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 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 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 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 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.

The CuH-catalyzed regio-, diastereo-, and enantioselective reduction of vinyl-substituted 1,2-diketones has been achieved, efficiently affording a range of vinyl-substituted syn-1,2-diols, motifs that are ubiquitous in bioactive molecules and serve as valuable building blocks in organic synthesis. Totally 24 diol products were obtained smoothly (up to 91% yield) with a high level of stereoselectivity control (up to 99% ee and > 20:1 dr). The protocol tolerates both aryl and alkyl substrates, and the products facilitate a range of further transformations. The work represents a new choice that addresses the limitations of known methods.