Facile synthesis of C-phosphanylformamidines via a carbene pathway

A direct synthetic approach to C-phosphanyl-N,N-dialkyl-N′-aryl(alkyl)-formamidines was developed. It was shown that phosphorylation of the formamidines proceeds at the nitrogen atom affording N-phosphanylformamidinium salts. Upon deprotonation, these salts gave C-phosphanylformamidines via formation of carbenes followed by a 1,2-phosphorus shift.     

New protic salts of aprotic polar solvents

Aprotic polar solvents such as DMF, acetonitrile or DMSO can be protonated to form stable triflate salts when treated with triflic acid. The reaction of the same solvents with N,N-bis(trifluoromethanesulfonyl)imide led to the isolation of the corresponding N,N-bis(trifluoromethanesulfonyl)imide salts.     

Synthetic studies of erythromycin derivatives: 6-O-methylation of (9S)-12,21-anhydro-9-dihydroerythromycin A derivatives

Synthetic studies on methylation of erythromycin derivatives were conducted. Methylation of 6 resulted in the formation of the C-3′ quaternary ammonium salts with a rate faster than 6-O-methylation. In dipolar aprotic solvent and under strong base conditions, 6-O-methylation, C-3′ quaternary ammonium salts formation and 2-C-methylation proceeded simultaneously to yield a mixture of three different products 7, 8 and 9. The quaternary ammonium salts were converted back to the corresponding tertiary amines 2, 10 and starting material 6 by employing sodium 4-pyridinethiolate as a N-demethylation reagent. The 6-O-methylation was eventually achieved in a good yield when a carbobenzyloxy (Cbz) group was utilized to protect the C-3′-dimethylamino group of 4. In this report, we will discuss the details of different reaction courses in the methylation of (9S)-12, 21-anhydro-9-dihydroerythromycin A derivatives.     

1-(N-Acylamino)alkyltriphenylphosphonium salts as synthetic equivalents of N-acylimines and new effective α-amidoalkylating agents

1-(N-Acylaminoalkyl)triphenylphosphonium salts 2a-f on reaction with DBU in MeCN are transformed into 1-(N-acylaminoalkyl)amidinium salts 3a-f. Amidinium salts 3d-f with a proton at the β-position undergo slow tautomerization into the corresponding enamides 6d-f. The same 1-(N-acylamino)alkyltriphenylphosphonium salts 2d-f in the presence of Hünig’s base are transformed directly into the corresponding enamides. Phosphonium salts 2, amidinium salts 3, and enamides 6 react with dialkyl malonates in the presence of DBU to give the corresponding amidoalkylation products. α-Amidoalkylation of dialkyl malonates is not observed in the presence of (i-Pr)₂EtN, yet proceeds well under these conditions with more acidic nucleophiles, for example, phthalimide or benzyl mercaptan.     

Synthesis of chiral imino- and amino-imidazolium salts and of chelating amino-N-heterocyclic carbene palladium(II) complexes

A new preparation of chiral imino-imidazolium salts has been developed by condensation of chiral primary amines with 1-(2-oxo-2-phenyl-ethyl)-imidazolium salts in chloroform. This reaction gave the (E)-imino-imidazolium salts with stereoselectivities superior to 95:5. The structure of the imines were determined by NMR analyses. Reduction of the chiral (E)-imino-imidazolium salts with NaBH₄ in MeOH led to amino-imidazolium salts as a mixture of diastereomers with selectivities ranging from 84:16 to 90:10. The major diastereoisomer could be purified in some cases by crystallization and the absolute configurations were determined by X-ray diffraction. Chelating amino-N-heterocyclic carbene dichloro palladium(II) complexes were obtained in two steps via formation of the corresponding silver(I) complexes and reaction of these latters with bis(acetonitrile)dichloropalladium. Crystal structure details of a cis-dichloro amino-imidazol-2-ylidene palladium complex are presented and confirmed the formation of a six-membered Pd-metallocycle.     

Unexpected course of rearrangement of substituted S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides

Three series of S-(1(3H)-isobenzofuranone-3-yl)isothiuronium bromides differing in substitution at the isothiuronium moiety (none, one or two methyl groups) and at the benzene ring were prepared and characterized. These salts were then treated with various bases (acetate, triethylamine, Na₂CO₃) to give either 1-hydroxy-3-oxo-1,3-dihydro-2H-isoindol-2-carbothioamides or the product of S to N isobenzofuranone-3-yl migration, i.e., 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas. If ammonia was used in reaction with N,N′-dimethyl isothiuronium salts then 3-hydroxy-2,3-dihydro-1H-isoindol-1-ones were formed together with 1,3-dimethyl-1-(3-oxo-1,3-dihydro-2-benzofuran-1-yl)thioureas in parallel reaction with the yields increasing with ammonia concentration. The formation of isoindolones takes place in two steps with an aldehyde intermediate, which can be trapped with N,N-dimethylhydrazine.     

Endo- and exocyclic N-alkylation of 1- and 5-aminotetrazoles with t-BuOH-HClO4: synthesis of mono-, di-, and tri-tert-butyl substituted aminotetrazolium salts

A new method for the synthesis of 1,3,5-trisubstituted aminotetrazolium salts based on alkylation of 1- and 5-aminotetrazoles with the t-BuOH-HClO₄ system is presented. Depending on the structure of the tetrazole substrate and reaction conditions, alkylation proceeds at the endocyclic nitrogen atoms as well as at the 1- and 5-amino groups giving mono-, di-, and tri-tert-butyl substituted tetrazolium salts. An X-ray diffraction investigation of 3-tert-butyl-1,5-bis(tert-butylamino)tetrazolium perchlorate and 5-amino-1,3-di-tert-butyltetrazolium chloride was carried out.     

Synthesis of new derivatives of 1,5,9,13-tetraaza[16]annulene using 2-substituted vinamidinium salts

New 7,15-dibromo-, 7,15-di(bromomethyl)-, and 7,15-di[4-(bromomethyl)phenyl]-1,5,9,13-tetraaza[16]annulene derivatives are synthesized via the condensation reaction of 2-substituted vinamidinium salts [2-substituted 3-(dimethylamino)-N,N-dimethyl-2-propen-1-aminium salts] with 1,8-diaminonaphthalene in acetonitrile/acetic acid. The ultraviolet spectral behavior of these compounds is examined in DMSO.     

Preparation and oxidative coupling of bis[o-(hydrosilyl)phenyl]cuprates and bis[o-(fluorosilyl)phenyl]cuprates

Bis[o-(hydrosilyl)phenyl]cuprates and bis[o-(fluorosilyl)phenyl]cuprates were prepared by reacting [o-(hydrosilyl)phenyl]lithiums and [o-(fluorosilyl)phenyl]lithiums, respectively, with copper salts, such as CuCN and Cu(OPiv)₂. The phenylcuprates underwent oxidative coupling to afford 2,2′-bis(hydrosilyl)biphenyls and 2,2′-bis(fluorosilyl)biphenyls.     

Synthesis and structural chemistry of arene-ruthenium half-sandwich complexes bearing an oxazolinyl-carbene ligand

Reaction of a series of directly connected oxazoline-imidazolium salts with silver(I) oxide and subsequent transmetallation with [Ru(p-cymene)Cl₂]₂ and anion exchange with KPF₆ cleanly gave the corresponding 2-oxazolinyl-(N-mesityl)imidazolidene(chloro)ruthenium(II) half-sandwich complexes [RuCl(oxcarb)(p-cymene)]PF₆, two derivatives of which were characterized by X-ray diffraction. Abstraction of the chloro ligand furnished the dicationic aqua complexes [Ru(H₂O)(oxcarb)(p-cymene)](PF₆)₂ which possess a similar coordination geometry. The syntheses were found to be highly diastereoselective, since only one diastereoisomer could be observed in all ruthenium complexes upon reaction of the chiral enantiopure oxazoline-imidazolium salts. Their potential as transfer hydrogenation and Lewis acid catalysts has been probed.     

Reaction of (diacetoxyiodo)benzene with excess of trifluoromethanesulfonic acid. A convenient route to para-phenylene type hypervalent iodine oligomers

Reaction of (diacetoxyiodo)benzene [PhI(OAc)₂] in trifluoromethanesulfonic acid (TfOH) resulted in oligomerization of PhI(OAc)₂. Quenching with NaBr gave the bromide salts of hypervalent iodine oligomers that were determined by thermolysis with KI to be a para phenylene type of oligomers. Neutralization of the reaction mixture of PhI(OAc)₂ and TfOH with aqueous NaHCO₃ yielded the triflate salts of iodine oligomers. Furthermore, quenching the reaction mixture with aromatic substrates afforded arylated iodine oligomers. These iodine oligomers were found to be 3-4 of the number average degree of polymerization (P_n) by GC analysis of the thermolysis products and ¹H NMR analysis. The major products, trimer and tetramer, were synthesized independently.     

Synthesis of Pd complexes bearing an enantiomerically resolved seven-membered N-heterocyclic carbene ligand and initial studies of their use in asymmetric Wacker-type oxidative cyclization reactions

The development of enantiomerically resolved, axially-chiral seven-membered N-heterocyclic carbene (⁷NHC) ligands for palladium is described. These ⁷NHC ligands are derived from enatiomerically pure 2,2′-diamino-6,6′-dimethylbiphenyl, which is transformed via a synthetic sequence consisting of ortho-arylation, N-alkylation, and cyclization to afford seven-membered-ring amidinium salts. Synthesis of the seven-membered amidinium salts benefits from microwave irradiation, and in-situ metalation of the amidinium salts yields ⁷NHC-Pd^II complexes. The chiral ⁷NHC-Pd complexes were examined as chiral catalysts under aerobic conditions in two intramolecular oxidative amination reactions of alkenes. In one case, enantioselectivities up to 63% ee were obtained, while the other substrate underwent cyclization to afford essentially racemic products. The catalytic data compare favorably to results obtained with a Pd^II catalyst bearing a chiral five-membered-ring NHC ligand and, thereby, highlight the potential significance of this new class of chiral NHC ligands.     

Highly efficient synthesis of spirocyclic (1R)-camphor-derived triazolium salts: application in the catalytic asymmetric benzoin condensation

New (1R)-camphor-derived triazolium salts, incorporating a spirocyclic system, are described. Benzoin condensation of aromatic aldehydes, mediated by these salts affords α-hydroxyketones in good yields and moderate enantiomeric excesses.     

Synthesis of a new donor, BEDT-HBDST and crystal structures, electrical and magnetic properties of (BEDT-HBDST)2MX4 (M=Fe, Ga, X=Cl, Br), where BEDT-HBDST=2,5-bis(4,5-ethylenedithio-1,3-diselenol-2-ylidene)-2,3,4,5-tetrahydrothiophene

A novel conjugation-elongated bis(ethylenedithio)tetraselenafulvalene (BETS) type donor, 2,5-bis(4,5-ethylenedithio-1,3-diselenol-2-ylidene)-2,3,4,5-tetrahydrothiophene (BEDT-HBDST) and its magnetic and non-magnetic anion salts, (BEDT-HBDST)₂MX₄ (MX₄⁻=FeCl₄⁻, GaCl₄⁻, FeBr₄⁻ and GaBr₄⁻), were prepared. These four salts are isostructural and belong to the space group of P2/c. They showed semiconducting behavior with small activation energies (59-64 meV). The band structures of these salts are quasi one-dimensional and there is a midgap between the upper band and the lower band, since the degree of dimerization is significant in the stacking direction. The MX₄⁻ ions are located between the donor columns and near to the ethylenedithio moieties of the donor molecules. The magnetic susceptibilities of the FeCl₄⁻ and FeBr₄⁻ salts follow the Curie-Weiss law with Curie constants of 4.6 and 4.8 emu K mol⁻¹ (sum of the spins of S=5/2 and S=1/2) and negative Weiss temperatures of θ=−1.2 and −4.9 K, respectively, revealing a weak antiferromagnetic interaction of 3d spins of the FeCl₄⁻ and FeBr₄⁻ anions. The Fe?Fe (6.66-7.60 Å), Cl?Cl (4.81-4.82 Å) and Br?Br (4.74-4.77 Å) distances in the crystal structures of these salts are significantly long. Therefore, the direct magnetic interaction between the 3d spins of the nearest neighboring Fe³⁺ ions appears to be not readily accessible.     

Synthesis of pyrazine-bridged diimidazolium salts and their application in palladium catalyzed Heck-type coupling reactions

Reaction of imidazole derivatives with 2,3-di(bromomethyl)pyrazine results in the formation of the new pyrazine-bridged diimidazolium salts 1-8. These salts proved to be valuable precursors for dinuclear complexes with mixed NHC/pyrazine ligands. Two of the pyrazine-bridged diimidazolium salts 3·H₂O and 8·2H₂O have been characterized by X-ray diffraction. Furthermore, the first catalytic studies with mixtures of palladium acetate and the imidazolium salts have been carried out. The in situ prepared palladium complexes derived from the diimidazolium salts 1-8 exhibit a modest catalytic activity in Heck-type coupling reactions between 4-bromo benzaldehyde and styrene or n-butyl acrylate.     

Improved methods for the synthesis and isolation of imidazolium based ionic salts

Solvent-free reactions were used for the synthesis of a series of imidazolium-based ionic salts: 3,3′-[pyridine-2,6-diylbis(methylene)]bis(1-R-1H-imidazol-3-ium)chloride; (R = methyl, ethyl, butyl, isobutyl, hexyl, and benzyl). A simple and effective filtration process was used to isolate all the products in high purity and with yields ?93% within a 24 h period. The highly pure ionic compounds which are precursors to N-heterocyclic carbene ligands used in catalysis were fully characterized as gray-white hygroscopic salts.     

Synthesis of cesium selective pyridyl azocalix[n]arenes

A series of pyridylazo calix[n]arenes (n=4, 6, 8) including the first examples of mixed hetroaryl azocalix(n)arenes have been synthesized by coupling calix[n]arenes with diazonium salts derived from amino pyridines. It has been observed that the coupling reaction of diazonium salt obtained from 3-aminopyridine with calix[n]arene gives tetrakis-, hexakis- and octakis (pyridylazo)calix[n]arenes (n=4,6,8) while those derived from 4-aminopyridine give partially substituted (4-pyridylazo)calix[n]arene analogs. There is no reaction of calix(n)arenes with diazonium salts derived from 2-aminopyridine under identical conditions of experiments. The conformational analysis of synthesized compounds have been ascertained by detailed spectral measurements and single crystal X-ray analysis of 5-(3′-pyridylazo)-25,26,27,28-tetrahydroxycalix[4]arene. A rational explanation for the observed partial and exhaustive coupling reaction in the synthesis of heteroaryl azocalix(n)arenes has been suggested. Preliminary evaluation of synthesized derivatives as molecular receptors for metal ions indicates that they have good potential to function as selective ionic filters for cesium ions.     

Molecular Conductors Based on M(dddt)2 Bisdithiolene Cation Complexes

The synthesis, structure and properties of molecular conductors based on M(dddt)₂ cation complexes (dddt = 5,6-dihydro-1,4-dithiin-2,3-dithiolate) which are metal complex analogs of bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF or ET) salts are considered. Formally, the central C=C bond of ET is substituted by a metal ion in the M(dddt)₂ complexes. The effect of metal (M=Ni, Pt, Pd) and counterion on crystal structure and conducting properties of M(dddt)₂ complexes is analyzed. The similarity and distinction in structures and properties of M(dddt)₂ and ET salts are discussed.     

Cyanosilylation of aldehydes catalyzed by N-heterocyclic carbenes

N-Heterocyclic carbenes produced in situ from salts of imidazolium, benzimidazolium, pyrido[1,2-c]imidazolium, imidazolinium, thiazolium, and triazolium catalyze the addition of trimethylsilylcyanide to aldehydes to yield cyanohydrin trimethylsilyl ethers. The use of C₂-symmetric imidazolidenyl carbene derived from (R,R)-1,3-bis[(1-naphthyl)ethyl]imidazolium chloride led to enantioselective cyanosilylation.     

On the cyclization of ortho-alkynylbenzene diazonium salts

Cyclization of ortho-(phenylethynyl)benzene diazonium salts containing groups of +C character at the para-position of the phenyl ring proceeds with closure to a pyrazole, but not to a pyridazine as is the case in the presence of neutral or −C groups.