Search

Chiral carboxylic acids are important compounds because of their prevalence in pharmaceuticals, natural products and agrochemicals. Asymmetric hydrogenation of α,β‐unsaturated carboxylic acids has been widely recognized as one of the most efficient synthetic approaches to afford such compounds. Although related asymmetric hydrogenation of di‐ and trisubstituted unsaturated acids with noble metals is well established, asymmetric hydrogenation of challenging tetrasubstituted α,β‐unsaturated carboxylic acids is rarely reported. We demonstrate enantioselective hydrogenation of cyclic and acyclic tetrasubstituted α,β‐unsaturated carboxylic acids via cobalt(II) catalysis. This protocol showed broad substrate scope and gave chiral carboxylic acids in good yields with excellent enantiocontrol (up to 98 % yield and 99 % ee). Combined experimental and computational mechanistic studies support a CoII catalytic cycle involving migratory insertion and σ‐bond metathesis processes. DFT calculations reveal that enantioselectivity may originate from the steric effect between the phenyl groups of the ligand and the substrate. [ABSTRACT FROM AUTHOR]

Iridium/f‐Amphol‐catalyzed asymmetric hydrogenation of various benzo‐fused five to seven‐membered cyclic ketones was successfully developed, affording a series of chiral benzo‐fused cyclic alcohols with excellent results (75%–99% yields, 93%–>99% ee, and TON up to 297 000). The enantioenriched products can be employed as key intermediates or motifs for the synthesis of some important biologically active compounds, such as rasagiline mesylate TVP‐1012 used for the treatment of Parkinson's disease, the enantiomer of anticonvulsant drug eslicarbazepine acetate (BIA 2‐093). [ABSTRACT FROM AUTHOR]

Abstract: A highly regio‐ and enantioselective hydrogenation of challenging tetrasubstituted allenyl sulfones has been developed, affording chiral allylic sulfones in good yields with excellent regio‐ and enantioselectivities (up to 99 % yield and 99 % ee). This method provides an efficient and concise route to chiral allylic sulfones, thus offering an atom‐economic process with a wide range of potential applications in organic synthesis and medicinal chemistry. [ABSTRACT FROM AUTHOR]

Asymmetric reductive amination for the synthesis of both chiral tetrahydroquinolines (THQs) and tetrahydroisoquinolines (THIQs) has been realized with an Ir/ZhaoPhos catalytic system via a one-pot N-Boc deprotection/intramolecular asymmetric reductive amination (ARA) sequence. Control experiments reveal that HCl plays a vital role to the success of this transformation. The HCl acid assists the removal of the N-Boc protecting group and also provides chloride ions to interact with the thiourea moiety in ZhaoPhos, thus leading to excellent reaction enantiocontrol. [ABSTRACT FROM AUTHOR]

Highly enantioselective transfer hydrogenation of β-keto sulfonamides was developed via dynamic kinetic resolution using a chiral Ru(ii) catalyst with an azeotropic solution of HCO2H/Et3N as a hydrogen donor, affording α-substituted β-hydroxyl sulfonamides in good yields with excellent diastereo- and enantioselectivities. This method is featured with mild conditions, easy operation, and a broad substrate scope, which make it possible to find wide applications in the synthesis of natural products and biologically active compounds containing the α-substituted β-hydroxyl sulfonamide core. [ABSTRACT FROM AUTHOR]

A diversity-oriented synthetic strategy was developed for the total synthesis of kainoid amino acids, which led to the enantioselective synthesis of (−)-kainic acid and the first total synthesis of (+)-acromelic acid C. Rh(i)-catalyzed asymmetric enyne cycloisomerization served as the key reaction in this strategy for the rapid construction of highly functionalized lactam, and the resulting vinyl acetate moiety was further utilized as a versatile building block for the installation of both isopropylidene and 2-pyridone units existing in natural kainoids. [ABSTRACT FROM AUTHOR]

A succinct and efficient protocol was developed for the synthesis of chiral aromatic ketones via asymmetric hydrogenation of β,β-disubstituted enones with rhodium catalysts based on chiral bisphosphine thiourea ligands. A series of substrates (17 examples) was smoothly catalyzed to afford the corresponding chiral aromatic ketones in high conversions (＞99%) with excellent enantioselectivities (up to 96% ee). [ABSTRACT FROM AUTHOR]

We have successfully developed the asymmetric hydrogenation of β-silyl-α,β-unsaturated esters to prepare chiral 3-substituted-3-silylpropionic ester products catalyzed by rhodium/bisphosphine-thiourea (ZhaoPhos) with excellent results (up to 97% yield, >99% ee, 1500 TON). Moreover, our hydrogenation products can be efficiently converted to other important organic molecules, such as chiral ethyl ( R)-3-hydroxy-3-phenylpropanoate or ( R)-3-[dimethyl(phenyl)silyl]-3-phenylpropanoic acid. [ABSTRACT FROM AUTHOR]

An asymmetric mono-hydrogenation of 2-acetamido-1,3-dienes catalyzed by a Rh–DuanPhos complex has been developed. This approach provides easy access to chiral allylic amines with excellent enantioselectivities and high regioselectivities. The products are valuable chiral building blocks for pharmaceuticals. [ABSTRACT FROM AUTHOR]

We successfully extended our Rh/bisphosphine-thiourea (ZhaoPhos) catalytic system to asymmetric hydrogenation of α,β-unsaturated N-acylpyrazoles affording products with high yields and excellent enantioselectivities (up to 97% yield, 99% ee). The pyrazole moiety played an important role in providing H-bond acceptor sites, which is critical for achieving high reactivities and enantioselectivities. [ABSTRACT FROM AUTHOR]

The highly efficient and direct asymmetric reductive amination of arylacetones catalyzed by an iridium complex for the preparation of enantiomerically pure β-arylamines is described. The monodentate phosphoramidite ligand exhibits superb reactivity (TONs of up to 20 000) and enantioselectivity (up to 99 % ee). Additives played important roles in this reductive coupling reaction. [ABSTRACT FROM AUTHOR]

Iridium-catalyzed asymmetric hydrogenation of N-alkyl-2-alkylpyridinium salts provided 2-aryl-substituted piperidines with high levels of enantioselectivity. Simple benzyl and other alkyl groups successfully activated the challenging pyridine substrates toward hydrogenation. The use of the unusual chiral-phosphole-based MP2-SEGPHOS was the key to the success of this approach which provides a versatile and practical procedure for the synthesis of chiral piperidines. [ABSTRACT FROM AUTHOR]

An efficient methodology for synthesizing a small library of easily tunable and sterically bulky ligands for asymmetric hydroformylation (AHF) has been reported. Five groups of alkene substrates have been tested with excellent conversions, moderate-to-excellent regio- and enantioselectivities. Among the best result of the reported literature, application of ligand 1 c in the highly selective AHF of the challenging substrate 2,5-dihydrofuran yielded almost one isomer in up to 99 % conversion along with enantiomeric excesses ( ee) of up to 92 %. Highly enantioselective AHF of dihydropyrrole substrates is achieved using the same ligand, with up to 95 % ee and up to >1:50 β-isomer/α-isomer ratio. [ABSTRACT FROM AUTHOR]

The direct route: A Rhodium‐catalyzed asymmetric hydrogenation method for the efficient synthesis of a broad range of chiral allylic amines and aliphatic amines from readily available materials was developed. A chiral Z‐allylic amine was obtained for the first time through a Rhodium–DuanPhos‐catalyzed asymmetric hydrogenation. TMS=Trimethylsilyl, cod=cyclooctadiene, TON=turnover number. [ABSTRACT FROM AUTHOR]

An efficient and highly regio- and enantioselective catalytic asymmetric hydrogenation of α,γ-dienamido esters to γ,δ-unsaturated amido esters has been achieved using Rh/TangPhos as the catalyst. A series of γ,δ-unsaturated amido acids were furnished in excellent yields with up to 99 % ee. This effective methodology was applied in the asymmetric synthesis of key intermediate of Ramipril, an ACE inhibitor. [ABSTRACT FROM AUTHOR]

Review: 232 refs. [ABSTRACT FROM AUTHOR]

Abstract: A new type of chiral phosphine–quinoline ligand bearing a spiro[4,4]-1,6-nonadiene scaffold was designed and synthesized. Its cationic iridium complex has been characterized by X-ray diffraction analysis and evaluated in the catalytic asymmetric hydrogenation of alkene and imine derivatives, giving the corresponding hydrogenation products with high activity albeit moderate enantioselecitivity. [ABSTRACT FROM AUTHOR]

Abstract: A kinetic resolution process of Rh-catalyzed intramolecular Alder-ene reaction is described along with the studies of the substrate scope and stereochemistry of this remarkably efficient process. 3,4,5-Trisubstituted γ-lactones were synthesized in high enantioselectivity (>99% ee) and efficiency. The formal asymmetric syntheses of (−)-blastmycinolactol and (+)-blastmycinone, degradation products of the macrocyclic dilactone (+)-antimycin, were reported to address the applications of this methodology. [Copyright &y& Elsevier]

Several DIOP derivatives have been developed as efficient ligands for Rh and Ir-catalyzed asymmetric hydrogenations. The conformational mobility of the backbone in this type of ligand plays an important role in governing both the reactivity and enantioselectivity. Isolation of pure pre-catalyst is another key factor to obtain high catalytic activity. [Copyright &y& Elsevier]

The first rhodium-catalyzed, highly chemo- and enantioselective hydrogenation of a variety of α,β-disubstituted nitroalkenes (I) and (III) is reported. The nitroalkane products, e.g. (II) and (IV), provide entry to valuable chiral amphetamine derivatives. [ABSTRACT FROM AUTHOR]

Highlyregioselective andenantioselective asymmetric hydrogenation of cyclic dienamides catalyzedby an Rh-DuanPhos complex has been developed, which provides a readilyaccessible method for the synthesis of chiral cyclic allylic aminesin excellent enantioselectivities (up to 99% ee). The products arevaluable chiral building blocks and could be easily transformed tomultisubstituted cyclohexane derivatives. [ABSTRACT FROM AUTHOR]

An efficient and highly enantioselective catalytic asymmetric hydrogenation of β-acylamino nitroolefins has been realized by using Rh-TangPhos as the catalyst. A series of β-amino nitroalkane products, which are versatile intermediates in organic synthesis, were obtained with high yield and good enantioselectivity. [ABSTRACT FROM AUTHOR]

A novel method to desymmetrize meso-anhydrides into lactones via asymmetric hydrogenation catalyzed by the Ir–C3*-TunePhos complex has been developed. Various chiral lactones were synthesized with full conversion and excellent enantioselectivity under high reaction temperature. [ABSTRACT FROM AUTHOR]

Abstract: Rh- or Ru-catalyzed highly enantioselective hydrogenation of N-phthaloyl enamides is presented. Electron-rich TangPhos and DuanPhos are found to be effective ligands for Rh-catalyzed hydrogenation of α-aryl enamides and up to 99% ee has been achieved. In contrast, for the hydrogenation of α-alkyl enamide, the Ru-C3-TunePhos complex is more effective and up to 69% ee can be observed. This work is the first report of the hydrogenation of N-phthaloyl enamides. [Copyright &y& Elsevier]

For the first time, a strategy for the enantioselective Rh-TaniaPhos catalyzed asymmetric hydrogenation of unprotected β-enamine phosphonates directly to free β-amino phosphonates is reported which occurs with high yields and good enantioselectivities (up to 86% ee). [ABSTRACT FROM AUTHOR]

Efficient asymmetric hydrogenation of α-dehydroamino ketones is achieved in excellent enantioselectivity using a Rh-DuanPhos catalyst. [ABSTRACT FROM AUTHOR]

Chiral amino alcohol is a key function group in biologically active molecules. Consequently, the construction of this structural motif attracts extensive efforts by organic chemists. Developing highly enantioselective methods to prepare amino alcohols with efficiency remains one of the major challenges. Without any doubt, asymmetric hydrogenation is the most powerful method to make chiral molecules. For example, asymmetric hydrogenation of ketones is regarded as the most successful method to form chiral alcohols.

An efficient enantioselective synthesis of β-amino alcohols is achieved by rhodium-catalyzed asymmetric hydrogenation of enamides. [ABSTRACT FROM AUTHOR]

The hydrogenation provides chiral amines in high yields and enantioselectivities up to 95% ee. [ABSTRACT FROM AUTHOR]

Mild conditions, broad substrate scope, and the commercially available Rh-DuanPhos catalyst are features of this hydrogenation. [ABSTRACT FROM AUTHOR]

By using TangPhos as chiral ligand a series of β-amino nitroalkanes are obtained in high yields and with good enantioselectivities. [ABSTRACT FROM AUTHOR]

Due to NEt3 mediated isomerization also mixtures of α,β- and β,γ-unsaturated nitroalkenes can be deployed in this reaction. [ABSTRACT FROM AUTHOR]