Enantioselective Hydrogenation of β‐Acylamino Acrylates Catalyzed by Rhodium(I)‐Monophosphite Complexes

Chiral rhodium(I) complexes bearing monophosphite ligands, prepared from chiral Binol and (L )‐menthol, were found to be efficient catalysts for the asymmetric hydrogenation of β‐acylamino acrylates with ee values up to 94%.     

Heptakis(2,3‐di‐O‐methyl‐6‐O‐sulfopropyl)‐β‐cyclodextrin: A Genuine Supramolecular Carrier for Aqueous Organometallic Catalysis

The behavior of heptakis(2,3‐di‐O‐methyl‐6‐O‐sulfopropyl)‐β‐cyclodextrin as inverse phase transfer catalyst in biphasic Tsuji–Trost and hydroformylation reactions has been investigated. In terms of activity, this methylated sulfopropyl ether β‐cyclodextrin is much more efficient than the randomly methylated β‐cyclodextrin, which was the most active cyclodextrin known to date. From a selectivity point of view, the intrinsic properties of the catalytic system are fully preserved in the presence of this cyclodextrin as the chemo‐ or regioselectivity was found to be identical to that observed without a mass transfer promoter in the hydroformylation reaction. The efficiency of this cyclodextrin was attributed to its high surface activity and to the absence of interactions with the catalytically active species and the water‐soluble phosphane used to dissolve the organometallic catalyst in the aqueous phase.     

Ethylene/1‐octadecene copolymerization using [η5:η1‐C5Me4‐4‐R1‐6‐R‐C6H2O]TiCl2 catalysts

Copolymerization of ethylene with 1‐octadecene was studied using [η⁵:η¹‐C₅Me₄‐4‐R₁‐6‐R‐C₆H₂O]TiCl₂ [R₁ = ^tBu (1), H (2, 3, 4); R = ^tBu (1, 2), Me (3), Ph (4)] as catalysts in the presence of Al(i‐Bu)₃ and [Ph₃C][B(C₆F₅)₄]. The effect of the concentration of comonomer in the feed and Al/Ti molar ratio on the catalytic activity and molecular weight of the resultant copolymer were investigated. The substituents on the phenyl ring of the ligand affect considerably both the catalytic activity and comonomer incorporation. The 1 /Al(i‐Bu)₃/[Ph₃C][B(C₆F₅)₄] catalyst system exhibits the highest catalytic activity and produces copolymers with the highest molecular weight, while the 2 /Al(i‐Bu)₃/[Ph₃C][B(C₆F₅)₄] catalyst system gives copolymers with the highest comonomer incorporation under similar conditions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Kinase in Motion: Insights into the Dynamic Nature of p38α by High‐Pressure NMR Spectroscopic Studies

Protein kinases are highly dynamic and complex molecules. Here we present high‐pressure and relaxation studies of the activated p38α mitogen‐activated protein kinase (MAPK). p38α plays a central role in inflammatory diseases such as rheumatoid arthritis and is therefore a highly attractive pharmaceutical target. The combination of high pressure and NMR spectroscopy allowed for a detailed per‐residue based assessment of the structural plasticity of p38α and the accessibility of low‐lying excited‐energy conformations throughout the kinase structure. Such information is uniquely accessible through the combination of liquid‐state NMR and high pressure and is of considerable value for the drug discovery process. The interactions of p38α and DFG‐in and DFG‐out ligands were studied under the application of high pressure, and we demonstrate how we can alter kinase dynamics by pressure in a similar way to what has previously only been observed by ligand binding. Pressure is shown to be a mild and efficient tool for manipulation of intermediate‐timescale dynamics.     

Synthesis of Chiral 2‐Hydroxy‐1‐methylpropanoates by Rhodium‐Catalyzed Stereoselective Hydrogenation of α‐(Hydroxymethyl)‐acrylate Derivatives

The synthesis of chiral 3‐hydroxy‐2‐methylpropanoic acid esters (e.g., “Roche ester” 3a ) based on the rhodium‐catalyzed stereoselective hydrogenation of Baylis–Hillman reaction products was investigated. Full conversions and enantioselectivities of up to 99% at a substrate/catalyst ratio of up to 500/1 were achieved by application of bisphospholanes of the catASium M series as ancillary ligands. An interesting kinetic resolution was observed by the diastereoselective hydroxy‐directed hydrogenation of related racemic β‐branched precursors affording mainly anti‐isomers with up to 96%ee.     

Axial Chirality Control by 2,4‐Pentanediol for the Alternative Synthesis of C3*‐TunePhos Chiral Diphosphine Ligands and Their Applications in Highly Enantioselective Ruthenium‐Catalyzed Hydrogenation of β‐Keto Esters

A highly efficient strategy for the synthesis of a series of C₃*‐TunePhos chiral diphosphine ligands was well established with several remarkable features. The synthetic utility of these ligands was explored for the ruthenium‐catalyzed asymmetric hydrogenation of β‐keto esters. Up to 99% ee values were achieved for the enantioselective synthesis of β‐hydroxy acid derivatives, which are very important chiral building blocks for the synthesis of a variety of natural products and biologically active molecules.     

High‐pressure synthesis of a 12CaO·7Al2O3–12SrO·7Al2O3 solid solution

Solid solutions of 12CaO·7Al₂O₃ (C12A7) and 12SrO·7Al₂O₃ (S12A7) crystals were synthesized under high pressure. X‐ray diffraction patterns revealed that the lattice constants of the synthesized samples depend linearly on the compositional ratio of C12A7 and S12A7. Electron‐probe X‐ray microanalyses show that the chemical compositions of the crystals are represented by xC12A7·(1?x)S12A7 (0<x<1). These results indicate that the variation in the lattice constants is originated from a difference in the ionic radii of Ca²⁺ and Sr²⁺ ions. From impedance measurements, it was found that S12A7 has the highest conductivity (~1 × 10^?3 Scm^?1 at 550°C) among the solid solutions in the C12A7–S12A7 system.     

Optically Pure 1,2‐Bis[(o‐alkylphenyl)phenylphosphino]ethanes and Their Use in Rhodium‐Catalyzed Asymmetric Hydrogenations of α‐(Acylamino)acrylic Derivatives

Optically pure (S,S)‐1,2‐bis[(o‐alkylphenyl)phenylphosphino]ethanes 1a–d were prepared in four steps from phenyldichlorophosphine via phosphine‐boranes as the intermediates. The rhodium complexes 5a–d of these diphosphines were used for the asymmetric hydrogenations of α‐(acylamino)acrylic derivatives including β‐disubstituted derivatives. Markedly high enantioselectivity (78–>99%) was observed for the reduction of β‐monosubstituted derivatives. β‐Disubstituted derivatives were also reduced in considerably high enantioselectivity (up to 90%). The single crystal X‐ray analysis of the rhodium complex 5c of (S,S)‐1,2‐bis[phenyl(5′,6′,7′,8′‐tetrahydronaphthyl)phosphino]ethane ( 1c) revealed its δ‐type structure with face orientation of the two tetrahydronaphthyl groups and edge orientation of the two phenyl groups. This conformation corresponds to that of the rhodium complex of 1,2‐bis[(o‐methoxyphenyl)phenylphosphino]ethane (DIPAMP); the rhodium complex of (R,R)‐DIPAMP, whose chirality at phosphorus is opposite that of 5c , exhibits a λ‐type structure with the face orientation of the two o‐methoxyphenyl groups and the edge orientation of the two phenyl groups. The conformational similarity of these rhodium complexes as well as the stereochemical outcome in the asymmetric hydrogenations means that the coordinative interaction of the methoxy group of DIPAMP with rhodium metal is not the main factor that affects asymmetric induction.     

Ruthenium‐Catalyzed O‐Allylation of Phenols from Allylic Chlorides via Cationic [Cp*(η3‐allyl)(MeCN)RuX][PF6] Complexes

The [Cp*(MeCN)₃Ru(II)][PF₆] complex is an efficient catalyst precursor for the O‐allylation of phenols with allylic chlorides in the presence of K₂CO₃ under mild conditions. This ruthenium precursor affords branched allyl aryl ethers according to a regioselective reaction, which contrasts with the uncatalyzed nucleophilic substitution from the same substrates. Stable (η³‐allyl)Ru(IV) cationic complexes resulting from the reaction of [Cp*(MeCN)₃Ru][PF₆] with allylic halides were identified as intermediate catalytic species. An X‐ray structure determination of the complex [Cp*(MeCHCHCH₂)(MeCN)RuBr][PF₆] disclosed an (endo‐trans‐MeCHCHCH₂) allylic ligand. The structural information obtained from the study of Cp*(allyl)Ru(IV) complexes indicated that electronic effects at the coordinated allylic ligand likely account for the better regioselectivity obtained from cinnamyl chloride as compared to aliphatic allylic chlorides.     

[CpRu(IV)(π‐C3H5)(2‐quinolinecarboxylato)]PF6 Complex: A Robust Catalyst for the Cleavage and Formation of Allyl Ethers

A facile and efficient method for the quantitative synthesis of [CpRu(IV)(π‐C₃H₅)(2‐quinolinecarboxylato)]PF₆ from [CpRu(CH₃CN)₃]PF₆, 2‐quinolinecarboxylic acid, and 2‐propen‐1‐ol has been established. The cationic Ru(IV) complex is air‐ and moisture‐stable, and can be stored in a vial for at least six months. This complex realizes a simple and easy operation for both the deallylation of allyl ethers in methanol and the dehydrative allylation of alcohols. Furthermore, with removal of the volatile allyl methyl ether co‐product from the reaction system, the robust catalyst can attain a turnover of 10000 cycles of allyl ether cleavage.     

(η6‐Arene)ruthenium(N‐heterocyclic carbene) Complexes for the Chelation‐Assisted Arylation and Deuteration of Arylpyridines: Catalytic Studies and Mechanistic Insights

A series of (η⁶‐arene)ruthenium complexes have been tested in the arylation of arylpyridines. One (η⁶‐p‐cymene)ruthenium(N‐heterocyclic carbene) complex (labelled as 1 in the text) was found to be the most effective, being capable of arylating a wide set of substantially different arylpyridines. Complex 1 is also able to promote the regioselective deuteration of a series of arylated N‐heterocycles, via a nitrogen‐directed mechanism. Two of the deuterated amines were used to measure the kinetic isotope effect (KIE) in the arylation process. The detection of an inverse KIE, together with the observation that the C H activation process does not require the addition of a base, suggest that the rate‐limiting step in the arylation process may be different to that of previously reported studies.     

A Convenient Synthesis of 2,2′,6,6′‐Tetramethoxy‐ 4,4′‐bis(dicyclohexylphosphino)‐3,3′‐bipyridine (Cy‐P‐Phos): Application in Rh‐Catalyzed Asymmetric Hydrogenation of α‐(Acylamino)acrylates

The first example of the synthesis of an axially chiral bis(aryldicyclohexylphosphine) dioxide via catalytic hydrogenation of the optically resolved parent bis(aryldiphenylphosphine) dioxide was reported. The procedure for the synthesis of Cy‐P‐Phos ( 4d ) has thus successfully avoided the need for an otherwise lengthy synthetic route owing to the π‐excessive nature of one of the aryl groups in the latter. The use of Cy‐P‐Phos in the Rh(I)‐catalyzed asymmetric hydrogenation of the derivatives of methyl (Z)‐2‐acetamidocinnamate gave significantly higher rates of reaction as compared to the use of the previously reported optimal ligand Xyl‐P‐Phos ( 4c ) whilst the level of enantioselectivity was essentially maintained.     

ansa‐Ruthenium(II) Complexes of R2NSO2DPEN‐(CH2)n(η6‐Aryl) Conjugate Ligands for Asymmetric Transfer Hydrogenation of Aryl Ketones

New 3^rd generation designer ansa‐ruthenium(II) complexes featuring N,C‐alkylene‐tethered N,N‐dialkylsulfamoyl‐DPEN/η⁶‐arene ligands, exhibited good catalytic performance in the asymmetric transfer hydrogenation (ATH) of various classes of (het)aryl ketones in formic acid/triethylamine mixture. In particular, benzo‐fused cyclic ketones furnished 98 to >99.9% ee using a low catalyst loading.

     

Mechanistic study of Sn(Oct)2‐catalyzed ε‐caprolactone polymerization using Sn(Oct)2/BF3 dual catalyst

A novel method was used to investigate the mechanism of Sn(Oct)₂‐catalyzed ε‐caprolactone polymerization by using Sn(Oct)₂/BF₃ dual catalyst. The bulk polymerization was conducted at 110 and 130°C with different Sn(Oct)₂/BF₃ ratios. The polymerization kinetics was followed using gel permeation chromatography, and the molecular structures of the low‐molecular weight polymers were examined using ¹H‐nuclear magnetic resonance (NMR). A polymerization induction period was observed in polymerizations containing the Sn(Oct)₂ catalyst, but it was not observed in the system containing only BF₃. After the induction period, BF₃ and Sn(Oct)₂ initiated the polymerization separately. For Sn(Oct)₂ catalyst with no purposely added alcohol, the actual initiation species is a tin hydroxide species formed in situ by the reaction of Sn(Oct)₂ and adventitious water. For BF₃ catalyst, the active species is the protonic acid formed by the reaction of BF₃ with the adventitious water. When mixed, the Sn(Oct)₂ reacts with the adventitious water faster than the BF₃, preventing the BF₃ catalyzing any polymerizations during the induction period. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Hydrogenation of cis‐1,4‐polyisoprene catalyzed by Ru(CHCH(Ph))Cl(CO)(PCy3)2

Hydrogenation is a useful method which has been used to improve oxidative and thermal degradation resistance of diene‐based polymers. The quantitative hydrogenation of cis‐1,4‐polyisoprene which leads to an alternating ethylene–propylene copolymer was studied in the present investigation. To examine the influence of key factors on the reaction, such as catalyst concentration, polymer concentration, hydrogen pressure, and temperature, a detailed study of the hydrogenation of cis‐1,4‐polyisoprene catalyzed by the Ru complex, Ru(CH?CH(Ph))Cl(CO)(PCy₃)₂ was carried out by monitoring the amount of hydrogen consumed. Infrared and ¹H‐NMR spectroscopic measurements confirmed the final degree of hydrogenation. The hydrogenation of cis‐1,4‐polyisoprene followed pseudo‐first‐order kinetics in double‐bond concentration up to high conversions of double bond, under all sets of conditions studied. The kinetic results suggested a first‐order behavior with respect to total catalyst concentration as well as with respect to hydrogen pressure. The apparent activation energy for the hydrogenation process, obtained from an Arrhenius plot, was 51.1 kJ mol^?1 over the temperature range of 130 to 180°C. Mechanistic aspects of the catalytic process are discussed. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 3259–3273, 2004     

High‐Pressure 31P{1H} NMR Studies of RhH(CO)(TPPTS)3 in the Presence of Methylated Cyclodextrins: New Light on Rhodium‐Catalyzed Hydroformylation Reaction Assisted by Cyclodextrins

The effect of methylated cyclodextrins on the RhH(CO)(TPPTS)₃ complex in hydroformylation conditions [50 atm of CO/H₂ (1/1) and 80 °C] has been investigated by high‐pressure ³¹P{¹H} NMR spectroscopy. In the presence of methylated β‐cyclodextrin, the equilibria between the rhodium species lie in favor of phosphine low‐coordinated rhodium species. The formation of a stable inclusion complex between this cyclodextrin and the trisulfonated triphenylphosphine ligand (TPPTS) was found to be the key to understanding the displacement of the equilibria. Indeed, the methylated α‐cyclodextrin which does not interact with the TPPTS and the methylated γ‐cyclodextrin which can weakly bind to the TPPTS have no and a very low effect on the equilibria, respectively. These results explain for the first time why a decrease in the normal to branched aldehydes ratio is always observed when cyclodextrins are used as mass‐transfer agents in aqueous biphasic hydroformylation processes.     

Solution NMR Studies of Recombinant Aβ(1–42): From the Presence of a Micellar Entity to Residual β‐Sheet Structure in the Soluble Species

Amyloid‐β (Aβ) peptide is the major component found in senile plaques of Alzheimer's disease patients. The 42‐residue fragment Aβ(1–42) is proposed to be one of the most pathogenic species therein. Here, the soluble Aβ(1–42) species were analyzed by various liquid‐state NMR methods. Transient formation of a micelle species was observed at the onset of the aggregation kinetics. This micelle is dissolved after approximately one day. Subsequent loss of this species and the formation of protofibrils are proposed to be the route of fibril formation. Consequently, the observed micelle species is suggested to be on an off‐pathway mechanism. Furthermore, characterization of the NMR‐observable soluble species shows that it is a random‐coil‐like entity with low propensities for four β‐strands. These β‐strands correlate with the β‐strand segments observed in Aβ fibrils. This finding indicates that the 3D structure of the fibrils might already be predisposed in the soluble species.     

Enantioselective Synthesis of Chiral β‐Aryloxy Alcohols by Ruthenium‐Catalyzed Ketone Hydrogenation via Dynamic Kinetic Resolution (DKR)

A highly efficient enantioselective synthesis of chiral β‐aryloxy alcohols by the {RuCl₂[(S)‐SDP][(R,R)‐DPEN]} [(S_a,R,R)‐ 1a ; SDP=7,7′‐bis(diarylphosphino)‐1,1′‐spirobiindane; DPEN=trans‐1,2‐diphenylethylenediamine] complex‐catalyzed asymmetric hydrogenation of racemic α‐aryloxydialkyl ketones via dynamic kinetic resolution (DKR) has been developed. Enantioselectivities of up to 99% ee with good to high cis/anti‐selectivities (up to>99:1) were achieved.