Synthesis and structure of silyl-substituted imidazol-2-ylidenes and their precursors

Previously unknown heterocyclic carbenes and their precursors containing a silicon atom in the side chain were prepared. Their structures were studied by multinuclear ¹H, ¹³C, ¹⁵N, and ²⁹Si NMR spectroscopy.     

Chiral bicyclic imidazolium salts as a new class of N-heterocyclic carbene precursors

A N(1)-C(5) bridged chiral bicyclic imidazole with a morpholine framework was synthesized from an enantiopure 2-amino alcohol. The resultant imidazole reacted with various electrophiles, including primary and secondary alkyl halides, benzyne, and an electron-deficient aryl halide, to give the corresponding imidazolium salts. Some of the imidazolium salts were found to have potential as the precursor of a chiral N-heterocyclic carbene catalyst; by the direct annulation of an enal and a ketone through the intermediacy of a homoenolate and an activated carboxylate, the target lactone was obtained in an enantiomerically enriched form (up to 66% ee).     

Cyclophane-type imidazolium salts with planar chirality as a new class of N-heterocyclic carbene precursors

Cyclophane-type imidazolium salts with planar chirality were synthesized from enantiopure 2-amino alcohols, of which the N(1) and N(3) positions were connected with a bridge. The structural profiles of the imidazolium salts and their derivative N-heterocyclic carbenes (NHCs) were investigated by means of several analyses. The chiral NHCs derived from these imidazolium salts were found to catalyze the asymmetric cross-annulation of an alpha,beta-unsaturated aldehyde with a ketone by means of the "conjugated" umpolung of the enal to give the target gamma-lactone with good to excellent enantioselectivity (up to 94% ee). Based on the expected structure of the NHCs and their intermediates, together with the absolute configuration of the products, a plausible mechanism for the stereocontrol was proposed.     

Electrochemical reduction of an imidazolium cation: a convenient preparation of imidazol-2-ylidenes and their observation in an ionic liquid

1,3-Bis(2,4,6-trimethylphenyl)imidazolium chloride is reduced electrochemically and chemically to produce a nucleophilic carbene, namely 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene. The carbene was also shown to be compatible with and persistent in the ionic liquid tetradecyl(trihexyl)phosphonium chloride.     

The reactions of imidazol-2-ylidenes with the hydrogen atom: a theoretical study and experimental confirmation with muonium

The possible radicals resulting from hydrogen atom addition to the imidazole rings of 1,3-bis(isopropyl)-4,5-dimethylimidazol-2-ylidene (1) and 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (2) have been studied by means of density functional calculations (B3LYP). The calculations included solvent effects estimated via the polarized continuum model (PCM) and an empirical treatment of vibrational averaging of hyperfine constants. Addition of a hydrogen (or muonium) atom to the carbeneic carbon of 1,3-bis(isopropyl)-4,5-dimethylimidazol-2-ylidene was found to give a radical 60.46 kJ mol(-)(1) more stable than the radical resulting from addition to the double bond. Estimation of the activation barriers for reaction at the two sites shows that addition at the carbeneic carbon is favored. The site of addition was confirmed experimentally using muonium (Mu), which can be considered a light isotope of hydrogen. Muon spin rotation and muon level-crossing spectroscopy were used to determine muon, (13)C, and (14)N hyperfine coupling constants (hfc's) for the radical products of addition to the two carbenes. Good agreement between the experimental and calculated hfc's confirms that Mu (and hence H) adds exclusively to the carbeneic carbon. The radicals that are produced have nonplanar radical centers with most of the unpaired electron spin density localized on the alpha-carbon.     

Synthesis and properties of 1-methyl-2-phenyl-5-(2-furyl)- and 1-methyl-2-phenyl-5-(2-thienyl)imidazoles

2-Phenyl-5-(2-furyl)- and 2-phenyl-5-(2-thienyl)imidazoles were synthesized by condensation of 2-furoylmethyl and 2-thenoylmethyl acetates with benzaldehyde under the conditions of Weidenhagen reaction. The products were converted to N-methyl derivatives in the KOH-acetone system. The electrophilic substitution reactions of the products (acylation, bromination, nitration, sulfonation, hydroxymethylation) were studied.     

A comparative study of hydroxyl‐ and carboxylate‐functionalized imidazolium and benzimidazolium salts as precursors for N‐heterocyclic carbene ligands

The preparation of imidazolium and benzimidazolium salts with hydroxyl or carboxylate functions has been achieved using straightforward synthetic pathways. These salts in combination with palladium(II) acetate give active catalytic systems for Suzuki reaction. A comparative study has been performed, which has revealed that both the heterocycle and the functional group are important for the catalytic activity and stability of the catalyst. Copyright © 2015 John Wiley & Sons, Ltd.     

Tubular microporous organic networks bearing imidazolium salts and their catalytic CO2 conversion to cyclic carbonates

Tubular microporous organic networks bearing imidazolium salts (T-IM) were prepared by Sonogashira coupling of tetrakis(4-ethynylphenyl)methane and diiodoimidazolium salts, which showed promising catalytic activities in heterogeneous conversion of CO(2) into cyclic carbonates.     

Unexpected oxidative C-C cleavage in the metallation of 2-substituted imidazolium salts to give N-heterocyclic carbene complexes

Imidazolium salts blocked at C2 with methyl or benzyl groups unexpectedly react with silver oxide to give N-heterocyclic carbene complexes of silver via an oxidative carbon-carbon bond cleavage.     

Copper powder-catalyzed N-arylation of imidazoles in water using 2-(hydrazinecarbonyl)pyridine N-oxides as the new ligands

2-(2-Hydrazinecarbonyl)pyridine N-oxides, which were derived from pyrrole-2-carbohydrazides and pyridine N-oxides, were synthesized and utilized as the ligands for copper powder-catalyzed N-arylation of imidazoles with aryl halides in water. Imidazoles could be arylated smoothly with various aryl halides to provide the title products in preferable yields without the need of an inert atmosphere.     

Sulfonyl imidazolium salts as reagents for the rapid and efficient synthesis of nucleoside polyphosphates and their conjugates

A procedure for the synthesis of nucleoside polyphosphates and their conjugates using sulfonylimidazolium salts as key reagents is described. The procedure is rapid and high yielding, does not require prior protection and subsequent deprotection of the donors or acceptors, and can be used to activate nucleoside mono-, di- and triphosphates, and a wide variety of acceptors and donors can be used.     

Synthesis and properties of 1-methylthiopropargylammonium salts and their use as key precursors to sulfur-containing enediynes

1-methylthiopropargylammonium salts were synthesized in a highly efficient manner by reaction of alkynyl S,N-acetals with methyl triflate. Reactions of the 1-methylthiopropargylammonium salts with Grignard reagents gave propargyl sulfides or allenyl sulfides, whereas the reaction with organocopper reagents led to exclusive formation of allenyl sulfides regardless of the nature of substituents on the acetylenic carbon. The salts undergo self-dimerization reactions when treated with organolithium and lithium amide bases.     

A versatile access to pyridazines with tethered imidazolium groups—new precursors for mono- and binucleating NHC/pyridazine hybrid ligands

One or two imidazolium groups have been attached to the 3- and 6-positions of the pyridazine heterocycle, providing valuable precursors for mono- and binucleating NHC/pyridazine hybrid ligands. For N-methyl imidazole with specific backbone substituents an unexpected methyl group transfer is observed, which defines the scope of the synthetic procedure. H-Bonding patterns in the solid state are elucidated by X-ray crystallography for seven chloride or salts of the new compounds.     

Abnormal ligand binding and reversible ring hydrogenation in the reaction of imidazolium salts with IrH(5)(PPh(3))(2)

We show that imidazolium salts do not always give normal or even aromatic carbenes on metalation, and the chemistry of these ligands can be much more complicated than previously thought. N,N'-disubstituted imidazolium salts of type [(2-py)(CH(2))(n)(C(3)H(3)N(2))R]BF(4) react with IrH(5)(PPh(3))(2) to give N,C-chelated products (n = 0, 1; 2-py = 2-pyridyl; C(3)H(3)N(2) = imidazolium; R = mesityl, n-butyl, i-propyl, methyl). Depending on the circumstances, three types of kinetic products can be formed: in one, the imidazole metalation site is the normal C2 as expected; in another, the metalation occurs at the abnormal C4 site; and in the third, C4 metalation is accompanied by hydrogenation of the imidazolium ring. The bonding mode is confirmed by structural studies, and spectroscopic criteria can also distinguish the cases. Initial hydrogen transfer can take place from the metal to the carbene to give the imidazolium ring hydrogenation product, as shown by isotope labeling; this hydrogen transfer proves reversible on reflux when the abnormal aromatic carbene is obtained as final product. Care may therefore be needed in the future in verifying the structure(s) formed in cases where a catalyst is generated in situ from imidazolium salt and metal precursor.     

Greener fluorous chemistry: Convenient preparation of new types of ‘CF3-rich’ secondary alkyl mesylates and their use for the synthesis of azides, amines, imidazoles and imidazolium salts

2,2,2-Trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, and nonafluoro-tert-butyl alcohol were used as precursors for the preparation of the appropriate bis(polyfluoroalkoxymethyl)carbinols [(R_FHOCH₂)₂CHOH, 1a-c, R_FH = (a) CF₃CH₂, (b) (CF₃)₂CH, and (c) (CF₃)₃C] and the corresponding mesylates [(R_FHOCH₂)₂CHOSO₂CH₃, 2a-c]. This novel design paradigm is introduced to eliminate the persistence and bioaccumulation problems of fluorous chemistry, which are associated with the use of longer linear perfluoroalkyl groups (e.g. R_fn ≥ n-C₈F₁₇, n-C₇F₁₅). Secondary mesylates 2a,b and the primary tosylate [(CF₃)₃COCH₂CH₂OTs, 2d] displayed acceptable reactivity towards azide and imidazole nucleophiles to allow the syntheses of novel fluorous azides, which on hydrogenolysis with H₂/Pd-C offered fluorous amines [(R_FHOCH₂)₂CHNH₂, 8a,b], and 1-(polyfluoroalkyl)imidazoles (5a,b,d), respectively, while 2c showed no reactivity due to steric hindrance. The reaction of 8a,b with formaline, glyoxal and hydrochloric acid gave symmetrical 1,3-dialkylated imidazolium chlorides (9a,b), while 5a,b,d were effectively alkylated using n-C₈F₁₇(CH₂)₃I, methyl iodide, 2-bromoethanol, and 2d to yield the corresponding 1,3-dialkylimidazolium iodides, bromides, and tosylates (7aa-ec). Some physical properties of new compounds including mp, bp and solubility patterns were also analyzed; and the fluorophilicity values of 1a-c, and 2a-c were experimentally determined by GC and/or ¹⁹F NMR spectroscopy.     

Efficient and beta-Stereoselective Synthesis of 4(5)-(beta-D-Ribofuranosyl)- and 4(5)-(2-Deoxyribofuranosyl)imidazoles(1)

A synthetic route to 4(5)-(beta-D-ribofuranosyl)imidazole (1), starting from 2,3,5-tri-O-benzyl-D-ribose (5), was developed via a Mitsunobu cyclization. Reaction of 5 with the lithium salt of bis-protected imidazole afforded the corresponding 5-ribosylimidazole 7RS. Hydrolysis of 7RS gave a 1:1 mixture of diol isomers 8R and 8S having an unsubstituted imidazole. Mitsunobu cyclization of the mixture 8RS using N,N,N',N'-tetramethylazodicarboxamide and Bu(3)P exclusively afforded benzylated beta-ribofuranosyl imidazole 9beta in 92% yield, accompanied by alpha-anomer 9alpha, in a ratio of 26.3:1. The configuration of 9beta was established by X-ray crystallography of ethoxycarbonyl derivative 10beta. Reductive debenzylation of 9beta over Pd/C was carried out, and the synthesis of 1 was attained from starting 5 in four steps and 87% overall yield. This synthetic methodology was extended to the synthesis of 4(5)-(2-deoxy-beta-D-ribofuranosyl)imidazole (2). Mitsunobu cyclization of a 1:1 mixture of the corresponding diol isomers 14RS produced 15beta and 15alpha in a ratio of 5.4:1. The synthesis of 2 was attained in a 59% overall yield from the starting 3,5-di-O-benzyl-2-deoxy-D-ribose (12). beta-Stereoselective glycosylation in the key step is discussed and explained by intramolecular hydrogen bonding between an NH in the imidazole and the oxygen functional group in the sugar moiety.     

The mass spectra of 2-aryl-4-arylidene-oxazol-5-ones,and the related thiazol-5-ones and imidazol-5-ones

Examination of the mass spectra of a series of substituted oxazol-5-ones and other related heterocycles showed no evidence of electron-impact induced isomerism. The electron-impact fragmentations of these compounds were characterized by a single dominant fragmentation process.