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Boronic acids as a tunable hydroxy source display a unique reactivity paradigm through hitherto unknown aryne-induced multicomponent reactions.

Aryne chemistry is a powerful synthetic technique that forms new bonds to aromatic rings. The recent resurgence of aryne-based multicomponent coupling strategies has led to an influx of methodologies for the mild synthesis of arene derivatives. In particular, these innovative discoveries broaden and streamline approaches toward phenol ether motifs, which are a prevalent structural component across a broad range of chemistry related research fields. Herein, this review aims to provide a comprehensive overview of the recent progress in the construction of C(sp2)–O bonds via aryne-induced multicomponent reactions. Special attention has been paid to reaction design and mechanistic pathways.1 Introduction2 Insertion-Based MCRs3 Nucleophilic-Addition-Based MCRs4 Cycloaddition-Based MCRs5 Summary

A visible-light-enabled, photocatalyst-free conjugate addition reaction of dehydroamino acids is disclosed. Employing 4-acyl-1,4-dihydropyridines as both a radical reservoir and reductant, various β-acyl α-amino acids and their deuterated analogues were obtained in good results. Both late-stage peptide modification and stereoselective synthesis of chiral oxazolidinones are successfully achieved. The protocol is characterized by mild conditions and efficient derivatization, thus unlocking a novel blueprint to access unnatural amino acid derivatives, important building blocks with potential application in the peptidomimetic toolbox.

Herein we reported a Hf(OTf)4-catalyzed carbon-carbon bond formation reaction between 2-alkyl-azaarenes and para-quinone methides (p-QMs). This 1,6-conjugate addition protocol offered rapid access to a large array of triarylethane products in good yields. The catalyst loading could be reduced to 1 mol %. Studies pertinent to scale-up reaction and product derivatization were also presented.

Sulfonium salts and sulfur ylides are important S(IV) motifs, and have displayed many unique reactivities to provide simple, effective, and often stereoselective synthesis toward sulfur containing compounds. Impressive developments have been witnessed within this field during the past several years. In light of the increasing demand of organosulfur compounds across the range of chemical sciences, our aim of this review is to provide a concise overview of recent advances of sulfonium salt and sulfur ylide chemistry. Selected examples are organized in three parts on the basis of their role in organic reactions (reactants, intermediates and catalysts).

Reported herein is the first example of electrochemical selenocyanation of imidazo[1,5-a]quinolines with KSeCN under metal catalyst- and chemical oxidant-free conditions. This sustainable strategy shows a broad scope and great compatibility with functional groups, and affords synthetically and biologically important selenocyanated imidazo[1,5-a]quinolines in good to excellent yields with cheap graphite and Ni plates as the electrodes. The gram-scale synthesis was also successfully conducted, which might demonstrate the potential value of this electrochemical protocol.

Herein, we report a Pd-catalyzed mono-α-arylation reaction for pyridine benzylic functionalization. This approach serves as an efficient alternative to synthesize di-heteroaryl acetates in good yields and selectivities. Moreover, the method is applicable to heteroaryl substrate combinations, and exhibits great functional group tolerance. A streamlined protocol also enables the rapid synthesis of diheteroaryl ketones. The synthetic value was also demonstrated by scale-up experiments

The transitions between surfactant aggregate structures are triggered by changes in chemical or physical stimulations, including addition of additives. Effects of added alcohols on aggregate morphologies correlate strongly with alcohol chain length. The local molarities of alcohol, water, and counterions in the interfacial regions play an important role in controlling the aggregate morphologies. However, direct experimental estimates of changes of interfacial alcohol molarities during alcohol induced micelle-to-vesicle transitions have never been reported. Ellipsoidal-wormlike micelle-vesicle transitions in CTAB/KBr aqueous solutions in the presence of long-chain octanol were characterized by using combined rheological, dynamic light scattering (DLS), transmission electron microscopy (TEM) and turbidity measurements. However, the transitions are absent with added butanol. The chemical trapping method (CT) was employed to understand the differences between medium- and long-chain alcohols in determining aggregate morphology. The CT method was used to estimate interfacial water, alcohol, and counterion molarities with increasing stoichiometric alcohol concentrations. With 55 mM alcohol added, the interfacial octanol molarity is 0.9 M, which is three times higher than that for butanol. With added octanol, the ellipsoidal-wormlike micelle-vesicle transition is accompanied by a concurrent sharp increase of interfacial water molarities and a decrease of interfacial counterion molarity, which is not observed with added butanol. The CT data was also employed to estimate the changes of Israelachvili's packing parameter with increasing added alcohol concentration. Our result provides critical molecular level information for understanding the morphological transitions of CTAB/additives.

A platform approach for the direct synthesis of 3-substituted 2H-indazole derivatives has been developed using a Ag(I)/Na2S2O8 system. This regioselective alkylation/acylation protocol operates under mild conditions, tolerates a wide range of structural moieties and delivers versatile 2H-indazole derivatives with high efficiency. The gram-scale reaction and the application to the synthesis of bioactive molecules further demonstrate the utility of our protocol.

Aziridines are ubiquitous in bioactive molecules and often serve as key synthetic building blocks. We report herein an intramolecular KI/TBHP mediated oxidative dehydrogenative C(sp3)–H amination reaction to synthesize a diverse array of trans-2,3-disubstituted aziridines in good yields under mild conditions. The synthetic utility of this protocol was further highlighted by a one-pot, two-step synthesis of unprotected aziridines.

Herein, we report a highly efficient ZnI2 -triggered oxidative cross-coupling reaction of P(O)-H compounds and amines. This operationally simple protocol provides unprecedented generic access to phosphinic amides/phosphoramidate derivatives in good yields and short reaction time. Besides, the reaction proceeds under mild conditions, which avoids the use of hazardous reagents, and is applicable to scale-up syntheses as well as late-stage functionalization of drug molecules. The stereospecific coupling is also achieved from readily available optically enriched P(O)-H compounds.

An electrochemical oxidative dehydrogenative C(sp3)–H amination reaction to construct trans-2,3-disubstituted aziridines is reported, which avoids using external oxidants and generates only hydroge...

A metal-free approach to inden-1-ones from 2-alkynylbenzaldehydes mediated by pyrrolidine has been developed. The reaction proceeds under mild conditions in a step- and atom-economy process by cleaving the C═O bond and constructing new C-C as well as C═O bonds. Oxygen-18 and deuterium labeling experiments revealed an aza-Petasis-Ferrier rearrangement of an intermediate 1-amino-3-methylene-dihydroisobenzofuran.

Herein we report a protocol for the visible-light-mediated alkylation/acylation reaction of benzothiazoles. Alkyl/acyl substituted Hantzsch esters are easily prepared and rationally used as radical precursors. In the presence of BF3·Et2O and Na2S2O8, various benzothiazole derivatives were readily obtained in good yields. Our user-friendly protocol can proceed by simple irradiation with blue LEDs (λ = 465 nm) and without the assistance of external photocatalysts. The reaction is also characterized by mild conditions and scalability, thus offering an alternative and efficient tool for the synthesis of 2-functionalized benzothiazoles.

Herein we reported a Hf(OTf)

The efficient synthesis of 2-substituted thiazoles and benzothiazoles has been accomplished employing readily available cysteine esters and 2-aminobenzenethiols as N and S sources. The reaction proceeds under an I2/TBHP system and involves a one-pot tandem cyclization and oxidation sequence. A diverse range of aldehydes is amenable for this transition-metal-free protocol, which provides an alternative method to rapidly access thiazole-containing molecules.

Organosulfur compounds are ubiquitous in natural products and active pharmaceutical ingredients. They are also versatile scaffold that are widely applicable in material and food chemistry. The increasing demand indeed lead to a continuous progress in developing of new methodologies in organosulfur chemistry. Among them, sulfur ylides and sulfonium salts with unique reactivities have been employed to provide simple, effective, and often stereoselective methods to gain access to sulfur containing molecules. The essential goal of this review is to provide a comprehensive account of representative research progress on sulfonium salt and sulfur ylide chemistry in the past three years. Seminal reports on this topic are occasionally covered with the purpose of providing a brief research background. For the sake of convenience, this review is organized in three parts based on the role they played in organic reactions (synthetic intermediates, reagents and catalysts). In the first section, the development of new approaches for generate sulfur ylide or sulfonium salt intermediates were summarized. Electrophilic aryne species could be employed to react with sulfides or sulfoxides to form the desired sulfur intermediates, which could underwent a variety of interesting transformations. Moreover, recent progress in metal carbene-based sulfur ylide approaches have also been introduced. Both the progress in asymmetric catalysis variants and reactions in aqueous solution have been presented. The second section describes the transformations using stabilized sulfonium salts and sulfur ylides as bench-stable reactants. The extra stability of these species is accompanied by a compromise in the reactivity, which usually requires developing activation methods. With transition metal catalysts to activate sulfonium salts, they have been discovered as efficient coupling partners in carbon-carbon bond and carbon-heteroatom bond formation reactions. Stable sulfur ylides could also be utilized to install fluorine-containing groups in a large variety of transformations. The third section covers recent progress in employing sulfonium salts as catalysts in organic reactions. The acidity of the α C−H in sulfonium salt is relatively high than its nitrogen and phosphine analogues. Therefore, it could be easily removed to form the sulfur ylide, which have restricted its application as catalysts. On one hand, scientists took advantage of these properties and developed new cyclic sulfonium salts as hydrogen bonding catalysts. On the other hand, sulfonium salts could be used as stable phase transfer catalysts under base free conditions in order to avoid degradations. Finally, the review discussed the limitations of the known chemistry in this field as well as the future opportunities. Sulfur ylide and sulfonium salts have displayed many unique reactivities as summarized in this review. New reactivity will still be the central theme of research given the importance of organosulfur compounds. In addition, insights into the factors controlling the reactivity via mechanistic studies will be of great importance for further research and development. Moreover, the applications of sulfonium salts as organocatalysts are still limited to a relatively narrow range of transformations. Therefore, it remains to be an elusive task to unlock their full potential, and future research must include the development of scalable and cost-efficient methods, broadening of reaction scopes, and integration with other catalytic manifolds. We hope that this review will pique the interests of readers and deliver inspiration for future development in this interesting and promising field.

Background: Spiro skeleton is an important structural motif in natural products, usually accounting for their formidable architectures and remarkable biological profiles. Recent advances demonstrated that a diverse range of scenarios held the promise for the assembly of spirocenter based on ortho-dearomatization strategy. In this article, we describe the latest development of ortho-dearomatization reaction in constructing spirocyclic scaffolds with an all-carbon ring junction from a methodological standpoint. Objective: The review focuses on recent progress in the area of ortho-dearomatization reaction in constructing spirocyclic scaffolds with an all-carbon ring junction. Conclusion: In summary, we have summarized the capability of ortho-dearomatization reaction to construct spirocyclic skeleton, a common structural pattern found at the core of numerous natural products with broad structural diversities and important bioactivities. Success in this area will benefit not only the area of synthetic chemistry through methodological development, but also medicinal chemistry and chemical biology by providing access to rapid assembly of bioactive compounds’ core scaffolds.

The direct dearomatization reaction of isoquinolines and quinolines with chloroform has been accomplished through in situ electrophilic aryne activation and nucleophile formation. This transition metal-free protocol shows a broad scope of substrates, providing consistently high yields of medicinally-important dihydro(iso)quinoline derivatives. The utility of this method has been further demonstrated in the synthesis of deuterated analogues.

Herein, we report an aryne triggered ring-opening fluorination protocol of a great variety of saturated sulfur heterocycles. A key factor for the success is the identification of a suitable mediator. Compared to previous methods, this transition-metal free protocol employs low-cost potassium fluoride as the fluorine source. The operational simplicity and mild reaction conditions allow for the rapid synthesis of a wide range of aliphatic fluoride compounds in good yields.

A model for the stereoselectivity of intramolecular alkylations by N,N'-disubstituted cinchona alkaloids reported by Xiang et al. was established using density functional theory (DFT) calculations. The stereocontrol is based on the minimal distortion of the transition state (TS) and catalyst required to achieve favorable electrostatic interactions in the favored TS. Counterions must be included in computational modeling of ion-paired catalysis in order to reproduce experimental enantioselectivity.

An electrochemical oxidative dehydrogenative C(sp

A cyanostilbene conjugated gelator was incorporated into the cavities of cyclodextrins via the host–guest interaction and the resulting supra-gelator from γ-CyD enabled chiroptical photo-switching, while the other gels showed enhanced circularly polarized luminescences.

A metal-free oxidation system employing tert-butyl hydroperoxide (TBHP) has been developed for selective oxidation of structurally diverse benzylic sp3 C–H bonds. This low-cost methodology allows for rapid generation of synthetically and biologically valued arylketones in good to excellent yields from readily available alkylarenes and diarylmethanes.

An efficient protocol for [2,3]-sigmatropic rearrangement of allyl and propargyl thioethers is reported. The key sulfonium ylide intermediate is in situ formed via S-arylation of arynes. This transition metal-free method allows for ready access to a wide array of functionalized thioether derivatives in good to excellent yields.

An efficient and practical (hetero)benzylic sp3 C–H oxidation method has been developed. Notably, this user-friendly protocol employs inexpensive potassium tert-butoxide (KOtBu) as a promoter and proceeds under mild conditions using oxygen as the oxidant. A large variety of oxidation products were prepared in good to excellent yields. The utility of this “green” methodology was further demonstrated by the scale-up preparation of a biologically valued molecule.

The efficient synthesis of 2-substituted thiazoles and benzothiazoles has been accomplished employing readily available cysteine esters and 2-aminobenzenethiols as N and S sources. The reaction proceeds under an I2/TBHP system and involves a one-pot tandem cyclization and oxidation sequence. A diverse range of aldehydes is amenable for this transition-metal-free protocol, which provides an alternative method to rapidly access thiazole-containing molecules.

Asymmetric phase transfer catalysis has been recognized as an approach that is greener and more sustainable than synthetic alternatives and has evolved into one of the most practical methods in challenging enantioselective synthesis. An overview of the current status of asymmetric phase transfer catalysis in industry is presented by summarizing research progress from both journal publications and patent applications.

Organosulfides are a common class of structure units in bioactive molecules and functional materials motivating continuous developments of efficient synthetic methods. Herein, we report an electrophilic aryne-activated ring opening protocol of one or two heteroatom containing saturated sulfur heterocycles. This three-component transformation proceeds under mild reaction conditions and displays exceptional generality of nucleophiles (C, O, S, N, and F centered nucleophiles), giving structurally diverse thioethers in good yields.

An efficient and practical (hetero)benzylic sp

A Cu-catalyzed enantioselective Claisen rearrangement of easily-accessible enolphosphonates using commercially available (R, R)-PhBOX as the chiral ligand was developed. A wide range of rearrangement products with contiguous tertiary and all carbon quaternary centers were obtained in excellent yields and stereoselectivities. The α-ketophosphonate products could be easily transformed into other functional groups in high efficiency.

The first cobalt-catalyzed decarboxylative acetoxylation reaction was accomplished. This methodology is applicable to a wide range of amino acids and arylacetic acids.

Asymmetric phase transfer catalysis has been recognized as an approach that is greener and more sustainable than synthetic alternatives and has evolved into one of the most practical methods in challenging enantioselective synthesis. An overview of the current status of asymmetric phase transfer catalysis in industry is presented by summarizing research progress from both journal publications and patent applications.

The first cobalt-catalyzed decarboxylative acetoxylation reaction was accomplished. This methodology is applicable to a wide range of amino acids and arylacetic acids.

An efficient protocol for the palladium-catalyzed Suzuki–Miyaura cross-coupling reaction of unprotected haloimidazoles is reported. The relatively mild reaction conditions allow for ready access to a wide array of functionalized imidazole derivatives in good to excellent yields. The synthetic utility of this method is demonstrated by the total synthesis of nortopsentin D.

A facile and efficient synthesis of pyrroles from readily available amino acids is described. The key step in the method is an aza-Wacker oxidative cyclization catalyzed by palladium(II)/Cu(OTf)2. A series of pyrroles were obtained by this method under mild conditions.

A novel Pd-catalyzed Wacker-type oxidative cyclization under air is described. By using this cyclization, a series of 2-methylquinolines are readily prepared with good yields under mild conditions.