Carbene Complexes in Organic Synthesis [New Synthetic Methods (47)]

Transition metals are finding increasing use in organic synthesis on the borderline between “organic” and “inorganic” chemistry. Advantage is taken thereby of the fact that metal-induced CC bond formation often takes place with remarkable selectivity. The rapid development that has taken place in this area of chemistry is clearly demonstrated by the carbene complexes, examples of which are now known for almost all transition elements, and which have transformed from organometallic curiosities into synthetically useful reagents in less than two decades since the first studies of E. O. Fischer. They are not only suitable as carbene-transfer agents but also undergo interesting cycloadditions with other ligands in the co-ligand sphere. Their manipulation requires techniques no more complicated than those for Grignard reactions. Thus, carbene complexes can also be used in the synthesis of natural products such as vitamins or antibiotics.     

Ketenimine Complexes from Carbene Complexes and Isocyanides: Versatile Building Blocks for Carbocycles and N-Heterocycles [New Synthetic Methods (74)]

Ketenimine complexes are readily available in great variety by reaction of isocyanides with carbene complexes. They have proven to be useful building blocks in new synthetic approaches to carbocyclic and N-heterocyclic four-, five-, and six-membered rings. The reactions involve new metal-induced bond formation patterns of the ketenimine ligands, which can be influenced across a wide range by varying the following five parameters: the metal, the ligands, and the three substituents on the N?C?C unit.     

Regio- and Diastereoselective Aldol Products through Three-Component Coupling Reactions of Difluoroboroxy Fischer Carbene Molybdenum Complexes

The reaction of difluoroboroxy Fischer carbene complexes , vinyl ketones, and aldehydes leads to the regioselective formation of aldol-like products (see reaction scheme). The reaction also shows a high degree of diastereofacial selectivity when chiral aldehydes are used. These results show that this is a very attractive process since the regioselective formation of aldols from nearly symmetrical ketones still remains an unsolved problem.     

Dötz Benzannulation Reactions: Heteroatom and Substituent Effects in Chromium Fischer Carbene Complexes

We have carried out a theoretical investigation of the Dötz reaction between acetylene and a series of chromium Fischer‐type carbenes [(CO)₅Cr?C(X)R] with different representative substituents (R=CH?CH₂, Ph) and heteroatom ligands (X=OH, NH₂, OCH₃, N(CH₃)₂) by using density functional theory with the B3LYP functional. We have studied the Dötz and chromahexatriene mechanisms of benzannulation and also the reaction mechanism leading to cyclopentannulation. For the benzannulation, it was found that the most likely mechanism in the case of vinylcarbenes is the chromahexatriene route, whereas for phenylcarbenes, the Dötz route via a ketene intermediate is clearly the most favorable. The reactions leading to the cyclopentannulated and benzannulated products are more exothermic with vinylcarbenes than with phenylcarbenes and also more exothermic with alkoxycarbenes than with aminocarbenes. The relative stability of the cyclopentannulated products as compared with the benzannulated products increases for bulkier X substituents and on going from alkoxy‐ to aminocarbenes. The kinetic data concurs with the experimental product distribution found for vinylcarbenes, by which mainly benzannulated products are obtained, and dimethylaminophenylcarbenes, which lead exclusively to cyclopentannulated adducts.     

Group 6 carbene complexes derived from lithiated azoles and the crystal structure of a molybdenum thiazolinylidene complex

Fischer-type (alkoxy)azolyl carbene complexes and Öfele–Lappert-type azolylinylidene complexes were synthesised by reaction of 1-phenylpyrazol-3-yllithium, 4-methylthiazol-2-yllithium, benzothiazol-2-yllithium, 1-methylimidazol-2-yllithium with M(CO)₅L (L=CO, THF or Cl⁻; M=Cr, Mo or W) and subsequent alkylation with CF₃SO₃CH₃. The alkylation of Fischer-type carbene complexes containing an azolyl as the organic substituent proceeded via ring opening of tetrahydrofuran. When the alkylation is carried out in THF, the carbocation CH₃O(CH₂)₄⁺ acts as an electrophile. Protonation rather than alkylation of coordinated imidazolyl furnished cyclic imine complexes. Changing the donor atom of a coordinated thiazole from N to C by deprotonation and alkylation afforded a carbene complex.     

A New Class of Ruthenium Carbene Complexes: Synthesis and Structures of Highly Efficient Catalysts for Olefin Metathesis

Cationic Ru^II carbene complexes with tBu₂PCH₂PtBu₂ (dtbpm) as a chelating ligand, which are accessible by chloride abstraction from neutral precursors [(κ²-dtbpm)Cl₂Ru=CHR] with trimethylsilyl triflate, are established as highly efficient ring opening metathesis polymerization catalysts (see scheme). Solv=solvent.     

Bis(N-Heterocyclic Carbene) Manganese(I) Complexes: Efficient and Simple Hydrogenation Catalysts

The use of bis(NHC) manganese(I) complexes 3 as catalysts for the hydrogenation of esters was investigated. For that purpose, a series of complexes has been synthesized via an improved two step procedure utilizing bis(NHC)-BEt₃ adducts. By applying complexes 3 with KHBEt₃ as additive, various aromatic and aliphatic esters were hydrogenated successfully at mild temperatures and low catalyst loadings, highlighting the efficiency of the novel catalytic system. The versatility of the developed catalytic system was further demonstrated by the hydrogenation of other substrate classes like ketones, nitriles, N-heteroarenes and alkenes. Mechanistic experiments and DFT calculations indicate an inner sphere mechanism with the loss of one CO ligand and reveal the role of BEt₃ as cocatalyst.     

C−C Bond Formation between Fischer Carbene Complexes and Allylic Alcohols by a [3,4] Sigmatropic Rearrangement Promoted by a [1,2] M(CO)5 Shift

A [1,2] M(CO) ₅ shift promotes a [3,4] sigmatropic rearrangement after the addition of allylic alcohols to Fischer alkenylcarbene complexes of tungsten or chromium in the presence of alkoxide ions. This opens a new synthetic route to the adducts 1 . The reaction is also applicable to propargylic alcohols. [M]=Mo(CO)₅, W(CO)₅.     

Copper-Catalysed Rearrangement of Cyclic Ethynylethylene Carbonates: Synthetic Applications and Mechanistic Studies

Transition-metal-catalysed reactions of cyclic ethynylethylene carbonates have been intensively studied because of their robustness in new bond formation and diversified molecule construction. Known reaction modes usually involve a substitution step occurring at either the propargylic or terminal alkyne positions. Here, we report an unprecedented reaction pattern in which cyclic ethynylethylene carbonates first undergo a rearrangement to release allenal intermediates, which subsequently react with diverse nucleophiles to furnish synthetically useful allylic and propargylic allenols, phosphorus ylides, and cyclopropylidene ketones through an addition process rather than a substitution pathway. The products enable various further transformations, and mechanistic studies and theoretical calculations reveal that the reaction does not proceed via a semipinacol type [1,2]-hydride shift, but through base-mediated deprotonation as the key step to induce the rearrangement.     

Biological and Catalytic Applications of Pd(II)-Indenyl Complexes Bearing Phosphine and N-Heterocyclic Carbene Ligands

A general synthetic entryway into novel cationic Pd(II) indenyl complexes bearing one alkyl/aryl phosphine and one N-heterocyclic carbene is reported. All metal complexes have been exhaustively characterized by spectroscopic and structural analyses, highlighting that the indenyl fragment has an hapticity intermediate between η³ and η⁵. Most of the target complexes are stable in solid state and in solution for a long time. Two different applications of these organopalladium compounds are proposed. Firstly, they have been tested as antiproliferative agents towards three different ovarian cancer cell lines, showing a cytotoxicity significantly higher than that of cisplatin, with a clear dependence on the nature of the coordinated phosphine. Moreover, the similar cytotoxicity towards cisplatin-sensitive and cisplatin-resistant cell lines suggests that these new palladium derivatives act with a different mechanism of action with respect to classical platinum-based drugs. Finally, the water-soluble palladium complexes bearing 1,3,5-triaza-7-phosphaadamantane (PTA) have demonstrated interesting catalytic performances in Suzuki–Miyaura coupling in aqueous media, being, inter alia, readily and efficiently recyclable.     

Exploring Molecular Complexity by N-Heterocyclic Carbene Organocatalysis: New Activation and Reaction Diversity

The development of catalytic synthetic approaches towards molecular complexity from simple materials continues to be an ultimate goal in synthetic chemistry. Over the past decades, N-heterocyclic carbene (NHC) organocatalysis has been extensively investigated to provide opportunities for a vast number of novel chemical transformations. Various activation modes and reactive intermediates enabled by NHC small-molecule catalysts, such as Breslow intermediates, (homo)enolates, acyl azoliums and their derived unsaturated azoliums exhibit great potential in the construction of complicated skeletons. This personal account will summarize our group's recent work in the exploration of new activation modes of NHC catalysis towards molecular complexity with a focus on the development and applications of NHC to achieve diversity and enantioselectivity in the preparation of functional molecules.     

The Electronic Structure and Photochemistry of Group 6 Bimetallic (Fischer) Carbene Complexes: Beyond the Photocarbonylation Reaction

The UV spectra of Group 6 metal carbene complexes bearing a CpM(CO)₃ (Cp=cyclopentadienyl) moiety bonded to the carbene carbon atom exhibit a redshift of the absorption maxima at higher wavelengths with respect to the parent monometallic complexes. This redshift is partly due to a higher occupation on the p_z atomic orbital of the carbene carbon atom. Time‐dependent DFT calculations accurately assign this band to a metal‐to‐ligand charge‐transfer transition, thus showing that the presence of a second metal center does not affect the nature of the transition. However, the photochemical reactivity of Group 6 metal carbene complexes bearing a CpM(CO)₃ moiety strongly depends on the nature of this metal fragment. A new photoslippage reaction leading to fulvenes occurs when Mn‐derived products 11 a , 11 b , and 12 a are irradiated (both Cr and W derivatives), whereas Re‐derived product 11 c behaves like standard Fischer complexes and yields the usual photocarbonylation products. A new photoreduction process occurring in the metallacyclopropanone intermediate is also observed for these complexes. Both computational and deuteration experiments support this unprecedented photoslippage process. The key to this differential photoreactivity seems to be the M–Cp back‐donation, which hampers the slippage process for Re derivatives and favors the carbonylation reaction.     

Synthesis of Polysubstituted Symmetrical BODIPYs via Fischer Carbene Complexes: Theoretical,Photophysical and Electrochemical Evaluation

A series of new symmetrical highly substituted BODIPYs 6 a – l was synthesized through a prefunctionalization approach in 35 %–89 % yields from the pyrrole core. This strategy allowed modulation of the substituents at the different positions based on the choice of Fischer's alkynyl carbenes, oxazolones and aldehydes used as precursors. The substituent variation at positions 2, 6, 3 and 5 had the greatest effect on the modulation of their photophysical properties such as absorption (λ_abs) and emission (λ_em) wavelengths, extinction coefficient (ϵ), quantum yields (ϕ), Stokes shifts (Δν), fluorescence decay, radiative (k_rad) and non-radiative (k_nr) constants and the CIE 1931 coordinates. Theoretical calculations allowed to corroborate the effect of the substituents of meso-position on the modification of the dihedral angles. Cyclic voltammetry studies revealed that the BODIPY series presents similar redox potential behavior, being electrochemically active even in successive cycles, which suggests that transport by diffusion is the dominant process.     

Catalytic Asymmetric Fluorination of Copper Carbene Complexes: Preparative Advances and a Mechanistic Rationale

The Cu-catalyzed reaction of substituted α-diazoesters with fluoride gives α-fluoroesters with ee values of up to 95 %, provided that chiral indane-derived bis(oxazoline) ligands are used that carry bulky benzyl substituents at the bridge and moderately bulky isopropyl groups on their core. The apparently homogeneous solution of CsF in C₆F₆/hexafluoroisopropanol (HFIP) is the best reaction medium, but CsF in the biphasic mixture CH₂Cl₂/HFIP also provides good results. DFT studies suggest that fluoride initially attacks the Cu- rather than the C-atom of the transient donor/acceptor carbene intermediate. This unusual step is followed by 1,2-fluoride shift; for this migratory insertion to occur, the carbene must rotate about the Cu−C bond to ensure orbital overlap. The directionality of this rotatory movement within the C₂-symmetric binding site determines the sense of induction. This model is in excellent accord with the absolute configuration of the resulting product as determined by X-ray diffraction using single crystals of this a priori wax-like material grown by capillary crystallization.