Six-membered N-heterocyclic Carbene Research Articles

Synthesis of Six-Membered N-Heterocyclic Carbene Precursors Based on Camphor.

The endo- and exo-N-heterocyclic carbene precursors based on camphor were prepared diastereoselectively in five synthetic steps starting from (1S)-(+)-ketopinic acid. The obtained N-heterocyclic carbene precursors were investigated in an asymmetric benzoin reaction. All new compounds were fully characterized, and the absolute configurations were determined via X-ray diffraction and NOESY measurements.

Mechanistic insights into the insertion and addition reactions of group 13 analogues of the six-membered N-heterocyclic carbenes: interplay of electrophilicity, basicity, and aromaticity governing the reactivity.

Three fundamental concepts (aromaticity/basicity/electrophilicity), being heavily used in modern chemistry, have been applied in this work to study the chemical reactivity of six-membered-ring group 13 N-heterocyclic carbenes (G13-6-Rea; G13 = group 13 elements) using density functional theory (BP86-D3(BJ)/def2-TZVP). G13-6-Rea is isolobal to benzene. Two model reactions have been used in the present study: the insertion reaction of G13-6-Rea with methane and the [1 + 2] cycloaddition reaction of G13-6-Rea with ethene. Our theoretical analysis reveals that the chemical reactivity of B-6-Rea, Al-6-Rea, and Ga-6-Rea is governed by their HOMO (the sp2-σ lone pair orbital on the G13 element), and thus they can be considered nucleophiles. Conversely, the chemical behavior of In-6-Rea and Tl-6-Rea is determined by their LUMO (the vacant p-π orbital on the G13 element), and thus they can be considered electrophiles. On the basis of the VBSCD (valence bond state correlation diagram) model and ASM (activation strain model), this theoretical evidence demonstrates that the origin of activation barriers for the above model reactions is due to the atomic radius of the pivotal group 13 element in the six-membered-ring of G13-6-Rea. Accordingly, our theoretical conclusions suggest that the lower the atomic number and the smaller the atomic radius of the G13 atom, the higher the aromaticity of the six-membered-ring of G13-6-Rea and the smaller the singlet–triplet energy splitting ΔEst of this N-heterocyclic carbene analogue, which will facilitate its chemical reactions. The theoretical findings originating from this study allow many predictions in experiments to be made.

Reactive Extrusion and Magnesium (II) N-Heterocyclic Carbene Catalyst in Continuous PLA Production.

Reactive extrusion and magnesium (II) N-heterocyclic carbene catalyst are successfully employed in continuous polylactide synthesis. The possibility of using six-membered N-heterocyclic carbene adducts to act as efficient catalysts towards the sustainable synthesis of poly(l-lactide) through ring-opening polymerization of l-lactide (LA) is first investigated in bulk batch reactions. Under optimized solvent-free conditions, polylactide (PLA) of moderate to high molecular weights and excellent optical activities are successfully achieved. These promising results are further applied in the continuous production of PLA in an extruder.

Access to a Cationic, Electron-Poor N-Heterocyclic Carbene with a Quinazolinium Core by Postsynthetic Modification of Related Neutral Derivatives

Derivatives of cationic six-membered N-heterocyclic carbene G with a quinazolinium scaffold are easily obtained by abstraction of an alcoholate group from related neutral precursors which are easily accessible. On the basis of this route, chalcogene adducts and metal complexes of G, which is a benzo-anellated pyrimidiniumylidene, could be prepared. Evaluation of the ligand properties by IR and 77Se NMR spectroscopy indicate that cationic carbene G is a much more powerful π-acceptor (δ(77Se): 768 ppm) and a significantly weaker overall donor (TEP: 2073 cm–1) than related neutral carbene 4 (361 ppm, 2054 cm–1). DFT calculations provide a rationale for these experimental observations. AuCl complexes of both carbenes were used as catalysts for the cyclization of a propargylamide to a methyleneoxazoline. The complex containing the cationic carbene featured a much higher activity.

Distinct Palladium(II) Carbene Complexes Supported by Six-Membered 1,3-Disubstituted Permidin-2-ylidene, Six-Membered N-Heterocyclic Carbenes.

The first synthesis, isolation, and characterization of permidin-2-ylidene complexes of Pd(II) is reported with entry resulting from either a direct reaction with isolable six-membered N-heterocyclic carbene or from the enetetramine, arising from dimerization of the carbene. Furthermore, a simplified method to prepare N,N′-disubstituted perimidinium bromide salts, precursors to 1,3-disubstituted perimidin-2-ylidene, was achieved using ammonium bromide as a source of weak acid. Through synthesis and nuclear magnetic resonance spectroscopic analysis of a carbene-phosphinidine adduct, an interrogation of the fundamental π-bonding ability of 1,3-diisopropylperimidin-2-ylidene revealed this interaction to be weak and of a similar order to unsaturated imidazol-2-ylidenes.

Nickel, Ruthenium, and Rhodium NCN-Pincer Complexes Featuring a Six-Membered N-Heterocyclic Carbene Central Moiety and Pyridyl Pendant Arms

NCN pincer ligand precursor 1·HX (X = Cl, PF6), having a six-membered N-heterocyclic carbene central moiety and pyridyl pendant arms, was prepared via N–C cross-coupling of 2-bromo-6-tert-butylpyridine with propane-1,3-diamine, followed by ring closure with triethylorthoformate. The free ligand 1 was not accessible via deprotonation, yet its copper(I) complex 2 was prepared by reacting 1·HCl with CuI and potassium hexamethyldisilazide. It was used further as a transmetalation agent to prepare nickel(II) and ruthenium(II) dihalide NCN-pincer complexes 3a, 4a, and 4b, featuring a distorted square-pyramidal geometry at the metal, with the carbene ligand in the axial position. The rhodium(III) NCN-pincer complex 6b was obtained from 2 and [Rh(cod)Cl]2 via transmetalation followed by oxidation with Cu(I) in THF. The rhodium(III) NCC-pincer complex 9b was prepared under similar conditions in acetonitrile, where a spontaneous rollover cyclometalation occurred. Complex 9b has a distorted octahedral geometry, with the acetonitrile ligand trans to the carbene. Very short Ru–CNHC and Rh–CNHC bonds were measured in complexes 4a, 4b, and 9b. Halogen exchange was observed by 1H and 13C NMR spectroscopy in both ruthenium and rhodium systems during the transmetalation stage, and the purification was accomplished by pushing the respective equilibrium with excess halide.

Probing the Effect of Six-Membered N-Heterocyclic Carbene—6-Mes—on the Synthesis, Structure and Reactivity of Me2MOR(NHC) (M = Ga, In) Complexes

The investigation of the reactivity of six membered N-heterocyclic carbene 1,3-bis(2,4,6-trimethylphenyl)-3,4,5,6-tetrahydropyrimidin-1-ylidene (6-Mes) towards dialkylgallium and dialkylindium alkoxides/aryloxides has shown that both steric hindrances and donor properties of 6-Mes significantly influence the strength of M–C6-Mes bond, as well as the formation, structure and reactivity of Me2MOR(6-Mes) (M = Ga, In) complexes. While the reactions of simple dimethylgallium alkoxides with 6-Mes lead to the formation of stable monomeric Me2Ga(OCH2CH2OMe)(6-Mes) (1) and Me2GaOMe(6-Mes) complexes, the analogous Me2InOR(6-Mes) are unstable and disproportionate to methylindium alkoxides and Me3In(6-Mes) (2). The use of bulky alkoxide ligand—OCPh2Me or aryloxide ligand—OC6H4OMe allowed for the synthesis of stable Me2M(OCPh2Me)(6-Mes) (M = Ga (3) and In (4)) as well as Me2M(OC6H4OMe)(6-Mes) (M = Ga (5) and In (6)). The structures of 1–6 have been determined using both spectroscopic methods in solution and X-ray diffraction studies, which confirmed the effect of both steric hindrances and donor properties of 6-Mes on their structure and catalytic properties in the ring-opening polymerization (ROP) of rac-lactide.

Synthesis of Different Classes of Six-Membered Gold(I) NHC Complexes by the Isonitrile Route

Different types of six-membered N-heterocyclic gold carbene complexes were prepared by using gold(I) isonitrile complexes as precursors in combination with suitably functionalized amines. The simple procedures provide an easy access to not only unsymmetrically substituted saturated carbene complexes but rarely reported types of carbene complexes such as six-membered N-heterocyclic oxo-carbene complexes, and six-membered partly unsaturated ligands can be obtained following the strategy.

Ammonia Activation by a Nickel NCN-Pincer Complex featuring a Non-Innocent N-Heterocyclic Carbene: Ammine and Amido Complexes in Equilibrium.

A Ni(0)-NCN pincer complex featuring a six-membered N-heterocyclic carbene (NHC) central platform and amidine pendant arms was synthesized by deprotonation of its Ni(II) precursor. It retained chloride in the square-planar coordination sphere of nickel and was expected to be highly susceptible to oxidative addition reactions. The Ni(0) complex rapidly activated ammonia at room temperature, in a ligand-assisted process where the carbene carbon atom played the unprecedented role of proton acceptor. For the first time, the coordinated (ammine) and activated (amido) species were observed together in solution, in a solvent-dependent equilibrium. A structural analysis of the Ni complexes provided insight into the highly unusual, non-innocent behavior of the NHC ligand.

Reaching for two new stable ambiphilic quinoline-derivedN-heterocyclic carbenes at DFT level

A detailed investigation on the thermodynamic and kinetic stability of four carbenic tautomers of quinoline 1, including quinoline-2-ylidene 2, quinoline-3-ylidene 3, quinoline-4-ylidene 4, and 3,4-dihydroquinoline-4-ylidene 5, reveals that singlet planar six-membered ring N-heterocyclic carbenes (NHCs) 2 and 4 have less stability than Arduengo type NHC but seems to have enough conceivably for reaching at B3LYP/aug-cc-pVTZ//B3LYP/6–31+G* and B3LYP/6–311++G**//B3LYP/6–31+G* levels. All these six-membered NHCs are extremely ambiphilic with the more nucleophilic and electrophilic characters compared to the Arduengo type one. The aromaticity of singlet 2 and 4 is a significant contributor to their stability which is confirmed through their Nucleus-independent chemical shift(1)zz values. Finally, among 2–5, the normal NHC 2 is thermodynamically preferred but the remote NHC 4 is kinetically proffered over the other isomeric carbenes. The effects of different N- or C-substituted NHCs of 2 are studied using appropriate isodesmic reactions. The trimethylsilyl substituent exhibits slightly larger carbene stabilization in quinoline-derived NHCs than the pyridine analogue. © 2014 Wiley Periodicals, Inc.

ChemInform Abstract: Enantioselective Addition of Silicon Nucleophiles to Aldimines Using a Preformed NHC‐Copper(I) Complex as the Catalyst.

A remaining major challenge in the asymmetric addition of silicon nucleophiles to typical prochiral acceptors, the enantioselective 1,2-addition to aldimines, is addressed. Activation of the SiB bond in the silicon pronucleophile by a copper(I) alkoxide with McQuade's chiral six-membered N-heterocyclic carbene as a supporting ligand releases the silicon nucleophile, which adds to various aldimines with high levels of enantioselectivity. The new method provides a catalytic asymmetric access to α-silylated amines.

Enantioselective Addition of Silicon Nucleophiles to Aldimines Using a Preformed NHC–Copper(I) Complex as the Catalyst

A remaining major challenge in the asymmetric addition of silicon nucleophiles to typical prochiral acceptors, the enantioselective 1,2-addition to aldimines, is addressed. Activation of the SiB bond in the silicon pronucleophile by a copper(I) alkoxide with McQuade's chiral six-membered N-heterocyclic carbene as a supporting ligand releases the silicon nucleophile, which adds to various aldimines with high levels of enantioselectivity. The new method provides a catalytic asymmetric access to α-silylated amines.

Spiro-fused six-membered N-heterocyclic carbene: a new scaffold toward unique properties and activities.

A six-membered N-heterocyclic carbene fused with a spiro-scaffold is designed. The new NHC shows stronger σ-donation ability than typical 5-membered NHCs. This property leads to interesting reactivities of this spiro-fused six-membered NHC. For example, the NHC-BF3 Lewis pair complex can be readily prepared by using LiBF4 as the BF3 source, or through a direct bond-reconstruction of the tetrafluoroborate salt NHC·HBF4.

Ring-Expanded N-Heterocyclic Carbene Complexes of Rhodium with Bifluoride, Fluoride, and Fluoroaryl Ligands

Thermolysis of Rh(PPh3)4H in the presence of the six-membered N-heterocyclic carbene 1,3-bis(2-propyl)-3,4,5,6-tetrahydropyrimidin-2-ylidine (6-iPr) gave the monocarbene complex Rh(6-iPr)(PPh3)2H as a 1:2 mixture of the cis- and trans-phosphine isomers 1a and 1b. This same isomeric mixture was formed as the ultimate product from treating Rh(PPh3)3(CO)H with 6-iPr at room temperature, although pathways involving both CO and PPh3 loss were observed at initial times. Treatment of 1a/1b with Et3N·3HF generated the bifluoride complex cis-Rh(6-iPr)(PPh3)2(FHF) (2a), which upon stirring with anhydrous Me4NF was converted to the rhodium fluoride complex cis-Rh(6-iPr)(PPh3)2F (3a). Thermolysis of 1a/1b with C6F6 resulted in C–F bond activation to afford a mixture of 3a and the pentafluorophenyl complex trans-Rh(6-iPr)(PPh3)2(C6F5) (5b). Complexes 1b, 2a, 3a, and 5b were structurally characterized.

Understanding the lability of a trans bound pyridine ligand in a saturated six-membered N-heterocyclic carbene based (NHC)PdCl2(pyridine) type complex: A case study

The lability of a trans “throwaway” pyridine ligand in a PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed saturated six-membered N-heterocyclic carbene complex namely, (1,3-difurfuryl tetrahydropyrimidin-2-ylidene)PdCl2(pyridine) (2), was investigated with the aid of a combined experimental and computational studies. In this regard, a new saturated six-membered N-heterocyclic carbene complex 2 was synthesized from the reaction of 1,3-difurfuryl tetrahydropyrimidin-1-ium chloride (1) with PdCl2 in the presence of KN(SiMe3)2 as a base in pyridine. Significantly enough, the complex 2 represents the first structurally characterized example of a PEPPSI themed trans-(NHC)PdX2(pyridine) (X=halide) type of a complex supported over a saturated six-membered N-heterocyclic carbene ligand. The lability of a trans “throwaway” pyridine ligand in 2 was probed by a displacement reaction with PPh3 to yield the corresponding phosphine analog, (1,3-difurfuryl tetrahydropyrimidin-2-ylidene)PdCl2(PPh3) (3), at room temperature under ambient condition. Detailed density functional theory (DFT) studies aimed at understanding the lability of the trans “throwaway” pyridine ligand in 2, against a PPh3 ligand yielding 3, points towards a kinetic factor rather than a thermodynamic one as a reason for the lability of the pyridine in 2.

Electronic Structure of Six-Membered N-Heterocyclic Carbenes and Its Heavier Analogues: Reactivity of the Lone Pair versus the Exocyclic Double Bond

Electronic structure of the six-membered N-heterocyclic carbene, silylene, germylene, and stannylene having an exocyclic double bond at the C3 carbon atom as well as the relative reactivity of the lone-pair on the divalent group 14 element and the exocyclic double bond have been studied at the BP86 level of theory with a TZVPP basis set. The geometrical parameters, NICS values, and NBO population analysis indicate that these molecules can be best described as the localized structure 1X(a), where a trans-butadiene (C1-C2-C3-C4) unit is connected with diaminocarbene (N1-X-N2) via N-atoms having a little contribution from the delocalized structure 1X(b). The proton affinity at X is higher than at C4 for 1C, and a reverse trend is observed for the heavier analogues. Hence, the lone pair on a heavier divalent Group 14 element is less reactive than the exocyclic double bond. This is consistent with the argument that, even though the parent six-membered carbene and its heavier analogues are nonaromatic in nature, the controlled and targeted protonation can lead to either the aromatic system 3X having a lone pair on X or the nonaromatic system 2X with readily polarizable C3-C4 π-bond. The energetics for the reaction with BH(3) and W(CO)(6) further suggest that both the lone pair of Group 14 element and the exocyclic double bond can act as Lewis basic positions, although the reaction at one of the Lewis basic positions in 1X does not considerably influence the reactivity at the other. The protonation and adduct formation with BH(3) and W(CO)(5) at X lead to nonaromatic systems whereas similar reactions at C4 lead to aromatic systems due to π-bond polarization at C3-C4. The degree of polarization of the C3-C4 π-bond is maximum in the protonated adduct and reduces in the complexes formed with BH(3) and W(CO)(5).

Dihydrogen Activation by Frustrated Carbene-Borane Lewis Pairs: An Experimental and Theoretical Study of Carbene Variation

A variety of Lewis acid-base pairs consisting of tris(pentafluorophenyl)borane, B(C(6)F(5))(3), in combination with sterically demanding five- and six-membered N-heterocyclic carbenes (NHCs) of the imidazolin-2-ylidene, imidazolidin-2-ylidene, and tetrahydropyrimidin-2-ylidene types were investigated with respect to their potential to act as frustrated Lewis pairs (FLP) by reaction with dihydrogen (H(2)) and tetrahydrofuran (THF). A sufficient degree of "frustration" was usually established by introduction of a 1,3-di-tert-butyl or 1,3-diadamantyl carbene substitution pattern, which allows an unquenched acid-base reactivity and thus leads to heterolytic dihydrogen activation and ring-opening of THF. In contrast, 1,3-bis(2,6-diisopropylphenyl)-substituted carbenes showed ambiguous behavior, and the corresponding five-membered imidazolin-2-ylidene formed a stable carbene-B(C(6)F(5))(3) adduct, whereas fast C-F activation and formation of a zwitterionic pyrimidinium-fluoroborate was observed for the six-membered tetrahydropyrimidin-2-ylidene. A stable adduct was also isolated for the combination of the acyclic carbene bis(diisopropylamino)methylene with B(C(6)F(5))(3), and consequently no reactivity toward H(2) and THF was observed. To rationalize the reactivity of the carbene-borane Lewis pairs, the thermodynamics of adduct formation with B(C(6)F(5))(3) were calculated for 10 different carbenes; the stability (or instability) of these adducts can be used as a good measure of the degree of "frustration".

Design of a New Six-Membered NHC Ligand for Copper-Catalyzed β-Borylation

The ligand design incorporates a six-membered N-heterocyclic carbene, providing a rigid chiral environment. Both the copper(I) complex and the precursor salt are bench stable solids.

Ring-Expanded N-Heterocyclic Carbene Complexes of Ruthenium

The six-membered N-heterocyclic carbene 1,3-bis(2,4,6-trimethylphenyl)-3,4,5,6-tetrahydropyrimidin-2-ylidene (6-Mes) reacts with Ru(PPh3)3(CO)HF to afford Ru(6-Mes)(PPh3)(CO)HF (1), which is converted to the five-coordinate C−H activated carbene complex Ru(6-Mes)′(PPh3)(CO)H (2) upon treatment with Et3SiH. The hydride chloride precursor Ru(PPh3)3(CO)HCl affords a mixture of products with 6-Mes, but reacts cleanly with 1,3-bis(isopropyl)-3,4,5,6-tetrahydropyrimidin-2-ylidene (6-iPr) to give the six-coordinate activated complex Ru(6-iPr)′(PPh3)2(CO)H (3a), in which the hydride is trans to the methylene arm of the activated NHC. This complex isomerizes in solution with ΔH⧧ and ΔS⧧ values of 98.2 ± 4.6 kJ mol−1 and 15.5 ± 14.5 J mol−1 K−1. The major product from the isomerization, 3b, in which the hydride ligand is trans to carbene, can be made directly by reaction of 6-iPr with Ru(PPh3)3(CO)H2.

A stable crystalline N-heterocyclic carbene with a 1,1′-ferrocenediyl backbone

A stable six-membered N-heterocyclic carbene with a redox-active ferrocene-based backbone was prepared, characterised by X-ray crystallography and utilised as a ligand for the preparation of expected and unexpected metal complexes.