A General Concept for the Electronic and Steric Modification of 1-Metallacyclobuta-2,3-dienes: A Case Study of Group 4 Metallocene Complexes.

The synthesis of group 4 metal 1-metallacyclobuta-2,3-dienes as organometallic analogues of elusive 1,2-cyclobutadiene has so far been limited to SiMe3 substituted examples. We present the synthesis of two Ph substituted dilithiated ligand precursors for the preparation of four new 1-metallacyclobuta-2,3-dienes [rac-(ebthi)M] (M=Ti, Zr; ebthi=1,2-ethylene-1,10-bis(η5-tetrahydroindenyl)). The organolithium compounds [Li2(RC3Ph)] (1 b: R=Ph, 1 c: R=SiMe3) as well as the metallacycles of the general formula [rac-(ebthi)M(R1C3R2)] (2 b: M=Ti, R1=R2=Ph, 2 c: M=Ti, R1=Ph, R2=SiMe3; 3 b: M=Zr, R1=R2=Ph; 3 c: M=Zr, R1=Ph, R2=SiMe3) were fully characterised. Single crystal X-ray diffraction and quantum chemical bond analysis of the Ti and Zr complexes reveal ligand influence on the biradicaloid character of the titanocene complexes. X-band EPR spectroscopy of structurally similar Ti complexes [rac-(ebthi)Ti(Me3SiC3SiMe3)] (2 a), 2 b, and 2 c was carried out to evaluate the accessibility of an EPR active triplet state. Cyclic voltammetry shows that introduction of Ph groups renders the complexes easier to reduce. 13C CPMAS NMR analysis provides insights into the cause of the low field shift of the resonances of metal-bonded carbon atoms and provides evidence of the absence of the ß-C-Ti interaction.

Highly (regio)selective hydroformylation of olefins using self-assembling phosphines.

New phosphines with self-assembling 6-pyridinone moities were prepared, characterized, and examined in the hydroformylation of diverse olefins. Testing various known and novel ligands in the presence of [Rh(acac)(CO)2] under industrially relevant conditions, the hydroformylation of 1-octene proceeds best with 6,6'-(phenylphosphanediyl)bis(pyridin-2(1H)-one) (DPONP). Control experiments and modelling studies indicate dimerization of this ligand at higher temperatures (>100 °C). The optimal catalyst system is able to conserve high product linearity (>90%) for a broad range of olefins at industrially-employed temperatures at low ligand loading.

Efficient Hydrogenation of N-Heterocycles Catalyzed by NNP-Manganese(I) Pincer Complexes at Ambient Temperature.

Manganese-catalyzed hydrogenation reactions have aroused widespread interest in recent years. Among the catalytic systems described, especially PNP- and NNP-Mn pincer catalysts have been reported for the hydrogenation of aldehydes, ketones, nitriles, aldimines and esters. Furthermore, NNP-Mn pincer compounds are efficient catalysts for the hydrogenolysis of less reactive amides, ureas, carbonates, and carbamates. Herein, the synthesis and application of specific imidazolylaminophosphine ligands and the corresponding Mn pincer complexes are described. These new catalysts have been characterized and studied by a combination of experimental and theoretical investigations, and their catalytic activities have been tested in several hydrogenation reactions with good to excellent performance. Especially, the reduction of N-heterocycles can be performed under very mild conditions.

Atroposelective Ir-Catalyzed C-H Borylation of Phthalazine Heterobiaryls.

The atroposelective iridium-catalyzed borylation of menthyloxy-substituted phthalazine heterobiaryls with diborons is reported. Utilizing [Ir(OMe)(COD)]2/2-aminopyridine as a rarely used efficient catalyst system, the heterobiaryls were selectively borylated in the 2-position of the carbocycle, exclusively yielding only one of the atropisomers, depending on the substitution of the phthalazine with (+)-menthyl or (-)-menthyl moieties. Exemplary further functionalization of a borylated atropisomer demonstrated that nickel-catalyzed Suzuki-Miyaura cross-coupling with an aryl halide was able to provide stereoretention to a certain degree (up to 75% de).

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.

A Selective and General Cobalt-Catalyzed Hydroaminomethylation of Olefins to Amines.

A new cobalt catalyst is presented for the domino hydroformylation-reductive amination reaction of olefins. The optimal Co-tert-BuPy-Xantphos catalyst shows good to excellent linear-to-branched (n/iso) regioselectivity for the reactions of aliphatic alkenes with aromatic amines under mild conditions. This system is far more selective than traditional cobalt(I) catalysts and even better than most known rhodium catalysts.

Palladium-Catalyzed Cascade Carbonylation to α,ß-Unsaturated Piperidones via Selective Cleavage of Carbon-Carbon Triple Bonds.

A direct and selective synthesis of α,ß-unsaturated piperidones by a new palladium-catalyzed cascade carbonylation is described. In the presented protocol, easily available propargylic alcohols react with aliphatic amines to provide a broad variety of interesting heterocycles. Key to the success of this transformation is a remarkable catalytic cleavage of the present carbon-carbon triple bond by using a specific catalyst with 2-diphenylphosphinopyridine as ligand and appropriate reaction conditions. Mechanistic studies and control experiments revealed branched unsaturated acid 11 as crucial intermediate.

Dehydropolymerisation of Methylamine Borane and an N-Substituted Primary Amine Borane Using a PNP Fe Catalyst.

Dehydropolymerisation of methylamine borane (H3 B⋅NMeH2 ) using the well-known iron amido complex [(PNP)Fe(H)(CO)] (PNP=N(CH2 CH2 PiPr2 )2 ) (1) gives poly(aminoborane)s by a chain-growth mechanism. In toluene, rapid dehydrogenation of H3 B⋅NMeH2 following first-order behaviour as a limiting case of a more general underlying Michaelis-Menten kinetics is observed, forming aminoborane H2 B=NMeH, which selectively couples to give high-molecular-weight poly(aminoborane)s (H2 BNMeH)n and only traces of borazine (HBNMe)3 by depolymerisation after full conversion. Based on a series of comparative experiments using structurally related Fe catalysts and dimethylamine borane (H3 B⋅NMe2 H) polymer formation is proposed to occur by nucleophilic chain growth as reported earlier computationally and experimentally. A silyl functionalised primary borane H3 B⋅N(CH2 SiMe3 )H2 was studied in homo- and co-dehydropolymerisation reactions to give the first examples for Si containing poly(aminoborane)s.

A Comparative Study on the Thermodynamics of Halogen Bonding of Group†10 Pincer Fluoride Complexes.

The thermodynamics of halogen bonding of a series of isostructural Group 10 metal pincer fluoride complexes of the type [(3,5-R2 -tBu POCOPtBu )MF] (3,5-R2 -tBu POCOPtBu =κ3 -C6 HR2 -2,6-(OPtBu2 )2 with R=H, tBu, COOMe; M=Ni, Pd, Pt) and iodopentafluorobenzene was investigated. Based on NMR experiments at different temperatures, all complexes 1-tBu (R=tBu, M=Ni), 2-H (R=H, M=Pd), 2-tBu (R=tBu, M=Pd), 2-COOMe (R=COOMe, M=Pd) and 3-tBu (R=tBu, M=Pt) form strong halogen bonds with Pd complexes showing significantly stronger binding to iodopentafluorobenzene. Structural and computational analysis of a model adduct of complex 2-tBu with 1,4-diiodotetrafluorobenzene as well as of structures of iodopentafluorobenzene in toluene solution shows that formation of a type I contact occurs.

P-Chirogenic Diphosphazanes with Axially Chiral Substituents and Their Use in Rh-Catalyzed Asymmetric Hydrogenation.

A convenient synthesis of enantiopure P-chirogenic diphosphazanes incorporating bulky bisphenol and 1,1'-bi-2-naphthol-derived substituents via the functionalization of a readily accessible enantiopure lithium phosphinoamide with chlorophosphoridites was developed. Since the product requires no subsequent deprotection, the protocol provides an easy, convenient synthesis of P-chirogenic ligands on the gram scale. The ligands were applied in the Rh-catalyzed asymmetric hydrogenation of benchmark substrates furnishing enantiomeric excess values up to 96%.

Efficient Palladium-Catalyzed Synthesis of 2-Aryl Propionic Acids.

A flexible two-step, one-pot procedure was developed to synthesize 2-aryl propionic acids including the anti-inflammatory drugs naproxen and flurbiprofen. Optimal results were obtained in the presence of the novel ligand neoisopinocampheyldiphenylphosphine (NISPCPP) (9) which enabled the efficient sequential palladium-catalyzed Heck coupling of aryl bromides with ethylene and hydroxycarbonylation of the resulting styrenes to 2-aryl propionic acids. This cascade transformation leads with high regioselectivity to the desired products in good yields and avoids the need for additional purification steps.

Cascade Synthesis of Pyrroles from Nitroarenes with Benign Reductants Using a Heterogeneous Cobalt Catalyst.

A bifunctional 3d-metal catalyst for the cascade synthesis of diverse pyrroles from nitroarenes is presented. The optimal catalytic system Co/NGr-C@SiO2 -L is obtained by pyrolysis of a cobalt-impregnated composite followed by subsequent selective leaching. In the presence of this material, (transfer) hydrogenation of easily available nitroarenes and subsequent Paal-Knorr/Clauson-Kass condensation provides >40 pyrroles in good to high yields using dihydrogen, formic acid, or a CO/H2 O mixture (WGSR conditions) as reductant. In addition to the favorable step economy, this straightforward domino process does not require any solvents or external co-catalysts. The general synthetic utility of this methodology was demonstrated on a variety of functionalized substrates including the preparation of biologically active and pharmaceutically relevant compounds, for example, (+)-Isamoltane.

Ligand-Controlled Palladium-Catalyzed Carbonylation of Alkynols: Highly Selective Synthesis of α-Methylene-ß-Lactones.

The first general and regioselective Pd-catalyzed cyclocarbonylation to give α-methylene-ß-lactones is reported. Key to the success for this process is the use of a specific sterically demanding phosphine ligand based on N-arylated imidazole (L11) in the presence of Pd(MeCN)2 Cl2 as pre-catalyst. A variety of easily available alkynols provide under additive-free conditions the corresponding α-methylene-ß-lactones in moderate to good yields with excellent regio- and diastereoselectivity. The applicability of this novel methodology is showcased by the direct carbonylation of biologically active molecules including natural products.

Preparation of a Series of Supported Nonsymmetrical PNP-Pincer Ligands and the Application in Ester Hydrogenation.

In contrast to their symmetrical analogues, nonsymmetrical PNP-type ligand motifs have been less investigated despite the modular pincer structure. However, the introduction of mixed phosphorus donor moieties provides access to a larger variety of PNP ligands. Herein, a facile solid-phase synthesis approach towards a diverse PNP-pincer ligand library of 14 members is reported. Contrary to often challenging workup procedures in solution-phase, only simple workup steps are required. The corresponding supported ruthenium-PNP catalysts are screened in ester hydrogenation. Usually, industrially applied heterogeneous catalysts require harsh conditions in this reaction (250-350 °C at 100-200 bar) often leading to reduced selectivities. Heterogenized reusable Ru-PNP catalysts are capable of reducing esters and lactones selectively under mild conditions.

Palladium-Catalyzed Tunable Carbonylative Synthesis of Enones and Benzofulvenes.

A palladium-catalyzed four-component carbonylative coupling reaction involving aryl halides, internal alkynes, arylboronic acids, and CO has been developed for the first time. All-carbon substituted α-unsaturated ketones and benzofulvenes can be selectively obtained in a highly regio- and stereocontrolled manner. Using Cu(TFA)2 as the additive, a series of tetrasubstituted α-unsaturated ketones were prepared in moderate to high yields. Using more acidic Lewis acid Cu(OTf)2 as the additive, multisubstituted benzofluvenes were synthesized in moderate yields. This efficient methodology involved the formation of three new C-C bonds, and provided a divergent method for the quick construction of multisubstituted α-unsaturated ketones and benzofulvenes from easily available starting materials.

Cobalt-Catalyzed Aqueous Dehydrogenation of Formic Acid.

Among the known liquid organic hydrogen carriers, formic acid attracts increasing interest in the context of safe and reversible storage of hydrogen. Here, the first molecularly defined cobalt pincer complex is disclosed for the dehydrogenation of formic acid in aqueous medium under mild conditions. Crucial for catalytic activity is the use of the specific complex 3. Compared to related ruthenium and manganese complexes 7 and 8, this optimal cobalt complex showed improved performance. DFT computations support an innocent non-classical bifunctional outer-sphere mechanism on the triplet state potential energy surface.

Additive-Free Isomerization of Allylic Alcohols to Ketones with a Cobalt PNP Pincer Catalyst.

Catalytic isomerization of allylic alcohols in ethanol as a green solvent was achieved by using air and moisture stable cobalt (II) complexes in the absence of any additives. Under mild conditions, the cobalt PNP pincer complex substituted with phenyl groups on the phosphorus atoms appeared to be the most active. High rates were obtained at 120 °C, even though the addition of one equivalent of base increases the speed of the reaction drastically. Although some evidence was obtained supporting a dehydrogenation-hydrogenation mechanism, it was proven that this is not the major mechanism. Instead, the cobalt hydride complex formed by dehydrogenation of ethanol is capable of double-bond isomerization through alkene insertion-elimination.

Intramolecular Base-Free Catalytic Wittig Reaction: Synthesis of Benzoxepinones.

A straightforward two-step synthesis of benzoxepinones was developed via base-free phosphane-catalyzed Wittig reaction. 3-Methyl-1-phenyl-2-phospholene 1-oxide was used as a precatalyst and trimethoxysilane as a reducing agent. Additionally benzoic acid is employed as a catalyst to facilitate the reduction of the phosphane oxide. Mechanistic investigation revealed the formation of a coumarin as a side product, which was identified by 2D NMR experiments. First results of metabolic activity tests on the prepared benzoxepinones are reported.

An Efficient Protocol to Synthesize N-Acyl-enamides and -Imines by Pd-Catalyzed Carbonylations.

For the first time, the bidentate phosphinite ligand 1,2-bis(di-tert-butylphosphinoxy)ethane (tBu2 POCH2 CH2 OPtBu2 ) was synthesized. In the presence of this ligand, various N-acyl enamides were obtained in good yields and chemoselectivity by Pd-catalyzed carbonylation reaction of imines containing α-H. Meanwhile, imines without α-H could be transformed to N-acyl imines, which form highly hindered amides by straightforward addition of Grignard reagents.

Cobalt Pincer Complexes for Catalytic Reduction of Carboxylic Acid Esters.

A selection of cobalt(I) and cobalt(II) pincer type complexes with different substitution patterns was tested in the catalytic reduction of carboxylic acid esters to alcohols. The cobalt pincer type complex 4 is suitable for the hydrogenation of aromatic as well as aliphatic and cyclic esters. Mechanistic investigation indicated a metal ligand cooperated reaction pathway.