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Herein, for the first time, we disclose the gold‐catalyzed alkoxy‐carbonylation of aryl and vinyl iodides utilizing ligand‐enabled Au(I)/Au(III) redox catalysis. The present methodology is found to be general, efficient, employs mild reaction conditions and showcases a broad substrate scope even with structurally complex molecules. Density functional theory (DFT) calculations revealed mechanistic pathways distinct from those of conventional transition metal‐catalyzed carbonylation reactions. [ABSTRACT FROM AUTHOR]

Herein, for the first time, we disclose the gold‐catalyzed alkoxy‐carbonylation of aryl and vinyl iodides utilizing ligand‐enabled Au(I)/Au(III) redox catalysis. The present methodology is found to be general, efficient, employs mild reaction conditions and showcases a broad substrate scope even with structurally complex molecules. Density functional theory (DFT) calculations revealed mechanistic pathways distinct from those of conventional transition metal‐catalyzed carbonylation reactions. [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]

An achiral Cp*Co(III)‐catalyzed enantioselective C−H activation/annulation of chiral sulfoximine‐enabled thioamides with ynamides is presented herein. This method successfully synthesizes axially chiral five‐membered 2‐amidoindenones with good enantiocontrol. Interestingly, the annulation with chiral oxazolidone‐containing ynamides could provide a separable mixture of diastereomers (up to ~10 : 1 dr). Moreover, enantiopure sulfoximines could be recovered with ~99 % purity, making this method practical. DFT studies show valuable insight into the mechanism and origin of asymmetric induction. [ABSTRACT FROM AUTHOR]

Decomposition of aryl and unsubstituted diazo ester into Rh(II)‐carbenes by the [(IMes)Rh2(OAc)4] complex is shown to be slower than with Rh2(OAc)4. Diazo esters substituted by a second electron‐withdrawing group do not suffer nitrogen extrusion when exposed for several hours to this (NHC)Rh(II) complex at room temperature. This chemoselective decomposition of diazo esters depending on their substituent (Ar, H, EWG) can furthermore be achieved on a mixture of substrates. The catalytic activity of [(IMes)Rh2(OAc)4] towards electron‐poor diazo compounds is also restored by heating to reflux in chloroform, or after decomplexation of the NHC by addition of GaCl3. The [(IMes)Rh2(OAc)4] complex was then used to induce a fully selective reaction cascade from a mixture of two diazo esters. First, a donor/acceptor diazo compound was decomposed selectively at room temperature to give an intermolecular O−H insertion product without any decomposition of the electron poor diazo compound. Addition of GaGl3 then triggered nitrogen extrusion from the diazo malonate to give a 1,5‐C−H insertion product. This transformation, where decomposition of diazo compounds catalyzed by Rh(II) complexes can be externally controlled, represents the first example of assisted tandem catalysis with two metal carbene precursors. [ABSTRACT FROM AUTHOR]

A tandem three‐component C−H bond addition involving the activation of an inert C(sp3)−H bond is reported. The process enables the direct regioselective synthesis of 1,2‐difunctionalized arenes with the formation of C(sp3)− and C(sp2)−C(arene) bonds. 2‐Iodobenzoic acid derivatives behave as masked bifunctional reagent (BFR) and react with 2‐pyridyl‐methyl sulfoximine (MPyS) protected aliphatic acids bearing α,α‐disubstituted groups, and alkenes to produce β‐aryl‐δ‐alkenyl amide derivatives in a single operation. The transformation involves Pd(II)/Pd(IV) and Pd(II)/Pd(0) catalytic systems. Detailed mechanistic studies, including density functional theory (DFT) calculations, reveal the formation of large T‐shaped palladacycles and the onset of a 1,2‐palladium migration via decarboxylation. [ABSTRACT FROM AUTHOR]

A tandem three‐component C−H bond addition involving the activation of an inert C(sp3)−H bond is reported. The process enables the direct regioselective synthesis of 1,2‐difunctionalized arenes with the formation of C(sp3)− and C(sp2)−C(arene) bonds. 2‐Iodobenzoic acid derivatives behave as masked bifunctional reagent (BFR) and react with 2‐pyridyl‐methyl sulfoximine (MPyS) protected aliphatic acids bearing α,α‐disubstituted groups, and alkenes to produce β‐aryl‐δ‐alkenyl amide derivatives in a single operation. The transformation involves Pd(II)/Pd(IV) and Pd(II)/Pd(0) catalytic systems. Detailed mechanistic studies, including density functional theory (DFT) calculations, reveal the formation of large T‐shaped palladacycles and the onset of a 1,2‐palladium migration via decarboxylation. [ABSTRACT FROM AUTHOR]

The successful realization of gold‐catalyzed chain‐walking reactions, facilitated by ligand‐enabled Au(I)/Au(III) redox catalysis, has been reported for the first time. This breakthrough has led to the development of gold‐catalyzed annulation reaction of alkenes with iodoarenes by leveraging the interplay of chain‐walking and π‐activation reactivity mode. The reaction mechanism has been elucidated through comprehensive experimental and computational studies. [ABSTRACT FROM AUTHOR]

The successful realization of gold‐catalyzed chain‐walking reactions, facilitated by ligand‐enabled Au(I)/Au(III) redox catalysis, has been reported for the first time. This breakthrough has led to the development of gold‐catalyzed annulation reaction of alkenes with iodoarenes by leveraging the interplay of chain‐walking and π‐activation reactivity mode. The reaction mechanism has been elucidated through comprehensive experimental and computational studies. [ABSTRACT FROM AUTHOR]

In this study, we present a methodology for synthesizing aza‐heterocyclic compounds using N‐tosylhydrazones as key reagents. Our primary objective was to obtain six or seven‐membered ring heterocycles; however, we unexpectedly observed the formation of bi‐indole compounds in high yields. Furthermore, our synthetic pathway enables modifications at the C3 or C2 position of the indole, leading to the formation of the respective 3′‐phenyl‐2′‐biindole or carbazole derivatives. [ABSTRACT FROM AUTHOR]

We report a synthetic endeavor towards the highly strained pentacyclic caged framework of the mavacuran alkaloids which culminated with the concise total synthesis of C‐fluorocurine, C‐profluorocurine, C‐mavacurine, normavacurine, 16‐epi‐pleiocarpamine and taberdivarine H. We designed a strategy involving late‐stage construction of the D ring by Michael addition of a vinylic nucleophile to a 2‐indolyl acrylate moiety. While the intramolecular Michael addition did not succeed, we were able to perform a diastereoselective unusual intermolecular 1,4‐addition of a functionalized vinyl lithium reagent to a readily accessible Michael acceptor with the assistance of the piperidine nitrogen atom through the formation of a complex as suggested by DFT computations. Final cyclization was achieved by nucleophilic substitution to form an ammonium intermediate. The first total syntheses of C‐profluorocurine and C‐fluorocurine were finalized by the dihydroxylation of C‐mavacurine and a pinacol rearrangement, respectively. [ABSTRACT FROM AUTHOR]

We report a synthetic endeavor towards the highly strained pentacyclic caged framework of the mavacuran alkaloids which culminated with the concise total synthesis of C‐fluorocurine, C‐profluorocurine, C‐mavacurine, normavacurine, 16‐epi‐pleiocarpamine and taberdivarine H. We designed a strategy involving late‐stage construction of the D ring by Michael addition of a vinylic nucleophile to a 2‐indolyl acrylate moiety. While the intramolecular Michael addition did not succeed, we were able to perform a diastereoselective unusual intermolecular 1,4‐addition of a functionalized vinyl lithium reagent to a readily accessible Michael acceptor with the assistance of the piperidine nitrogen atom through the formation of a complex as suggested by DFT computations. Final cyclization was achieved by nucleophilic substitution to form an ammonium intermediate. The first total syntheses of C‐profluorocurine and C‐fluorocurine were finalized by the dihydroxylation of C‐mavacurine and a pinacol rearrangement, respectively. [ABSTRACT FROM AUTHOR]

Inflammation is a complex physiological process triggered in response to harmful stimuli1. It involves cells of the immune system capable of clearing sources of injury and damaged tissues. Excessive inflammation can occur as a result of infection and is a hallmark of several diseases2–4. The molecular bases underlying inflammatory responses are not fully understood. Here we show that the cell surface glycoprotein CD44, which marks the acquisition of distinct cell phenotypes in the context of development, immunity and cancer progression, mediates the uptake of metals including copper. We identify a pool of chemically reactive copper(ii) in mitochondria of inflammatory macrophages that catalyses NAD(H) redox cycling by activating hydrogen peroxide. Maintenance of NAD+ enables metabolic and epigenetic programming towards the inflammatory state. Targeting mitochondrial copper(ii) with supformin (LCC-12), a rationally designed dimer of metformin, induces a reduction of the NAD(H) pool, leading to metabolic and epigenetic states that oppose macrophage activation. LCC-12 interferes with cell plasticity in other settings and reduces inflammation in mouse models of bacterial and viral infections. Our work highlights the central role of copper as a regulator of cell plasticity and unveils a therapeutic strategy based on metabolic reprogramming and the control of epigenetic cell states.Cellular uptake of copper(ii) by CD44 has a key role in regulating cellular plasticity via copper(ii)-dependent downstream signalling events. [ABSTRACT FROM AUTHOR]

The first example of Pd(II)-catalyzed anomeric arylation of 3-aminosugars is reported by using an L,X-type transient directing group (TDG) approach combined with an external 2-pyridone ligand. The released free amine was in situ transformed into an azide function, which was then exploited in a CuAAC to increase the molecular complexity and prepare a variety of complex substituted C3-triazolo C-glycosides in good yields. [ABSTRACT FROM AUTHOR]

A series of enantioenriched substituted tetrahydropyrrolo[3,2‐c]azepine products possessing an axial chirality were synthesized in 63–99% yield through a gold(I)‐catalyzed hydroarylation. DFT calculations rationalized the reactivity observed for the formation of such complex molecular frameworks and guided our choice in the pyrrole N‐substituent to isolate configurationally stable compounds. [ABSTRACT FROM AUTHOR]

Herein, development and detailed investigation of a SN′‐type intramolecular aromatic substitution reaction involving α‐arylazaoxyallyl cation intermediate, is disclosed. The study showcased that while α‐aryl‐α‐chlorohydroxamate could be activated by a combination of base and 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) into the corresponding azaoxyallyl cations, it could further emerge into a π‐extended species involving the adjacent α‐aryl moiety, and this transition is contingent on electronic effects of the aromatic ring as well as on α‐substituents. An effective activation of the α‐aromatic ring could pave the path for intramolecular Ar(Csp2)‐N bond formation towards oxindoles. Control experiments and DFT calculations suggested that a non‐pericyclic nucleophilic amination pathway is most likely operative and precluded the possibility of concerted or electrophilic amination mechanism. HFIP as the reaction solvent plays pivotal roles in the transformation. [ABSTRACT FROM AUTHOR]

This work reports a mild and operationally accessible method for synthesizing 1,3‐diphenyl‐1H‐indene derivatives from N‐tosylhydrazones and bromobenzhydrols as readily available reactants. Moreover, the cyclization step does not require metal catalysis, the addition of an acid, or a very high temperature. We report a combined experimental and computational study on the mechanism of this cyclization. In addition, we demonstrate the utility of this methodology by synthesizing a large number of products, even on the gram‐scale, and by the obtention of new biologically relevant molecules. [ABSTRACT FROM AUTHOR]

The direct dearomative addition of arenes to the C3 position of unprotected indoles is reported under operationally simple conditions, using triflic acid at room temperature. The present regioselective hydroarylation is a straightforward manner to generate an electrophilic indole at the C3 position from unbiased indoles in sharp contrast to previous strategies. This atom‐economical method delivers biologically relevant 3‐arylindolines and 3,3‐spiroindolines in high yields and regioselectivities from both intra‐ and intermolecular processes. DFT computations suggest the stabilization of cationic or dicationic intermediates with H‐bonded (TfOH)n clusters. [ABSTRACT FROM AUTHOR]

The direct dearomative addition of arenes to the C3 position of unprotected indoles is reported under operationally simple conditions, using triflic acid at room temperature. The present regioselective hydroarylation is a straightforward manner to generate an electrophilic indole at the C3 position from unbiased indoles in sharp contrast to previous strategies. This atom‐economical method delivers biologically relevant 3‐arylindolines and 3,3‐spiroindolines in high yields and regioselectivities from both intra‐ and intermolecular processes. DFT computations suggest the stabilization of cationic or dicationic intermediates with H‐bonded (TfOH)n clusters. [ABSTRACT FROM AUTHOR]

The formation of a rare type of diphosphazenium cation is described. Its synthesis features a unique oxidative dealkylation of an iminophosphorane-phosphole by a silver(I) salt. DFT study of this compound reveals the low valent character of the N(I) center. [ABSTRACT FROM AUTHOR]

An overlooked pericyclic reaction between allyl alcohols and alkenes to form carbonyl compounds is analyzed. It combines the characteristic features of the Alder-ene reaction and of the oxy-Cope rearrangement. This oxy-ene reaction could be involved in biosynthetic pathways. [ABSTRACT FROM AUTHOR]

The palladium‐catalyzed silylcyanation of ynamides is described. This reaction is fully regioselective, delivering tetrasubstituted 2‐aminoacrylonitriles derivatives exclusively. Unexpectedly, the nature (aryl or alkyl) of the substituent located at the β‐position of the ynamide directly controls the stereoselectivity. The reaction tolerates a number of functional groups and can be considered as the first general access to fully substituted 2‐aminoacrylonitriles. Given the singular reactivity observed, a computational study was performed to shed light on the mechanism of this intriguing transformation. Relying on the specific reactivity of the newly installed vinylsilane functionality, the scope of 2‐aminoacrylonitriles has been enlarged by postfunctionalization. [ABSTRACT FROM AUTHOR]

The palladium‐catalyzed silylcyanation of ynamides is described. This reaction is fully regioselective, delivering tetrasubstituted 2‐aminoacrylonitriles derivatives exclusively. Unexpectedly, the nature (aryl or alkyl) of the substituent located at the β‐position of the ynamide directly controls the stereoselectivity. The reaction tolerates a number of functional groups and can be considered as the first general access to fully substituted 2‐aminoacrylonitriles. Given the singular reactivity observed, a computational study was performed to shed light on the mechanism of this intriguing transformation. Relying on the specific reactivity of the newly installed vinylsilane functionality, the scope of 2‐aminoacrylonitriles has been enlarged by postfunctionalization. [ABSTRACT FROM AUTHOR]

π-Extended tetrasubstituted olefins are widely found motifs in natural products, leading drugs, and agrochemicals. Thus, development of modular strategies for the synthesis of complex all-carbon-substituted olefins always draws attention. The difunctionalization of unsymmetrical alkynes is an attractive approach but it has remained faced with regioselectivity issues. Here we report the discovery of a regio- and stereoselective syn-1,2-dicarbofunctionalization of unsymmetrical internal alkynes. A cationic Pd-catalyzed three-component coupling of aryl diazonium salts, aryl boronic acids (or olefins) and yne-acetates enables access to all-carbon substituted unsymmetrical olefins. The transformation features broad scope with labile functional group tolerance, building broad chemical space of structural diversity (94 molecules). The value of this synthetic method is demonstrated by the direct transformation of natural products and drug candidates containing yne-acetates, to enable highly substituted structurally complex allyl acetate analogues of biologically important compounds. Synthetic versatility of the carboxylate bearing highly substituted olefins is also presented. The reaction outcome is attributed to the in situ formation of stabilized cationic aryl-Pd species, which regulates regioselective aryl-palladation of unsymmetrical yne-acetates. Control experiments reveal the synergy between the carboxylate protecting group and the cationic Pd-intermediate in the regioselectivity and reaction productivity; density functional theory (DFT) studies rationalize the selectivity of the reaction. Methods to regioselectively difunctionalize unsymmetrical alkynes with two diverse carbon-based substituents are rare. Here the authors show a method to add two C(sp2)-based units in a syn, regioselective fashion across a triple bond, via palladium catalysis without an added ligand. [ABSTRACT FROM AUTHOR]

Cycloisomerization of N-tethered indole- and dihydropyrrole-arylpropargyl substrates into complex polycycles was investigated by using gold(I) catalysis. Enantioselectivities up to 93% ee were obtained in the asymmetric version of this process. DFT calculations rationalized the reactivity observed for the formation of such complex molecular frameworks. [ABSTRACT FROM AUTHOR]

Herein we report for the first time that the thiosugar moiety can be used both as a directing group enabling the regioselective activation of a C–H bond of biaryl scaffolds and as a chiral source inducing axial chirality. Our approach enables the easy generation of complex thioglycoside atropoisomers, thus paving the way to new products of potential biological interest. [ABSTRACT FROM AUTHOR]

The development of a stereoselective aza‐Piancatelli reaction to access 4‐aminocyclopentenones is reported. This transformation relies on the use of chiral o‐sulfinyl anilines as chiral inductors to afford the targeted products in good to excellent yields. Remarkably, the high value‐added cyclopentenones could be obtained in drs up to >95:5, depending upon the furan substitution pattern. [ABSTRACT FROM AUTHOR]

Reported herein is a syn-thioallylation of ynamides incorporating a sulfide moiety at the α-position and an allyl group at the β-position of the ynamide. The transformation is successful under ytterbium(III)-catalysis, providing access to highly substituted thioamino-skipped-dienes with broad substrate scope. Thus, tetrasubstituted olefins (with four different functional groups: amide, phenyl, thioaryl/alkyl, and allyl on the carbon centers) are made in a single step from readily accessible ynamides, preserving complete atom economy. The reaction can be extended to the synthesis of selenoamino dienes by ynamide syn-selenoallylation. DFT studies and control experiments provide insight into the reaction mechanism. [ABSTRACT FROM AUTHOR]

Tertiary amines bearing a benzyl‐type group (CH2Ar) undergo Au(I)‐catalyzed intramolecular addition to allenes. A formal 1,3‐transfer of the CH2Ar group takes place during the cyclization. As demonstrated by both experimental and DFT studies, these unprecedented intramolecular carboaminations involve two consecutive [3,3] rearrangements via a dearomatized intermediate. Because of the poor stability of the enamine products, protocols were developed to convert them in situ to more stable polycyclic chiral compounds. [ABSTRACT FROM AUTHOR]

Upon Brønsted base organocatalysis, ketone‐derived alkylidene Meldrum's acids proved to be competent vinylogous platforms able to undergo a formal (4+2) cycloaddition reaction with dihydro‐2,3‐furandione, providing an unprecedented route to 3,6‐dihydropyran‐2‐ones as spiro[4.5]decane derivatives with up to 98 % ee thanks to the commercially available Takemoto catalyst. Preliminary investigation showed that this reaction could be extended to other activated ketones, establishing these alkylidene Meldrum's acids as a novel C4‐synthon in the vinylogous series. [ABSTRACT FROM AUTHOR]

Upon Brønsted base organocatalysis, ketone‐derived alkylidene Meldrum's acids proved to be competent vinylogous platforms able to undergo a formal (4+2) cycloaddition reaction with dihydro‐2,3‐furandione, providing an unprecedented route to 3,6‐dihydropyran‐2‐ones as spiro[4.5]decane derivatives with up to 98 % ee thanks to the commercially available Takemoto catalyst. Preliminary investigation showed that this reaction could be extended to other activated ketones, establishing these alkylidene Meldrum's acids as a novel C4‐synthon in the vinylogous series. [ABSTRACT FROM AUTHOR]

Pyrrolidine and piperidine derivatives bearing halide functional groups are prevalent building blocks in drug discovery as halides can serve as an anchor for post‐modifications. In principle, one of the simplest ways to build these frameworks is the haloamination of alkenes. While progress has been made in this field, notably with the development of enantioselective versions, this reaction is still fraught with limitations in terms of reactivity. Besides, a major question remaining is to understand the mechanism at work. The formation of a haliranium intermediate is typically mentioned, but limited mechanistic evidence supports it. Reported here is an efficient metal‐ and oxidant‐free protocol to achieve the haloamidation of olefins, promoted by hexafluoroisopropanol, along with a DFT investigation of the mechanism. These findings should guide the future development of more complex transformations in the field of halofunctionalization. [ABSTRACT FROM AUTHOR]

Pyrrolidine and piperidine derivatives bearing halide functional groups are prevalent building blocks in drug discovery as halides can serve as an anchor for post‐modifications. In principle, one of the simplest ways to build these frameworks is the haloamination of alkenes. While progress has been made in this field, notably with the development of enantioselective versions, this reaction is still fraught with limitations in terms of reactivity. Besides, a major question remaining is to understand the mechanism at work. The formation of a haliranium intermediate is typically mentioned, but limited mechanistic evidence supports it. Reported here is an efficient metal‐ and oxidant‐free protocol to achieve the haloamidation of olefins, promoted by hexafluoroisopropanol, along with a DFT investigation of the mechanism. These findings should guide the future development of more complex transformations in the field of halofunctionalization. [ABSTRACT FROM AUTHOR]

The catalytic activity of cationic NHC‐ZnII and NHC‐AlIII (NHC=N‐heterocyclic carbene) complexes in reactions that require the electrophilic activation of soft C−C π bonds has been studied. The former proved able to act as a soft π‐Lewis acid in a variety of transformations. The benefit of the bulky IPr NHC ligand was demonstrated by comparison with simple ZnX2 salts. The tested NHC‐AlIII catalyst is not able to activate C−C π bonds but simple AlX2+ ions were found potent in some cases. [ABSTRACT FROM AUTHOR]

The synthesis and structural features of several families of unsolvated molecular complexes of the heavy alkaline earths (Ae = calcium, strontium and barium) supported by bis(phenolate)s or bis(fluoroalkoxide)s are described. These dianionic, multidentate ligands are built around diaza-macrocycles that contain either five or six N- and O-heteroatoms. Several of these complexes have been characterised by X-ray diffraction crystallography. A list of comparative features was drawn upon close examination of the molecular structures of these complexes. It highlights the subtle influences of the identity of the central Ae metal, denticity and nature -fluoroalkoxide vs. phenolate- of the anionic tethers in the ligands. All complexes are seven- or eight-coordinate. It is observed in particular that a decrease of the number of heteroatoms in the macrocyclic backbone of the ligand will be compensated by the establishment of intramolecular Ae⋯F interactions (accounting for ca. 3.8–6.4% of the pertaining coordination spheres according to bond valence sum analysis), dimerisation of the complex, or, in one case, solvent (thf) retention. Attempts to gauge the Lewis acidity in these series of complexes were carried out by three independent methods (Childs, Gutmann–Beckett and global electrophilicity index). However, conflicting results were obtained and no clear trend can be delineated, even if on the whole, these measurements concur to suggest relatively low Lewis acidity. [ABSTRACT FROM AUTHOR]

Hexafluoroisopropanol (HFIP) is a solvent with unique properties that has recently gained attention for promoting a wide range of challenging chemical reactions. It was initially believed that HFIP was almost exclusively involved in the stabilization of cationic intermediates, owing to its high polarity and low nucleophilicity. However, in many cases, the mechanism of action of HFIP appears to be more complex. Recent findings reveal that many Lewis and Brønsted acid-catalyzed transformations conducted in HFIP additionally involve cooperation between the catalyst and HFIP hydrogen-bond clusters, akin to Lewis- or Brønsted acid-assisted-Brønsted acid catalysis. This feature article showcases the remarkable versatility of HFIP in Lewis and Brønsted acid-catalyzed reactions, with an emphasis on examples yielding mechanistic insight. [ABSTRACT FROM AUTHOR]

The aza‐Piancatelli cyclization provides an expedient synthesis of 4‐aminocyclopentenone building blocks that may be converted into aminocyclopentitols, which are heavily represented motifs among natural products. However, its use as a key step in total synthesis was still unprecedented. Here, we disclose our in‐depth investigations regarding this reaction in order to access highly complex structures representing the core of some natural molecules. The applicability of the cyclization was highlighted by the 3‐step total synthesis of bruceolline D. Thus, we anticipate that this work will lay the ground for further applications in total synthesis. [ABSTRACT FROM AUTHOR]

The reactivity of 7‐alkynycycloheptatrienes tethered to an aryl group under π‐acid catalysis has been studied. A variety of useful cyclic products were synthesized via Au(I)‐catalyzed skeletal reorganization, Cu(II)‐catalyzed hydroarylation, or Brønsted acid‐catalyzed tandem hydroarylation/Friedel‐Crafts reaction. We also report a rare type of skeletal reorganization involving the 1,3‐acetonide tether in the presence of a univalent cationic Ga(I)+ complex. [ABSTRACT FROM AUTHOR]

An enantioselective Au(I)-catalyzed cyclization/nucleophilic addition process is developed, starting from 1,5-enyne substrates. A broad scope of O-, N- and C-nucleophiles was introduced in order to provide the corresponding chiral cyclopentene derivatives in moderate to high yields and up to 96 : 4 enantiomeric ratio. [ABSTRACT FROM AUTHOR]

An efficient regio- and diastereoselective arylation method of readily available 2,3-glycals with various aryl iodides has been established. Using the Pd(OAc)2/AsPh3 precatalytic system, this protocol proved to be general to prepare a variety of substituted C2-aryl glycosides in good yields with complete diastereoselectivity. [ABSTRACT FROM AUTHOR]

A three‐component Pd‐catalyzed coupling of ynamides, aryl diazonium salts, and aryl boronic acids for the synthesis of novel triaryl‐substituted enamides is described. This transformation represents the first example of an umpolung regioselective unsymmetrical syn‐1,2‐diarylation/aryl‐olefination of ynamides. The aryl moieties of the diazonium salt (electrophile) and boronic acid (nucleophile) are explicitly incorporated in the electrophilic α‐ and nucleophilic β‐position, respectively, of the ynamide, resulting in a single isomer of the N‐bearing tetrasubstituted olefin. The scope is broad (68 examples), showing excellent functional‐group tolerance. DFT calculations substantiate the rationale of the mechanistic cycle and the regioselectivity. The chemoselectivity and synthetic potential of the enamide products were also studied. [ABSTRACT FROM AUTHOR]

A three‐component Pd‐catalyzed coupling of ynamides, aryl diazonium salts, and aryl boronic acids for the synthesis of novel triaryl‐substituted enamides is described. This transformation represents the first example of an umpolung regioselective unsymmetrical syn‐1,2‐diarylation/aryl‐olefination of ynamides. The aryl moieties of the diazonium salt (electrophile) and boronic acid (nucleophile) are explicitly incorporated in the electrophilic α‐ and nucleophilic β‐position, respectively, of the ynamide, resulting in a single isomer of the N‐bearing tetrasubstituted olefin. The scope is broad (68 examples), showing excellent functional‐group tolerance. DFT calculations substantiate the rationale of the mechanistic cycle and the regioselectivity. The chemoselectivity and synthetic potential of the enamide products were also studied. [ABSTRACT FROM AUTHOR]

Styrene derivatives can be easily synthesized from vinyl triflates and arenes under mild reaction conditions, using [Li][Al(OC(CF3)3)4] as a catalyst and LiHMDS as a base. This transformation is likely to involve a vinyl cation intermediate as an electrophile, which is corroborated by DFT calculations, deuterium-labeling and other control experiments. The use of an inert weakly coordinating anion is a decisive factor in this bimolecular vinylation process. [ABSTRACT FROM AUTHOR]

An uncommon sulfur → selenium → carbon radical transfer process is employed to develop an unprecedented selenyl radical-mediated regioselective cyclization of yne-tethered-ynamides. Density functional theory studies and HRMS experiments are used to establish a reactivity scale between thiyl and selenyl radicals. The unique features of this transformation include, (1) the chemoselective reactivity of RSe˙ over RS˙, (2) regioselective RSe˙ attack on alkyne over ynamide, (3) 5-exo-dig cyclization of yne-ynamide to unusual 4-selenyl-pyrroles, and (4) the green synthetic method. The reaction of methyldiselenide with yne-ynamides to methylselenopyrroles is also described. [ABSTRACT FROM AUTHOR]

For the first time, azaoxyallyl cations were used as cycloaddition partners with tropone derivatives to access nitrogen-containing [7,6]-fused bicycles in a metal-free process under mild reaction conditions. DFT computations have been used to shed light on the selectivities observed during the course of the reaction. [ABSTRACT FROM AUTHOR]

A stable asymmetric intramolecular Povarov reaction has been established to provide an efficient method to access structurally diverse trans,trans‐trisubstituted tetrahydrochromeno[4,3‐b]quinolines in high stereoselectivities of up to >99:1 diastereomeric ratio and 99 % enantiomeric excess, without any purification step. Additionally, to facilitate large‐scale application of this method, a low catalyst loading protocol was employed, 0.2 mol % chiral phosphoric acid, which provided the cycloadducts without any loss in yield and enantioselectivity. Theoretical studies revealed that the reaction occurred through a sequential Mannich reaction and an intramolecular Friedel–Crafts reaction, wherein the phosphoric acid acted as a bifunctional catalyst to activate the para‐phenolic dienophile and N‐2‐hydroxy‐2‐azadiene simultaneously. [ABSTRACT FROM AUTHOR]

The first total synthesis of the caged monoterpene indole alkaloid cymoside is reported. This natural product displays a unique hexacyclic‐fused skeleton whose biosynthesis implies an early oxidative cyclization of strictosidine. Our approach to the furo[3,2‐b]indoline framework relied on an unprecedented biomimetic sequence which started by the diastereoselective oxidation of the indole ring into a hydroxyindolenine which triggered the addition of an enol ether and was followed by the trapping of an oxocarbenium intermediate. [ABSTRACT FROM AUTHOR]