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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]

Owing to their distinctive 1,3‐dipolar structure, the catalytic asymmetric hydrogenation of nitrones to hydroxylamines has been a formidable and longstanding challenge, characterized by intricate enantiocontrol and susceptibility to N−O bond cleavage. In this study, the asymmetric hydrogenation and transfer hydrogenation of nitrones were accomplished with a tethered TsDPEN‐derived cyclopentadienyl rhodium(III) catalyst (TsDPEN: p‐toluenesulfonyl‐1,2‐diphenylethylene‐1,2‐diamine), the reaction proceeds via a novel 7‐membered cyclic transition state, producing chiral hydroxylamines with up to 99 % yield and >99 % ee. The practical viability of this methodology was underscored by gram‐scale catalytic reactions and subsequent transformations. Furthermore, mechanistic investigations and DFT calculations were also conducted to elucidate the origin of enantioselectivity. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Transition metal‐catalyzed asymmetric transfer hydrogenation has been proven to be a powerful approach for the synthesis of chiral alcohols. Herein, a highly efficient and enantioselective transfer hydrogenation of dibenzoheptaheterocyclic ketones catalyzed by an arene‐tethered TsDPEN‐based Rh(III) catalyst has been successfully developed, and a variety of dibenzoheptaheterocyclic ketones were reduced by a 1/1 mixture of formic acid and DBU (1,8‐diazabicyclo[5.4.0]undec‐7‐ene) with high yields and enantioselectivities. With this method, the asymmetric reduction of 7,8‐difluorodibenzo[b,e]thiepin‐11(6H)‐one has been realized, providing the key intermediate of baloxavir marboxil with >99% yield and >99% ee at a substrate/catalyst molar ratio of 1000. [ABSTRACT FROM AUTHOR]

We herein reported the design and synthesis of a ferrocene‐based tetradentate ligand that is featured with modular synthesis and rigid skeleton. Its iron(II) complex facilitates asymmetric direct hydrogenation of ketones without the participation of extra strong‐field ligand such as CO and isocyanide. Hydride donor lithium aluminum hydride (LAH) converted non‐reactive Fe(II) species to reactive Fe(II) hydride species. With this catalyst, various chiral alcohols including the intermediate for montelukast could be prepared with satisfactory yields and enantioinduction. [ABSTRACT FROM AUTHOR]

The atom‐ and step‐efficient synthesis of chiral fused tricyclic lactams from readily available ketoesters using cheap ammonium salts as the nitrogen source is reported. This ruthenium‐catalyzed system operates through an efficient tandem dynamic kinetic asymmetric reductive amination (ARA)/lactamization and produces chiral fused tricyclic lactams in high yields with excellent diastereo‐ and enantioselectivity (up to >99 % ee, >20 : 1 dr and 98 % yield). The robust method was also applied to the concise synthesis of key intermediates in the synthesis of rivastigmine analogues and chiral N‐heterocyclic carbene catalysts. [ABSTRACT FROM AUTHOR]

By combining the concept of flash chemistry and radial synthesis, a novel microreactor (Flashstop reactor) was designed to study isomerization process of hydroformylation by a Rh/tetraphosphite catalyst in a time scale of seconds. It was found that in the initial 313 seconds, 60–99 % of 1‐octene was isomerized to 2‐ and 3‐octenes before the formation of aldehydes. Within this period, two different types of isomerization reactions were observed. It was proposed that a monohydride complex without CO ligand accounts for the ultrafast isomerization in the initial 30 seconds. The isomerization rate with such monohydride species was calculated much faster than that with the well‐known H(CO)Rh(P−P) species. Both experimental and DFT computational studies were carried out to support this assumption. Fast transformations early on in catalytic cycles have been rarely studied due to the lack of proper tools. We believe that the Flashstop reactor is a powerful tool for analysis of kinetics in gas‐liquid biphasic reactions within a time scale of seconds to minutes. [ABSTRACT FROM AUTHOR]

Chiral primary amines widely exist in drugs and are exceptionally important subunits or synthons in the syntheses of chiral secondary and tertiary amines of medicinal interest. Metal-catalyzed enantioselective reductive amination (ERA) of ketones with ammonium salts or ammonia provides a direct method for their synthesis. Although very useful, progress in this field has been very slow and important advances have only been achieved in the last few years. Several major challenges exist in this reaction, including (1) the reversible formation of unstable NH-imine intermediates; (2) the strong coordination property of N-containing reagents toward metal species; and (3) the lack of efficient catalytic systems that enable high enantiocontrol. Generally, the efficiency and enantiocontrol of this reaction is dependent on the substrate type, for instance, the use of α-keto esters/amides or aryl alkyl ketones is well established and they have even been used in the industrial production of chiral amine drugs. However, highly enantioselective control in dialkyl ketones, cyclic ketones, and α-keto acids remains unsolved. Herein, the historical development of ERA reactions with ammonium salts or ammonia gas is summarized, and novel synthetic applications toward useful synthons or drugs are presented. In addition, the factors restricting the growth of this method are also discussed. 1 Introduction 2 Enantioselective Reductive Amination via Hydrogenation 2.1 Enantioselective Reductive Amination of β-Keto Esters/Amides 2.2 Enantioselective Reductive Amination of Simple Ketones 2.3 Enantioselective Reductive Amination of α-Functionalized Ketones 2.4 Enantioselective Reductive Amination/Cyclization Cascade Reactions 2.5 Others 3 Enantioselective Reductive Amination via Transfer Hydrogenation 4 Synthetic Applications 5 Conclusions and Outlook [ABSTRACT FROM AUTHOR]

Arene hydrogenation is the most straightforward method to prepare carbo‐ and heterocycles. However, the high resonance energy prevents aromatic substrates from hydrogenation. Herein the homogeneous, nucleophilic hydrogenation of less electron‐rich arenes and heteroarenes is reported. The Co(P4N2)H species that has been demonstrated to be a strong hydride donor could deliver a hydride ion to the cyano (hetero)arene substrates. Deuterium labeling experiments supported a Michael‐type reaction pathway. Theoretical analyses have been conducted to investigate the hydricity of the catalytically active CoH species and the electrophilicity of the arene substrates. An outlook for the synthesis of more challenging substituted benzenes was proposed based on the in silico modification of the CoH species. [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]

The first rhodium‐catalyzed highly chemo‐, regio‐ and enantioselective hydroformylation of cyclopropyl‐functionalized trisubstituted alkenes affording useful chiral cyclopropyl entities is reported. Compared to generally used diphosphine ligands for asymmetric catalysis, the modified hybrid phosphorus ligand, named (R,S)‐DTBM‐Yanphos, can convert a series of readily available cyclopropyl‐functionalized trisubstituted alkenes into high‐value chiral cyclopropyl‐functionalized aldehydes with high selectivities (81–98 % ee). Gram‐scale reactions (TON up to 1500) and follow‐up transformations to the corresponding alcohol, acid, esters and nitrile are also presented. Finally, a possible hydroformylation mechanism involving ring‐open‐hydroformylation pathways is proposed based on control and deuteroformylation reactions. [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]