Chiral Chemistry (CC, Online ISSN 3106-8405) is an open-access quarterly journal dedicated to publication and dissemination of high-impact, original, and leading research in the field of chiral chemistry and technologies. The journal provides a platform for pioneering theoretical, experimental, and applied studies, promoting fundamental understanding, advancements, and applied innovations across a broad range of scientific and industrial applications.
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Chiral Chemistry (CC, Online ISSN 3106-8405) is an open-access quarterly journal dedicated to publication and dissemination of high-impact, original, and leading research in the field of chiral chemistry and technologies. The journal provides a platform for pioneering theoretical, experimental, and applied studies, promoting fundamental understanding, advancements, and applied innovations across a broad range of scientific and industrial applications.
more >
N-heterocyclic carbene (NHC) organocatalysis enables umpolung activation of enals to deliver chiral α,β-unsaturated acylazolium electrophiles, realizing a highly selective cascade Friedel-Crafts (F-C) alkylation/lactamization of 4-aminoindoles with regioselective C5-site functionalization and excellent enantioselectivity. Nevertheless, the underlying mechanism and origins of selectivities remain poorly understood. Herein, we report a comprehensive density functional theory (DFT) investigation to fully characterize the complete catalytic cycle of this cascade transformation. The computational results indicate that the electrophilic addition of 4-aminoindole to the α,β-unsaturated acylazolium intermediate governs the stereoselectivity and regioselectivity. Activation-strain model (ASM) and energy decomposition analysis (EDA) reveal that electrostatic interactions and dispersion forces constitute the dominant stabilizing factors for the energetically favorable S-configured transition state. For regioselectivity, projection of orbital coefficient vector (POCV) analysis quantifies intrinsic atomic reactivity of different indole carbon sites, verifying that higher atomic reactivity at C5 position accounts for the preferential C5-functionalization. This work establishes a full mechanistic map of NHC-catalyzed asymmetric F-C reaction of indole and provides quantitative theoretical tools (ASM, EDA, POCV) to predict and rationalize stereo- and regioselectivity, offering guidance for rational design of NHC catalytic systems for indole functionalization.
The development of asymmetric catalytic methods using CO2 as a C1 synthon is an important strategy for constructing chiral carboxylic acids and heterocyclic compounds. In recent years, through the design of innovative catalytic systems, efficient ...
The development of asymmetric catalytic methods using CO2 as a C1 synthon is an important strategy for constructing chiral carboxylic acids and heterocyclic compounds. In recent years, through the design of innovative catalytic systems, efficient and highly selective syntheses of chiral carboxylic acids, spanning central to axial chirality, have been achieved from diverse substrates, including alkenes, alkynes, and organic electrophiles. Concurrently, significant progress has also been made in the synthesis of chiral heterocycles, particularly 2-oxazolidinones and cyclic carbonates. This review systematically summarizes key advances in this field from 2021 to mid-2026. Organized by target product structure, the discussion first addresses chiral carboxylic acids, categorized by substrate type (carbon-carbon unsaturated bonds and organic electrophiles). Key strategies, including carbo-carboxylation, boracarboxylation, hydrocarboxylation, dicarboxylation, and electroreductive carboxylation, are elaborated in detail, along with their stereoselectivity control mechanisms. The discussion then covers chiral heterocycles, summarizing the catalytic asymmetric construction of chiral 2-oxazolidinones and chiral cyclic carbonates. Finally, the major challenges and future directions in this field are discussed.
We report an organocatalytic enantioselective desymmetrization of 2-aminophenyl malonates enabled by intramolecular ester aminolysis. This protocol efficiently delivers C3-disubstituted oxindole derivatives bearing quaternary stereocenters under ...
We report an organocatalytic enantioselective desymmetrization of 2-aminophenyl malonates enabled by intramolecular ester aminolysis. This protocol efficiently delivers C3-disubstituted oxindole derivatives bearing quaternary stereocenters under mild conditions with excellent chemo- and enantioselectivities. Notably, this reaction follows an acid-promoted dehydration pathway instead of an alcohol elimination pathway, which differs from conventional ester aminolysis reactions reported previously. Gram-scale synthesis and further derivatization of the resulting products demonstrate the synthetic utility of this transformation.
Owing to their stable axial chirality, atropisomeric biaryl compounds have found widespread applications in medicinal chemistry, natural product chemistry, and agricultural chemistry. Up to now, two principal strategies have been established for the ...
Owing to their stable axial chirality, atropisomeric biaryl compounds have found widespread applications in medicinal chemistry, natural product chemistry, and agricultural chemistry. Up to now, two principal strategies have been established for the synthesis of axially chiral biaryls: the enantioselective construction of the aryl-aryl axis via asymmetric coupling reactions, and the stereoselective modification of a pre-existing axis, which includes asymmetric construction of one aromatic ring, desymmetrization of prochiral substrates, and dynamic kinetic resolution (DKR) of biaryl skeletons. Among these strategies, enantioselective C−H functionalization avoids the use of pre-functionalized substrates and installs sterically demanding groups that enhance rotational barriers, thereby serving as an ideal DKR tool for the construction of atropisomeric biaryls directly from biaryl substrates with low rotational barriers. In this review, based on the nature of the directing groups, we summarize three distinct strategies for enantioselective C−H functionalization of biaryls with free axial rotation: directing group (DG)-mediated, transient DG-enabled, and DG-free approaches. The mechanisms and substrate scopes of selected representative reactions are also briefly discussed.
Although significant progress has been made in constructing three-dimensional, C(sp3)-rich bioisosteres for pyridines, the development of catalytic enantioselective approaches to access chiral nitrogen-containing bridged scaffolds ...
Although significant progress has been made in constructing three-dimensional, C(sp3)-rich bioisosteres for pyridines, the development of catalytic enantioselective approaches to access chiral nitrogen-containing bridged scaffolds remains limited and challenging. Herein, we report a chiral Brønsted acid-catalyzed enantioselective reduction of imines harnessing Hantzsch ester as the hydrogen source under mild conditions, delivering structurally diverse chiral 3-azabicyclo[3.1.1]heptanes (27 examples) in generally good yields with high enantiocontrol (up to 93% yield, 97% ee). The reaction can be scaled up to 2 mmol with full preservation of the excellent outcomes. These saturated heterocycles serve as versatile precursors, as demonstrated by conversion to bicyclo[2.1.1]hexanes via a facile nitrogen-deletion strategy with complete retention of enantiopurity. Notably, the enantioenriched 3-aza-BCHep can serve as a secondary amine organocatalyst, promoting the asymmetric Friedel–Crafts alkylation of indole with an α,β-unsaturated aldehyde in excellent yield and promising stereoinduction. This work establishes a practical route to access enantiopure saturated heterocyclic scaffolds, offering new three-dimensional candidates as potential pyridine isosteres in drug discovery and asymmetric catalysis.
Sulfonylhydrazones are valuable carbene precursors in asymmetric synthesis; however, their use typically generates sulfinic acid, which is inevitably discarded as stoichiometric waste. In this work, the carbene chemistry and sulfur chemistry are integrated ...
Sulfonylhydrazones are valuable carbene precursors in asymmetric synthesis; however, their use typically generates sulfinic acid, which is inevitably discarded as stoichiometric waste. In this work, the carbene chemistry and sulfur chemistry are integrated in Rh-catalyzed asymmetric sulfonyl retentive S,N-difunctionalization of alkynyl N-sulfonylhydrazones with sulfenamides. The sulfonyl group or the corresponding sulfinic acid is retained in a formal migration. This mild and efficient protocol allows for straightforward construction of enantioenriched sulfonyl-based allylic sulfenamides with excellent chemo-, E/Z-, and enantioselectivity, thereby offering a creative strategy for achieving more atom-economic transformations of carbene precursors. Mechanistic studies reveal a three-step process involving S-allenylation, hydrosulfonylation, and an aza-Mislow-Evans rearrangement, with the hydrosulfonylation step governing enantioselectivity.
Over the past few decades, denitrogenation has proven to be an effective method for synthesizing high-value chiral heterocyclic compounds. These compounds find widespread applications in pharmaceutical chemistry, drug development, and natural product ...
Over the past few decades, denitrogenation has proven to be an effective method for synthesizing high-value chiral heterocyclic compounds. These compounds find widespread applications in pharmaceutical chemistry, drug development, and natural product synthesis. Denitrogenation demonstrates high activity and can engage in cyclization reactions with olefins, alkynes, carbon-heterocycles, aldehydes, and other reagents. This one-step operation enables the rapid construction of chiral heterocycles such as pyrroles and indoles, significantly shortening complex synthetic pathways. Innovations in chiral ligands, optimization of catalytic systems, and detailed studies on mechanisms have significantly enhanced the enantioselectivity and substrate applicability of denitrogenation reactions. This review highlights recent advancements in the synthesis of chiral heterocycles via denitrogenation reactions and systematically examines the reaction characteristics of various metal catalytic systems.
The asymmetric hydrogenation of vinyl silanes, vinyl sulfides, vinyl phosphines, and vinyl chlorides, those substituted with heteroatoms from the third-row of the periodic table, has emerged as a valuable and environmentally friendly method for the construction ...
The asymmetric hydrogenation of vinyl silanes, vinyl sulfides, vinyl phosphines, and vinyl chlorides, those substituted with heteroatoms from the third-row of the periodic table, has emerged as a valuable and environmentally friendly method for the construction of the related optically active organosilanes, organosulfides, organophosphine, and organochlorides. These compounds have shown considerable potential for preparing functional molecules and synthesizing natural products. Over the past few decades, considerable research efforts have focused on the design and development of transition-metal catalysts featuring chiral ligands for the asymmetric hydrogenation of such substrates. In parallel, in-depth mechanistic studies have been conducted to elucidate the pathways of these enantioselective hydrogenation reactions, significantly advancing the understanding of their catalytic behavior and stereocontrol. This review focuses on the recent momentum and key advancements in the enantioselective hydrogenation of vinyl silanes, vinyl sulfides, and vinyl chlorides. In addition, given the widespread industrial interest in these compounds, the practical utility of this transformation in the synthesis of chiral silanes, chiral thioethers, chiral alkyl chlorides, as well as related derivatives, is also discussed.
Chiral organogermanes hold great potential as bioisosteres in medicinal chemistry and functional materials, yet their development has long been hindered by a scarcity of efficient synthetic strategies. This review offers a comprehensive overview of recent ...
Chiral organogermanes hold great potential as bioisosteres in medicinal chemistry and functional materials, yet their development has long been hindered by a scarcity of efficient synthetic strategies. This review offers a comprehensive overview of recent advances in the catalytic asymmetric synthesis of chiral organogermanes, highlighting a shift from traditional resolution methods toward asymmetric catalytic approaches. The content is organized into three main categories: (i) synthesis of C-stereogenic germanes, (ii) synthesis of Ge-stereogenic germanes, and (iii) synthesis of other chiral germanes, including planar, inherent, and axially chiral types. Key synthetic methodologies are systematically examined, such as enantioselective alkene hydrofunctionalization, carbene insertion, coupling reactions, and [2+2+2] cycloaddition, utilizing a variety of catalytic systems ranging from transition metals (Rh, Cu, Ni, Co) and Lewis acids to engineered metalloenzymes. Particular emphasis is placed on the mechanistic insights and ligand design principles that enable stereochemical control in these transformations. We hope this review will inspire chemists working in related areas and contribute to the future advancement of this field.
Sulfonylhydrazones are valuable carbene precursors in asymmetric synthesis; however, their use typically generates sulfinic acid, which is inevitably discarded as stoichiometric waste. In this work, the carbene chemistry and sulfur chemistry are integrated ...
Sulfonylhydrazones are valuable carbene precursors in asymmetric synthesis; however, their use typically generates sulfinic acid, which is inevitably discarded as stoichiometric waste. In this work, the carbene chemistry and sulfur chemistry are integrated in Rh-catalyzed asymmetric sulfonyl retentive S,N-difunctionalization of alkynyl N-sulfonylhydrazones with sulfenamides. The sulfonyl group or the corresponding sulfinic acid is retained in a formal migration. This mild and efficient protocol allows for straightforward construction of enantioenriched sulfonyl-based allylic sulfenamides with excellent chemo-, E/Z-, and enantioselectivity, thereby offering a creative strategy for achieving more atom-economic transformations of carbene precursors. Mechanistic studies reveal a three-step process involving S-allenylation, hydrosulfonylation, and an aza-Mislow-Evans rearrangement, with the hydrosulfonylation step governing enantioselectivity.
The asymmetric hydrogenation of vinyl silanes, vinyl sulfides, vinyl phosphines, and vinyl chlorides, those substituted with heteroatoms from the third-row of the periodic table, has emerged as a valuable and environmentally friendly method for the construction ...
The asymmetric hydrogenation of vinyl silanes, vinyl sulfides, vinyl phosphines, and vinyl chlorides, those substituted with heteroatoms from the third-row of the periodic table, has emerged as a valuable and environmentally friendly method for the construction of the related optically active organosilanes, organosulfides, organophosphine, and organochlorides. These compounds have shown considerable potential for preparing functional molecules and synthesizing natural products. Over the past few decades, considerable research efforts have focused on the design and development of transition-metal catalysts featuring chiral ligands for the asymmetric hydrogenation of such substrates. In parallel, in-depth mechanistic studies have been conducted to elucidate the pathways of these enantioselective hydrogenation reactions, significantly advancing the understanding of their catalytic behavior and stereocontrol. This review focuses on the recent momentum and key advancements in the enantioselective hydrogenation of vinyl silanes, vinyl sulfides, and vinyl chlorides. In addition, given the widespread industrial interest in these compounds, the practical utility of this transformation in the synthesis of chiral silanes, chiral thioethers, chiral alkyl chlorides, as well as related derivatives, is also discussed.
Chiral organogermanes hold great potential as bioisosteres in medicinal chemistry and functional materials, yet their development has long been hindered by a scarcity of efficient synthetic strategies. This review offers a comprehensive overview of recent ...
Chiral organogermanes hold great potential as bioisosteres in medicinal chemistry and functional materials, yet their development has long been hindered by a scarcity of efficient synthetic strategies. This review offers a comprehensive overview of recent advances in the catalytic asymmetric synthesis of chiral organogermanes, highlighting a shift from traditional resolution methods toward asymmetric catalytic approaches. The content is organized into three main categories: (i) synthesis of C-stereogenic germanes, (ii) synthesis of Ge-stereogenic germanes, and (iii) synthesis of other chiral germanes, including planar, inherent, and axially chiral types. Key synthetic methodologies are systematically examined, such as enantioselective alkene hydrofunctionalization, carbene insertion, coupling reactions, and [2+2+2] cycloaddition, utilizing a variety of catalytic systems ranging from transition metals (Rh, Cu, Ni, Co) and Lewis acids to engineered metalloenzymes. Particular emphasis is placed on the mechanistic insights and ligand design principles that enable stereochemical control in these transformations. We hope this review will inspire chemists working in related areas and contribute to the future advancement of this field.
Over the past few decades, denitrogenation has proven to be an effective method for synthesizing high-value chiral heterocyclic compounds. These compounds find widespread applications in pharmaceutical chemistry, drug development, and natural product ...
Over the past few decades, denitrogenation has proven to be an effective method for synthesizing high-value chiral heterocyclic compounds. These compounds find widespread applications in pharmaceutical chemistry, drug development, and natural product synthesis. Denitrogenation demonstrates high activity and can engage in cyclization reactions with olefins, alkynes, carbon-heterocycles, aldehydes, and other reagents. This one-step operation enables the rapid construction of chiral heterocycles such as pyrroles and indoles, significantly shortening complex synthetic pathways. Innovations in chiral ligands, optimization of catalytic systems, and detailed studies on mechanisms have significantly enhanced the enantioselectivity and substrate applicability of denitrogenation reactions. This review highlights recent advancements in the synthesis of chiral heterocycles via denitrogenation reactions and systematically examines the reaction characteristics of various metal catalytic systems.
P-Stereogenic centers are important structural motifs prevalent in natural products, bioactive molecules, and high-performance ligands. Their presence confers significant value across medicinal chemistry, materials science, and asymmetric ...
P-Stereogenic centers are important structural motifs prevalent in natural products, bioactive molecules, and high-performance ligands. Their presence confers significant value across medicinal chemistry, materials science, and asymmetric catalysis. In recent years, catalytic asymmetric hydrophosphination has emerged as a powerful and efficient strategy for constructing such P-stereogenic compounds. Distinguished by high atom economy, broad substrate compatibility, and excellent stereocontrol under mild conditions, these transformations align closely with the principles of sustainable and green synthesis. This review summarizes recent advances in the catalytic asymmetric hydrophosphination of unsaturated C–C bonds for the synthesis of P-stereogenic centers. It covers substrates including alkenes bearing electron-withdrawing groups, alkynes, as well as specialized systems such as enynes, allenes, and conjugated dienes. Emphasis is placed on the design of catalytic systems, encompassing transition-metal catalysts (e.g., Pd, Ni, Cu, Co, Mn) and organocatalysts, along with their mechanisms. Current challenges, such as the low reactivity of unactivated or sterically hindered substrates and difficulties in achieving stereochemical differentiation between phosphorus substituents, are also discussed. This review aims to provide a reference for further innovation and methodological development in the synthesis of P-stereogenic molecules.
