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A new approach for the synthetically important γ‐functionalized enals has been developed. The strategy involves rhodium‐catalyzed direct C−C & C−S bond forming site‐selective γ‐difunctionalization of diazoenals with aryl propargyl sulfides via sulfur ylide [2,3] sigmatropic rearrangement, resulting in the highly functionalized γ‐allenyl(sulfanyl)enals in excellent yield at ambient temperature. This highly versatile approach constitutes a viable alternative to the remote carbonyl‐directed γ‐functionalization of unmodified enals which suffer from competitive side reactions. The synthetic utility of the γ‐allenyl(sulfanyl)enals was demonstrated by the InCl3‐catalyzed cycloisomerization to the trisubstituted furanyl‐enals via an unusual 1,4‐sulfanyl migration. In addition, an operationally simple and efficient one‐pot [3+2] annulation of diazoenals and propargyl sulfides, involving combined γ‐difunctionalization and cycloisomerization was successfully developed for the diverse enal‐functionalized furans. [ABSTRACT FROM AUTHOR]

The mechanistic study of the gold-catalyzed cycloisomerization of alcohols or amine tethered-vinylidenecyclopropanes has been performed using high-level DFT calculations to find the reasons for the observed selectivity of the products. Two possible pathways were observed, in the first product, during the cyclization process, the vinylidenecyclopropane moiety converts to methylidenecyclopropane-containing product (P1) via an ionic (non-carbene) intermediate, and in the second product, converts to cyclobutene-containing product (P2) via a carbene intermediates. In all six examined derivatives (containing different alkyl groups at C1 allenic carbon) P2 was the major product by both thermodynamic (the more stability of P1 than P2) and kinetic (the smaller barrier for producing P2 versus P1) criteria in both gas phase and solvent (THF, using PCM model) media. However, in the derivatives with low-strain allenic group (R), I1 (which leads to P1) is more stable than I3 intermediates (which leads to P2) by 0.6–4.2 kcal/mol in the gas phase and 1.0–3.1 kcal/mol in the solvent and the derivatives with high-strain allenic group, I3 is more stable than I1 by 2.1–2.5 kcal/mol in the gas phase and 3.5–4.2 kcal/mol in the solvent. Therefore, both gas phase and solvent data show that because of the different hindrance between the alkyl group and gold cation complex, the selectivity of the reaction is yielded by the favorability of I1 or I3 intermediates. Interestingly, another evidence was provided by atomic charges in the reactants using NBO calculations. These calculations showed that when the atomic charge of C1 allenic carbon was higher than C3, the gold cation prefers to produce I1, leading to P1, and when the atomic charge of C3 allenic carbon was higher than C1, the gold cation prefers to produce I2, leading to P2. [ABSTRACT FROM AUTHOR]

Oxazoles are important five-membered heterocycles that contain both nitrogen and oxygen atoms. Due to their wide range of biological activities, many oxazoles demonstrate potential for extensive application in various fields, including medicinal chemistry. Trifluoromethyl carbinol, an important pharmacophore, contains both trifluoromethyl and hydroxyl groups and is common in molecules with important biological activities. Constructing oxazoles that contain a trifluoromethyl carbinol unit is undoubtedly important and valuable for expanding the chemical space in drug discovery. In this study, a simple and efficient method was developed for the synthesis of oxazoles containing a CF3-substituted alcohol unit via the tandem cycloisomerization/hydroxyalkylation of N-propargylamides with trifluoropyruvates through a rational Lewis acid catalytic mechanism. This Zn(OTf)2-catalyzed synthetic protocol is operationally simple and provides a series of oxazoles in moderate to good yields. The protocol demonstrates broad substrate scope, high functional group tolerance, and high atom economy and can achieve gram-level reactions, indicating the strong possibility of its practical application. [ABSTRACT FROM AUTHOR]

Gold-catalyzed propargylic substitution of propargylic alcohols 1 with 1,3-dicarbonyl compounds 2 followed by cycloisomerization in ionic liquid enables the environmentally friendly synthesis of polysubstituted furans 3 in good-to-high yields. The reaction proceeds via the hydrated propargylic substitution product 3″aa. The gold catalyst can be recycled at least three times. [ABSTRACT FROM AUTHOR]

Cyclopentene rings possessing a chiral quaternary center are important structural motifs found in various natural products. In this work, we disclose expedient and efficient access to this class of synthetically valuable structures via highly enantioselective desymmetrization of prochiral propargylic alcohols. The efficient chirality induction in this asymmetric gold catalysis is achieved via two‐point bindings between a gold catalyst featuring a bifunctional phosphine ligand and the substrate homopropargylic alcohol moiety—an H‐bonding interaction between the substrate HO group and a ligand phosphine oxide moiety and the gold‐alkyne complexation. The propargylic alcohol substrates can be prepared readily via propargylation of enoate and ketone precursors. In addition to monocyclic cyclopentenes, spirocyclic and bicyclic ones are formed with additional neighboring chiral centers of flexible stereochemistry in addition to the quaternary center. This work represents rare gold‐catalyzed highly enantioselective cycloisomerization of 1,5‐enynes. Density functional theory (DFT) calculations support the chirality induction model and suggest that the rate acceleration enabled by the bifunctional ligand can be attributed to a facilitated protodeauration step at the end of the catalysis. [ABSTRACT FROM AUTHOR]

The activation of various homopropargylic pyridines by cis‐[RuII/OsII(dppm)2Cl2] (dppm=1,1‐bis(diphenylphosphino)methane) has previously been shown to generate a diverse array of metallacycles and metalated heterocyclic complexes. However, a minor structural modification of introducing a halide onto the pyridyl group of the alkyne substrate resulted in the formation of unprecedented Ru(II)/Os(II)−haloquinolizine complexes. These complexes display (1) κ2(X,C)‐haloquinolizine chelates arising from the cycloisomerization of HC≡CC(OH)(CH2(6‐X‐2‐py))(Ph) on [RuII/OsII(dppm)2]2+ moieties via a vinylidene pathway, (2) five‐membered Ru/Os−X−C−N−C rings (X=F, Cl, Br) ortho‐ and peri‐fused to quinolizinium skeletons, and (3) uncommon M−X−R bonding interactions that are atypical in coordination complexes. Despite being divalent and integrated into a five‐membered Ru−X−C−N−C ring system, the X atoms in the Ru(II) complexes are susceptible to substitution by O in the presence of −OH, resulting in the formation of quinolizinium‐fused ruthenaoxazole complexes. Overall, this work highlights the importance of considering metal−halocarbon bonding interactions in catalytic or coordination designs. [ABSTRACT FROM AUTHOR]

A strategy to access fluorinated spiroindolenines has been developed, involving a selective functionalization of indoles with fluorinated moieties and subsequent catalytic dearomatization. Trifluomethylthio (SCF3), diethyl phosphono(difluoromethyl)thio (SCF2P(O)(OEt)2) and (phenylsulfonyl)difluoromethyl (CF2SO2Ph) groups were embedded at the C2 position of indole derivatives substituted with alkynes, allenes, and allyl carbonate moieties at the C3 position. A gold‐catalyzed cycloisomerization gave access to five spiroindolenines, and an enantioselective palladium catalyzed cyclization provided 10 fluorinated spirocyclic products with up to 77% ee. [ABSTRACT FROM AUTHOR]

Studies on a cycloisomerization reaction of 2‐prenylated‐2H‐pyrans towards cis‐fused tetrahydro‐6H‐benzo[c]chromene systems (reduced cis‐THC analogues) are reported. The transformation is catalyzed by iron chloride and proceeds with the formation of two new bonds and two stereocenters diastereoselectively. The same catalyst also promotes the formation of these products via a one‐pot tandem Knoevenagel condensation of 1,3‐cyclohexanediones and citral or farnesal aldehydes, followed by cycloisomerization establishing a direct assembly of this important scaffold. [ABSTRACT FROM AUTHOR]

A concise and efficient synthesis of the γ‐lactam‐fused azaphenanthrene alkaloid eupolauramine has been achieved. The key feature of the synthesis involves Au(I)‐catalyzed cycloisomerization of N‐naphthyl aminobutynamide intermediate and subsequent intramolecular Ullmann‐type coupling reaction. This study clearly demonstrated the usefulness of coinage metal‐catalyzed cycloisomerization strategy in the construction of architecturally sophisticated pyridine‐fused heterocyclic scaffolds. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed cycloisomerization of carbamimidothioates with the formation of a quaternary carbon and a sulfide is described. The use of (IPr)Pd(allyl)Cl (CX21), K3 PO4 , and Me-C(OTBS)=NTBS in refluxing xylenes was optimal, and the methoxycarbonyl group was the most suitable substituent for the nitrogen atom of the carbamimidothioate. Phenyl and alkyl groups can be used as tethers for carbamimidothioates, and alkyl and aryl carbamimidothioates can undergo Pd-catalyzed cycloisomerization in high yields. [ABSTRACT FROM AUTHOR]

Pyrroles and indoles bearing N‐allenyl tethers participate in a variety of iridium‐catalyzed cycloisomerization processes initiated by a C−H activation step, to deliver a diversity of synthetically relevant azaheterocyclic products. By appropriate selection of the ancillary ligand and the substitution pattern of the allene, the reactions can diverge from simple intramolecular hydrocarbonations to tandem processes involving intriguing mechanistic issues. Accordingly, a wide range of heterocyclic structures ranging from dihydro‐indolizines and pyridoindoles to tetrahydroindolizines, as well as cyclopropane‐fused tetrahydroindolizines can be obtained. Moreover, by using chiral ligands, these cascade processes can be carried out in an enantioselective manner. DFT studies provide insights into the underlying mechanisms and justify the observed chemo‐ regio‐ and stereoselectivities. [ABSTRACT FROM AUTHOR]

The regioselective synthesis of 1‐alkyl‐5‐arylpyrazoles, which are potential drug candidates, has been difficult to achieve thus far. In this study, we developed an auto‐tandem Pd‐catalyzed C−C bond cleavage/Heck arylation of N‐cyclopropylhydrazones followed by cycloisomerization to afford diverse 1‐alkyl‐5‐arylpyrazoles. This step‐economical synthesis involves the cleavage of two C−H bonds and one C−C bond as well as the incorporation of directing groups. The identification of the reaction intermediates indicated an auto‐tandem catalytic pathway. The further transformation of products to 1,4,5‐substituted pyrazole and functional group transformations were carried out. [ABSTRACT FROM AUTHOR]

Recent advances in the isolation of tamed bismuth radicals and the selective in situ generation of highly reactive bismuth radicals have set the stage for the application of these compounds in organic and organometallic synthesis and catalysis. Here, we provide a summary of the methodological approaches in the field. Important strategies for accessing bismuth radical species are presented and key examples of their applications in organic synthesis are outlined, highlighting how this class of compounds has emerged as new set of valuable tools for synthetic practitioners. 1 Introduction 2 Generation of Bismuth Radical Species by Homolysis 2.1 Temperature-Induced Homolysis 2.2 Light-Induced Homolysis 2.3 Light-/Temperature-Induced Bi–C Homolysis of Polar Oxidative Addition Complexes 3 Applications of Bismuth-Centered Radical Species in Organic Synthesis 3.1 Bismuth-Catalyzed Cycloisomerization of Iodo Olefins 3.2 Controlled Radical Polymerization Reactions 3.3 Bismuth-Promoted Pn–Pn and C–S Coupling 3.4 Bismuth-Catalyzed Dehydrocoupling of Silanes with TEMPO 3.5 Bismuth-Catalyzed C–N Coupling with Redox-Active Electrophiles 3.6 Bismuth-Catalyzed Giese-Type Coupling Reactions 3.7 Oxidative Addition of Aryl Electrophiles to Photoactive Bismuthinidenes 4 Conclusions [ABSTRACT FROM AUTHOR]

The supported Ni-P catalysts (marked as s-Ni-P/Hβ(3) and s-Ni-P/Ce-β(3)) were prepared by an incipient wetness step-impregnation method, and characterized by XRD, N2 physisorption, TEM, XPS, and NH3-TPD. The catalytic hydrodeoxygenation (HDO) performance was assessed using phenol in water (5.0 wt%) or in decalin (1.0 wt%) as the feed. After the introduction of Ce, the conversion of phenol increased due to the high dispersity of the active site. However, compared to s-Ni-P/Hβ(3), the amount of total and strong acid sites of s-Ni-P/Ce-β(3) decreased, restraining the cycloisomerization of cyclohexane to form methyl-cyclopentane. Moreover, the kinetics of the APHDO and OPHDO of phenol catalyzed by s-Ni-P/Hβ(3) and s-Ni-P/Ce-β(3) were investigated. [ABSTRACT FROM AUTHOR]

Carbene–metal–amide (CMA) complexes of gold, silver, and copper have been studied extensively for their photochemical/photocatalytic properties and as potential (pre-)catalysts in organic synthesis. Herein, the design, synthesis, and characterization of five bench-stable Au-, Ag-, and Cu-NHC complexes bearing the benzotriazolyl anion as an amide donor, are reported. All complexes are synthesized in a facile and straightforward manner, using mild conditions. The catalytic activity of the Ag and Cu complexes was studied in propargylamide cycloisomerization and carbonyl hydrosilylation reactions. Both CMA-catalyzed transformations proceed under mild conditions and are highly efficient for a range of propargylamides and carbonyl compounds, respectively, affording the desired corresponding products in good to excellent yields. [ABSTRACT FROM AUTHOR]

The cascade reaction of ynamides with propargyl thiols by Au(I) catalysis involving regioselective hydrothiolation, thio‐Claisen rearrangement, and cycloisomerization to generate 2‐aminothiophenes in a one‐pot manner is described. In this reaction, the selection of reaction temperature is crucial, with the initial step, namely hydrothiolation, conducted at a low temperature (40 °C), followed by the subsequent reaction requiring an increase in temperature (>110 °C). Furthermore, it was revealed that multi‐substituted anilines could be synthesized from the resulting 2‐aminothiophenes. [ABSTRACT FROM AUTHOR]

Alkyne cycloisomerization of 2,7,10,15-tetra(ortho-alkynylphenyl)benzo[g,p]chrysene containing bulky 4-alkoxy-2,6-dimethylphenyl groups at the alkyne terminals selectively proceeded at the sterically crowded bay-region. The obtained double helicene adopts a distorted structure with a high racemization barrier due to the intramolecular steric repulsion. [ABSTRACT FROM AUTHOR]

The cascade functionalizations of alkynes have provided many elegant methods for the synthesis of useful scaffolds. Amongst these functionalizations, the ones comprising C−C and C−O bond formation have been utilized extensively due to the abundant presence of oxygenated motifs in various bio‐active natural as well as unnatural products. Transition‐metal catalysis is a mainstay for these tandem functionalizations as they are very efficient. However, their utilization does typically involve stoichiometric additives like other metal salts and/or Lewis acids/Brønsted acids (LA/BA). Thus, approaches that rely solely on using LA/BA, make these vital transformations not only eco‐friendly and atom economical but also cost beneficial are fast emerging as complementary alternatives. The present review addresses the gap in the literature by summarizing recent developments in LA/BA mediated 1,1/1,2‐carboxygenation and carboalkoxylation of alkynes for the synthesis of oxa‐cycles. The reaction mechanisms are particularly emphasized to bring out understanding needed from the point of future developments in this domain. [ABSTRACT FROM AUTHOR]

Germacranolides, secondary metabolites produced by plants, have garnered academic and industrial interest due to their diverse and complex topology as well as a wide array of pharmacological activities. Molephantin, a highly oxygenated germacranolide isolated from medicinal plants, Elephantopus mollis and Elephantopus tomentosus, has exhibited antitumor, inflammatory, and leishmanicidal activities. Its chemical structure is based on a highly strained ten‐membered macrocyclic backbone with an (E,Z)‐dienone moiety, which is fused with an α‐methylene‐γ‐butyrolactone and adorned with four successive stereogenic centers. Herein, we report the first synthesis of molephantin in 12 steps starting from readily available building blocks. The synthesis features the highly diastereoselective intermolecular Barbier allylation of the β,γ‐unsaturated aldehyde with optically active 3‐bromomethyl‐5H‐furan‐2‐one intermediate and ensuing Nozaki–Hiyama–Kishi (NHK) macrocyclization for the construction of the highly oxygenated ten‐membered macrocyclic framework. This synthetic route enabled access to another germacranolide congener, tomenphantopin F. Furthermore, cycloisomerization of molephantin into 2‐deethoxy‐2β‐hydroxyphantomolin could be facilitated by irradiation with ultraviolet A light (λmax=370 nm), which opened a versatile and concise access to the related furanogermacranolides such as EM‐2, phantomolin, 2‐O‐demethyltomenphantopin C, and tomenphantopin C. [ABSTRACT FROM AUTHOR]

We report a general, intramolecular cycloisomerization of unactivated olefins with pendant nucleophiles. The reaction proceeds under mild conditions and tolerates ethers, esters, protected amines, acetals, pyrazoles, carbamates, and arenes. It is amenable to N‐, O‐, as well as C‐nucleophiles, yielding a number of different heterocycles including, but not limited to, pyrrolidines, piperidines, oxazolidinones, and lactones. Use of both a benzothiazinoquinoxaline as organophotocatalyst and a Co‐salen catalyst obviates the need for stoichiometric oxidant or reductant. We showcase the utility of the protocol in late‐stage drug diversification and synthesis of several small natural products. [ABSTRACT FROM AUTHOR]

Ullazines and their π-expanded derivatives have gained much attention as active components in various applications, such as in organic photovoltaic cells or as photosensitizers for CO2 photoreduction. Here, we report the divergent synthesis of functionalized diazaullazines by means of two different domino-reactions consisting of either a Povarov/cycloisomerization or alkyne–carbonyl metathesis/cycloisomerization protocol. The corresponding quinolino-diazaullazine and benzoyl-diazaullazine derivatives were obtained in moderate to good yields. Their optical and electronic properties were studied and compared to related, literature-known compounds to obtain insights into the impact of nitrogen doping and π-expansion. [ABSTRACT FROM AUTHOR]

We report an efficient iron-catalyzed cycloaddition procedure leading to the construction of (hetero)aromatic rings by alkyne [2+2+2] cycloisomerization. This method relies on the use of an air-stable (N,N)Fe(II) precursor easily prepared from a commercially available ligand derived from 1,10-phenanthroline, reduced in situ into a catalytically active non-innocent (N,N *-)2Fe(II) species. This system displays a large scope application, operates under mild conditions and at low catalytic charges (25 cycloadducts formed, up to 1.5 mol% catalyst). Moreover, this method also enables access to 29 cycloadducts by crosscycloisomerization between 1,6- or 1,7-diynes and alkynes in near-equimolar conditions. 1,3,5-Triazines can also be prepared with this procedure starting from the corresponding cyanamides. Scale-up reactions and post-functionalization of several cycloadducts also show that this [2+2+2] cycloaddition can be used in multistep sequences. [ABSTRACT FROM AUTHOR]

We identify the dominant structures of the intermediates of gold(I)‐catalyzed cyclizations of 1,5‐enynes and 1,5‐allenenes through computational analysis as gold(I) cyclopropylcarbenes, endocyclic vinylgold complexes and previously unreported non‐classical carbocationic minima. In contrast to 1,6‐enynes, the exocyclic carbocations are found to be less stable. Cyclopropylcarbene structures are consistently favoured as the most stable intermediates for all studied substitution patterns. We validate the computational methods used by using DLPNO‐CCSD(T) energies as a benchmark, indicating that the B3LYP‐D3 and M06‐D3 functionals are most accurate for energy determination, while NPA charges are mostly insensitive to functional. The evolution of a 1,6‐enyne in a single‐cleavage or double‐cleavage rearrangement is attributed to the barrierless evolution of a common cyclopropyl–gold(I) carbocation non‐stationary geometry. Our findings provide insights into reaction pathways and substrate dependence of the cycloisomerization processes. [ABSTRACT FROM AUTHOR]

Two Zn(II) clusters were synthesized by the reaction of Zn(OAc)2·2H2O and 1,2‐bis(2‐hydroxy‐3‐methoxybenzylidene)hydrazine as a N2O4‐donor Schiff base ligand in 1:3 molar ratio. The reaction in methanol gave yellow‐brown needle crystals, while block yellow crystals were achieved in a mixture of methanol:water (50:50 v/v). Investigation of the crystals by single crystal X‐ray analysis showed that solvent has considerable effect on the structure and composition of the products. In methanol, two independent pentanuclear Zn(II) clusters with the same general formula of [Zn5(L)2(μ‐OAc)4(OAc)2(CH3OH)2] but different coordination environments around Zn(II) cores, and bridging mode of the acetate ligands are present in the unit cell. In a mixture of methanol:water, a pentanuclear cluster and a 1D coordination polymer with pentanuclear repetitive unit are simultaneously present in the crystal structure. These compounds were further characterized by spectroscopic techniques, and they were used as catalysts for intramolecular cycloisomerization of 1,4‐diphenylbut‐3‐yn‐1‐one. The results indicated that these Zn(II) clusters can efficiently produce 2,5‐diphenylfuran through catalytic cycloisomerization reaction. [ABSTRACT FROM AUTHOR]

Dinuclear bisNHC (bis(N‐heterocyclic carbene)) gold(I) complexes 3 a and 4 a of general formula [Au2Br2(bisNHC)] were tested as catalysts in the cycloisomerization of N‐(prop‐2‐yn‐1‐yl)benzamide and in the hydromethoxylation of 3‐hexyne in the presence of silver(I) activators bearing different counteranions. The catalytic performance of mononuclear NHC complexes (1 a, 2 a) in the same reactions was also studied. The results highlighted the fundamental role of both NHC ligand and counterion in the catalytic cycles and activation process: dinuclear catalysts exhibit higher initial activity even under milder conditions but suffer in terms of stability with respect to mono NHCs. Furthermore, a new dinuclear bisNHC gold(I) complex 4 b of general formula [Au2(OTs)2(bisNHC)] (OTs=p‐toluenesulfonate) was successfully synthesized and characterized by means of NMR and ESI‐MS analyses. [ABSTRACT FROM AUTHOR]

We report herein an unprecedented hypervalent iodine(III)‐catalysis using the activated sulfoxide. Since the present catalytic systems promote the dehydrogenative cycloisomerization‐arylation reaction of 2‐propargyl 1,3‐dicarbonyl compounds with aromatics, this report also provides one of the few methods for iodine(III)‐catalyzed intermolecular carbon‐carbon bond formation of aromatics. [ABSTRACT FROM AUTHOR]

Tandem cycloisomerization reactions of functionalized 1,6‐enynes under indium(III) catalysis are described. This atom‐economic transformation proceeds smoothly with 5‐exo‐dig regioselectivity using commercial In(III) halides and 1,6‐enynes furnished with alcohol, carboxylic acid or amine functional groups to give bicyclic structures in good yields and diastereoselectivities. The reaction with enynals involves a three–step mechanism to give an oxatricycle and a conjugated 1,3‐diene. In the absence of the internal nucleophile the enyne cycloisomerization evolves through a skeletal rearrangement or a cyclopropanation reaction after the regioselective 5‐exo‐dig cyclization. The 1,6‐enyne cycloisomerization is stereospecific and the stereoselectivity appears to be independent of the internal nucleophile. Experimental data support a common reaction mechanism involving an initial alkyne electrophilic π‐coordination of In(III) followed by Markovnikov electrophilic alkene addition and ring‐closure by nucleophilic attack. DFT studies hold up a stepwise mechanism involving the formation of a chiral non‐classical carbocation intermediate that determines the diastereoselectivity of this tandem cycloisomerization reaction. [ABSTRACT FROM AUTHOR]

In this study we present a method for functionalizing C60 through a Rh‐catalyzed cyclization reaction with 1,6‐enynes, resulting in the formation of a fused bicyclic structure. Additionally, fullerene derivatives are further functionalized through regioselective photooxygenation reactions. Our DFT calculations reveal two distinct reaction pathways: one involving rhodium‐catalyzed cycloisomerization of the enyne followed by Diels‐Alder with C60, and the other featuring a rhodium‐catalyzed [2+2+2] cycloaddition of enyne and C60 followed by isomerization. Surprisingly, both pathways exhibit nearly identical energy barriers. However, experimental tests indicate that the predominant pathway varies depending on the substitution motifs of the substrates. [ABSTRACT FROM AUTHOR]

We report the Ni‐catalyzed cycloisomerization of 1,5‐allenynes. Substrates containing terminal alkynes afford cyclopentene derivatives, whereas internal alkynes lead to the formation of two consecutive C−C bonds to give fused 5–5 bicyclic compounds. The reaction shows a wide scope. Experimental and computational mechanistic studies suggest a Ni(0)−Ni(II) catalytic cycle. The reaction starts with an oxidative cyclometallation followed by a β‐hydrogen elimination. The trans arrangement of alkenyl and hydride ligands is key to allow formation of the second carbocycle. [ABSTRACT FROM AUTHOR]

(Difluoromethylated cyclopropane represents an important motif, which is widely found in bioactive and functional molecules. Despite significant progress in modern chemistry, the atom‐economic and enantioselective synthesis of difluoromethylated cyclopropanes is still challenging. Herein, an Rh2(II)‐catalyzed asymmetric enyne cycloisomerization is described to construct chiral difluoromethylated cyclopropane derivatives with up to 99% yield and 99% ee in low catalyst loading (0.2 mol%), which can be easily transformed into highly functionalized difluoromethylated cyclopropanes with vicinal all‐carbon quaternary stereocenters by ozonolysis. Mechanistic studies and the crystal structures of alkyne‐dirhodium complexes reveal that the cooperative weak hydrogen bondings between the substrates and the dirhodium catalyst may play key roles in this reaction.) [ABSTRACT FROM AUTHOR]

Gold‐catalyzed cycloisomerization reaction of 1‐bromoalkynes allowed for the preparation of a variety of 1‐bromocyclopentene derivatives. These have been used as substrates in a 3‐step synthetic sequence comprising a cross‐coupling reaction, followed by ozonolysis, and final condensation towards the corresponding 2,5‐disubstituted pyridine. In addition, bicyclic fused pyridines are achieved, including the first total synthesis of the natural product Sinensine B. [ABSTRACT FROM AUTHOR]

The total synthesis of Laetevirenol A, a natural product with antioxidant activity, has been achieved. A gold‐catalyzed cycloisomerization of an o‐alkenyl‐o'‐alkynylbiphenyl has been used as the key step for the construction of the phenanthrene moiety present in Laetevirenol A. Several studies in model substrates have been carried out to unveil the effect of substituents in different locations in the outcome of this cyclization, which allowed the design of an appropriate precursor for the fundamental gold‐catalyzed cycloisomerization. The suitably functionalized phenanthrene intermediate obtained in this key step could be further transformed into Laetevirenol A via a Friedel‐Crafts cyclization, which also turned out to be dependent on the nature of the substituents. Finally, Laetevirenol A was obtained in 10 steps from commercially available substrates, with a 20% global yield. [ABSTRACT FROM AUTHOR]

The treatment of N-tosylpropargyl amines 1 with 1,3-dicarbonyl compounds 2 in the presence of AuBr3 (5 mol%) and AgOTf (15 mol%) afforded poly-substituted furans 3 in good-to-high yields via the gold-catalyzed cleavage of the sp3 carbon–nitrogen bond. [ABSTRACT FROM AUTHOR]

The incorporation of heteroatoms into polycyclic aromatic hydrocarbons (PAHs) has been recognized as valuable tool to alter their inherent optical and electrochemical properties and are thought as promising next‐generation semiconductor materials. We herein report the synthesis of diindenopyrene, a fragment of C70 and two of its nitrogen‐doped aza‐analogs. The developed synthetic procedure is based on Brønsted‐acid‐mediated cycloisomerization followed by Pd‐catalyzed C−H‐activation as key‐steps. The impact of N‐doping on the optical and electrochemical properties has been studied and the experimental results are supported by DFT calculations. [ABSTRACT FROM AUTHOR]

While still rare, cationic ligands offer much promise as tunable electron‐withdrawing ligands for π‐acid catalysis. Recently, we introduced pincer‐type sulfonium cations into the list of available strongly π‐acidic ancillary ligands. However, the M−S bond in sulfonium complexes of these ligands was found highly labile, precluding their catalytic applications. Herein we demonstrate that this obstacle can be overcome by increasing the rigidity of the sulfonium pincer scaffold. X‐ray analyses confirm that despite bearing a formal positive charge, the sulfur atom of this newly designed sulfonium ligand maintains its coordination to the Pt(II)‐center, while DFT calculations indicate that by doing so it strongly enhances the electrophilic character of the metal. Kinetic studies carried out on three model cycloisomerization reactions prove that such a tris‐cationic sulfonium‐Pt(II) complex is highly reactive, compared to its thioether‐based analogue. This proof‐of‐concept study presents the first example of employing sulfonium‐based ligands in homogeneous catalysis. [ABSTRACT FROM AUTHOR]

An efficient synthetic route to access highly substituted pyrrolo[1,2‐a]quinoline‐3,5‐diones in which the core is formed by fusion of quinolone and pyrrolone moieties is discussed. The method involves Ag(I) catalyzed cyclization of 4‐Hydroxyquinolinyl‐2‐ynones which in turn may be accessed from kynurenic acid derivatives through Weinreb amide intermediate, followed by alkyne addition. Studies involving substrates with different substitution pattern revealed that factors increasing the nucleophilicity of quinoline nitrogen or Lewis acid‐coordination of the ynone unit gives high yields in short reaction times. It was possible to execute tandem cyclization‐arylation sequence by using Pd(II) generated by oxidative addition of Pd(0) with aryl iodide as the electrophilic species to get substitution pattern as seen in Discoipyrrole A. [ABSTRACT FROM AUTHOR]

The development of functionally distinct catalysts for enantioselective synthesis is a prominent yet challenging goal of synthetic chemistry. In this work, we report a family of chiral N-heterocyclic carbene (NHC)-ligated boryl radicals as catalysts that enable catalytic asymmetric radical cycloisomerization reactions. The radical catalysts can be generated from easily prepared NHC-borane complexes, and the broad availability of the chiral NHC component provides substantial benefits for stereochemical control. Mechanistic studies support a catalytic cycle comprising a sequence of boryl radical addition, hydrogen atom transfer, cyclization, and elimination of the boryl radical catalyst, wherein the chiral NHC subunit determines the enantioselectivity of the radical cyclization. This catalysis allows asymmetric construction of valuable chiral heterocyclic products from simple starting materials. [ABSTRACT FROM AUTHOR]

A ligand‐free palladium‐promoted [1,8]‐sigmatropic hydrogen shift reaction of 1,6‐allene‐ene was reported, which went through an intramolecular Ene cyclization using base as a hydrogen shuttle. Notably, the transformation could realize the HAT process via the hydrogen shift from an old allylic C−H bond to a new one in the presence of oxidant, between which have low BDE distinction. The mild reaction conditions, high atom economy and good chemo/regioselectivity proved the valuable of this strategy. The control experiments using acetone‐D6/D2O proved that neither solvent nor water were involved in the cycloisomerization process and HAT process was more convincible. The target products could achieve more valuable molecules via convenient synthetic transformation. [ABSTRACT FROM AUTHOR]

We report the rhodium(I) complex [Rh(CNC−NDI)(CO)]+, in which CNC−NDI refers to a pincer‐CNC ligand decorated with a naphthalenediimide moiety. Due to the presence of the planar CNC ligand and the naphthalenediimide moiety, the electronic nature of the complex can be modulated by means of supramolecular and redox stimuli, respectively. The metal complex shows a strong π–π‐stacking interaction with coronene. This interaction has an impact on the electron‐richness of the metal, as demonstrated by the shifting of the ν(CO) stretching band to a lower frequency. The addition of tetrabutylammonium fluoride facilitates the sequential one‐ and two‐electron reduction of the NDI moiety of the ligand, thus resulting in a situation in which the ligand can increase its electron‐donor strength in two levels. The nature of the interaction with the fluoride anion was studied computationally. The catalytic activity of the [Rh(CNC−NDI)(CO)]+ complex was tested in the cycloisomerization of alkynoic acids, where it is observed that the activity of the catalyst can be modulated between four levels of activity, which correspond to i) the use of the unmodified catalyst, ii) catalyst+coronene, iii) catalyst+2 equivalents of fluoride, and iv) catalyst+5 equivalents of fluoride. [ABSTRACT FROM AUTHOR]

Over the last century, the fragrance industry had relied on the synthetic chemists for the development of new odors, but also for the replacement of some known materials due to allergy or toxicity. Transition metal‐catalyzed transformations have allowed atom economy and synthetic efficiency for several transformations and they caught the attention of fragrance industrials. The metal‐catalyzed cyclization reactions have been particularly successful toward the synthesis of key skeletons. This review highlights the developments of selected hedonic materials according to transition metal‐catalyzed according to cycloisomerization reactions and related rearrangements. [ABSTRACT FROM AUTHOR]

Altering the donor properties of phosphane ligands through substituent variation is an established tool in coordination chemistry and catalysis. This contribution describes the synthesis of two new hybrid donors (L) combining 1,3,5,7‐tetramethyl‐2,4,6‐trioxa‐8‐phosphaadamantane‐8‐yl (PCg) and nitrile donor groups at different molecular scaffolds, viz. ferrocene‐1,1′‐diyl (fc) and 1,2‐phenylene. These ligands were used to prepare dimeric Au(I) complexes [Au2(μ(P,N)‐L)2][SbF6]2, which were evaluated as silver‐free, preformed catalysts in Au‐mediated cycloisomerization of (Z)‐3‐methylpent‐2‐en‐4‐yn‐1‐ol to 2,3‐dimethylfuran. The catalyst featuring the ferrocene‐based ligand, viz. [Au2(μ(P,N)‐CgPfcCN)2][SbF6]2, showed the best catalytic performance at low catalyst loading (0.5 or 0.15 mol.%), which exceeded that of its diphenylphosphanyl analog [Au2(μ(P,N)‐Ph2PfcCN)2][SbF6]2 studied earlier and the prototypical Au(I) precatalyst [Au(PPh3)(MeCN)][SbF6]. [ABSTRACT FROM AUTHOR]

Spirocyclic frameworks could enhance the drug‐like properties of planar bioactive molecules by increasing their three‐dimensionality, making the development of synthetic methodology and bioactivity assays for spiro compounds highly attractive. This work reported the silver‐catalyzed tandem cycloisomerization/Povarov reaction between β‐alkynyl ketones and hexahydro‐1,3,5‐triazines, access to spiro[isochromene‐1,4'‐quinoline]. This synthetic protocol was characterized by remarkable efficiency, low catalyst‐loading and high diastereoselectivity. Moreover, the spirocyclic quinolines exhibited good cytotoxicity in U937 cells by activating the Notch‐signaling pathway exclusively. [ABSTRACT FROM AUTHOR]

Chiral biscyclopropanes are an important skeleton in many bioactive molecules. However, there are few routes to synthesize these molecules with high stereoselectivity due to the nature of multiple stereocenters. Herein, we report the first example of Rh2(II)‐catalyzed enantioselective synthesis of bicyclopropanes with alkynes as dicarbene equivalents. The bicyclopropanes with 4–5 vicinal stereocenters and 2–3 all‐carbon quaternary centers were constructed in excellent stereoselectivity. This protocol features high efficiency and excellent functional group tolerance. Moreover, the protocol was also extended to the cascaded cyclopropanation/cyclopropenation with excellent stereoselectivities. In these processes, both sp‐carbons of alkyne were converted into stereogenic sp3‐carbons. Experimental and density functional theory (DFT) calculations revealed that the cooperative weak hydrogen bonds between the substrates and the dirhodium catalyst may play key roles in this reaction. [ABSTRACT FROM AUTHOR]

Enyne diesters derived from biaryls and related substrates undergo intramolecular [2+2]‐cycloaddition and concomitant cyclo‐reversion when treated with 10 mol% In(OTf)3 in 1,2‐dichloroethane. This enyne metathesis type cycloisomerization reaction enables the synthesis of phenanthrene, benzophenanthrene, benzotetraphene and other polycyclic (hetero)aromatic compounds bearing a synthetically useful diethyl β‐(hetero)arylidene malonate moiety in a step‐ and atom‐economic manner. In(OTf)3‐catalyzed two independent intramolecular cycloisomerization on substrates 5 a and 5 b provides direct access to benzotetraphenes 6 a and 6 b containing bis(diethyl β‐phenylmethylene malonate) moiety. Tetrasubstituted vinylidene malonate 4 a, substiututed by two different aromatic groups, is stereoselectively converted into E‐ and Z‐isomer of triaryl group containing all carbon tetrasubstituted olefins (8 a, 8 a′ and 8 b) via Pd‐catalyzed stereoselective decarboxylative arylation reaction. [ABSTRACT FROM AUTHOR]

In this study, we use density functional theory calculations to investigate the discrepancy between two experimental results of Au(I)‐catalyzed cycloisomerization reactions of alkynylhydroxyallyl tosylamide under similar reaction conditions, with the only variations being reaction temperature and time. The experimental results reported by Yeh and Chung groups, respectively, showed that 3‐acyl‐4‐alkenylpyrrolidines are produced dominantly at ambient temperature, while 4‐aza‐6‐oxatricyclo[3.3.0.02,8]octanes are produced in higher yield at elevated temperature. Using (Z)‐4‐([3‐phenylprop‐2‐yn‐1‐yl]amino)but‐2‐en‐1‐ol and [Au(PPh3)]+ as the model starting material and active catalyst species, respectively, we identified two major pathways leading to 4‐aza‐6‐oxatricyclo[3.3.0.02,8]octane (pathway I) and 3‐acyl‐4‐alkenylpyrrolidine (pathway II). The overall free energy barrier (ΔG‡max) and the energetic span (ΔG‡span) of each pathway were 38.3 and 48.4 kcal/mol for pathway I and 29.0 and 37.1 kcal/mol for pathway II. Our analysis shows that the disparate outcomes observed in the experiments by two separate groups mainly originate in the reaction kinetics, with both the overall activation barrier and energetic span being the important factor. [ABSTRACT FROM AUTHOR]

We herein report a nickel‐catalyzed migratory cycloisomerization of o‐alkynylanilides, giving 2,3‐disubstituted indoles in good yields. The cyclization proceeded via acyl transfer on the nitrogen atom of the substrate to C3‐position in the product, and an N‐heterocyclic carbene (NHC) ligand such as ICy or SICy was found to be suitable in this reaction. It was thought that the reaction proceeds via an aza‐nickelcyclepentene intermediate formed from alkyne and the C=O bond of the amide moiety in o‐alkynylanilides. [ABSTRACT FROM AUTHOR]

Selective functionalization of non‐activated C(sp3)−H bonds is a major challenge in chemistry, so functional groups are often used to enhance reactivity. Here, we present a gold(I)‐catalyzed C(sp3)−H activation of 1‐bromoalkynes without any sort of electronic, or conformational bias. The reaction proceeds regiospecifically and stereospecifically to the corresponding bromocyclopentene derivatives. The latter can be readily modified, comprising an excellent library of diverse 3D scaffolds for medicinal chemistry. In addition, a mechanistic study has shown that the reaction proceeds via a so far unknown mechanism: a concerted [1,5]‐H shift / C−C bond formation involving a gold‐stabilized vinylcation‐like transition state. [ABSTRACT FROM AUTHOR]

Merging the latest advances in the field of gold catalysis and the efficiency of hexafluoro‐2‐propanol (HFIP), a gold‐catalyzed orthogonal tandem reaction has been developed to access carbocyclic ketone on naphthalene substrates. The methodology involved a cycloisomerization/nucleophilic addition and a C→O rearrangement. The HFIP solvent most probably acted as a Lewis‐acid on isochromene derivatives, through hydrogen donor bond activity. A large range of acenaphthylene carbaldehyde has been engaged in this process coupling gold catalysis and Lewis‐acid behavior of HFIP leading to cyclic ketones with a yield ranging from 15 to 91% (27 compounds). The mechanism was investigated, and the reaction most presumably occurred via a classical cyclization process followed by a [Au]‐HFIP interaction for the final rearrangement. The interest of such transformation was demonstrated by performing it on a gram‐scale. Moreover, a post‐functionalization bromination was performed, as well as the isomerization of some functionalized ketones leading to full trans derivatives with a yield ranging from 78 to 90% yields. [ABSTRACT FROM AUTHOR]

As an ambident nucleophile, controlling the reaction selectivities of nitrogen and oxygen atoms in amide moiety is a challenging issue in organic synthesis. Herein, we present a chemodivergent cycloisomerization approach to construct isoquinolinone and iminoisocoumarin skeletons from o-alkenylbenzamide derivatives. The chemo-controllable strategy employed an exclusive 1,2-aryl migration/elimination cascade, enabled by different hypervalent iodine species generated in situ from the reaction of iodosobenzene (PhIO) with MeOH or 2,4,6-tris-isopropylbenzene sulfonic acid. DFT studies revealed that the nitrogen and oxygen atoms of the intermediates in the two reaction systems have different nucleophilicities and thus produce the selectivity of N or O-attack modes. Amide-bearing organic compounds are important building blocks in organic synthesis, however, the ambident reactivities of the nitrogen and oxygen atoms in the amide moiety requires catalysts and reagents that are able to control the reaction selectivity. Here, hypervalent iodine reagents are shown to mediate the intramolecular cycloisomerization of O-alkenylbenzamides to selectively generate isoquinolinone and iminoisocoumarin derivatives. [ABSTRACT FROM AUTHOR]