FeCl3-NaI mediated reactions of aryl azides with 3,4-dihydro-2H-pyran: a convenient synthesis of pyranoquinolines

The tetrahydroquinoline moiety is an important structural component of a number of natural products. The reaction of aryl azides with 3,4-dihydro-2H-pyran in the presence of FeCl₃-NaI affords the corresponding tetrahydroquinoline derivatives in an efficient manner. Most of the cyclizations exhibited cis selectivity.     

Regioselective ortho-acetoxylation/methoxylation of N-(2-benzoylphenyl)benzamides via substrate directed C-H activation

A highly regioselective ortho-acetoxylation of N-(2-benzoylphenyl)benzamides has been achieved using a catalytic amount of Pd(OAc)₂ (10 mol %) and a stoichiometric amount of PhI(OAc)₂ in a mixture of acetic anhydride and acetic acid via C-H activation to produce the corresponding 2-acetoxybenzamides in good yields. ortho-Methoxylation has been accomplished using methanol under similar conditions.     

Ruthenium-catalyzed arylation of fluorinated aromatic ketones via ortho-selective carbon-fluorine bond cleavage

We report here ruthenium-catalyzed arylation of fluorinated aromatic ketones via ortho-selective carbon-fluorine bond cleavage. In the presence of trimethylvinylsilane and cesium fluoride, ortho carbon-fluoride bonds of aromatic ketones were phenylated by 5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane using RuH₂(CO)(PPh₃)₃ as a catalyst. Tandem C-F phenylation/C-H alkylation was observed for substrates bearing both one ortho hydrogen and one ortho fluorine atoms.     

Complete thermodynamic analysis of the ionization of ortho-methoxybenzoic acid. Influence of the medium on the ortho effects

The ionization and solution enthalpies of o-methoxybenzoic acid have been measured in H₂O-DMSO mixtures. In the same solutions, the ΔG⁰ values for the ionization process have been determined by potentiometric measurements. A study of the ortho effects by means of a linear combination of the ordinary polar, proximity polar, and steric effects was also performed. The CH₃O group seems to undergo a partial steric inhibition of resonance. Finally, the proton transfer process from the ortho derivative to benzoic acid, compared with the same process in the gaseous phase, is presented.     

Et-duphos-nickel-catalyzed asymmetric arylation of benzaldehyde derivatives bearing an ortho-Me2PhSi group with potassium aryltriolborates

The Ni-catalyzed asymmetric arylation of benzaldehydes bearing an ortho-masked H group with potassium aryltriolborates has been developed. The keys to success were (i) steric tuning of benzaldehyde derivatives with an ortho-Me₂PhSi group, and (ii) the use of potassium aryltriolborates as aryl sources.     

Synthesis, structure, and conformation of ortho-linked oxacalix[n]arene[n]hetarenes

ortho-Linked oxacalix[n]arene[n]hetarenes (n=2, 3) were prepared by one-step cyclooligomerization of catechol and meta-dichlorinated nitrogen containing heterocycles or via a two-step reaction process. Solid state structure of the ortho-linked oxacalix[n]arene[n]hetarenes (n=2, 3) has been determined by X-ray crystallography. 1,3-Alternate and 1,3,5-alternate conformations were found for ortho-linked oxacalix[2]arene[2]pyrazine (1) and oxacalix[3]arene[3]pyrazine (2), respectively. However, a core conformation with C₃ symmetry was found for ortho-linked oxacalix[3]arene[3]pyrimidine (4), which is completely different from that of its isomer, compound 2.     

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.     

Metalations utilizing aryllithiums; ortho-functionalization of p-bromoanisole (pBrA)

An ortho-metalation protocol has been developed, which permits the survival of a bromine substituent in p-bromoanisole. Eight derivatives of the generated ortho-lithiated intermediate have been prepared. A neglected metalation concept is being explored here; one which proposes that minimizing the pK_a difference between the aryl substrate and the conjugate acid of the metalating agent will lead to a regiospecific and selective metalation process.     

Studies on bis(1′-ortho-carboranyl)benzenes and bis(1′-ortho-carboranyl)biphenyls

Reactions between the C,C′-dicopper(I) derivative of ortho-carborane and ortho-, meta- and para-diiodobenzene are reported. The reaction with 1,2-C₆H₄I₂ unexpectedly afforded 2,2′-bis(1′-ortho-carboranyl)biphenyl, [HCB₁₀H₁₀CC₆H₄]₂2, whereas reactions with 1,3- or 1,4-C₆H₄I₂ provided alternative routes to 1,3-bis(1′-ortho-carboranyl)benzene 3 and 1,4-bis(1′-ortho-carboranyl)benzene 4, respectively. The crystal structure of the biphenyl derivative 2 revealed significant distortions in the biphenylene framework attributable to the proximity of the two bulky carborane cages. UV absorption spectra and electrochemical data on 2 and 3 showed little electronic communication between the two carborane cages in either, and negligible π-conjugation between the two ortho-phenylene rings in 2. However, substantial evidence was found of electronic communication between the carborane cages via the para-phenylene bridge in 4. B3LYP/6-31G^∗ computations have been carried out on compounds 2 and 4, on 4,4′-bis(ortho-carboranyl)biphenyl 6 and on 1,2-bis(1′-ortho-carboranyl)benzene 7. Those on 2, 4 and 6 show the computed geometries to be in very good agreement with the experimental geometries: those on 7 allowed the reported molecular geometry of this compound to be revised and revealed a long cage C–C bond of 1.725(3) Å.     

Chemical behavior of ortho-hydroquinone-based bis(pyrazol-1-yl)methane ligands in the presence of palladium(II) chloride

The synthesis, structural characterization, and coordination behavior of ditopic ortho-hydroquinone-based bis(pyrazol-1-yl)methane ligands (ortho-(OH)₂C₆H₃-4-CHpz₂, ortho-(OH)₂C₆H₃-4-CH(3-Phpz)₂, and ortho-(OH)₂C₆H₃-4-CH(3-tBupz)₂) with pyrazole, 3-phenylpyrazole, and 3-tert-butylpyrazole as donors are described. The reaction of a soluble PdCl₂-source with ortho-(OH)₂C₆H₃-4-CHpz₂ in acetonitrile yielded the related square-planar N,N-coordinated Pd(II) dichloride complex, whereas treatment of ortho-(OH)₂C₆H₃-4-CH(3-Phpz)₂ or ortho-(OH)₂C₆H₃-4-CH(3-tBupz)₂ with PdCl₂ in acetonitrile resulted in degradation of these ligands. The Pd(II) complexes trans-(3-PhpzH)₂PdCl₂ and trans-(3-tBupzH)₂PdCl₂ were isolated and fully characterized including X-ray diffraction analyses.     

One‐Pot Cascade Transformation of Glucal into Structurally Diverse Drug‐Like Scaffolds

A diversity‐oriented synthesis strategy to produce three types of structurally drug‐like N‐heterocyclic‐fused rings has been developed from abundant biomass‐derived d ‐glucal, aniline and water in a stereoselective manner. The overall transformation which entails a cascade of Ferrier reaction and 4π conrotatory imino‐Nazarov cyclization was performed in one‐pot allowing convenient preparation of scaffolds of high molecular complexity from relatively simple starting materials. While indoline‐fused products were readily accessible using ortho‐unsubstituted secondary anilines as substrates, reactions with ortho‐hydroxyl‐anilines furnished fused 1,4‐benzoxazines instead. In both cases, InBr₃ acted as the Lewis acid catalyst. By altering InBr₃ to Ln(OTf)₃, the indoline‐fused products could be further converted into tetrahydroquinoline‐fused cyclopentenones via ensuing retro‐ene rearrangement.     

Indium chloride catalyzed intramolecular cyclization of N-aryl imines: synthesis of pyrrolo[2,3-d]pyrimidine annulated tetrahydroquinoline derivatives

The intramolecular aza Diels-Alder cyclization reaction of aldimines derived from aromatic amines and N-prenyl/cinnamyl derivatives of pyrrolo[2,3-d]pyrimidine were efficiently catalyzed by InCl₃ to afford the corresponding tetrahydroquinoline derivatives in good yields.     

The crystal and molecular structure of tris(ortho-aminobenzoato)aquoyttrium(III), Y(H2NC6H4COO)3 · H2O

Tris(ortho-aminobenzoato)aquoyttrium(III), Y(H₂NC₆H₄COO)₃ · H₂O, crystallizes in the monoclinic space group, $\text{C2}\text{c}$, with eight molecules in a unit cell of dimensions: a = 30.89(1) Å, b = 9.09(1) Å, c = 14.85(1) Å, and β = 109.3(1)°. The structure was determined using three-dimensional X-ray diffraction data gathered on multiple-film equi-inclination, integrated Weissenberg, and precession photographs taken about two crystal axes. The structure, excluding the hydrogen atoms, was solved from Patterson and electron density maps and refined by least-squares methods to a final R of 0.081. The coordination about the yttrium atom is sevenfold, best described by a capped trigonal prism. Each ortho-aminobenzoate ligand acts as a bridging bidentate ligand, resulting in six ortho-aminobenzoate residues coupled to each yttrium atom. The water molecule occupies the seventh position. This bonding configuration generates a structure in which each yttrium atom in (100) is attached to two other yttrium atoms via carboxylate bridges to give parallel sets of polymeric chains coincident with (100). It is suggested that this polymeric character accounts for the extreme insolubility of Y(H₂NC₆H₄COO)₃ · H₂O.     

Thermodynamic analysis of the ionization of ortho and para toluic acids : influence of the medium on the hyperconjugative and steric effects

The hyperconjugative effect of the methyl group in the para and ortho position of the benzene ring is studied as a function of the medium. The ionization and solution enthalpies of ortho and para toluic acids have been measured in H₂O/DMSO mixtures. A study of the ortho effects by means of the linear combination of the ordinary polar, proximity polar and steric effects has also been performed.The methyl group both in ortho and para position seems to be forced out by the benzene ring at X_dmso= 0.5 mole fraction with a consequent decrease of hyperconjugation effect. A study of enthalpic and entropic contributions to substituent and reaction constants and the proton transfer process from ortho and para derivatives to benzoic acid, compared with the same process in the gaseous phase are also presented.     

ortho-Difunctionalization of arynes by LiZnEt2(TMP)-mediated deprotonative zincation/elimination of aryl triflates

Generation of arynes from aryl triflates has been achieved using lithium diethyl(tetramethylpiperidyl)-zincate base LiZnEt₂(TMP), via a directed ortho-deprotonative zincation and subsequent elimination of the triflate group. The aryne formation has been demonstrated by the cycloaddition reaction with diene and insertion reactions with ureas. Furthermore, the nucleophilic addition of LiZnEt₂(TMP) to arynes was observed in the absence of external aryne partners, offering a new cascade strategy for diverse difunctionalization of arynes.     

AuCl-catalyzed reaction of ortho-alkynyl(oxo)benzene with benzenediazonium 2-carboxylate as a synthetic method towards anthracene, triptycene, and phthalazine derivatives

The AuCl-catalyzed benzannulation of ortho-alkynylphenyl ketones with benzenediazonium 2-carboxylate proceeded efficiently at 40 °C in (CH₂Cl)₂ and a variety of anthracene derivatives, having a ketone group at 9-position, were produced in good to high yields. On the other hand, the reaction of ortho-alkynylbenzaldehydes with benzenediazonium 2-carboxylate afforded triptycyl ketones. The reactions most probably proceed through the formation of a zwitterionic intermediate by the gold-induced electrophilic cyclization of ortho-alkynyl(oxo)benzenes, followed by the cycloaddition of benzyne. In contrast, when the above reaction was carried out at rt in 1,4-dioxane, phthalazine derivative was produced without the generation of benzyne.     

Preparation and structural characterization of a new class of stable thioketones: ortho-hydroxythioacetophenones

ortho-Hydroxythioacetophenone and four structurally related ortho-hydroxyaryl methyl thioketones have been prepared from the corresponding ketones by reaction with gaseous H₂S and HCl in ethanol under strictly controlled reaction conditions. The remarkable stability of the new monomeric thioketones seems to be due to a strong intramolecular O-H?SC hydrogen bonding.     

Transition-metal-free approach to synthesis of indolines from N-(ortho-chloromethyl)aryl amides and iodonium ylides

A transition-metal-free method for the synthesis of indolines has been developed. In the presence of K₂CO₃, the cyclization reaction of N-(ortho-chloromethyl)aryl amides and iodonium ylides proceeded smoothly at room temperature in moderate to good yields.     

An effective synthetic route to ortho-difluoromethyl arylphosphosphonates: studies on the reactivity of phosphorus- and fluorine-containing functions

Herein, we report a new and convenient methodology for the synthesis of ortho-XCF₂ arylphosphonates via Diels-Alder reaction of selected 1,3-butadienes with XCF₂-≡-P(O)(OEt)₂, followed by the aromatization of the cyclic vinylphosphonates obtained using the KMnO₄/Al₂O₃ system. The reactivity of ortho-XCF₂ arylphosphonates was then examined to give the respective dichlorides that were converted to the corresponding phosphonic acids, phosphine oxides or a carboxylic acid (upon hydrolysis of the CF₂Br group). When ortho-XCF₂ arylphosphonates (X=Br) were treated with Zn/CuBr and an electrophile, the dimeric product ArCFCFAr was isolated only. The lithiation of the CF₂H group (X=H) allowed however to obtain products of nucleophilic substitution with various electrophiles.     

Ortho selectivity in SNAr substitutions of 2,4-dihaloaromatic compounds. Reactions with piperidine

A broad survey of aromatic compounds with halogens positioned both ortho and para to activating groups was studied in S_NAr reactions with piperidine. Regioselectivities varied with the substituent group and the polarity of the solvent. Many activating groups exhibited an overall bias toward ortho-substitution, and this led in nonpolar solvents to very high ortho selectivity. More polar solvents uniformly shifted the product ratio toward para substitution. Evidence is presented that argues for coordination via hydrogen bonding as a driver of much of the ortho selectivity observed. The data presented show ample evidence of the generality and synthetic utility of the ortho-directing ability of several common activating groups for this reaction type.