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Cyclodehydration using the Burgess reagent provided a novel approach toward the synthesis of N-bridged 5,6-bicylic pyridines including pyrolo-, imidazo-, and triazolopyridines under mild and neutral conditions. The methodology tolerates acid-sensitive functional groups. A novel addition product was observed between the resulting pyrrolo- or imidazopyridine and an additional equivalent of the Burgess reagent, producing the corresponding sulfonylcarbamate adduct. [ABSTRACT FROM AUTHOR]

A highly efficient Au(I)-catalyzed cascade reaction between bispropargylic alcohols and pyridine- N -oxides has been realized. The reaction process involved a gold(I)-catalyzed sequential oxidation/Pinacol rearrangement/oxacyclization. Moreover, 1,2-aryl, 1,2-alkyl, or 1,2-vinyl migration was favored over 1,2-alkynyl in the crucial gold(I)-catalyzed Pinacol rearrangement step. A range of 2,4,5-trisubstituted 3(2 H )-furanones were synthesized in high yields (up to 88%) with excellent regioselectivities (up to >19:1) under mild reaction conditions.

We disclose herein an asymmetric synthesis of axially chiral oxazepine-containing bridged biaryls via CPA-catalyzed kinetic asymmetric alcoholysis. Control experiments showed that this CPA-catalyzed alcoholysis was reversible, and lowering the reaction temperature could almost suppress the reversible reaction, thus providing a series of axially chiral oxazepine-containing bridged biaryl compounds in good to excellent enantioselectivities. The gram-scale reactions and facile derivatizations of the enantioenriched products demonstrate the practical utility of this reaction.

Asperalins represent a novel class of viridicatin natural products with potent inhibitory activities against fish pathogens. In this study, we elucidated the biosynthesis of asperalins in the Aspergillus oryzae NSAR1 heterologous host and identified the FAD-dependent monooxygenase AplB stereoselectively hydroxylates viridicatin to yield a unique 3 R ,4 S configuration. The monomodular NRPS AplJ catalyzes a rare intramolecular ester bond formation reaction using dihydroquinoline as a nucleophile. Subsequent modifications by cytochrome P450 AplF, chlorinase AplN, and prenyltransferase AplE tailor the anthranilic acid portion, leading to the formation of asperalins. Additionally, we explored the potential of AplB for the hydroxylation of viridicatin analogs, demonstrating its relaxed substrate specificity. This finding suggests that AplB could be developed as a biocatalyst for the synthesis of viridicatin derivatives.

Thioesterase (TE) domain exerts a great influence over the structure of the final product and TE-released nonreduced polyketides (nrPKs) retain aromaticity. 3-Methylene isochromanones are lactones with a unique olefin at C3 that disrupts the aromaticity, whose biosynthetic details are speculative. Our study unveils the complete biosynthesis of ascochin, in which the construction of the 3-methylene isochromanone backbone is achieved by a nonreducing polyketide synthase (nrPKS) alone and two subsequent oxidations are involved. Intriguingly, the TE AscD serves as a gatekeeper to direct the product release toward formation of nonaromatic 3-methylene isochromanone, rather than the typical aromatic product.

Selective dehydrogenative C-H silylation is one of the most powerful tools to synthesize silacycles. Herein, we developed Ru-catalyzed sequential hydrosilylation/C-H silylation of allyl-indoles and dehydrogenative O-H/C-H silylation of pyrrole phenols. Both six-membered indole silacycles and pyrrole silyl ether cycles were successfully synthesized with good functional group tolerance. Furthermore, the RuHCl(CO)(PPh 3 ) 3 catalyst exhibited high reaction compatibility in hydrosilylation of alkene, dehydrogenative O-H silylation, and C-H silylation.

We have developed a highly regio-, diastereo-, and enantioselective Cu-catalyzed desymmetrization of inert meso -diethers using Grignard reagents. Moreover, previous inaccessible sterically hindered organometallic reagents are realized in the reaction with broad secondary alkyl Grignard reagents. Finally, detailed control experiments and density functional theory calculations revealed the desymmetrization of meso -diethers exploits a direct anti -S N 2' pathway, in the absence of an in situ -generated allyl bromine intermediate. The following oxidative addition is the crucial rate-determining and enantioselectivity-determining step.

Here, we present a silver-catalyzed decarboxylative nitrooxylation via a radical-based approach. The substrate scope of this reaction prototype extends to nonactivated primary and secondary carboxylic acids. This protocol provides a practical method for the synthesis of an unprecedented family of organic nitrates and exhibits wide functional group compatibility. Preliminary mechanistic studies reveal that a high-valent silver(II) nitrate complex is a versatile NO 3 resource pool, allowing for facile C-O bond formation.

Three dithio-fused boron dipyrromethenes (BODIPYs), DTFB-1 , DTFB-2 , and DTFB-3 , in which symmetrically S-heteroaromatic ring units fused at [ a ], zigzag, and [ b ] bonds of the parent BODIPY core, respectively, were prepared from the facile and efficient post-functionalization of tetra-halogenated BODIPYs through Pd-catalyzed cyclization. Dithio-fusion at various positions of BODIPY effectively tunes their photophysical properties and single-crystal structural packing arrangements. The single-crystalline microribbons of DTFB-2 exhibit commendable hole mobilities in air, reaching up to 0.03 cm 2 V -1 s -1 .

Herein, we describe a novel approach to the synthesis of benzocycloheptene derivatives via base-promoted (5 + 2) annulation between 2-(alkynylaryl)acetonitriles and arylalkynes. In this chemistry, 2-(alkynylaryl)acetonitriles are employed as a new C5 synthon to construct various benzocycloheptene(s) derivatives by building two C-C bonds in one single step. This method features excellent regioselectivity, the use of readily available starting materials, and good functional group tolerance. The practicality of the strategy was further demonstrated by gram-scale synthesis, late-stage functionalizations, and the post-modification of natural products such as probenecid and tetrahydrofurfuryl alcohol.

Exploiting novel fused cyclic frameworks through simple and efficient methods has provided a blueprint for developing advanced explosives. In this study, six new [5,6,5]-tricyclic fused energetic compounds ( I - VI ) were synthesized through an intramolecular cyclization strategy involving a C-NH 2 directed cyclization reaction. The work not only boosts the development of fused cyclic energetic compounds but also highlights their potential applications as secondary or heat-resistant explosives.

A de novo method for direct construction of cyclopenta[ b ]indolines via a photocatalytic fluoroalkylative radical cyclization cascade of ynamides has been established, which proceeds via a sequence of radical addition, 1,5-HAT, 5- endo - trig cyclization, intramolecular arylation, and oxidative deprotonation. This protocol allows for the controllable assembly of a tricyclic architecture with three contiguous stereocenters, showcasing its high efficiency, compatibility, and regio- and diastereoselectivity for accessing pharmacologically significant fluoroalkylated cyclopenta[ b ]indolines. It represents one of the very few examples of tetrafunctionalization of alkynes.

To realize strong donor-acceptor face-to-face stacking for efficient through-space charge transfer-type thermally activated delayed fluorescence, a conceptually new design strategy is proposed to couple flexible bridges with adequate rigidity via built-in intramolecular hydrogen bonds (IHBs). The resulting emitter ACE-CN has a planarized benzyl methyl ether bridge self-anchored by the C-H···O IHB and shows a high photoluminescence quantum efficiency of 93%. The solution- and vacuum-processed devices exhibited high external quantum efficiencies of 11.8% and 24.7%, respectively.

Enamides and their derivatives are prominent bioactive pharmacophores found in various bioactive molecules. Herein we report a palladium-catalyzed oxidative N -α,β-dehydrogenation of amides to produce a range of enamides with high yields and excellent tolerance toward different functional groups. Mechanistic studies indicate that the reaction involves allylic C(sp 3 )-H activation followed by β-H elimination. The effectiveness of this approach is demonstrated through late-stage functionalization of bioactive molecules and the synthesis of valuable compounds through product elaboration.

An efficient method for remote radical C(sp 3 )-H azidation at unactivated sites is described. C-H functionalization proceeds via intramolecular 1,5-hydrogen atom transfer to N-centered radicals that are generated via azido group transfer and/or fragmentation. The readily installed sulfamoyl azide serves as both an amidyl radical precursor and an azido source. This reaction features excellent site selectivity for tertiary, secondary, primary, and benzylic C(sp 3 )-H bonds and exhibits broad functional group compatibility.

Here, we report a novel strategy for the direct construction of polycyclic fused ortho -quinone scaffolds through palladium(II)-catalyzed tandem γ-C(sp 2 )-H arylation and cyclization of arylglyoxals with aryl iodides. This transformation features unique tandem transient directing of γ-C(sp 2 )-H arylation and cyclization reaction mode, broad substrate scope, especially for the aromatic substrates containing oxygen and sulfur atoms, and avoiding the common issue of aromatization due to the construction of the hexatomic ring.

Here, we present the straightforward synthesis of N -fluorosulfonyl guanidine ( 1 ) from two industrial feedstocks, guanidine hydrochloride and sulfuryl fluoride (SO 2 F 2 ), using SuFEx chemistry. Compound 1 exhibits excellent stability under ambient conditions and displays unique SuFEx reactivity toward amines and phenols to generate N -guanyl sulfamides and sulfamates that have rarely been accessed. Notably, water serves as an effective solvent in this process. Our protocol provides a reliable pathway for the synthesis and investigation of these novel guanidine-containing molecules.

Herein, we report a catalyst-free reaction of cyclobutanone oximes with chlorophosphines (R 2 PCl), which forms a fragile C═N-O-PR 2 species that undergoes N-O homolysis, fragmentation, and radical-radical coupling, leading to the formation of cyano-containing phosphine oxides in good yields. The reaction features an in situ activation of cyclobutanone oximes for radical generation, in which R 2 PCl plays a dual role as both an activator and a reactant.

A copper-mediated [3 + 2] cyclization of CF 3 -imidoyl sulfoxonium ylides and terminal alkynes has been demonstrated. This work provides a practical approach for assembling 5-trifluoromethylpyrroles with the merits of a broad substrate scope, good functional tolerance, and mild reaction conditions. Control experiments and DFT studies indicate that this reaction may involve the addition of π-bonds of terminal alkynes by copper-carbene radicals and hydrogen migration.

A sustainable, cyanide-free synthesis of alkyl nitriles via the aerobic oxidative deconstruction of unstrained cycloalkanones with ammonium salts has been developed. Using inexpensive and stable ammonium salts as the nitrogen source, a variety of alkyl nitriles containing a distal carbonyl group were obtained in good yields under visible-light-promoted iron catalysis. This protocol is characterized by mild conditions, abundant and environmentally benign materials, and high atom and step economy with minimal waste generation. The primary mechanism study revealed that 1 O 2 is likely to be involved in this reaction.

A silver-catalyzed decarboxylative remote fluorination via a zwitterion-promoted 1,4-heteroaryl migration has been developed. A variety of heteroaryl-tethered benzyl fluorides have been readily synthesized with good regioselectivity under mild conditions. The zwitterion of the substrate is suggested to accelerate the 1,4-heteroaryl migration, which determines the regioselectivity of this transformation.

A chemical synthesis of a unique nanosaccharide fragment from Helicobacter pylori lipopolysaccharide was achieved via a convergent glycosylation method. Challenges involved in the synthesis include the highly stereoselective construction of β-3-deoxy-d- manno -oct-2-ulosonic acid (Kdo) and two 1,2- cis -glycosidic linkages, as well as the formation of a branched 2,7-disubstituted heptose subunit. Hydrogen-bond mediated aglycone delivery strategy and benzoyl-directing remote participation effect were employed, respectively, for the efficient generation of the desired β-Kdo glycoside and 1,2- cis -α-l-fucoside/d-glucoside. Moreover, the key branched framework was successfully established through a [(7 + 1) + 1] assembly approach involving the stepwise glycosylation of the heptasaccharide alcohol with two monosaccharide donors. The synthesized 1 containing a propylamine linker at the reducing end can be covalently bound to a carrier protein for further immunological studies.

We disclosed a Ni/CPA cocatalyzed protocol to access diverse C -acyl glycosides under mild conditions with broad functional group compatibility through the coupling of readily available glycosyl bromides and carboxylic esters. The potential application of the methodology was demonstrated by the C -acyl glycosylation of bioactive molecules and the transformation of products to a variety of value-added molecules. Mechanistic studies revealed that CPA might serve as a bifunctional H-bond catalyst to activate carboxylic esters and nickel catalyst.

Herein, we disclose a radical desulfurative C-C coupling protocol for the synthesis of 4-alkylpyridines. A variety of substituents on both benzyl thiols and 4-cyanopyridines are tolerated. The reaction is carried out under mild and photocatalyst- and transition-metal-free conditions. Preliminary mechanistic studies show that an electron donor-acceptor complex is formed between benzyl thiols and 4-cyanopyridines under alkaline conditions. Then, a variety of 1°, 2°, and 3° C(sp 3 )-centered radicals was formed by cleavage of the C-S bond, and the 4-alkylpyridines were achieved through a radical-radical coupling with the pyridyl radical anion.

Difluoroenoxysilane, a commonly used difluoroallylating reagent, has attracted considerable attention in recent years. However, its application in the annulation reaction for the construction of fluorinated heterocyclic compounds remains relatively limited. Presented here is the Brønsted acid-catalyzed efficient formal [4 + 2] annulation of difluoroenoxysilanes with α-cyano chalcones. The developed protocol demonstrates tolerance to various substituents under mild reaction conditions, providing a reliable approach to construct gem -difluoro-3,4-dihydro-2 H -pyrans in good to excellent yields with high diastereoselectivities.

We present a straightforward one-step process to access a range of novel p -diindolepyrazines via an unprecedented [ n -Bu 4 N][Fe(CO) 3 (NO)] (TBA[Fe])-catalyzed intermolecular nitrogenative dimerization of various indole derivatives. Remarkably, tosylazide functions as a N1-synthon forming the central pyrazine unit that joins the two indole subunits. The catalytic transformation shows a good substrate scope, and the obtained products show interesting electronic properties.

The propargylic dialkyl effect (PDAE) has a significant impact on the cyclization reaction of enynes, partly reflected in changing the types of products. Herein, we described the influence of the propargylic dialkyl effect on the Ir(III)-catalyzed cycloisomerization of 1,6-enynes to provide strained cyclobutenes. A series of substituted 1,6-enynes were proved to be excellent substrate candidates in the presence of [Cp*IrCl 2 ] 2 in toluene. Mechanistic investigation, based on deuterium labeling experiments and control experiments, indicated that the propargylic dialkyl effect might boost C(sp)-H activation by preventing the coordination of active iridium species to the C(sp)≡C(sp) bond of enynes. This finding contributes to the fundamental understanding of enyne cyclization reactions and offers valuable insight into the propargylic dialkyl effect.

Multicomponent reactions, particularly the Passerini reaction, serve as efficient tools for the synthesis of druglike molecules and the creation of compound libraries. Despite the effectiveness of the Passerini reaction, the limited alternatives to the crucial carboxylic acid component pose a structural constraint. Here, we have discovered that the phthalimide moiety and its derivatives react in the Passerini reaction as an acid component. We explored their potential in synthesizing diverse and intricate molecules. The phthalimide moiety stands out as a favorable building block due to its oxidative stability, heat-stable characteristics, and resistance to solvents. Our approach introduces a novel perspective to multicomponent reactions by incorporating NH-based acid components, addressing the ongoing need for the development of innovative molecular scaffolds.

A highly diastereoselective [3 + 2] cycloaddition of aziridines with difluorinated silyl enol ethers has been developed. This approach provides a facile methodology for highly functionalized gem -difluorinated pyrrolidines in good to excellent yields with good functional group tolerance. A one-pot, two-step approach for synthesis of structurally interesting fluorinated pyrroles has also been developed through a cycloaddition/aromatization/desulfonation sequence. Moreover, readily available substrates, mild reaction conditions, and easy scale-up synthesis show practical advantages.

The convenient and precise preparation of N , N '-diarylhydrazides, especially from readily available raw materials, remains highly challenging. Here, a photoredox catalytic phosphine-mediated deoxygenative hydroacylation of azobenzenes with abundant and readily available carboxylic acids has been developed. With Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 as the photocatalyst, the reactions proceeded smoothly in the presence of PPh 3 under visible light irradiation, delivering various N , N '-diarylhydrazides in up to 92% yields. Mechanistic studies revealed that the reaction proceeds via photoredox catalysis and phosphoranyl-radical-mediated C-O bond cleavage of carboxylic acids.

A highly diastereo- and enantioselective phosphinative cyclization of ketone-enamides with secondary diarylphosphines enabled by copper catalysis is reported, providing a range of chiral tertiary cyclohexylphosphines bearing three contiguous stereogenic centers in high yields. This asymmetric phosphination-aldol cyclization protocol can also be extended to desymmetrization of dione-enamides to create four contiguous stereogenic centers in a highly selective manner.

Herein we employed ethynylethylene carbonates (EECs) to achieve formal [4 + 1] and [3 + 3] cycloaddition with cyclic 1,3-dicarbonyl compounds. On one hand, EECs with styryl substitution could undergo a remotely controlled enantioselective [4 + 1] cycloaddition reaction. This reaction exhibits good chemoselectivity, regioselectivity, and enantioselectivity. In addition, a [3 + 3] cycloaddition reaction of EECs with cyclic 1,3-dicarbonyl compounds was also achieved, leading to a series of 4 H -pyrans with impressive chemoselectivity and enantioselectivity.

A heterobifunctional cross-linker with one sulfhydryl-reactive dinitroimidazole end and another amine-reactive N -hydroxysuccinimide (NHS) ester end was designed and synthesized. The two motifs of this cross-linker, dinitroimidazole and NHS ester, proved to react with thiol and amine, respectively, in an orthogonal way. The cross-linker was further applied to construct stapled peptides of different sizes and mono- and dual functionalization (including biotinylation, PEGylation, and fluorescence labeling) of protein.

A catalyst-free gem -difluorination/spirocyclization reaction has been successfully developed for the synthesis of gem -difluorinated C2-spiroindoline derivatives from indole-2-carboxamides. The resulting gem -difluorinated C2-spiroindolines can be easily converted into 2-spiropseudoindoxyls through hydrolysis. This method offers the benefits of simple operation, convenient access to raw materials, and mild conditions. Dual function of Selectfluor in this reaction is noteworthy as it can serve as both a fluorinating agent and an alkaline accelerator precursor.

CO 2 -assisted and Ni-catalyzed direct reductive allylation of aldehydes utilizing allylic alcohols as allylic precursor has been reported. Various homoallyl alcohols could be synthesized in excellent yield with enhanced regioselectivity and stereoselectivity for alkyl- and aryl-substituted aldehydes under mild conditions. For different substrates, proper collocation of the catalytic precursor and ligand is crucial. Preliminary mechanistic studies supported the reaction pathway through a sequential allyl hydrocarbonate formation/allylnickelation/coordination insertion process by the Ni(I)/Ni(III) catalytic cycle, which has been proven by cyclic voltammetry analysis.

Selective C-H annulation with alkynes is one of the most useful tools to synthesize heterocycles. Herein, we developed novel porous organic polymers supported ruthenium (POPs-Ru) as highly efficient catalysts for cascade aromatization of quinoxalin-2(1 H )-one and C-H annulation with alkynes. Both terminal and internal alkynes were successfully transferred to furo[2,3 -b ]quinoxaline derivatives with good functional group tolerance and high regioselectivity by using POPs-Ru catalysts. Furthermore, the catalyst exhibited high activity and could be reused at least five times without obvious deactivation of this coupling reaction. This study offers an important platform for the immobilization of molecular metal catalysts for C-H functionalization.

NHC-catalyzed diastereoselective and enantioselective [12 + 2] higher-order cycloadditions of 5H-benzo[a]-pyrrolizine-3-carbaldehydes with cyclic sulfonic imines are described. Various optically pure polycyclic piperazin-2-ones were successfully constructed under mild reaction conditions with excellent diastereoselectivities and enantioselectivities. The generated chiral polycyclic piperazin-2-ones could be transformed to planar-chiral nine-membered cyclic amides via squaramide-catalyzed asymmetric ring-expansion reactions.

A facile approach toward chromenopyrrolidines was achieved under mild conditions via organophotocatalyzed aerobic decarboxylative [2 + 2 + 1] annulation of chromones with N -arylglycines, in which N -arylglycines perform dual roles (i.e., radical precursor and methylene provider). Mechanistic studies suggested that a Giese-type radical addition and consequent Mannich pathway were likely responsible for the annulation reaction.

Herein is developed a base-promoted approach for the synthesis of C2-substituted indoles and N -fused polycyclic indoles via 5- endo - dig cyclization of 2-alkynyl anilines, followed by a 1,3'-acyl migration or a dearomatizing Michael addition process. A range of N-H free indoles and 8,9-dihydropyrido[1,2- a ]indol-6(7 H )-one scaffolds were synthesized in good to excellent yields with broad scope.

A novel copper-catalyzed cross-dehydrogenative-coupling (CDC) process of arylglycine derivatives with N-heteroarenes for the straightforward synthesis of α-aryl-α-heteroaryl α-amino acid scaffolds has been successfully developed. This protocol exhibits a broad substrate scope with good functional group compatibility by utilizing air as the sole oxidant. The use of the reaction is also displayed through the late-stage functionalization of arylglycines bearing natural compounds or drug motifs.

The cross-coupling of epoxides with acyl chlorides or anhydrides by a nickel/titanocene dual catalytic system is established. A variety of synthetically useful β-hydroxy ketones were obtained in good to high yields by using modified pyridine-oxazoline ligand. The reaction proceeds via the cooperation of titanocene-catalyzed ring-opening of epoxides and nickel-catalyzed acylation of the benzylic radical intermediate.

Here, we report the first catalytic enantioselective 1,4-addition of diarylphosphine oxides to α,β-unsaturated thioesters. Importantly, the most common and commercial oxazaborolidine (CBS) was employed as a catalyst for its new application without being activated by strong protonic acids or Lewis acids and led to the chiral thioesters in excellent yields and enantioselectivities. Furthermore, this method features mild reaction conditions (room temperature and air-insensitive), good substrate tolerance, and easy scalability.

An operationally simple and efficient method for the cyclization of tertiary amines and hypervalent iodine reagents enabled by an EDA complex has been developed. A series of [1,2-α]indoles derivatives were obtained in good yields, including some key intermediates for the synthesis of biologically active molecules. In addition, this established strategy features a broad substrate scope and good functional group tolerance.

An unprecedented route for the preparation of fused tetracyclic N-heterocycles is presented through the palladium-catalyzed cyclization of isocyanides with alkyne-tethered aryl iodides. In this transformation, a novel amino-to-alkyl 1,5-palladium migration/intramolecular C(sp 3 )-C(sp 2 ) coupling sequence was observed first. More importantly, isocyanide exhibited three roles, serving simultaneously as a C1 synthon, a C1N1 synthon, and the donor of C(sp 3 ) for C(sp 3 )-C(sp 2 ) coupling, and the reaction was the sole successful example that achieved C(sp 3 )-H activation of isocyanide.

A collective synthesis of 3,6-dideoxysugars, including seven naturally known congeners, has been reported using commercially available methyl lactates in five steps. The essential tandem process involving the olefin cross-metathesis and isomerization steps was enabled by the dual function of Grubbs-II catalyst, affording the products in good yields and providing concise and practical access to a class of biologically important deoxysugars.

The direct construction of 1,3-hydroxyfunctionalized molecules is still a significant challenge, as they can currently be obtained through multiple synthetic steps. Herein, we report a general and efficient 1,3-hydroxyfunctionalization of arylcyclopropanes by electrochemical oxidation with a strategic choice of nucleophiles and H 2 O. 1,3-Amino alcohols, 1,3-alkynyl alcohols, 1,3-hydroxyesters, and 1,3-halo alcohols are achieved with high levels of chemo- and regio-selectivity, opening a new dimension for 1,3-difunctionalization reaction.