Regioselective hydrostannation of highly hindered arylalkynes under ortho-directing effects

Palladium-catalyzed hydrostannation reactions of ortho-disubstituted arylalkynes were achieved with total stereo- and regio-selectivity in THF at room temperature. The regioselectivity was found to be under the control of the ortho-substituents (ortho-directing effects, ODE) and pure α-vinylstannanes are produced in good yields and as single isomers regardless of the substituents’ nature. These hydrostannation α-products are precursors of choice for the preparation of stereo-defined triarylolefins.     

Rh(I)-catalyzed solvent-free ortho-alkylation of aromatic imines under microwave irradiation

The synthesis of ortho-alkylated ketones through a chelation-assisted Rh (I) catalyzed ortho-alkylation reaction of aromatic imines under microwave activated solvent-free conditions in monomode reactors was performed. These conditions have been also applied to hydroacylation and ortho-alkylation reactions with aldimines.     

Synthesis of chiral ortho-thio-substituted phenyl phosphonodiamidates via a P-S to P-C rearrangement

The ortho-lithiation of a phenyl phosphorodiamidothioate derived from an enantiopure C₂-symmetric diamine is studied. It is shown that the migration of the diaminophosphoryl group from sulfur to carbon, leading to an ortho-sulfanylated phenyl phosphonodiamidate, only occurs in the presence of an alkylating agent or a Lewis acid as BF₃·Et₂O. The influence of the chiral diaminophosphoryl group on the stereoselectivity of the oxidation of the ortho-sulfanyl or alkylsulfanyl group is also examined.     

An efficient synthesis of ortho-N-Boc-arylmethyl ketone derivatives

A new and efficient method for the preparation of ortho-N-Boc-arylmethyl ketone derivatives is reported. The reaction involves the intermediacy of a 4-methylene-3,1-benzoaxin-2-one moiety which smoothly converts to the target compounds under acidic conditions. The ortho-N-Boc-arylmethyl ketone derivatives can be formed in a one-pot reaction or alternatively the 4-methylene-3,1-benzoaxin-2-ones can be isolated and subsequently transformed into the desired products.     

Efficient stereoselective synthesis of oligosaccharides of Streptococcus pneumoniae serotypes 6A and 6B containing multiple 1,2-cis glycosidic linkages

The synthesis of the repeating units of pneumococcal polysaccharide serotypes 6A and 6B and derivatives thereof is described. Application of S-benzoxazolyl and S-thiazolinyl glycosides allowed rapid oligosaccharide assembly and provided complete stereoselectivity in challenging 1,2-cis glucosylations and galactosylations. The oligosaccharide assembly was accomplished in an efficient manner by selective activation of thioimidoyl leaving groups over thioglycosides.     

1-Fluoropyridinium triflates: versatile reagents for transformation of thioglycoside into O-glycoside, glycosyl azide and sulfoxide

1-Fluoropyridinium triflates are versatile reagents to transform thioglycoside into O-glycoside, glycosyl azide and sulfoxide. The electronic nature of the substituents on the pyridine ring can control their ability to activate thioglycosides.     

Experimental and theoretical study of the structure of N,N-dimethyl-4-nitroaniline derivatives as model compounds for non-linear optical organic materials

Molecular and crystal structure of a series of derivatives of N,N-dimethyl-4-nitroaniline has been studied by both X-ray diffraction method and high-level ab initio calculations. According to these data, the dimethylamino groups were found to have a trigonal-pyramidal configuration and are considerably turned with respect to the ring plane in all molecules having a substituent in the ortho-position; on the contrary, this group is planar in the meta-substituted molecules. Topological analysis of the electron density function for all molecules studied within the framework of Bader's ‘atoms in molecules’ (AIM) theory revealed that introduction of a substituent into the ortho- or meta-position of the ring results in increasing of the contribution of the resonance forms different from the quinoid one. Contribution of the latter form is predominant for the structure of N,N-dimethyl-4-nitroaniline (1). Topological analysis of the electron density distribution was used to explain a decreasing of the molecular hyperpolarisabilites of the ortho- and meta-substituted compounds as compared with those for 1.     

Synthesis of novel fused azecine ring systems through application of the tert-amino effect

Novel fused azecine ring systems were synthesized via the microwave-assisted thermal isomerization of terphenyl or biphenyl-pyridazine compounds possessing a vinyl and a tert-amino group, through application of a new extension of the tert-amino effect. Substrates for the ring closure were prepared from ortho-dihalobenzene or pyridazinone by consecutive Suzuki couplings with ortho-sec-amino- and formylphenylboronic acids, followed by Knoevenagel condensation of the aldehydes obtained.     

An efficient catalyst for the synthesis of ortho-substituted biaryls by the Suzuki cross-coupling: Triphenylphosphine adduct of cyclopalladated ferrocenylimine

The air and moisture stable triphenylphosphine adduct of cyclopalladated ferrocenylimine 2 has been successfully used in palladium-catalyzed Suzuki cross-coupling for the synthesis of ortho-substituted biaryls in air. In the presence of 0.05 mol% of 2 as catalyst and 3 equivalent of CsF as base in dioxane at 100 °C, ortho-substituted biaryls were synthesized with moderate to high yields in the reactions of 2-methoxy-1-naphthylboronic acid with aryl halides, and 14 new ortho-substituted biaryls were obtained and characterized.     

Synthesis of ortho-substituted cyanopyridines through lithio intermediate trapping

Ortholithiation of 4-cyanopyridine using 2,2,6,6-tetramethylpiperidide (LiTMP) and trapping the lithio intermediate with electrophiles represents an efficient and straightforward access to ortho-substituted-4-cyanopyridines. The cyano group can be used as an ortho-directing group and allows the preparation of 3-halogeno-4-cyanopyridines. Reactivity of 2- and 3-cyanopyridines is also investigated and seems to give similar results.     

Fast and selective oxidation of thioglycosides to glycosyl sulfoxides using KF/m-CPBA

A very fast and selective oxidation of thioglycosides to glycosyl sulfoxides has been achieved using KF/m-CPBA in CH₃CN-H₂O. This protocol has many advantages compared to the currently available methodologies for this transformation in terms of selectivity, yield, reaction time, control of temperature, etc. The yields obtained were excellent in all cases.     

Regioselective ortho-nitration of N-phenyl carboxamides and primary anilines using bismuth nitrate/acetic anhydride

An efficient and one-pot synthetic method for the regioselective ortho-nitration of the N-phenyl carboxamides and primary anilines has been developed by using bismuth nitrate and acetic anhydride as the nitrating reagents. Reaction proceeds at room temperature and results in corresponding ortho-nitrated products in moderate to excellent yields. This method provides an operationally simple, regioselective, and efficient access to synthesize o-nitro anilines under the mild conditions.     

Stereoselective cycloadditions of (1Z,4R,5R)-1-arylmethylidene-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines to maleimides

A library of 15 1,6,7,9-tetrasubstituted 6,7,9,9a-tetrahydro-5H-pyrazolo[1,2-a]pyrrolo[3,4-c]pyrazole-1,3,5(2H,3aH)-triones was prepared by combinatorial stereoselective cycloadditions of (1Z,4R^∗,5R^∗)-1-arylmethylidene-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines to N-substituted maleimides. Stereochemistry was controlled by the stereodirecting phenyl group at position-3 and by the ortho-substituents at the aromatic ring at position-1′ in azomethine imines. Consequently, two sets of diastereomeric cycloadducts were obtained, one set from the ortho-unsubstituted dipoles and the other set from the ortho-disubstituted dipoles.     

Direct alkenylation of arylamines at the ortho-position

Treatment of magnesium alkylidene carbenoids, which were generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride at −78 °C in toluene, with N-lithio arylamines gave ortho-alkenylated arylamines in moderate to good yields. The reaction was found to proceed in a highly stereospecific manner at the carbenoid carbon. This reaction offers a quite novel and direct alkenylation of arylamines at the ortho-position of the aromatic ring.     

An effective procedure for the preparation of 3-substituted-4- or 6-azaindoles from ortho-methyl nitro pyridines

3-Substituted-4- and 6-azaindoles were prepared from ortho-methyl-nitropyridines in a practically convenient, one-pot process based on the Leimgruber-Batcho reaction. The procedure comprises a sequence of (a) condensation of an ortho-methyl-nitropyridine with N,N-dimethylformamide dimethyl acetal; (b) alkylation or acylation of the enamine intermediate; (c) reduction of the nitro group to an aniline with in situ cyclization and elimination of dimethylamine to generate the 3-substituted azaindole heterocycle.     

Lithiation of 2-(chloroaryl)-2-methyl-1,3-dioxolanes and application in synthesis of new ortho-functionalized acetophenone derivatives

2-(4-Chlorophenyl)-2-methyl-1,3-dioxolane 2a was lithiated ortho to the ketal group by treatment with butyllithium in THF at 0°C. Related 2-aryl-2-methyl-1,3-dioxolanes possessing a chlorine substituent at the meta position of the aryl group 2b,c were lithiated with butyllithium in THF at −78°C at the position between the two directing groups. The lithio species thus generated were treated with various electrophiles to give ortho-functionalized acetophenone derivatives.     

Stabilization of ortho-quinone methides by a bis(sulfonium ylide) derived from 2,5-dihydroxy-[1,4]benzoquinone

The zwitterionic intermediates (2a) in the oxidation of ortho-alkylphenols (1) and bis(sulfonium ylide) 3 form reasonably stable 2:1-complexes (4), in which the ortho-quinone methide (oQM) moieties are not present in quinoid form with the exocyclic in-plane methylene group, but as zwitterionic, aromatic conformer having an out-of-plane exocyclic methylene group. The complex 7 derived from the α-tocopherol model compound PMC (5) was comprehensively characterized. As exemplarily demonstrated, the adducts can be advantageously employed in organic synthesis as ‘stabilized oQMs’.     

An efficient synthesis of sterically hindered arylboronic acids

Boronic acids are important intermediates and molecular recognition moieties in a wide variety of applications. In our research, we have found that the synthesis of ortho-substituted arylboronic acids is problematic with the commonly used bis(pinacolato)diboron in palladium-mediated borylation reactions. As a substitute, we have found that bis(neopentyl glycolato)diboron is a much more efficient borylation agent for the synthesis of sterically hindered ortho-substituted arylboronic acids.     

Efficient one-pot syntheses of α-d-arabinofuranosyl tri- and tetrasaccharides present in cell wall polysaccharide of Mycobacterium tuberculosis

Two α-d-arabinofuranosyl oligosaccharides (2 and 3) found as constituent parts of the polysaccharide portion from the cell wall of Mycobacterium tuberculosis have been efficiently synthesized via a one-pot glycosylation procedure in which a key step is the chemoselective activation between d-arabinofuranosyl trichloroacetimidate donor 4 and partially protected aryl thioglycosides 5 or 7, respectively.