Asymmetric addition of Grignard reagents to ketones: culmination of the ligand-mediated methodology allows modular construction of chiral tertiary alcohols.

A new class of biaryl chiral ligands derived from 1,2-diaminocyclohexane (1,2-DACH) has been designed to enable the asymmetric addition of aliphatic and, for the first time, aromatic Grignard reagents to ketones for the preparation of highly enantioenriched tertiary alcohols (up to 95% ee). The newly developed ligands L12 and L12' together with the previously reported L0 and L0' define a set of complementary chiral promoters, which provides access to the modular construction of a broad range of structurally diverse non-racemic tertiary alcohols, bearing challenging quaternary stereocenters. The present advancements bring to completion our asymmetric Grignard methodology by expanding the scope to aromatic organomagnesium reagents, while facilitating its implementation in organic synthesis thanks to improved synthetic routes for the straightforward access to the chiral ligands. The synthetic utility of the method has been demonstrated by the development of a novel and highly enantioselective formal synthesis of the antihistamine API clemastine via intermediate (R)-3a. Exploiting the power of the 3-disconnection approach offered by the Grignard synthesis, (R)-3a is obtained in 94% ee with ligand (R,R)-L12. The work described herein marks the finalization of our ongoing effort towards the establishment of an effective and broadly applicable methodology for the asymmetric Grignard synthesis of chiral tertiary alcohols.

Cationic Aluminium Complexes as Catalysts for Imine Hydrogenation.

Strongly Lewis acidic cationic aluminium complexes, stabilized by ß-diketiminate (BDI) ligands and free of Lewis bases, have been prepared as their B(C6 F5 )4 - salts and were investigated for catalytic activity in imine hydrogenation. The backbone (R1) and N (R2) substituents on the R1,R2 BDI ligand (R1,R2 BDI=HC[C(R1)N(R2)]2 ) influence sterics and Lewis acidity. Ligand bulk increases along the row Me,DIPP BDI

Insights into LiAlH4 Catalyzed Imine Hydrogenation.

Commercial LiAlH4 can be used in catalytic quantities in the hydrogenation of imines to amines with H2 . Combined experimental and theoretical investigations give deeper insight in the mechanism and identifies the most likely catalytic cycle. Activity is lost when Li in LiAlH4 is exchanged for Na or K. Exchanging Al for B or Ga also led to dramatically reduced activities. This indicates a heterobimetallic mechanism in which cooperation between Li and Al is crucial. Potential intermediates on the catalytic pathway have been isolated from reactions of MAlH4 (M=Li, Na, K) and different imines. Depending on the imine, double, triple or quadruple imine insertion has been observed. Prolonged reaction of LiAlH4 with PhC(H)=NtBu led to a side-reaction and gave the double insertion product LiAlH2 [N]2 ([N]=N(tBu)CH2 Ph) which at higher temperature reacts further by ortho-metallation of the Ph ring. A DFT study led to a number of conclusions. The most likely catalyst for hydrogenation of PhC(H)=NtBu with LiAlH4 is LiAlH2 [N]2 . Insertion of a third imine via a heterobimetallic transition state has a barrier of +23.2 kcal mol-1 (ΔH). The rate-determining step is hydrogenolysis of LiAlH[N]3 with H2 with a barrier of +29.2 kcal mol-1 . In agreement with experiment, replacing Li for Na (or K) and Al for B (or Ga) led to higher calculated barriers. Also, the AlH4 - anion showed very high barriers. Calculations support the experimentally observed effects of the imine substituents at C and N: the lowest barriers are calculated for imines with aryl-substituents at C and alkyl-substituents at N.

Metallic Barium: A Versatile and Efficient Hydrogenation Catalyst.

Ba metal was activated by evaporation and cocondensation with heptane. This black powder is a highly active hydrogenation catalyst for the reduction of a variety of unactivated (non-conjugated) mono-, di- and tri-substituted alkenes, tetraphenylethylene, benzene, a number of polycyclic aromatic hydrocarbons, aldimines, ketimines and various pyridines. The performance of metallic Ba in hydrogenation catalysis tops that of the hitherto most active molecular group 2 metal catalysts. Depending on the substrate, two different catalytic cycles are proposed. A: a classical metal hydride cycle and B: the Ba metal cycle. The latter is proposed for substrates that are easily reduced by Ba0 , that is, conjugated alkenes, alkynes, annulated rings, imines and pyridines. In addition, a mechanism in which Ba0 and BaH2 are both essential is discussed. DFT calculations on benzene hydrogenation with a simple model system (Ba/BaH2 ) confirm that the presence of metallic Ba has an accelerating effect.

d-d Dative Bonding Between Iron and the Alkaline-Earth Metals Calcium, Strontium, and Barium.

Double deprotonation of the diamine 1,1'-(tBuCH2 NH)-ferrocene (1-H2 ) by alkaline-earth (Ae) or EuII metal reagents gave the complexes 1-Ae (Ae=Mg, Ca, Sr, Ba) and 1-Eu. 1-Mg crystallized as a monomer while the heavier complexes crystallized as dimers. The Fe⋅⋅⋅Mg distance in 1-Mg is too long for a bonding interaction, but short Fe⋅⋅⋅Ae distances in 1-Ca, 1-Sr, and 1-Ba clearly support intramolecular Fe⋅⋅⋅Ae bonding. Further evidence for interactions is provided by a tilting of the Cp rings and the related 1 H NMR chemical-shift difference between the Cp α and ß protons. While electrochemical studies are complicated by complex decomposition, UV/Vis spectral features of the complexes support Fe→Ae dative bonding. A comprehensive bonding analysis of all 1-Ae complexes shows that the heavier species 1-Ca, 1-Sr, and 1-Ba possess genuine Fe→Ae bonds which involve vacant d-orbitals of the alkaline-earth atoms and partially filled d-orbitals on Fe. In 1-Mg, a weak Fe→Mg donation into vacant p-orbitals of the Mg atom is observed.

Highly Active Superbulky Alkaline Earth Metal Amide Catalysts for Hydrogenation of Challenging Alkenes and Aromatic Rings.

Two series of bulky alkaline earth (Ae) metal amide complexes have been prepared: Ae[N(TRIP)2 ]2 (1-Ae) and Ae[N(TRIP)(DIPP)]2 (2-Ae) (Ae=Mg, Ca, Sr, Ba; TRIP=SiiPr3 , DIPP=2,6-diisopropylphenyl). While monomeric 1-Ca was already known, the new complexes have been structurally characterized. Monomers 1-Ae are highly linear while the monomers 2-Ae are slightly bent. The bulkier amide complexes 1-Ae are by far the most active catalysts in alkene hydrogenation with activities increasing from Mg to Ba. Catalyst 1-Ba can reduce internal alkenes like cyclohexene or 3-hexene and highly challenging substrates like 1-Me-cyclohexene or tetraphenylethylene. It is also active in arene hydrogenation reducing anthracene and naphthalene (even when substituted with an alkyl) as well as biphenyl. Benzene could be reduced to cyclohexane but full conversion was not reached. The first step in catalytic hydrogenation is formation of an (amide)AeH species, which can form larger aggregates. Increasing the bulk of the amide ligand decreases aggregate size but it is unclear what the true catalyst(s) is (are). DFT calculations suggest that amide bulk also has a noticeable influence on the thermodynamics for formation of the (amide)AeH species. Complex 1-Ba is currently the most powerful Ae metal hydrogenation catalyst. Due to tremendously increased activities in comparison to those of previously reported catalysts, the substrate scope in hydrogenation catalysis could be extended to challenging multi-substituted unactivated alkenes and even to arenes among which benzene.

Lewis acidic alkaline earth metal complexes with a perfluorinated diphenylamide ligand.

Alkaline earth metal (Ae) chemistry with the anion [N(C6F5)2]- has been explored. Deprotonation of the amine (C6F5)2NH, abbreviated in here as NFH, with 0.5 equivalent of AeN''2 (N'' = N(SiMe3)2) is fast and gave, dependent on the solvent, the complexes AeNF2, AeNF2·(THF)2 and AeNF2·(Et2O)2 (Ae = Mg, Ca, Sr). Using a 1/1 ratio, mixed amide complexes were obtained: NFAeN'' (Ae = Mg, Ca, Sr). Crystal structures of the monomers AeNF2·(THF)2 (Ae = Mg, Ca, Sr) and AeNF2·(Et2O)2 (Ae = Mg, Ca) are presented and compared with those of AeN''2·(THF)2. In addition, crystal structures of the homoleptic dimer (MgNF2)2 and the heteroleptic dimers (NFAeN'')2 (Ae = Mg, Ca, Sr) are discussed. All structures are strongly influenced by very short AeF contacts down to circa 2.11 Å (Mg), 2.50 Å (Ca) and 2.73 Å (Sr). AIM analysis illustrates that, although AeF contacts are short, there is no bond-critical-point along this axis, indicating an essentially electrostatic interaction. The monomeric complexes feature strong C6F5C6F5π-stacking, resulting in unusually acute NF-Ae-NF angles as small as 95°. Heteroleptic (NFAeN'')2 complexes retain their dimeric structure in C6D6 solution and there is no indication of ligand scrambling by the Schlenk equilibrium, suggesting that an electron withdrawing ligand may stabilize heteroleptic complexes. According to DFT calculations, the heteroleptic arrangement is 70 kJ mol-1 more stable than the homoleptic dimers. The Lewis acidity of MgNF2 has been quantified with the Gutmann-Beckett method and by calculation of the Fluoride-Ion-Affinity. The latter calculations show that the Lewis acidity of MgNF2 and CaNF2 is comparable to that of B(C6F5)3. Dimeric (MgNF2)2 fully abstracts Et3PO from Et3PO·B(C6F5)3 and may have potential in Lewis acid catalysis.

Nucleophilic Aromatic Substitution at Benzene with Powerful Strontium Hydride and Alkyl Complexes.

Key to the isolation of the first alkyl strontium complex was the synthesis of a strontium hydride complex that is stable towards ligand exchange reactions. This goal was achieved by using the super bulky ß-diketiminate ligand DIPeP BDI (CH[C(Me)N-DIPeP]2 , DIPeP=2,6-diisopentylphenyl). Reaction of DIPeP BDI-H with Sr[N(SiMe3 )2 ]2 gave (DIPeP BDI)SrN(SiMe3 )2 , which was converted with PhSiH3 into [(DIPeP BDI)SrH]2 . Dissolved in C6 D6 , the strontium hydride complex is stable up to 70 °C. At 60 °C, H-D isotope exchange gave full conversion into [(DIPeP BDI)SrD]2 and C6 D5 H. Since H-D exchange with D2 is facile, the strontium hydride complex served as a catalyst for the deuteration of C6 H6 by D2 . Reaction of [(DIPeP BDI)SrH]2 with ethylene gave [(DIPeP BDI)SrEt]2 . The high reactivity of this alkyl strontium complex is demonstrated by facile ethylene polymerization and nucleophilic aromatic substitution with C6 D6 , giving alkylated aromatic products and [(DIPeP BDI)SrD]2 .

Simple Access to the Heaviest Alkaline Earth Metal Hydride: A Strongly Reducing Hydrocarbon-Soluble Barium Hydride Cluster.

Reaction of Ba[N(SiMe3 )2 ]2 with PhSiH3 in toluene gave simple access to the unique Ba hydride cluster Ba7 H7 [N(SiMe3 )2 ]7 that can be described as a square pyramid spanned by five Ba2+ ions with two flanking BaH[N(SiMe3 )2 ] units. This heptanuclear cluster is well soluble in aromatic solvents, and the hydride 1 H NMR signals and coupling pattern suggests that the structure is stable in solution. At 95 °C, no coalescence of hydride signals is observed but the cluster slowly decomposes to undefined barium hydride species. The complex Ba7 H7 [N(SiMe3 )2 ]7 is a very strong reducing agent that already at room temperature reacts with Me3 SiCH=CH2 , norbornadiene, and ethylene. The highly reactive alkyl barium intermediates cannot be observed and deprotonate the (Me3 Si)2 N- ion, as confirmed by the crystal structure of Ba14 H12 [N(SiMe3 )2 ]12 [(Me3 Si)(Me2 SiCH2 )N]4 .

A Simple Route to Calcium and Strontium Hydride Clusters.

The first strontium hydride complex has been obtained by simply treating Sr[N(SiMe3 )2 ]2 with PhSiH3 in the presence of PMDTA. The Sr complex Sr6 H9 [N(SiMe3 )2 ]3 ⋅(PMDTA)3 crystallizes as an "inverse cryptand": an interstitial H- is surrounded by a Sr6 H84+ cage decorated with amide and PMDTA ligands. The analogous Ca complex could also be obtained and both retain their solid-state structures in solution: 1 H NMR spectra in C6 D6 show two doublets and one nonet (4:4:1). Up to 90 °C, no coalescence is observed. The Ca cluster was investigated by DFT calculations and shows atypically low charges on Ca (+1.14) and H (-0.59) which signifies an unexpectedly low ionicity. AIM analysis shows hydride⋅⋅⋅hydride bond paths with considerable electron densities in the bond critical point. The clusters thermally decompose into larger, undefined, metal hydride aggregates.

A capacitance ultrasonic transducer for high-temperature applications.

This paper introduces a novel ultrasonic capacitance transducer for operation at elevated gas temperatures of several hundred degrees Celsius. The transducer design is based on a metallic membrane foil and a backplate made of an electrically conducting substrate coated with an insulation layer. Guidelines are given for selecting suitable materials for the membrane foil, the backplate substrate, and the coating. Manufacturing techniques applied for fabrication of different transducer types are described in detail. Transducers tested were composed of titanium substrates with insulation layers of silicon nitride or of silicon substrates with silicon oxide coatings. Experimental setup and test procedures are described. Results of transducer characterization and performance tests at elevated temperatures are presented and discussed. Transducer functionality is proven for air temperatures of up to 500 degrees C.