Labile Ligands Research Articles

Effective Labeling of Amine Pharmacophores through the Employment of 2,3-Pyrazinedicarboxylic Anhydride and the Generation of fac-[M(CO)3(PyA)P] and cis-trans-[M(CO)2(PyA)P2] Complexes (PyA = Pyrazine-2-carboxylate, P = Phosphine, M = Re, 99mTc).

The fac-[M(CO)3(PyA)(P)] and cis-trans-[M(CO)2(PyA)(P)2] neutral complexes (M is Re or 99mTc), based on the mixed ligand strategy with pyrazine-2-carboxylic acid (PyAH) as the bidentate N,O and triphenylphosphine as the monodentate P ligand, are presented. Through the employment of the anhydride of pyrazine-2,3-dicarboxylic acid (PyDA), the PyAH scaffold was conveniently derivatized with the model bioactive amine 1-(2-methoxyphenyl)piperazine, the active part of the 5-HT1A antagonist WAY100635. Reaction of either PyAH or the pharmacophore-bearing PyAH ligand (L1H) with fac-[M(CO)3]+ core in water yielded the intermediate fac-[M(CO)3(PyA)(H2O)] complexes. The labile aqua ligand was easily replaced by PPh3 to yield the fac-[Re(CO)3(PyA)(PPh3)] complexes, while in toluene under reflux, the cis-trans-[Re(CO)2(PyA)(PPh3)2] complexes were obtained. The latter complexes were alternatively obtained from mer-[Re(CO)3(PPh3)2Cl] by refluxing with the PyA ligand in toluene. The analogous 99mTc complexes were synthesized quantitatively, showing excellent stability in competition studies. The methodology described herein represents a practical procedure for the effective integration of the fac-[M(CO)3]+ core with amine-bearing biologically active compounds for diagnosis/therapy.

Chiral Iron Complexes in Asymmetric Organic Transformations

AbstractTransition metal chiral catalysts can feature metal stereocenters in different coordination geometries. In the case of iron, both octahedral and tetrahedral geometries possessing a chirotopic iron atom have been synthesized and tested in stereoselective organic transformations. The configurational stability of these complexes, which in some cases is hampered by decomplexation and recomplexation of labile ligands, is achieved by the use of multidentate ligands in octahedral complexes, and of cyclopentadienyl anions (half sandwich complexes) in the case of tetrahedral structures. The use of octahedral iron complexes featuring configurationally stable iron stereocenters is reviewed in highly enantioselective reductions (hydrogenation and transfer hydrogenation of ketones) and oxidations (cis‐dihydroxylation of alkenes, epoxidation, sulfoxidation), while the use tetradentate iron complexes is described in C−C bond‐forming reactions and reductions.magnified image

Development and Molecular Understanding of a Pd‐Catalyzed Cyanation of Aryl Boronic Acids Enabled by High‐Throughput Experimentation and Data Analysis

AbstractA synthetic method for the palladium‐catalyzed cyanation of aryl boronic acids using bench stable and non‐toxic N‐cyanosuccinimide has been developed. High‐throughput experimentation facilitated the screen of 90 different ligands and the resultant statistical data analysis identified that ligand σ‐donation, π‐acidity and sterics are key drivers that govern yield. Categorization into three ligand groups – monophosphines, bisphosphines and miscellaneous – was performed before the analysis. For the monophosphines, the yield of the reaction increases for strong σ‐donating, weak π‐accepting ligands, with flexible pendant substituents. For the bisphosphines, the yield predominantly correlates with ligand lability. The applicability of the designed reaction to a wider substrate scope was investigated, showing good functional group tolerance in particular with boronic acids bearing electron‐withdrawing substituents. This work outlines the development of a novel reaction, coupled with a fast and efficient workflow to gain understanding of the optimal ligand properties for the design of improved palladium cross‐coupling catalysts.

Tc(OH2)(CO)3(PPh3)2]+: A Synthon for Tc(I) Complexes and Its Reactions with Neutral Ligands.

A scalable synthesis of the novel and highly reactive [Tc(OH2)(CO)3(PPh3)2]+ cation is described. The ligand-exchange chemistry of this compound with neutral ligands coordinating through C, N, O, S, Se, and Te has been explored systematically. The complexes either retain the original mer-trans tricarbonyl core under exclusive exchange of the aqua ligand or form dicarbonyl complexes by thermal decarbonylation. Ligand exchange reactions starting from [Tc(OH2)(CO)3(PPh3)2]+ proceed under mild conditions and are generally almost quantitative. Some of the formed complexes are remarkably stable and inert, while others provide products with one labile ligand for further reactions. The derived complexes of the type [Tc(L)(CO)3(PPh3)2]+ and [Tc(L)2(CO)2(PPh3)2]+ represent an interesting opportunity for the development of 99mTc complexes with potential use in radiopharmacy. The ready displacement of the aqua ligand highlights the synthetic value of [Tc(OH2)(CO)3(PPh3)2]+ as a reactive entry point for further studies in the little explored field of the organometallic chemistry of technetium.

Lewis Acid-Promoted Oxidative Addition at a [Ni0 (diphosphine)2 ] Complex: The Critical Role of a Secondary Coordination Sphere.

Oxidative addition represents a critical elementary step in myriad catalytic transformations. Here, the importance of thoughtful ligand design cannot be overstated. In this work, we report the intermolecular activation of iodobenzene (PhI) at a coordinatively saturated 18-electron [Ni0 (diphosphine)2 ] complex bearing a Lewis acidic secondary coordination sphere. Whereas alkyl-substituted diphosphine complexes of Group 10 are known to be unreactive in such reactions, we show that [Ni0 (P2 BCy 4 )2 ] (P2 BCy 4 =1,2-bis(di(3-dicyclohexylboraneyl)-propylphosphino)ethane) is competent for room-temperature PhI cleavage to give [NiII (P2 BCy 4 )(Ph)(I)]. This difference in oxidative addition reactivity has been scrutinized computationally - an outcome that is borne out in ring-opening to provide the reactive precursor - for [Ni0 (P2 BCy 4 )2 ], a "boron-trapped" 16-electron κ1 -diphosphine Ni(0) complex. Moreover, formation of [NiII (P2 BCy 4 )(Ph)(I)] is inherent to the P2 BCy 4 secondary coordination sphere: treatment of the Lewis adduct, [Ni0 (P2 BCy 4 )2 (DMAP)8 ] with PhI provides [NiII (P2 BCy 4 )2 (DMAP)8 (I)]I via iodine-atom abstraction and not a [NiII (Ph)(I)(diphosphine)] compound - an unusual secondary sphere effect. Finally, the reactivity of [Ni0 (P2 BCy 4 )2 ] with 4-iodopyridine was surveyed, which resulted in a pyridyl-borane linked oligomer. The implications of these outcomes are discussed in the context of designing strongly donating, and yet labile diphosphine ligands for use in a critical bond activation step relevant to catalysis.

Cis-Divacant Octahedral Fe(II) in a Dimensionally Reduced Family of 2-(Pyridin-2-yl)pyrrolide Complexes.

Four-coordinate transition-metal complexes can adopt a diverse array of coordination geometries, with square planar and tetrahedral coordination being the most prevalent. Previously, we reported the synthesis of a trinuclear Fe(II) complex, Fe3TPM2, supported by a 3-fold-symmetric 2-pyridylpyrrolide ligand [i.e., tris(5-(pyridin-2-yl)-1H-pyrrol-2-yl)methane] that featured a rare cis-divacant octahedral (CDO) geometry at each Fe(II) center. Here, a series of truncated 2-pyridylpyrrolide ligands are described that support mono- and binuclear Fe(II) complexes that also exhibit CDO geometries. Metalation of the tetradentate ligand bis[5-(pyridin-2-yl)-1H-pyrrol-2-yl]methane (H2BPM) in tetrahydrofuran (THF) results in the binuclear complex Fe2(BPM)2(THF)2 in which both Fe(II) ions are octahedrally coordinated. The coordinated THF solvent ligands are labile: THF dissociation leads to Fe2(BPM)2, which features five-coordinate Fe(II) ions. The Fe-Fe distance in these binuclear complexes can be elongated by ligand methylation. Metalation of bis[5-(6-methylpyridin-2-yl)-1H-pyrrol-2-yl]methane (H2BPMMe) in THF leads to the formation of four-coordinate, CDO Fe(II) centers in Fe(BPMMe)2. Further ligand truncation affords bidentate ligands 2-(1H-pyrrol-2-yl)pyridine (PyrPyrrH) and 2-methyl-6-(1H-pyrrol-2-yl)pyridine (PyrMePyrrH). Metalation of these ligands in THF affords six-coordinate complexes Fe(PyrPyrr)2(THF)2 and Fe(PyrMePyrr)2(THF)2. Dissociation of labile solvent ligands provides access to four-coordinate Fe(II) complexes. Ligand disproportionation at Fe(PyrPyrr)2 results in the formation of Fe(PyrPyrr)3 and Fe(0). Ligand methylation suppresses this disproportionation and enables isolation of Fe(PyrMePyrr)2, which is rigorously CDO. Complete ligand truncation, by separating the 2-pyridylpyrrolide ligands into the constituent monodentate pyridyl and pyrrolide donors, affords Fe(Pyr)2(Pyrr)2 in which Fe(II) is tetrahedrally coordinated. Computational analysis indicates that the potential energy surface that dictates the coordination geometry in this family of four-coordinate complexes is fairly flat in the vicinity of CDO coordination. These synthetic studies provide the structural basis to explore the implications of CDO geometry on Fe-catalyzed reactions.

Direct Optical Lithography of CsPbX3 Nanocrystals via Photoinduced Ligand Cleavage with Postpatterning Chemical Modification and Electronic Coupling.

Microscale patterning of solution-processed nanomaterials is important for integration in functional devices. Colloidal lead halide perovskite (LHP) nanocrystals (NCs) can be particularly challenging to pattern due to their incompatibility with polar solvents and lability of surface ligands. Here, we introduce a direct photopatterning approach for LHP NCs through the binding and subsequent cleavage of a photosensitive oxime sulfonate ester (-C═N-OSOO-). The photosensitizer binds to the NCs through its sulfonate group and is cleaved at the N-O bond during photoirradiation with 405 nm light. This bond cleavage decreases the solubility of the NCs, which allows patterns to emerge upon development with toluene. Postpatterning ligand exchange results in photoluminescence quantum yields of up to 79%, while anion exchange provides tunability in the emission wavelength. The patterned NC films show photoconductive behavior, demonstrating that good electrical contact between the NCs can be established.

Ligand coordination in [Re2(CO)9(NCMe)] and [H3Re3(CO)11(NCMe)] by triphenylantimony: Reactivity studies and Sb–Ph bond cleavage to give new antimony-containing di- and trirhenium complexes

The reactions of the MeCN-substituted compounds [Re2(CO)9(NCMe)] and [H3Re3(CO)11(NCMe)] with SbPh3 are described. Treatment of [Re2(CO)9(NCMe)] with SbPh3 in refluxing benzene furnished [Re2(CO)9(SbPh3)] (1) in good yield. Complex 1 reacts with SbPh3 in the presence of Me3NO in acetonitrile to give [Re2(CO)8(σ-C6H5)(µ-SbPh2)(NCMe)] (2), which on further reaction with additional SbPh3 in refluxing benzene afforded the known complex [Re2(CO)8(σ-C6H5)(µ-SbPh2)(SbPh3)] (3). Heating 1 with SbPh3 at 110 °C yields 3, which on prolonged heating at 110 °C in the presence of SbPh3 furnished the known stibene-bridged compound [Re2(CO)7(µ-SbPh2)2(SbPh3)] (4). Complex 2 is a rare example of a dirhenium complex containing a sigma-bonded phenyl group and a labile acetonitrile ligand in the same molecule. The stibene-bridged dirhenium complexes (2−4) result from the cleavage of antimony-carbon and Re–Re bonds. Heating [H3Re3(CO)11(NCMe)] with SbPh3 in refluxing toluene afforded the new compounds [H3Re3(CO)11(SbPh3)] (5), [H2Re3(CO)11(µ-SbPh2)(SbPh3)] (6), and [HRe2(CO)6(µ-SbPh2)(SbPh3)2] (8) together with previously reported compound [HRe2(CO)7(µ-SbPh2)(SbPh3)] (7). Compound 5 is a simple monosubstituted product, while 6 contains a terminally coordinated SbPh3 ligand and a bridging SbPh2 group formed by Sb–Ph bond scission. Compound 8 results from cluster fragmentation and SbPh3 ligand activation by Sb–Ph bond cleavage. A series of separate thermolysis experiments have been performed in order to establish the relationship between the different products. Compounds 1, 2, 5, 6, and 8 have been structurally characterized by X-ray crystallography. The bonding in these new compounds has been investigated by electronic structure calculations.

Molecular Valence Tautomeric Metal Complexes for Chemosensing.

Switchable valence tautomeric metal complexes have been long suggested for applications as chemosensors. However, no such molecular sensors have been yet reported. Here, we present a concept for sensing and the first prototype molecular sensor based on valence tautomeric cobalt-dioxolenes. A valence tautomeric cobalt-dioxolene complex [ls-CoIII(SQ•)(Cat)(stypy)2] ⇄ [hs-CoII(SQ•)2(stypy)2] 1 (ls = low spin, hs = high spin, Cat = 3,5-di-tert-butylcatecholate(2-), SQ = one-electron oxidized, benzosemiquinone(1-) form of Cat, stypy = trans-4-styrylpyridine) has been used as a molecular sensor. The lability of axial stypy ligands of 1 in solution allows us to exchange stypy ligands by dimethyl sulfoxide and simple pyridine analytes in a controllable way, which triggers colorimetric and magnetic responses.

Organometallic single-chain polymer nanoparticles via intra-chain cross-linking with dinuclear μ-halo(diene)Rh(I) complexes

An approach towards the expansion of Rh(I)-containing single-chain polymer nanoparticles (SCNPs) using linear polymers and μ-halo(diene)Rh(I) dimers as cross-linkers in high dilution was explored. Initially, the effects of utilizing different anionic ligands, i.e., halides, together with various labile alkene ligands, such as ethylene, 1,5-cyclooctadiene and 1,5-hexadiene, on the stability and activity of the resulting Rh(I) cross-linking complexes were examined. While the ethylene complexes for bromide and iodide bridges resulted too unstable and the 1,5-cyclooctadiene ligand produced inert complexes, the 1,5-hexadiene ligands provided the proper equilibrium of stability and lability to achieve efficient polymer folding. Thus, a range of new organometallic nanoparticles could be obtained via a direct exchange between the 1,5-hexadiene labile ligands of the Rh(I) complexes, and the corresponding 1,5-hexadiene elements present in ROMP derived 1,5-polycyclooctadiene (PCOD) and 1,4-polybutadiene (PBD). Notably, SEC analysis of the single-chain nanoparticles both for PCOD and PBD revealed the expected decrease in the hydrodynamic radius (Rh) of the parent polymer, indicating that other anions can also be used as elements in the cross-linking moieties to form these organometallic nanoparticles. Moreover, all of the Rh-SCNPs displayed intrinsic semi-conductivities in the range of similar undoped organic conjugated polymers, expanding the possible uses of this methodology for many applications.

Single-Crystal-to-Single-Crystal Transformations of Metal-Organic-Framework-Supported, Site-Isolated Trigonal-Planar Cu(I) Complexes with Labile Ligands.

Transition-metal complexes bearing labile ligands can be difficult to isolate and study in solution because of unwanted dinucleation or ligand substitution reactions. Metal-organic frameworks (MOFs) provide a unique matrix that allows site isolation and stabilization of well-defined transition-metal complexes that may be of importance as moieties for gas adsorption or catalysis. Herein we report the development of an in situ anion metathesis strategy that facilitates the postsynthetic modification of Cu(I) complexes appended to a porous, crystalline MOF. By exchange of coordinated chloride for weakly coordinating anions in the presence of carbon monoxide (CO) or ethylene, a series of labile MOF-appended Cu(I) complexes featuring CO or ethylene ligands are prepared and structurally characterized using X-ray crystallography. These complexes have an uncommon trigonal planar geometry because of the absence of coordinating solvents. The porous host framework allows small and moderately sized molecules to access the isolated Cu(I) sites and displace the "place-holder" CO ligand, mirroring the ligand-exchange processes involved in Cu-centered catalysis.

Routes to High-Performing Ruthenium-Iodide Catalysts for Olefin Metathesis: Ligand Lability Is Key to Efficient Halide Exchange.

Clean, high-yielding routes are described to ruthenium–diiodide catalysts that were recently shown to enable high productivity in olefin metathesis. For the second-generation Grubbs and Hoveyda catalysts (GII: RuCl2(H2IMes)(PCy3)(=CHPh); HII: RuCl2(H2IMes)(=CHAr), Ar = C6H4-2-OiPr), slow salt metathesis is shown to arise from the low lability of the ancillary PCy3 or ether ligands, which retards access to the four-coordinate intermediate required for efficient halide exchange. To exploit the lability of the first-generation catalysts, the diiodide complex RuI2(PCy3)(=CHAr) HI-I2 was prepared by treating “Grubbs I” (RuCl2(PCy3)2(=CHPh), GI) with NaI, H2C=CHAr (1a), and a phosphine-scavenging Merrifield iodide (MF-I) resin. Subsequent installation of H2IMes or cyclic (alkyl)(amino)carbene (CAAC) ligands afforded the second-generation iodide catalysts in good to excellent yields. Given the incompatibility of the nitro group with a free carbene, the iodo-Grela catalyst RuI2(H2IMes)(=CHAr′) (nG-I2: Ar′ = C6H3-2-OiPr-4-NO2) was instead accessed by sequential salt metathesis of GI with NaI, installation of H2IMes, and finally cross-metathesis with the nitrostyrenyl ether H2C=CHAr′ (1b), with MF-I as the phosphine scavenger. The bulky iodide ligands improve the selectivity for macrocyclization in ring-closing metathesis.

Stereogenic-at-Iron Catalysts with a Chiral Tripodal Pentadentate Ligand

A class of stereogenic-at-iron catalysts is introduced and applied to asymmetric 3d-transition metal catalysis. The pentadentate coordination of a tripodal ligand creates a stereogenic iron center, while an isopropyl group in the ligand backbone serves as a chiral lever to thermodynamically favor one diastereomer (>20:1 dr) of the obtained iron complexes. The coordination sphere is completed with a labile acetonitrile ligand. Ligand coordination and dynamics were studied by NMR spectroscopy. A modular design of the tripodal ligand enables the convenient implementation of different modifications, which have been incorporated and investigated in this work. The catalytic performance of the obtained complexes was evaluated in the ring contraction of isoxazoles to chiral 2H-azirines in up to 99% yield and with up to 93% ee and features a remarkably high catalytic activity with up to 10,000 turnover numbers (TON).

Oxo versus Sulfido Coordination at Tungsten: A Spectroscopic and Correlated Ab Initio Electronic Structure Study.

The tungsten ion that resides at the active site of a unique class of enzymes only found in esoteric hyperthermophilic archaea bacteria is known to possess at least one terminal chalcogenide ligand. The identity of this as either an oxo or sulfido (or both) is difficult to ascertain from structural studies; therefore, small-molecule analogues are developed to calibrate and substantiate spectroscopic signatures obtained from native proteins. The electronic structures of Tp*WECl2 (E = O, S; Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate) have been scrutinized using electronic, electron paramagnetic resonance (EPR), and X-ray absorption spectroscopy to assess the impact of terminal chalcogen on the adjacent cis chloride ligands. Examination at the Cl K-edge provides a direct probe of the bonding and therein lability of these chloride ligands, and in conjunction with density functional theoretical and multireference calculations reveals greater bond covalency in Tp*WOCl2 compared to Tp*WSCl2. The computational model and electronic structure assignment are corroborated by the reproduction of spin-Hamiltonian parameters, whose magnitude is dominated by the sizeable spin-orbit coupling of tungsten.

Redox Potential and Crystal Chemistry of Hexanuclear Cluster Compounds.

Most of TM6-cluster compounds (TM = transition metal) are soluble in polar solvents, in which the cluster units commonly remain intact, preserving the same atomic arrangement as in solids. Consequently, the redox potential is often used to characterize structural and electronic features of respective solids. Although a high lability and variety of ligands allow for tuning of redox potential and of the related spectroscopic properties in wide ranges, the mechanism of this tuning is still unclear. Crystal chemistry approach was applied for the first time to clarify this mechanism. It was shown that there are two factors affecting redox potential of a given metal couple: Lever’s electrochemical parameters of the ligands and the effective ionic charge of TM, which in cluster compounds differs effectively from the formal value due to the bond strains around TM atoms. Calculations of the effective ionic charge of TMs were performed in the framework of bond valence model, which relates the valence of a bond to its length by simple Pauling relationship. It was also shown that due to the bond strains the charge depends mainly on the atomic size of the inner ligands.

Unraveling the Guest-Induced Switchability in the Metal-Organic Framework DUT-13(Zn)*.

The switching mechanism of the flexible framework Zn4O(benztb)1.5 (benztb=N,N,N’,N’‐benzidine tetrabenzoate), also known as DUT‐13, was studied by advanced powder X‐ray diffraction (PXRD) and gas physisorption techniques. In situ synchrotron PXRD experiments upon physisorption of nitrogen (77 K) and n‐butane (273 K) shed light on the hitherto unnoticed guest‐induced breathing in the MOF. The mechanism of contraction is based on the conformationally labile benztb ligand and accompanied by a reduction in specific pore volume from 2.03 cm3 g−1 in the open‐pore phase to 0.91 cm3 g−1 in the contracted‐pore phase. The high temperature limit for adsorption‐induced contraction of 170 K, determined by systematic temperature variation of methane adsorption isotherms, indicates that the DUT‐13 framework is softer than other mesoporous MOFs like DUT‐49 and does not support the formation of overloaded metastable states required for negative gas‐adsorption transitions.

Recent Advances in Ligand Design and Engineering in Lead Halide Perovskite Nanocrystals

Lead halide perovskite (LHP) nanocrystals (NCs) have recently garnered enhanced development efforts from research disciplines owing to their superior optical and optoelectronic properties. These materials, however, are unlike conventional quantum dots, because they possess strong ionic character, labile ligand coverage, and overall stability issues. As a result, the system as a whole is highly dynamic and can be affected by slight changes of particle surface environment. Specifically, the surface ligand shell of LHP NCs has proven to play imperative roles throughout the lifetime of a LHP NC. Recent advances in engineering and understanding the roles of surface ligand shells from initial synthesis, through postsynthetic processing and device integration, finally to application performances of colloidal LHP NCs are covered here.

Cyclobutadiene cobalt complexes as catalysts for insertion of diazo compounds into X–H bonds

Novel cyclobutadiene cobalt complex with labile naphthalene ligand [(C4Et4)Co(C10H8)]PF6 catalyzes the insertion of ethyl diazoacetate into X–H bonds giving the corresponding products in 15–75% yields. The reaction proceeds with primary and secondary aliphatic amines, hydrosilanes and triethylamine borane but not with anilines and alcohols.

Cyclobutadiene cobalt complexes as catalysts for insertion of diazo compounds into X–H bonds

Novel cyclobutadiene cobalt complex with labile naphthalene ligand [(C 4 Et 4 )Co(C 10 H 8 )]PF 6 catalyzes the insertion of ethyl diazoacetate into X–H bonds giving the corresponding products in 15–75% yields. The reaction proceeds with primary and secondary aliphatic amines, hydrosilanes and triethylamine borane but not with anilines and alcohols.

Postsynthetic Modification of Half-Sandwich Ruthenium Complexes by Mechanochemical Synthesis

A mild and environmentally friendly method to synthesize half-sandwich ruthenium complexes through the Wittig reaction between an aldehyde-tagged half-sandwich ruthenium complex and phosphorus ylide mechanochemically is reported herein. The mechanochemical synthesis of valuable half-sandwich ruthenium complexes resulted in a fast reaction, good yield with simple workup, and the avoidance of harsh reaction conditions and organic solvents. The synthesized half-sandwich ruthenium complexes exhibited high catalytic activity for transfer hydrogenation of ketones using 2-propanol as the hydrogen source and solvent. Density functional theory was carried out to propose a mechanism for the transfer hydrogenation process. The modeling suggests the importance of the labile p-cymene ligand in modulating the reactivity of the catalyst.