Regio- and Enantioselective Hydromethylation of 3-Pyrrolines and Glycals Enabled by Cobalt Catalysis.

Enantioenriched 3-methylpyrrolidine, with its unique chiral nitrogen-containing core skeleton, exists widely in various functional molecules, including natural products, bioactive compounds, and pharmaceuticals. Traditional methods for synthesizing these valuable methyl-substituted heterocycles often involve enzymatic processes or complex procedures with chiral auxiliaries, limiting the substrate scope and efficiency. Efficient catalytic methylation, especially in an enantioselective manner, has been a long-standing challenge in chemical synthesis. Herein, we present a novel approach for the remote and stereoselective installation of a methyl group onto N-heterocycles, leveraging a CoH-catalyzed asymmetric hydromethylation strategy. By effectively combining a commercial cobalt precursor with a modified bisoxazoline (BOX) ligand, a variety of easily accessible 3-pyrrolines can be converted to valuable enantiopure 3-(isotopic labeling)methylpyrrolidine compounds with outstanding enantioselectivity. This efficient protocol streamlines the two-step synthesis of enantioenriched 3-methylpyrrolidine, which previously required up to five or six steps under harsh conditions or expensive starting materials.

CoH-catalyzed asymmetric remote hydroalkylation of heterocyclic alkenes: a rapid approach to chiral five-membered S- and O-heterocycles.

Saturated heterocycles, which incorporate S and O heteroatoms, serve as fundamental frameworks in a diverse array of natural products, bioactive compounds, and pharmaceuticals. Herein, we describe a unique cobalt-catalyzed approach integrated with a desymmetrization strategy, facilitating precise and enantioselective remote hydroalkylation of unactivated heterocyclic alkenes. This method delivers hydroalkylation products with high yields and excellent stereoselectivity, representing good efficiency in constructing alkyl chiral centers at remote C3-positions within five-membered S/O-heterocycles. Notably, the broad scope and good functional group tolerance of this asymmetric C(sp3)-C(sp3) coupling enhance its applicability.

Design, synthesis, antibacterial evaluation of isopropylamine linked with different substituted phenol and piperazine novel derivatives.

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) is often considered one of the most destructive bacterial pathogens causing bacterial leaf blight (BLB), resulting in significant yield and cost losses in rice. In this study, a series of novel derivatives containing the isopropanolamine moiety linked to various substituted phenols and piperazines were designed, synthesized and screened. RESULTS: Antibacterial activity results showed that most compounds had good inhibitory effects on Xoo, among which compound W2 (EC50 = 2.74 µg mL-1) exhibited the most excellent inhibitory activity, and W2 also had a certain curative effect (35.89%) on rice compared to thiodiazole copper (TC) (21.57%). Scanning electron microscopy (SEM) results indicated that compound W2 could cause rupture of the Xoo cell membrane. Subsequently, proteomics and quantitative real-time polymerase chain reaction revealed that compound W2 affected the physiological processes of Xoo and may exert antibacterial activity by targeting the two-component system pathway. Interestingly, W2 upregulated Xoo's methyltransferase to impact on its pathogenicity. CONCLUSION: The present study offers a promising phenolic-piperazine-sopropanolamine compound as an innovative antibacterial strategy by specifically targeting the two-component system pathway and inducing upregulation of methyltransferase to effectively impact Xoo's pathogenicity. © 2024 Society of Chemical Industry.

Interfacial Rivet to Fill Structural Defects: A Spacer Engineering Gift for 3D Solar Cells.

The combination of 2D and 3D perovskites to passivate surfaces or interfaces with a high concentration of defects shows great promise for improving the efficiency of perovskite solar cells (PSCs). Constructing high-quality perovskite film systems by precisely modulating 2D perovskites with good morphologies and growth sites on 3D perovskite films remains a formidable challenge due to the complexity of spacer-engineered surface reactions. In this study, phase-pure 2D (HA)2(MA)n-1PbnI3n+1 perovskites with a controlled number of layers (n) are separated on a large scale and exploited as interface rivets to optimize 3D perovskite films, resulting in tunable film structural defects and grain boundaries. The optimized PSCs system benefits from a reduction in non-radiative recombination, resulting in improved optical performance, higher mobility, and lower trap density. The corresponding device achieves a champion power conversion efficiency (PCE) of more than 25%, especially for voltage (VOC) and fill factor (FF). The quality and uniformity of the perovskite films are further confirmed using large-area devices with an active area of 14 cm2, which exhibits a PCE of more than 21.24%. The high-quality thin-film system based on the 2D perovskites presented herein provides a new perspective for improving the efficiency and stability of PSCs.

Chromosome-level genomes of three key Allium crops and their trait evolution.

Allium crop breeding remains severely hindered due to the lack of high-quality reference genomes. Here we report high-quality chromosome-level genome assemblies for three key Allium crops (Welsh onion, garlic and onion), which are 11.17 Gb, 15.52 Gb and 15.78 Gb in size with the highest recorded contig N50 of 507.27 Mb, 109.82 Mb and 81.66 Mb, respectively. Beyond revealing the genome evolutionary process of Allium species, our pathogen infection experiments and comparative metabolomic and genomic analyses showed that genes encoding enzymes involved in the metabolic pathway of Allium-specific flavor compounds may have evolved from an ancient uncharacterized plant defense system widely existing in many plant lineages but extensively boosted in alliums. Using in situ hybridization and spatial RNA sequencing, we obtained an overview of cell-type categorization and gene expression changes associated with spongy mesophyll cell expansion during onion bulb formation, thus indicating the functional roles of bulb formation genes.

Divergent Access to Chiral C2- and C3-Alkylated Pyrrolidines by Catalyst-Tuned Regio- and Enantioselective C(sp3)-C(sp3) Coupling.

Novel-substituted pyrrolidine derivatives are widely used in drugs and bioactive molecules. The efficient synthesis of these valuable skeletons, especially enantiopure derivatives, is still recognized as a key bottleneck to overcome in chemical synthesis. Herein, we report a highly efficient catalyst-tuned regio- and enantioselective hydroalkylation reaction for the divergent synthesis of chiral C2- and C3-alkylated pyrrolidines through desymmetrization of the readily available 3-pyrrolines. The catalytic system consists of CoBr2 with a modified bisoxazoline (BOX) ligand, which can achieve the asymmetric C(sp3)-C(sp3) coupling via the distal stereocontrol, providing a series of C3-alkylated pyrrolidines in high efficiency. Moreover, the nickel catalytic system allows the enantioselective hydroalkylation to synthesize the C2-alkylated pyrrolidines through the tandem alkene isomerization/hydroalkylation reaction. This divergent method uses readily available catalysts, chiral BOX ligands, and reagents, delivering enantioenriched 2-/3-alkyl substituted pyrrolidines with excellent regio- and enantioselectivity (up to 97% ee). We also demonstrate the compatibility of this transformation with complex substrates derived from a series of drugs and bioactive molecules in good efficiency, which offers a distinct entry to more functionalized chiral N-heterocycles.

Metal-Catalyst-Controlled Divergent Synthesis of γ-Butyrolactones via Intramolecular Coupling of Epoxides with Alcohols.

A metal-controlled divergent protocol for the synthesis of α- and ß-substituted γ-butyrolactones was developed through intramolecular coupling of epoxides with alcohols. This method provides an efficient and practicable way to afford γ-butyrolactones with good efficiency, excellent regioselectivity, and broad substrate scope.

Nickel-catalyzed cross-coupling of epoxides with aryltriflates: rapid and regioselective construction of aryl ketones.

Aryl ketones are one of the most important classes of organic compounds, and widely present in various pharmacological compounds, biologically active molecules and functional materials. Presented herein is a facile synthetic method for the construction of ketones via Ni-catalyzed cross coupling of epoxides with aryltriflates. A range of easily accessible epoxides can be highly regioselectively converted to the corresponding aryl ketones with good yields in a redox neutral fashion.

Stereoselective access to [5.5.0] and [4.4.1] bicyclic compounds through Pd-catalysed divergent higher-order cycloadditions.

Medium-sized rings, including those embedded in bridged and fused bicyclic scaffolds, are common core structures of myriad bioactive molecules. Among various synthetic strategies towards their synthesis, intermolecular higher-order cycloaddition provides great potential to build complex medium-sized rings from simple building blocks. Unfortunately, such transformations are often plagued with competitive reaction pathways and low levels of site- and stereoselectivity. Herein, we report catalyst-controlled divergent access to three classes of medium-sized bicyclic compounds in high efficiency and stereoselectivity, by palladium-catalysed cycloadditions of tropones with γ-methylidene-δ-valerolactones. Mechanistic studies and density functional theory calculations disclosed that the divergent reactions stem from the different reaction profiles of the diastereomeric intermediates. While one undergoes either O- or C-allylation to provide [5.5.0] or [4.4.1] bicyclic compounds, the unique conformation of the other diastereomer allows an unconventional alkene isomerization to deliver bridgehead alkene-containing bicyclo[4.4.1] compounds. The conversion of these products to diverse complex polycyclic scaffolds has also been demonstrated.

NHC-Catalyzed Atroposelective Acylation of Phenols: Access to Enantiopure NOBIN Analogs by Desymmetrization.

Herein we present a highly efficient N-heterocyclic-carbene (NHC)-catalyzed atroposelective acylation of amino bisphenols to provide access to a wide range of 1,1'-biaryl-2,2'-amino alcohols (NOBIN analogs) in high yield and with uniformly excellent enantioselectivity. This catalytic system is shown to proceed through a combination of desymmetrization and secondary kinetic resolution to produce the axially chiral products in excellent enantioselectivity.

Palladium-Titanium Relay Catalysis Enables Switch from Alkoxide-π-Allyl to Dienolate Reactivity for Spiro-Heterocycle Synthesis.

Reported herein is the divergent syntheses of [5,5] and [6,5] spiro-heterocycles under Lewis-acid-assisted palladium catalysis. In particular, an unprecedented switch from alkoxide-π-allyl to dienolate reactivity was achieved by the use of palladium-titanium relay catalysis, and represents umpolung reactivity of vinylethylene carbonates. This method uses a simple procedure and commercially available catalysts, and delivers both classes of spiro-heterocycles, bearing three contiguous stereocenters, in high yield and uniformly excellent diastereoselectivity.

Pd-Catalyzed Enantioselective [6+4] Cycloaddition of Vinyl Oxetanes with Azadienes to Access Ten-Membered Heterocycles.

We report herein the first enantioselective cycloaddition of vinyl oxetanes, the reaction of which with azadienes provided unprecedented access to ten-membered heterocycles through a [6+4] cycloaddition. By using a commercially available chiral Pd-SIPHOX catalyst, a wide range of benzofuran- as well as indole-fused heterocycles could be accessed in excellent yield and enantioselectivity. A unique Lewis acid induced fragmentation of these ten-membered heterocycles was also discovered.

Intramolecular Acetyl Transfer to Olefins by Catalytic C-C Bond Activation of Unstrained Ketones.

A rhodium-catalyzed intramolecular acetyl-group transfer has been achieved through a "cut and sew" process. The challenge arises from the existence of different competitive pathways. Preliminary success has been achieved with unstrained enones that contain a biaryl linker. The use of an electron-rich N-heterocycilc carbene (NHC) ligand is effective to inhibit undesired ß-hydrogen elimination. Various 9,10-dihydrophenanthrene derivatives can be prepared with excellent functional-group compatibility. The 13 C-labelling study suggests that the reaction begins with cleavage of the unstrained C-C bond, followed by migratory insertion and reductive elimination.

Nine-Membered Benzofuran-Fused Heterocycles: Enantioselective Synthesis by Pd-Catalysis and Rearrangement via Transannular Bond Formation.

The first enantioselective formal [5+4] cycloaddition is realized under palladium catalysis to deliver benzofuran-fused nine-membered rings. These medium-sized heterocycles and derivatives undergo unique rearrangements induced by transannular bond formation, resulting in the production of two classes of densely substituted polycyclic heterocycles in excellent efficiency and stereoselectivity.

Construction of Nine-Membered Heterocycles through Palladium-Catalyzed Formal [5+4] Cycloaddition.

The first catalytic formal [5+4] cycloaddition to prepare nine-membered heterocycles is presented. Under palladium catalysis, the reaction of N-tosyl azadienes and substituted vinylethylene carbonates (VECs) proceeds smoothly to produce benzofuran-fused heterocycles in uniformly high efficiency. Highly diastereoselective functionalization of the nine-membered heterocycles through peripheral attack is also demonstrated.

A Catalyst-Enabled Diastereodivergent Aza-Diels-Alder Reaction: Complementarity of N-Heterocyclic Carbenes and Chiral Amines.

Highly efficient and diastereodivergent aza-Diels-Alder reactions have been developed to access either diastereomeric series of benzofuran-fused δ-lactams and dihydropyridines in nearly perfect stereoselectivity (d.r. >20:1, >99 % ee for all examples). The complementarity of N-heterocyclic carbene and chiral amine as the catalyst was demonstrated for the first time, together with an excellent level of catalytic efficiency (1 mol % loading).

Dynamic Kinetic Asymmetric Amination of Alcohols: From A Mixture of Four Isomers to Diastereo- and Enantiopure α-Branched Amines.

The first dynamic kinetic asymmetric amination of alcohols via borrowing hydrogen methodology is presented. Under the cooperative catalysis by an iridium complex and a chiral phosphoric acid, α-branched alcohols that exist as a mixture of four isomers undergo racemization by two orthogonal mechanisms and are converted to diastereo- and enantiopure amines bearing adjacent stereocenters. The preparation of diastereo- and enantiopure 1,2-amino alcohols is also realized using this catalytic system.

Stereoselective synthesis of ε-lactones or spiro-heterocycles through NHC-catalyzed annulation: divergent reactivity by catalyst control.

NHC-catalyzed divergent annulation of enals with heterocyclic enones was developed to produce benzofuran/indole-containing ε-lactones or spiro-heterocycles in a highly diastereo- and enantioselective fashion. The chemo-selectivity controlled by the chiral catalyst backbone is particularly noteworthy.

Enantioselective oxidation of 1,2-diols with quinine-derived urea organocatalyst.

Quinine-derived urea has been identified as a highly efficient organocatalyst for the enantioselective oxidation of 1,2-diols using bromination reagents as the oxidant. This simple procedure utilizes readily available reagents and operates at ambient temperature to yield a wide range of α-hydroxy ketones in good yield (up to 94%) and excellent enantioselectivity (up to 95% ee).