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A novel synthetic route was developed for the construction of chiral cis-vicinal halohydrins derivatives through Ir/f-phamidol-catalysed asymmetric hydrogenation of corresponding α-halogenated ketones with high yields (up to 99% yield), excellent diastereoselectivities (>20 : 1 dr), enantioselectivities (up to 99% ee), and high substrate catalyst ratio (S/C = 1000). [ABSTRACT FROM AUTHOR]

Chiral β-heteroaryl amino alcohols are key fragments of many bioactive compounds and antibiotics, and the development of efficient synthetic methods for these compounds is of great value. The highly enantioselective hydrogenation of α-N-heteroaryl ketones was realized with a ruthenium-diphosphine–diamine catalyst, providing the corresponding chiral β-heteroaryl amino alcohols with up to 99% yield and up to >99% ee. The synthetic utilities of the current reaction were demonstrated by gram-scale synthesis of key intermediates of Sertaconazole and Cenobamate. [ABSTRACT FROM AUTHOR]

Owing to the biological significance and great synthetic value of chiral lactones and their derivatives, increasing attention has been paid to developing effective synthetic methods for chiral lactones. We herein report an efficient asymmetric hydrogenation of benzo-fused ketoesters, γ-ketoesters and biaryl-bridged ketoesters catalyzed by chiral iridium complexes bearing ferrocene-based chiral ligands, furnishing a series of chiral lactones in superb yields and excellent enantioselectivities (up to 99% yields and up to 99% ee). [ABSTRACT FROM AUTHOR]

A novel synthetic route was developed for the construction of a chiral cis-hexahydro-γ-carboline derivative through Ir/ZhaoPhos-catalyzed asymmetric hydrogenation of corresponding tetrahydro-γ-carboline with high yields (up to 99% yield), excellent diastereoselectivities (up to >99 : 1 dr) and enantioselectivities (up to 99% ee), and high substrate-to-catalyst ratios (up to 5000). [ABSTRACT FROM AUTHOR]

We report an efficient and straightforward method to synthesize enantio-enriched N-unprotected α-amino acetals via ruthenium-catalyzed direct asymmetric reductive amination. The α-amino acetal products are versatile and valuable platform molecules that can be converted to the corresponding α-amino acids, amino alcohols, and other derivatives by convenient transformations. [ABSTRACT FROM AUTHOR]

Owing to the biological significance and great synthetic value of 1,4-diarylbutane-1,4-diols and their derivatives, increasingly considerable attention has been paid to developing effective synthetic methods for chiral 1,4-diarylbutane-1,4-diols. We herein report an efficient asymmetric hydrogenation of 1,4-diaryldiketones catalyzed by a chiral iridium complex bearing f-amphox as ligand, furnishing a series of 1,4-diarylbutane-1,4-diols in excellent yields (up to >99%) with exceptional enantioselectivities (up to >99.9% ee) and diastereoselectivities (up to >100 : 1 dr). [ABSTRACT FROM AUTHOR]

This review provides a comprehensive view of the application of first-row transition metals in asymmetric hydrogenation and asymmetric transfer hydrogenation. The catalytic behavior of 3d metals is significantly different from that of 4d and 5d metals. The replacement of noble metals with first-row transition metals has encountered challenges such as different reaction mechanisms and unexpected deactivation of the catalyst. The potential involvement of a single-electron process has been the most notorious feature of first-row metals. This review aims to give readers a picture of how first-row transition metals catalyze hydrogenation reactions and the corresponding enantioinduction models. Although this article is partitioned according to the substrate type, it is mechanism-oriented and is focused on catalytic systems. A certain catalytic system could be applied in the hydrogenation of different types of double bonds. Similarities within first-row metals and differences from their 4d and 5d congeners were emphasized. [ABSTRACT FROM AUTHOR]

Phosphine – oxazoline (PHOX) ligands are a very important class of privileged ligands in asymmetric catalysis. A series of highly rigid oxa-spiro phosphine – oxazoline (O-SIPHOX) ligands based on O-SPINOL was synthesized efficiently, and their iridium complexes were synthesized by coordination of the O-SIPHOX ligands to [Ir(cod)Cl]2 in the presence of sodium tetrakis-3,5-bis(trifluoromethyl)phenylborate (NaBArF). The cationic iridium complexes showed high reactivity and excellent enantioselectivity in the asymmetric hydrogenation of 1-methylene-tetrahydro-benzo[d]azepin-2-ones (up to 99% yield and up to 99% ee). A key intermediate of the anti-obesity drug lorcaserin could be efficiently synthesized using this protocol. [ABSTRACT FROM AUTHOR]

Chiral α-hydroxy-β-lactams are key fragments of many bioactive compounds and antibiotics, and the development of efficient synthetic methods for these compounds is of great value. The highly enantioselective dynamic kinetic resolution (DKR) of α-keto-β-lactams was realized via a novel proton shuttling strategy. A wide range of α-keto-β-lactams were reduced efficiently and enantioselectively by Ni-catalyzed asymmetric hydrogenation, providing the corresponding α-hydroxy-β-lactam derivatives with high yields and enantioselectivities (up to 92% yield, up to 94% ee). Deuterium-labelling experiments indicate that phenylphosphinic acid plays a pivotal role in the DKR of α-keto-β-lactams by promoting the enolization process. The synthetic potential of this protocol was demonstrated by its application in the synthesis of a key intermediate of Taxol and (+)-epi-Cytoxazone. [ABSTRACT FROM AUTHOR]

α-Chiral primary amines are one among the most valuable and versatile building blocks for the synthesis of numerous amine-containing pharmaceuticals and natural compounds. They also serve as chiral ligands or organo-catalysts for asymmetric catalysis. However, most of the existing chemocatalytic methods toward enantiopure primary amines rely on multistep manipulations on N-substituted substrates, which are not ideally atom-economical and cost-effective. Among the catalytic methods including the asymmetric transformations of the pre-prepared or in situ formed NH imines, biomimetic chemocatalysis inspired by enzymatic transaminations has recently emerged as an appealing and straightforward method to access chiral primary amines. This tutorial review highlights the state-of-the-art catalytic methods for the direct asymmetric synthesis of α-chiral primary amines and demonstrates their utility in the construction of molecular complexities, which may attract extensive attention and inspire applications in synthetic and medicinal chemistry. [ABSTRACT FROM AUTHOR]

Highly efficient Ni-catalyzed asymmetric hydrogenation of cyclic N-sulfonyl ketimino esters was, for the first time, successfully developed, providing various chiral α-monosubstituted α-amino acid derivatives with excellent results (97–99% yields, 90 to >99% ee). Cyclic N-sulfonyl ketimines were also hydrogenated well to afford chiral amine derivatives with 98–99% yields and 97 to >99% ee. The gram-scale asymmetric hydrogenation was performed well with 85% yield and 99% ee using only 0.2 mol% catalyst. [ABSTRACT FROM AUTHOR]

A highly efficient diastereoselective transfer hydrogenation of α-aminoalkyl α′-chloromethyl ketones catalyzed by a tethered rhodium complex was developed and successfully utilized in the synthesis of the key intermediates of HIV protease inhibitors. With the current Rh(III) catalyst system, a series of chiral 3-amino-1-chloro-2-hydroxy-4-phenylbutanes were produced in excellent yields and diastereoselectivities (up to 99% yield, up to 99 : 1 dr). Both diastereomers of the desired products could be efficiently accessed by using the two enantiomers of the Rh(III) catalyst. [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 secondary phosphine oxide–phosphine mixed tridentate ligand and its ruthenium complex have been developed. This complex shows excellent catalytic activity for carbonyl reduction, especially for the reduction of α,β-unsaturated aldehydes. The turnover number and selectivity can reach up to 36 500 and 99%, respectively. Control experiments and DFT calculations supported an outer-sphere mechanism during the hydrogenation reaction. [ABSTRACT FROM AUTHOR]

Upon incorporation of a noncovalent ion pair interaction, a new chiral ferrocenyl bisphosphorus ligand t-Bu-Wudaphos was developed. t-Bu-Wudaphos can be easily synthesized with very high diastereoselectivity as a highly air stable solid. The new ligand exhibited excellent reactivities and enantioselectivities in the asymmetric hydrogenation of α-methylene-γ-keto-carboxylic acids via an ion pair noncovalent interaction (up to ＞99% conversion, ＞99% ee). [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]

A rhodium-catalyzed asymmetric hydrogenation of challenging tetrasubstituted β-acetoxy-α-enamido esters was developed, giving chiral β-acetoxy-α-amido esters in high yields with excellent enantioselectivities (up to ＞99% ee). The products could be easily transformed to β-hydroxy-α-amino acid derivatives which are valuable chiral building blocks and a novel route for the synthesis of droxidopa was also developed. [ABSTRACT FROM AUTHOR]

Cobalt-catalyzed highly (Z)-selective semihydrogenation of alkynes using molecular H2 was developed using commercially available and cheap cobalt precursors. A variety of (Z)-alkenes were obtained in moderate to excellent selectivities [(Z)-alkene/(E)-alkene/alkane ratio up to ＞99 : 1 : 1] and it was found that the readily available ethylenediamine ligand is crucial in determining the selectivity. [ABSTRACT FROM AUTHOR]

Asymmetric hydrogenation of various 3-substituted maleic anhydrides catalyzed by Rh/bisphosphine-thiourea (ZhaoPhos) under mild conditions was successfully developed. A wide range of 3-alkyl and 3-aryl maleic anhydrides were hydrogenated well to provide the desired products 3-substituted succinic anhydrides in one hour with excellent results (full conversions, up to 99% yield, 99% ee, 3000 TON). Importantly, we developed a creative and efficient synthetic route to construct the key intermediate of the hypoglycemic drug mitiglinide through our catalytic system. [ABSTRACT FROM AUTHOR]

An efficient rhodium-catalyzed asymmetric hydrogenation of α-amino acrylonitriles has been developed, affording α-acylamino nitriles with high yields and excellent enantioselectivities (up to 99% yield and ＞99% ee). This novel methodology provides an efficient and concise synthetic route to chiral α-amino nitriles, which are versatile intermediates in organic synthesis. [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]

Rhodium complexes coordinated by Chenphos are very effective catalysts for the enantioselective hydrogenation of α-aryloxy- and α-alkoxy-substituted α,β-unsaturated carboxylic acids under mild conditions in CF3CH2OH. The catalytic system could be successfully employed in building the core structure of a new FDA approved drug LCZ 696. [ABSTRACT FROM AUTHOR]

A hydrazine group-containing nitrogen–phosphine ligand and corresponding ruthenium complexes were synthesized. When these complexes were used for hydrogenation of esters, excellent performance was observed (TON up to 17 200). A wide substrate scope was suitable for this catalytic system. [ABSTRACT FROM AUTHOR]

(S,R)-Indan–ambox ligand and its ruthenium(ii) complex have been prepared and successfully applied to asymmetric hydrogenation of prochiral simple ketones. A wide range of unfunctionalized ketones are reduced by Ru(ii)-indan–ambox catalyst with excellent enantioselectivities (up to 97% ee). [ABSTRACT FROM AUTHOR]