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A synthetic novel strategy involving a pseudo-three-component reaction to obtain 1,6-dihydroazaazulenes derivates via cyclization of pyrrolyl-enones was developed. This reaction is carried out under mild conditions from simple starting materials and catalyzed with ionic liquid. Notably, three new C–C bonds are formed in the one-pot process. The target molecules are of interest in medicinal chemistry as they contain a privileged scaffold and are considered indole homologues. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A safe, convenient, and regioselective synthesis of 3-halo coumarins using a metal halide (CuX2 alone or with ZnX2) promoted halogenation with N -halosuccinimide (NXS) as halide source is reported. The synthesis involved the steady in situ generation of highly reactive positive halogen (X+) by the coordination of copper or zinc with the N -halosuccinimide and subsequent electrophilic aromatic substitution of the electron-deficient coumarins. This procedure works well also for the halogenation of less electron-rich naphthoquinones, flavones, and methoxypsoralen in moderate to quantitative yields. This protocol features simple experimental conditions using readily available inexpensive reagents and provides a convenient approach to the chlorination or bromination of some useful heteroaromatic compounds. [ABSTRACT FROM AUTHOR]

A simple and efficient methodology for the direct halogenation of N-phenylureas was developed using trihaloisocyanuric acids in acetonitrile at room temperature. This protocol proved to be effective for the construction of N-phenylureas with different patterns of substitution. Additionally, less reactive N-benzylureas were halogenated in the presence of a mixture of trifluoroacetic acid and acetonitrile at room temperature. [ABSTRACT FROM AUTHOR]

Four new azafullerene monoadducts (DPS-C59N, HDP-C59N, DBOP-C59N, DHOP-C59N) have been prepared and applied as electron acceptors in solution-processed bulk heterojunction solar cells. The four compounds were designed so that their solubility in organic solvents was maximized and that structure-property comparisons could be drawn with a previously synthesized azafullerene electron acceptor. With the photovoltaic devices that were prepared from the four azafullerenes and polymeric electron donor PTB7 we found that only one of the four new electron acceptors resulted in a power conversion efficiency that exceeded the one observed with a previously reported azafullerene monoadduct. Atomic force microscopy and electron mobility measurements suggest that azafullerenes bearing two alkyl chains lead to non-optimal film morphologies as well as electron mobilities and that future efforts should focus on single n-alkyl substitution. [ABSTRACT FROM AUTHOR]

Sixfold electrophilic bromination and iodination of the molecular periphery of the bridgehead-tetramethylated tribenzotriquinacene (TBTQ) with N-bromosuccinimide (NBS) and N-iodosuccinimide (NIS), respectively, under various conditions was studied to develop an alternative preparative approach to the classical Lewis acid catalyzed bromination. Running these reactions in trifluoroacetic acid either in pure form or with chloroform as a co-solvent at elevated temperatures, or under sonication or microwave irradiation was found to give increasingly fast and efficient conversion of TBTQ to the target hexahalogenated TBTQ derivatives in excellent yields. NIS was found to be markedly more reactive than NBS, whereas N-chlorosuccimide reacted hardly. The new method was applied to the sixfold functionalization of the 4b,8b,12b-tripropyl-12d-methyl-TBTQ analogue to give the corresponding hexabromo and hexaiodo derivatives. Some sixfold C-C crosscoupling reactions of hexahalo derivatives of TBTQ were carried out in excellent yields to enlarge the three spatially orthogonal indane wings of the TBTQ core. [ABSTRACT FROM AUTHOR]

1-Alkylprolines undergo decarbonylative reactions with oxalyl chloride and subsequent Mannich reactions with nonactivated C-H nucleophiles to give 2-substituted pyrrolidines as Mannich adducts. We showed that 1-alkyl-1-pyrrolinium compounds are the reactive intermediates formed by the decarbonylative reactions of 1-alkylprolines. Our results also confirmed that an azomethine ylide, although unreactive toward the Mannich reaction and not involved in the decarbonylative Mannich reaction, can be generated by deprotonation of the corresponding 1-alkyl-1-pyrrolinium compound under mild conditions. [ABSTRACT FROM AUTHOR]

Further synthetic utility of 3-substituted N-arylisoindolinones obtained from N-aryl-3-hydroxyisoindolinones and alkyl aryl ketones under Lewis acid mediated anhydrous conditions is reported. Herein, substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)-ones were synthesized from 3-substituted isoindolinones following a NaBH4 ketone reduction and carbocation-mediated intramolecular electrophilic aromatic substitution using BF3·OEt2. Representative final products were unambiguously characterized by single-crystal X-ray crystallography. [ABSTRACT FROM AUTHOR]

An efficient practical synthetic procedure has been developed for the synthesis of 2,2-dimethyl-5-{aryl[(hetero)aryl]methyl}-1,3-dioxane-4,6-diones through Friedel--Crafts alkylation. The scope and limitation of the reaction of 2,2-dimethyl-5-arylidene-1,3-dioxane-4,6-diones with π-excess aromatic systems have been delineated. [ABSTRACT FROM AUTHOR]

Aryl and heteroaryl iodides are ubiquitous synthetic building blocks used in a wide range of transformations including coupling and radical reactions. These compounds are also found as components of many pharmaceutically active agents and used for medical imaging. Due to their importance, a range of transition-metal-catalyzed methods have recently been developed for their efficient preparation. This short review gives an overview of the progress made and highlights the benefits of transition-metal-catalyzed methods over more traditional approaches. [ABSTRACT FROM AUTHOR]

Starting with the parent compound [2.2.2]paracyclophane several routes were developed to synthesize its 4-vinyl derivative. From the 4-aldehyde and the bromomethyl derivative the stilbenophanes were prepared which photocyclize to the phenanthrenophanes. A new route to a bridged ketone was developed which was subjected to the addition of phenyllithium and to typical aromatic substitution reactions (inter alia Rieche formylation, Friedel-Crafts acylation). Bromination of the bridged ketone yielded an unusual tropone derivative. Electrophilic substitution reactions were also carried out for the bridged hydrocarbon, the reduction product of the bridged ketone. For both the bridged ketone and the bridged hydrocarbon the electrophilic substitutions occur regioselectively, favoring the introduction of the new substituent in a syn orientation to the bridging keto and methylene group, respectively. [ABSTRACT FROM AUTHOR]

Pyrene-2-carboxylic acid is a versatile intermediate for introducing the unusual 2-pyrenyl unit into functional organic molecules. A classical preparation for this molecule has been revised and improved to give a robust and efficient three-step process. The method has been applied on a multigram scale to give pyrene-2-carboxylic acid in >70% overall yield from pyrene. [ABSTRACT FROM AUTHOR]

The synthesis of the Cinnamomum homosesquiterpenoid tenuifolin has been accomplished by way of an intramolecular Nicholas reaction of the [Co2(CO)6] complex of an alkyne-substituted biaryl for construction of the seven-membered ring. The cyclization features the reaction of a nonactivated arene ring with the propargyldicobalt cation to give the dibenzocycloheptyne-Co2(CO)6. [ABSTRACT FROM AUTHOR]

Chiral di- and trimethoxysubstituted alkylbenzenes underwent oxidative cross-dehydrogenative coupling reactions with arenes and related oxidative coupling reactions with silyl nucleophiles in moderate to good yields (41-99%) and with significant diastereoselectivities (dr = 71:29 to >95:5). [ABSTRACT FROM AUTHOR]

The degree of hydrolysis of polyphosphoric acid (PPA) has a crucial effect on the regioselectivity of the PPA-mediated synthesis of indanones. It was found that the regioselectivity can be switched by employing PPA with either a high or low content of P2O5. This methodology was used for the regioselective synthesis of a range of electron-rich indanones, including a natural sesquiterpene. [ABSTRACT FROM AUTHOR]

An efficient two-step synthesis of 4(5)-benzyl-L-histidine from L-histidine was developed. A Pictet-Spengler reaction between L-histidine and benzaldehyde in the presence of excess strong base yielded 4-L-phenylspinacine within one hour. Catalytic transfer hydrogenolysis in methanol at reflux using ammonium formate rapidly converted 4-L-phenylspinacine to 4(5)-benzyl-L-histidine within five minutes. No racemization of the final product 4(5)- benzyl-L-histidine was observed using the Marfey reagent. To show the utility of this method, a series of fluorinated benzylhistidines were prepared. [ABSTRACT FROM AUTHOR]

A wide variety of electron-rich arenes were efficiently converted into the corresponding iodinated compounds via a gold(I)-catalyzed reaction under mild conditions. [ABSTRACT FROM AUTHOR]

Functionalized indolizines were prepared by a one-pot cascade reaction from bispyridinium salts. This mild experimental procedure allowed the isolation of the product in very good yield. Combination of the indolizine derivative with electrophiles confirmed the reactivity of the C3 ring carbon and allowed the bromination, formylation, hydroxymethylation, and dimerization of the indolizine scaffold [ABSTRACT FROM AUTHOR]

We describe an organocatalytic iodination of activated aromatic compounds using 1,3-diiodo-5,5-dimethylhydantoin (DIH) as the iodine source with thiourea catalysts in acetonitrile. The protocol is applicable to a number of aromatic substrates with significantly different steric and electronic properties. The iodination is generally highly regioselective and provides high yields of isolated products. NMR kinetic investigations conducted in THF-d8 indicate the role of sulfur in the thiourea motif as a nucleophile that is assisted by H-bonding in the key steps of the reaction. [ABSTRACT FROM AUTHOR]

Starting from different heterocyclic imines, a large number of annulated tricyclic lactams were prepared in a two-step synthesis. First, methoxyamides with a phenyl ring in a- or ß-position were generated. Finally, these substrates were converted to valeroand caprolactams, respectively, via intramolecular Friedel-Crafts cyclization in the presence of a Lewis acid. Additionally, effects of substituent groups at the phenyl ring in the electrophilic aromatic substitution were investigated. [ABSTRACT FROM AUTHOR]

A convenient, general procedure for formylation of di-verse range of phenols with the Duff protocol has been developed. The procedure gives dialdehydes when possible. [ABSTRACT FROM AUTHOR]

3-(Trimethylstannyl)benzyl alcohol was coupled in a Mitsunobu reaction with bis(Boc)-guanidine to give bis(Boc)-protected 3-(trimethylstannyl)benzylguanidine used as precursor for [*I]MIBG. Radioiodination with [131I]iodine generated from [131I]NaI and chloramine-T, removal of Boc groups, and purification by HPLC gave no-carrier-added tracer [*I]MIBG (81% radiochemical yield, 99% chemical purity) used for imaging tumors of neuroendocrine origin. The structures of bis(Boc)-guanidine and bis(Boc)-protected 3-(trimethylstannyl)benzylguanidine were secured by single crystal X-ray structure analyses. [ABSTRACT FROM AUTHOR]

Direct electrophilic arene borylation is introduced as a new synthetic approach to aryl boronate esters. This perspective covers both the key historic breakthroughs and the more recent developments in this area. [ABSTRACT FROM AUTHOR]

Diglycosylated heteroaromatics may serve as metabolically stable mimetics of trisaccharides. Herein, the preparation of several 1,3- and 2,3-diglycosylindoles by direct C-glycosylation of monoglycosylated precursors is described. [ABSTRACT FROM AUTHOR]

A simple and convenient synthetic method to prepare N-substituted pyrrole-3-carbaldehydes by Vilsmeier-Haack formylation of pyrroles using sterically crowded formamides was developed. The dependence of the formylation regioselectivity on steric features of substrates and reagents is discussed. [ABSTRACT FROM AUTHOR]

The intramolecular vinylogous Nicholas reactions of aryl substituted acetoxy enyne-Co2(CO)6 complexes afford tricyclic 6,7,6-ring systems and related systems in good yield. [ABSTRACT FROM AUTHOR]

A new short and reasonably efficient synthesis of N-(2- ethylhexyl)-2,7-diiodocarbazole is presented. 4,4′-Diiodobiphenyl was nitrated and the resulting 4,4′-diiodo-2-nitrobiphenyl was converted via Freeman's modification of the Cadogan ring closure into 2,7-diiodocarbazole, which was then alkylated in the final step. The synthesis represents a significant simplification of the reported fivestep procedure. [ABSTRACT FROM AUTHOR]

The palladium-mediated intramolecular coupling reaction of 2-[(3-substituted-phenoxy)methyl]quinolines for preparing chromeno[3,4-b]quinolines was explored. The results of the cyclizations gave convincing evidence for an electrophilic aromatic substitution mechanism under standard Heck conditions. [ABSTRACT FROM AUTHOR]

With the purpose to synthesize novel ADAs (adenosine deaminase) and IMPDH (inosine 5′-monophosphate dehydroge�nase) inhibitors the reaction of 5-amino-1-tert-butyl-1H-pyrrolo-3-carbonitrile with fluorinated 1,3-biselectrophiles was studied. An efficient and convenient synthetical approach to obtain fluorinated pyrrolo[2,3-b]pyridines was developed. tert-Butyl protecting group was successfully cleaved by treating of synthesized pyrrolo�pyridines with concentrated sulfuric acid. [ABSTRACT FROM AUTHOR]

Nicholas reactions on 2,7-dioxygenated naphthalenes give C-1 monosubstitution and C-1/C-8 disubstitution in most �cases. From γ-carbonyl cation monocondensation product 3b or alkyne-unsubstituted dicondensation product 4a, cyclohepta[de]naphthalenes bearing no substituents, gem-dimethyl substituents, and a ketone function, and the rearranged abietane framework of microstegiol may be prepared. [ABSTRACT FROM AUTHOR]

A direct synthesis of symmetric and unsymmetric electron-rich diaryliodonium salts is described. The use of MCPBA and toluenesulfonic acid delivers diaryliodonium tosylates in high yields. An in situ anion exchange has also been developed, giving access to the corresponding triflate salts. [ABSTRACT FROM AUTHOR]

In situ generated benzofuran-2-amine reacts with 1,3-CCC-dielectrophiles, such as CF3-containing β-diketones, 3-formylchromone, methyl-2,4-dioxopentanoate and pentafluoro�benzaldehyde, and the reaction leads to the formation of benzofuro[2,3-b]pyridine ring system. By using a similar approach 4-trifluoromethyl-α-carbolines were synthesized starting from indole-2-amine. [ABSTRACT FROM AUTHOR]

A new family of N-(2,4-dinitrophenyl)-2-pyrazolino[60]fullerene derivatives has been synthesized by electrophilic nitration using nitronium triflate. As evidenced by CV and OSWV experiments, these species show enhanced electron-accepting �properties (up to 90 mV) with respect to C60. [ABSTRACT FROM AUTHOR]

Phenones can be efficiently transformed into β-substituted chalcones in a two-step process. First, propargylic alcohols were obtained by addition of ethoxyacetylene anion to aromatic ketones. Activation of the propargylic alcohols using a catalytic amount of acid in the presence of an electron-rich aromatic ketone affords the title enones in moderate to good yields. [ABSTRACT FROM AUTHOR]