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ion of a pyridine ligand from Weiss’ reagent ([PhI(Pyr)2]2+) using BF3-Et2O was found to activate Weiss’ reagent towards electrophilic aromatic substitution reactions. The activated species can be isolated when 4-DMAP is used as the pyridine ligand and was determined to be [PhI(4-DMAP)]2+ in solution. The isolated cation was reactive in electrophilic aromatic substitution reactions towards mesitylene, xylene and toluene that Weiss’ reagent itself does not react with.

A long-term goal is to gain synthetic access to native photosynthetic bacteriochlorophylls. A recently developed route entails Knoevenagel condensation of an AD dihydrodipyrrin (I, bearing a carboxaldehyde attached to pyrroline ring D) and a BC dihydrodipyrrin (II, bearing a β-ketoester attached to pyrrole ring C) to form the Z/E-enone. Acid-mediated double-ring closure of the E-enone III-E (Nazarov cyclization, electrophilic aromatic substitution, and elimination of methanol) affords the bacteriochlorophyll skeleton BC-1 containing the isocyclic ring (ring E), a trans-dialkyl group in ring D, and a gem-dimethyl group in ring B. Prior work established the synthesis and the integrity of the resulting trans-dialkyl groups and bacteriochlorin chromophore. The counterpart report here concerns an in-depth study of conditions for the double-ring closure: catalyst/solvent surveys; grid search including time courses of [III-E] versus [acid] concentrations emphasizing equimolar, inverse molar, and variable acid lines of inquiry; and chlorin byproduct quantitation. Key findings are that (1) the double-ring closure can be carried out in 4 h (t1/2 ∼ 40 min) instead of 20 h, affording ∼1/5th the chlorin byproduct (0.16%) while maintaining the yield of BC-1 (up to 77%); (2) the separate Z/E-enones of III have comparable reactivity; (3) sub-stoichiometric quantities of acid are ineffective; (4) the Knoevenagel condensation (40 mM, room temperature, piperidine/acetic acid in acetonitrile) and the acid-mediated double-ring closure (0.20 mM, 80 °C, Yb(OTf)3 in acetonitrile) can be carried out in a two-step process; and (5) zinc insertion to form ZnBC-1 is straightforward. Together, the results enable streamlined conversion of dihydrodipyrrin reactants to the bacteriochlorophyll model compounds.

The primary objective of this study is to identify the aromatic intermediate products in p-cresol degradation by ozonation, peroxone, and ozone-persulfate, and elucidate the pathways and mechanisms...

Intermolecular asymmetric haloamination reactions are challenging due to the inherently high halenium affinity (HalA) of the nitrogen atom, which often leads to N-halogenated products as a kinetic trap. To circumvent this issue, acetonitrile, possessing a low HalA, was used as the nucleophile in the catalytic asymmetric Ritter-type chloroamidation of allyl-amides. This method is compatible with Z and E alkenes with both alkyl and aromatic substitution. Mild acidic workup reveals the 1,2-chloroamide products with enantiomeric excess greater than 95% for many examples. We also report the successful use of the sulfonamide chlorenium reagent dichloramine-T in this chlorenium-initiated catalytic asymmetric Ritter-type reaction. Facile modifications lead to chiral imidazoline, guanidine, and orthogonally protected 1,2,3 chiral tri-amines., Intermolecular haloamination reactions are challenging due to the high halenium affinity of the nitrogen atom. This is circumvented by using acetonitrile as an attenuated nucleophile, resulting in an enantioselective halo-Ritter reaction.

Electrophilic aromatic substitution reactions are of profound importance for the synthesis of biologically active compounds and other advanced materials. They represent an important means to activate specific aromatic C–H bonds without requiring transition-metal catalysts. Surprisingly, few stereoselective variants are known for electrophilic aromatic substitutions, which limits the utility of these classical reactions for stereoselective synthesis. While many electrophilic aromatic substitutions lead to achiral products (due to the planar nature of aromatic rings), there are important examples where chiral products are produced, including desymmetrization reactions of aromatic cyclophanes and of prochiral substrates with multiple aromatic rings. This Synpacts article now illustrates how chiral arms, when placed precisely above and underneath delocalized carbocations, can act as chiral auxiliaries to convert classical electrophilic aromatic substitution reactions into powerful diastereo- and enantioselective transformations.

Since the advent of metal-catalyzed cross-coupling technology more than 40 years ago, the field has grown to be ever-increasingly enabling, yet the employed coupling partners are largely still those that were originally employed in the context of Pd-catalyzed cross-coupling, namely, arylboronic esters/acids, aryl silanes, aryl stannanes, or organometallic reagents (RMgX, RZnX). Aryl germanes have little precedent in the literature; they were historically explored in the context of Pd0/PdII-catalyzed cross-coupling reactions but were found to be much less reactive than the already established reagents. Consequently, few efforts were made by the community on their further mechanistic or synthetic exploration.In 2019, our group described trialkyl aryl germanes as robust, convenient, and nontoxic reagents. Although structurally similar to trialkyl aryl stannanes or silanes, the GeEt3 site does not engage in the traditional transmetalation mode of PdII complexes. Our studies instead provided strong support for an unprecedented and orthogonal reactivity of organogermanes that follows electrophilic aromatic substitution (SEAr)-type reactivity. This mode of bond activation allowed us to devise a number of synthetic strategies in which the Ge functionality was for the first time more reactive and exclusively functionalized in preference over several of the established coupling partners (e.g., silanes, boronic acids/esters, halogens).Within the past year we have showcased the unique reactivity of organogermanes in C-C and C-X bond-forming transformations. Because of the exquisite mode of bond activation, the new strategies offer access to complementary chemical transformations, tolerating other cross-coupling enabling functionalities, and allow for their further downstream diversification. We have for instance demonstrated that organogermanes can be coupled efficiently with aryl halides under Pd nanoparticle conditions with tolerance of all other established cross-coupling partners, while under homogeneous Pd0/PdII catalysis all of the other established groups can be functionalized preferentially over the Ge functionality. We similarly were able to harness this orthogonal reactivity mode in oxidative gold catalysis, where organogermanes proved to be more reactive than the established silanes or boronic esters. We have also developed an orthogonal approach for metal-free halogenation of organogermanes with convenient halogenation agents, offering access to the chemo- and regioselective installation of valuable halide motifs in the presence of alternative groups that can also engage in electrophilic halogenations.In this Account, we wish to provide an overview of (i) the historic versus current reactivity findings and synthetic utility of organogermanes, (ii) the current state of mechanistic understanding of their reactivity, and (iii) the synthetic repertoire and ease of installing the germanium functionality in organic molecules.

Multisubstituted pyrroles are commonly found in many bioactive small molecule scaffolds, yet the synthesis of highly-substituted pyrrole cores remains challenging. Herein, we report an efficient catalytic synthesis of 2-heteroatom-substituted (9-BBN or SnR3) pyrroles via Ti-catalyzed [2 + 2 + 1] heterocoupling of heteroatom-substituted alkynes. In particular, the 9-BBN-alkyne coupling reactions were found to be very sensitive to Lewis basic ligands in the reaction: exchange of pyridine ligands from Ti to B inhibited catalysis, as evidenced by in situ11B NMR studies. The resulting 2-boryl substituted pyrroles can then be used in Suzuki reactions in a one-pot sequential fashion, resulting in pentasubstituted 2-aryl pyrroles that are inaccessible via previous [2 + 2 + 1] heterocoupling strategies. This reaction provides a complementary approach to previous [2 + 2 + 1] heterocouplings of TMS-substituted alkynes, which could be further functionalized via electrophilic aromatic substitution., Multisubstituted pyrroles are commonly found in many bioactive small molecule scaffolds, yet the synthesis of highly-substituted pyrrole cores remains challenging.

Summary Functionalization of arenes represents the most efficient approach for constructing a core backbone of important aryl compounds. Compared with the well-developed electrophilic aromatic substitution and transition-metal-catalyzed C–H activation, nucleophilic aromatic substitution remains challenging because of the lack of a convenient route for rapid conversion of the σH adduct to other stable and versatile intermediates in situ. Guided by computational design, we were able to realize asymmetric nucleophilic aromatic substitution by introducing a nitroso group on naphthalene via chiral phosphoric acid catalysis. This strategy enables efficient construction of atropisomeric indole-naphthalenes and indole-anilines with excellent stereocontrol. Density functional theory (DFT) calculations provide further insights into the origins of enantioselectivity and the reaction mechanisms. The successful application in the synthesis of NOBINs (2-amino-2′-hydroxy-1,1′-binaphthyl) extends the utility of this strategy.

Site-selective functionalization of arenes that is complementary to classical aromatic substitution reactions remains a long-standing quest in organic synthesis. Exploiting the generation of halenium ion through oxidative process and the protonation of the nitrogen containing function in HF/SbF5 , the chlorination and iodination of classically inert Csp2 -H bonds of aromatic amines occurs. Furthermore, the superacid-promoted (poly)protonation of the molecules acts as a protection, favoring the late-stage selective halogenation of natural alkaloids and active pharmaceutical ingredients.

The reactions of quinoline-2(6,8)-carbaldehydes with arenes by the action of strong Bronsted (H2SO4, CF3SO3H) or Lewis (AlCl3, AlBr3) acids led to the formation of substituted diarylmethylquinolines in high yields.

A computational approach has been developed to automatically generate and analyse the structures of the intermediates of palladium-catalysed carbon–hydrogen (C–H) activation reactions as well as to predict the final products. Implemented as a high-performance computing cluster tool, it has been shown to correctly choose the mechanism and rationalise regioselectivity of chosen examples from open literature reports. The developed methodology is capable of predicting reactivity of various substrates by differentiation between two major mechanisms – proton abstraction and electrophilic aromatic substitution. An attempt has been made to predict new C–H activation reactions. This methodology can also be used for the automated reaction planning, as well as a starting point for microkinetic modelling.

A laboratory exercise for the synthesis of a sulfonated styrene-co-maleic anhydride polymer and its application as a stain blocker on nylon-6,10, is described. The effectiveness of the sulfonated polymer to prevent the conjugate base of an acid dye from staining the polyamide is demonstrated. This experiment is designed for second-semester, second-year undergraduate organic chemistry students. Specifically, this laboratory experiment focuses on providing experience with radical chain and step-growth polymerizations, interfacial reactions, electrophilic aromatic substitution (sulfonation), and the importance of intermolecular forces.

Nucleophilic substitution of hydrogen in nitroarenes has become a powerful synthetic tool for functionalization of these important organic substrates, complementary to other modern methods. In this review we present new developments in the area of introduction of alkyl and functionalized alkyl substituents into nitroarene rings via nucleo­philic substitution of hydrogen, followed by application of these processes in the construction of carbo- and heterocyclic rings. Finally, new developments in the investigation of the mechanism of SNArH are summarized.1 Introduction2 Alkylation and Haloalkylation3 Functionalized Carbon Substituents4 Formation of Carbo- and Heterocyclic Rings5 Mechanistic Aspects of SNArH6 Conclusion

We report the dual postsynthetic modification (PSM) of a metal-organic framework (MOF) involving the microscopic conversion of C-H bonds into C-C bonds and the mesoscopic introduction of hierarchical porosity. MOF crystals underwent single-crystal-to-single-crystal transformations during the electrophilic aromatic substitution of Co2 (m-DOBDC) (m-DOBDC4- =4,6-dioxo-1,3-benzenedicarboxylate) with alkyl halides and formaldehyde. The steric hindrance caused by the proximity of the introduced functional groups to the coordination bonds reduced bond stability and facilitated the transformation into hierarchically porous mesostructures by etching with in situ generated protons (hydroniums) and halides. The numerous defect sites in the mesostructural MOFs are potential water-sorption sites. However, since the introduced functional groups are close to the main adsorption sites, even methyl groups are able to considerably decrease water adsorption, whereas hydroxy groups increase adsorption at low vapor pressures.

A transformation of fluxional into configurationally stable axially chiral N‐arylpyrroles was achieved with a highly atroposelective electrophilic aromatic substitution catalyzed by a chiral‐at‐metal rhodium Lewis acid. Specifically, N‐arylpyrroles were alkylated with N‐acryloyl‐1H‐pyrazole electrophiles in up to 93 % yield and with up to >99.5 % ee, and follow‐up conversions reveal the synthetic utility of this new method. DFT calculations elucidate the origins of the observed excellent atroposelectivity., Freeze, don't move: A transformation of fluxional into configurationally stable axially chiral N‐arylpyrroles was achieved through a highly atroposelective electrophilic aromatic substitution catalyzed by a chiral‐at‐metal rhodium Lewis acid, with follow‐up transformations leading to structurally diverse axially chiral N‐arylpyrroles.

Being able to utilise a protecting group to influence remote regiocontrol offers a simple alternative approach to direct late-stage functionalisation of complex organic molecules. However, protecting groups that have the ability to influence reaction regioselectivity remote to their local chemical environment are not widely reported in the literature. Herein, we report the development of remote regioselective electrophilic aromatic substitution (SEAr) reactions that are enabled via the application of the tetrafluoropyridyl (TFP) phenol protecting group. We demonstrate that through sequential reactions and protection/deprotection of the TFP group, substitution patterns which do not conform to classical SEAr regioselectivity rules can be readily accessed.

Challenges to the de novo synthesis of bacteriochlorophyll a (BChl a), the chief pigment for anoxygenic bacterial photosynthesis, include creating the macrocycle along with the trans-dialkyl substituents in both pyrroline rings (B and D). A known route to a model bacteriochlorophyll with a gem-dimethyl group in each pyrroline ring has been probed for utility in the synthesis of BChl a by preparation of a hybrid macrocycle (BC-1), which contains a trans-dialkyl group in ring D and a gem-dimethyl group in ring B. Stereochemical definition began with the synthesis of (2S,3S)-2-ethyl-3-methylpent-4-ynoic acid, a precursor to the trans-dialkyl-substituted AD dihydrodipyrrin. Knoevenagel condensation of the latter and a gem-dimethyl, β-ketoester-substituted BC dihydrodipyrrin afforded the enone (E, 70%; Z, 3%); subsequent double-ring cyclization of the E-enone (via Nazarov, electrophilic aromatic substitution, and elimination reactions) gave BC-1 (53% yield) along with a trace of chlorin byproduct (1.4% relative to BC-1 upon fluorescence assay). BC-1 exhibited the desired trans-dialkyl stereochemistry in ring D and was obtained as a 7:1 mixture of (expected) epimers owing to the configuration of the 132-carbomethoxy substituent. The strategy wherein trans-dialkyl substituents are installed very early and carried through to completion, as validated herein, potentially opens a synthetic path to native photosynthetic pigments.

The synthesis of bi‐ and tetra‐functional tri‐aryl ether epoxy resin isomers and their subsequent cure with 44 diamino diphenyl sulphone (DDS) is presented here. The effect of varying aromatic substitution and cross‐link density on the structure, property, and processing relationships is explored for 1,3 bis(3‐glycidyloxyphenoxy)benzene (133 BGOPB), 1,4 bis(4‐glycidyloxyphenoxy)benzene (144 BGOPB), N,N,N,N‐tetraglycidyl 1,3‐bis (3‐aminophenoxy) benzene (133 TGAPB), and N,N,N,N‐tetraglycidyl 1,4‐bis (4‐aminophenoxy) benzene (144 TGAPB). Meta substitution to the aromatic ring reduces the rate of reaction, glass transition temperature, yield strain and crosslink density, coefficient of thermal expansion, and side reactions, while increasing strain softening, compressive modulus and strength, and methyl ethyl ketone ingress. Increasing crosslink density increases the glass transition temperature, promotes side reactions during cure, and increases compressive modulus, strength, and yield strain, while reducing coefficients of thermal expansion, methyl ethyl ketone ingress, and density. The results are discussed in terms of packing efficiency of the meta‐substituted epoxy resins and the role of short range molecular mobility caused by the lack of an aromatic axis of rotation.

Herein, we report an efficient and operationally simple synthesis of 6,7-dihydro-5H-pyrrolo[2,3-c]pyridazines and 6,7-dihydro-5H-pyrrolo[2,3-b]pyrazines via a tandem hydroamination–SNAr sequence th...

Oligosulfonic acids are promising linker compounds for coordination polymers and metal-organic frameworks, however, compared to their carboxylic acid congeners, often not readily accessible by established synthetic routes. This Account highlights the synthesis of recently developed aromatic and aliphatic di-, tri- and tetrasulfonic acids. While multiple electrophilic sulfonations of aromatic substrates are rather limited, the nucleophilic aromatic substitution including an intramolecular variant, the Newman–Kwart rearrangement, allows the flexible introduction of up to four sulfur-containing moieties at an aromatic ring. Sulfonic acids are then accessed by oxidation of thiols, thioethers, or thioesters either directly with hydrogen peroxide or in two steps with chlorine (generated in situ from N-chlorosuccinimide/hydrochloric acid) to furnish sulfochlorides which are subsequently hydrolyzed. In the aliphatic series, secondary alcohols as starting materials are converted into thioethers, thioesters, or thiocarbonates by nucleophilic substitutions, which are also subsequently oxidized to furnish sulfonic acids.1 Introduction2 Electrophilic Aromatic Substitution3 Nucleophilic Aromatic Substitution3.1 Intermolecular SNAr3.2 Intermolecular with Subsequent Oxidation3.3 Intramolecular with Subsequent Oxidation4 Nucleophilic Aliphatic Substitution with Subsequent Oxidation5 Oxidation5.1 Oxidation of Thiocarbonates5.2 Oxidation of Thioethers5.3 Oxidation of Thioesters6 Thermolysis of Neopentylsulfonates7 Functionalization via Diazonium Ions8 Conclusion

A one‐pot regioselective method for the preparation of 2‐arylbenzoxazoles from N‐arylbenzamides has been developed using iron(III)‐catalyzed bromination of the aryl ring, followed by copper(I)‐catalyzed O‐cyclization with the benzamide side chain. In contrast, reaction of N‐arylthiobenzamides with N‐bromosuccinimide and iron triflimide led directly to the isolation of the corresponding 2‐arylbenzothiazoles via intramolecular C–S bond formation. Mechanistic and control experiments suggest that in this case, bromination occurs at the sulfur atom, resulting in a reactive intermediate that can undergo electrophilic aromatic substitution and S‐cyclization. The scope of both processes was explored yielding a range of structural analogues, including a pharmaceutically active compound for the treatment of Duchenne muscular dystrophy and an affinity agent of the amyloid‐beta protein in Alzheimer's disease.

Outlined here are studies exploring the scope of the sequential photoelectrocyclization, [1,5]-hydride shift of conjugated bis-aryl cycloalkenone substrates. We have found not only that the cyclization precursors can be synthesized in a modular fashion but also that the cyclization is efficient and amenable to the presence of a range of cycloalkenones and aromatic systems. Among the interesting discoveries from this work is that the electrocyclization intermediate can be competitively captured with protons and that the nature of the excited state (singlet vs triplet) is dependent on aromatic substitution.

In this study, a visible-light-induced intermolecular C-H bond imidation of arenes was achieved at ambient condition. By using simple phthalimide with (diacetoxyiodo)benzene and molecular iodine, direct metal-/photocatalyst-free C-N bond formation was achieved. The imidation protocol was designed by using time-dependent density functional theory calculations and experimentally demonstrated for 28 substrates with as high as 96% yield. Mechanistic studies indicated that radical-mediated aromatic substitution occurred via photolysis of N-iodophthalimide under visible-light irradiation.

Cyclodehydration of α-phenoxy ketones promoted by Eaton’s reagent (phosphorus pentoxide–methanesulfonic acid) is used to prepare 3-substituted or 2,3-disubstituted benzofurans with moderate to excellent yields under mild conditions. The method provides a facile access to benzofurans from readily available starting materials such as phenols and α-bromo ketones. The reaction is highly efficient, which is attributed to the good reactivity and fluidity of Eaton’s reagent. The reaction can be applied to prepare naphthofurans, furanocoumarins, benzothiophenes, and benzopyrans.

Subtle differences in reaction conditions facilitated unprecedented photocatalytic reactions of oxadiazolines by energy transfer catalysis. A set of compounds, sulfoximines and benzimidazoles, were ingeniously prepared from oxadiazolines via nitrene intermediates by photocatalytic N-O/C-N bond cleavages. The synthesis of sulfoximines was realized through intermolecular N-S bond formation between nitrene intermediates and sulfoxides, whereas benzimidazoles were obtained via intramolecular aromatic substitution of the nitrene to the tethered aryl substituent.

A novel reactivity-triggering strategy for inert organic molecules was developed via the chemical properties of a crystal-solution interface. Upon self-assembling to form a {002} crystal interface, inactive 9-anthracene boric acid was transformed into an ultra-high active state, triggering a catalyst-free, environmentally benign, aromatic substitution and oxidation reaction, which achieved 99% yield in 1 h under ambient conditions.

Herein, we report a modular synthetic approach of (C-10 to C-13)-substituted 9,14-diaryl-9,14-dihydrodibenzo[a,c]phenazine derivatives. This synthetic route enables the aromatic substitution in a predictable and programmed manner to obtain products in synthetically useful isolated yield.

Photoinitiated perfluorobutylation reactions of 2-anisidine 1, propenyloxybenzene 2, and 2-mercaptoethanol 3 have been carried out employing commercially available n-C4F9I as the source of C4F9 radicals under three different photocatalysts (PCs) absorbing in the violet (Ir[dF(CF3)ppy]2(dtbbpy)+ (PC-1)), green (Rose Bengal (PC-2)) and red (zinc phthalocyanine PhZn (PC-3)) regions of the electromagnetic spectrum, in order to explore the quantum yields and radical chain lengths for each type of transformation and photoinitiated system. For substrates 1-3 and their different types of reactions, the comparative study between PCs seeks to establish the extent to which regioproducts, yields, and mechanistic proposals are influenced by the intervention of each PC. The different overall quantum yields and chain lengths obtained for each type of reaction under each PC are a direct consequence of the efficiency of the photoinitiation events, i.e., primary radical production, propagation and termination steps. This will have important implications in the understanding and representations of the mechanisms postulated, in terms of closed and open catalytic cycles. One strategy we apply to uncover radical propagating chains in our mechanisms is to explore photocatalysts that operate in oxidative and reductive quenching manners for each type of transformation. Fil: Yerien, Damián Emilio. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Barata Vallejo, Sebastian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Centre National de la Recherche Scientifique; Francia Fil: Mora Flores, Erwin Wilfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Postigo, Jose Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina

meta-Selective C–H nitration of phenol derivatives was developed using a Ru-catalyzed σ-activation strategy. Cu(NO3)2·3H2O was employed as the nitrating source, whereas Ru3(CO)12 was found to be the most suitable metal catalyst for the protocol. Mechanistic studies suggested involvement of an ortho-CAr–H metal intermediate, which promoted meta-electrophilic aromatic substitution and silver-assisted free-radical pathway.

Sustainable biomaterial binders developed from lignin plus collagen have offered effective binder systems for the fabrication of specialty graphites and graphite electrodes. To further chronicle collagen's synergistic effects and benefits, the authors appraised the formation and evolution of the chars pyrolyzed from lignin, collagen and their blends. Following pyrolysis in a vertical tube furnace at 1000 °C, the lignin-collagen blend yielded more char than did mere lignin or mere collagen. Elemental analysis indicated that along with the release of the oxygenated, nitrogenated, and hydrogen-containing gases, the collagen's presence facilitated carbon-enriched chars with more oxygenated polyaromatic structures. Collagen yielded an aryl (aromatic) carbon source in the aromatic condensation reactions, leading to the continuous cross-linking and growth of the lignin aromatic rings. Per Fourier-transform infrared spectroscopy (FTIR), during pyrolysis, collagen enhanced the hydrogen aromaticity index, and reduced the extent of aromatic substitution. The collagen presence facilitated more removal of functional groups, as indicated by bonded O–H stretching, symmetric CH3 stretching in O–CH3, and aliphatic C–H stretching. Scanning electron microscope (SEM) revealed that collagen served as a thermoplastic bio-binder that formed a thermally-fused framework with lignin. Thus, collagen induced significant differences in solidification behaviors and surface morphologies.

An efficient method for nucleophilic aromatic substitution on 7-azaindoles has been developed. The reaction is facilitated by the unique dual influence of SEM as both protecting and activating group, permitting mild conditions and short reaction times that are compatible with sensitive functional groups. The method is suitable for the synthesis of a broad range of products, most notably ethers.

Summary A gold-catalyzed 6-endo-dig carbocyclization of alkyne with the pendent diazo group is reported. It provides an expeditious approach for the synthesis of multi-functionalized naphthalene derivatives under mild conditions. Mechanistic studies suggest that a vinyl gold carbene is generated as the key intermediate in this cascade transformation that smoothly delivers naphthalene products through an unprecedented stepwise aromatization or an intermolecular aromatic substitution process. The unique endocyclic vinyl species is inaccessible with other precursors; thus, novel carbene cascade transformations could be envisioned with the current catalytic model. Functional groups, such as alkenyl, hydroxyl, amino, and carboxyl groups, remain untouched under these conditions. In addition, the utility of these generated 2-carboxyl naphthalenes is illustrated by the synthesis of chiral 1,2′-binaphthalene ligands and π-conjugated polycyclic hydrocarbons (CPHs)., Graphical Abstract, Highlights • A general method for the construction of multi-functionalized naphthalenes • First 6-endo-dig diazo-yne carbocyclization leading to the vinyl gold carbene • Expeditious access to naphthalenes with broad functional group compatibility • Applications for the synthesis of chiral 1,2′-binaphthalene ligands and CPHs, Catalysis; Organic Synthesis; Organic Reaction