An asymmetric relay catalysis strategy merging gold and oxidative N-heterocyclic carbenes (NHCs) for trimolecular reactions was disclosed. Racemic α-amino-ynones undergo facile conversion to racemic pyrrolin-3-ones under gold catalysis, which serve as potent nucleophilic C1 synthons, which engage easily available enals and phenols to generate linear products in moderate yields and excellent diastereo- and enantioselectivities under oxidative NHC catalysis. Synthetic utility of 2,2-disubstituted pyrrolinones is also demonstrated by facile conversion to pyrrolinone-fused γ-lactames in high yields.

Ortho-quinone methides (o-QMs) constitute a class of highly reactive and versatile intermediates in organic synthesis, characterized by a unique polarized electronic structure that combines an electron-deficient quinoid ring with an exocyclic electrophilic methylene or alkylidene unit. This distinctive feature renders powerful C4 synthons capable of participating in a wide range of higher-order cyclization reactions. In particular, [4 + n] cyclizations involving o-QMs (e.g., [4 + 1], [4 + 2], and [4 + 3]) have emerged as effective strategies for the rapid construction of structurally complex carbocyclic and heterocyclic frameworks, many of which serve as privileged scaffolds in natural products and functional materials. This review provides a comprehensive overview of recent advances in this rapidly developing field, with a systematic discussion of reaction design, mechanistic insights, and synthetic applications across various [4 + n] cyclization modes. Furthermore, current challenges are critically evaluated, and future opportunities are proposed, particularly in the development of novel catalytic systems, asymmetric variants, and innovative o-QM precursors. Overall, this review aims to offer researchers a clear understanding of the state of the art in o-QM chemistry and to inspire further innovation in this dynamic area of organic synthesis.

The asymmetric catalytic [3+2] cycloannulation of benzoxazinones with isatin-derived ketimines for the efficient construction of imidazo[5,1-c]oxazinones has been developed, which realized the first asymmetric reaction of benzoxazinones with excellent stereoselectivities. A series of imidazo[5,1-c]oxazinones containing three stereogenic centers with one gem-diamine-type spiro tetrasubstituted center were obtained in this organocatalytic reaction with good yields and high functional group tolerance.

A strategy for trifluoroacetylation of quinoxaline-2(1H)-ones has been investigated. This strategy employs masked trifluoroacyl reagents to obtain trifluoroacetylated quinoxaline-2(1H)-ones under metal-, catalyst-, and light-free conditions. This approach is distinguished by its functional group compatibility and tolerance, as well as the simplicity of the experimental process, making it suitable for gram-scale synthesis.

Genetically encoding a proximal reactive warhead into the protein binder/drug has emerged as an efficient strategy for covalently binding to protein targets, enabling broad applications. To expand the reactivity scope for targeting the diverse natural residues under physiological conditions, the development of a genetically encoded reactive warhead with excellent stability and broad reactivity is highly desired. Herein, we reported the genetic encoding of epoxide-containing tyrosine (EPOY) for developing covalent protein drugs. Our study demonstrates that EPOY, when incorporated into a nanobody (KN035), can cross-link with different side chains (mutations) at the same position of PD-L1 protein. Significantly, a single genetically encoded reactive warhead that is capable of covalent and site-specific targeting to 10 different nucleophilic residues was achieved for the first time. This would largely expand the scope of covalent warhead and inspire the development of covalent warheads for both small-molecule drugs and protein drugs. Furthermore, we incorporate the EPOY into a designed ankyrin repeat protein (Darpin(K13)) to create the covalent binders of KRAS. This covalent KRAS binder holds the potential to achieve pan-covalent targeting of KRAS based on the structural similarity among all oncogenic KRAS mutants while avoiding off-target binding to NRAS/HRAS through a covalent interaction with KRAS-specific residues (H95 and E107). We envision that covalently targeting to H95 will be a promising strategy for the development of covalent pan-KRAS inhibitors in the future.

This study investigates the feasibility and inherent benefits of combining transition-metal- and organoasymmetric-catalyzed reactions in one pot. The reported transformation features Au-catalyzed tandem hydration-oxacyclization and NHC-catalyzed enantioselective annulation, effectively converting simple skipped diynones, water, and enals into highly diastereo- and enantioenriched fused heterocycles. Furthermore, the chemoselectivity controlled by the base is particularly noteworthy, enabling facile access to epsilon-lactones or spiro heterocycles from the same set of starting materials.

The construction of N–N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and chiral ligands. One efficient method is the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis of N–N atropisomers with simultaneous creation of contiguous axial and central chirality by oxidative NHC ( N -heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able to synthesize structurally diverse N–N axially chiral pyrroles and indoles with vicinal central chirality or bearing a 2,3-dihydropyrimidin-4-one moiety in moderate to good yields and excellent enantioselectivities. Further synthetic transformations of the obtained axially chiral pyrroles and indoles derivative products are demonstrated. The reaction mechanism and the origin of enantioselectivity are understood through DFT calculations.

We report herein an unprecedented N-heterocyclic carbene-catalyzed formal[3+3]annulation of ynals with N-Ts indolin-3-ones un-der the oxidation condition affording the functionalized pyrano[3,2-b]indol-2-ones.The alkynyl acylazoliums via the combination of a carbene with ynals in the presence of oxidate proved to be the important intermediates for the success of this transformation.This method features a broad substrate scope and mild conditions,including axially chiral skeletons with suitable substitutions.

An efficient and highly enantioconvergent and diastereoselective ternary catalysis in a one-pot process is reported, which represents an integrated strategy for the synthesis of atropisomeric hydrazides with defined vicinal central and axial chirality from readily available racemic alpha-amino-ynones, azodicarboxylates, and Morita-Baylis-Hillman (MBH) carbonates. This method utilizes in situ-generated racemic pyrrolin-4-ones via hydroamination of racemic alpha-amino-ynones by AuCl catalysis as a novel and versatile C1 synthon, which engage commercially available azodicarboxylates to generate amination products in high yields and uniformly excellent enantioselectivities under the catalysis of a chiral phosphoric acid. Following amination, N-alkylation catalyzed by diastereoselective organocatalyst afforded axially chiral hydrazides with excellent diastereoselectivities (>98 : 2 dr). The synthetic utility of the amination products and axially chiral hydrazides was also demonstrated by their facile conversion to diverse molecules in high yields with excellent stereopurity. Density functional theory calculations were performed to understand the origin of diastereoselectivity.

Indolo[2,1-b]quinazolin-12(6H)-one derivatives are prevalent in many synthetic intermediates, pharmaceuticals, and organic materials. Herein, we developed a photoredox radical cascade cyclization reaction that uses visible light as the primary energy input to promote the reaction, leading to a series of indolo[2,1-b]quinazolin-12(6H)-one derivatives under oxygen conditions.

A BF3OEt2-mediated transamidation between unactivated amides and amines is reported, enabling access to diverse secondary and tertiary amides under transition-metal-free and solvent-free conditions. The operationally simple procedure provides a novel manifold for converting amide-amide bonds with excellent chemoselectivity. In particular, a series of amides including challenging thioamides enable direct transamidation to products with modest to excellent yields. Meanwhile, additional experiments were conducted to elucidate the mechanism of this transformation, and a plausible mechanism was proposed based on the results and related literature.

A reliable solid electrolyte interphase (SEI) on the metallic Zn anode is imperative for stable Zn-based aqueous batteries. However, the incompatible Zn-ion reduction processes, scilicet simultaneous adsorption (capture) and desolvation (repulsion) of Zn2+(H2O)(6), raise kinetics and stability challenges for the design of SEI. Here, we demonstrate a tandem chemistry strategy to decouple and accelerate the concurrent adsorption and desolvation processes of the Zn2+ cluster at the inner Helmholtz layer. An electrochemically assembled perforative mesopore SiO2 interphase with tandem hydrophilic -OH and hydrophobic -F groups serves as a Janus mesopores accelerator to boost a fast and stable Zn2+ reduction reaction. Combining in situ electrochemical digital holography, molecular dynamics simulations, and spectroscopic characterizations reveals that -OH groups capture Zn2+ clusters from the bulk electrolyte and then -F groups repulse coordinated H2O molecules in the solvation shell to achieve the tandem ion reduction process. The resultant symmetric batteries exhibit reversible cycles over 8000 and 2000 h under high current densities of 4 and 10 mA cm(-2), respectively. The feasibility of the tandem chemistry is further evidenced in both Zn//VO2 and Zn//I-2 batteries, and it might be universal to other aqueous metal-ion batteries.

Heterojunction interfacial engineering plays a crucial role for the CIGS efficiency promotion. Chemical bath deposition (CBD) prepared CdS is the most preferred buffer for CIGS solar cells. Hence, manipulating the CdS properties to further boost heterojunction quality is a promising way to achieve higher efficiency CIGS solar cells. In this work, CdS buffer layer was modified by (NH4)2S (AS-treatment) solutions. The results showed that after AS treatment, the impurities on CdS film were cleaned and the S vacancy was passivated. Moreover, it introduced larger build-in electric field, wider depletion width and less interface defect densities, which contributed to suppressed interface recombination and more efficient carrier separation and collection. Consequently, the CIGS solar cell based on AS-treatment achieved champion efficiency of 15.52

Heterojunction interfacial engineering plays a crucial role for the CIGS efficiency promotion. Chemical bath deposition (CBD) prepared CdS is the most preferred buffer for CIGS solar cells. Hence, manipulating the CdS properties to further boost heterojunction quality is a promising way to achieve higher efficiency CIGS solar cells. In this work, CdS buffer layer was modified by (NH4)(2)S (AS-treatment) solutions. The results showed that after AS treatment, the impurities on CdS film were cleaned and the S vacancy was passivated. Moreover, it introduced larger build-in electric field, wider depletion width and less interface defect densities, which contributed to suppressed interface recombination and more efficient carrier separation and collection. Consequently, the CIGS solar cell based on AS-treatment achieved champion efficiency of 15.52%, with improved V-OC of 643 mV and FF of 73.3%.

The effect of the counter-anion in the azolium pre-catalyst on enantio-control in oxidative NHC catalysis is demonstrated systematically for the first time in acylative kinetic resolution of oxindole-derived tertiary alcohols.

We present herein an unprecedented stereoselective synthesis of triaryl-2-pyrones with monoaxial or contiguous diaxes from readily available starting materials. This N-heterocyclic carbene catalysis method adopts an atroposelective annulation of 2-aryketones with ynals under oxidative conditions. The annulation includes the construction of one or two axes in a single operation, achieves step economy, and affords axially chiral triaryl-2-pyrones in moderate to good yields, with high to excellent enantioselectivities. DFT calculations of the relative energies of stereoisomers and rotational barriers were performed.

C13H15CdN5Cl2, monoclinic, P21/c (no. 14), a = 11.5514(4) Å, b = 16.7843(5) Å, c = 8.9691(3) Å, β = 101.927(3)∘, Z = 4, V = 1701.41(10) Å3, Rgt(F) = 0.0379, wRref(F2) = 0.1020, T = 293(2) K.

Molecular engineering of aptamers can confer exogenous biomedical properties that may be beneficial for various applications. In this study, a tumor-homing peptide modification strategy was developed to considerably enhance the accumulation and penetration abilities of the Sgc8c aptamer. Notably, the S2PM conjugate induced a much higher level of morphological variation in three-dimensional tumor microspheres (HCT116 cells) than in control groups, highlighting the importance of the homing and penetrating abilities derived from peptide. Moreover, the S2P accumulated at the tumor sites in a more selective manner in both HCT116 and 4T1 tumor models and was retained at the tumor sites for a much longer time than the control groups. These findings indicate that this newly developed molecular engineering strategy has great application potential in aptamer-mediated drug delivery. [GRAPHICS] .

We report herein an unprecedented gold and oxidative NHC relay catalysis that enables highly enantioselective cascade annulation between readily available α-amino-ynones with enals. This method utilizes the in situ-generated pyrrolin-4-ones as a novel and versatile synthon, which engage with α,β-unsaturated acylazolium intermediates generated from enals by oxidative NHC catalysis to produce pyrrole-fused lactones in high yield and excellent enantioselectivity. Synthetic utility of the lactone products is also demonstrated by facile conversion to densely functionalized pyrroles and pyrrolin-4-ones in high yields with excellent stereopurity.

N-Aryl phenothiazines and phenoxazines are of significant importance in various disciplines throughout academia and industry. The conventional synthetic strategy for the construction of these structures centers on the transition-metal-catalyzed cross-coupling of aryl halides with phenothiazines or phenoxazines. Here we present an organocatalytic approach to access N-naphthyl phenothiazine and phenoxazine scaffolds through a straightforward C-H amination of arenes as enabled by an azo group. This reaction features operational simplicity, adequate substrate generality and excellent functional group compatibility. Notably, the efficiency of the catalyst could be perfectly preserved after 5 catalytic cycles.