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Hetero-bis(carbene) complexes of palladium(II) and gold(I) containing expanded-ring N-heterocyclic carbenes (erNHCs) have been prepared in order to study their electronic properties. erNHCs with mesityl substituents were found to exhibit anisotropic interferences, which hampered ranking of their donicities by 13C NMR spectroscopy. The anisotropy effects were found to be stronger in the linear gold complexes, where a smaller coordination number allows the wingtips to spread out more. erNHCs with flexible N-benzyl groups are more suitable, and their donor strengths were found to gradually increase from 5- to 7-membered heterocycles. The same trend can also be obtained by comparing the 1J(C−H) coupling constants of the respective salts, although significant differences between 7- and 8-membered erNHCs could not be detected. The %Vbur values of erNHCs obtained from structures of their palladium and gold complexes revealed that the anisotropic interferences increase with overall steric bulk.
The room temperature reaction of [Os3(CO)12] (1) with three molar equivalents of [PtCl(allyl)(NHC)] (2) in the presence of KOtBu afforded the heterometallic clusters [PtOs3(CO)12(NHC)] (3), [Pt2Os3(CO)12(NHC)2] (4) and [Pt3Os3(CO)12(NHC)3] (5), together with a trace amount of the tetraosmium cluster [Os4(CO)10(µ‐H)2(NHC)] (6). The reaction pathway is thus similar to that for Pd analogues, with the exception of cluster 6. Unlike their Pd analogues, however, these clusters do not appear to readily interconvert. With a valence electron count of 58, the clusters 6 are deficient by four electrons.
Site-selective mono-palladation of potentially pentadentate dipropyl-pyridine-2,6-dicarboxamide bridged diNHC proligands 1Bn/Me can be achieved by using different bases affording complexes of the type trans-[PdCl2(diNHC)] (3Bn/Me) and [PdCl(N’,N,N’)]BF4 (4Bn/Me), respectively, as metallo-proligands capable of binding additional metals. The 2nd palladation of both metallo-ligands using Pd(OAc)2, however, gave the same tetrapalladium complex 5, in which the ligand coordinates in a μ,κ4CN3,κC mode due to the entropically favorable tetradentate encapsulation of one PdII ion leaving a monodentate NHC coordination to the 2nd palladium center. Single deprotonation of the diazolium complex 4Bn affords the benzimidazolium complex 7 as the key intermediate in the formation of the tetrapalladium complex 5. Metallo-NHC precursor 7 also provides easy access to the hetero-bimetallic palladium/gold complex 8.
A series of 16 benzimidazolium salts of the type iPr2-bimyH+X– with various anions X were synthesized and characterized by various spectroscopic and spectrometric methods. Significant anion and solvent effects on the chemical shifts of the C2–H protons were found, which allows for a ranking of the anions in terms of their hydrogen-bond acceptor properties. Stronger acceptors could increase the acidity of their respective salts leading to a faster H/D exchange. Similar but less pronounced anion influences were detected for the 13CC2 NMR resonances, while 1JC2–H coupling constants appear to be anion and solvent independent.
The postmodification approach allows convenient access to charge-tagged ammonium-functionalized bis(1,2,4-triazolin-5-ylidene)palladium(II) complexes even when the respective azolium salts are elusive. Bromo-functionalized 1,2,4-triazolium salts were first metalated to form the respective bromo-functionalized bis(NHC) complexes trans-[PdBr2(R-tazy-Br)2] (R = Ph, Cy, 1a,b). Subsequent postcoordinative nucleophilic substitutions converted the bromo into ammonium functions, leading to the water-soluble, charge-tagged complexes trans-[PdBr2(R-tazy-NEt3)2]Br2 (R = Ph, Cy, 2a,b). The catalytic activities of 2a,b in the aqueous Suzuki-Miyaura reaction were compared to those of their analogues 2c,d bearing more bulky mesityl and diisopropylphenyl substituents, and a detailed stereoelectronic profiling of the NHCs using %Vbur, HEP, and DFT calculations was conducted to rationalize their catalytic differences. Although all complexes are active, the more donating and less bulky complexes 2a,b performed significantly better than 2c,d at a very low catalyst loading of 0.001 mol %. 2a was found to be highly active for various aryl and heteroaryl bromides and some aryl chlorides. More importantly, this study discloses that NHCs with N-phenyl and N-cyclohexyl groups exhibit stereoelectronic flexibility, which could be the cause for the greater activities of their complexes.
We report the profiling of the metabolic stability, normal cell inhibition, and genotoxicity of the two gold complexes [Au(iPr2-bimy)2]PF6 (1) and [Au(Fpyr)(iPr2-bimy)]PF6 (2), which show strong apoptotic activities in lung cancer cells. Liver microsomal tests revealed that the compounds have a relatively high half-life compared to midazolam and do not suffer rapid metabolism and in vitro clearance. The cytotoxic potential of these compounds were also relatively weak in normal cells, with higher IC50 values compared to cancer cells, with a 2–60 times difference. The Ames test revealed that the compounds do not give rise to any mutations as well. Overall, the compounds showed stability in liver microsomes, specificity for cancer cells, and a lack of genotoxic potential.
A series of NHC-containing [C^N]- or [C^C’]-type palladacyclic complexes of the general formula [PdBr(iPr2-bimy)(L^X)] (5–8, 11, 12, iPr2-bimy = 1,3-diisopropylbenzimdiazolin-2-ylidene) have been synthesized and fully characterized. Using these complexes, the donating capabilities of monoanionic chelators were probed for the first time. The [C^N]-type palladacycles 5–8 were prepared from acetato-bridged dipalladium complexes [Pd(μ-CH3COO)(C^N)]2 (1–4) and iPr2-bimy∙H+Br–as precursors. In the case of the [C^C’]-type NHC-palladacycles (11, 12), the hetero-bis(NHC) complexes trans-[PdBr2(iPr2-bimy)(trz)] (8, 9, trz = 1,2,3-triazolin-5-ylidene) containing the iPr2-bimy probe were first prepared followed by acetate-assisted cyclopalladations. The 13Ccarbene NMR signals of the iPr2-bimy ligands in all complexes (i.e. HEP & HEP2 values) are found to rationally reflect the donating abilities of the incorporated trz or [L^X]-type chelators with the exception of the Bzpy ligand (Bzpy = 2-(2-pyridinylmethyl)phenyl-C,N). This has been attributed to its larger bite angle, the resulting varied coordination geometry and the lack of electronic delocalization between the two donor units. The donicities of [L^X]-type chelators studied in this work were found to surpass those of all other bidentate ligands evaluated by HEP2 thus far.
The structure-activity relationship of expanded-ring N-heterocyclic carbenes (NHCs) in the iron-catalysed Kumada aryl-aryl coupling reaction was explored. This was achieved by comparing the catalytic performance of Fe-NHC catalysts generated in situ containing 20 NHCs that differ in steric bulk. In particular, the influences of ring sizes (five to eight) and N-aryl substituents were explored in terms of spectroscopic and structural features, which affect their %Vbur values. The three best performing ligands were found on a diagonal of a 5 × 4 structural matrix revealing an optimal steric bulk and significant influences of subtle steric variations on the catalytic activities.
N-Heterocyclic carbenes (NHCs) have become without doubt one of the most exciting and popular species in chemical science due to the ease of their preparation and modularity in stereoelectronic properties. Numerous types of NHCs have been prepared, and various experimental methodologies have been proposed for the study of their electronic properties in order to rationalize reactivities observed. The objective of this article is to provide a comprehensive overview of the most common and popular ones among them. In particular, these include the nickel(0)-based TEP, its rhodium(I) and iridium(I) variants, LEP and related electrochemical methods, the palladium(II)-based HEP, phosphinidene- and selenourea-based methods, as well as the use of direct 1J(C-H) coupling constants of the precarbene carbon in azolium salts. Each individual method and the underlying principle of detection it utilizes will be critically discussed in terms of strength and weakness. In addition, comprehensive amounts of data from various NHCs are compiled for the purpose of comparison. These are also meant to help the scientist in better understanding their own research data and possibly providing directions for their future research, which rely on the unique electronic properties of NHCs.
A series of heteroleptic platinum(II) complexes of the general formula [PtX(iPrEug)(NHC)] (2-7) bearing the organometallic π/σ chelator iPrEug (isopropyl eugenoxyacetate), varying halido and NHCs ligands derived from imidazole, benzimidazole and triazole have been prepared and fully characterized by elemental analyses, ESI mass spectrometry, IR and NMR spectroscopies. Complexes 3 and 5-7 were also characterized by single-crystal X-ray diffraction. The air-stable complexes are rare examples of platinum(II) compounds containing three different types of carbon donors, i.e. aryl, carbene and olefin. Unsymmetrical NHCs lead to rotameric pairs of 4 and 5 exhibiting different NMR spectroscopic features. Spectroscopic studies also revealed that the introduction of a NHC leads to a weakening of the metal-olefin bond and strengthening of the metal-aryl bond. Backbone and thus electronic variations among the NHCs on the other hand show little influence on the bonding of the iPrEug chelator.
A series of rare [NiX2(MeCCprop)] complexes bearing the cis-chelating benzimidazole-derived dicarbene ligand MeCCprop and varying anionic coligands (2, X = N3; 3, X = NCS; 4, X = I; 5, X = O2CCF3) have been prepared and coligand dependent structural and spectroscopic features have been evaluated. This study also revealed an unusual ‘reversed’ carbene transfer reaction from nickel to silver giving disilver species [Ag2X2(μ-κ2-MeCCprop)] (6, X = OAc; 7, X = O2CCF3). A preliminary catalytic study of two representative NiII diNHC complexes in the aqueous and phosphine-free Suzuki-Miyaura coupling of aryl halides is reported as well. These reactions provide good yields of coupling products, but do not require inert conditions.
Charge-tagged bis(1,2,4-triazolin-5-ylidene)palladium(II) complexes have been successfully synthesized via a post-modification strategy. Reacting PdBr2 with bromo-functionalized 1,2,4-triazolium salts A·HBr and B·HBr in the presence of silver oxide afforded the bis(carbene)palladium(II) complexes trans-[PdBr2(A)2] (1a) and trans-[PdBr2(B)2] (1b), which contain tethered bromoalkyl chains. Subsequent post-coordinative nucleophilic substitution converted the bromo- into ammonium groups, producing water-soluble complexes trans-[PdBr2(C)2]Br2 (2a) and trans-[PdBr2(D)2]Br2 (2b), while attempts to prepare ammonium-functionalized triazolium salts for direct metalation were futile. All four complexes were fully characterized by means of multinuclear NMR spectroscopy, ESI mass spectrometry, elemental analysis and X-ray diffraction analysis. The presence of trans-anti and trans-syn rotameric complexes in solution was elucidated by 1H, 13C NMR spectroscopy and theoretical calculations. Additionally, the two charged-tagged complexes, 2a and 2b, were found to be highly active precatalysts for the Suzuki-Miyaura and Mizoroki-Heck reactions in iPrOH/H2O and molten TBAB as ionic liquid.
99. W. Wu, Q. Teng, Y.-Y. Chua, H. V. Huynh,* H. A. Duong* "Iron-Catalyzed Cross-Coupling Reactions of Arylmagnesium Reagents with Aryl Chlorides and Tosylates: Influence of Ligand Structural Parameters and Identification of a General N‑Heterocyclic Carbene Ligand" Organometallics, 2017, 36, 2293–2297.
A systematic evaluation of N-heterocyclic carbene ligands in the iron-catalyzed cross-coupling reactions of aryl chlorides and arylmagnesium reagents is performed. There is no clear correlation between the donor strength of the N-heterocyclic carbene and the reaction outcome. Instead, the highest yields of the desired biaryl product are obtained with sterically demanding ligands possessing large %Vbur values. Through this study, SIPrNap has been identified as an efficient and general ligand for the coupling of both aryl chlorides and tosylates.
98. M. Meier, T. T. Y. Tan, F. E. Hahn,* H. V. Huynh,* "Donor Strength Determination of Benzoxazolin-2-ylidene, Benzobisoxazolin-2-ylidene, and Their Isocyanide Precursors by 13C NMR Spectroscopy of Their PdII and AuI Complexes" Organometallics, 2017, 36, 275–284.
A series of mono- and dinuclear palladium(II) and gold(I) complexes containing the iPr2-bimy reporter ligand and monodentate or Janus-type β-functionalized aryl (di)isocyanides have been prepared. Cyclization of the isocyanide ligands afforded complexes of monodentate or Janus-type N,O-heterocyclic carbenes (NOHCs) via a template-directed process. Using the iPr2-bimy 13Ccarbene signals in these complexes, the electron-donating ability of NOHCs and their isocyanide precursors could be evaluated and compared for the first time. Overall, NOHCs were found to be rather weakly donating carbenes. Spectroscopic comparison of mono- with dinuclear complexes indicated that electronic communication between two metal centers occurs only across the Janus-type diNOHC, but not for the diisocyanide ligand. Support for this claim was also found in the solid-state molecular structures, which revealed coplanarity of all ligands only in the diNOHC complex as a prerequisite for π-electron delocalization.
97. Q. Teng, H. V. Huynh,* "A unified ligand electronic parameter based on 13C NMR spectroscopy of N-heterocyclic carbene complexes" Dalton Trans., 2017, 46, 614–627.
The properties and reactivities of transition metal complexes are rooted in the stereoelectronic properties of their ligands. While the bulk of a ligand can be easily evaluated and compared by the drawing of its Lewis structure, prediction on the electronic contributions is often less straightforward. Thus, several electronic parameters have been developed for the experimental evaluation of ligands throughout the years. This article accounts for the most recent one developed by the Huynh group, which employs 13C NMR spectroscopy to determine ligand donor strengths using N-heterocyclic carbene complexes. This parameter not only proves to be safer, more convenient and accurate in comparison to existing methodologies, but it also provides, in certain cases, more intuitive and reliable results. Furthermore, it is currently the only one that allows the direct comparison of various Werner-type and organometallic ligands on a unified scale.
96. B. Y. Tay, C. Wang, P. H. Phua, L. P. Stubbs,* H. V. Huynh,* "Selective hydrogenation of levulinic acid to γ-valerolactone using in situ generated ruthenium nanoparticles derived from Ru–NHC complexes" Dalton Trans., 2016, 45, 3558–3563.
Hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) was studied by using mono- and bidentate p-cymene ruthenium(II) N-heterocyclic carbene (NHC) complexes as catalyst precursors. In water, all complexes were found to be reduced in situ to form ruthenium nanoparticles (RuNPs) with a high hydrogenation activity. In organic solvents, complexes with monodentate NHC ligands also formed nanoparticles, while complexes with bidentate ligands gave rise to stable homogeneous catalysts with moderate hydrogenation activities.
95. Z. Li, L. Qian, L. Li, J. C. Bernhammer, H. V. Huynh, J.-S. Lee, S. Q. Yao,* "Tetrazole Photoclick Chemistry: Reinvestigating Its Suitability as a Bioorthogonal Reaction and Potential Applications" Angew. Chem. Int. Ed., 2016, 55, 2002–2006.
The bioorthogonality of tetrazole photoclick chemistry has been reassessed. Upon photolysis of a tetrazole, the highly reactive nitrile imine formed undergoes rapid nucleophilic reaction with a variety of nucleophiles present in a biological system, along with the expected cycloaddition with alkenes. The alternative use of the tetrazole photoclick reaction was thus explored: tetrazoles were incorporated into Bodipy and Acedan dyes, providing novel photo-crosslinkers with one- and two-photon fluorescence Turn-ON properties that may be developed into protein-detecting biosensors. Further introduction of these photo-activatable, fluorogenic moieties into staurosporine resulted in the corresponding probes capable of photoinduced, no-wash imaging of endogenous kinase activities in live mammalian cells.
94. X. Xie, H. V. Huynh,* "Cyclometallated Ruthenium(II) Complexes with ditopic Thienyl-NHC Ligands: Syntheses and Alkyne Annulations" Org. Chem. Front., 2015, 2, 1598–1603.
A series of six [RuX(2-thienyl-NHC)(p-cymene)] complexes (9a-c and 10-14; X = halido) have been prepared via NHC directed C-H activation. All complexes have been fully characterized, and the molecular structures of four complexes are reported. The rotational barrier of the N-benzyl substituent in the bromido complex 9b has been measured by variable temperature 1H NMR spectroscopy. Preliminary reactivity studies of complex 12 with alkynes provided four new annulated aza-heterocyclic thiophenes.
93. X. Xie, H. V. Huynh,* "Tunable Dehydrogenative Amidation versus Amination using a single Ruthenium-NHC Catalyst" ACS Catal., 2015, 5, 4143–4151.
Mixed NHC/phosphine complexes of the type [RuCl(p-cymene)(bimy)(PPh3)]PF6 (bimy = benzimidazolin-2-ylidene) have been synthesized and fully characterized. Complex 1 bearing the 1,3-dibenzylbenzimidazolin-2-ylidene ligand is able to selectively catalyze both dehydrogenative amidation, mono- and di-amination (N-alkylation) through coupling of simple alcohols with amines effectively yielding a range of amides, secondary and tertiary amines. Selectivity is achieved by controlling the fate of the common hemiaminal intermediate, which in turn can be simply influenced by the choice of base and solvent.
92. S. Guo, J. C. Bernhammer, H. V. Huynh,* "1,2,4-Triazole-derived carbene complexes of gold: characterization, solid-state aggregation and ligand disproportionation" Dalton Trans., 2015, 44, 15157–15165.
Ligand redistribution reactions are well documented for silver(I) N-heterocyclic carbene (NHC) complexes of the type [AgX(NHC)] (X = halido ligand), but only two reports have been described in the literature for gold analogues of the general formula [AuX(NHC)]. In both cases, the NHCs in question were exceptionally strong donors. To probe the dependence of ligand redistribution processes on NHC donor strength, a model study was conducted using a weakly donating 1,2,4-triazolin-5-ylidene (tazy) ligand and different halido coligands. For [AuX(tazy)] (X = Cl, Br, OAc, tazy = 4-benzyl-1-methyl-1,2,4-triazolin-5-ylidene), no ligand redistribution was found, while a reversible disproportionation between [AuI(tazy)] in solution and [Au(tazy)2][AuI2] in the solid state was observed and studied by means of X-ray crystallography, NMR and UV-Vis spectroscopy, as well as DFT calculations.
91. A. M. Seayad,* S. P. Shan, X. Xiaoke, B. Gnanaprakasam, T. T. Dang, B. Ramalingam, H. V. Huynh,* "Benzimidazolin-2-ylidene N-heterocyclic Carbene complexes of Ruthenium as a Simple Catalyst for the N-alkylation of Amines using Alcohols and Diols" RSC Advances, 2015, 5, 4434–4442.
Simple air and moisture stable ruthenium complexes 1–3 and 3a were synthesized from readily available benzannulated N-heterocyclic carbene ligands (bimy = benzimidazolin-2-ylidene). These complexes were found to be efficient catalysts for the alkylation of amines using alcohols as alkylating agents. Catalysts 1, 2 and 3a gave excellent yields of up to 99% for the alkylation of various amines using benzylic and aliphatic alcohols at 130 °C for 18 h under solventless conditions. Catalyst 3a bearing both phosphine and carbene ligands gave excellent yields of up to 98% for the synthesis of heterocyclic amines by double alkylation of primary amines using linear diols. The practical utility of these catalysts was demonstrated for the synthesis of pharmaceutically important amines in a more environmentally benign way under solventless conditions.
90. Q. Teng, H. V. Huynh,* "Controlled access to a heterometallic N-heterocyclic carbene helicate" Chem. Commun., 2015, 51, 1248–1251.
Metallation of a pentadentate diNHC proligand bearing a dipropylpyridine-2,6-dicarboxamide with silver and gold affords mono- and dinuclear, double-stranded bis(NHC) complexes as useful building blocks for metallo-supramolecules. The digold(I) complex acts as a metallo-bis(pincer) ligand to furnish the first example of an organometallic NHC-helicate upon coordination to cobalt.
89. D. Yuan, H. V. Huynh,* "Hetero-dicarbene Complexes of Palladium(II): Syntheses and Catalytic Activities" Organometallics, 2014, 33, 6033–6043.
A series of Pd(II) dibromido complexes 2–6 bearing cis-chelating hetero-dicarbenes, which contain two different types of NHCs linked by a propylene chain, have been synthesized. In most cases, the N-methyl-benzimidazolin-2-ylidene moiety was kept as one NHC donor, while the other one varies with different heterocyclic backbones. As an exception, the hetero-diNHC in complex 8 is derived by combining 1,2,4-triazole and indazole precursors instead. Analogous complexes 9–17 carrying more labile CF3CO2– or CH3CN ligands were synthesized by reacting the aforementioned bromido complexes with AgO2CCF3 or AgOTf in CH3CN. A systematic catalytic comparison of 9–17 in the direct arylation of pentafluorobenzene with 4-chlorobromobenzene was carried out, and complexes that contain bulkier and less electron-donating ligands were found to be more active. Complex 12 carrying the mesitylimidazolin-2-ylidene unit proved to be the most efficient, and its activity was also tested in the direct arylation of tetrafluorobenzenes.
88. Q. Teng, H. V. Huynh,* "Determining the Electron-Donating Properties of Bidentate Ligands by 13C NMR Spectroscopy" Inorg. Chem., 2014, 53, 10964–10973.
A series of 15 mononuclear complexes [PdBr(iPr2-bimy)(L2)]PF6 (1–15) (iPr2-bimy = 1,3-diisopropylbenzimidazolin-2-ylidene, L2 = aromatic 1,2-diimines, diazabutadienes, or methylene-, ethylene- and propylene-bridged di-N-heterocyclic carbenes) and two dicarbene-bridged, dinuclear complexes [Pd2Br4(iPr2-bimy)2(diNHC)] (16 and 17) were synthesized and characterized by multinuclear NMR spectroscopy, electrospray ionization mass spectrometry, and in some cases X-ray diffraction analysis. The influence of the 15 bidentate ligands L2 on the 13Ccarbene signals of the iPr2-bimy reporter ligand in the chelate complexes was studied, on the basis of which a facile methodology for the donor strength determination of bidentate ligands was developed.
87. J. C. Bernhammer, H. V. Huynh,* "Nickel(II) Benzimidazolin-2-ylidene Complexes with Thioether-Functionalized Side Chains as Catalysts for Suzuki–Miyaura Cross-Coupling" Organometallics, 2014, 33, 5845–5851.
Four bis(benzimidazolin-2-ylidene) nickel(II) complexes featuring thioether moieties in the side chain have been synthesized by reactions of the respective benzimidazolium salts with nickel(II) acetate in molten tetrabutylammonium bromide as an ionic liquid. All complexes were obtained as inseparable mixtures of trans-syn and trans-anti rotamers, as evidenced by NMR spectroscopy. For one of the complexes, X-ray diffraction confirmed the square-planar coordination geometry. The catalytic activity of all complexes for Suzuki–Miyaura cross-coupling was examined. Under the optimized conditions, both aryl bromides and aryl chlorides were successfully coupled in the presence of triphenylphosphine as additive. Yields ranged from good to moderate for electron-deficient aryl halides, while electron-rich aryl halides were found to be unreactive.
86. J. C. Bernhammer, H. V. Huynh,* "Amine-Functionalized Indazolin-3-ylidene Complexes of Palladium(II) by Post-Modification of a Single Precursor" Organometallics, 2014, 33,4295–4301.
A series of five trans-[PdBr2(amine)(indy)] complexes (amine = diethylamine, dipropylamine, dibutylamine, diisobutylamine, morpholine; indy = indazolin-3-ylidene) with pendant teriary amine functionalities in the side chain of the NHC ligand has been prepared by postcoordinative modification of a single bromoalkyl-functionalized precursor complex. This approach allows for a synthesis of functionalized N-heterocyclic carbene complexes more efficient than the metalation of prefunctionalized azolium salts. All complexes have been fully characterized, and the molecular structures of three complexes are reported. A correlation exists between the 13C NMR shift of Ccarbene and the pKb values of the coordinated amines. Furthermore, all complexes were found to be active catalysts for the direct arylation of 1-methylpyrrole with good to excellent yields.
85. J. C. Bernhammer, H. V. Huynh,* "Palladium(II) Complexes Bearing an Indazole-Derived NHeterocyclic Carbene and Phosphine Coligands as Catalysts for the Sonogashira Coupling and the Hydroamination of Alkynes" Organometallics, 2014, 33, 3607–3617.
Indazolin-3-ylidenes (indy) are among the most strongly donating N-heterocyclic carbenes, but the structural diversity of their complexes is still limited. Two dimeric palladium(II) complexes, [PdBr2(indy-5)]2 (2a) and [PdBr2(indy-6)]2 (2b) (indy-5 = 2,3-dihydro-1H-pyrazolo[1,2-a]indazolin-3-ylidene, indy-6 = 6,7,8,9-tetrahydropyridazino[1,2-a]indazolin-3-ylidene], bearing indazolin-3-ylidene ligands with different sizes of the fused aliphatic ring can be obtained by silver carbene transfer. The reaction of these dimers with pyridine yielded trans-[PdBr2(indy)(pyridine)] complexes (3a,b), while the poorly soluble monophosphine complexes cis-[PdBr2(indy)(PPh3)] (4a,b) were obtained by reaction with triphenylphosphine. Ligand substitution of the latter with silver trifluoroacetate afforded cis-[Pd(O2CCF3)2(indy)(PPh3)] complexes (5a,b) with improved solubilities, allowing for their detailed characterizations. In the presence of sodium tetrafluoroborate, cationic bis(phosphine) complexes trans-[PdBr(PPh3)2][BF4] (6a,b) could be obtained. Similarly, cis-[PdBr(dppe)][BF4] (7a,b) and cis-[PdBr(dppp)][BF4] (8a,b) were obtained (dppe = bis(diphenylphosphino)ethane; dppp = bis(diphenylphosphino)propane) with the respective chelating diphosphines. A preliminary catalytic study revealed that the complexes incorporating monodentate phosphine ligands are good catalysts for the Sonogashira cross-coupling, while moderate to good yields were achieved with all complexes for the hydroamination of carbon–carbon triple bonds.
84. Q. Teng, D. Upmann, S. A. Z. N. Wijaya, H. V. Huynh,* "Bis(functionalized NHC) Palladium(II) Complexes via a Postmodification Approach" Organometallics, 2014, 33, 3373–3384.
83. J. C. Bernhammer, G. Frison,* H. V. Huynh,* "Pincer versus pseudopincer: isomerism in palladium(II) complexes bearing κ3C,S,C ligands" Dalton Trans., 2014, 43, 8591–8594.
In NHC pincer complexes incorporating a hemilabile donor site, there exists an equilibrium between the true pincer form and a pseudopincer coordination isomer. The influence of the NHC moieties on this isomerism has been studied by DFT calculations.
82. S. Guo, H. V. Huynh,* "Dinuclear Triazole-Derived Janus-type N-heterocyclic Carbene Complexes of Palladium: Syntheses, Isomerizations, and Catalytic Studies towards Direct C5-Arylation of Imidazoles" Organometallics, 2014, 33, 2004–2011.
The dipalladium triazolidin-diylidene complex all-trans-[PdBr2(CH3CN)]2(μ-ditz) (1) (ditz = 1,2,4-trimethyl-triazolidin-3,5-diylidene) was synthesized via in-situ deprotonation of the precursor salt with a basic metal precursor. Ligand replacements of all-trans-1 with monodentate or chelating phosphines afforded the dicarbene-bridged complexes all-cis-[PdBr2(PPh3)]2(μ-ditz) (2) and [PdBr(DPPP)]2(μ-ditz)Br2 (3), respectively. Bromido substitution of all-cis-2 gave tetra-acetato complex all-cis-[Pd(CH3COO)2(PPh3)]2(μ-ditz) (4) with retention of the configuration as the predominant product. In addition, mono-palladium triazolin-5-ylidene complexes trans-[PdBr2(CH3CN)(tazy)] (6, tazy = 1,4-dimethyltriazolin-5-ylidene), cis-[PdBr2(PPh3)(tazy)] (7), [PdBr(DPPP)(tazy)]Br (8), and cis-[Pd(CH3COO)2(PPh3)(tazy)] (9), were also synthesized as the respective mononuclear equivalents for comparison. A comparative catalytic study revealed the general superiority of dinuclear complexes 1–4 over their respective mononuclear counterparts 6–9 in the direct C5-arylation reaction of 1-methylimidazoles. Overall, mixed dicarbene/diphosphine complex 3 showed the best catalytic performance.
81. D. Yuan, Q. Teng, H. V. Huynh,* "Template-Directed Synthesis of Palladium(II) Sulfonate-NHC Complexes and Catalytic Studies in Aqueous Mizoroki–Heck Reactions" Organometallics, 2014, 33, 1794−1800.
Oxidation of easily accessible thiolato-functionalized dinuclear Pd(II) NHC complexes 1−3 by Oxone gave rise to sulfonate-NHC complexes 4−6. This represents the first template-directed approach to NHC complexes bearing sulfonate functions, where the sulfur atoms undergo a six-electron oxidation, changing their oxidation states from −II to +IV. The catalytic activities of water-soluble 4−6 were also tested in aqueous Mizoroki−Heck reactions
80. J. C. Bernhammer, H. V. Huynh,* "Benzimidazolin-2-ylidene Complexes of Palladium(II) Featuring a Thioether Moiety: Synthesis, Characterization, Molecular Dynamics, and Catalytic Activities" Organometallics, 2014, 33, 1266–1275.
Six benzimidazolin-2-ylidene palladium(II) complexes with an alkyl−alkyl thioether moiety in the side chain have been synthesized. Due to the hemilabile metal−sulfur bond, the complexes exhibit a marked fluxionality, as evidenced by NMR studies. The thioether moiety is readily displaced by pyridine as well as by another NHC ligand. Hetero(bis)-NHC complexes formally derived from all six chelating mono-NHC complexes have been synthesized as well. For both series of complexes, the catalytic activity has been explored, and they were found to be active catalysts for the intermolecular hydroamination reaction between a sterically hindered aniline and an alkyne in the presence of triflic acid. Furthermore, the complexes catalyze the direct arylation of 1-methylpyrrole.
79. J. C. Bernhammer, H. V. Huynh,* "Platinum(II) Complexes with Thioether-Functionalized Benzimidazolin-2-ylidene Ligands: Synthesis, Structural Characterization, and Application in Hydroelementation Reactions" Organometallics, 2014, 33, 172−180.
A series of six benzimidazolium salts with an alkyl−alkyl thioether moiety in the side chain has been synthesized. While it was impossible to obtain the platinum(II) complexes by direct reaction between ligand precursors and basic platinum salts, the mild silver carbene transfer reaction gave the desired complexes in all cases. X-ray crystallography confirmed the expected κ2C,S coordination mode of the benzimidazolin-2-ylidene ligands, with a cis arrangement of the carbene and the hemilabile thioether moieties in all complexes. Preliminary studies of the catalytic activity of these complexes showed them to be active catalysts for the intermolecular hydroamination of alkynes with sterically hindered anilines in conjunction with silver triflate. Additionally, the complexes catalyzed the hydrosilylation of alkenes with excellent yields and good regioselectivity.
78. Y. Liu, R. Ganguly, H. V. Huynh,* W. K. Leong* "Palladium−Osmium Heterometallic Clusters Containing N‐Heterocyclic Carbene Ligands" Organometallics, 2013, 32, 7559−7563.
The room-temperature reaction of [Os3(CO)12] with [PdCl(allyl)(NHC)], where NHC (N-heterocyclic carbene) = SIPr [N,N′-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene] or IPr [N,N′-bis(2,6-diisopropylphenyl)imidazolin-2- ylidene], afforded Pd−Os mixed metal clusters with formulas of [PdnOs3(CO)12(NHC)n] (n = 1−3). These are the first examples of Pd−Os heterometallic clusters containing NHC ligands, and they have all been structurally characterized. In all these clusters, the metal cores are raftlike, with carbonyl ligands bridging all the Os−Pd edges.
77. S. Guo, M. H. Lim, H. V. Huynh,* "Copper(I) Heteroleptic Bis(NHC) and Mixed NHC/Phosphine Complexes: Syntheses and Catalytic Activities in the One-Pot Sequential CuAAC Reaction of Aromatic Amines" Organometallics, 2013, 32, 7225−7233.
A series of 2-coordinate heteroleptic Cu(I) complexes of the general formula [Cu(IPr)(L)]PF6 (2–5, L = NHC or phosphine) have been synthesized via either (i) chlorido substitution by phosphine or in situ generated free NHC or (ii) the Ag–NHC transfer protocol using [CuCl(IPr)] (1) as a precursor (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene). The reactions of precursor 1 with diphosphine ligands afforded 3-coordinate heteroleptic Cu(I) complexes of the type [Cu(IPr)(L2)]PF6 (6 and 7, L2 = diphosphine). Complexes 1–7 have been subjected to a catalytic one-pot sequential CuAAC study, in which aromatic amines serve as the precursors to aryl azides. Hetero-bis(NHC) complexes 2–4 proved to be generally superior compared to their mixed NHC/phosphine counterparts 5–7. Overall, complex [Cu(Bn2-imy)(IPr)]PF6 (2), bearing the Bn2-imy (Bn2-imy = 1,3-dibenzyl-imidazolin-2-ylidene) co-ligand, showed the best catalytic performance.
76. Y. Liu, R. Ganguly, H. V. Huynh,* W. K. Leong* "Direct Evidence for the Attack of a Free N-Heterocyclic Carbene at a Carbonyl Ligand: A Zwitterionic Osmium Carbonyl Cluster" Angew. Chem., 2013, 125, 12332−12335;
Angew. Chem. Int. Ed., 2013, 52, 12110−12113.
DOI: 10.1002/ange.201307102 or DOI: 10.1002/anie.201307102
A key suspect arrested: The initial site of attack of a free N-heterocyclic carbene (NHC) on the triosmium carbonyl cluster [Os3(CO)12] was found to be a carbonyl ligand. The stable zwitterionic species thus formed (blue background in the scheme) was characterized crystallographically. CO substitution proceeds from this intermediate by the loss of a CO group and migratory deinsertion.
75. H. V. Huynh,* S. Guo, W. Wu "Detailed Structural, Spectroscopic, and Electrochemical Trends of Halido Mono- and Bis(NHC) Complexes of Au(I) and Au(III)" Organometallics, 2013, 32, 4591−4600.
A complete series of ten Au(I) and Au(III) NHC complexes of the general formula [AuIX(iPr2-bimy)] (1–3, X = Cl, Br, I), [AuI(iPr2-bimy)2]BF4 (4), [AuIIIX3(iPr2-bimy)] (5–7, X = Cl, Br, I) and trans-[AuIIIX2(iPr2-bimy)]BF4 (8–10, X = Cl, Br, I) bearing the iPr2-bimy ligand and all three common halido ligands have been synthesized and fully characterized. Detailed trends in their NMR and UV–Vis spectroscopic properties have been studied, and their electrochemical behavior have been probed by cyclic voltammetry. The solid state molecular structures of all new complexes determined by single crystal X-ray diffraction are also described.
74. J. C. Bernhammer, G. Frison,* H. V. Huynh* "Electronic Structure Trends in N-Heterocyclic Carbenes (NHCs) with Varying Number of Nitrogen Atoms and NHC-Transition-Metal Bond Properties" Chem. Eur. J., 2013, 19, 12892−12905.
Carbenes derived from five-membered heterocycles with different numbers of nitrogen atoms ranging from two to four lead formally either to normal N-heterocyclic or mesoionic carbenes with, in some cases, the same skeletal structure. The electronic structures of fourteen of these compounds were examined by means of DFT calculations at the B3LYP/aug-cc-pVTZ level. The examined parameters include the energies of the σ-lone pair at Ccarbene and the π-HOMO of the protonated form, which are correlated to the first and second proton affinities. The singlet–triplet energy gap was used as a measure of the stability of the N-heterocyclic carbene (NHC) towards dimersation. Natural population analysis provided insight into the variation of the pπ population and the natural charge at Ccarbene with NHC structure. Additionally, the transition metal-NHC bond in L-AuCl and L-TiCl4 and the nature of the orbital interactions between the NHC and the transition-metal fragment were analysed in detail by the extended transition state–natural orbitals for chemical valence (ETS–NOCV) approach at the BP86/TZ2P level. Similarities and differences between the NHC-gold and the NHC-titanium bond are discussed, and trends in key bonding properties can be traced back to the variation of the electronic parameters of the NHC.
73. H. Sivaram, J. Tan, H. V. Huynh* "Cationic gold(I) heteroleptic complexes bearing a pyrazole-derived N-heterocyclic carbene: syntheses, characterizations, and cytotoxic activities" Dalton Trans., 2013, 42, 12421−12428.
A series of cationic gold(I) heteroleptic complexes bearing the pyrazole-derived N-heterocyclic carbene (NHC) FPyr (1,2,3,4,6,7,8,9-octahydropyridazino[1,2-a]indazolin-11-ylidene), and either a 1,3-disubstituted benzimidazole-derived NHC of the type RR′-bimy (3: R = R′ = CHPh2; 4: R = CHPh2, R′ = iPr; 5: R = R′ = CH2Ph; 6: R = R′ = iBu; 7: R = R′ = n-Pr; 8: R = R′ = Et; 9: R = R′ = 2-propenyl) or a non-NHC co-ligand L (10: L = PPh3; 11: L = P(OPh)3; 12: L = DMAP) (DMAP = 4-dimethylaminopyridine) have been synthesized from [AuCl(FPyr)] (1). Complexes 3-12 have been characterized using multinuclei NMR spectroscopies, ESI mass spectrometry, and elemental analysis. X-ray diffraction analyses have been performed on complexes 5, 6, and 9-11. To the best of our knowledge, 11 represents the first gold–NHC complex to bear the P(OPh)3 ligand. The cytotoxic activities of complexes 3-12 have been studied in vitro with the NCI-H1666 non-small cell lung cancer cell line.
72. H. V. Huynh,* H. L. Ong, J. C. Bernhammer, G. Frison "A Pd(II) complex bearing a benzimidazole-derived ligand with potentially ”mesoionic and remote” character and its catalytic activity" Eur. J. Inorg. Chem., 2013, 4654−4661.
Oxidative addition of Palladium(0) to the C2 protected 5-bromo-2-methyl-benzimidazolium tetrafluoroborate (3) affords the complex trans-[PdBr(bimy)(PPh3)2]BF4 (4), which is the first complex of an unprecedented benzimidazole-derived ligand (bimy) with a potentially “mesoionic and remote” character. DFT calculations revealed that the bimy ligand bridges the gap between the mesoionic pyrazolin-4-ylidene and the anionic phenyl ligand. A preliminary catalytic study revealed the promising activity of complex 4 in the Sonogashira coupling of aryl bromides with phenylacetylene.
71. S. Guo, H. Sivaram, D. Yuan, H. V. Huynh* "Gold and Palladium Hetero-Bis-NHC Complexes: Characterizations, Correlations, and Ligand Redistributions" Organometallics, 2013, 32, 3685−3696.
A series of new Au(I) hetero-bis-NHC complexes [Au(iPr2-bimy)(NHC)]X (X = BF4, PF6, 2–6) and the hetero-tetrakis-NHC complex [Au2(iPr2-bimy)2(μ-ditz)](BF4)2 (7) have been synthesized using the Au(I) acetato complex [Au(O2CCH3)(iPr2-bimy)] (C) as a basic metal precursor (iPr2-bimy = 1,3-diisopropylbenzimidazolin-2-ylidene, ditz = 1,2,4-triazolidine-3,5-diylidene). The Au(III) hetero-bis-NHC complex trans-[AuCl2(iPr2-bimy)(Bn2-bimy)]BF4 (12; Bn2-bimy = 1,3-dibenzylbenzimidazolin-2-ylidene) and the hetero-tetrakis-NHC complex all-trans-[Au2Cl4(iPr2-bimy)2(μ-ditz)](BF4)2 (13) were obtained by oxidation of their corresponding Au(I) hetero-NHC precursors. For all Au(I) hetero-NHC complexes, the 13C carbene signals of the constant iPr2-bimy ligand are found to be highly correlated with those in Pd(II) analogues of the type trans-[PdBr2(iPr2-bimy)(NHC)], which could be applied to detect the σ-donating ability of the trans-standing NHC. In addition, an interesting ligand redistribution process was observed for some of the Au(I) hetero-bis-NHC complexes.
70. D. Yuan, H. V. Huynh* "A Comparative Study on Di- and Multinuclear Ni(II), Pd(II) and Pt(II) Complexes of a Thiolato-Functionalized, Benzannulated N-Heterocyclic Carbene Ligand" Inorg. Chem., 2013, 52, 6627−6634.
Dimeric thiolato-bridged Ni(II) and Pt(II) NHC complexes 2 and 4 have been synthesized from ligand precursor A through a combined and in situ deprotonation/hydrolysis protocol of a thioester-functionalized benzimidazolium salt in the presence of the respective metal salts. Reactivity studies of 2 and 4, and their previously reported Pd(II) analogue 1a toward either Me3OBF4, NaOH or Na2S•9H2O revealed clear differences. Complex 2 decomposed when treated with Me3OBF4. On the other hand, its reaction with aqueous NaOH solution in the presence of NaBF4 yielded trinuclear [Ni3S3O] complex 6, which possesses an interesting [Ni3S3] triangle with a capping μ3-oxido ligand. Pt(II) analogue 4 was converted to the tetranuclear [Pt4S4] macrocycle 5 when treated with Me3OBF4, in analogy to the result from 1a, while no defined products could be isolated when 4 was treated with either NaOH or Na2S•9H2O. Pd(II) analogue 1a reacted with Na2S•9H2O to give the tri-palladium [Pd3S3S] complex 7 bearing a capping μ3-sulfido ligand.
69. H. V. Huynh*, Chen-Shiang Lee "Pincer-type di(1,2,4-triazolin-5-ylidene)Pd(II) complexes and their catalytic activities towards Cu- and amine-free Sonogashira reaction" Dalton Trans., 2013, 42, 6803–6809.
Pd(II) complexes [PdBr(A-κ3CNC)]Br (1) and [PdBr(B-κ3CNC)]Br (2) with new CNC pincer-type ligands derived from 1,2,4-triazolin-5-ylidenes have been synthesized and characterized by multinuclei NMR spectroscopies, ESI mass spectrometry and X-ray diffraction analysis. The more soluble complex 1 proved to be an efficient pre-catalyst in copper- and amine-free Sonogashira reaction with high turnover numbers. The potential for recycling of the catalyst was also demonstrated.
68. S. M. Puah, H. V. Huynh, J. C. Wu* "Novel two-in-one bioreactor greatly improves lactic acid production from xylose by Lactobacillus pentosus" J. Chem. Technol. Biotechnol. 2013, 88, 594–598.
Simultaneous xylose isomerization and fermentation was investigated to improve the lactic acid production from xylose by Lactobacillus pentosus in a novel two-in-one bioreactor constructed by packing the immobilized xylose isomerase (65 g) in a fixed bed reactor (diameter 56 mm × 66 mm, packing volume 154 mL) with a permeable wall, which was installed inside a conventional fermenter (2 L) and rotated along the axis together with the mechanical stirrer of the fermenter.
67. H. V. Huynh*, Q. Teng "Highly modular access to functionalised metal-carbenes via post-modifications of a single bromoalkyl-substituted NHC–Pd(II) complex" Chem. Commun., 2013, 49, 4244–4246.
(invited contribution for the Chemical Communication's ‘Emerging Investigators 2013’ themed issue)
The synthesis of a bromopropyl-substituted NHC–Pd(II) complex, which can undergo exemplary and versatile 2nd and 3rd generation post-modifications easily affording 7 new functionalised NHC complexes, is demonstrated.
66. H. V. Huynh, G. Frison* "Electronic structural trends in divalent carbon compounds" J. Org. Chem., 2013, 78, 328–338.
This work aims to analyze and compare the intrinsic electronic densities in a series of neutral and anionic divalent carbon-donor derivatives. The σ-lone pair at the divalent carbon is the HOMO of these species. Structural factors have been identified that influence its energy, which is a measure of the σ-basicity. The π-electronic structure has been described as a function of the π-population. Our results show that no straightforward structural criteria correlate with the π-electronic distribution. However, the π-population, as well as the π-acidity and π-basicity, are related to the π-MOs. In all cases these π-MOs can be qualitatively obtained based on those of the protonated analogues by simply increasing the energy of the pπ orbital at the divalent carbon atom compared to normal sp2 carbon. Such an analysis allows a rationalization of the trends observed for the π-electronic structure of these ligands. Notably, this explains the values of the π-population at the divalent carbon center, which shows an increasing and continuous range from classical NHCs to mesoionic "carbenes".
65. H. Sivaram, J. Tan, H. V. Huynh* "Syntheses, Characterizations, and a Preliminary Comparative Cytotoxicity Study of Gold(I) and Gold(III) Complexes Bearing Benzimidazole- and Pyrazole-Derived N-Heterocyclic Carbenes" Organometallics 2012, 31, 5875−5883.
A series of Au(I) and Au(III) mono-, homobis-, and heterobis(carbene) complexes, [AuCl(FPyr)] (2), [Au(iPr2-bimy)2]PF6 (3), [Au(FPyr)2]PF6 (4), [Au(FPyr)(iPr2-bimy)]PF6 (5), [AuCl3(iPr2-bimy)] (6), [AuCl3(FPyr)] (7), [AuCl2(iPr2-bimy)2]PF6 (8), [AuCl2(FPyr)2]PF6 (9), and [AuCl2(FPyr)(iPr2-bimy)]PF6 (10), bearing the benzimidazole-derived iPr2-bimy (1,3-diisopropylbenzimidazolin-2-ylidene) and/or the pyrazole-derived FPyr (1,2,3,4,6,7,8,9-octahydropyridazino[1,2-a]indazolin-11-ylidene) N-heterocyclic carbene (NHC) ligands have been synthesized. Complexes 2–10 have been fully characterized using multinuclei NMR spectroscopy, ESI mass spectrometry, and elemental analysis. X-ray diffraction analyses have been performed on 2, 3, 5, 6, and 8. Together with the previously reported [AuCl(iPr2-bimy)] (1), the cytotoxic activities of all 10 complexes have been studied in vitro with the NCI-H1666 non-small cell lung cancer cell line. The cationic bis(carbene) complexes 3–5 and 8–10 show better cytotoxicity in comparison to cisplatin. In particular, the heterobis(carbene) complexes 5 and 10 have superior activity, with IC50 values of around 0.2 μM.
64. C. Bernhammer, H. V. Huynh* "Pyrazolin-5-ylidene Palladium(II) Complexes: Synthesis, Characterization, and Application in the Direct Arylation of Pentafluorobenzene" Organometallics 2012, 31, 5121–5130.
Ten palladium(II) complexes bearing a pyrazolin-5-ylidene ligand have been synthesized by oxidative addition and silver carbene transfer pathways. The weakly bound acetonitrile ligand in the initially obtained trans-[PdBr2(MeCN)(Pyry)] complex (6, Pyry = 1-phenyl-2,3-dimethylpyr-11 azolin-5-ylidene) could be replaced by other donor ligands, and additional NHC ligands were introduced either by silver carbene transfer reactions or via reaction with in situ generated free carbenes. Using our previously reported 13C NMR-based electronic parameter, the pyrazolin-5-ylidene ligand is estimated to be among the most strongly donating ligands on our scale so far. The complexes obtained were employed as catalysts for the direct arylation of pentafluorobenzene with moderate to good yields under optimized conditions.
63. S. Guo, H. V. Huynh* "Dipalladium Complexes with Triazolidin-Diylidene Bridges and Their Catalytic Activities" Organometallics 2012, 31, 4565−4573.
62. J. C. Bernhammer, H. V. Huynh* "Correlation of spectroscopically determined ligand donor strength and nucleophilicity of substituted pyrazoles" Dalton Trans. 2012, 41, 8600–8608.
61. D. Yuan, H. V. Huynh* "Sulfur-Functionalized N-Heterocyclic Carbene Complexes of Pd(II): Syntheses, Structures and Catalytic Activities" Molecules 2012, 17, 2491–2517.
N-heterocyclic carbenes (NHCs) can be easily modified by introducing functional groups at the nitrogen atoms, which leads to versatile coordination chemistry as well as diverse catalytic applications of the resulting complexes. This article summarizes our contributions to the field of NHCs bearing different types of sulfur functions, i.e., thioether, sulfoxide, thiophene, and thiolato. The experimental evidence for the truly hemilabile coordination behavior of a Pd(II) thioether-NHC complex has been reported as well. In addition, complexes bearing rigid CSC-pincer ligands have been synthesized and the reasons for pincer versus pseudo-pincer formation investigated. Incorporation of the electron-rich thiolato function resulted in the isolation of structurally diverse complexes. The catalytic activities of selected complexes have been tested in Suzuki-Miyaura, Mizoroki-Heck and hydroamination reactions.
60. H. Sivaram, R. Jothibasu, H. V. Huynh* "Gold Complexes of an Alicyclic Indazole-Derived N-Heterocyclic Carbene: Syntheses, Characterizations, and Ligand Disproportionation" Organometallics 2012, 31, 1195–1203.
A gold(I) NHC complex bearing a heteroalicyclic indazolin-3-ylidene ligand, [AuCl(Indy)] (1) (Indy = 6,7,8,9-tetrahydropyridazino[1,2-a]indazolin-3-ylidene), has been synthesized via the silver-carbene transfer method. Conversion of complex 1 to its heavier halido analogues [AuBr(Indy)] (2) and [AuI(Indy)] (3) was achieved by metathesis reactions involving LiBr and NaI in acetone, respectively. In contrast to 1 and 2, complex 3 undergoes ligand disproportionation/autoionization upon crystallization forming the solid complex salts [Au3I2(Indy)4][Au3I4(Indy)2] (3') or [Au(Indy)2][AuI2] (3") depending on the solvent used. This reversible process assisted by aurophilic interactions, and only occurring in the iodido complex 3, has been studied further by spectroscopic comparison with [Au(Indy)2]BF4 (4) and selective conversion of 3 to the gold(III) species [AuI3(Indy)] (5). All complexes 1–5 have been fully characterized using multinuclei NMR spectroscopies, ESI mass spectrometry and X-ray diffraction analysis.
59. D. Yuan, H. V. Huynh* "1,2,3-Triazolin-5-ylidenes: Synthesis of Hetero-bis(carbene) Pd(II) Complexes, Determination of Donor Strengths, and Catalysis" Organometallics 2012, 31, 405–412.
A series of hetero-bis(carbene) complexes trans-[PdBr2 (iPr2-bimy)(trz)] 1–4 (iPr2-bimy = 1,3-diisopropylbenzimidazolin-2-ylidene; trz = 1,2,3-triazolin-5-ylidene) bearing the constant iPr2-bimy and varying mesoionic 1,2,3-triazolin-5-ylidenes with different N-substituents has been synthesized as complex probes. Their 13C NMR spectroscopic evaluation shows that mesoionic 1,2,3-triazolin-5-ylidenes are in general stronger donors than classical NHCs, while weaker than some nonclassical NHCs such as pyrazolin-3-ylidenes and mesoionic imidazolin-4-ylidenes. More important and for the first time, this methodology proves useful in establishing substituent effects in the donating abilities of 1,2,3-triazolin-5-ylidenes on a finer level. In addition, the trifluoroacetato analogues [Pd(O2CCF3)2 (iPr2-bimy)(trz)] 5–7 have been synthesized through salt metathesis of 1, 2 and 4 with AgO2CCF3. The catalytic activities of complexes 1, 2 and 4–7 were examined in the direct arylation of pentafluorobenzene. Complexes bearing less donating trz ligands perform better in this catalysis, and trifluoroacetato complexes outperformed their bromido analogues.
58. D. Yuan, H. V. Huynh* "Synthesis and characterization of thiolato-functionalized N-heterocyclic carbene Pd(II) complexes with normal and mesoionic binding modes" Dalton Trans. 2011, 40, 11698–11703.
The thiolato-bridged dimeric Pd(II) NHC complex 1 has been synthesized from the reaction of thioester-functionalized imidazolium salt B and Pd(OAc)2. The isolation of its interesting constitutional isomer 2 bearing both classical C(2)-bound and mesoionic C(4)-bound ligands coordinating to two different metal centers in the same complex allowed for a direct comparison of these isomeric carbenes. Reactivity study of 1 with NaSCH(CH3)2 and NaBF4 afforded the tetranuclear compound 3 with a [Pd4S4] macrocycle. All complexes have been fully characterized by multinuclei NMR spectroscopies, ESI mass spectrometry and X-ray diffraction analysis.
57. H. V. Huynh*, R. Jothibasu "Syntheses and catalytic activities of Pd(II) dicarbene and hetero-dicarbene complexes" J. Organomet. Chem. 2011, 696, 3369–3375.
A series of palladium(II) complexes (1-6) bearing cis-chelating homo-dicarbene ligands with varying alkyl bridges (C1-C3) and N-heterocyclic backbones (imidazole and benzimidazole) have been synthesized by reaction of Pd(OAc)2 with the respective diazolium bromides (A•2HBr – F•2HBr) in DMSO. A comparative catalytic study employing aryl chlorides in the Mizoroki-Heck reaction revealed the superiority of methylene- and propylene-bridged dibenzimidazolin-2-ylidenes over their imidazole-derived analogues. Based on these results, two new propylene-bridged hetero-dicarbene complexes (7 and 8) were designed containing a mixed benzimidazole/imidazole derived NHC-donor set. Notably, both complexes outperformed their homo-dicarbene analogues, which may be due to the electronic asymmetry induced by hetero-dicarbene ligands. The molecular structures of complex 6 and 8 are also presented.
56. H. V. Huynh*, W. Sim, C. F. Chin "Rotaxanes with Palladium(II)-NHC stoppers" Dalton Trans. 2011, 40, 11690–11692.
Bridge cleavage reactions of the dimeric monocarbene complex [PdBr2(iPr2-bimy)]2 can be effectively used to end-cap pyridine containing pseudorotaxanes affording stable rotaxanes.
55. D. Yuan, H. Tang, L. Xiao, H. V. Huynh* "CSC-pincer versus pseudo-pincer complexes of palladium(II): a comparative study on complexation and catalytic activities of NHC complexes" Dalton Trans. 2011, 40, 8788–8795.
(Cover article and invited contribution for a special issue "Pincers and other hemilabile ligands" and "Hot article")
Three thioether bridged diimidazolium dibromides with different steric and electronic properties have been synthesized as precursors to carbene-based CSC pincer ligands. Palladation afforded CSC Pd(II) pincer complexes for bulky and electron rich ligand systems, whereas the least donating ligand led to the formation of a pseudo-pincer complex. All complexes have been fully characterized by multinuclei NMR spectroscopies, ESI mass spectrometry and X-ray diffraction analysis. The catalytic activities of pincer versus pseudo-pincer complexes have been compared in the intermolecular hydroamination of alkynes with anilines as well.
54. L. Xue, L. Shi, Y. Han, C. Xia, H. V. Huynh*, F. Li* "Pd-carbene catalyzed carbonylation reactions of aryl iodides" Dalton Trans. 2011, 40, 7632–7638.
A series of carbene complexes [PdBr2(iPr2-bimy)L] (C2-C13) with different types of co-ligands (L) have been tested for their catalytic activities in the carbonylative annulation of 2-iodophenol with phenylacetylene in DMF to afford the respective flavone 2a. Complex C12 with an N-phenylimidazole co-ligand showed the best activity and also afforded high yields when the substrate scope was extended to other aryl or pyridyl acetylenes. In addition, catalyst C12 was also efficient in the carbonylative annulation of 2-iodoaniline with acid chlorides giving the desirable 2-substituted 4H-3,1-benzoxazin-4-ones (4) in good yields. Additionally, this Pd-NHC complex also proved to be a very efficient catalyst for the hydroxycarbonylation of iodobenzene derivatives at low catalyst loading and under low CO pressure. These results demonstrate the versatility and efficiency of this phosphine-free Pd(II)-NHC complex in different types of carbonylations of aryl iodides under mild conditions.
53. H. V. Huynh*, Invited Book Review "Functionalised N-Heterocyclic Carbene Complexes" by Olaf Kühl, Wiley, 2010, 364 pp. (hardback) ISBN 978-0-470-71215-3" App. Organomet. Chem., 2011, 25, 565.
52. Y. Han, D. Yuan, Q. Teng, H. V. Huynh* "Reactivity Differences of Pd(II) Dimers bearing Heterocyclic Carbenes with two, one or no α-Nitrogen Atoms toward Isocyanides" Organometallics 2011, 30, 1224–1230.
Pd(II) dimers [PdI2(rNHC)]2 (1a/b) of pyrazole-based remote N-heterocyclic carbenes (rNHCs) have been synthesized through oxidative addition of 4-iodopyrazolium iodides (A/B) to [Pd2(dba)3]. Reaction of 1a with aromatic (CN-Xyl) or aliphatic (CN-Cy) isocyanides led to the template-assisted formation of novel Pd(II) dimers 8/9 bearing betainic C-imino ligands via isocyanide insertion into Pd-CrNHC bonds and subsequent dimerization. In contrast, both isocyanides reacted with dimers [PdI2(Me2-indy)]2 (2) and [PdI2(Me2-bimy)]2 (3) bearing indazolin-3-ylidenes and benzimidazolin-2-ylidenes under formation of mononuclear mixed carbene/isocyanide complexes 4-7. Notably, only dimer 8 underwent further bridge-cleavage with excess isocyanide yielding the mixed C-imino/CN-Xyl complex 10, while dimer 9 remained intact. These results highlight the uniquely different reactivity of complexes with carbenes with no α-nitrogen versus those with one or two α-nitrogen atoms as a result of their decreasing donor abilities.
51. Y. Han, H. V. Huynh* "Pyrazolin-4-ylidenes: a new class of intriguing ligands" Dalton Trans. 2011, 40, 2141–2147.
(invited contribution for a special issue "New Talent: Asia")
The immense success of N-heterocyclic carbenes in recent years has initiated the search for even stronger ligands leading to the discovery of abnormal and remote NHCs. This article reﬂects our particular interest in the coordination chemistry of pyrazolin-4-ylidenes as a contribution to this ﬁeld. A modular approach to 4-iodopyrazolium salts with different substitution patterns is described, which upon oxidative addition to Pd0 gave rise to a library of new Pd(II) pyrazolin-4-ylidene complexes. A preliminary study showed that selected complexes are active precatalysts in Suzuki–Miyaura and Mizoroki–Heck coupling reactions. The 3,5-substituents of pyrazolin-4-ylidenes are found to have signiﬁcant effects on complexation and catalytic activities. Finally, the nature of this new class of ligands is discussed, and a future direction for further explorations in this exciting ﬁeld is envisioned.
50. A. D. Yeung, P. S. Ng, H. V. Huynh* "Co-ligand Effects in the Catalytic Activity of Pd(II)-NHC Complexes" J. Organomet. Chem. 2011, 696, 112–117.
(invited contribution for a special issue on Catalytic addition of E-H bonds to non-activated carbon-carbon multiple bonds)
Three cis-chelating di-N-heterocyclic carbene palladium(II) complexes [PdX2(diNHC)] (X = I, 1; X = SCN, 2; X = CF3CO2, 3) bearing different anionic co-ligands were synthesized and fully characterized. A comparison of their catalytic activities in the Mizoroki-Heck reaction and conjugate addition of arylboronic acids to cyclic enones revealed increasing efficiency in the order SCN- < I- < CF3CO2-. The di(trifluoroacetato) complex 3 showed the best activity in both transformations highlighting the importance of co-ligands effects in catalysis. In addition, the molecular structure of an unusual poly-heteronuclear complex salt 4 is reported, which has been isolated as a byproduct in the synthesis of complex 3.
49. D. Yuan, H. V. Huynh* "Dinuclear and Tetranuclear Palladium(II) Complexes of a Thiolato-Functionalized, Benzannulated N-Heterocyclic Carbene Ligand and Their Activities toward Suzuki-Miyaura Coupling" Organometallics 2010, 29, 6020–6027.
The thiolato-bridged dimeric Pd(II) benzimidazolin-2-ylidene complex 1, with a [Pd2S2] core, was conveniently prepared by the reaction of the thiol-functionalized benzimidazolium salt C and Pd(OAc)2. More straightforwardly, 1 can also be synthesized by direct treatment of the thioester-functionalized benzimidazolium salt B with Pd(OAc)2 in wet DMSO under in situ hydrolysis of the thioester function. A subsequent salt metathesis reaction of 1 with AgO2CCF3 afforded the mixed dicarboxylato/NHC analogue 2 in quantitative yield, leaving the sulfur bridges of the [Pd2S2] core unaffected despite the use of the soft Ag(I) ions. Treatment of 1 with Me3OBF4 resulted in an unexpected bromido abstraction of 1 leading to an unusual rearrangement/dimerization reaction to give the tetranuclear NHC complex 3, which features a [Pd2S2] macrocylic square with sulfur corners. These reactions demonstrate the structural diversity of the thiolato-functionalized N-heterocyclic carbene complexes and may offer access to metallo-NHC-based supramolecular architectures. A comparative catalytic study revealed the superiority of NHC/thiolato complex 2 over complexes 1 and 3 in aqueous Suzuki-Miyaura couplings at very low catalyst loading.
48. R. Jothibasu, K.-W. Huang, H. V. Huynh* "Synthesis of cis- and trans-Diisothiocyanato-Bis(NHC) Complexes of Nickel(II) and Applications in the Kumada-Corriu Reaction" Organometallics 2010, 29, 3746–3752.
Metathetical reaction of AgSCN with a series of trans-dihalido-bis(carbene) nickel(II) complexes in CH3CN readily afforded the novel diisothiocyanato-bis(carbene) complexes [Ni(NCS)2(NHC)2] (trans-2a, NHC = 1,3-diisopropylbenzimidazolin-2-ylidene; trans-2b, NHC = 1,3-diisobutylbenzimidazolin-2-ylidene; trans-2c, NHC = 1,3-dibenzylbenzimidazolin-2-ylidene; cis-2d, NHC = 1,3-di(2-propenyl)benzimidazolin-2-ylidene; cis-2e, NHC = 1-propyl-3-methylbenzimidazolin-2-ylidene) as greenish yellow powders in moderate to good yields. While dihalido-bis(carbene) Ni(II) complexes exclusively form trans-complexes, a trans-cis isomerization occurs upon halido-isothiocyanato exchange with complexes bearing less bulky carbene ligands, i.e. cis-2d/e. DFT calculations indicated that this isomerization can be attributed to a reduced energy difference between trans and cis isomers of diisothiocyanato complexes. All complexes have been characterized by multinuclear NMR spectroscopy, ESI mass spectrometry and X-ray diffraction analysis. A catalytic study revealed that cis-complexes generally exhibit greater activities in the Kumada-Corriu coupling reaction.
47. H. V. Huynh*, Y. X. Chew "Synthesis, structural characterization and catalytic activity of a palladium(II) complex bearing a new ditopic thiophene-N-heterocyclic carbene ligand" Inorg. Chim. Acta 2010, 363, 1979–1983.
(invited contribution for a special issue on Metals in Organic Chemistry)
A new thiophene-functionalized benzimidazolium salt (2) has been prepared by reacting N-methylbenzimidazole with 2-bromomethylthiophene (1), which in turn was obtained by bromination of 2 thiophenemethanol with PBr3. Subsequent reaction of salt 2 with Pd(OAc)2 afforded the cis configured bis(carbene) Pd(II) complex (cis-3), which in solution exists as an inseparable mixture of cis-anti and cis-syn-rotamers in a 3.5:1 ratio. All new compounds have been fully characterized by spectroscopic and spectrometric methods. A preliminary catalytic study shows that cis-3 is highly active in the Suzuki-Miyaura coupling of aryl bromides with phenylboronic acid in/on water as environmentally benign reaction media.
46. R. Jothibasu, H. V. Huynh* "Versatile coordination chemistry of indazole-derived carbenes" Chem. Commun. 2010, 46, 2986–2988.
The versatile coordination chemistry of strongly donating indazolin-3-ylidene ligands as new members of the NHC family is demonstrated on 12 new PdII, AuI and RhI complexes, which were fully characterized by multinuclear NMR spectroscopies, ESI mass spectrometry and X-ray diffraction studies.
45. H. V. Huynh*, C. H. Yeo, Y. X. Chew "Syntheses, Structures, and Catalytic Activities of Hemilabile Thioether-Functionalized NHC Complexes" Organometallics 2010, 29, 1479–1486.
Four imidazolium (5a/b) and benzimidazolium (6a/b) salts with hemilabile alkyl-aryl thioether functions have been prepared via a straightforward and modular pathway in order to compare their reactivities toward palladation. Reaction of 5a/b with Pd(OAc)2 gave complex product mixtures, whereas 6a/b afforded the desired bis(benzimidazolin-2-ylidene) complexes 8a/b in good yields. The difference in reactivities of benzimidazole versus imidazole derivatives was attributed to the presence of additional acidic protons at C4/5 positions of the imidazolium ring, leading to competing and unselective deprotonation reactions. The milder Ag-NHC transfer reaction, on the other hand, provided either mono- or bis(imidazolin-2-ylidene) complexes (9 or 7a/b) in good yields depending on the ligand:metal ratio. The interesting hemilability in monocarbene complex 9 was investigated by spectroscopy and thioether displacement reaction with PPh3, yielding the mixed NHC-PPh3 complex 10 in high yields. An initial comparative catalytic study also reveals that the mixed-donor complex 10 exhibits the highest activity among the complexes tested.
44. Y. Han, L. J. Lee, H. V. Huynh* "Pyrazole-Derived Remote Dicarbenes: Versatile Ligands for Di- and Tetranuclear Complexes" Chem. Eur. J. 2010, 16, 771-773.
Influence your neighbor: The first examples of pyrazole-based dicarbene complexes are described (for an example see figure). Remote changes in the ligand topology four bonds away from the carbon donor have substantial influences on the nuclearity of the resulting complexes.
43. S. K. Yen, D. J. Young, H. V. Huynh, L. L. Koh, T. S. A. Hor* “Unexpected coordination difference in geometric-isomerism between N,S- and N,N-heterocyclic carbenes in cyclometallated platinum(II)” Chem. Commun. 2009, 6831-6833.
The reaction of [PtII(2-phenylpyridine)(acac)] and benzothiazolium bromide yields the N,S-heterocyclic carbene ligand trans to pyridyl while, surprisingly, a very similar N,N-heterocyclic carbene coordinates predominantly trans to the cyclometallated carbon.
42. H. V. Huynh*, Y. Han, R. Jothibasu, J. A. Yang "13C NMR Spectroscopic Determination of Ligand Donor Strengths using N-Heterocyclic Carbene Complexes of Palladium(II)" Organometallics 2009, 28, 5395–5404.
The electronic parameters of 25 Werner-type and organometallic ligands have been experimentally determined and ranked on an unprecedented unified 13C NMR scale using safe and easily obtainable complexes of the type trans-[PdBr2(iPr2-bimy)L]n- (iPr2-bimy = 1,3-diisopropylbenzimidazolin-2-ylidene; L = ligand in question) as spectroscopic probes. The methodology is based on the sensitivity of the constant iPr2-bimy carbene signal to the donor strengths of the varying co-ligands, which even allows detection of backbone and substituent effects more accurately than previous carbonyl-based systems. For the evaluation of N-heterocyclic carbenes (NHCs), a one-pot approach to novel hetero-bis(carbene) complexes bearing two different NHCs is introduced. Furthermore, the first complex of a strongly donating indazolin-3-ylidene ligand is presented. The molecular structures of ten complex-probes have been characterized by single-crystal X-ray diffraction analyses.
41. S. K. Yen, L. L. Koh, H. V. Huynh, T. S. A. Hor* “Benzothiazolin-2-ylidene and Azole Mixed-Ligand Complexes of Palladium” Eur. J. Inorg. Chem. 2009, 4288–4297.
A series of mixed-ligand, mononuclear complexes trans-[PdX2(NSHC)(azole)] [NSHC = N,S-heterocyclic carbene; azole = imidazole, 1-(2,4,6-trimethylphenyl)-1H-imidazole, benzimidazole, benzothiazole and benzoxazole] have been prepared and characterised by X-ray single-crystal diffraction. These complexes catalyse the sp2–sp3 cross-coupling of fluoroaryl halides with arylboronic acid to give diarylmethanes with good yields and high turnovers.
40. H. V. Huynh*, D. Yuan, Y. Han “Syntheses and catalytic activities of pseudo-pincer and CSC pincer-type Pd(II) complexes derived from benzannulated N-heterocyclic carbenes” Dalton Trans. 2009, 7262-7268.
(invited contribution for a special issue on NHC chemistry)
Reaction of thioether- and sulfoxide-functionalized dibenzimidazolium dibromides B⋅ 2HBr and C⋅ 2HBr with Pd(OAc)2 afforded two new pseudo-pincer complexes cis-[PdBr2(B-κ2C)] (1) and cis-[PdBr2(C-κ2C)] (2), which contain pendant sulfur-functions. On the other hand, palladation of the dinitrate analogue B⋅ 2HNO3 in the presence of 1 equiv of KBr yields the first NHC-based CSC pincer complex [PdBr(B-κ3CSC)]NO3 (3). All three complexes have been fully characterized by multinuclei NMR spectroscopies, ESI mass spectrometry and X-ray diffraction analysis. Their catalytic activities in the Mizoroki-Heck reaction are reported as well.