Asymmetric Transformation Driven by Confinement and Self-Release in Single-Layered Porous Nanosheets

Reported here is the use of single-layered, chiral porous sheets with induced pore chirality for repeatable asymmetric transformations and self-separation without the need for chiral catalysts or chiral auxiliaries. The asymmetric induction is driven by chiral fixation of absorbed achiral substrates inside the chiral pores for transformation into enantiopure products with enantioselectivities of greater than 99 % ee. When the conversion is completed, the products are spontaneously separated out of the pores, enabling the porous sheets to perform repeated cycles of converting achiral substrates into chiral products for release without compromising pore performance. Confinement of achiral substrates into two-dimensional chiral porous materials provides access to a highly efficient alternative to current asymmetric synthesis methodologies.     

Remarkable salt effect on In-mediated allylation of N-tert-butanesulfinyl imines in aqueous media: highly practical asymmetric synthesis of chiral homoallylic amines and isoindolinones

A highly practical and efficient asymmetric synthesis of chiral homoallylic amines by In-mediated allylation of chiral N-tert-butanesulfinyl imines in aqueous media at room temperature was developed. With 2-formylbenzoate imine substrates, the method allows the highly enantioselective achievement of a variety of pharmacologically important 3-allyl isoindolinone compounds.     

Enantioselective synthesis of binaphthyl polymers using chiral asymmetric phenolic coupling catalysts: oxidative coupling and tandem glaser/oxidative coupling

A series of functionalized and optically active polybinaphthyls have been synthesized from achiral substrates by asymmetric oxidative phenolic coupling using a chiral 1,5-diaza-cis-decalin copper catalyst. In most cases, a copper tetrafluoroborate catalyst was found to be superior to the copper iodide catalyst, as ortho-iodination of the substrates could be prevented. Three methods for the formation of chiral polymers are described. In the first method, two 2-naphthols linked together at C-6 are subjected to the optimized asymmetric oxidative phenolic coupling conditions to form chiral polynaphthyls. A combination of NMR and HPLC measurements secured the selectivity of the asymmetric coupling. In the second method, substrates containing only one naphthalene were utilized. By incorporating a 2-naphthol and a terminal alkyne, the chiral copper catalysts effect both Glaser-Hay coupling of the alkyne and oxidative asymmetric coupling of the 2-naphthol with remarkable chemoselectivity. The relative reaction rates of various moieties with the chiral catalysts follows the order: benzyl cyanides > aryl alkynes > electron-rich 2-naphthols > electron-deficient 2-naphthols > alkyl alkynes. Because of high chemoselectivity, this approach is useful for the organized assembly of multifunctional substrates in a single operation. In all cases, no cross-coupling is observed between the alkyne and the 2-naphthol. This approach was thus applied to a set of highly functionalized precursors. In this third case, the biaryl coupling was performed first and a Glaser-Hay coupling was performed in a separate step to generate a highly functionalized polymer. In some cases, the resultant chiral polymers exhibit very large optical rotations.     

Asymmetric Synthesis of Chiral Atropisomeric Bis‐Aryl Organophosphorus from Menthyl H‐Phosphinate

This review describes new methods for the synthesis of chiral monophosphine ligands with menthyl phenylphosphinate as a chiral auxiliary through asymmetric Suzuki‐Miyaura cross‐coupling reactions and asymmetric C–H functionalization. The chiral menthyl phenylphosphinate as a chiral auxiliary is easy to prepare and the menthyl group can easily be transformed into other functional groups, with the chiral center synchronously remaining. These methodologies provide highly efficient and practical strategies for the synthesis of novel axially chiral biaryl monophosphine oxides and their corresponding phosphines. Meanwhile, these reactions are easy to handle and exhibit wide scope for substrates with excellent diastereomeric ratios.     

Asymmetric synthesis of highly functionalized γ-lactams through an organocatalytic aza-Michael–Michael reaction cascade using fumaric acid amide esters as multi-reactive substrates

We developed a novel method for the asymmetric synthesis of highly functionalized γ-lactams through an organocatalytic aza-Michael–Michael reaction cascade using fumaric acid amide esters as multi-reactive substrates. Using chiral primary or secondary amine organocatalysts, we obtained two types of γ-lactams with three contiguous chiral centers in moderate to good yield with excellent enantioselectivity and diastereoselectivity.     

Development of highly potent chiral discrimination methods that solve the problems of diastereomer method.

The development of highly potent chiral discrimination methods that solve the problems of the diastereomer method is described. Explaining the significant results of separations of diastereomers having chiral centers separated by 13 - 27 bonds with reversed-phase HPLC was hitherto impossible. To attract more scientific interest toward the mechanism of the separation, the author proposes a hypothesis, Induced Chiral Fields, that the achiral reversed phases can provide chiral fields depending on the structures of the substrates.     

Rh(Ⅰ)-catalyzed regio-and enantioselective allylic alkylation of Meldrum's acid

A Rh(Ⅰ)-catalyzed highly regio-and enantioselective allylic alkylation of Meldrum acid with racemic allylic substrates bearing alkyl groups has been developed.The applying of chiral bisoxazopinephosphine ligand is essential for the high yields and selectivities.This method provides a rapid access to various chiral β-alkyl-γ,δ-unsaturated carboxylic acids and their derivatives.     

Modulating the acidity: highly acidic Brønsted acids in asymmetric catalysis

Recently, chiral highly acidic Brønsted acids have emerged as powerful catalysts for enantioselective C C and C X bond‐forming reactions. Their strong acidity renders them valuable tools for the activation of imines, carbonyl compounds, and other weakly basic substrates. As a result, new perspectives are opened and highly stereoselective transformations based on the concept of chiral contact‐ion‐pair catalysis can be realized. This Minireview gives an overview of the design and application of these new organocatalysts and presents recent results in this rapidly growing field.     

Tandem Sakurai-aldol addition reactions as a route to structurally complex carbocycles

Tandem intramolecular Sakurai-aldol reactions provide a concise and highly diastereoselective route to substituted cyclohexenone derivatives. The cyclization substrates are readily obtained using olefin isomerization-Claisen rearrangement (ICR) reactions to prepare the key chiral allyl silane precursors. The Claisen reaction products are elaborated to the chiral Sakurai-aldol substrates by an efficient two-step sequence involving vinyl organometallic-aldehyde addition and oxidation of the resulting alcohol. The reaction of the resulting enones with TiCl(4) elicits a highly stereoselective allyl silane conjugate addition to produce a trichlorotitanium enolate as the reaction intermediate; intermolecular trapping of the enolate with an aldehyde provides pentasubstituted cyclohexanone derivatives in which the annulation reaction establishes four stereocenters and two new C-C bonds. A fully intramolecular variant of the Sakurai-aldol reaction that creates four stereocenters, two new C-C bonds, and establishes two new carbocyclic rings is also described.     

Relay catalysis: combined metal catalyzed oxidation and asymmetric iminium catalysis for the synthesis of bi- and tricyclic chromenes

A catalytic asymmetric oxidative iminium-allenamine cascade allows the use of propargyl alcohols as stable substrates and yields valuable chiral bicyclic 4H-chromenes. A subsequent Michael addition-condensation domino reaction provides complex tricyclic 4H-chromenes in a highly enantioselective fashion.     

Regio‐ and Stereoselective Modification of Chiral α‐Amino Ketones by Pd‐Catalyzed Allylic Alkylation

Chiral α‐amino ketones are excellent nucleophiles for stereoselective palladium‐catalyzed allylic alkylations. Both chiral as well as achiral allylic substrates can be applied, while the stereochemical outcome of the reaction is controlled by the chiral ketone enolate. The substituted amino ketones formed can be reduced stereoselectively, and up to five consecutive stereogenic centers can be obtained. This approach can be used for the synthesis of highly substituted piperidine derivatives.     

Rh-Catalyzed Asymmetric Hydrogenation of α,β- and β,β-Disubstituted Unsaturated Boronate Esters

A highly enantioselective hydrogenation of α,β-unsaturated boronate esters catalyzed by Rh-(S)-DTBM-Segphos complex has been developed. Both (Z)-α,β- and β,β-disubstituted substrates can be successfully hydrogenated to afford chiral boronates with excellent enantioselectivities, up to 98 % ee. Furthermore, the obtained chiral boronate esters, as important versatile synthetic intermediates are successfully transformed to the corresponding chiral alcohols, amines and other important derivatives with maintained enantioselectivities.     

Enantioselective intramolecular hydroarylation of alkenes via directed C-H bond activation

Highly enantioselective catalytic intramolecular ortho-alkylation of aromatic imines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using [RhCl(coe)2]2 and chiral phosphoramidite ligands. Cyclization of substrates containing 1,1- and 1,2-disubstituted as well as trisubstituted alkenes were achieved with enantioselectivities >90% ee for each substrate class. Cyclization of substrates with Z-alkene isomers proceeded much more efficiently than substrates with E-alkene isomers. This further enabled the highly stereoselective intramolecular alkylation of certain substrates containing Z/E-alkene mixtures via a Rh-catalyzed alkene isomerization with preferential cyclization of the Z-isomer.     

Synthesis of Axially Chiral Biaryls through Sulfoxide‐Directed Asymmetric Mild CH Activation and Dynamic Kinetic Resolution

A mild and robust direct C? H functionalization strategy has been applied to the synthesis of axially chiral biaryls. Such an efficient and stereoselective transformation occurs through an original dynamic kinetic resolution pathway enabling the conversion of diastereomeric mixtures of non‐prefunctionalized substrates into atropisomerically pure, highly substituted biaryl scaffolds. The main feature of this transformation is the use of an enantiopure sulfoxide as both chiral auxiliary and traceless directing group. The potential of newly synthesized biaryls as valuable building blocks is further illustrated.     

A Chiral Nitrogen Ligand for Enantioselective,Iridium‐Catalyzed Silylation of Aromatic C−H Bonds

Iridium catalysts containing dative nitrogen ligands are highly active for the borylation and silylation of C−H bonds, but chiral analogs of these catalysts for enantioselective silylation reactions have not been developed. We report a new chiral pyridinyloxazoline ligand for enantioselective, intramolecular silylation of symmetrical diarylmethoxy diethylsilanes. Regioselective and enantioselective silylation of unsymmetrical substrates was also achieved in the presence of this newly developed system. Preliminary mechanistic studies imply that C−H bond cleavage is irreversible, but not the rate‐determining step.     

Synthesis of Axially Chiral Biaryls through Sulfoxide‐Directed Asymmetric Mild C?H Activation and Dynamic Kinetic Resolution

A mild and robust direct C H functionalization strategy has been applied to the synthesis of axially chiral biaryls. Such an efficient and stereoselective transformation occurs through an original dynamic kinetic resolution pathway enabling the conversion of diastereomeric mixtures of non‐prefunctionalized substrates into atropisomerically pure, highly substituted biaryl scaffolds. The main feature of this transformation is the use of an enantiopure sulfoxide as both chiral auxiliary and traceless directing group. The potential of newly synthesized biaryls as valuable building blocks is further illustrated.     

Microwave-promoted three-component coupling of aldehyde, alkyne, and amine via C-H activation catalyzed by copper in water

[reaction: see text] An efficient three-component coupling of aldehyde, alkyne, and amine to generate propargylamines has been effected under microwave irradiation in water using only CuI catalyst without the noble metal cocatalyst. This method has proved to be applicable to a wide range of substrates. In addition, the preliminary experiment using (S)-proline methyl ester as a chiral source demonstrated that it could be developed to be a direct and highly diastereoselective method for construction of chiral propargylamines.     

A recyclable chiral Ru catalyst for enantioselective olefin metathesis. Efficient catalytic asymmetric ring-opening/cross metathesis in air

The synthesis and structure of a new chiral bidentate imidazolinylidene ligand and a derived chiral Ru-based carbene are disclosed. The Ru complex is stereogenic at the metal center; it can be prepared in >98% diastereoselectivity and purified by silica gel chromatography with undistilled solvents. The air-stable Ru complex efficiently catalyzes ring-closing and ring-opening metathesis and is recyclable. The chiral complex is highly effective (0.5-10 mol % loading) in promoting enantioselective ring-opening/cross metathesis reactions (up to >98% ee). These enantioselective transformations can be effected in air, with unpurified solvent and with substrates that would only polymerize with Mo-based catalysts.     

Lewis‐Base‐Mediated Diastereoselective Silylations of Alcohols: Synthesis of Silicon‐Stereogenic Dialkoxysilanes Controlled by Chiral Aryl BINMOLs

In the past years, stereoselective functionalizations of hydroxyl groups of alcohol substrates with chlorosilanes leading to silyl ether formation have evolved from a functional‐group protection to an enantioselective synthetic strategy. This work comprises a controlled desymmetrization of dichlorosilanes by using a family of structurally specific chiral diols, chiral 1,1′‐binaphthalene‐2‐α‐arylmethanol‐2′‐ol (Ar‐BINMOL). This process led to the facile construction of silicon‐stereogenic organosilicon compounds with high yields and good diastereoselectivities. In addition, the diasteroselective silylation of chiral diols might not only be of interest for the development of highly stereoselective nucleophilic silylation, but also shed light on the construction of novel chiral phosphine ligands bearing a silicon‐stereogenic center.     

Chiral‐Organotin‐Catalyzed Kinetic Resolution of Vicinal Amino Alcohols

A highly efficient kinetic resolution of racemic amino alcohols has been achieved for the first time with a chiral tin catalyst. A chiral organotin compound with 3,4,5‐trifluorophenyl groups at the 3,3′‐positions of the binaphthyl framework enabled this transformation with excellent yield and high enantioselectivity. The process tolerates aryl‐ and alkyl‐substituted amino alcohols and a variety of other substrates, affording the corresponding products in high enantioselectivity and with s factors up to >500.