Catalytic Asymmetric Hydrogenation of α-Acetamido Cinnamic Acids

Abstract

The homogeneous catalytic asymmetric hydrogenations of substituted cinnamic acids by (l-Benzyl-3,4-(R,R)-bis(diphenyl-phosphino) pyrrolidine (COD) Rh)BF₄ 6, easily prepared from L-tartaric acid has been studied. Contrary to other catalysts, this Rhodium (I) complex affords very high chemical and optical yields of N-acetylated amino acids under mild conditions even when using substrate to catalyst ratio as high as 16000. The method has been successfully applied for the preparation of L-Phenylalanine and L-Dopa.     

Asymmetric Synthesis IX1: Preparation of Chiral α-Substituted Phenethylamines

(S)-N-methyl-α-methyl-phenethylamines 5a-d were obtai-ned in 56–62% e.e. from the chiral synthoh (-)-N-cyano-methyl-4-phenyl-1,3-oxazolidine-1.     

Rh(I)-Catalyzed Enantioselective Hydrogenation of α-Substituted Ethenylphosphonic Acids

A class of chiral Rh(I) catalysts containing monodentate phosphorous acid diesters tautomerized from the corresponding secondary phosphine oxides was discovered by serendipitous hydrolysis of phosphoramidite ligands. The evolved catalysts demonstrated unprecedented enantioselectivities (98-99% ee) and high catalytic activities (as low as 0.01 mol% catalyst loading) in asymmetric hydrogenations of a wide variety of α-aryl-/alkyl-substituted ethenylphosphonic acids, providing a facile approach to the corresponding enantiopure phosphonic acids with significant biological importance.     

Efficient Cluster-Based Catalysts for Asymmetric Hydrogenation of α-Unsaturated Carboxylic Acids

The new clusters [H(4) Ru(4) (CO)(10) (μ-1,2-P-P)], [H(4) Ru(4) (CO)(10) (1,1-P-P)] and [H(4) Ru(4) (CO)(11) (P-P)] (P-P=chiral diphosphine of the ferrocene-based Josiphos or Walphos ligand families) have been synthesised and characterised. The crystal and molecular structures of eleven clusters reveal that the coordination modes of the diphosphine in the [H(4) Ru(4) (CO)(10) (μ-1,2-P-P)] clusters are different for the Josiphos and the Walphos ligands. The Josiphos ligands bridge a metal-metal bond of the ruthenium tetrahedron in the "conventional" manner, that is, with both phosphine moieties coordinated in equatorial positions relative to a triangular face of the tetrahedron, whereas the phosphine moieties of the Walphos ligands coordinate in one axial and one equatorial position. The differences in the ligand size and the coordination mode between the two types of ligands appear to be reflected in a relative propensity for isomerisation; in solution, the [H(4) Ru(4) (CO)(10) (1,1-Walphos)] clusters isomerise to the corresponding [H(4) Ru(4) (CO)(10) (μ-1,2-Walphos)] clusters, whereas the Josiphos-containing clusters show no tendency to isomerisation in solution. The clusters have been tested as catalysts for asymmetric hydrogenation of four prochiral α-unsaturated carboxylic acids and the prochiral methyl ester (E)-methyl 2-methylbut-2-enoate. High conversion rates (>94?%) and selectivities of product formation were observed for almost all catalysts/catalyst precursors. The observed enantioselectivities were low or nonexistent for the Josiphos-containing clusters and catalyst (cluster) recovery was low, suggesting that cluster fragmentation takes place. On the other hand, excellent conversion rates (99-100?%), product selectivities (99-100?% in most cases) and good enantioselectivities, reaching 90?% enantiomeric excess (ee) in certain cases, were observed for the Walphos-containing clusters, and the clusters could be recovered in good yield after completed catalysis. Results from high-pressure NMR and IR studies, catalyst poisoning tests and comparison of catalytic properties of two [H(4) Ru(4) (CO)(10) (μ-1,2-P-P)] clusters (P-P=Walphos ligands) with the analogous mononuclear catalysts [Ru(P-P)(carboxylato)(2) ] suggest that these clusters may be the active catalytic species, or direct precursors of an active catalytic cluster species.     

Copper-Catalyzed Asymmetric Arylation of α-Substituted Cyanoacetates Enabled by Chiral Amide Ligands

The (S)-nobin-embodied picolinamide and L-hydroxyproline-derived amide are effective ligands for Cu-catalyzed enantioselective coupling reaction of (hetero)aryl iodides with α-alkyl substituted cyanoacetates. This arylation reaction gave α-(heteroaryl)-α-alkyl cyanoacetates in good to excellent enantioselectivities (up to 95 % ee). A variety of functionalized (hetero)aryl and alkyl groups could be introduced to the quaternary center and therefore provided a valuable tool for preparing enantioenriched compounds with an all-carbon quaternary center tethered with convertible functional groups. The size of both α-alkyl and ester groups was proven as the key factor for asymmetric induction.     

Synthesis of Dendritic BINAP Ligands and Their Applications in Asymmetric Hydrogenation

Ｄｅｎｄｒｉｍｅｒｓａｒｅｈｉｇｈｌｙｂｒａｎｃｈｅｄｍａｃｒｏｍｏｌｅｃｕｌｅｓｔｈａｔｈａｖｅｐｒｅｃｉｓｅｌｙｄｅｆｉｎｅｄｍｏｌｅｃｕｌａｒｓｔｒｕｃｔｕｒｅｓｗｉｔｈｎａｎｏ ｓｃａｌｅｓｉｚｅ .ＳｉｎｃｅｔｈｅｐｉｏｎｅｅｒｉｎｇｗｏｒｋｏｆｖａｎＫｏｔｅｎｅｔａｌ.ｒｅｐｏｒｔｅｄｉｎ 1994 ,1ｄｅｎｄｒｉｔｉｃｃａｔａｌｙｓｔｓｈａｖｅｂｅｃｏｍｅａｓｕｂ ｊｅｃｔｏｆｉｎｔｅｎｓｉｖｅｒｅｓｅａｒｃｈ .2 ,3 Ａｌｔｈｏｕｇｈａｎｕｍｂｅｒｏｆｄｅｎ ｄｒｉｔｉｃｃａｔａｌｙｓｔｓｈａ…     

Improved Synthesis of 5,5-Diamino BINAP and Application to Asymmetric Hydrogenation

5,5-Diamino BINAP has been synthesized via three steps using BINAPO as starting material with high reaction yield. Present method needed only a stoichiometric quantity of nitric acid in the step of nitration of BINAPO, giving almost quantitative reaction yield. Based on 5,5-diamino BINAP, other three new BINAP derivatives have been synthesized. These modified BINAP ligands showed better catalytic properties as compared to BINAP itself in the asymmetric hydrogenation of 2-(6‘-methoxyl-2‘-naphthyl)acrylic acid.     

Asymmetric Hydrogenation of α-Hydroxy Ketones: A Reaction Sensitive toward Electronic Effect of Substrates

以[RuCl2(benzene)]2 和 SunPhos为原料现场制备的催化剂,催化不对称氢化α-羟基酮类化合物可获得手性1, 2-二醇类化合物,ee值最高达99%。     

In Situ Shell-Isolated Nanoparticle-Enhanced Raman Spectroscopy of Nickel-Catalyzed Hydrogenation Reactions

Synthesis methods to prepare lower transition metal catalysts and specifically Ni for Shell-Isolated Nanoparticle-Enhanced Raman Spectroscopy (SHINERS) are explored. Impregnation, colloidal deposition, and spark ablation have been investigated as suitable synthesis routes to prepare SHINERS-active Ni/Au@SiO₂ catalyst/Shell-Isolated Nanoparticles (SHINs). Ni precursors are confirmed to be notoriously difficult to reduce and the temperatures required are generally harsh enough to destroy SHINs, rendering SHINERS experiments on Ni infeasible using this approach. For colloidally synthesized Ni nanoparticles deposited on Au@SiO₂ SHINs, stabilizing ligands first need to be removed before application is possible in catalysis. The required procedure results in transformation of the metallic Ni core to a fully oxidized metal nanoparticle, again too challenging to reduce at temperatures still compatible with SHINs. Finally, by use of spark ablation we were able to prepare metallic Ni catalysts directly on Au@SiO₂ SHINs deposited on a Si wafer. These Ni/Au@SiO₂ catalyst/SHINs were subsequently successfully probed with several molecules (i. e. CO and acetylene) of interest for heterogeneous catalysis, and we show that they could be used to study the in situ hydrogenation of acetylene. We observe the interaction of acetylene with the Ni surface. This study further illustrates the true potential of SHINERS by opening the door to studying industrially relevant reactions under in situ or operando reaction conditions.     

Synthesis,Characterization, and Structures of α-Substituted Selenenyl-Acetophenones

Abstract

A series of α-substituted selenenyl acetophenone derivatives of the types, [PhC(OCH₂CH₂O)CH₂Se]₂, [PhC(OCH₂CH₂O)CH₂SeR], (PhCOCH₂Se)_2, and [PhCOCH₂SeR] have been prepared. These compounds have been characterized by elemental analyses, IR and NMR (¹H, ¹³C, ⁷⁷Se) spectroscopy. The compounds, [PhC(OCH₂CH₂)CH₂Se]₂ and (PhCOCH₂Se)₂ have been structurally characterized by single crystal X-ray diffraction analyses. The former shows intra-molecular Se‐?‐?‐O interaction, while the latter exhibits inter-molecular nonbonding Se‐?‐?‐O interaction.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]     

Copper-Catalyzed Chemoselective Asymmetric Hydrogenation of C=O Bonds of Exocyclic α,β-Unsaturated Pentanones

A highly chemoselective earth-abundant transition metal copper catalyzed asymmetric hydrogenation of C=O bonds of exocyclic α,β-unsaturated pentanones was realized using H₂. The desired products were obtained with up to 99 % yield and 96 % ee (enantiomeric excess) (99 % ee, after recrystallization). The corresponding chiral exocyclic allylic pentanol products can be converted into several bioactive molecules. The hydrogenation mechanism was investigated via deuterium-labelling experiments and control experiments, which indicate that the keto-enol isomerization rate of the substrate is faster than that of the hydrogenation and also show that the Cu−H complex can only catalyze chemoselectively the asymmetric reduction of the carbonyl group. Computational results indicate that the multiple attractive dispersion interactions (MADI effect) between the catalyst with bulky substituents and substrate play important roles which stabilize the transition states and reduce the generation of by-products.     

Cu-Catalyzed Asymmetric Kinetic Boron Conjugate Addition of γ-Substituted α,β-Unsaturated γ-Lactams

Chiral α,β-unsaturated γ-lactams bearing simple γ- substituents are found in biologically active molecules and natural products, however, their synthesis still remains difficult. Herein, we report an efficient kinetic resolution (KR) of γ-substituted α,β-unsaturated γ-lactams via a Cu-catalyzed asymmetric boron conjugate addition, which also leads to the efficient synthesis of chiral β-hydroxy-γ-lactams with β,γ-stereogenic carbon centers. The KR proceeded smoothly with a wide range of γ-alkyl or aryl substituted substrates including those bearing aromatic heterocycles and different N-protected substrates in up to 347 of s value. Their highly versatile transformations, synthetic utility in biologically active molecules, and inhibitory activities against cisplatin-sensitive ovarian cancer cell A2780 have also been demonstrated. Differing from the well-known mechanism involving Cu−B species in Cu-catalyzed boron conjugate additions, our mechanistic studies using density functional theory (DFT) calculations and experiments indicate that a Lewis acid Cu^I-catalyzed mechanism is the likely pathway in the catalytic reaction.     

Asymmetric Synthesis of Chiral-at-P Alkenylphosphonamidates through Nickel-Catalyzed C−P Coupling of Phosphoramidites and Alkenyl Halides

P-stereogenic compounds are widely used as ligands in asymmetric catalysis and are present in a myriad of bioactive compounds and pharmaceuticals. Yet, their stereocontrolled preparation remains challenging. Herein, we report a novel strategy towards versatile chiral-at-P alkenylphosphonamidates through a one-pot Ni-catalyzed C−P coupling/diastereoselective hydrolysis of readily available phosphoramidites and alkenyl halides. Remarkably, a chemo- and diastereodivergent behavior was observed upon subtle changes in the reaction conditions. Additionally, selective derivatizations of chiral alkenylphosphonamidates demonstrate their versatility as building blocks for the synthesis of structurally diverse P-stereogenic compounds.     

Hydrogenation and Skeleton Rearrangements of α-Pinene on Heterogeneous Catalysts

Hydrogenation and isomerization of -pinene on heterogeneous catalysts were studied, and conditions were found for hydrogenation of pinene to cis-pinane on nickel catalysts and for its dehydrogenation to p-cymene on decationized zeolite Y.     

Synthesis of New Chiral Phosphine Ligands and Their Application in Asymmetric Hydrogenation of Ketones

The design of new chiral ligands is the key in the development of transition metal catalyzed asymmetric synthesis. Many chiral diphosphine ligands have been prepared and applied in asymmetric catalytic reactions with excellent enantioselectivities. Among the chiral diphosphine ligands that have been reported, the atropisomeric C2-symmetric phosphines with a biaryl scaffold initiated by Noyori and co-workers with BINAP were found to have the widest application in the transition metal catalyze…     

Enantioselective Hydrogenation of α-Substituted Acrylic Acids Catalyzed by Iridium Complexes with Chiral Spiro Aminophosphine Ligands

Highly active: Iridium complexes with chiral spiro aminophosphine ligands were synthesized and applied as catalysts for the asymmetric hydrogenation of α-substituted acrylic acids. The complexes were highly active catalysts, showing turnover frequencies of up to 6000?h(-1) , and catalyst loadings could be reduced to 0.01?mol?%.     

Hydrogenation of α-cyanoacrylic acid and its esters by organohydridesilanes

The C=C bond in -cyanoacrylic acid is readily hydrogenated by organohydridesilanes in the absence of catalyst. The hydrogenation of -cyanoacrylate esters requires the presence of acid.A. N. Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 7, pp. 1655–1657, July, 1992.     

Synthesis of Novel Monophosphoramidite Ligands Derived from L-Proline for Rh-catalyzed Asymmetric Hydrogenation of α-Dehydroamino Acid Esters

Two novel monophosphoramidites were synthesized through a five-step transformation from commercially available L-proline. In the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives, ligand （Sc,Rα）-1b showed good enantioselectivity and up to 91% e.e. was obtained.     

Asymmetric Aminations and Kinetic Resolution of Acyclic α-Branched Ynones

An efficient method for asymmetric synthesis of acyclic α-tertiary amine derivatives has been achieved through enantioselective aminations of α-branched ynones with azodicarboxylates enabled by chiral phosphoric acid catalysis.Moreover,kinetic resolution of racemic starting material was realized under these conditions,which gave access to valuable enantioenriched α-substituted ketones.