Dynamic Kinetic Resolution of Heterobiaryl Ketones by Zinc‐Catalyzed Asymmetric Hydrosilylation

A diastereo‐ and highly enantioselective dynamic kinetic resolution (DKR) of configurationally labile heterobiaryl ketones is described. The DKR proceeds by zinc‐catalyzed hydrosilylation of the carbonyl group, thus leading to secondary alcohols bearing axial and central chirality. The strategy relies on the labilization of the stereogenic axis that takes place thanks to a Lewis acid–base interaction between a nitrogen atom in the heterocycle and the ketone carbonyl group. The synthetic utility of the methodology is demonstrated through stereospecific transformations into either N,N‐ligands or appealing axially chiral, bifunctional thiourea organocatalysts.     

Counterion‐Induced Asymmetric Control in Ring‐Opening of Azetidiniums: Facile Access to Chiral Amines

Counterion‐induced stereocontrol is a powerful tool in organic synthesis. However, such enantiocontrol on tetrahedral ammonium cations remains challenging. Described here is the first example of using chiral anion phase‐transfer catalysis to achieve intermolecular ring‐opening of azetidiniums with excellent enantioselectivity (up to 97 % ee). Precise control over the formation and reaction of the chiral ion pair as well as inhibition of the background reaction by the biphasic system is key to the success of the reaction.     

Asymmetric Synthesis of Hydrocarbazoles Catalyzed by an Octahedral Chiral‐at‐Rhodium Lewis Acid

A bis‐cyclometalated chiral‐at‐metal rhodium complex catalyzes the Diels–Alder reaction between N‐Boc‐protected 3‐vinylindoles (Boc=tert‐butyloxycarbonyl) and β‐carboxylic ester‐substituted α,β‐unsaturated 2‐acyl imidazoles with good‐to‐excellent regioselectivity (up to 99:1) and excellent diastereoselectivity (>50:1 d.r.) as well as enantioselectivity (92–99 % ee) under optimized conditions. The rhodium catalyst serves as a chiral Lewis acid to activate the 2‐acyl imidazole dienophile by two‐point binding and overrules the preferred regioselectivity of the uncatalyzed reaction.     

New Aspects of Cyclodextrin Chemistry Induced by Outside Type Complex Formation; Asymmetric Reduction of Indol-3-Pyruvic Acid with NaBH4 in Aqueous Solution

Asymmetric reduction of indol-3-pyruvic acid (IPA) with NaBH₄ in aqueous solution in the presence of various cyclodextrins (α-, β-, γ-, mono-6-amino-6-deoxy-β- and di-6^ABamino-6^AB-deoxy-β-cyclodextrin) was investigated. From the NMR and circular dichroism spectral studies, the conformation of the CyD–substrate complexes is suggested; the part of carboxylic group stay in the cavity of α-CyD, whole of IPA in β-CyD, two molecules in a γ-CyD cavity, and IPA(s) is/are on the rim of the cavity of mono-6-amino-6-deoxy-β- and di-6^ABamino-6^AB-deoxy-β-CyD (AβCyD, DAβCyD) with electrostatic interaction between amino group and carboxylic group. This conformational difference provides in the difference in the optical selectivity of reduction.     

Kinetic Resolution of 2H‐Azirines by Asymmetric Imine Amidation

Highly efficient kinetic resolution of 2H‐azirines by an asymmetric imine amidation was achieved in the presence of a chiral N,N′‐dioxide/Sc^III complex, thus providing a promising method to obtain the enantioenriched 2H‐azirine derivatives and protecting‐group free aziridines at the same time. It is rare to find an example of N1 of an oxindole participating in a reaction over C3. Moreover, chiral 2H‐azirines were stereospecifically transformed into an unprotected aziridine and α‐amino ketone.     

Asymmetric Catalysis Mediated by the Ligand Sphere of Octahedral Chiral‐at‐Metal Complexes

Due to the relationship between structure and function in chemistry, access to novel chemical structures ultimately drives the discovery of novel chemical function. In this light, the formidable utility of the octahedral geometry of six‐coordinate metal complexes is founded in its stereochemical complexity combined with the ability to access chemical space that might be unavailable for purely organic compounds. In this Minireview we wish to draw attention to inert octahedral chiral‐at‐metal complexes as an emerging class of metal‐templated asymmetric “organocatalysts” which exploit the globular, rigid nature and stereochemical options of octahedral compounds and promise to provide new opportunities in the field of catalysis.     

Kinetic Resolution of Azomethine Imines by Brønsted Acid Catalyzed Enantioselective Reduction

Azomethine imines are valuable substrates in asymmetric catalysis, and can be precursors to β‐amino carbonyl compounds and complex hydrazines. However, their utility is limited because complex and enantioenriched azomethine imines are often unavailable. Reported herein is a kinetic resolution of N,N′‐cyclic azomethine imines by enantioselective reduction (s=13–43). This resolution was accomplished using a Brønsted acid catalyst, and represents the first example of the asymmetric reduction of azomethine imines. The pyrazolidinone product (up to 86 % ee) and the recovered azomethine imine (up to 99 % ee) can both be used to access the opposite enantiomers of valuable products.     

Chiral Phosphoric Acid Catalyzed Asymmetric Ugi Reaction by Dynamic Kinetic Resolution of the Primary Multicomponent Adduct

Reaction of isonitriles with 3‐(arylamino)isobenzofuran‐1(3H)‐ones in the presence of a catalytic amount of an octahydro (R)‐binol‐derived chiral phosphoric acid afforded 3‐oxo‐2‐arylisoindoline‐1‐carboxamides in high yields with good to high enantioselectivities. An enantioselective Ugi four‐center three‐component reaction of 2‐formylbenzoic acids, anilines, and isonitriles was subsequently developed for the synthesis of the same heterocycle. Mechanistic studies indicate that the enantioselectivity results from the dynamic kinetic resolution of the primary Ugi adduct, rather than from the C?C bond‐forming process. The resulting heterocycle products are of significant medicinal importance.     

Chiral Phosphoric Acid Catalyzed Kinetic Resolution of Indolines Based on a Self‐Redox Reaction

A strategy for oxidative kinetic resolution of racemic indolines was developed, employing salicylaldehyde derivative as the pre‐resolving reagent and chiral phosphoric acid as the catalyst. The iminium intermediate, formed by the condensation reaction of an enantiomer of indoline with salicylaldehyde derivative, was hydrogenated by the same enantiomer of indoline to afford another enantiomer of indoline by a self‐redox mechanism. The oxidative kinetic resolution of 2‐aryl‐substituted indolines proceeded to give enantiomers in good yields with excellent enantioselectivities.     

Spontaneous Formation of Biocompatible Vesicles in Aqueous Mixtures of Amino Acid‐Based Cationic Surfactants and SDS/SDBS

The spontaneous formation of vesicles by six amino acid‐based cationic surfactants and two anionic surfactants (sodium dodecylbenzene sulfonate (SDBS) and sodium dodecyl sulfate (SDS)) is reported. The head‐group structure of the cationic surfactants is minutely altered to understand their effect on vesicle formation. To establish the regulatory role of the aromatic group in self‐aggregation, both aliphatic and aromatic side‐chain‐substituted amino acid‐based cationic surfactants are used. The presence of aromaticity in any one of the constituents favors the formation of vesicles by cationic/anionic surfactant mixtures. The formation of vesicles is primarily dependent on the balance between the hydrophobicity and hydrophilicity of both cationic and anionic surfactants. Vesicle formation is characterized by surface tension, fluorescence anisotropy, transmission electron microscopy, dynamic light scattering, and phase diagrams. These vesicles are thermally stable up to 65 °C, determined by temperature‐dependent fluorescence anisotropy. According to the MTT assay, these catanionic vesicles are nontoxic to NIH3T3 cells, thus indicating their wider applicability as delivery vehicles to cells. Among the six cationic surfactants examined, tryptophan‐ and tyrosine‐based surfactants have the ability to reduce HAuCl₄ to gold nanoparticles (GNPs), which is utilized to obtain in‐situ‐synthesized GNPs entrapped in vesicles without the need for any external reducing agent.     

Quaternary β2,2‐Amino Acids: Catalytic Asymmetric Synthesis and Incorporation into Peptides by Fmoc‐Based Solid‐Phase Peptide Synthesis

β‐Amino acid incorporation has emerged as a promising approach to enhance the stability of parent peptides and to improve their biological activity. Owing to the lack of reliable access to β^2,2‐amino acids in a setting suitable for peptide synthesis, most contemporary research efforts focus on the use of β³‐ and certain β^2,3‐amino acids. Herein, we report the catalytic asymmetric synthesis of β^2,2‐amino acids and their incorporation into peptides by Fmoc‐based solid‐phase peptide synthesis (Fmoc‐SPPS). A quaternary carbon center was constructed by the palladium‐catalyzed decarboxylative allylation of 4‐substituted isoxazolidin‐5‐ones. The N?O bond in the products not only acts as a traceless protecting group for β‐amino acids but also undergoes amide formation with α‐ketoacids derived from Fmoc‐protected α‐amino acids, thus providing expeditious access to α‐β^2,2‐dipeptides ready for Fmoc‐SPPS.     

Use of a Catalytic Chiral Leaving Group for Asymmetric Substitutions at sp3‐Hybridized Carbon Atoms: Kinetic Resolution of β‐Amino Alcohols by p‐Methoxybenzylation

A catalytic strategy was developed for asymmetric substitution reactions at sp³‐hybridized carbon atoms by using a chiral alkylating agent generated in situ from trichloroacetimidate and a chiral phosphoric acid. The resulting chiral p‐methoxybenzyl phosphate selectively reacts with β‐amino alcohols rather than those without a β‐NH functionality. The use of an electronically and sterically tuned chiral phosphoric acid enables the kinetic resolution of amino alcohols through p‐methoxybenzylation with good enantioselectivity.     

Bifunctional Ammonium Salt Catalyzed Asymmetric α‐Hydroxylation of β‐Ketoesters by Simultaneous Resolution of Oxaziridines

Chiral bifunctional urea‐containing ammonium salts were found to be very efficient catalysts for asymmetric α‐hydroxylation reactions of β‐ketoesters with oxaziridines under base‐free conditions. The reaction is accompanied by a simultaneous kinetic resolution of the oxaziridine and a plausible and so far unprecedented bifunctional transition‐state model has been obtained by means of DFT calculations.     

Chiral Phosphoric Acid Catalyzed Kinetic Resolution of 2‐Amido Benzyl Alcohols: Asymmetric Synthesis of 4H‐3,1‐Benzoxazines

An efficient method for the asymmetric synthesis of 4H‐3,1‐benzoxazines was developed by kinetic resolution of 2‐amido benzyl alcohols using chiral phosphoric acid catalyzed intramolecular cyclizations. A broad range of benzyl alcohols (both secondary and tertiary alcohols) were kinetically resolved with high selectivities, with an s factor of up to 94. Mechanistic studies were performed to elucidate the mechanism of these reactions, wherein the amide moieties reacted as the electrophiles. Gram‐scale reaction and facile transformations of the chiral products demonstrate the potential of this method in asymmetric synthesis of biologically active chiral heterocycles.     

Asymmetric Reduction of α‐Amino Ketones with a KBH4 Solution Catalyzed by Chiral Lewis Acids

An efficient enantioselective reduction of α‐amino ketones with potassium borohydride solution catalyzed by chiral N,N′‐dioxide–metal complex catalysts was accomplished under mild reaction conditions for the first time. It provided a simple, convenient, and practical approaches for obtaining synthetically important chiral β‐amino alcohols in good to excellent yields (up to 98 %) and enantioselectivities (up to 97 % ee).