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Molecular weight distribution of polymers, termed dispersity (Đ), is a fundamental parameter for determining polymer material properties. This paper reports a novel approach for controlling Đ by exploiting a temperature‐selective radical generation in organocatalyzed living radical polymerization. The polymers with tailored Đ were synthesized in a batch system without the assistance of an external pump. A unique aspect of this approach is that Đ was tuneable from 1.11 to 1.50 in any segment in diblock, triblock, and multiblock copolymers and in any form of star and brush polymer without segmental or topological restriction. This approach is amenable to various monomers and free from metals and thus attractive for applications. The approach also generated polymer brushes on surfaces with tailored Đ. An interesting finding was that the polymer brushes exhibited unique interaction with external molecules, depending on the Đ value. Brush up: A novel approach for modulating polymer dispersity was developed. It is based on temperature‐selective organocatalyzed living radical polymerization and enabled dispersity modulation in any segment in linear and branched block copolymers as well as polymer brushes. A dispersity‐dependent size‐exclusion effect to external molecules was observed for the polymer brushes. [ABSTRACT FROM AUTHOR]

The formation of carbon-carbon bonds through the functionalization of aromatic carbon-nitrogen bonds is a highly attractive synthetic strategy in the synthesis of aromatic molecules. In this paper, we report a novel aromatic carbon-nitrogen bond functionalization reaction by using a simple dearomatization strategy. Through this process para-substituted anilines serve as a potential aryl source in the construction of a range of functionalized aromatic molecules, such as quaternary carbon centers, α-keto esters, and aldehydes. [ABSTRACT FROM AUTHOR]

Indolines are important moieties present in various biologically significant molecules and have attracted considerable attention in synthetic chemistry. This paper describes a Heck reaction/CH activation/amination sequence for forming indolines using di-tert-butyldiaziridinone. The reaction process likely proceeds via a pallada(II)cycle, which is converted into an indoline by oxidative addition to the diaziridinone and two subsequent CN bond formations. [ABSTRACT FROM AUTHOR]

The development of biomimetic chemistry based on the NAD(P)H with hydrogen gas as terminal reductant is a long‐standing challenge. Through rational design of the chiral and regenerable NAD(P)H analogues based on planar‐chiral ferrocene, a biomimetic asymmetric reduction has been realized using bench‐stable Lewis acids as transfer catalysts. A broad set of alkenes and imines could be reduced with up to 98 % yield and 98 % ee, likely enabled by enzyme‐like cooperative bifunctional activation. This reaction represents the first general biomimetic asymmetric reduction (BMAR) process enabled by chiral and regenerable NAD(P)H analogues. This concept demonstrates catalytic utility of a chiral coenzyme NAD(P)H in asymmetric catalysis. Through rational design of chiral and regenerable NAD(P)H analogues based on planar‐chiral ferrocene, a biomimetic asymmetric reduction has been realized using bench‐stable Lewis acids as transfer catalysts. A broad set of tetrasubstituted alkenes and imines could be reduced with up to 98 % yield and 98 % ee. This protocol represents the first general biomimetic asymmetric reduction process enabled by NAD(P)H analogues. [ABSTRACT FROM AUTHOR]

Organic nitrates are broadly applied as pharmaceuticals (acting as efficient nitric oxide donor), energetic materials, building blocks in organic synthesis, etc. However, practical and direct methods to access organic nitrates efficiently are still rare, mainly due to the lack of powerful nitrooxylating reagents. Herein, we report bench‐stable and highly reactive noncyclic hypervalent iodine nitrooxylating reagents, oxybis(aryl‐λ3‐iodanediyl) dinitrates (OAIDNs, 2), which are prepared just by using aryliodine diacetate and HNO3. The reagents are used to achieve a mild and operationally simple protocol to access diverse organic nitrates. By employing of 2, zinc‐catalyzed regioselective nitrooxylation of cyclopropyl silyl ethers is realized efficiently to access the corresponding β‐nitrooxy ketones with high functional‐group tolerance. Moreover, a series of direct and catalyst‐free nitrooxylations of enolizable C−H bonds are carried out smoothly to afford the desired organic nitrates within minutes by just mixing the substrates with 2 in dichloromethane. [ABSTRACT FROM AUTHOR]

Oxycyanation of alkenes would allow the direct construction of useful β‐hydroxy nitrile scaffolds. However, only limited examples of such reactions have been reported, and some problems including limited substrate scope and the lack of diastereocontrol in the case of the oxycyanation of internal alkenes have arisen. We herein report on the intermolecular oxycyanation of alkenes using p‐toluenesulfonyl cyanide (TsCN) in the presence of tris(pentafluorophenyl)borane (B(C6F5)3) as a catalyst, affording products that contain a sulfinyloxy group and a cyano group at the vicinal position. The reaction features a stereospecific syn‐addition. The reaction also shows a broad substrate scope with good functional group tolerance. Mechanistic investigations by experimental studies and density functional theory (DFT) calculations revealed that the reaction proceeds via an unprecedented stereospecific mechanism through the electrophilic cyanation of alkenes, in which B(C6F5)3 efficiently activates TsCN through the coordination of the cyano group to the boron center. [ABSTRACT FROM AUTHOR]

Abstract: Reported is the first organocatalytic asymmetric 1,3‐alkyl shift in alkyl aryl ethers for the synthesis of chiral 3,3′‐diaryloxindoles using a chiral Brønsted acid catalyst. Preliminary results showed that each enantiomer of the 3,3′‐diaryloxindole, and a racemic mixture, showed different antiproliferative activities against HeLa cell lines by using an MTT assay. [ABSTRACT FROM AUTHOR]

The synthesis of four membered heterocycles usually requires multi‐step procedures and prefunctionalized reactants. A straightforward alternative is the photochemical [2+2]‐heterocycloaddition between an alkene and a carbonyl derivative, conventionally based on the photoexcitation of this latter. However, this approach is limited by the absorption profile of the carbonyl, requiring in most of the cases the use of high‐energy UV‐light, that often results in undesired side reactions and/or the degradation of the reaction components. The development of new and milder visible light‐driven [2+2]‐heterocycloadditions is, therefore, highly desirable. In this Review, we highlight the most relevant achievements in the development of [2+2]‐heterocycloadditions promoted by visible light, with a particular emphasis on the involved reaction mechanisms. The open challenges will also be discussed, suggesting new possible evolutions, and stimulating new methodological developments in the field. [ABSTRACT FROM AUTHOR]

Atropisomers bearing multiple stereogenic axes are of increasing importance to the field of material science, pharmaceuticals, and catalysis. However, the atroposelective construction of multi‐axis atropisomers remains rare and challenging, due to the intrinsical difficulties in the stereo‐control of the multiple stereogenic axes. Herein, we demonstrate a single‐step construction of a new class of 1,2‐diaxially chiral triaryl α‐pyranones by an N‐heterocyclic carbene organocatalytic asymmetric [3+3] annulation of well‐designed alkynyl acylazolium precursors and enolizable sterically hindered 2‐aryl ketones. The protocol features broad substrate scope (>50 examples), excellent stereo‐control (most cases >20 : 1 dr, up to 99.5 : 0.5 er), and potentially useful synthetic applications. The success of this reaction relies on the rational design of structurally matched reaction partners and the careful selection of the asymmetric catalytic system. DFT calculations have also been performed to discover and rationalize the origin of the high stereoselectivity of this reaction. [ABSTRACT FROM AUTHOR]

Chiral oxindoles are important chemical scaffolds found in many natural products, and their enantioselective synthesis thus attracts considerable attention. Highly diastereo‐ and enantioselective synthetic methods for constructing C3 quaternary oxindoles have been well‐developed. However, the efficient synthesis of chiral 3‐substituted tertiary oxindoles has been rarely reported due to the ease of racemization of the tertiary stereocenter via enolization. Therefore, we herein report on the multicomponent assembly (from N‐aryl diazoamides, aldehydes, and enamines/indoles) of complex oxindoles by enantioselective cooperative catalysis. These reactions proceed under mild conditions and show broad substrate scope, affording the desired coupling products (>90 examples) with good to excellent stereocontrol. Additionally, this research also demonstrates the synthetic potential of this annulation by constructing the 6,6,5‐tricyclic lactone core structure of Speradine A. [ABSTRACT FROM AUTHOR]

We report that O‐selective arylation of 2‐ and 4‐pyridones with arylboronic acids is affected by a modular, bismacycle‐based system. The utility of this umpolung approach to pyridyl ethers, which is complementary to conventional methods based on SNAr or cross‐coupling, is demonstrated through the concise synthesis of Ki6783 and picolinafen, and the formal synthesis of cabozantib and golvatinib. Computational investigations reveal that arylation proceeds in a concerted fashion via a 5‐membered transition state. The kinetically‐controlled regioselectivity for O‐arylation—which is reversed relative to previous BiV‐mediated pyridone arylations—is attributed primarily to the geometric constraints imposed by the bismacyclic scaffold. [ABSTRACT FROM AUTHOR]

A new iridium-catalyzed reductive Strecker reaction for the direct and efficient formation of α-amino nitrile products from a broad range of (hetero)aromatic and aliphatic tertiary amides, and N-alkyl lactams is reported. The protocol exploits the mild and highly chemoselective reduction of the amide and lactam functionalities using IrCl(CO)[P(C6H5)3]2 (Vaska's complex) in the presence of tetramethyldisiloxane, as a reductant, to directly generate hemiaminal species able to undergo substitution by cyanide upon treatment with TMSCN (TMS=trimethylsilyl). The protocol is simple to perform, broad in scope, efficient (up to 99 % yield), and has been successfully applied to the late-stage functionalization of amide- and lactam-containing drugs, and naturally occurring alkaloids, as well as for the selective cyanation of the carbonyl carbon atom linked to the N atom of proline residues within di- and tripeptides. [ABSTRACT FROM AUTHOR]

Fluorinated fused rings are challenging to construct from simple starting materials. Herein, we report the first photocatalyzed cascade reactions of readily available cyclopropanols and α‐trifluoromethyl‐substituted olefins for the synthesis of fused gem‐difluorooxetanes. Two rings and three bonds were efficiently constructed in one reaction. The reaction showed broad substrate scope and the downstream transformations of the products demonstrated the synthetic potential of the reaction. The mechanistic study supported the presence of cascade photoredox catalysis and energy transfer catalysis/direct photo‐excitation processes. [ABSTRACT FROM AUTHOR]

Diaryl difluoromethanes are valuable targets for medicinal chemistry because they are bioisosteres of diaryl ethers and can function as replacements for diaryl methane, ketone, and sulfone groups. However, methods to prepare diaryl difluoromethanes are scarce, especially methods starting from abundant aryl halides. We report the Pd‐catalyzed aryldifluoromethylation of aryl halides with aryldifluoromethyl trimethylsilanes (TMSCF2Ar). The reaction occurs when the catalyst contains a simple, but unusual, dialkylaryl phosphine ligand that promotes transmetallation of the silane. Computational studies show that reductive elimination following transmetallation occurs with a low barrier, despite the fluorine atoms on the α‐carbon, due to coordination of the difluorobenzyl π‐system to palladium. The co‐development of a cobalt‐catalyzed synthesis of the silanes broadened the scope of the process including several applications to the synthesis biologically relevant diaryl difluoromethanes. [ABSTRACT FROM AUTHOR]

Cyclopropane‐fused N‐heterocycles are featured in various biologically active compounds and represent attractive scaffolds in medicinal chemistry. However, synthesis routes to access structurally and functionally diverse cyclopropane‐fused N‐heterocycles remain underexplored. Leveraging novel α‐diazo acylating agents, we report a general approach for the direct and modular synthesis of cyclopropane‐fused lactams from unsaturated amines. The operationally simple transformation, which proceeds through successive acylation, (3+2) cycloaddition and fragmentation, tolerates a broad range of functional groups and yields a wide spectrum of complex molecular scaffolds, including fused, bridged and spiro ring systems. We demonstrate the utility of this transformation in the concise syntheses of therapeutic agents milnaciprane and amitifadine. [ABSTRACT FROM AUTHOR]

Most of the bowl‐shaped molecules are synthesized via a core‐periphery strategy with the bowl rim closed at the final stage. However, the construction of heteroatom‐doped buckybowls by the periphery‐core method with the bowl bottom sealed by inserting new atoms in the last step is quite limited. Herein we report the synthesis of a bowl‐shaped compound containing four sulfur atoms and two embedded N−B bonds with the ratio of carbon atom and heteroatom as low as four through a periphery‐core strategy. Crystallographic analysis confirms the formation of a bowl‐shaped structure. The multiple heteroatoms alter the molecular electronic structure, thus resulting in the distinct aromaticity when compared with its all‐carbon congener. The electron‐rich buckybowl shows a strong interaction with the electron‐deficient fullerene C60 by forming a 1 : 1 complex in toluene. [ABSTRACT FROM AUTHOR]

Cyclization of silylenolether-ynesulfonamides proceeds at ambient temperature under mild reaction conditions under silver catalysis. Bridged compounds were obtained exclusively through 7 -exo-dig reactions. The protocol is applicable to a wide range of substrates, thus leading to azabicyclic frameworks. [ABSTRACT FROM AUTHOR]

An endo‐directing group strategy enables enantioselective (3+1+2) cycloadditions that are triggered by carbonylative C−C bond activation of cyclopropanes. These processes are rare examples of cycloadditions where C−C bond oxidative addition is enantiodetermining, and the first where this is achieved within the context of a multicomponent (higher order) reaction design. [ABSTRACT FROM AUTHOR]

The nucleophilic aromatic BH substitution reaction of carboranes is uncommon, compared to the electrophilic one. This work reported a pyridine‐enabled transition‐metal‐free regioselective nucleophilic aromatic cage B(4)‐H amination of 1,2‐diaryl‐o‐carboranes with magnesium bisamides, giving a series of B(4)‐aminated o‐carboranes. DFT calculations showcased a stepwise B−N formation/B−H cleavage process, in which Mg−H formation/cage closure is the rate‐determining step. Unprecedentedly, in the presence of 4,4′‐di‐tert‐butyl‐2,2′‐dipyridyl (dtbpy), a tandem B(4)‐amination/cage isomerization reaction of o‐carboranes was discovered for the facile preparation of B(2)‐aminated m‐carboranes. Control experiments indicated that magnesium complex, bidentate ligand (dtbpy) and reaction temperature were crucial in the cage isomerization process. This direct nucleophilic aromatic cage B−H amination reaction offers an alternative strategy for selective amination of o‐ and m‐carboranes. [ABSTRACT FROM AUTHOR]

Although the synthesis of common cyclopropenes has been well studied, the access to cyclopropenols is rather limited. Herein, we report the first synthesis of α‐trifluoromethylated cyclopropenols via 2+1 cycloaddition reactions between alkynes and trifluoroacylsilanes, enabled by visible‐light‐induced organocatalysis. The novel ambiphilic donor–acceptor carbenes derived from trifluoroacetylsilanes reacted efficiently with both activated and non‐activated alkynes. The reaction features simple operation, mild conditions, broad substrate scope and good functional group tolerance. The synthetic potential of the reaction is highlighted by the gram‐scale reactions and first synthesis of α‐trifluoromethylated cyclopropanols through the combination of the 2+1 cyclization and high diastereoselective hydrogenation reaction in one pot. [ABSTRACT FROM AUTHOR]

Low‐valent Ti‐mediated homolytic C−O bond cleavage offers unified access to carbon radicals from ubiquitous non‐activated tertiary, secondary, and even primary alcohols. In contrast to the representative Ti reagents, which were ineffective for this purpose, "TiCl2(cat)"/Zn (cat=catecholate) was found to be specifically active. This method was applied to the addition reactions of radicals to alkenes and exhibited high generality and yields. More than 50 combinations were examined. The excellent cost‐efficiency and accessibility of "TiCl2(cat)"/Zn further enhance its applicability. Control experiments proved the presence of a carbon radical intermediate and excluded the pathway via alkyl chlorides. Further mechanistic study indicated that the 1 : 2 complex of alkoxide (R−O−) and TiIII is an active species in the C−O cleavage. [ABSTRACT FROM AUTHOR]

Efficient synthetic approaches for the incorporation of nitrogen into polyaromatic compounds (PACs) in different patterns as stabilising moiety for π‐extended systems and modification tool for optoelectronic properties remain a challenge until today. Herein, we developed a new versatile pathway to napthyridine‐based PACs as non‐symmetric and regioisomeric pendant to pyrazine‐based PACs. A combination of a gold‐catalysed synthesis of 2‐aminoquinolines and the development of an in situ desulfonation and condensation of these precursors are the key steps of the protocol. The shape and type of attached functional groups of the PACs can be designed in a late stage of the overall synthetic procedure by the chosen anthranile and backbone of the ynamide introduced in the gold‐catalysed step. Single‐crystal X‐ray diffraction and the investigation of electronic properties of the compounds show the influence of the attached substituents. All naphthyridine‐based PACs show halochromic behaviour implying their use as highly sensitive proton sensor in non‐protic solvents. [ABSTRACT FROM AUTHOR]

A palladium‐catalyzed strategy is presented to synthesize unsymmetrically linked heterocycles within stereoselective tetrasubstituted olefins. This reaction is proposed to occur via a vinyl‐PdII intermediate capable of initiating the cyclization of various alkyne‐tethered nucleophiles. Products are formed in up to 96 % yield and excellent stereoselectivities are obtained using low catalyst loadings. This transformation was scalable up to 1 mmol and mechanistic studies suggest a syn‐carbopalladation of the carbamoyl chloride followed by PdII‐catalyzed cyclization of alkyne‐tethered nucleophiles. [ABSTRACT FROM AUTHOR]

N‐Trifluoromethyl azoles are valuable targets in medicinal chemistry, but their synthesis is challenging. Classical preparation of N‐CF3 azoles relies on the functional group interconversions but suffers from tedious N‐pre‐functionalization and unfriendly agents. Introduction of the CF3 onto the nitrogen of heterocycles provides a direct route to such motifs, but the N‐trifluoromethylation remains underdeveloped. Reported here is an alternative and scalable cyclization strategy based on NCF3‐containing synthons for constructing N‐CF3 azoles. The approach involves the N‐trifluoromethylation of nitriles followed by a [3+2] cyclization between resulting N‐CF3 nitrilium derivatives and 1,3‐dipoles. PhICF3Cl was an effective CF3 source for the transformation. As a result, a generic platform is established to divergently synthesize N‐trifluoromethylated tetrazoles, imidazoles, and 1,2,3‐triazoles by using sodium azide, activated methylene isocyanides, and diazo compounds as dipoles. [ABSTRACT FROM AUTHOR]

Canonical nucleosides are vulnerable to enzymatic and chemical degradation, yet their stable mimics—C‐aryl nucleosides—have demonstrated potential utility in medicinal chemistry, chemical biology, and synthetic biology, although current synthetic methods remain limited in terms of scope and selectivity. Herein, we report a cross‐electrophile coupling to prepare C‐aryl nucleoside analogues from readily available furanosyl acetates and aryl iodides. This nickel‐catalyzed modular approach is characterized by mild reaction conditions, broad substrate scope, excellent β‐selectivity, and high functional‐group compatibility. The exclusive chemoselectivity with respect to the aryl iodide enables efficient preparation of a variety of C‐aryl halide furanosides suitable for various downstream transformations. The practicality of this transformation is demonstrated through the synthesis of a potent analogue of a naturally occurring NF‐κB activator. [ABSTRACT FROM AUTHOR]

Organophosphonium salts containing C(sp3)−+P bonds are among the most utilized reagents in organic synthesis for constructing C−C double bonds. However, their use as C‐selective electrophilic groups is rare. Here, we explore an efficient and general transition‐metal‐free method for sequential chemo‐ and regioselective C−H and C(sp3)−+P bond functionalizations. In the present study, C−H alkylation resulting in the synthesis of benzhydryl triarylphosphonium salts was achieved by one‐pot, four‐component cross‐coupling reactions of simple and commercially available starting materials. The utility of the resulting phosphonium salt building blocks was demonstrated by the chemoselective post‐functionalization of benzylic C(sp3)−+PPh3 groups to achieve aminations, thiolations, and arylations. In this way, benzhydrylamines, benzhydrylthioethers, and triarylmethanes, structural motifs that are present in many pharmaceuticals and agrochemicals, are readily accessed. These include the synthesis of two anticancer agents from simple materials in only two to three steps. Additionally, a protocol for late‐stage functionalization of bioactive drugs has been developed using benzhydrylphosphonium salts. This new approach should provide novel transformations for application in both academic and pharmaceutical research. [ABSTRACT FROM AUTHOR]

Catalyst‐free 1,2‐carboboration of ynamides is presented. Readily available aryldichloroboranes react with alkyl‐ or aryl‐substituted ynamides in high yields with complete regio‐ and stereoselectivity to valuable β‐boryl‐β‐alkyl/aryl α‐aryl substituted enamides which belong to the class of trisubstituted alkenylboronates. The 1,2‐carboboration reaction is experimentally easy to conduct, shows high functional group tolerance and broad substrate scope. Gram‐scale reactions and diverse synthetic transformations convincingly demonstrate the synthetic potential of this method. The reaction can also be used to access 1‐boraphenalenes, a class of boron‐doped polycyclic aromatic hydrocarbons. [ABSTRACT FROM AUTHOR]

Polymerizations of perfluorinated vinyl ethers (PFVEs) provide an important category of fluoropolymers that have received considerable interests in applications. In this work, we report the development of an organocatalyzed controlled radical alternating terpolymerization of PFVEs and vinyl ethers (VEs) under visible‐light irradiation. This method not only enables the synthesis of a broad scope of fluorinated terpolymers of low dispersities and high chain‐end fidelity, facilitating tuning the chemical compositions by rationally choosing the type and/or ratio of comonomers, but also allows temporal control of chain‐growth, as well as the preparation of a variety of novel fluorinated block copolymers. To showcase the versatility of this method, fluorinated alternating terpolymers have been synthesized and customized to simultaneously display a variety of desirable properties for solid polymer electrolyte design, creating new opportunities in high‐performance energy storage devices. [ABSTRACT FROM AUTHOR]

The asymmetric construction of vicinal quaternary carbon stereocenters with at least one moiety in acyclic systems is a formidable challenge. We disclose a solution involving diastereo‐ and enantioselective oxidative 1,6‐conjugate addition. The practical asymmetric cross‐dehydrogenative coupling of 2,2‐diarylacetonitriles and diverse α‐substituted cyclic 1,3‐dicarbonyls proceeds, for vicinal quaternary carbon stereocenters with one center in acyclic systems, in excellent yields and stereoselectivities. The generality of the approach is further demonstrated by the stereoselective creation of vicinal quaternary carbon stereocenters with both centers in acyclic systems using acyclic β‐ketoesters as coupling partners. Computational studies elucidate the origins of both diastereo‐ and enantioselectivity. [ABSTRACT FROM AUTHOR]

Herein, we report the preparation of silver(I) pentafluorooxosulfate from commercially available AgF and OSF4. The compound is surprisingly stable in a MeCN solution. Apart from that, AgOSF5 has been stabilised by the addition of 2,2′‐bipyridine ligands. Starting from solutions of the unstabilised silver(I) salt, OSF5 complexes with NiII, CuI, and CuII‐centres have been obtained. In addition, AgOSF5 has proven to be generally capable of mediating the transfer of OSF5 groups to aryne moieties, thus furnishing a new and safe method for the preparation of OSF5‐substituted arenes. X‐ray crystal structure analysis of selected transition‐metal OSF5 compounds have revealed distorted octahedral [OSF5]− anions which are extensively stabilised by hydrogen bonding. [ABSTRACT FROM AUTHOR]

As a consequence of their intrinsic advantageous properties, luminogens that show aggregation‐induced emission (AIEgens) have received increasing global interest for a wide range of applications. Whereas general synthetic methods towards AIEgens largely rely on tedious procedures and limited reaction types, various innovative synthetic methods have now emerged as complementary, and even alternative, strategies. In this Review, we systematically highlight advancements made in metal‐catalyzed functionalization and metal‐free‐promoted pathways for the construction of AIEgens over the past five years, and briefly illustrate new perspectives in this area. The development of innovative synthetic procedures will enable the facile synthesis of AIEgens with great structural diversity for multifunctional applications. [ABSTRACT FROM AUTHOR]

trans‐Cyclooctenes (TCOs) are essential partners in the fastest known bioorthogonal reactions, but current synthetic methods are limited by poor diastereoselectivity. Especially hard to access are hydrophilic TCOs with favorable physicochemical properties for live cell or in vivo experiments. Described is a new class of TCOs, "a‐TCOs", prepared in high yield by stereocontrolled 1,2‐additions of nucleophiles to trans‐cyclooct‐4‐enone, which itself was prepared on a large scale in two steps from 1,5‐cyclooctadiene. Computational transition‐state models rationalize the diastereoselectivity of 1,2‐additions to deliver a‐TCO products, which were also shown to be more reactive than standard TCOs and less hydrophobic than even a trans‐oxocene analogue. Illustrating the favorable physicochemical properties of a‐TCOs, a fluorescent TAMRA derivative in live HeLa cells was shown to be cell‐permeable through intracellular Diels–Alder chemistry and to wash out more rapidly than other TCOs. [ABSTRACT FROM AUTHOR]

Methyl groups are ubiquitous in biologically active molecules. Thus, new tactics to introduce this alkyl fragment into polyfunctional structures are of significant interest. With this goal in mind, a direct method for the Markovnikov hydromethylation of alkenes is reported. This method exploits the degenerate metathesis reaction between the titanium methylidene unveiled from Cp2Ti(μ‐Cl)(μ‐CH2)AlMe2 (Tebbe's reagent) and unactivated alkenes. Protonolysis of the resulting titanacyclobutanes in situ effects hydromethylation in a chemo‐, regio‐, and site‐selective manner. The broad utility of this method is demonstrated across a series of mono‐ and di‐substituted alkenes containing pendant alcohols, ethers, amides, carbamates, and basic amines. [ABSTRACT FROM AUTHOR]

Dearomatization is an effective method to transform readily available N‐heterocycles into partially saturated motifs. Manipulation of dihydro‐derivatives holds great potential and provides access to a variety of semi‐saturated N‐heterocyclic building blocks. However, current strategies are limited in scope and the use of sensitive reagents restricts the applicability in synthetic laboratories. Herein, we report the synthesis of a broad variety of N‐substituted 1,4‐ and 1,2‐dihydropyridines by very mild and selective reduction with amine borane for the first time. [ABSTRACT FROM AUTHOR]

Azine‐containing biaryls are ubiquitous scaffolds in many areas of chemistry, and efficient methods for their synthesis are continually desired. Pyridine rings are prominent amongst these motifs. Transition‐metal‐catalysed cross‐coupling reactions have been widely used for their synthesis and functionalisation as they often provide a swift and tuneable route to related biaryl scaffolds. However, 2‐pyridine organometallics are capricious coupling partners and 2‐pyridyl boron reagents in particular are notorious for their instability and poor reactivity in Suzuki–Miyaura cross‐coupling reactions. The synthesis of pyridine‐containing biaryls is therefore limited, and methods for the formation of unsymmetrical 2,2′‐bis‐pyridines are scarce. This Review focuses on the methods developed for the challenging coupling of 2‐pyridine nucleophiles with (hetero)aryl electrophiles, and ranges from traditional cross‐coupling processes to alternative nucleophilic reagents and novel main group approaches. [ABSTRACT FROM AUTHOR]

Examples from different research areas of Siegfried Hünig are displayed to remind us that organic chemistry owes much more than Hünig's base to this exceptionally versatile and creative chemist. The main research lines dealing with the synthesis and physical characterization of new dyes, multistage redox systems, and organic metals will be presented as well as his contributions to enamine chemistry, the discovery of diimine as a hydrogenation agent, and nucleophilic acylation with trimethylsilyl cyanide, which are less well‐known nowadays. In addition, exotic compounds with parallel C=C and N=N bonds were systematically studied in Hünig's group. Reflecting on the development of his research demonstrates both the importance of a systematic approach and how fruitful entirely unexpected results are if they meet a "well‐prepared mind". During Hünig's academic career, teaching played an indisputable role. His efforts in modernizing the chemistry institute at Würzburg and his support of young researchers in the academic system in Germany are also highlighted. [ABSTRACT FROM AUTHOR]

An open‐cage fullerene incorporating phosphorous ylid and carbonyl group moieties on the rim of the orifice can be filled with gases (H2, He, Ne) in the solid state, and the cage opening then contracted in situ by raising the temperature to complete an intramolecular Wittig reaction, trapping the atom or molecule inside. Known transformations complete conversion of the product fullerene to C60 containing the endohedral species. As well as providing an improved synthesis of large quantities of 4He@C60, H2@C60, and D2@C60, the method allows the efficient incorporation of expensive gases such as HD and 3He, to prepare HD@C60 and 3He@C60. The method also enables the first synthesis of Ne@C60 by molecular surgery, and its characterization by crystallography and 13C NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Rearrangement reactions incorporated into cascade reactions play an important role in rapidly increasing molecular complexity from readily available starting materials. Reported here is a Cu‐catalyzed cascade reaction of α‐(hetero)aryl‐substituted alkyl (hetero)aryl ketones with primary amines that incorporates an unusual 1,2‐aryl migration induced by amide C−N bond formation to produce a class of structurally novel α,α‐diaryl β,γ‐unsaturated γ‐lactams in generally good‐to‐excellent yields. This cascade reaction has a broad substrate scope with respect to primary amines, allows a wide spectrum of (hetero)aryl groups to smoothly undergo 1,2‐migration, and tolerates electronically diverse α‐substituents on the (hetero)aryl ring of the ketones. Mechanistically, this 1,2‐aryl migration may stem from the intramolecular amide C−N bond formation which induces nucleophilic migration of the aryl group from the acyl carbon center to the electrophilic carbon center that is conjugated with the resulting iminium moiety. [ABSTRACT FROM AUTHOR]

An atom‐economical method for the direct B−H functionalization of nido‐carboranes (7,8‐nido‐C2B9H12−) has been developed under electrochemical reaction conditions. In this reaction system, anodic oxidation serves as a green alternative for traditional chemical oxidants in the oxidation of nido‐carboranes. No transition‐metal catalyst is required and different heteroatoms bearing a lone pair are reactive in this transformation. Coupling nido‐carboranes with thioethers, selenides, tellurides, N‐heterocycles, phosphates, phosphines, arsenides and antimonides demonstrates high site‐selectivity and efficiency. Importantly, nido‐carboranes can be easily incorporated into drug motifs through this reaction protocol. [ABSTRACT FROM AUTHOR]

The synthesis of robust high‐spin carbon radicals is an important topic in organic chemistry. Toward this end, several porphyrin‐stabilized radicals have been systematically explored. A singly naphthalene‐fused porphyrin radical was synthesized by a reaction sequence consisting of a Suzuki–Miyaura coupling of β‐borylated porphyrin with 2‐bromobenzaldehyde, addition of mesityl Grignard reagent, intramolecular Friedel–Crafts alkylation, and final oxidation with DDQ or tBuOK/O2. This strategy was also used to synthesize doubly naphthalene‐fused porphyrins and syn‐ and anti‐fused‐anthracene‐bridged porphyrin dimers. While singly naphthalene‐fused porphyrin radical has been shown to be a stable monoradical, doubly naphthalene‐fused porphyrins and anti‐fused‐anthracene‐bridged porphyrin dimers have been shown to be closed‐shell molecules. Finally, the syn‐dimer was characterized as a surprisingly stable radical (t1/2=28 days under ambient air and at 80 °C) that is storable for more than several months, despite its high‐spin triplet ground‐state carbon diradical. [ABSTRACT FROM AUTHOR]

We herein report amide directed enantioselective β‐C(sp3)−H borylation of unbiased methylene C−H bonds of acyclic amides enabled by iridium catalysis for the first time. The key to the success of this transformation relies on the careful selection of the combination of iridium precursor and chiral bidentate boryl ligands. A variety of functional groups are well‐tolerated, affording chiral β‐functionalized amides in good to excellent enantioselectivities. We also demonstrate the application of the current method by stereospecific conversion of C−B bond into other functionalities. [ABSTRACT FROM AUTHOR]

Synthetic routes for heteroatom‐containing polycyclic aromatic hydrocarbons (H‐PAHs) with alkyl and aryl substitution are demonstrated. Three H‐PAHs, including heteroatom‐containing rubicenes (H‐rubicenes), angular‐benzothiophenes (ABTs), and indenothiophene (IDTs) were successfully synthesized by two key steps, including polysubstituted olefin formation and cyclization. Specifically, ABT and H‐rubicenes were comprehensively investigated by single‐crystal X‐ray diffraction, NMR spectroscopy, UV‐vis absorption, cyclic voltammetry, transient absorption, and single‐crystal OFET measurements. [ABSTRACT FROM AUTHOR]

The participation of reactants undergoing a polarity inversion along a multicomponent reaction allows the continuation of the transformation with productive domino processes. Thus, indole aldehydes in Groebke–Blackburn–Bienaymé reactions lead to an initial adduct which spontaneously triggers a series of events leading to the discovery of novel reaction pathways together with direct access to a variety of linked, fused, and bridged polyheterocyclic scaffolds. Indole 3‐ and 4‐carbaldehydes with suitable isocyanides and aminoazines afford fused adducts through oxidative Pictet–Spengler processes, whereas indole 2‐carbaldehyde yields linked indolocarbazoles under mild conditions, and a bridged macrocycle at high temperature. These novel structures are potent activators of the human aryl hydrocarbon receptor signaling pathway. [ABSTRACT FROM AUTHOR]

The generated databases (GDBs) enumerate billions of possible molecules following simple rules of chemical stability and synthetic feasibility. Exploring the GDBs shows that many chiral, 3D‐shaped ring systems, often containing quaternary centers, have never been exploited for drug design. Shown herein is that such ring systems can be useful for medicinal chemistry by using the example of the enantioselective synthesis of triquinazine, a novel chiral piperazine analogue derived from angular triquinane. It is used to design a nanomolar and selective inhibitor of Janus Kinase 1 and is related to the marketed drug Tofacitinib, which is useful for treating autoimmune diseases. [ABSTRACT FROM AUTHOR]

Regioselective transformation is among the long‐standing challenges in organic synthesis. In this communication, a copper‐catalyzed selectivity controlled regiodivergent borocarbonylation of imines with alkyl iodides has been developed. Various α‐amino ketones and α‐boryl amides were produced in moderate to good yields from the same substrates. The choice of the ligand is key for the regioselectivity control: α‐amino ketones were produced selectively in good yields with (p‐CF3C6H4)3P as the ligand, whereas the corresponding α‐boryl amides were obtained with high regioselectivities when using MeIMes as the ligand. [ABSTRACT FROM AUTHOR]

Reported here is the Pd‐catalyzed C–N coupling of hydrazine with (hetero)aryl chlorides and bromides to form aryl hydrazines with catalyst loadings as low as 100 ppm of Pd and KOH as base. Mechanistic studies revealed two catalyst resting states: an arylpalladium(II) hydroxide and arylpalladium(II) chloride. These compounds are present in two interconnected catalytic cycles and react with hydrazine and base or hydrazine alone to give the product. The selectivity of the hydroxide complex with hydrazine to form aryl over diaryl hydrazine was lower than that of the chloride complex, as well as the catalytic reaction. In contrast, the selectivity of the chloride complex closely matched that of the catalytic reaction, indicating that the aryl hydrazine is derived from this complex. Kinetic studies showed that the coupling process occurs by rate‐limiting deprotonation of a hydrazine‐bound arylpalladium(II) chloride complex to give an arylpalladium(II) hydrazido complex. [ABSTRACT FROM AUTHOR]

We have rationally designed a new class of alkyne‐tethered oximes and applied them in an unprecedented iron‐catalyzed radical relay protocol for the rapid assembly of a wide array of structurally new and interesting fused pyridines. This method shows broad substrate scope and good functional‐group tolerance and enabled the synthesis of several biologically active molecules. Furthermore, the fused pyridines could be diversely functionalized through various simple transformations, such as cyclization, C−H alkylation, and a click reaction. DFT calculation studies indicate that the reactions involve cascade 1,5‐hydrogen atom transfer, 5‐exo‐dig radical addition, and cyclization processes. Moreover, preliminary biological investigations suggest that some of the fused pyridines exhibit good anti‐inflammatory activity by restoring the imbalance of inflammatory homeostasis of macrophages in a lipopolysaccharide‐induced model. [ABSTRACT FROM AUTHOR]

The application of piezoelectricity for the generation of trifluoromethyl (CF3) radicals is reported together with the development of a method for the mechanochemical C−H trifluoromethylation of aromatic compounds. As compared to conventional solution‐based approaches, this mechanoredox C−H trifluoromethylation enables cleaner and more sustainable access to a wide range of trifluoromethylated N‐heterocycles and peptides, which are important structural motifs in modern drug discovery. This study thus represents an important milestone for future applications of mechanoredox systems to medicinal and pharmaceutical science. [ABSTRACT FROM AUTHOR]

A straightforward alkali‐metal‐mediated hydroamination of styrenes using biorenewable 2‐methyltetrahydrofuran as a solvent is reported. Refuting the conventional wisdom of the incompatibility of organolithium reagents with air and moisture, shown here is that the presence of moisture is key in favoring formation of the target phenethylamines over competing olefin polymerization products. The method is also compatible with sodium amides, with the latter showing excellent promise as highly efficient catalysts under inert atmosphere conditions. [ABSTRACT FROM AUTHOR]

By integration of iminyl radical‐triggered 1,5‐hydrogen atom transfer and (5+2) or (5+1) annulation processes, a series of structurally novel and interesting azepine and spiro‐tetrahydropyridine derivatives have been successfully prepared in moderate to good yields. This method utilizes FeCl2 as the catalyst and readily available oximes as five‐atom units, while showcasing broad substrate scope and good functional group compatibility. The annulation products can be easily converted into many valuable compounds. Moreover, DFT calculation studies are performed to provide some insights into the possible reaction mechanisms for the (5+2) and (5+1) annulations. [ABSTRACT FROM AUTHOR]