Amide‐Substituted Titanocenes in Hydrogen‐Atom Transfer Catalysis

Two new catalytic systems for hydrogen‐atom transfer (HAT) catalysis involving the N?H bonds of titanocene(III) complexes with pendant amide ligands are reported. In a monometallic system, a bifunctional catalyst for radical generation and reduction through HAT catalysis depending on the coordination of the amide ligand is employed. The pendant amide ligand is used to activate Crabtree's catalyst to yield an efficient bimetallic system for radical generation and HAT catalysis.     

Nickel-Catalyzed Asymmetric Hydrogenation of α-Substituted Vinylphosphonates and Diarylvinylphosphine Oxides

Chiral α-substituted ethylphosphonate and ethylphosphine oxide compounds are widely used in drugs, pesticides, and ligands. However, their catalytic asymmetric synthesis is still rare. Of the only asymmetric hydrogenation methods available at present, all cases use rare metal catalysts. Herein, we report an efficient earth-abundant transition-metal nickel catalyzed asymmetric hydrogenation affording the corresponding chiral ethylphosphine products with up to 99 % yield, 96 % ee (enantiomeric excess) (99 % ee, after recrystallization) and 1000 S/C (substrate/catalyst); this is also the first study on the asymmetric hydrogenation of terminal olefins using a nickel catalyst under a hydrogen atmosphere. The catalytic mechanism was investigated via deuterium-labelling experiments and calculations which indicate that the two added hydrogen atoms of the products come from hydrogen gas. Additionally, it is believed that the reaction involves a Ni^II rather than Ni⁰ cyclic process based on the weak attractive interactions between the Ni catalyst and terminal olefin substrate.     

Rhodium-catalyzed asymmetric hydrogenation of olefins with PhthalaPhos, a new class of chiral supramolecular ligands

A library of 19 binol-derived chiral monophosphites that contain a phthalic acid diamide group (PhthalaPhos) has been designed and synthesized in four steps. These new ligands were screened in the rhodium-catalyzed enantioselective hydrogenation of prochiral dehydroamino esters and enamides. Several members of the library showed excellent enantioselectivity with methyl 2-acetamido acrylate (6 ligands gave >97% ee), methyl (Z)-2-acetamido cinnamate (6 ligands gave >94% ee), and N-(1-phenylvinyl)acetamide (9 ligands gave >95% ee), whilst only a few representatives afforded high enantioselectivities for challenging and industrially relevant substrates N-(3,4-dihydronaphthalen-1-yl)-acetamide (96% ee in one case) and methyl (E)-2-(acetamidomethyl)-3-phenylacrylate (99% ee in one case). In most cases, the new ligands were more active and more stereoselective than their structurally related monodentate phosphites (which are devoid of functional groups that are capable of hydrogen-bonding interactions). Control experiments and kinetic studies were carried out that allowed us to demonstrate that hydrogen-bonding interactions involving the diamide group of the PhthalaPhos ligands strongly contribute to their outstanding catalytic properties. Computational studies carried out on a rhodium precatalyst and on a conceivable intermediate in the hydrogenation catalytic cycle shed some light on the role played by hydrogen bonding, which is likely to act in a substrate-orientation effect.     

Chiral Proline‐Based P,O and P,N Ligands for Iridium‐Catalyzed Asymmetric Hydrogenation

Two new classes of proline‐based P,O and P,N ligands were prepared and applied in the iridium‐catalyzed asymmetric hydrogenation of alkenes. Both types of ligands induced high enantioselectivities in the hydrogenation of trisubstituted C?C bonds. Iridium complexes derived from P,O ligands bearing sterically demanding amide or urea groups at the pyrrolidine N‐atom proved to be especially efficient catalysts for the conjugate reduction of α,β‐unsaturated esters and ketones, whereas analogous P,N ligands led to better results with dialkyl‐phenyl‐substituted alkenes and an allylic alcohol as substrates.     

Synthesis of C3-symmetric tris(beta-hydroxy amide) ligands and their Ti(IV) complex-catalyzed enantioselective alkynylation of aldehydes

[reaction: see text]. A series of new chiral C3-symmetric tris(beta-hydroxy amide) ligands have been synthesized via the reaction of 1,3,5-benzenetricarboxylic chloride and optically pure amino alcohols (up to 96% yield). The asymmetric catalytic alkynylation of aldehydes with these new C3-symmetric chiral tris(beta-hydroxy amide) ligands and Ti (O(i)'Pr)4 was investigated. Ligand 4c synthesized from (1R,2S)-(-)-2-amino-1,2-diphenylethanol is effective for the enantioselective alkynylation of various aldehydes, and high enantioselectivity was obtained with aromatic aldehydes and alpha,beta-unsaturated aldehyde (up to 92% ee).     

Catalytic asymmetric hydrogenation of 3-substituted benzisoxazoles

A variety of 3-substituted benzisoxazoles were reduced with hydrogen using the chiral ruthenium catalyst, {RuCl(p-cymene)[(R,R)-(S,S)-PhTRAP]}Cl. The ruthenium-catalyzed hydrogenation proceeded in high yield in the presence of an acylating agent, affording α-substituted o-hydroxybenzylamines with up to 57% ee. In the catalytic transformation, the N-O bond of the benzisoxazole substrate is reductively cleaved by the ruthenium complex under the hydrogenation conditions. The C-N double bond of the resulting imine is saturated stereoselectively through the PhTRAP-ruthenium catalysis. The hydrogenation produces chiral primary amines, which may work as catalytic poisons, however, the amino group of the hydrogenation product is rapidly acylated when the reaction is conducted in the presence of an appropriate acylating agent, such as Boc?O or Cbz-OSu.     

Asymmetric Catalysis with Bis(hydroxyphenyl)diamides/Rare‐Earth Metal Complexes

A series of asymmetric catalysts composed of conformationally flexible amide‐based chiral ligands and rare‐earth metals was developed for proton‐transfer catalysis. These ligands derived from amino acids provide an intriguing chiral platform for the formation of asymmetric catalysts upon complexation with rare‐earth metals. The scope of this arsenal of catalysts was further broadened by the development of heterobimetallic catalytic systems. The cooperative function of hydrogen bonding and metal coordination resulted in intriguing substrate specificity and stereocontrol, and the dynamic nature of the catalysts led to a switch of their function. Herein, we summarize our recent exploration of this class of catalysts.     

Catalytic Enantioselective Amination of Alcohols by the Use of Borrowing Hydrogen Methodology: Cooperative Catalysis by Iridium and a Chiral Phosphoric Acid

The catalytic asymmetric reduction of ketimines has been explored extensively for the synthesis of chiral amines, with reductants ranging from Hantzsch esters, silanes, and formic acid to H₂ gas. Alternatively, the amination of alcohols by the use of borrowing hydrogen methodology has proven a highly atom economical and green method for the production of amines without an external reductant, as the alcohol substrate serves as the H₂ donor. A catalytic enantioselective variant of this process for the synthesis of chiral amines, however, was not known. We have examined various transition‐metal complexes supported by chiral ligands known for asymmetric hydrogenation reactions, in combination with chiral Brønsted acids, which proved essential for the formation of the imine intermediate and the transfer‐hydrogenation step. Our studies led to an asymmetric amination of alcohols to provide access to a wide range of chiral amines with good to excellent enantioselectivity.     

Chloride‐Bridged Dinuclear Rhodium(III) Complexes Bearing Chiral Diphosphine Ligands: Catalyst Precursors for Asymmetric Hydrogenation of Simple Olefins

Efficient rhodium(III) catalysts were developed for asymmetric hydrogenation of simple olefins. A new series of chloride‐bridged dinuclear rhodium(III) complexes 1 were synthesized from the rhodium(I) precursor [RhCl(cod)]₂, chiral diphosphine ligands, and hydrochloric acid. Complexes from the series acted as efficient catalysts for asymmetric hydrogenation of (E)‐prop‐1‐ene‐1,2‐diyldibenzene and its derivatives without any directing groups, in sharp contrast to widely used rhodium(I) catalytic systems that require a directing group for high enantioselectivity. The catalytic system was applied to asymmetric hydrogenation of allylic alcohols, alkenylboranes, and unsaturated cyclic sulfones. Control experiments support the superiority of dinuclear rhodium(III) complexes 1 over typical rhodium(I) catalytic systems.     

Remote dipole effects as a means to accelerate [Ru(amino alcohol)]-catalyzed transfer hydrogenation of ketones

A new generation of 2-aza-norbornyl amino alcohol ligands for the catalytic transfer hydrogenation reaction of aromatic ketones was synthesized. Extremely active catalysts were formed by introducing a ketal functionality at the rear end of the ligand. Acetophenone was reduced in 96% ee at low catalyst loading, substrate to catalyst ratio, S/C 5000, within 90 minutes with isopropyl alcohol as the hydrogen donor. It was found that the dioxolane substituent in the ligand increased the turnover frequency, TOF50, from 1050 h(-1) to 3000 h(-1) at an S/C ratio of 1000. Introduction of a methyl group at the carbinol carbon resulted in TOF50 as high as 8500 h(-1). Transfer hydrogenation of a range of aromatic ketones was evaluated and found to reach completion within 30 minutes at room temperature, and excellent enantioselectivity, up to 99 % ee, was obtained. A possible explanation for the enhanced activity was provided by density functional calculations, which showed that the presence of a remote dipole in the ligand lowered the transition state energy.     

金属催化的不对称氢化反应研究进展与展望

手性过渡金属络合物催化的不对称氢化反应是合成光学活性化合物的重要方法. 本文从手性配体及手性催化剂、不对称催化新反应、新方法和新策略三个方面简要评述新世纪以来过渡金属催化的不对称氢化反应研究领域的新进展. 从新世纪初至今, 手性单磷配体得到了复兴, 出现了如MonoPhos、SiPhos、DpenPhos等高效单齿亚磷酰胺酯配体; 磷原子手性(P-手性)配体也得到了快速发展, 如BenzP*、ZhanPhos、TriFer等已成为新的高效手性双膦配体; 螺环骨架手性配体成为新世纪手性配体设计合成的亮点, 除了SiPhos、SIPHOX、SpinPHOX等高效手性螺环配体外, 手性螺环吡啶胺基磷配体SpiroPAP的铱催化剂成为目前最高效的分子催化剂. 不对称催化氢化新反应研究也取得了突破, 如非保护烯胺、杂芳环化合物及N-H亚胺的氢化等反应都实现了高对映选择性. 自组装手性催化剂、树枝状手性催化剂、铁磁性纳米负载的可回收手性催化剂, 以及“混合”配体手性催化剂等新方法和新策略也在不对称催化氢化反应中得到了应用. 然而, 手性过渡金属络合物催化的不对称氢化研究仍然充满挑战, 也期待新的突破.     

Employing the structural diversity of nature: development of modular dipeptide-analogue ligands for ruthenium-catalyzed enantioselective transfer hydrogenation of ketones

A library of novel dipeptide-analogue ligands based on the combination of tert-butoxycarbonyl(N-Boc)-protected alpha-amino acids and chiral vicinal amino alcohols were prepared. These highly modular ligands were combined with [[RuCl(2)(p-cymene)](2)] and the resulting metal complexes were screened as catalysts for the enantioselective reduction of acetophenone under transfer hydrogenation conditions using 2-propanol as the hydrogen donor. Excellent enantioselectivity of 1-phenylethanol (up to 98 % ee) was achieved with several of the novel catalysts. Although most of the ligands contained two stereocenters, it was demonstrated that the absolute configuration of the product alcohol was determined by the configuration of the amino acid part of the ligand. Employing ligands based on L-amino acids generated S-configured products, and catalysts based on D-amino acids favored the formation of the R-configured alcohol. The combination N-Boc-L-alanine and (R)-phenylglycinol (Boc-L-Ab) or its enantiomer (N-Boc-D-alanine and (S)-phenylglycinol, Boc-D-Aa) proved to be the best ligands for the reduction process. Transfer hydrogenation of a number of aryl alkyl ketones were evaluated and excellent enantioselectivity, up to 96 % ee, was obtained.     

Ruthenium(II) Tris-Pyrazolylmethane Complexes in Transfer Hydrogenation Reactions

While ruthenium(II) arene complexes have been widely investigated for their potential in catalytic transfer hydrogenation, studies on homologous compounds replacing the arene ligand with the six-electron donor tris(1-pyrazolyl)methane (tpm) are almost absent in the literature. The reactions of [RuCl(κ³-tpm)(PPh₃)₂]Cl, 1 , with a series of nitrogen ligands (L) proceeded with selective PPh₃ mono-substitution, affording the novel complexes [RuCl(κ³-tpm)(PPh₃)(L)]Cl (L=NCMe, 2 ; NCPh, 3 ; imidazole, 4 ) in almost quantitative yields. Products 2 – 4 were fully characterized by IR and multinuclear NMR spectroscopy, moreover the molecular structure of 4 was ascertained by single crystal X-ray diffraction. Compounds 2 – 4 were evaluated as catalytic precursors in the transfer hydrogenation of a series of ketones with isopropanol as the hydrogen source, and 2 exhibited the highest activity. Extensive NMR experiments and DFT calculations allowed to elucidate the mechanism of the transfer hydrogenation process, suggesting the crucial role played by the tpm ligand, reversibly switching from tri- to bidentate coordination during the catalytic cycle.     

Ru(Schiff-base)/Y复合材料对苯加氢反应的催化性能研究

一种新的低温苯加氢催化剂Ru(Schiff-base)金属配合物, 通过自由配体法封装于Y型沸石的孔腔中。使用XRD、N2吸附、FT-IR、DRS、DTA对催化剂进行表征。结果表明, 复合催化剂中希夫碱(Schiff-base)配体改变了中心离子的电子结构，使其更容易与反应物分子形成配位过渡态，络合活化的反应物分子更容易转化为产物。与离子交换法制备的母体Ru/Y相比，对纯苯的催化加氢性能明显提高。希夫碱配体的几何尺寸对复合材料的催化性能也有很大影响。     

Quasi-continuous synthesis of cobalt single atom catalysts for transfer hydrogenation of quinoline

Improving the transfer hydrogenation of N-heteroarenes is of key importance for various industrial processes and remains a challenge so far. We reported here a microcapsule-pyrolysis strategy to quasicontinuous synthesis S, N co-doped carbon supported Co single atom catalysts(Co/SNC), which was used for transfer hydrogenation of quinoline with formic acid as the hydrogen donor. Given the unique geometric and electronic properties of the Co single atoms, the excellent catalytic activity, selectiv...     

Mechanism of asymmetric hydrogenation of alpha-(acylamino)acrylic esters catalyzed by BINAP-ruthenium(II) diacetate

The mechanism of asymmetric hydrogenation of alpha-(acylamino)acrylic esters with Ru(CH(3)COO)(2)[(S)-binap] (BINAP = 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl), giving the S saturated products in >90% ee, has been investigated by means of a kinetic study, deuterium labeling experiments, isotope effect measurements, and NMR and X-ray analysis of certain Ru complexes. The hydrogenation in methanol under a low H2 pressure proceeds via a monohydride-unsaturate mechanism that involves the initial RuH formation followed by a reaction with an olefinic substrate. The migratory insertion in the enamide-RuH chelate complex occurs reversibly and endergonically in an exo manner, giving a five-membered metallacycle intermediate. The cleavage of the Ru-C bond is achieved with either H2 (major) or CH3OH (minor). Both of the pathways result in overall cis hydrogenation products. The hydrogen at C3 is mainly from an H2 molecule, and the C2 hydrogen is from another H2 or protic CH3OH. The major S and minor R enantiomers are produced via the same mechanism involving diastereomeric intermediates. The turnover rate is limited by the step of hydrogenolysis of a half-hydrogenated metallacyclic intermediate. The participation of two different hydrogen donor molecules is in contrast to the pairwise dihydrogenation using a single H2 molecule in the RhI-catalyzed reaction which occurs via a dihydride mechanism. In addition, the sense of asymmetric induction is opposite to that observed with S-BINAP-RhI catalysts. The origin of this phenomenon is interpreted in terms of stereocomplementary models of the enamide/metal chelate complexes. A series of model stoichiometric reactions mimicking the catalytic steps has indicated that most NMR-observable Ru complexes are not directly involved in the catalytic hydrogenation but are reservoirs of real catalytic complexes or even side products that retard the reaction.     

Application of a Supramolecular‐Ligand Library for the Automated Search for Catalysts for the Asymmetric Hydrogenation of Industrially Relevant Substrates

A procedure is described for the automated screening and lead optimization of a supramolecular‐ligand library for the rhodium‐catalyzed asymmetric hydrogenation of five challenging substrates relevant to industry. Each catalyst is (self‐) assembled from two urea‐functionalized ligands and a transition‐metal center through hydrogen‐bonding interactions. The modular ligand structure consists of three distinctive fragments: the urea binding motif, the spacer, and the ligand backbone, which carries the phosphorus donor atom. The building blocks for the ligand synthesis are widely available on a commercial basis, thus enabling access to a large number of ligands of high structural diversity. The simple synthetic steps enabled the scale‐up of the ligand synthesis to multigram quantities. For the catalyst screening, a library of twelve new chiral ligands was prepared that comprised substantial variation in electronic and steric properties. The automated procedures employed ensured the fast catalyst assembly, screening, and direct acquisition of samples for analysis. It appeared that the most selective catalyst was different for every substrate investigated and that small variations in the building blocks had a major impact on the catalyst performance. For two substrates, a catalyst was found that provided the product with outstanding enantioselectivity. The subsequent automated optimization of these two leads showed that an increase of catalyst loading, dihydrogen pressure, and temperature had a positive effect on the catalyst activity without affecting the catalyst selectivity.     

Application of parahydrogen for mechanistic investigations of heterogeneous catalytic processes

Parahydrogen-induced polarization technique (PHIP), based on the pairwise addition of molecular hydrogen to a substrate, was successfully applied to obtain novel information on the mechanisms of heterogeneous catalytic hydrogenation, hydrodesulfurization, and oligomerization processes. In particular, the PHIP effects were observed upon hydrogenation with parahydrogen catalyzed by the immobilized neutral complexes of rhodium and iridium, which confirms the similarity in the mechanisms of homogeneous and heterogeneous hydrogenation for such systems. In the study of acetylene oligomerization, a significant NMR signal enhancement was revealed for a number of C₄ oligomers, with the enhancement levels by far exceeding that observed in hydrogenation of carbon-carbon triple bonds. The mechanistic features of heterogeneous hydrogenation of a number of six-membered cyclic hydrocarbons over supported metal catalysts were investigated, and their hydrogenation scheme based on the pairwise addition of molecular hydrogen was proposed. Furthermore, the PHIP technique revealed that heterogeneous hydrodesulfurization of thiophene mainly proceeds via hydrogenation followed by a C—S bond cleavage. A significant enhancement of sensitivity in combination with characteristic line shapes of NMR signals make the PHIP method a unique and highly informative tool for the investigation of heterogeneous catalytic processes.     

Aminosulf(ox)ides as ligands for Iridium(I)-catalyzed asymmetric transfer hydrogenation

A new class of efficient catalysts was developed for the asymmetric transfer hydrogenation of unsymmetrical ketones. A series of chiral N,S-chelates (6-22) was synthesized to serve as ligands in the iridium(I)-catalyzed reduction of ketones. Both formic acid and 2-propanol proved to be suitable as hydrogen donors. Sulfoxidation of an (R)-cysteine-based aminosulfide provided a diastereomeric ligand family containing a chiral sulfur atom. The two chiral centers of these ligands showed a clear effect of chiral cooperativity. In addition, aminosulfides containing two asymmetric carbon atoms in the backbone were synthesized. Both the sulfoxide-containing beta-amino alcohols and the aminosulfides derived from 1,2-disubstituted amino alcohols gave rise to high reaction rates and moderate to excellent enantioselectivities in the reduction of various ketones. The enantioselective outcome of the reaction was favorably affected by selecting the most appropriate hydrogen donor. Enantioselectivities of up to 97% were reached in the reduction of aryl-alkyl ketones.     

Enantiopure Narrow Bite‐Angle POP Ligands: Synthesis and Catalytic Performance in Asymmetric Hydroformylations and Hydrogenations

Herein is reported the preparation of a set of narrow bite‐angle P–OP ligands the backbone of which contains a stereogenic carbon atom. The synthesis was based on a Corey–Bakshi–Shibata (CBS)‐catalyzed asymmetric reduction of phosphomides. The structure of the resulting 1,1‐P–OP ligands, which was selectively tuned through adequate combination of the configuration of the stereogenic carbon atom, its substituent, and the phosphite fragment, proved crucial for providing a rigid environment around the metal center, as evidenced by X‐ray crystallography. These new ligands enabled very good catalytic properties in the Rh‐mediated enantioselective hydrogenation and hydroformylation of challenging and model substrates (up to 99 % ee). Whereas for asymmetric hydrogenation the optimal P–OP ligand depended on the substrate, for hydroformylation, a single ligand was the highest‐performing one for almost all studied substrates: it contains an R‐configured stereogenic carbon atom between the two phosphorus ligating groups, and an S‐configured 3,3′‐diphenyl‐substituted biaryl unit.