A novel ditopic ring-expanded N-heterocyclic carbene ligand-assisted Suzuki-Miyaura coupling reaction in aqueous media

A series of seven-membered ditopic ring-expanded N-heterocyclic carbene (dre-NHC) precursors, bearing sterically demanding and electron-rich aryl groups, were synthesised in moderate yields via the reaction of 1,2,4,5-tetrakis(bromomethyl)benzene with the corresponding N,N′-diarylformamidines in the presence of K₂CO₃ in acetonitrile under an air atmosphere. All new compounds were characterised by HRMS, NMR spectroscopy, and microanalysis, as well as X-ray crystallography for compound 1c. The development of an efficient catalytic system for the Suzuki-Miyaura coupling reaction of aryl chlorides with various boronic acids was also investigated using the in situ generated dre-NHC ligands.     

金属氮杂环卡宾配合物的抗肿瘤活性研究进展

自1978年顺铂成功地被开发成癌症临床治疗药物以来,金属配合物作为小分子抗癌药物的开发成为人们的研究热点。其中,氮杂环卡宾能与多种过渡金属中心形成稳定的共价键,这种特殊的稳定性使得金属氮杂环卡宾配合物具有被开发成药物的潜能。近年来,金属氮杂环卡宾配合物被发现具有良好的抗癌活性,激发了广大无机药物化学研究者的研究热情。综合笔者课题组在金属氮杂环卡宾抗肿瘤配合物方面的前期研究,本文将对银、金、铑和铂氮杂环卡宾配合物的抗肿瘤活性及作用机制进行综述,以期为新型金属氮杂环卡宾抗肿瘤化合物的设计合成提供参考。     

PEPPSI-Pd-NHC catalyzed Suzuki-Miyaura cross-coupling reactions in aqueous media

A series of unsymmetrical 1,3-disubstituted benzimidazolium chlorides were synthesized as N-heterocyclic carbene (NHC) precursors. These compounds were used to synthesize of the PEPPSI-type palladium NHC complexes. The structures of all compounds were characterized by ¹H NMR, ¹³C NMR, FT-IR spectroscopy and elemental analyses. The catalytic activity of the PEPPSI-type palladium–NHC complexes has been evaluated with respect to the Suzuki-Miyaura cross-coupling reactions of phenyl boronic acid with various aryl halides in aqueous media.     

Novel and efficient bridged bis(N-heterocyclic carbene)palladium(II) catalysts for selective carbonylative Suzuki–Miyaura coupling reactions to biaryl ketones and biaryl diketones

Bridged N,N′-substituted bisbenzimidazolium bromide salts (L1, L2, and L3) were synthesized and fully characterized. Reactions of palladium acetate with L1, L2, and L3 afforded corresponding new bridged bis(N-heterocyclic carbene)palladium(II) complexes (C1, C2, and C3) in high yields. The X-ray structure of complex C1 showed that the Pd(II) ion is bonded to the two carbon atoms of the bis(N-heterocyclic carbene) and two bromido ligands are in the cis position, resulting in a distorted square planar geometry. The three Pd(NHC)₂Br₂ complexes C1, C2, and C3 were evaluated in carbonylative Suzuki–Miyaura coupling reactions of aryl boronic acids with aryl halides and displayed high catalytic activity with low catalyst loading. The coupling reactions of aryl bromides were selective towards the carbonylation product at higher carbon monoxide pressure.     

N-Functionalised heterocyclic dicarbene complexes of silver: Synthesis and structural studies

A range of new diimidazolium salts, held together by an alkyl unit and bearing alcohol pendant arms on their nitrogen, was synthesized. A short modular reaction pathway leads to the N-heterocyclic carbene (NHC) precursors, differing by the flexibility of the bridge, the steric bulk of substituents in α-position of the OH groups and the anions. Treatment of diimidazolium salts with Ag₂O yields Ag^I(carbene)₂ complexes. The related trimethylene-bridged bis-NHC silver complexes 6 and 7 were crystallised with di-tosylate and di-hexafluorophosphate anions, respectively. Their X-ray structures revealed dimeric species, involving two ligands with different arrangements around the Ag cations, leading to crossed and parallel conformations.     

Six- and seven-membered ring carbenes: Rational synthesis of amidinium salts, generation of carbenes, synthesis of Ag(I) and Cu(I) complexes

Reactions of neat 1,3- and 1,4-dibromides with N,N′-diarylformamidines in the presence of diisopropylethylamine (DIPEA) afford corresponding amidinium salts in high yields (>80%). Six- and seven-membered ring amidinium salts bearing bulky Mes (2,4,6-Me₃C₆H₂) and Dipp (2,6-ⁱPr₂C₆H₃) aryl groups were prepared using this method. Free six-membered ring carbene 6-Dipp was generated from amidinium salt using LiHMDS as a base. NHC-Ag(I) complexes were obtained by the reactions of amidinium salts with Ag₂O. NHC complexes of Pd and Rh are not accessible by deprotonation of amidinium salts, nor by transmetallation of Ag(I) complexes. However NHC-Cu(I) complexes were obtained by transmetallation of NHC-Ag(I). Thus, transmetallation of six- and seven-membered NHC-Ag(I) complexes was documented for the first time.     

Palladium(II) N-heterocyclic carbene complexes: synthesis,structures and cytotoxicity potential studies against breast cancer cell line

Abstract

Mononuclear trans-Pd(II)–NHC complexes (where NHC?=?N-heterocyclic carbene) bearing asymmetrically substituted NHC-ligand have been synthesized via transmetalation reaction between Ag(I)–NHC complexes and [Pd(NCCH₃)₂Cl₂]. The NHC precursors are accessible in two steps by N-n-alkyl reactions of benzimidazole. The resultant benzimidazolium salts were deprotonated with Ag₂O by in situ deprotonation to facilitate the formation of mononuclear Ag(I)–NHC complexes. Single-crystal structural study for Pd(II)–NHC shows that the palladium(II) ion exhibits a square-planar geometry of two NHC ligands and two chloride ions. The cytotoxicity study was investigated against breast cancer cell line (MCF-7). The Ag(I)–NHC complexes exhibit better activities than their corresponding Pd(II)–NHC complexes, whereas all benzimidazolium salts are inactive toward MCF-7 cancer cell line.     

Synthesis,characterization, and transfer hydrogenation of Ru(II)-N-heterocyclic carbene complexes

A new series of ruthenium(II) N-heterocyclic carbene complexes [RuL^1,2,3(p-cymene)Cl₂] (3a–c) (where L is a N-heterocyclic carbene), have been synthesized via transmetalation. The new ruthenium(II)-NHC complexes were applied to transfer hydrogenation of acetophenone derivatives and aldehydes using 2-propanol as a hydrogen source and KOH as a co-catalyst. The results show that the corresponding alcohols could be obtained in good yield with high catalyst activity (up to 100%) under mild conditions. [RuL¹(p-cymene)Cl₂] (3a) is much more active than the other complexes in transfer hydrogenation. Reactions, catalyzed by 3a–c, showed the highest reaction rates and yields of alcohol when the substrates bear more electron-withdrawing substituents. All new compounds were characterized by IR, elemental analysis, LC–MS (ESI), and NMR spectroscopy.     

Intramolecular C-H insertion in ring-expanded N-heterocyclic carbenes

Mild heating of the ring-expanded N-heterocyclic carbenes 7-Mes and 6-Mes results in intramolecular insertion of the carbene into an ortho-methyl C-H bond. In the presence of traces of acid, the resulting products ring-open to afford N-alkyl indoles.     

Well-defined PEPPSI-themed palladium–NHC complexes: synthesis,and catalytic application in the direct arylation of heteroarenes

In this study, a series of benzimidazolium salts were synthesized as unsymmetrical N-heterocyclic carbene (NHC) precursors. Benzimidazolium salts were used for synthesis of the PEPPSI (pyridine enhanced precatalyst preparation stabilization and initiation)-themed, six new Pd-complexes with the general formula [PdX₂(NHC)(pyridine)]. The structures of all compounds were characterized by various spectroscopic techniques such as ¹H NMR, ¹³C NMR and FT-IR. The more detailed structural characterization of four of the complexes was determined by single-crystal X-ray diffraction study. The catalytic activities of all Pd-complexes were evaluated in the direct arylation of the 2-acetylfuran and 2-acetylthiophene with aryl bromides in the presence of 1 mol% catalyst loading.     

Novel scorpionate-type triscarbene ligands and their silver and gold complexes

New silver(I) carbene complexes were obtained starting from the N-heterocyclic carbene ligand precursors {[HB(RImH)₃]Br₂} (R = Bn, Mes and t-Bu) and {[HC(MeBImH)₃](BF₄)₃}, by treatment of the imidazolium salt with Ag₂O. Use of the tris-imidazolylborate precursors resulted in stable, well-characterized trimetallic complexes of general formula {Ag₃[HB(RIm)₃]₂}Br, which were successfully employed as carbene transfer reagents in the synthesis of related gold(I) complexes by transmetallation. The silver complexes also proved to be active catalysts of the coupling of aryl iodides with terminal alkynes (the Sonogashira reaction), although related bimetallic silver complexes were found to exhibit enhanced reactivity.     

A series of (NHC)Pd(N˄O)(OAc) complexes: synthesis,characterization and catalytic activities towards desulfinative Sonogashira coupling of arylsulfonyl hydrazides with arylalkynes

A series of well-defined N-heterocyclic carbene palladium (II) complexes with general formula (NHC)Pd(N^˄O)(OAc) were prepared through reaction of Pd (NHC)(OAc)₂(H₂O) with 1-methyl-1H-pyrazole-3-carboxylic acid or 1-methyl-1H-indazole-3-carboxylic acid in the presence of K₂CO₃. These complexes were then used for desulfinative Sonogashira coupling of arylsulfonyl hydrazides with terminal alkynes. With low catalyst loading, all synthesized palladium compounds exhibited moderate to high catalytic activities for the reactions.     

Synthesis of new alkoxy/sulfonate-substituted carbene precursors derived from [2.2]paracyclophane and their application in the asymmetric arylation of aldehydes

A series of novel planar chiral alkoxy/sulfonate-substituted carbene precursors have been designed and synthesized. They were used as N-heterocyclic carbene ligands in the Rh-catalyzed asymmetric addition of arylboronic acids to aromatic aldehydes, affording chiral diarylmethanols with high yields and moderate enantioselectivities.     

Half-Sandwich Manganese Complex Bearing Fused Oxazoline-NHC Ligand: Conformational Analysis and Evaluation in Asymmetric Ketone Hydrosilylation

The first manganese complex bearing a chiral N-heterocyclic carbene (NHC) ligand was prepared and studied by spectroscopic methods and X-ray diffraction. While IR spectroscopy revealed the existence of two isomers in solution with distinct ν_CO band patterns, DFT calculations indicated that these isomers correspond to rotamers around the Mn−NHC bond and their different spectroscopic properties were rationalized by the occurrence of attractive π(C=C)⋅⋅⋅π*(C≡O) or σ(C−H)⋅⋅⋅π*(C≡O) intramolecular interligand interactions. The evaluation of this complex in catalytic hydrosilylation of acetophenone using Ph₂SiH₂ under UV irradiation led to the formation of the corresponding (R)-alcohol with low enantioselectivity.     

Expedient Synthesis of Oxaboracyclic Compounds Based on Naphthalene and Biphenyl Backbone and Phase-Dependent Luminescence of their Chelate Complexes

The approach to a series of six- and seven-membered oxaboraheterocycles based on naphthalene or biphenyl backbones was developed. The key synthetic step involved Br/Li exchange in respective potassium (bromoaryl)trifluoroborates followed by quenching with selected electrophiles (CO₂, DMF, Me₂Si(H)Cl) and hydrolytic workup. Two ring-expanded benzoxaborole congeners were obtained by an additional reduction step with LiAlH₄ or NaBH₄. The obtained boracyclic compounds were characterized in detail by NMR spectroscopy and single-crystal X-ray diffraction. Specifically, biphenyl-based systems show dynamic behaviour interpreted in terms of inversion of non-planar seven-membered boraheterocycles. The acidity of the obtained compounds varies very strongly (pK_a ranges from 3.1–9.6) depending on their structure. Due to the enhanced boron Lewis acidity, selected compounds were used as a basis for luminescent complexes with 8-hydroxyquinoline. A strong phase-dependent variation of emission-band maximum (480–527 nm) and photoluminescence quantum yield (10–95 %) was observed, which was rationalized in terms of specific aggregation effects.     

Synthesis and spectral characterization of new benzimidazolium compounds containing sulfur

Abstract

N-heterocyclic carbene (compound b) was synthesized from reaction of 1-(3-phenylpropyl)-3-methylbenzimidazolium iodide (a) and a strong base in an argon atmosphere. Then, 1-(3-phenylpropyl)-3-methylbenzimidazolium-2-carbodithioate (c) was prepared with carbene and CS₂. Finally, a group of alkyl 1-(3-phenylpropyl)-3-methylbenzimidazolium-2-carbodithioate halides was synthesized with alkyl halides and compound c, occurring products 1-6. Structural characterization of compounds was performed ¹H, and ¹³C NMR, IR, and MS spectroscopy and elemental analysis.     

4-Vinylbenzyl-substituted silver(I) N-heterocyclic carbene complexes and ruthenium(II) N-heterocyclic carbene complexes: synthesis and transfer hydrogenation of ketones

4-Vinylbenzyl-substituted Ag(I) N-heterocyclic carbene (NHC) complexes and Ru(II) NHC complexes have been synthesized. The Ag(I) complexes were synthesized from the imidazolium salts and Ag₂O in dichloromethane at room temperature. The Ru(II) complexes were prepared from Ag(I) NHC complexes by transmetallation. The six 4-Vinylbenzyl-substituted Ag(I) NHC complexes and six 4-Vinylbenzyl-substituted Ru(II) NHC complexes have been characterized by spectroscopic techniques and elemental analyses. The Ru(II) NHC complexes show catalytic activity for the transfer hydrogenation of ketones.     

Chiral bisimidazolium salts derived from amino acids and their palladium(II)- and platinum(II)-biscarbene complexes

We report new chiral bisimidazolium salts synthesized from naturally occurring l-amino acids. They served as precursors for bidentate N-heterocyclic carbene metal complexes. The chiral imidazoles could be synthesized in good yields via a one-pot ring closing reaction, followed by esterification. The methylene bridged bisimidazolium iodide salts are accessible in moderate yields. Corresponding palladium(II)- and platinum(II)-NHC complexes could be synthesized and fully characterized, but do not show optical activity. We also report a solid state structure of one of the synthesized palladium(II) biscarbene compounds derived from alanine.     

Synthesis and structures of 4,5-dimethyl-1,3-bis(pyridin-2-ylmethyl)-1H-imidazolium chloride and 1,1′-bis(pyridin-2-ylmethyl)-2,2′-bis(4,5-dimethylimidazole)

4,5-Dimethyl-1,3-bis(pyridin-2-ylmethyl)-1H-imidazolium chloride (1) was synthesized and characterized by IR and NMR spectroscopy and X-ray diffraction. An attempt to prepare the free tridentate N-heterocyclic carbene pincer ligand by the reaction of 1 with KN(SiMe₃)₂ resulted in the formation of 1,1′-bis(pyridin-2-ylmethyl)-2,2′-bis(4,5-dimethylimidazole) as a product of dimerization of the target carbene followed by the rearrangement accompanied by the elimination of dipyridylethane.

     

<Emphasis Type="Italic">N</Emphasis>-Propylphthalimide-substituted bis-(NHC)PdX<Subscript>2</Subscript> complexes: synthesis,characterization and catalytic activity in direct arylation reactions

Palladium-catalyzed direct arylation of heteroaromatics has become a popular method for producing carbon–carbon bonds via C–H bond activation. A wide diversity of heteroaromatics such as furan, thiophenes and thiazoles can be used for this reaction. This paper reports the synthesis of N-propylphthalimide-substituted bis-(NHC)PdX₂ complexes (NHC = N-heterocyclic carbene), and their catalytic activity in direct arylation reactions. The complexes have been prepared from Ag(I)NHC precursors by transmetallation and characterized by spectroscopy and elemental analysis. The bis-(NHC)PdX₂ complexes show excellent activity as catalysts in the direct arylation reactions of 2-n-butylfuran, 2-n-butylthiophene and 2-isopropylthiazole.