂NMe₂}]PdCl (7), [Ph-C{-NH(η¹-C₆H₄)}{N(CH₂Py)}]PdCl (8) and [Ph-C{-NH(η¹-C₆H₄)}{N(o-C₆H₄)(oxazoline)}]PdCl (9). The crystal and molecular structures are reported for compounds 1, 3, 5, 6 and 7. The application of these palladacyclic complexes to the Suzuki and Heck coupling reactions was examined.     

Synthesis of a paramagnetic boronic acid as a useful synthetic building block and carbohydrate affinity spin probe

A paramagnetic boronic acid was synthesized by lithiation of 1-acetoxy-3-bromo-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole followed by treatment with trimethyl borate. This paramagnetic boronic acid proved to be a useful starting compound in Suzuki cross-coupling reactions and it exhibited affinity toward fructose and inulin.     

Synthesis of substituted tetralones as intermediates of CNS agents via palladium-catalyzed cross-coupling reactions

A series of substituted tetralones as intermediates of CNS agents has been synthesized via Pd-catalyzed coupling reactions of 3-(methoxycarbonyl)-1,2,3,4-tetrahydro-1-oxonaphthalen-6-yl trifluoromethanesulfonate (5) with a variety of organometallic reagents.     

Trifluoromethyl-substituted hydantoins, versatile building blocks for rational drug design

Preparatively simple, one-pot syntheses of trifluoromethyl-substituted hydantoins starting from Boc-protected imines of hexafluoroacetone and trifluoropyruvate are described. They represent valuable building blocks for the construction of constrained peptides or as scaffolds for the synthesis of highly potent VLA-4 antagonists.     

Synthetic studies on Ecteinascidin-743: synthesis of building blocks through Sharpless asymmetric dihydroxylation and aza-Michael reactions

A practical and an efficient synthesis of three building blocks of tetrahydroisoquinoline alkaloid Ecteinascidin-743 was accomplished, starting from readily available piperonal, 2-methyl anisole, and veratraldehyde. A combination of Vilsmeier-Haack reaction and Sharpless asymmetric dihydroxylation was employed for the synthesis of building blocks A and B whereas a Heck reaction in PEG-2000 and aza-Michael reactions were employed for the synthesis of building block C.     

Synthesis of 5-aminothiazoles as building blocks for library synthesis

A convenient route to 4-phenyl-5-aminothiazoles is described, which offers control over substitution at the 2-position. 2-N-Acylglycinamides were dithionated and a subsequent TFAA-mediated cyclisation step was followed by removal of the 5-N-trifluoroacetyl group providing the free amines. Though applicable generally the method was found to be most effective when introducing aromatic substituents at the 2-position, whereupon moderate overall yields of the 5-amino compounds were obtained.     

The nitrosocarbonyl hetero-Diels-Alder reaction as a useful tool for organic syntheses

Organic transformations that result in the formation of multiple covalent bonds within the same reaction are some of the most powerful tools in synthetic organic chemistry. Nitrosocarbonyl hetero-Diels-Alder (HDA) reactions allow for the simultaneous stereospecific introduction of carbon-nitrogen and carbon-oxygen bonds in one synthetic step, and provide direct access to 3,6-dihydro-1,2-oxazines. This Review describes the development of the nitrosocarbonyl HDA reaction and the utility of the resulting oxazine ring in the synthesis of a variety of important, biologically active molecules.     

Flow synthesis of tricyclic spiropiperidines as building blocks for the histrionicotoxin family of alkaloids

A domino cyclization reaction of the bis-unsaturated ketone 3 with hydroxylamine proceeds with good yield and high stereoselectivity, in a flow reactor system. The tricyclic spiropiperidine products 5 and 2 obtained are valuable building blocks for the synthesis of analogues of the histrionicotoxin alkaloids.     

Efficient imidazolium salts for palladium-catalyzed Mizoroki-Heck and Suzuki-Miyaura cross-coupling reactions

The system, Pd(OAc)2/imidazolium salts (L2), was found as an efficient catalyst in the Heck coupling reaction of olefins with aryl halides and Suzuki reactions of various aryl halides with aryl boronic acids under aerobic condition. This catalytic system demonstrates great tolerance to a wide range of groups on all substrates of aryl halides, alkenes and aryl boronic acids.     

Naphthalene-1,8-diyl bis(halogenophosphanes): novel syntheses and structures of useful synthetic building blocks

A series of new bay region disphospha-functionalised naphthalenes is reported. The reduction of ylidic phosphonium phosphoride NapP(2)Cl(6) (1) (Nap=naphthalene-1,8-diyl) with MeOPCl(2) gives the important synthon Nap(PCl(2))(2) (2) in nearly quantitative yield. Reaction of 1 with magnesium metal affords (NapP(2))(n) (3), which reacts with Br(2) and I(2), yielding Nap(PBr(2))(2) (4) and Nap(PI)(2) (5), respectively. X-ray structure determinations reveal a twisted geometry of the naphthalene ring in sterically strained 2 and 4, whilst the presence of a P-P bond in 5 results in the release of the steric strain and generation of the planar NapP(2) moiety. Although the tetrahedral P environments are severely distorted the sigma(3)P-sigma(3)P bonding in 5 represents a new type of P-P bonding environment in 1,8-diphosphanaphthalenes. Compounds 1, 4 and 5 each represent the highest coordination, achievable by direct halogenation. The new compounds 2-5 were fully characterised by NMR, IR, and Raman spectroscopy, mass spectrometry, and elemental analysis.     

Ultrasound irradiation promoted catalyst-free construction of formamidine framework using isocyanide as building blocks

Reactions of isocyanides with 2-mercaptobenzothiazole and 2-mercaptobenzoxazole afforded a series of compounds containing formamidine framework in moderate to high yields. These organic transformations were performed under mild and catalyst-free conditions. In addition to promoting the reactions, the use of ultrasound irradiation also allowed the process to be carried out under air atmosphere. A possible reaction mechanism was proposed based on the experimental results.