Creating artificial organelles that sequester and release specific proteins in response to a small molecule in mammalian cells is an attractive approach for regulating protein function. In this work, ...

We designed and developed a phosphine–heteroarenesulfonamide ligand and found that it functions as a chiral dinuclear silver catalyst capable of cooperatively activating both nucleophiles and electrophiles. As a result, a highly enantioselective Mannich-type reaction between glycinate Schiff bases and acyclic ketiminoesters, unattainable by mononuclear catalytic systems, was achieved, affording α,β-diamino acid derivatives bearing tetrasubstituted chiral carbon centers in excellent yields and enantioselectivities. The resulting α,β-diamino acid derivatives were readily transformed into optically active 2-imidazolidinone and a dipeptide. Comprehensive mechanistic studies combining global reaction route mapping (GRRM), artificial force-induced reaction (AFIR), and density functional theory calculations revealed a cooperative bimetallic transition-state architecture responsible for the observed stereocontrol. These findings establish a new design principle for asymmetric catalysis based on homodinuclear activation and highlight the potential of dinuclear silver catalysis for the construction of complex chiral molecules.

“One thing I was not good at in the lab that I now really enjoy is computational calculations because this technique can provide transition states, interactions, and reaction mechanisms that I would ...

We present a synergistic strategy combining photocatalytic direct C─F borylation of polyfluoroarenes with Suzuki–Miyaura cross-coupling. The high nucleophilicity of amine-ligated boryl radicals enabl...

Heteroaromatic installation and peripheral modifications are the most common reactions in the pharmaceutical industry. However, the synthesis of biologically important aminonitrile-functionalized hete...

Catalytic decarboxylative reactions are attractive as biomimetic and environmentally friendly reaction processes. This review summarizes the recent results of organocatalytic enantioselective decarbox...

The enantioselective synthesis of chiral N,N-acetals derived from α-dicarbonyl compounds has been achieved. Good yields and enantioselectivities were observed for the reaction with various α-dicarbon...

The enantioselective reaction of 2H-azirines with oxazol-5-(4H)-ones (oxazolones) using a cinchona alkaloid sulfonamide catalyst has been developed. The reaction proceeded at the C-2 position of oxazolones to afford products with consecutive tetrasubstituted stereogenic centers in high yield with high diastereo- and enantioselectivity. The obtained aziridines were converted into various chiral compounds without loss of enantiopurity.

The first enantioselective vinylogous Mannich reaction of acyclic vinylketene silyl acetals with acyclic ketimines derived from alkynyl ketoesters was developed. Excellent yields and enantioselectivi...

We report the enantiodivergent reaction of ketimines derived from α-ketoesters with malononitriles using a single chiral source. The reactions using an 8-quinolinesulfonyl cinchona alkaloid catalyst ...

The first enantioselective aza-Henry reaction of non-activated cyclic iminoesters, derived from cyclic amino acids, has been developed. Good yields and enantioselectivities were observed for the react...

The enantioselective reaction of imines bearing a cyano group as an activating group with malonic acid half thioesters gave chiral cyanamide derivatives with high enantioselectivity. The density funct...

The first enantioselective Pictet–Spengler reaction of acyclic α-ketoesters with tryptamines has been developed. Excellent yields and enantioselectivity were obtained for the reaction using chiral imidazoline-phosphoric acid catalysts. Density functional theory calculations suggested possible transition states that explain the origin of chiral induction. This process provides an efficient route for the synthesis of tetrahydro-β-carboline derivatives.

The first enantioselective hydrophosphonylation of ketimines with phosphine oxides was developed. The reaction of unprotected ketimines with phosphine oxides using a bis(imidazoline)-phosphoric acid catalyst gave chiral α-quaternary aminophosphorous compounds having a primary amino group in excellent yields and enantioselectivities. Based on experimental results and DFT calculation, transition states were proposed to explain the stereoselectivity of the reaction.

The catalytic enantioselective allenylation of ketimines derived from isatins is described. Products with high regio- and enantioselectivities were obtained in the presence of a bis(imidazoline)-pall...

The first enantioselective synthesis of cyclic N,S-ketals having tetrasubstituted chiral center through intramolecular cyclization between carbonyl compounds and aminothiols has been developed. The r....

The first enantioselective reaction of α-isocyanoacetonitriles was developed. The reaction of various α-isocyanoacetonitriles with ketimines using cinchona alkaloid amide–Cu(II) catalysts afforded imidazolines with consecutive tetrasubstituted stereogenic carbon centers in good yields and high diastereo- and enantioselectivities. The stereoselectivity of the reaction is explained on the basis of the control experiment and density functional theory (DFT) calculations. The products were subsequently converted into chiral compounds. This process highlights the possible use of α-isocyanoacetonitriles for asymmetric and organic syntheses.

The enantioselective reaction of α-substituted β-nitroacrylates with oxazol-5-(4H)-ones (oxazolones) to construct consecutive tetrasubstituted stereogenic centers was accomplished. A cinchona alkaloid sulfonamide catalyst afforded products bearing vicinal chiral centers with excellent enantio- and diastereoselectivities. The obtained products were successively converted into various chiral compounds without loss of their enantiopurity. Furthermore, density functional theory (DFT) calculations were performed to elucidate the mechanism and origin of the observed stereoselectivity of the reaction.

The stereoselective reaction of α-amido-substituted malonic acid half oxyesters (α-amido-MAHOs) with isatins was developed. A cinchona alkaloid thiourea catalyst gave products bearing a tetrasubstitu...

Chiral unnatural amino acids (UAAs) are important structural units that are commonly found in a wide range of natural products and bioactive molecules. Chiral α-aminonitriles, which are one of the most important precursors for chiral α-amino acid synthesis, are widely accessible via the asymmetric Strecker reaction. However, the construction of α-heteroatom-substituted α-aminonitriles presents a challenge due to the lack of reactivity of electrophiles (ester, amide, thioamide, etc.) and their ability as leaving groups. Therefore, a practical and robust approach to their enantioselective synthesis is highly desirable. We herein describe an efficient method for the preparation of chiral α-heteroatom-substituted α-aminonitriles containing a tetrasubstituted stereogenic carbon center. This protocol displayed a broad substrate scope for both reactants in high yield and with high enantioselectivity. Several mechanistic studies revealed that the presence of nitrile is crucial for enhancing the reactivity and controlling the selectivity of the reaction. This work not only provides N,S- and N,Se-ketal motifs but also a powerful strategy for overcoming the limitation of synthesizable α-aminonitriles.

An Eosin Y-catalyzed visible light-promoted 1,4-peroxidation–sulfonylation of enynones was achieved to give tetrasubstituted allenes. The photoredox catalysis of Eosin Y allowed the concomitant formation of peroxy and sulfonyl radicals, where the preferential peroxy radical addition to the alkene moiety of enynones resulted in the subsequent α-keto radical–sulfonyl radical cross couplings. The developed photoredox catalysis of Eosin Y demonstrates a regioselective 1,4-diradical addition strategy, opening up a new possibility of diradical functionalization of conjugate systems.

The first enantioselective reaction of acyclic α-ketiminoesters with thiols has been developed. Good yields and enantioselectivities were obtained using our original cinchona alkaloid amide/zinc(II) ...

Chiral 2,3-dihydro-4H-imidazol-4-ones are key motifs in both synthetic and biological chemistry. However, their accessibility is classically limited to optical resolution of enantioenriched products. Herein, we report the catalytic asymmetric synthesis of these 4-imidazolones via the cyclocondensation of N-silyl iminoesters and N-unprotected ketimines using a chiral phosphoric acid catalyst. The enantioselective reaction has a broad substrate tolerance and maintains high yields and enantioselectivities (up to 99%, 99% ee). Furthermore, the enantioselective dimerization of N-silyl iminoesters to afford various chiral imidazolones was performed in the same catalytic system (up to 95%, 99% ee). The obtained products were easily converted into significant chiral heterocyclic molecules such as imidazoles, imidazolidines, and nitrones. Experimental results and density functional theory (DFT) calculations revealed a plausible reaction mechanism and the origin of the asymmetric induction.

Chiral phosphine-containing amino acids are useful motifs in pharmaceutical compounds. In this study, we developed the asymmetric conjugate addition of phosphine sulfides with α-substituted β-nitroacrylates to synthesize phosphine-containing amino acid precursors with chiral tetrasubstituted carbon centers. This method showed a wide substrate scope, and the obtained products were converted into various chiral compounds. The origin of the enantioselectivity was clarified by computational analysis.

Herein, we present the enantioselective synthesis of 2,3-dihydro-4-quinolones bearing chiral tetrasubstituted carbons from isatins and 2′-aminoacetophenones. The transformation is mediated by a chiral...