Asymmetric Ring Opening/Cyclization/Retro‐Mannich Reaction of Cyclopropyl Ketones with Aryl 1,2‐Diamines for the Synthesis of Benzimidazole Derivatives

A highly efficient asymmetric ring‐opening/cyclization/retro‐Mannich reaction of cyclopropyl ketones with aryl 1,2‐diamines has been realized using a chiral N,N′‐dioxide/Sc^III catalyst. Benzimidazoles containing chiral side chains were generated under mild reaction conditions in excellent outcomes (up to 99 % yield and 97 % ee). This method also provides efficient access to chiral benzimidazole‐substituted amide and cycloheptene derivatives.     

Selective oxidation of benzylic or allylic hydroxyl group of sec-1,2-diols

A mild and efficient method to selectively oxidize chiral sec-1,2-diols has been developed, which demonstrates that 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) can selectively oxidize benzylic or allylic hydroxyl group of sec-1,2-diols under ultrasound wave promotion. The configuration of the adjacent chiral center is retained.     

Synthesis of chiral isoindolinones via asymmetric propargylation/lactamization cascade

A Zn-mediated propargylation/lactamization cascade reaction with chiral 2-formylbenzoate derived N-tert-butanesulfinyl imines was realized, which provided a practical and efficient method for the synthesis of chiral isoindolinones. High diastereoselectivities (up to 97:3 dr) and good reaction yields were observed for most examined cases.     

One-pot and microwave-assisted synthesis of N-sulfonylaziridines

A novel and efficient microwave-assisted one-step reaction was developed to synthesize chiral N-sulfonylaziridines by the reaction of different chiral amino alcohols and sulfonic chlorides. The newly developed microwave synthetic method has the advantage of reducing the reaction time from 24 to 0.5 h with improved yields (84-93%) and minimizing by-products.     

Concise Synthesis of Chiral Tricyclic Lactams by Tandem Dynamic Kinetic Asymmetric Reductive Amination/Lactamization Using Ammonium Salts

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.     

Enantioselective Hydroarylation of Olefins Using Palladium/Chiral Quinoline Oxazolines

Palladium-catalyzed arylation and alkenylation of olefins, known as the Heck reaction, is one of the most efficient catalytic methods for carbon-carbon bond formation in organic synthesis^[1]. During the last decade, asymmetric Heck reactions have attracted great attention, and a number of highly enantioselective chiral ligands have been developed to enhance chiral discrimination in these reactions^[2]. However, asymmetric Heck-type hydroarylations of olefins, addition of aryl halides or triflates to carbon-carbon double bonds, have not been well studied. In 1991, Brunner reported an asymmetric hydroarylation of norbornene and norbornadiene with aryl iodides using chiral bisphosphine ligands, and around 40% ee was achieved^[3]. Later on, Achiwa reached around 70% ee in the asymmetric hydroarylation of norbornene with phenyl triflate by using chiral P-N ligands^[4,5]. Herein, we wish to describe our investigations on chiral quinolinyl-oxazoline ligands that provide the first examples of efficient bisnitrogen ligands in Heck-type hydroarylation and the application of this reaction in the asymmetric synthesis of Epibatidine.     

对环糊精手性固定相的柱上在线处理

鉴于环糊精类手性固定相长期使用后手性分离能力变坏,提出联机柱上在线处理反应。在处理过程中,可使某些手性物质的分离因子逐渐改善,直至达到基线分离,证明这种处理是行之有效的,同时发现有其局限性。     

Synthesis of (αR,βS)-epoxyketones by asymmetric epoxidation of chalcones with cinchona phase-transfer catalysts

An efficient method to synthetically produce optically enriched (αR,βS)-epoxyketones was developed using a quaternary ammonium salt derived from cinchona alkaloid as the chiral phase-transfer catalyst. (αR,βS)-Epoxyketones were prepared in high optical purities (91-99% ee) by the asymmetric epoxidation of 1,3-diarylenones with aqueous sodium hypochlorite in the presence of a hydrocinchonine-derived chiral phase-transfer catalyst bearing a 2,3,4-trifluorobenzyl group.     

InBr3-catalyzed direct alkynylation of nitrones with terminal alkynes: an efficient synthesis of N-hydroxy-propargyl amines

An InBr₃-catalyzed direct and efficient alkynylation of nitrones with terminal alkynes was developed. The process enables practical synthesis of a wide range of synthetically useful N-hydroxy-propargyl amine derivatives in good yields under mild conditions. The application of this method to optically active propargylic N-hydroxyamines syntheses was also described. With chiral nitrones, good diastereoselectivities were obtained. Moreover, the first chiral indium(III) complex-catalyzed asymmetric alkynylation of nitrone was achieved with moderate enantioselectivity.     

Synergistic Pd/Cu Catalysis in Organic Synthesis

Synergistic Pd/Cu catalysis has been utilized in the Sonogashira reaction since 1975. However, this strategy has not received much attention from the organic chemist community until recently. Synergistic Pd/Cu catalysis is becoming a proficient method for the development of catalytic reactions, including several new and efficient cross-coupling reactions. Additionally, several challenging asymmetric reactions, including stereodivergent synthesis, have been discovered by the combined use of a chiral metal catalyst and a second achiral metal catalyst or two chiral metal catalysts. This review provides an overview of this field, with the aims of highlighting both the development of synergistic Pd/Cu catalysis in organic synthesis and the reaction mechanisms involved in this research area.     

A highly efficient and direct approach for synthesis of enantiopure beta-amino alcohols by reductive cross-coupling of chiral N-tert-butanesulfinyl imines with aldehydes

A highly efficient and practical approach for the synthesis of optically pure beta-amino alcohols by the SmI2-induced reductive cross-coupling of chiral N-tert-butanesulfinyl imines with aldehydes was developed. This method allows the preparation of a broad range of chiral beta-amino alcohols, including functionalized ones under mild conditions. It provides a straightforward access to enantiopure beta-amino alcohols that are widely applicable in asymmetric synthesis.     

Synthesis of Chiral Aminocyclopropanes by Rare‐Earth‐Metal‐Catalyzed Cyclopropene Hydroamination

The search for efficient and selective routes for the synthesis of chiral aminocyclopropane derivatives is of great interest and importance as these structures are important components of biologically active natural products and pharmaceuticals. We herein report the enantioselective intermolecular hydroamination of substituted cyclopropenes with various amines catalyzed by chiral half‐sandwich rare‐earth‐metal complexes. This method constitutes a 100 % atom‐efficient route for the synthesis of a variety of chiral α‐aminocyclopropane derivatives in high yields (up to 96 %) and excellent stereoselectivity (up to >20:1 d.r. and 99 % ee) under mild reaction conditions (25 °C).     

Efficient Asymmetric Synthesis of Structurally Diverse P‐Stereogenic Phosphinamides for Catalyst Design

The use of chiral phosphinamides is relatively unexplored because of the lack of a general method for the synthesis. Reported herein is the development of a general, efficient, and highly enantioselective method for the synthesis of structurally diverse P‐stereogenic phosphinamides. The method relies on nucleophilic substitution of a chiral phosphinate derived from the versatile chiral phosphinyl transfer agent 1,3,2‐benzoxazaphosphinine‐2‐oxide. These chiral phosphinamides were utilized for the first synthesis of readily tunable P‐stereogenic Lewis base organocatalysts, which were used successfully for highly enantioselective catalysis.     

tert-Butanesulfinylthioether ligands: synthesis and application in palladium-catalyzed asymmetric allylic alkylation

A class of novel chiral SO-S-type bidentate ligands based on the tert-butylsulfinyl moiety as the sole chiral source were designed and synthesized through a simple and efficient pathway. These ligands are effective catalyst precursors for the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate and moderate to good stereoselectivities (up to 84% ee) were obtained.     

Asymmetric Synthesis of Chiral Sulfimides through the O-Alkylation of Enantioenriched Sulfinamides and Addition of Carbon Nucleophiles

Chiral sulfimides, the aza-analogues of sulfoxides, are valuable compounds in organic synthesis and medicinal chemistry. Herein, we report an efficient method for preparing chiral sulfimides from easily available enantioenriched sulfinamides. The key step of this method is a stereospecific oxygen-selective alkylation of enantioenriched sulfinamides, which is accomplished by using isopropyl iodide, K₂CO₃, and DMPU. The resulting chiral sulfinimidate esters are transformed to chiral sulfimides by the nucleophilic addition of the Grignard reagents under simple conditions. This transformation enables access to the enantioenriched diaryl or dialkyl sulfimides bearing two similar carbon substituents, which are difficult to synthesize by previous methods.     

Enantioselective synthesis of (S)-4-methyleneglutamic acid via tandem conjugate addition-elimination under phase-transfer catalytic conditions

An efficient enantioselective synthetic method for (S)-4-methyleneglutamic acid is reported. Phase-transfer catalytic conjugate addition-elimination of the benzophenone imine of glycine tert-butyl ester in the presence of chiral Cinchona-derived catalysts give the corresponding conjugated addition products (>99% ee), which could be hydrolyzed to chiral (S)-4-methyleneglutamic acid.     

Stereoselective synthesis of spirocyclic oxindoles based on a one-pot Ullmann coupling/Claisen rearrangement and its application to the synthesis of a hexahydropyrrolo[2,3-b]indole alkaloid

An efficient and convenient approach to the synthesis of spirocyclic oxindoles from iodoindoles has been developed. The most striking feature of this approach is that the sequential intramolecular Ullmann coupling and Claisen rearrangement proceeds in a one-pot manner to afford 3-spiro-2-oxindoles in good yield with excellent diastereoselectivity. Application of this one-pot reaction to chiral non-racemic tertiary alcohol substrates resulted in complete chirality transfer to the spirocyclic quaternary carbon. Using this method, asymmetric total synthesis of (−)-debromoflustramine B was accomplished.     

Facile synthesis of chiral glycine using D-glucose as a chiral template

A facile synthetic method of chiral glycine and a new access to chiral acetic acid based on a concept of chirality transfer from glucose are described.     

Synthesis of Chiral Tertiary Boronic Esters by Oxime‐Directed Catalytic Asymmetric Hydroboration

Chiral boronic esters are useful intermediates in asymmetric synthesis. We have previously shown that carbonyl‐directed catalytic asymmetric hydroboration (CAHB) is an efficient approach to the synthesis of functionalized primary and secondary chiral boronic esters. We now report that the oxime‐directed CAHB of alkyl‐substituted methylidene and trisubstituted alkene substrates by pinacolborane (pinBH) affords oxime‐containing chiral tertiary boronic esters with yields up to 87 % and enantiomeric ratios up to 96:4 e.r. The utility of the method is demonstrated by the formation of chiral diols and O‐substituted hydroxylamines, the generation of quaternary carbon stereocenters through carbon–carbon coupling reactions, and the preparation of chiral 3,4,4‐trisubstituted isoxazolines.     

Chiral Method Development Strategies for HPLC using Macrocyclic Glycopeptide-Based Stationary Phases

Chiral HPLC methods using macrocyclic glycopeptide-based chiral stationary phases have been widely used and reported; however, the development of efficient methods to separate and quantify the analytes with high resolution is a challenging task. Therefore, the knowledge regarding the optimization of chromatographic parameters regarding this type of chiral chromatography is essential. This review presents and discusses the optimization of HPLC conditions and parameters for the chiral resolution of racemic drugs on macrocyclic glycopeptide-based chiral stationary phases. Strategies for chiral method development are presented, using polar ionic, reversed phase, normal phase and polar organic modes. The effect of the most important chromatographic parameters, such as mobile phase composition, flow rate and temperature on the enantioseparation are discussed aiming the adequate screening and optimization protocol for each mode.