Discovery of Succinate Dehydrogenase Inhibitors Containing a Diphenylacetylene Fragment as Antifungal Agents.

The scaffold hopping strategy of chain extension is widely used in medicines and pesticides, many of which have introduced alkynes to increase rigidity and activity. Therefore, an alkyne molecule is introduced into the biphenyl structure to form alkyne-containing difluoropyrazole derivatives. Most of the compounds had excellent activity in activity tests against .

Organocatalytic enantioselective α-difluoromethylketone thiolation of β-keto esters using phthalimide-SCFCOAr.

The first asymmetric α-difluoromethylketone thiolation of diverse β-keto esters using an electrophilic phthalimide-SCFCOAr reagent (PhthN-SCFCOAr) was reported. In the presence of cinchona-alkaloid-based catalyst (DHQD)PHAL, the reaction was achieved in moderate yields with a moderate to excellent enantioselectivity (up to 93% ee) under mild reaction conditions and exhibited functional group compatibility. An ammonium hydrogen-bonded induction model was proposed to rationalize the origin of enantioselectivity.

Novel Synthetic Method and Insecticidal Evaluation of CF-Containing Polycyclic Neonicotinoid Derivatives.

The modification of active ingredients with a trifluoromethyl group represents a significant approach for the discovery of highly active pesticides. Herein, we developed a novel [3 + 3] annulation reaction of neonicotinoid precursors and trifluoromethyl-α,β-ynones and synthesized a series of CF-containing polycyclic neonicotinoid derivatives in high efficiency. The insecticidal activity results indicated that most of the target compounds showed good insecticidal activities against and at a concentration of 100 mg/L.

Discovery of Novel Neonicotinoids with Conjugated Diene Enabled by Cascade Allylation/Isomerization Synthetic Methodology.

As one of the most significant insecticides, neonicotinoids have played a pivotal role in crop protection and public sanitation. However, the high resistance and bee toxicity of neonicotinoid insecticides have attracted considerable attention. Herein, a series of neonicotinoid compounds with conjugated diene moieties were synthesized through the cascade allylation/isomerization reaction.

Design, Synthesis, and Biological Activity of Silicon-Containing Carboxamide Fungicides.

Bioisosteric silicon replacement has proven to be a valuable strategy in the design of bioactive molecules for crop protection and drug development. Twenty-one novel carboxamides possessing a silicon-containing biphenyl moiety were synthesized and tested for their antifungal activity and succinate dehydrogenase (SDH) enzymatic inhibitory activity. Among these novel succinate dehydrogenase inhibitors (SDHIs), compounds , , and possessing appropriate log and topological polar surface area values showed excellent inhibitory effects against , , , and at 10 mg/L in vitro, and the EC values of and were 0.

Brønsted acid catalyzed [4 + 2] cycloaddition for the synthesis of bisbenzannulated spiroketals with antifungal activities.

The intermolecular [4 + 2] cycloaddition of -hydroxy benzyl alcohols with isochroman ketals was realized by CFCOH catalysis. A broad range of bisbenzannulated [6,6]-spiroketals were formed under the metal-free mild conditions in moderate to excellent yields (45-98%) with mostly excellent diastereoselectivities (up to >20 : 1 dr). Furthermore, the enantioselective version was also preliminarily investigated and the bisbenzannulated [6,6]-spiroketal was obtained with 61% ee in the presence of Sc(OTf)/Feng's chiral ,'-dioxide ligand.

Iridium/Acid Dual-Catalyzed Enantioselective Aza-ene-type Allylic Alkylation of Nitro Ketene Aminals with Racemic Allylic Alcohols.

The enantioselective allylic alkylation of nitro ketene aminals with racemic allylic alcohols was realized by iridium/acid dual catalysis. An allyl group was installed on the α-position of nitro ketene aminals in a branched-selective manner in high efficiency with excellent enantioselectivities (93-99% ee). The protocol was applied to the late-stage modification of neonicotinoid insecticides, which directly furnished a novel neonicotinoid analogue with good insecticidal activity against (LC = 6.

Design, Synthesis, and Insecticidal Evaluation of Neonicotinoids with Conjugated Diene.

Neonicotinoid insecticides acting on the insect nicotinic acetylcholine receptors (nAChRs) play an essential role in contemporary pest control. In the present study, a series of novel neonicotinoid analogues with conjugated diene were synthesized. Bioassays indicated that compounds and had LC values of 1.

Ir-Catalyzed Asymmetric Cascade Allylation/Spiroketalization Reaction for Stereoselective Synthesis of Oxazoline-Spiroketals.

An asymmetric cascade allylation/spiroketalization reaction between 2-(1-hydroxyallyl)phenols and 5-methyleneoxazolines is accomplished by using a chiral Ir(I) catalyst derived from commercially available iridium precursor and the Carreira ligand. This protocol furnishes a class of structurally novel and unique oxazoline-spiroketals in up to 86% yield, >99% ee and >20:1 dr. Moreover, control experiments reveal that 4,4-disubstitution on 5-methyleneoxazolines is necessary to avoid the aromatization and for the spiroketalization to occur.

Diastereo- and Enantioselective Synthesis of Bisbenzannulated Spiroketals and Spiroaminals by Ir/Ag/Acid Ternary Catalysis.

We reported herein an iridium/silver/acid ternary catalytic system to access bisbenzannulated [6,6]-spiroketals in high efficiency with generally high diastereo- and enantioselectivities (up to >20 : 1 dr, >99 % ee). In this procedure, readily available o-alkynylacetophenones undergo cycloisomerization to generate isochromenes in situ that participate in stereoselective allylation/spiroketalization sequence with 2-(1-hydroxyallyl)phenols. Meanwhile, 2-(1-hydroxyallyl)anilines were also compatible in this cascade reaction, furnishing structurally novel bisbenzannulated [6,6]-spiroaminals with good diastereoselectivities (8 : 1-12 : 1 dr) and excellent enantioselectivities (98 %->99 % ee).

Enantioselective Synthesis of Spiroketals and Spiroaminals via Gold and Iridium Sequential Catalysis.

The enantioselective cascade reaction between racemic 2-(1-hydroxyallyl)phenols and alkynols/alkynamides was realized by using a gold and iridium sequential catalytic system. In this procedure, the in situ generated exocyclic vinyl ethers or enamides undergo the asymmetric allylation/spiroketalization with π-ally-Ir amphiphilic species, which provides an efficient and straightforward access to spiroketals and spiroaminals with excellent enantioselectivities. Moreover, racemic 2-(1-hydroxyallyl)anilines were also suitable in this reaction along with a kinetic resolution process, affording enantioenriched spiroaminals and 2-(1-hydroxyallyl)anilines in good yields.

Regio- and Enantioselective γ-Allylic Alkylation of In Situ-Generated Free Dienolates via Scandium/Iridium Dual Catalysis.

An unprecedented asymmetric γ-allylic alkylation of free dienolates via Sc/Ir dual catalysis is reported, which affords a range of synthetically versatile γ-allylic crotonaldehydes in high efficiency with excellent chemo-, regio-, and enantioselectivities. The dienolates bearing no essential auxiliary groups were generated in situ by scandium triflate-mediated Meinwald rearrangement of vinyloxiranes atom-economically. With the assistance of computational density functional theory calculations, a Sc/Ir bimetallic catalytic cycle was proposed to illustrate the reaction mechanism.

TRIM32 Deficiency Impairs the Generation of Pyramidal Neurons in Developing Cerebral Cortex.

Excitatory-inhibitory imbalance (E/I) is a fundamental mechanism underlying autism spectrum disorders (ASD). TRIM32 is a risk gene genetically associated with ASD. The absence of TRIM32 causes impaired generation of inhibitory GABAergic interneurons, neural network hyperexcitability, and autism-like behavior in mice, emphasizing the role of TRIM32 in maintaining E/I balance, but despite the description of TRIM32 in regulating proliferation and differentiation of cultured mouse neural progenitor cells (NPCs), the role of TRIM32 in cerebral cortical development, particularly in the production of excitatory pyramidal neurons, remains unknown.

Iridium-Catalyzed Asymmetric Cascade Allylation/Pictet-Spengler Cyclization Reaction for the Enantioselective Synthesis of 1,3,4-Trisubstituted Tetrahydroisoquinolines.

An iridium-catalyzed trifluoroacetic acid-promoted asymmetric cascade allylation/Pictet-Spengler cyclization reaction of azomethine ylides with aromatic allylic alcohols is reported. This protocol provides a facile and scalable method for the construction of 1,3,4-trisubstituted tetrahydroisoquinolines containing two stereogenic centers in good yields (up to 96%) with generally excellent diastereo- and enantioselectivities (up to >20:1 dr and >99% ee). Furthermore, a series of aromatic heterocycle-fused piperidines were also obtained with excellent enantiocontrol by this methodology.

Sulfone as a Transient Activating Group in the Palladium-Catalyzed Asymmetric [4 + 3] Cycloaddition of Trimethylenemethane Enabling the Enantioselective Synthesis of Fused Azepines.

The palladium-catalyzed asymmetric [4 + 3] cycloaddition of a sulfonyl-trimethylenemethane (TMM) donor with azadienes furnished various sulfonyl-fused azepines with exclusive regioselectivities and excellent stereoselectivities (up to >20:1 dr, >99% ee) in high yields (up to 93%). Moreover, sulfone, serving as a transient activating group of the TMM species, can be easily removed from the cycloadducts to provide the structurally simple fused azepines with excellent enantioselectivities. This strategy demonstrates sulfonyl-TMM as an effective surrogate of naked TMM with high reactivity, exclusive regioselectivity, and excellent stereoselectivity.

Iridium-Catalyzed Diastereo- and Enantioselective [4 + 3] Cycloaddition of 4-Indolyl Allylic Alcohols with Azomethine Ylides.

An unprecedented iridium-catalyzed asymmetric [4 + 3] cycloaddition of racemic 4-indolyl allylic alcohols with azomethine ylides is reported. The ability of acid promoter zinc triflate to perform multiple roles is the key factor for the success of this strategy. This method provides scalable and efficient access to biologically important azepino[3,4,5-] indoles in good yields with generally excellent diastereo- and enantioselectivities (up to >20:1 dr and >99% ee).

Catalytic Asymmetric [3 + 2] Annulation via Indolyl Copper-Allenylidene Intermediates: Diastereo- and Enantioselective Assembly of Pyrrolo[1,2-]indoles.

A catalytic asymmetric decarboxylative [3 + 2] annulation via indolyl copper-allenylidene amphiphilic intermediates has been developed. This protocol offers a straightforward method for the synthesis of biologically important pyrrolo[1,2-]indoles bearing contiguous quaternary and tertiary stereogenic centers with excellent diastereo- and enantioselectivities (up to >20:1 dr and >99% ee). In addition, the diversity-oriented synthesis of pyrrolo[1,2-]indoles was achieved via versatile transformations of the alkyne-containing cycloadducts.

Organocatalytic Regiodivergent Ring Expansion of Cyclobutanones for the Enantioselective Synthesis of Azepino[1,2-]indoles and Cyclohepta[]indoles.

A regiodivergent organocatalytic enantioselective Michael addition/three-atom ring expansion sequence of electron-withdrawing group activated cyclobutanones with 2-nitrovinylindoles was developed. A series of azepino[1,2-]indoles were obtained with exclusive regioselectivities and high diastereo- and enantioselectivities (up to >20:1 dr, 96% ee) with the application of the N1 nucleophilic site of the indole nucleus. Meanwhile, various cyclohepta[]indoles could be accessed with high enantiopurity (up to 96% ee) through the Michael addition/boron-trifluoride-etherate-promoted indole C3-attack ring expansion process.

Enantioselective Iron/Bisquinolyldiamine Ligand-Catalyzed Oxidative Coupling Reaction of 2-Naphthols.

An iron-catalyzed asymmetric oxidative homo-coupling of 2-naphthols for the synthesis of 1,1'-Bi-2-naphthol (BINOL) derivatives is reported. The coupling reaction provides enantioenriched BINOLs in good yields (up to 99%) and moderate enantioselectivities (up to 81:19 er) using an iron-complex generated in situ from Fe(ClO) and a bisquinolyldiamine ligand [(1,2)-,-di(quinolin-8-yl)cyclohexane-1,2-diamine, ]. A number of ligands (-) and the analogs of , with various substituents and chiral backbones, were synthesized and examined in the oxidative coupling reactions.

Palladium-Catalyzed Asymmetric [4+3] Cyclization of Trimethylenemethane: Regio-, Diastereo-, and Enantioselective Construction of Benzofuro[3,2-b]azepine Skeletons.

The palladium-catalyzed asymmetric [4+3] cyclization of trimethylenemethane donors with benzofuran-derived azadienes furnishes chiral benzofuro[3,2-b]azepine frameworks in high yields (up to 98 %) with exclusive regioselectivities and excellent stereoselectivities (up to >20:1 d.r., >99 % ee).

Synthesis of 2,3-Ring Fused Pyrroles via Cu-Catalyzed 5--dig Annulation of Alkyne-Tethered Enaminones.

A copper-catalyzed annulation of alkyne-tethered enaminones for the synthesis of 2,3-ring fused pyrroles is reported. The 5--dig cyclization/olefin migration reaction delivers the multisubstituted pyrroles in 59-99% yields with 16 examples. This strategy features easily available starting materials, mild reaction conditions, and a cheap ligand-free copper catalyst.

Enantioselective Construction of Dihydropyrido[1,2-]indoles via Organocatalytic Arylmethylation of 2-Enals with Inert Aryl Methane Nucleophiles.

An organocatalytic asymmetric arylmethylation/-hemiacetalization of 2-indolyl methane derivatives and 2-enals was developed. Notably, the 2-methyl of indole was readily deprotonated to produce highly reactive nucleophilic species by introducing the nitro group at the C3 position of the indole ring. A spectrum of valuable chiral dihydropyrido[1,2-]indoles were efficiently constructed with excellent enantioselectivity (up to >99% ee).

Ligand-controlled switch in diastereoselectivities: catalytic asymmetric construction of spirocyclic pyrrolidine-azetidine/oxe(thie)tane derivatives.

An efficient catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with four-membered ring-containing exocyclic alkenes has been developed, and either the exo or endo spirocyclic pyrrolidine-azetidine/oxe(thie)tane derivatives were diastereodivergently generated by employing Cu(i)/tBu-Phosferrox and a Cu(i)/N,O-ligand complex, respectively. Notably, various heteroatom-containing (N, O, S) exocyclic alkenes were found to be well-tolerated in this transformation.

Enantioselective Construction of CF-Containing Spirooxindole γ-Lactones via Organocatalytic Asymmetric Michael/Lactonization.

A highly enantioselective Michael/lactonization cascade reaction of 3-hydroxyoxindoles with 3-trifluoroethylidene oxindoles was developed. The use of a cinchona-derived squaramide catalyst is essential in achieving high diastereo- and enantioselectivities. This reaction represents the first example of intramolecular amide C-N bond cleavage and lactonization of 3-hydroxyoxindoles with 3-trifluoroethylidene oxindoles, which provides an efficient and convenient approach to diverse CF-containing spirooxindole γ-lactones in high yields and good to excellent diastereo- and enantioselectivities.