A synthetic method for the efficient preparation of a structurally diverse range of spirocyclic pyrrolidines and piperidines, which relies on the gold(I)-catalyzed spirocyclization of 1-ene-4,9- and 3-ene-1,7-diyne esters, has been developed. For substrates containing a terminal alkyne moiety, the reaction was shown to proceed via a tandem 1,2- or 1,3-acyloxy migration/Nazarov cyclization/5-exo-dig cyclization/1,5-acyl migration pathway to provide the azaspiro[4.4]nonenone ring system. In the case of substrates with an internal alkyne substituent, the reaction was found to proceed via a cascade 1,2- or 1,3-acyloxy migration/Nazarov cyclization/6-endo-dig cyclization/1,5-acyl migration pathway to give the azaspiro[4.5]decadienone derivative. The suggested spirocyclization mechanism is the first example of accessing two members of the family of compounds containing an all-carbon quaternary center from an acyclic precursor. It is also a rare instance of intramolecular trapping of a 1,3-cyclopentadienyl intermediate generated from the cycloisomerization of a 1,3-enyne ester with an appropriately placed tethered alkyne functional group. The synthetic utility of this divergent catalytic protocol was demonstrated by its applicability in the spirocyclization of all-carbon or O-tethered substrates and access to a variety of spirocyclic cyclopentane and furan derivatives. It was further exemplified by the late-stage modification of an array of structurally complex natural products and drug molecules under mild reaction conditions at room temperature.

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A metal-free synthetically useful catalytic approach for the preparation of 2-acyl benzofurans and indoles from easily accessible o-hydroxyphenyl and o-aminophenyl propargylic alcohols in the presence of pyridine N-oxide is disclosed. This protocol comprises the acid promoted formation of a carbocation and subsequent nucleophilic trapping by pyridine N-oxide, which leads to umpolung of the allenyl ether moiety. The following intramolecular attack at the umpolung allenyl carbon furnishes the final benzofurans and indoles via a nucleophile-intercepted Meyer–Schuster rearrangement.

In contrast to the electrophilic chemistry of N-sulfenyl phthalimide, its radical chemistry has been rarely developed for C–S bond formation. Herein, employing N-sulfenyl phthalimides as efficient radicalophile reagents enables the challenging Markovnikov radical hydrothiolation of unactivated alkenes under mild conditions by cobalt catalysis. The ligand around the cobalt center plays an important role in promoting the reaction. This protocol exhibits exclusive regio-selectivity, wide functional group tolerance and broad substrate scope. Mechanistic investigations suggest that the reaction proceeded via the Co–H mediated hydrogen atom transfer with alkenes and subsequent trapping of alkyl radicals by N-sulfenyl phthalimides. Scalable synthesis and late-stage modification of biologically active molecules demonstrate the practicality of this protocol.

In the frame of developing easily oxidizable compounds for the photorelease of carbon-based radicals, we describe herein the use of 2-substituted-1,3-imidazolidines. These compounds (Eoxca. 1 V vs. SCE) were used to generate (substituted) alkyl radicals under photoredox conditions. The radicals smoothly added to electron-poor CC bonds for the forging of C(sp3)–C(sp3) bonds under metal-free conditions. Acridinium salts and even 4-CzIPN could be used as photocatalysts thanks to the favorable redox properties of these heterocycles.

A nickel-catalyzed C–SS reductive cross-coupling reaction of dithiosulfonate and unactivated alkyl halides for producing unsymmetric disulfides is developed. Ligands can greatly promote the conversion or inhibition of the occurrence of reactions, hence the selection of ligands is very important. In this approach, 1–10-phen can maximize the promotion of the reaction. The approach features the unprecedented use of dithiosulfonate in reductive cross-coupling chemistry and is highlighted by the broad substrate scope under mild conditions with excellent functional group tolerance. The approach is applicable to different halogenated alkanes. It is worth noting that the reaction is also applicable to the later modification of the anti-inflammatory drug indomethacin, the anti gout drug probenecid, and Boc-L-phenylalanine.

The first asymmetric total syntheses of (+)-pancratinines B and C and the asymmetric total syntheses of (−)-montanine, (−)-pancracine and (−)-brunsvigine were realized in a divergent fashion. Our synthetic strategy features a copper-catalyzed [3 + 2] annulation reaction, Pictet–Spengler cyclization and an epoxide opening and hydroxyl elimination to form the challenging C1C11a bond.

Olefin synthesis is a fundamentally important process in organic chemistry. Among the numerous approaches to obtaining olefins such as alcohol/halide eliminations, alkyne-based reductions and additions, pericyclic reactions, metal-mediated cross-couplings, olefin metathesis, etc., carbonyl olefinations are particularly of significance, as exemplified by the Wittig-type reactions. In this report, we describe a new decarboxylative carbonyl olefination in one step with a broad substrate scope under mild conditions by merging an aldehyde and the α-halo carboxylic N-hydroxyphthalimide (NHPI) ester. Mechanistic investigations reveal that this reaction takes place via a tandem nucleophilic addition/reductive E1cb process. The operational simplicity, the ready availability of both starting materials and the versatility of the olefin product demonstrate the potential synthetic utility of this decarboxylative carbonyl olefination.

A concise preparation of halophenols directly from (hetero)aryl boronic acids/esters via tungstate-catalyzed one-pot ipso-hydroxylation bromination and iodination has been developed in the current work. A broad substrate scope, good functional group tolerance and formal synthesis of several bioactive molecules have been achieved. Utilizing environmentally and costlyfriendly reagents (NaBr, NaI, H2O2, weak organic acids) and green solvents (EtOH/H2O), this reaction can work at room temperature in the open air. It was also found to be dependent on pH, and to work smoothly with weak/moderate-strength organic acids without a tungsten catalyst. Compared to strategies developed in previous research with the same starting materials, this one-pot strategy was more step-economically friendly. Notably, the (hetero)aryl boronic acid played an interesting “one stone, two birds” role: as a starting material and promoter of the reaction by releasing B(OH)3 as a co-catalyst. B(OH)3 has normally been treated as waste in ipso-hydroxylation, but we expect the “turn waste into wealth (catalyst)” approach of the current work to inspire related research.

We herein report a chiral phosphoric acid-catalyzed Paal–Knorr reaction of N-amino(aza)quinolinones and 1,4-diketones for constructing N–N axially chiral pyrrolyl(aza)quinolinones with ‘6–5’-membered rings. The protocol proceeds smoothly under mild conditions, exhibiting excellent functional group compatibility and delivering a diverse set of pyrrolyl(aza)quinolinones in excellent yields with high atroposelectivities. Moreover, this strategy is applicable for the atroposelective synthesis of N–N axially chiral pyrrolyl-dihydroquinolinone/pyridinone and shows broad further synthetic transformations. Additionally, density functional theory studies unveiled that the key to control axially chiral N–N atropisomers is based on the second dehydroxylation process as the rate-determining step, not the first cyclization step. Therefore, this work not only offers a new family member of N–N atropisomers but also reveals the origin of the atroposelectivity.

We have synthesized two geometric isomers of a cyclohexane-5-spirohydantoin derivative (1,3-diazaspiro[4.5]decane-2,4-dione) incorporating a hydrophobic phenyl 3,4,5-tris(dodecyloxy)benzoate unit at position 8. Separation of these diastereomers was accomplished through silica gel flash chromatography. The interplay of intermolecular hydrogen bonding and micro-segregation between the polar hydantoin unit and nonpolar aliphatic chains within the molecule endows them with remarkable self-assembly capabilities, both in solution and in the solid state. These hydantoin derivatives spontaneously form rosette-shaped structures composed of six molecules. In the solid state, these compounds display hexagonal columnar liquid crystal phases, with hydrogen-bonded disks as their fundamental building blocks. Similarly, when exposed to apolar solvents such as cyclohexane or dodecane, they adopt a columnar arrangement, resulting in gel formation comprising nanoscale fibers that intricately interlace to form a network. Remarkably, the two isomers exhibit markedly different properties. The major isomer behaves as a glassy liquid crystalline material, while the minor one exhibits liquid crystalline behavior with a high propensity to crystallize. Our experimental findings, in combination with theoretical studies, underscore the fundamentally distinct supramolecular organizations present in these isomers, shedding light on their unique self-assembling properties.

We report herein a chiral Cu(II)-Lewis acid (LA)/Brønsted base-catalyzed process for the enantio- and diastereoselective conjugate addition of various 2-pyridyl alkyl ketones to β-substituted enones under mild conditions. Acid and base catalysts cooperatively deprotonate an α-proton of pyridyl ketones containing diverse alkyl chains, facilitating the generation of α-pyridyl enolates bound to Cu(II)-LA involving carboxylate ligands. The carboxylate ligands which contain extended alkyl chains such as cyclohexanebutyrates, along with a chiral bisphosphine ligand, play a significant role in stereocontrol, supported by experimental and DFT studies. Cu(II) (Z)-enolate complexes, of which one face is effectively blocked by a carboxylate, react with enones to create the stereogenic carbon–carbon bond in the rate-determining step.

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Herein, we report the first total synthesis of 17(15 → 16)-abeo-abietane diterpenoids (±)-villosin C (5) and (±)-teuvincenone B (4) in 11 steps. The A/B/C ring system was assembled via a modified three-step sequence on gram-scale, while the D ring was constructed by intramolecular iodoetherification. This synthesis relied largely on the rational design of the order for oxidation state escalation (C6/11/14 → C7 → C12 → C17), which was realized through sequential benzylic iodination/Kornblum oxidation, Siegel–Tomkinson C–H oxidation and iodoetherification. In addition, villosin C (5) and its epimer (5a) were found to have indistinguishable NMR data and the correct configuration for villosin C was elucidated by comparing HPLC trace with a natural sample.

This cutting-edge research work presents a comprehensive and in-depth theoretical investigation into the mechanism of Au(I)-catalyzed annulations between ynamides and 1,2-benzisoxazoles, as well as the chemoselectivity of the reactions in the presence of different ligands (L = JohnPhos, IPr) and the factors influencing the Z/E-configuration of the resulting 6-membered cyclic products. State-of-the-art density functional theory calculations reveal that (i) the reaction mechanism involves three distinct processes: process 1 corresponds to the transformation of a gold-π-alkyne precursor into a gold–carbene intermediate; process 2 involves the conversion of gold–carbene intermediates into 6-membered/7-membered cyclic intermediates; process 3 involves the conversion of 6-membered/7-membered cyclic intermediates to furnish 6-membered/7-membered cyclic products, respectively. (ii) The distinct chemoselectivity exhibited by the two ligands, JohnPhos and IPr, has been thoroughly explored through distortion/interaction analysis. The distortion energy is responsible for ligand-controlled chemoselectivity. (iii) The Z/E-configuration of 6-membered cyclic products is determined by the N-attack step of 1,2-benzisoxazole on the gold-π-alkyne. These theoretical findings hold significant implications for synthetic chemists, providing valuable insights into the design of novel catalytic systems and the prediction of reaction pathways and selectivity patterns in related organic transformations involving ynamides and isoxazoles.

A synthetic method to prepare (E)-3-arylazoindoles efficiently that relies on the gold(I)-catalysed azo coupling of 1,2- and 1,4-diazoquinones with 1H-indoles under mild reaction conditions that did not require the exclusion of air or moisture is described. The suggested azo coupling mechanistic pathway delineates the first instance of a α-diazocarbonyl compound acting as a N-centred electrophile instead of undergoing decomposition of the dinitrogen functional group. Experimental studies based on a (1H-indol-3-yl)gold species that is proposed to be preferentially generated from the direct reaction of the group 11 metal complex and N-heterocycle over α-diazocarbonyl compound decomposition provides insight into this observed product regio- and chemoselectivity. The utility of the synthetic method was exemplified by the efficient preparation of one example at the 2 mmol scale at a catalyst loading of 1 mol %, assembly of two known (E)-diazene-based molecular photoswitches and late-stage functionalisation of two biologically relevant molecules.

An efficient and convenient metal-free aerobic deborohydroxylation of boronic acids into phenols and alcohols in air is reported. The approach utilizes inexpensive and readily available N-aminophthalimide as a mediator to activate molecular oxygen, which enables the process to occur under relatively mild conditions. Due to the excellent chemoselectivity, the transformation tolerates various functional groups, especially oxidatively sensitive functionalities. Possible mechanisms are discussed based on primary experimental and theoretical mechanistic investigations.

Molecules with spiro-linked π-conjugated structures have attracted considerable attention in the realm of organic functional materials due to their advantageous structural features. In this review, we comprehensively summarize the synthetic methodologies utilized to create spiro molecules encompassing cyclopentane, cyclohexane, and cycloheptane frameworks. Furthermore, we investigate the diverse applications of these spiro molecules in the field of photovoltaics. Additionally, we elaborate on the synthesis of spiro molecules incorporating an embedded carbonyl group and probe their multifaceted applications across various domains.

[CN] species were generated in the course of electrochemical oxidation of SCN anions and used in the three-component electrosynthesis of 1-cyano-imidazo[1,5-a]pyridines from pyridine-2-carboxaldehydes, amines, and NH4SCN. In contrast to previously known electrochemical methods, NH4SCN acts as a CN source rather than a SCN source. A variety of 1-cyano-imidazo[1,5-a]pyridines were obtained in good yields under constant current conditions in an undivided electrochemical cell. The electrosynthesis presumably involves the generation of a cyanating reagent, its addition to the CN bond of the imine, formed from pyridine-2-carboxaldehyde and amine, followed by a cascade of DMSO-mediated or Shono-type anodic oxidation and cyclization. The leading 1-cyano-imidazo[1,5-a]pyridines exhibit better antifungal activity against Venturia inaequalis, Rhizoctonia solani, and Bipolaris sorokiniana than the commercial fungicide triadimefon.