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A new approach exploiting the dual properties of thiol-grafted cellulose paper for promoting copper-catalyzed [3+2]-cycloadditions of organic azides with alkynes and adsorbing residual copper species in solution was developed. The thiol-grafted cellulose paper, used as a paper strip, effects the reduction of CuII to catalytically active CuI and acts as a powerful adsorbent for copper, thereby facilitating the work-up process and leaving the crude mixture almost free of copper residues after a single filtration. [ABSTRACT FROM AUTHOR]

As a compliment to several other publications that present and honor Rolf Huisgen's research achievements, the first part of this paper reveals the human side of this eminent chemist. From excerpts from many of his personal and professional writings, Huisgen's personality and philosophies of life are revealed. Also revealed is Huisgen functioning as a historian of chemistry. The second part of this paper examines the scientometrics of Huisgen's publication history. In the late 1950s and early 1960s, Huisgen's career experienced a major transition in terms of publication metrics and the influence these papers had on the organic chemistry community. This was the result of his research into 1,3‐dipolar cycloadditions. Citations to his scientific contributions are well spread over many of his papers, demonstrating his constant work and the building up of a research topic, which continued after his official retirement in 1988. In fact, 17 % of his more than 600 publications appeared after 1988. The majority of Huisgen's papers were co‐authored with his many graduate and postdoctoral students. Consistent with the trend of that era, Huisgen was the sole author of most of his Review articles, and not just those of his many plenary lectures, and it is those Review articles that proved to be his most cited publications. This demonstrates the power and influence of Review articles—secondary sources, in the vocabulary of historians and sociologists of science. In those Review articles, Huisgen principally described the state of the art of 1,3‐dipolar cycloadditions—his golden offspring. [ABSTRACT FROM AUTHOR]

This review article describes the evolution of Woodward's mechanistic thinking, beginning in the late 1930s and early 1940s with his proposal of a charge‐transfer mechanism for the Diels–Alder reaction, eventually leading to the Woodward–Katz two‐stage concerted mechanism in 1959, and then to its mechanistic solution in terms of orbital symmetry control. Houk′s research in the Woodward labs, testing the predictions of this theory, is described. Subsequent modern calculations with quantum mechanics and molecular dynamics simulations have shown that Woodward indeed had perfectly described not only the cyclopentadiene dimerization mechanism, but a new class of transition states now known as ambimodal or bis‐pericyclic transition states. In recent years, the Houk group has found that ambimodal reactions are operative in the [6+4] cycloaddition. Molecular dynamics simulations of many Diels–Alder and ambimodal cycloadditions provide a time‐resolved picture of how these reactions occur. Lastly, Roald Hoffmann provides a Coda in which he describes his joy in "being taken along the journey" of the cycloaddition story from Woodward's youth to today's trajectory simulations. [ABSTRACT FROM AUTHOR]

In this paper is described an easily synthesized chiral diazaborolidine that is inexpensive, stable, and provides excellent stereoselection across a number of reaction classes. These versatile compounds possess utility in four different classes of cycloaddition reactions, offering good yield and stereoselectivity. X‐ray structure analysis provides insight about the origin of stereocontrol. [ABSTRACT FROM AUTHOR]

Huisgen's 1960 announcement of the concept of 1,3‐dipolar cycloadditions was published the year before Alder's study of the reaction of diazomethane and dimethylfulvene. The diazomethane reaction was studied again in 1970 by Houk et al. and shown to give a [6+4] adduct. Padwa's nitrile ylide cycloaddition to dimethylfulvene (1978) gave [6+4] and [4+2] adducts. We performed computational studies of these reactions with density functional theory (DFT) and show that they involve ambimodal [6+4]/[4+2] transition states that can lead to either type of cycloadduct from one transition state. We dedicate this paper to the extraordinary life and humanity of Rolf Huisgen, and to the undying influence of his discoveries on chemistry. [ABSTRACT FROM AUTHOR]

We have achieved the divergent total synthesis of four kopsane alkaloids which share a complex heptacyclic caged ring system. Key transformations include an asymmetric Diels–Alder reaction to assemble the central bicyclo[2.2.2]octane moiety and the quaternary stereocenter at C20, a SmI2‐mediated cascade reduction/aldol reaction to construct the five‐membered ring and the quaternary stereocenter at C7, and a late‐stage cascade reductive amination/cyclization to establish the highly strained caged ring system. [ABSTRACT FROM AUTHOR]

Synthesis and properties of anthracene‐based cyclic π‐clusters which possess two and four anthracene units are discussed. The optimal cyclization conditions were determined based on a nickel(0)‐mediated reaction that afforded a cyclic anthracene dimer as the major product. Bringing two anthracene planes in close proximity in a face‐to‐face manner resulted in red‐shifted absorption owing to the narrowing of the HOMO–LUMO gap. The cyclic anthracene dimer exhibits multi‐stimuli responsiveness due to high π‐congestion. For example, photoirradiation on the anthracene dimer affords its photoisomer having C−C bonds that are longer than 1.65 Å, which can undergo thermal reversion under gentle heating. This enabled mechanochromism of the photoisomer (colorless) to the original anthracene dimer (red). Photoisomerization was also observed in the crystalline state, accompanied by crystal jumping or collapsing, that is, the photosalient effect. [ABSTRACT FROM AUTHOR]

Monofluoroalkenes are nonhydrolyzable mimetics of amides. Previous work focused on the synthesis of non‐cyclic monofluoroalkenes. However, diastereoselective synthesis of monofluorocyclohexenes from non‐cyclic substrates is challenging. Herein, we report the first photocatalyzed cascade cyclization reactions of readily available α,β‐unsaturated carbonyl compounds and gem‐difluoroalkenes for the synthesis of highly functionalized monofluorocyclohexenes. The reaction shows broad substrate scope with high diastereoselectivity (>30 examples, up to 86 % yield, >20 : 1 dr). The post‐reaction transformations of the products demonstrate the synthetic potential of this methodology. [ABSTRACT FROM AUTHOR]

The palladium catalyzed cyclotrimerization of ortho‐silylaryl triflates as aryne precursors is meanwhile an established method to synthesize polycyclic aromatic hydrocarbons (PAHs) with triphenylene cores. During the palladium‐catalyzed reaction of a pyrene with an o‐silylaryl triflate moiety in the K‐region higher homologues with central eight‐ and ten‐membered rings (the pyrenylenes) were found, besides the expected trimer and a protocol was developed to isolate all members of this series. This unprecedented new class of PAHs was fully investigated by all means, including X‐ray diffraction of single‐crystals, UV/Vis and fluorescence spectroscopy and theoretical calculations. Supported by density‐functional theory (DFT) calculations, a mechanism of all higher cyclooligomers is proposed. [ABSTRACT FROM AUTHOR]

Catalytic enantioselective coupling of 1,1‐disubstituted allenes and aldehydes through regiodivergent oxidative cyclization followed by stereoselective protonation or reductive elimination promoted by chiral phosphine‐Co complexes is presented. Such processes represent unprecedented and unique reaction pathways for Co catalysis that enable catalytic enantioselective generation of metallacycles with divergent regioselectivity accurately controlled by chiral ligands, affording a wide range of allylic alcohols and homoallylic alcohols that are otherwise difficult to access without the need of pre‐formation of stoichiometric amounts of alkenyl‐ and allyl‐metal reagents in up to 92 % yield, >98 : 2 regioselectivity, >98 : 2 dr and >99.5 : 0.5 er. [ABSTRACT FROM AUTHOR]

Enantiopure [6]helicene containing an embedded seven‐membered ring and carbo[7]helicene (>99 % ee) with opposite helicity were simultaneously and quantitatively (>99 %) synthesized with a perfect stereospecificity through stepwise acid‐promoted intramolecular alkyne annulations of doubly axial‐chiral cyclization precursors. The helical handedness of the [6]‐ and [7]helicenes was fully stereocontrolled by the doubly axial chirality of the precursors as a result of complete axial‐to‐helical chirality transfer. The cyclizations proceeded in a stepwise manner; the first six‐membered ring formation was followed by the kinetically controlled seven‐ or six‐membered ring formation with or without helix‐inversion of a [4]helicene intermediate generated during the first cyclization step, thus quantitatively producing enantiopure circularly polarized luminescent [6]‐ and [7]helicenes with opposite helicity. [ABSTRACT FROM AUTHOR]

The 2π electron 1,3‐dipole boradigermaallyl, valence‐isoelectronic to an allyl cation, is synthesized from a bis(germylene). It reacts with benzene at room temperature by insertion of a boron atom into the benzene ring. Computational investigation of the mechanism shows the boradigermaallyl reacting with a benzene molecule in a concerted (4+3) or [π4s+π2s] cycloaddition reaction. Thus, the boradigermaallyl acts as a highly reactive dienophile in this cycloaddition reaction with nonactivated benzene as diene unit. This type of reactivity provides a novel platform for ligand assisted borylene insertion chemistry. [ABSTRACT FROM AUTHOR]

We report the first highly selective kinetic resolution of racemic α‐chiral azides via Cu‐catalyzed azide‐alkyne cycloaddition (CuAAC). Newly developed pyridine‐bisoxazoline (PYBOX) ligands, bearing a C4 sulfonyl group, enable effective kinetic resolution of racemic azides derived from privileged scaffolds such as indanone, cyclopentenone, and oxindole, and their asymmetric CuAAC to afford α‐tertiary 1,2,3‐triazoles with high to excellent ee values. DFT calculations and control experiments reveal that the C4 sulfonyl group decreases the Lewis basicity of the ligand and increases the electrophilicity of the copper center for better recognition of azides, and functions as a shielding group to make the chiral pocket of the catalyst more effective. [ABSTRACT FROM AUTHOR]

We describe a novel type of photoclick reaction between 2,3‐diaryl indenone epoxide (DIO) and ring‐strained dipolarophiles, in which DIO serves as a P‐type photoswitch to produce mesoionic oxidopyrylium ylide (PY) to initiate an ultra‐fast [5+2] cycloaddition (k2hν=1.9×105 M−1 s−1). The photoisomerization between DIO and PY can be tightly controlled by either 365 or 520 nm photo‐stimulation, which allows reversion or regeneration of the reactive PY dipole on demand. Thus, this reversible photoactivation was exploited to increase the chemoselectivity of the [5+2] cycloaddition in complex environments via temporal dual‐λ stimulation sequences and to recycle the DIO reagent for batch‐wise protein conjugation. A dynamic photoswitching strategy is also proposed to compensate for molecular diffusion of PY in aqueous solution, enhancing the spatial resolution of lithographic surface decoration and bioorthogonal labeling on living cells via a spatiotemporal dual‐λ photo‐modulation. [ABSTRACT FROM AUTHOR]

A divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been accomplished featuring the following key steps: a) a catalyst‐controlled asymmetric Pictet–Spengler reaction of 6‐methoxytryptamine with a chiral α‐ketoester affording a 1,1‐disubstituted tetrahydro‐β‐carboline in excellent yield and diastereoselectivity; b) oxidative cleavage of a 3,5‐disubstituted cyclopentene furnishing a dialdehyde intermediate, which was effectively differentiated through spontaneous cyclization with the neighboring hydroxy and secondary amine functions; c) intramolecular nucleophilic addition of a tertiary amino nitrogen atom to the in situ generated oxonium species generating stereoselectively an unprecedented 8‐alkyl octahydro‐2H‐5,8‐methanofuro[2,3‐b]azepin‐8‐ium motif bearing five contiguous stereocenters. The synthesis confirmed the absolute configuration of these two natural products. [ABSTRACT FROM AUTHOR]

We have developed the Rh+/H8‐binap‐catalyzed chemo‐, regio‐, diastereo‐, and enantioselective intermolecular [2+2+2] cycloaddition of three unsymmetric 2π components. Thus, two arylacetylenes react with a cis‐enamide to yield a protected chiral cyclohexadienylamine. Moreover, replacing one arylacetylene with a silylacetylene enables the [2+2+2] cycloaddition of three distinct unsymmetric 2π components. These transformations proceed with excellent selectivity (complete regio‐ and diastereoselectivity and up to >99 % yield and >99 % ee). Mechanistic studies suggest the chemo‐ and regioselective formation of a rhodacyclopentadiene intermediate from the two terminal alkynes. [ABSTRACT FROM AUTHOR]

Metabolic pathways are highly regulated by effector molecules that influences the rate of enzymatic reactions. Inspired by the catalytic regulation found in living cells, we report a Pt2L4 cage of which the activity can be controlled by effectors that bind inside the cage. The cage shows catalytic activity in the lactonization of alkynoic acids, with the reaction rates dependent on the effector guest bound in the cage. Some effector guests enhance the rate of the lactonization by up to 19‐fold, whereas one decreases it by 5‐fold. When mixtures of specific substrates are used, both starting materials and products act as guests for the Pt2L4 cage, enhancing its catalytic activity for one substrate while reducing its activity for the other. The reported regulatory behavior obtained by the addition of effector molecules paves the way to the development of more complex, metabolic‐like catalyst systems. [ABSTRACT FROM AUTHOR]

Herein we report a two‐directional cyclization strategy for the synthesis of highly strained depth‐expanded oxygen‐doped chiral molecular belts of the zigzag‐type. From the easily accessible resorcin[4]arenes, an unprecedented cyclization cascade generating fused 2,3‐dihydro‐1H‐phenalenes has been developed to access expanded molecular belts. Stitching up the fjords through intramolecular nucleophilic aromatic substitution and ring‐closing olefin metathesis reactions furnished a highly strained O‐doped C2‐symmetric belt. The enantiomers of the acquired compounds exhibited excellent chiroptical properties. The calculated parallelly aligned electric (μ) and magnetic (m) transition dipole moments are translated to the high dissymmetry factor (|glum| up to 0.022). This study provides not only an appealing and useful strategy for the synthesis of strained molecular belts but also a new paradigm for the fabrication of belt‐derived chiroptical materials with high CPL activities. [ABSTRACT FROM AUTHOR]

Despite the significance of sultines in synthesis, medicine, and materials science, the chemistry of sultines has remained unexplored due to their inaccessibility. Herein, we demonstrate the development of a photoredox‐catalyzed multifluoromethyl radical addition/SO2 incorporation/polar cyclization cascade approach to multifluoromethylated γ‐sultines. The reactions proceed by single electron transfer induced multifluoromethyl radical addition to an alkene followed by SO2 incorporation, and single‐electron reduction for polar 5‐exo‐tet cyclization. Key to the success of the protocol is the use of easily oxidizable multifluoroalkanesulfinates as bifunctional reagents. The reactions proceed with excellent functional‐group tolerance to deliver γ‐sultines in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

We report here computational evidence for a metalla‐Claisen rearrangement (MCR) in the case of gold‐catalyzed [4+2] cycloaddition reaction of yne‐dienes. The [4+2] reaction starts from exo cyclopropanation, followed by MCR and reductive elimination. The cyclopropane moiety formed in the first step is crucial for a low barrier of the MCR step. In addition, the importance of an appropriate combination of the tether group and the terminal substituent on alkyne in the yne‐diene substrates was studied. The mechanism of rhodium‐catalyzed [4+2] reaction of yne‐dienes was also investigated to see whether an MCR mechanism is involved or not. The findings and new understanding hereby reported represent an important advance in the catalysis field. [ABSTRACT FROM AUTHOR]

Dearomative cycloadditions are a powerful tool to access a large chemical space exploiting simple and ubiquitous building blocks. The energetic burden due to the loss of aromaticity has however greatly limited their synthetic potential. We devised a general intramolecular method that overcomes these limitations thanks to the photosensitization of allenamides. The visible‐light‐promoted process gives complex [2.2.2]‐(hetero)‐bicyclooctadienes at room temperature, likely through the stabilization of transient (bi)radicals by naphthalene. The reaction tolerates several valuable functionalities, offering a convenient handle for a myriad of applications, including original isoindoles and metal complexes. [ABSTRACT FROM AUTHOR]

The C−H functionalization strategy provides access to valuable molecules that previously required convoluted synthetic attempts. Dual C−H unsymmetrical functionalization, with a single bifunctional reagent, is an effective tactic. Propargyl alcohols (PAs), despite containing a reactive C≡C bond, have not been explored as building blocks via oxidative cleavage. Annulations via C−H activation are a versatile and synthetically attractive strategy. We disclose PA as a new bifunctional reagent for unsymmetrical dual C−H functionalization of biphenylamine for regioselectively annulated outcomes. On tuning the conditions, the annulation bifurcated towards an unusual dual oxidative cyclization. This method accommodates a wide range of PAs and showcases late‐stage diversification of some natural products. [ABSTRACT FROM AUTHOR]

A conceptually novel catalytic domino approach is presented for the synthesis of highly functional 1,4‐dihydro‐2H‐1,3‐benzoxazine‐2‐one derivatives. Key to the chemoselectivity is a proper design of the precursor to override thermodynamically favored parasitic cyclization processes and empower the formation of the desired product through Thorpe–Ingold effects. The synthetic diversity of these CO2‐based heterocycles is further demonstrated, and the isolation of a reaction intermediate supports an unusual ring‐expansion sequence from an α‐alkylidene, five‐membered cyclic carbonate to a six‐membered cyclic carbamate by N‐induced isomerization. [ABSTRACT FROM AUTHOR]

2‐Aminoallyl cations are versatile 1,3‐dipoles that could potentially be used for diverse (3+n) cycloaddition reactions. Despite some preliminary studies, the asymmetric catalytic transformation of these species is still underdeveloped. We herein report a binuclear copper‐catalyzed generation of 2‐aminoallyl cations from ethynyl methylene cyclic carbamates and their enantioselective (3+2) cycloaddition reaction with indoles to construct chiral pyrroloindolines. This transformation features a novel C1,N‐dipolar reactivity for 2‐aminoallyl cations. [ABSTRACT FROM AUTHOR]

Alkynes and 1,3‐dienes are among the most readily available precursors for organic synthesis. We report two distinctly different, catalyst‐dependent, modes of regio‐ and enantioselective cycloaddition reactions between these classes of compounds providing rapid access to highly functionalized 1,4‐cyclohexadienes or cyclobutenes from the same precursors. Complexes of an earth abundant metal, cobalt, with several commercially available chiral bisphosphine ligands with narrow bite angles catalyze [4+2]‐cycloadditions between a 1,3‐diene and an alkyne giving a cyclohexa‐1,4‐diene in excellent chemo‐, regio‐ and enantioselectivities. In sharp contrast, complex of a finely tuned phosphino‐oxazoline ligand promotes unique [2+2]‐cycloaddition between the alkyne and the terminal double bond of the diene giving a highly functionalized cyclobutene in excellent regio‐ and enantioselectivities. [ABSTRACT FROM AUTHOR]

Herein, an I2‐catalyzed unprecedented cycloisomerization of ynamides is developed, furnishing various functionalized bis(indole) derivatives in generally good to excellent yields with wide substrate scope and excellent atom‐economy. This protocol not only represents the first molecular‐iodine‐catalyzed tandem complex alkyne cycloisomerizations, but also constitutes the first chemoselective cycloisomerization of tryptamine‐ynamides involving distinctively different C(sp3)−C(sp3) bond cleavage and rearrangement. Moreover, chiral tetrahydropyridine frameworks containing two stereocenters are obtained with moderate to excellent diastereoselectivities and excellent enantioselectivities. Meanwhile, cycloisomerization and aromatization of ynamides produce pyrrolyl indoles with high efficiency enabled by I2. Additionally, control experiments and theoretical calculations reveal that this reaction probably undergoes a tandem 5‐exo‐dig cyclization/rearrangement process. [ABSTRACT FROM AUTHOR]

Dearomatization reactions involving radical cyclizations can facilitate the synthesis of complex polycyclic systems that find applications in medicinal chemistry and natural product synthesis. Here we employ redox‐neutral photocatalysis to affect a radical spirocyclization that transforms biaryls into spirocyclic cyclohexadienones under mild reaction conditions. In a departure from previously reported methods, our work demonstrates the polarity mismatched addition of a nucleophilic radical to an electron rich arene, and allows the regioselective synthesis of 2,4‐ or 2,5‐cyclohexadienones with broad functional group tolerance. By transforming biaryls into spirocycles, our methodology accesses underexplored three‐dimensional chemical space, and provides an efficient means of creating quaternary spirocenters that we apply to the first synthesis of the cytotoxic plant metabolite denobilone A. [ABSTRACT FROM AUTHOR]

The first examples of halogen bonding (XB) heteroditopic homo[2]catenanes were prepared by discrete Na+ template‐directed assembly of oligo(ethylene glycol) units derived from XB donor‐containing macrocycles and acyclic bis‐azide precursors, followed by a CuI‐mediated azide‐alkyne cycloaddition macrocyclisation reaction. Extensive 1H NMR spectroscopic studies show the [2]catenane hosts exhibit positive cooperative ion‐pair recognition behaviour, wherein XB‐mediated halide recognition is enhanced by alkali metal cation pre‐complexation. Notably, subtle changes in the catenanes' oligo(ethylene glycol) chain length dramatically alters their ion‐binding affinity, stoichiometry, complexation mode, and conformational dynamics. Solution‐phase and single‐crystal X‐ray diffraction studies provide evidence for competing host‐separated and direct‐contact ion‐pair binding modes. We further demonstrate the [2]catenanes are capable of extracting solid alkali‐metal halide salts into organic media. [ABSTRACT FROM AUTHOR]

The field of strain‐driven, radical formal cycloadditions is experiencing a surge in activity motivated by a renaissance in free radical chemistry and growing demand for sp3‐rich ring systems. The former has been driven in large part by the rise of photoredox catalysis, and the latter by adoption of the "Escape from Flatland" concept in medicinal chemistry. In the years since these broader trends emerged, dozens of formal cycloadditions, including catalytic, asymmetric variants, have been developed that operate via radical mechanisms. While cyclopropanes have been studied most extensively, a variety of strained ring systems are amenable to the design of analogous reactions. Many of these processes generate lucrative, functionally decorated sp3‐rich ring systems that are difficult to access by other means. Herein, we summarize recent efforts in this area and analyze the state of the field. [ABSTRACT FROM AUTHOR]

Hydroboration of styrene or vinylcyclohexane with the IMes(C6F5)BH+ cation followed by deprotonation provided a convenient synthetic entry to the [B]=CHCH2R boraalkenes 9 a and 9 b. The in situ generated IMes(SCN)BH+ system reacted similarly with 1,1‐diphenylethene followed by deprotonation to give the isothiocyanato substituted boraalkene 9 c. The boraalkenes underwent [2+2] cycloaddition reactions with a small series of heterocumulenes to give the respective four‐membered heterocycles. The [B]=CHCH2R+CO2 cycloadducts 13 a and 13 b added the borane HB(C6F5)2 with cleavage of the central B−C σ‐bond. CS2 underwent an unusual reaction with the boraalkenes, namely insertion into the B=C bond with formation of the borylated dithioketene acetal under complete rupture of the strong B=C double bond. The intermediate dithiobora‐β‐lactone type intermediate was isolated in the case of the isothiocyanato‐boraalkene reaction and characterized by X‐ray diffraction. [ABSTRACT FROM AUTHOR]

We herein disclose a mild and efficient access to chiral 3‐azabicyclo[3.1.0]hexanes via a Pd‐catalyzed asymmetric 5‐exo‐trig cyclization/cyclopropanation/carbonylation of 1,6‐enynes. Various nucleophiles, such as alcohols, phenols, amines and water, are well compatible with the reaction system. This reaction forms three C−C bonds, two rings, two adjacent quaternary carbon stereocenters as well as one C−O/C−N bond with excellent regio‐ and enantioselectivities. The products could be further functionalized to generate a library of 3‐azabicyclo[3.1.0]hexane frameworks. [ABSTRACT FROM AUTHOR]

Phenyl azides substituted by an (alkylphenyl)ethynyl group facilitate benzylic sp3(C−H) functionalization in the presence of a JohnPhosAu catalyst, resulting in indole‐fused tetra‐ and pentacycles via divergent N‐ or C‐cyclization. The chemoselectivity is influenced depending on the counter‐anion, the electron density of the α‐imino gold(I) carbene, and the alkyl groups stabilizing the benzylic carbocation originating from a 1,5‐hydride shift. An isotopic labeling experiment demonstrates the involvement of an indolylgold(I) species resulting from a tautomerization that is much faster than the deauration. The formation of a benzylic sp3(C−H) functionalization leading to an indole‐fused seven‐membered ring is also demonstrated. [ABSTRACT FROM AUTHOR]

Ring‐opening transformations of donor‐acceptor (D‐A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium‐catalyzed highly diastereo‐ and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron‐withdrawing groups, a subset of D‐A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five‐membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and >19 : 1 dr). In‐depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H‐bonding in stereocontrol. [ABSTRACT FROM AUTHOR]

Enzymes facilitate chemical conversions through the collective activity of aggregated components, but the marriage of aggregation‐induced emission (AIE) with molecular containers to emulate enzymatic conversion remains challenging. Herein, we report a new approach to construct a PtII‐based octahedral cage with AIE characteristics for the photocyclization of alkynylaniline by restricting the rotation of the pendant phenyl rings peripheral to the PtII corner. With the presence of water, the C−H⋅⋅⋅π interactions involving the triphenylphosphine fragments resulted in aggregation of the molecular cages into spherical particles and significantly enhanced the PtII‐based luminescence. The kinetically inert Pt‐NP chelator, with highly differentiated redox potentials in the ground and excited states, and the efficient coordination activation of the platinum corner facilitated excellent catalysis of the photocyclization of alkynylaniline. The enzymatic kinetics and the advantages of binding and activating substrates in an aqueous medium provide a new avenue to develop mimics for efficient photosynthesis. [ABSTRACT FROM AUTHOR]

A novel class of highly activated donor‐acceptor cyclopropanes bearing only a single, vinylogous acceptor is presented. These strained moieties readily undergo cycloadditions with aldehydes, ketones, thioketones, nitriles, naphth‐2‐ols and various other substrates to yield the corresponding carbo‐ and heterocycles. Diastereocontrol can be achieved through the choice of catalyst (Brønsted or Lewis acid). The formation of tetrahydrofurans was shown to be highly enantiospecific when chiral cyclopropanes are employed. A series of mechanistic and kinetic experiments was conducted to elucidate a plausible catalytic cycle and to rationalize the stereochemical outcome. [ABSTRACT FROM AUTHOR]

Sapphyrin is a pentapyrrolic expanded porphyrin with a 22π aromatic character. Herein, we report the synthesis of a 20π antiaromatic sapphyrin isomer 1 by oxidative cyclization of a pentapyrrane precursor P5 with a terminal β‐linked pyrrole. The resulting isomer 1, containing a mis‐linked bipyrrole unit in the skeleton, exhibits a reactivity for further oxidation due to the distinct antiaromatic electronic structure, affording a fused macrocycle 2, possessing a spiro‐carbon‐containing [5.6.5.6]‐tetracyclic structure. Subsequent treatment with an acid afforded a weakly aromatic pyrrolone‐appended N‐confused corrole 3, and thermal fusion gave a [5.6.5.7]‐tetracyclic‐ring‐embedded 14π aromatic triphyrin(2.1.1) analog 4. The cyclization at the mis‐linked pyrrole moiety of P5 played a crucial role in synthesizing the antiaromatic porphyrinoid susceptible to facile transformation to novel porphyrinoids with variable aromaticity. [ABSTRACT FROM AUTHOR]

A novel and expedient cascade strategy has been demonstrated for the synthesis of fused benzo‐aza‐oxa‐[5‐6‐5] tetracycles in high yields and diastereoselectivities (up to 20 : 1 dr). The strategy was fulfilled through palladium‐catalyzed oxidative convergent assembly of functionally divergent anilines and 3‐butenoic acid with five chemical bonds constructed. Coupled with control experiments and deuterium labelled studies, DFT calculations were performed for the proposed mechanism. The utility of the illustrated strategy is emphasized by gram‐scale syntheses, late‐stage functionalization, and the transformation to a key core of natural products such as martinellic acid and seneciobipyrrolidine. [ABSTRACT FROM AUTHOR]

Alkene difunctionalization featuring an intramolecular carbometallation step has been developed into a powerful transformation in organic synthesis. The 5‐exo‐trig carbometallation is in general highly favored over the alternative 6‐endo‐trig cyclization. We report herein a formal 6‐endo‐trig carbofluorination protocol by combining the conventional 5‐exo‐trig carbopalladation with a chemoselective 1,2‐aryl/Pd dyotropic rearrangement. Treatment of 2‐(2‐alkylallyloxy)phenyl boronic acid derivatives in the presence of a catalytic amount of Pd(dba)2, 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine and Selectfluor affords chromanes with concurrent generation of a tertiary alkyl fluoride function. A σ‐alkyl‐PdII species resulting from the 5‐exo‐trig carbopalladation process is isolated and characterized by X‐ray crystallographic analysis. Its oxidation to PdIV complex triggers the chemoselective dyotropic rearrangement leading to the ring expansion product. [ABSTRACT FROM AUTHOR]

A new FeCl3 and BF3⋅OEt2 co-catalyzed tandem hetero-[5+2] cycloaddition of 2-(2-aminoethyl)oxiranes with a wide range of alkynes, including terminal alkynes and alkyl-substituted internal alkynes is presented. This is the first example of rapid and facile production of diverse 2,3-dihydro-1 H-azepines through a sequence of epoxide ring-opening, annulation, and dehydroxylation with broad substrate scope and exquisite selectivity control. [ABSTRACT FROM AUTHOR]

Silaspiranes have attracted particular attention due to their chiral spiro‐silicon center, which serves as an ideal carbon isostere and can endow spiro‐analogs with distinct properties. Distinct from previously reported cyclization or cycloaddition strategies to form 5/5‐silaspiranes, we report herein the asymmetric dual ring expansion of spirosilabicyclobutanes with alkynes to synthesize axially chiral spirosilabicyclohexenes bearing a novel 6/6‐silaspirane framework. DFT (density functional theory) calculations provide the deep insight into the origin of the high enantioselectivity controlled by the sterically demanding binaphthyl phosphoramidite ligand. Preliminary studies of chiroptical properties indicate that one of the spirosilabicyclohexene analogs exhibit fluorescence emission, Cotton effects and CPL (circularly polarized luminescence) activity. [ABSTRACT FROM AUTHOR]

A systematic study to access stable stannaimines is reported, by combining different heteroleptic stannylenes with a range of organic azides. The reactions of terphenyl‐/hypersilyl‐substituted stannylenes yield the putative tin nitrogen double bond, but is directly followed by 1,2‐silyl migration to give SnII systems featuring bulky silylamido ligands. By contrast, the transition from a two σ donor ligand set to a mixed σ‐donor/π‐donor scaffold allows access to three new stannaimines which can be handled at room temperature. The reactivity profile of these Sn=N bonded species is crucially dependent on the substituent at the nitrogen atom. As such, the Sn=NMes (Mes=2,4,6‐Me3C6H2) system is capable of activating a broad range of substrates under ambient conditions via 1,2‐addition reactions, [2+2] and [4+2] cycloaddition reactions. Most interestingly, very rare examples of main group multiple bond metathesis reactions are also found to be viable. [ABSTRACT FROM AUTHOR]

Rh‐catalyzed dynamic kinetic intramolecular [4+2] cycloaddition reaction of 1,3‐disubstituted allene‐1,3‐dienes afforded cis‐fused [4.3.0]bicyclic products with an excellent chemo‐, diastereo‐, and enantio‐selectivity. Many synthetically useful functional groups are tolerated. The synthetic utility has been demonstrated. Based on the careful experimental studies, a mechanism involving the rapid racemization of the allene moiety in the starting materials has been proposed. [ABSTRACT FROM AUTHOR]

The introduction of fluorine‐containing groups into organic molecules can significantly affect their physical and chemical properties and has long been used as an effective strategy for drug discovery and development. Consequently, the development of catalytic asymmetric methods for the synthesis of fluorine‐containing heterocycles is highly desirable and sought after. Herein, we describe a nickel‐catalyzed defluorinative asymmetric cyclization of fluoroalkyl‐substituted 1,6‐enynes, providing an expedient access to synthetically attractive 4‐fluorovinyl‐substituted 2‐pyrrolidones in good yields with remarkable high levels of chemo‐, regio‐, and enantioselectivities (90–99 % ee,>35 examples). This protocol features readily available starting materials and excellent functional group compatibility, and exhibits complementary regioselectivity. The utility of this strategy was demonstrated in the enantioselective synthesis of the antiepileptic drug Seletracetam. [ABSTRACT FROM AUTHOR]

An efficient catalytic asymmetric [2+2] cycloaddition of allenyl imide and mono‐ or disubstituted alkenes is disclosed. The key feature of this method is the use of bidentate allenyl imide and weakly activated and less steric hindered alkene pair by utilizing chiral magnesium(II) complex of N,N′‐dioxide, which could provide through‐space dispersion interactions to orientate the arrangement of the alkene. This protocol allows the generation of a series of axially chiral cyclobutenes and four‐membered ring‐containing spirocycles (80 examples) in high yield (up to 99 %) with excellent enantioselectivity (up to >99 % ee), and the late‐stage modification of biologically active molecules as well. Experimental studies and DFT calculations revealed that this [2+2] cycloaddition proceeded via a stepwise mechanism involving a short‐lived zwitterionic intermediate. The π‐π interaction between the alkenes and the amide moiety in the ligand was crucial for the enantiocontrol. [ABSTRACT FROM AUTHOR]

Regioselective Huisgen cycloaddition reaction between 1,2‐diboraallene and azide proceeds under catalyst‐free and mild conditions to furnish a diboratriazole (2). X‐ray diffraction analysis and computational studies confirmed the delocalization of π electrons over the B2N3 five‐membered ring of (2), indicating its aromatic features. Molecule (2) spontaneously releases N2 to form the 2,3‐dibora‐4‐aza‐1,3‐butenyne derivative (3). The mechanism of a whole reaction profile was extensively investigated by density functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

A broadly applicable diastereo‐ and enantioselective inverse‐electron‐demand Diels–Alder reaction of 2‐pyrones and acyclic enol ethers is reported herein. Using a copper(II)‐BOX catalytic system, bridged bicyclic lactones are obtained in very high yields (up to 99 % yield) and enantioselectivities (up to 99 % ee) from diversely substituted 2‐pyrones and acyclic enol ethers. Mechanistic experiments as well as DFT calculations indicate the occurrence of a stepwise mechanism. The synthetic potential of the bridged bicyclic lactones is showcased by the enantioselective synthesis of polyfunctional cyclohexenes and cyclohexadienes, as well as a carbasugar unit. [ABSTRACT FROM AUTHOR]

In this study, we describe a synthetic method for incorporating arenes into closed tubes that we name capsularenes. First, we prepared vase‐shaped molecular baskets 4–7. The baskets comprise a benzene base fused to three bicycle[2.2.1]heptane rings that extend into phthalimide (4), naphthalimide (6), and anthraceneimide sides (7), each carrying a dimethoxyethane acetal group. In the presence of catalytic trifluoroacetic acid (TFA), the acetals at top of 4, 6 and 7 change into aliphatic aldehydes followed by their intramolecular cyclization into 1,3,5‐trioxane (1H NMR spectroscopy). Such ring closure is nearly a quantitative process that furnishes differently sized capsularenes 1 (0.7×0.9 nm), 8 (0.7×1.1 nm;) and 9 (0.7×1.4 nm;) characterized by X‐Ray crystallography, microcrystal electron diffraction, UV/Vis, fluorescence, cyclic voltammetry, and thermogravimetry. With exceptional rigidity, unique topology, great thermal stability, and perhaps tuneable optoelectronic characteristics, capsularenes hold promise for the construction of novel organic electronic devices. [ABSTRACT FROM AUTHOR]

As the aromatic tryptophan (Trp) side chain plays a pivotal role in influencing the structure and function of peptides and proteins, it has become an attractive target for the late‐stage modification of these important biomolecules. Herein, we report an electrochemical approach for late‐stage functionalization of peptides containing a Trp side chain through manganese‐catalyzed tandem radical azidation/heterocyclization. This electrochemical oxidative strategy provides access to azide‐substituted tetrazolo[1,5‐a]indole‐containing peptides with broad functional group tolerance, high site selectivity, and good yields of products (up to 87 %) under mild buffer conditions. Moreover, the modified Trp‐containing peptides bearing an azide functionality are promising building blocks, paving the way for the construction of various derivatives, such as "click" chemistry products. [ABSTRACT FROM AUTHOR]

We report the density functional theory (DFT) guided discovery of ethynyl‐triazolyl‐phosphinates (ETPs) as a new class of electrophilic warheads for cysteine selective bioconjugation. By using CuI‐catalysed azide alkyne cycloaddition (CuAAC) in aqueous buffer, we were able to access a variety of functional electrophilic building blocks, including proteins, from diethynyl‐phosphinate. ETP‐reagents were used to obtain fluorescent peptide‐conjugates for receptor labelling on live cells and a stable and a biologically active antibody‐drug‐conjugate. Moreover, we were able to incorporate ETP‐electrophiles into an azide‐containing ubiquitin under native conditions and demonstrate their potential in protein–protein conjugation. Finally, we showcase the excellent cysteine‐selectivity of this new class of electrophile in mass spectrometry based, proteome‐wide cysteine profiling, underscoring the applicability in homogeneous bioconjugation strategies to connect two complex biomolecules. [ABSTRACT FROM AUTHOR]

Regiochemistry of topochemical reactions depends on the crystal packing and biasing the regiochemistry necessitates precise crystal engineering. The pristine crystals of monomer 1 upon topochemical azide‐alkyne cycloaddition (TAAC) reaction give a 1 : 1 blend of 1,4‐ and 1,5‐triazole‐linked polymers due to the presence of two self‐sorted reactive conformers in the crystal. We designed a binary isomorphous cocrystal of monomer 1 and a structurally similar dummy molecule 2 to limit the number of reactive conformers of 1 to one and thus to get one type of polymer. Equimolar solution of 1 and 2 in chloroform‐acetone mixture gave two 1 : 1 cocrystals Co‐I and Co‐II. The Co‐II, a chloroform adduct, on heating undergoes desolvation and polymorphic transition to Co‐I. Co‐I is isomorphic to 1 and 2 and possess self‐sorted arrays of 1 and 2. Heating Co‐I results in the TAAC polymerization giving 1,4‐triazolyl‐linked polymer of 1 selectively, showing the power of crystal engineering in regiocontrol. [ABSTRACT FROM AUTHOR]