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An experimental protocol to achieve the Meerwein−Ponndorf−Verley (MPV) reduction of ketones under mildly basic conditions is reported. The transformation is tolerant of a range of ketone substrates, including O- and S-containing heterocycles, is scalable, and shows potential to be used as a platform to access enantioenriched products. These studies provide a general method for achieving the reduction of ketones under mildly basic conditions and offer an alternative protocol to more well-known Al-based MPV reduction conditions.

The Ni-catalyzed [8 + 3]-cycloaddition of tropone with 2-aryl-N-tosylaziridines proceeded smoothly under mild reaction conditions, affording various 4-tosyl-2,3,4,4a-tetrahydrocyclohepta[b][1,4]oxazine derivatives in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

The xanthate-mediated addition of tertiary alkyl radicals to heteroarenes enabled the easy functionalization of heteroaromatic rings as well as more decorated structures, such as marketed drugs or agrochemicals. This work provides a synthetic tool for efficiently exploring the chemical space by allowing late-stage diversification with a high tolerance toward functional groups. [ABSTRACT FROM AUTHOR]

A method for the radical chlorodifluoromethylation of (hetero)arenes using chlorodifluoroacetic anhydride is reported. This operationally simple protocol proceeds under mild photochemical conditions with high functional group compatibility and complements the large body of literature for the trifluoromethylation of (hetero)arenes. Introduction of the chlorodifluoromethyl motif enables rapid diversification to a wide array of aromatic scaffolds. This work showcases the chlorodifluoromethyl group as an attractive entryway to otherwise synthetically challenging electron-rich difluoromethyl(hetero)arenes. Furthermore, facile conversion of the CF2Cl moiety into the corresponding aryl esters, gem-difluoroenones, and β-keto-esters is demonstrated. [ABSTRACT FROM AUTHOR]

Unfunctionalized indoles can be directly converted into 3,3′-spirocyclic indolenines and indolines upon reaction with electrophilic dihalides in the presence of t-BuOK/BEt3. This double C–C bond forming reaction, which simultaneously generates a quaternary spirocyclic center, typically proceeds in high yield and has good functional group tolerance. In contrast to existing dearomatizing spirocyclization approaches, there is no need to prepare a prefunctionalized aromatic precursor, enabling faster access to valuable spirocyclic products from simple, commercially available aromatics in one step. [ABSTRACT FROM AUTHOR]

o-Phenylene tetramers have been coassembled with linkers into macrocycles through imine condensation. Variation of linker connectivity and length allows both [1 + 1] and [2 + 2] macrocycles to be obtained, complementing (previously reported) [3 + 3] macrocycles. For the [1 + 1] macrocycles, linker length has a clear effect on o-phenylene geometry and macrocycle stability. For the [2 + 2] macrocycles, both homo- and heterochiral configurations are observed, suggesting limited communication of helix handedness in these systems. [ABSTRACT FROM AUTHOR]

Preorganized structures suitable for anion binding were prepared by introducing dipyrrolyldiketone BF2 complexes as acyclic anion-responsive π-electronic molecules into macrocycles. Pyrrole-inverted conformations, which typically present low stability in the case of acyclic derivatives, were obtained by covalent linkages through ring-closing olefin metathesis, exhibiting extremely high affinity for different anions. [ABSTRACT FROM AUTHOR]

This report describes an efficient nitrating system for the nitration of arenes at room temperature by using an equivalent of nitric acid in HFIP (1,1,1,3,3,3-hexafluoroisopropanol). The π-complex intermediate of an arene with a nitronium ion stabilized by HFIP can be directly observed by UV–vis spectra and is supported by theoretical calculations. [ABSTRACT FROM AUTHOR]

Two hybrid dyes possessing tetraphenylethylene moieties weakly conjugated with a pyrrolo[3,2-b]pyrrole core have been synthesized. Both dyes display a weak emission in solution, however, in the solid state a ∼100-fold increase in the fluorescence quantum yield is observed. The position of the molecular rotors about the core greatly influences the photophysical characteristics. The variances in emission properties were assigned to entirely different changes in dihedral angles upon excitation, which in turn have substantial effects on radiative rate constants, allowed transitions, and HOMO/LUMO distribution. [ABSTRACT FROM AUTHOR]

Copper- or silver-catalyzed cascade radical addition/dearomative spirocyclization of biaryl ynones with fluoroalkyl bromides or diethylphosphite has been realized for the first time. This method provides a novel and step-economical protocol for the divergent synthesis of a wide range of difluoromethylated or monofluoromethylated and phosphorated spiro[5.5]trienones in moderate to high yields. [ABSTRACT FROM AUTHOR]

Hydrogen gas can be generated from simple alkanes (e.g., n-pentane, n-hexane, etc.) and diethyl ether (Et2O) by mechanochemical energy using a planetary ball mill (SUS304, Fritsch Pulverisette 7), and the use of stainless steel balls and vessel is an important factor to generate the hydrogen. The reduction of organic compounds was also accomplished using the in-situ-generated hydrogen. While the use of pentane as the hydrogen source facilitated the reduction of the olefin moieties, the arene reduction could proceed using Et2O. Within the components (Fe, Cr, Ni, etc.) of the stainless steel, Cr was the metal factor for the hydrogen generation from the alkanes and Et2O, and Ni metal played the role of the hydrogenation catalyst. [ABSTRACT FROM AUTHOR]

An unprecedented catalytic reductive cleavage of aromatic and heteroaromatic methyl ester functions was successfully achieved with a cheap, nontoxic, and air-stable Cu(OAc)2 catalyst. This reaction is fast, features good functional group tolerance, does not require inert atmosphere or anhydrous solvent, and can be scaled up to 1 g. Moreover, carboxylic acids and t-butyl esters also reacted smoothly under these conditions. [ABSTRACT FROM AUTHOR]

The extension of the family of dyn[n]arenes toward a three-membered macrocycle is reported. Through a templated approach, a single diastereoisomer of a dyn[3]arene that bears six carboxyl groups could be isolated by precipitation in 59-63% yield and excellent purity (≥95%). A combination of experimental and computational experiments in water at physiological pH revealed that the macrocycle could bind parent biogenic polyamines with a unique diversity of surface-binding modes. Whereas no binding event could be accurately measured with 1,3-diaminopropane, spermidine formed a classical stoichiometric complex with the dyn[3]arene in the millimolar concentration range. On the other hand, the data obtained for spermine could only be attributed to a more complex binding event with the formation of a 2:1 complex at high [host]/[guest] ratios and redistribution toward a 1:1 complex upon further addition of guest. [ABSTRACT FROM AUTHOR]

Lithiation of the calix[6]arene methyl ether 2 followed by reaction with O2 yields derivatives with two opposite methylene groups hydroxylated. Calix[6]arenes with two opposite bridges functionalized with alkoxy, azido, and m-xylyl groups were prepared via reaction of a dichlorocalix[6]arene derivative with nucleophiles. [ABSTRACT FROM AUTHOR]

1,1′-Carbonyldiimidazole was found to induce the formation of a variety of 3,4-disubstituted 1,2,5-oxadiazoles (furazans) from the corresponding bisoximes at ambient temperature. This method enables these inherently energetic compounds to be prepared at temperatures well below their decomposition points and with improved functional group compatibility relative to prior methods. Conditions were developed that allowed for the first high-yielding synthesis of chlorofurazans from their amino counterparts, enabling the mild synthetic manipulation of these heterocycles. [ABSTRACT FROM AUTHOR]

The first examples of nonenzymatic N-oxidation of heteroarenes in the presence of amines are reported. Pyridine, quinoline, and isoquinoline N-oxides are selectively formed in the presence of more reactive aliphatic and alicyclic amines by use of an in situ protonation strategy and an iminium salt organocatalyst. Application to late-stage functionalization that mimics phase 1 metabolism of small-molecule drugs is also demonstrated. [ABSTRACT FROM AUTHOR]

A Ru(II)-catalyzed, redox-free, two-fold aromatic/allylic C–H bond activation of aromatic acids with allylic acetates to give (Z)-3-ylidenephthalides is described. In the reaction, H2 was formed as a side product. The detailed mechanistic investigation and DFT studies including the transition-state analysis support the postulate that the C–H allylation takes place at the ortho position of aromatic acids with allylic acetates followed by intramolecular cyclization at the allylic C(sp3)–H via a π-allylruthenium intermediate. [ABSTRACT FROM AUTHOR]

The utilization of the transient directing strategy into the direct oxidative dehydrogenative arylation of aldehydes with arenes was reported for the first time. Featured by mild reaction conditions, good functional group compatibility, and great regioselectivity, the method should find broad applications in new medicine and material development and discovery processes. [ABSTRACT FROM AUTHOR]

The synthesis and structure of a C3-symmetric propeller-shaped polycyclic aromatic hydrocarbon that bears three seven-membered rings is reported. The synthesis was accomplished in three steps from benzo[c]naphtho[2,1-p]chrysene, including a Pd-catalyzed intramolecular C–H arylation for the formation of the seven-membered rings. The combination of the helicities (P/M) of the three seven-membered-ring moieties and three [4]helicene moieties affords 24 possible conformers, and two relatively stable conformations were observed by 1H NMR spectroscopy. [ABSTRACT FROM AUTHOR]

A nontrivial Ru-catalyzed one-pot sequential oxidative coupling of a (hetero)arene/vinylic/chromene system with alkyne and quinone is presented; the methyl phenyl sulfoximine (MPS) directing group is vital. This cyclization forms four (two C–C and two C–N) bonds in a single operation and produces unusual spiro-fused-isoquinolones with a broad scope. The release of phenyl methyl sulfoxide makes the MPS group transformable. A deuterium scrambling study sheds light on the reaction path. [ABSTRACT FROM AUTHOR]

A Pd-catalyzed site-selective C(sp2)–H activation/cycloimidoylation of 2-isocyano-2,3-diarylpropanoates to construct diverse cyclic imine products has been developed. Six-membered 3,4-dihydroisoquinolines containing a C3 quaternary carbon center were generated dominantly by using bulky Ad2Pn-Bu as a ligand, while five-membered 1,1-disubstituted 1H-isoindoles were formed preferentially in the presence of bidentate phosphine ligand DPPB. The selectivity for 1H-isoindole formation was enhanced by using steric hindered aryl iodides. DFT calculations suggested that the experimentally observed ligand-controlled selectivity was a result of trans effect. [ABSTRACT FROM AUTHOR]

C–N-linked bi(heteroaryl)s are synthesized by a rhodium-catalyzed N-heteroarylation reaction of N-benzoyl heteroarenes including azoles/azolones, pyridones, cyclic ureas, and cyclic imides using heteroaryl aryl ethers. The reaction involves the covalent bond-exchange reaction of N–CO and HetAr–O bonds without using metal bases and exhibits a broad applicability, giving diverse C–N-linked bi(heteroaryl)s containing five- and six-membered heteroarenes. The N-heteroarylation of N–H azoles/azolones and pyridone proceeds at higher reaction temperatures. [ABSTRACT FROM AUTHOR]

A radical C-H arylation reaction of oxazoles with (hetero)aryl iodides using Cs2CO3 as base/electron donor and 1,1'-bis(diphenylphosphino) ferrocene (dppf) as a catalytic SET mediator is reported. The overall reaction likely follows the general base-promoted homolytic aromatic substitution mechanism through a radical-chain pathway. DFT calculations suggest that dppf forms a complex with CsCO3-, enhancing its SET reducing ability to generate an aryl radical from ArI. [ABSTRACT FROM AUTHOR]

The Diels-Alder addition of arynes to appropriately substituted vinyl/aryl glycals followed by π-extension via pyran ring opening smoothly furnished meta-disubstituted fused aromatic cores containing a stereodefined orthogonally protected chiral side chain. The method is broad in terms of aryl homologation, affording benzene, naphthalene, and phenanthrene derivatives. Base-induced deprotonation followed by cleavage of the allylic C-O bond appear to be the crucial steps leading to the development of aromaticity, which is the driving force behind the annulative π-extension process. The present protocol can be used for the synthesis of meta-disubstituted naphthalene aldehydes and substrates for aldolases. [ABSTRACT FROM AUTHOR]

Connecting basic hydrogen-bonding units with lengthened flexible or rigid linkers generates oligoamide strands that carry new H-bonding sequences and association specificity, leading to H-bonded homo- and heteroduplexes with association constants in the 104 M-1 range in chloroform. Computational and experimental studies indicate that in duplexes with rigid aromatic linkers the oligoamide strands adopt bent conformations that allow the formation of interstrand H-bonds and accommodate the introduced aromatic liners, offering a new series of association units. [ABSTRACT FROM AUTHOR]

The mechanism and regioselectivity of iridium-mediated cleavage of aromatic C-C bonds in a series of monomethylated, dimethylated, and trimethylated benzenes without the activation of weaker C-H and C-C bonds are clarified using density functional theory (DFT) calculations. The calculations explained why the reactivity of the coordinated arene in the observed C-C bond cleavage reaction decreases as the degree of substitution decreases. [ABSTRACT FROM AUTHOR]

Rhodium(III)-catalyzed C–H activation of (hetero)arenes and redox-neutral coupling with 2-carboxyl allylic alcohols has been realized for the construction of β-aryl ketones. This reaction occurred efficiently at a relatively low catalyst loading via initial dehydrogenative alkylation to give a β-keto carboxylic acid, followed by decarboxylation. [ABSTRACT FROM AUTHOR]

Weakly coordinating, ketone-directed, regioselective monoallylation of arenes and indoles is reported using a stable and cost-effective high-valent cobalt(III)-catalyst to access several important molecular building blocks. The allylation proceeds smoothly with a variety of substrates in the presence of various electron-rich and -deficient substituents. The method was applied to the formal synthesis of an ancisheynine alkaloid, a highly conjugated azatetracene, and isochroman. The mechanistic study reveals that the allylation reaction follows a base-assisted intermolecular electrophilic substitution pathway. [ABSTRACT FROM AUTHOR]

A novel method for the synthesis of p-conjugated phosphindolium salts via copper-mediated C-H functionalization of trisubstituted phosphines with alkynes in a single step is reported. The reactions are highly regioselective with unsymmetrical aryl-alkyl-substituted alkynes. This protocol provides an unprecedented atom- and step-efficient access to valuable phosphindolium salts. [ABSTRACT FROM AUTHOR]

The meta-carboxylation of arenes containing pyridine and other azine-directing groups is reported. Using carbon tetrabromide as the C1 source, ruthenium(III) trichloride catalysis enables functionalization of the arene meta-C-H position, affording carboxy methyl ester products after in situ reaction with methanol. [ABSTRACT FROM AUTHOR]

A copper-catalyzed nucleophilic displacement of α-triflyloxy nitriles and esters with silicon nucleophiles allows for the stereospecific generation of highly enantioenriched α-silylated carboxyl compounds. The enantioselective synthesis of α-silylated nitriles is unprecedented. The catalytic system exhibits good functional group tolerance. The stereochemical course of the substitution is shown to proceed with inversion of the configuration. The new reaction is an addition to the still limited number of methods for catalytic C(sp³)-Si cross-coupling. [ABSTRACT FROM AUTHOR]

The untraditional iron-catalyzed, ortho-preferred, radical alkylation of electron-deficient (hetero)arenes is reported. A variety of electron-deficient arenes were shown to react with various primary alkyl sources, producing the alkylated (hetero)arenes in good yields. This reaction might be an alkyl radical, nucleophilic aromatic substitution reaction, rather than the traditional electrophilic Friedel-Crafts reaction. HOMO-LUMO analysis and DFT studies on the key transition states underlying the regioselectivity are consistent with the observed reactions and the conclusions. [ABSTRACT FROM AUTHOR]

Herein it is shown, for the first time, that enolonium species are powerful electrophiles capable of reacting with aromatic compounds in an intermolecular manner to afford a-arylated ketones. The reaction is compatible with a variety of functional groups, is of wide scope with respect to aromatic compounds and ketone, and even works for polymerization-prone substrates such as substituted pyrroles, thiophenes, and furans. Only 1.6 to 5 equiv of the commodity aromatic substrates is needed. [ABSTRACT FROM AUTHOR]

A copper-catalyzed, enantioselective method for the borylallylation of vinyl arenes is reported. The reaction produces enantioenriched and functionalized organoboron compounds by sequentially incorporating boryl and allyl groups onto the C═C bond of vinyl arenes. Copper-catalyzed borylative coupling of vinyl arenes with allyl phosphates successfully proceeds in a regio- and enantioselective manner in the absence of a palladium cocatalyst. [ABSTRACT FROM AUTHOR]

An efficient synthesis of disubstituted acrylic acids has been realized via Rh(III)-catalyzed C-H activation of (hetero)arenes and coupling with four-membered methyleneoxetanones under redox-neutral conditions. In most cases, the reactions are silver-free, and the products are exclusively E-selective with a broad substrate scope. The transformation proceeds via ortho C-H activation followed by selective olefin insertion and β-oxygen elimination. [ABSTRACT FROM AUTHOR]

Deuterium labeled compounds find widespread application in life science. Herein, the deuteration of electron-rich (hetero)aromatic compounds employing B(C6F5)3 as the catalyst and D2O as the deuterium source is reported. This protocol is highly efficient, simply manipulated, and successfully applied in the deuteration of 23 substrates including natural neurotransmitter-like melatonin. It is assumed that the weakening of the O-D bond ultimately results in the formation of electrophilic D+. [ABSTRACT FROM AUTHOR]

The organocatalytic alkylation of 2-methyl-N-heteroaromatics with alcohols has been achieved via SN1-type C(sp³)-H functionalization, providing a green and efficient synthesis of indole and ferrocene-functionalized N-heteroaromatics in high yields. [ABSTRACT FROM AUTHOR]

Based upon a radical polar effect, an intermolecular azidoheteroarylation of simple alkenes via a metal-free radical multicomponent cascade process was achieved. It allows a mild, rapid, and step-economic access to a broad range of azidoalkylated heteroaromatics. Given the diversity in transformations of organic azides and medicinally privileged scaffolds of heteroarenes, this strategy enables efficient synthesis and late-stage derivatization of drugs and candidates. [ABSTRACT FROM AUTHOR]

Azulene-fused polycyclic aromatic hydrocarbons (PAHs) were synthesized from commercially available azulene in four steps. The resulting azulene conjugates exhibited significantly narrow HOMO-LUMO bandgaps with high air stability, confirmed by photophysical study. Introduction of azulene also enabled the unique reversible stimuli-responsiveness even with the weak acid and base, which can potentially control the degree of conjugation and optoelectronic properties by simple acid-base and redox processes. [ABSTRACT FROM AUTHOR]

A free-radical-promoted aryl/heteroaryl C-H silylation using hydrosilane was developed. This cross-dehydrogenative silylation enables both electron-rich and electron-poor aromatics to afford the desired arylsilanes in unique selectivity. A "para-selectivity" was observed by examination of over 54 examples. This exceptional orientation is quite different from that in Friedel-Crafts C-H silylation or transition-metal-catalyzed dehydrogenative silylation. [ABSTRACT FROM AUTHOR]

A diastereomeric mixture of secondary phosphine oxide is stereospecifically converted to chlorophosphine salt by treatment with oxalyl chloride, which stereoselectively affords P-inverted or retained tertiary phosphines, depending on the substitution with aliphatic or aromatic Grignard reagents, respectively, in high to 99% yield and 99:1 dr. The repulsion of π-electron on aryl to lone electron pair on phosphorus is proposed for the P-retained substitution. [ABSTRACT FROM AUTHOR]

Two new bowl-shaped polycyclic aromatic hydrocarbons, based on corannulene and naphthalene dicarboximide, are synthesized by an improved Suzuki--Miyaura cross-coupling and C--H arylation cascade reaction. Crystallographic analyses confirm structural assignments and provide insight into molecular interactions in the solid state. The new bowl-shaped molecules show reversible oxidation and reduction, intense visible range absorption, and high fluorescence quantum yields. These molecules can be considered bowl-shaped congeners of planar perylene dicarboximides. [ABSTRACT FROM AUTHOR]

The synthesis and optoelectronic properties of 24 π-electron, formally antiaromatic fluoreno[3,2-b]fluorene and fluoreno[4,3-c]fluorene (FF), are presented. The solid-state structure of [4,3-c]FF along with computationally analogous molecules shows that the outer rings are aromatic while the central four rings possess a bond-localized 2,6-naphthoquinodimethane motif. The antiaromaticity and biradical character of the FFs is assessed computationally, the results of which indicate the dominance of the closed-shell ground state for these molecules. [ABSTRACT FROM AUTHOR]

The first example of transition-metal-catalyzed ortho/meta-selective dual C--H functionalizations of arenes in one reaction is described. In this transformation, ortho-C--H chlorination and meta-C--H sulfonation of 2-phenoxypyri(mi)dines were achieved simultaneously under catalysis by [Ru(p-cymene)Cl2]2. The other reactant, namely, an arylsulfonyl chloride, played the role of both a sulfonation and chlorination reagent. More importantly, the arylsulfonyl chloride was also an oxidant in the process. Mechanistic studies indicated that six-membered ruthenacycles were the key intermediate in the reaction. [ABSTRACT FROM AUTHOR]

Chiral spiro polycyclic aromatic compounds with thiophene and/or thiophene S,S-dioxide units were synthesized as a new family of circularly polarized luminescence (CPL) materials. Oxidation of the thiophene unit to its S,S-dioxide provided significant changes in photophysical properties such as much higher fluorescence quantum yield and positive solvatochromism in photoluminescence spectra. Density functional theory calculations qualitatively demonstrated the observed absorption properties. The prepared chiral spiro compounds exhibit intense CPL signals with a relatively large dissymmetry factor for small organic molecules. [ABSTRACT FROM AUTHOR]

The first general two-step, one-pot synthetic route to 6-azopurines is presented. Microwave-assisted nucleophilic aromatic substitution of protected 6-chloropurines with hydrazines or hydrazides, followed by metal-free oxidation with oxygen, gives 6-azopurines in high to excellent yields. Photophysical studies revealed intensive n--π* absorption band that makes trans-to-cis photoswitching possible using visible light (λ = 530 nm). [ABSTRACT FROM AUTHOR]

Fluoroalkyl amino reagents 1a and 2a have been developed from commercially available trifluoromethyl trifluorovinyl ether via a hydroamination reaction with diethylamine or dimethylamine. These reagents can be activated by treatment with a Lewis acid and subsequently used as a mono- or dielectrophile for the introduction of the fluoro(trifluoromethoxy)methyl group, either in Vilsmeier-type acylations of aromatic substrates or in the synthesis of fluorinated pyrazoles from CH-acidic substrates and of bis-fluorinated pyrazoles, all being important building blocks for medicinal and agricultural chemistry. [ABSTRACT FROM AUTHOR]

The synthesis and redox properties of first generation S-confused isophlorins are described. Despite structural resemblance to a confused porphyrin, spectroscopic and computational studies reveal weak paratropic ring current effects in these 20π macrocycles. They display redox properties atypical of parent tetrathia isophlorins. Experimental evidence supports the oxidation of an unstable 19π neutral radical, as a transient intermediate, for the formation of a unique 18π aromatic monocationic species. Spectroscopic and structural characterization revealed the substituent dependent macrocycle oxidation unfamiliar to the chemistry of antiaromatic isophlorinoids. [ABSTRACT FROM AUTHOR]