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A palladium-catalyzed decarboxylative allylic sulfonylation reaction of vinyloxazolidine-2,4-diones with inexpensive and readily available sodium sulfinates as sulfonylation reagents has been developed. Under the catalysis of Pd(PPh 3 ) 4 , a wide range of γ-sulfonyl-α,β-unsaturated amides can be synthesized in good to excellent yields. The developed protocol is characterized by exclusive regioselectivity, mild reaction conditions, broad substrate scope, good functional group tolerance, and suitable for gram-scale synthesis.

We report a domino reaction of 2-(2-acylvinyl)indoles as well as the corresponding pyrroles with styrylsulfonium salts under mild conditions, affording cyclopropamitosene analogues in high yields and complete diastereoselectivity. A wide range of ( E )-β-hetaryl-α,β-unsaturated ketones were successfully employed for the synthesis of potentially bioactive cyclopropa[3,4]pyrrolo[1,2- a ]indoles and related cyclopropa[ a ]pyrrolizines, demonstrating the versatility of the developed method. In contrast, ( Z )-isomers of the substrates fail to give cyclopropamitosene derivatives but undergo cyclopropanation of the terminal methyl group.

1,3-Imidazole-4,5-dicarboxylic acid derivatives were investigated with respect to the properties of the underlying N-heterocyclic carbenes. Their selenium adducts were prepared as diesters, monoesters, and dianionic dicarboxylates. Se-methylation yielded selenenyls (cationic selenoethers). 77 Se NMR shifts of selenium adducts are considered a measure of the electronic properties of the underlying N-heterocyclic carbene. Since they are very sensitive to external (solvent, pH, temperature, reference reagent, reference method) and internal parameters (substituent effects, steric effects, nonclassical H-bonding, anisotropy), difficulties can arise in reliably interpreting these values. Our model compounds allow the systematic investigation of the influence of charges on the 77 Se NMR shifts since both structural changes and changes of the measurement conditions have been minimized. Depending on the charge, the 77 Se NMR shifts cover the range from 42.1 ppm (dianionic dicarboxylate) via 65.0 ppm (monoanionic dicarboxylate) and 92.5 ppm (neutral diester) to 153.8 ppm (cationic selenoether) in DMSO- d . The signals also show considerable solvent and pH dependence, which was investigated with a selection of NMR solvents (MeOD, CDCl 6 . The signals also show considerable solvent and pH dependence, which was investigated with a selection of NMR solvents (MeOD, CDCl 3 , CD 2 Cl 2 , CD 3 COOD, CD 3 CN, acetone-d 6 , THF- d 8 , pyridine-d 5 , toluene-d 8 , DMSO- d 6 ) and pH values in D 2 O. Linear relationships were found between the HOMO and LUMO energies and the 77 Se NMR shifts, respectively.

Transition metal-catalyzed and noncatalytic reactions of acrylic thioamides with N -sulfonyliminoiodinanes enabling the selective synthesis under mild conditions of a series of fully decorated S- and N,S-containing heterocycles are described. Fine-tuning of the thioamide structure allows selective preparation in good yields of ortho-fused thiophenes, 1,2-thiazines, and spiro-fused isothiazolines. A one-pot thermally induced rearrangement of sulfonylisothiazolines was discovered as a complementary route to thiophenes.

The harmonic oscillator model of aromaticity (HOMA) offers a straightforward route to quantifying aromaticity that requires no other information than the bond lengths of the conjugated ring in question. Given that such information is often readily obtainable from quantum-chemical calculations, it is pertinent to improve this parametrized model as much as possible. Here, a new version of HOMA is presented where, atypically, the corresponding parameters are derived from the actual bond lengths of both aromatic and antiaromatic (rather than nonaromatic) reference compounds, as calculated with a high-level method. The resulting model, which we denote HOMAc, covers CC, CN, NN, and CO bonds and is tested at eight different levels of theory for 45 (single-ring, multi-ring, carbocyclic, N,O-heterocyclic) molecules across the aromatic-antiaromatic spectrum. Thereby, it is found that HOMAc provides a description of aromaticity and antiaromaticity in better accord with magnetic, energetic, and π-delocalization-based reference data than does the standard parametrization of HOMA. Altogether, the results highlight the possibility to realize more reliable geometry-based probing of (anti)aromaticity with the use of HOMAc and with substantial freedom in the choice of quantum-chemical method.

In contrast to what one can be led to believe upon inspecting some of the recent literature, the dehydrogenative phenothiazination reaction does not require onerous technologies, complicated setups, or advanced catalysts in order to be mild and sustainable. We demonstrate this herein with a most facile, cost-effective, and sustainable Cu(II) catalyzed method, under 1 atm of O 2 at room temperature in methanol, providing broad scope and high yields. These new results further set the dehydrogenative phenothiazination reaction among the green and practical coupling concepts of chemistry.

We disclosed a new strategy for the synthesis of 1,2-amino alcohols enabled by visible light without the requirement of a photocatalyst and metal. Under light irradiation at 400 nm, the reaction of carbonyl derivatives and N -arylamines proceeds via an electron-donor-acceptor (EDA) intermediate, obtaining diverse vicinal amino alcohols decorated with a two-electron-rich/-deficient aryl group.

Herein, an efficient electrochemical three-component C-H functionalization of indoles with sodium bisulfite and alcohols is described, providing a sustainable and convenient synthetic route for the construction of structurally valuable indole-containing sulfonate esters in moderate to good yields. This protocol proceeds in an undivided cell without any metal catalysts or oxidants, features a broad substrate scope, and has an excellent functional group tolerance. Preliminary mechanistic studies suggest that a radical-radical pathway may be involved in this three-component reaction system.

Drastic changes to the character of the acidic catalyst enable the reversal of the double alkyne benzannulation reaction output. In the presence of a strong Brønsted acid, 1,4-dihydropyrrolopyrroles undergo transformation which results in the formation of two 7-membered rings. Computational studies imply that the thermodynamically unfavored 7-membered ring is forged via the kinetically favored 6-endo-dig attack of a protonated alkyne at the position 3a of pyrrolopyrrole followed by a 1,2-vinyl shift.

The generation, interconversion, and reactivity of electrophilic species generated upon activation of nitroalkanes with protic acids (the Nef and Meyer reactions) were investigated by quantum-chemical calculations. N , N -Bis(hydroxy)iminium (R 2 C═N + (OH) 2 ) and N -oxoiminium (R 2 C═N + ═O) cations were shown to be produced independently from aci -nitroalkanes, while N -hydroxynitrilium cations (RC≡N + -OH) were formed via nearly barrierless C-H bond cleavage in N -oxoiminium cations. The N -oxoiminium and N -hydroxynitrilium cations whose formation is favored under highly acidic anhydrous conditions are strong electrophiles capable of reacting even with nonactivated arenes under ambient conditions. The N -oxoiminium cations R 2 C═N + ═O are highly unusual ambident species containing three contiguous electrophilic centers (C, N, and O atoms). Nucleophilic addition at the oxygen atom is less preferred than the C- and N-attack yet possible in an intramolecular variant. These computational results shed light on some key aspects of the mechanisms of the Nef and Meyer reactions and predict the possibility of numerous interrupted versions of these reactions.

By employing electrophilic TsSCF 3 as an efficient SCF 3 source, we reported Cu/ SOP (chiral sulfoxide-phosphine ligand)-catalyzed enantioselective nucleophilic substitutions. Under this protocol, α-pyridyl-α-fluoro esters as latent carbon nucleophiles, compounds containing a C-SCF 3 stereocenter along with azacycles and fluorine atoms, were obtained in good yields and enantioselectivities under mild conditions (up to 68% yield, 92% ee).

A direct electrochemical sulfonylation between indoles, inorganic sulfites, and alcohols was developed, in which various indoyl sulfonate esters were prepared efficiently. In this transformation, the easy-handle and cost-effective inorganic sulfite was disclosed to engage in a Csp 2 -H sulfonylation as the SO 2 source in an undivided electrolysis cell under mild conditions. In addition, the unexpected paired electrosynthesis has been achieved, owing to the dual role of inorganic sulfites, and led to a sulfonylation/reduction sequence to rapidly deliver hydroxyl substituted indole sulfonate esters.

Optical detection of the HSO 4 ion in pure aqueous medium is rare, owing to the very high Gibbs free energy of hydration and ambiguity to distinguish with the isostructural H - ion in pure aqueous medium is rare, owing to the very high Gibbs free energy of hydration and ambiguity to distinguish with the isostructural H 2 ion. Herein, a pair of triphenylamine-based push-pull dyes with different numbers of terminal pyridine fragments, connected via an acetylenic linker, were synthesized by Sonogashira cross-coupling reaction. These two dyes displayed highly selective (LOD = 15.1/8.3 ppb), dual-mode color-changing responses toward the HSO 4 - ion. Herein, a pair of triphenylamine-based push-pull dyes with different numbers of terminal pyridine fragments, connected via an acetylenic linker, were synthesized by Sonogashira cross-coupling reaction. These two dyes displayed highly selective (LOD = 15.1/8.3 ppb), dual-mode color-changing responses toward the HSO 4 was engaged in a bifurcated intermolecular hydrogen bonding interaction (leading to proton transfer) with pyridine nitrogen atoms that altered the extent of intramolecular charge transfer (ICT). The self-assembly of such protonated species was found to be prominent when sulfate was present as the counteranion. The extent of self-assembly was found to be more prominent for the trisubstituted, Y-shaped quadrupolar derivative than that observed for the linear, monosubstituted one. Furthermore, the present system was utilized for the detection of HSO - ion in pure aqueous medium without any interference. Despite the halochromic behavior, both compounds exhibited very distinct optical responses with the HSO 4 - ion. The mechanistic investigation indicated that HSO 4 - was engaged in a bifurcated intermolecular hydrogen bonding interaction (leading to proton transfer) with pyridine nitrogen atoms that altered the extent of intramolecular charge transfer (ICT). The self-assembly of such protonated species was found to be prominent when sulfate was present as the counteranion. The extent of self-assembly was found to be more prominent for the trisubstituted, Y-shaped quadrupolar derivative than that observed for the linear, monosubstituted one. Furthermore, the present system was utilized for the detection of HSO 4 - ions in commercially available samples with satisfactory responses.

An expedient approach to the synthesis of 4-azaspiro[2.3]hexane derivatives is described. The synthetic scheme consists of Tebbe olefination of N -Boc-protected 2-azetidinone (including the first use of the deuterated Petasis reagent Cp 2 Ti(CD 3 ) 2 in the building block preparation) and cyclopropanation of the resulting intermediate. The developed protocols allowed for the preparation of target building blocks on a multigram scale (up to 52 g). To illustrate the potential of the obtained 4-azaspiro[2.3]hexane derivatives for isosteric replacements in drug discovery, their physicochemical and structural characterization was performed, i.e., basicity (p K a ) and lipophilicity (Log  P ) measurements, X-ray diffraction studies, and exit vector plot (EVP) analysis.

A series of novel spirocyclic α-proline building blocks with a spiro conjunction in position 3 of the pyrrolidine ring was prepared to employ two convenient and practical synthetic approaches. Both alternative routes utilize simple and readily available starting materials─cyclic ketones and esters─and comprise 6 and 7 steps, respectively. The methodologies feature distinct advantages, using routine organic chemistry transformations, and are suitable for producing multigram amounts of the target prolines. The approach also became valuable for spirocyclic pyroglutamic acids.

A catalyst-free reductive radical-polar crossover cyclization with alkenes and sodium dithionite to construct densely functionalized cyclic sultines was described. The key to the success of this practical protocol relies not only on a bifunctional role of sodium dithionite, that is, serving as radical initiator and SO 2 source, but also on the diversified conversions (RPCC/SO 2 insertion/S N 2 cyclization and RPCC/SO 2 insertion/1,4-addition cyclization processes), which enabled efficient construction of target compounds with the high efficiency and atom- and step-economy under mild conditions.

N -Nitro derivatives of primary alkyl, aryl and heteroarylamines can be directly alkylated with functionalized alcohols under Mitsunobu conditions at the N and/or O atoms of the nitramino moiety to give secondary nitramines or 1-alkoxydiazene 1-oxides, respectively.

The evolution of energetic materials science presents new challenging tasks associated with the creation of advanced technologies for sustainable development of the future. In this work, a set of new heat-resistant high-energy materials incorporating the polynitrophenyl-1,2,5-oxadiazole scaffold enriched with azo/azoxy moieties have been designed and synthesized. Due to a smart combination of explosophoric groups and 1,2,5-oxadiazole rings, the prepared high-energy substances have excellent thermal stability (up to 300 °C), good densities (up to 1.75 g cm -3 ), high enthalpies of formation (340-538 kJ mol -1 ), and high combined nitrogen-oxygen content (63-68%). In-depth structural analysis revealed the presence of strong intra- and intermolecular hydrogen bonds in aminodinitrophenyl derivatives, which in combination with the small deviation of electrostatic potential values explains the low mechanical sensitivity of these materials. At the same time, trinitrophenyl-1,2,5-oxadiazoles incorporating three adjacent non-coplanar nitro groups demonstrated higher sensitivity to impact, albeit retaining complete insensitivity to friction. The overall performance of the thus prepared high-energy substances exceeds that of the known heat-resistant explosive hexanitrostilbene. Therefore, the newly synthesized family of energetic polynitrophenyl-1,2,5-oxadiazoles provides a fruitful foundation for the creation of the advanced heat-resistant energetic materials of the future.

An iron-catalyzed nitrene transfer reaction for the rapid synthesis of sulfinamidines from readily available sulfenamides is reported. This method features mild conditions, short reaction times, and a broad substrate scope, allowing the preparation of a variety of sulfinamidines in good to excellent yields. The synthetic utility of the sulfinamidine products was further demonstrated through their conversion to other valuable sulfur(VI) compounds, such as sulfondiimidoyl fluorides, sulfinamidiate esters, and sulfonimidamides. Preliminary efforts in the development of an asymmetric variant showed moderate enantioselectivity.

Herein, a cobalt-catalyzed intramolecular enantioselective reductive Heck reaction is disclosed. Starting from N - ortho -iodoaryl-2-(trifluoromethyl)acrylamides, a plethora of chiral oxindoles bearing trifluoromethylated quaternary stereogenic centers at the C3-position are achieved in moderate to good yields (up to 88% yield) and good to excellent enantioselectivities (up to 94% ee) by employing zinc/silane as reducing agent. Other than the trifluoromethyl group, a number of chiral oxindoles bearing alkyl, aryl, and ester groups at C3-position were also obtained albeit in relatively lower enantioselectivities (68-78% ee).

Isoindolones constitute a dominant structural class in synthetic and medicinal chemistry. In this research, an electrochemical reaction involving 2-alkynylbenzamides, inorganic sulfites, and alcohols was first established to provide sulfonyl ester-substituted 3-hydroxyisoindolinone derivatives in moderate to good yields with excellent functional group tolerance. When bulky aryl-substituted 2-alkynylbenzamides are utilized as substrates, sulfonyl ester-substituted 3-alkylideneisoindolinones can be selectively generated with good chemoselectivity. Alkoxysulfonyl radicals derived from the anodic oxidation of inorganic sulfite with alcohols are involved in this transformation.

Reductive deoxygenation of alcohols is particularly challenging because of the high bond dissociation energy of the C-OH bond and the poor leaving ability of the hydroxyl group. Herein we describe a Ph 3 P═O-catalyzed reductive deoxygenation of benzyl alcohols with PhSiH 3 under an air atmosphere within 30 min of reaction time. The use of catalytic loading of Ph 3 P═O enhances the practicality of this protocol.

The outcome of the reaction of tetracyanoethylene with 1,4-dihydropyrrolo[3,2- b ]pyrroles (DHPPs) strongly depends on the character of the substituents present at positions 2 and 5. With electron-withdrawing substituents, the reaction does not occur at all, while, in contrast, the presence of electron-donating substituents yields addition-elimination products. When thiazol-2-yl substituents are located at positions 2 and 5, addition occurs at the thiazole ring, rather than of the DHPP core. In cases where very electron-rich heterocycles are present at positions 2 and 5, a second addition occurs followed by aromatization, leading to the formation of an additional benzene ring bridging two heterocyclic scaffolds. The reaction occurs only at one site since the presence of the strongly electron-withdrawing tricyanoethylene group has a profound impact on electron density at the remaining free position 6. The DHPPs possessing a tricyanoethylene group are strongly polarized and thus enable a push-pull system showing red-shifted absorption and negligible fluorescence. In contrast, dyes possessing a 1,2-dicyanobenzene moiety exhibit strong emission bathochromically shifted by over 100 nm compared to parent 1,4-dihydrotetraarylpyrroles[3,2- b ]pyrroles (TAPPs). Computational studies shed light on the evolution of the photophysical properties as a function of the substitution pattern of the final systems.

A direct and novel transformation of propargylic alcohols with sodium sulfinates for the regio- and stereoselective synthesis of ( E )-1,3-disulfonylpropenes and ( E )-1-sulfonylpropenols was successfully developed in the presence of TMSCl under mild conditions. The preliminary mechanistic experiments demonstrated that the reaction underwent an unprecedented dual nucleophilic substitution/radical addition process, in which sodium sulfinates were used not only as nucleophiles but also as a sulfonyl radical source.

Phthalimide and N -phenylphthalimide smoothly condense with di- p -tolyl ether in triflic acid (CF 3 SO 3 H, TfOH) to obtain the corresponding spiro[isoindoline-1,9'-xanthen]-3-ones. Structural analogs of phthalimide, such as phthalic anhydride and 1,3-indandione (but not saccharin), show similar reactivity. In contrast, N-(tetrafluoropyridin-4-yl)phthalimide reacts with DTE by an alternative pathway, yielding isobenzofuran dispiro derivative. The mechanistic aspects of these reactions are discussed on the basis of in situ NMR and theoretical (DFT) studies, providing insights on the key intermediacy of O,O-diprotonated forms of the starting compounds.

A two-step umpolung approach to the diastereoselective synthesis of aldols was developed, in which a conjugated nitroalkene is used as the synthetic equivalent of the enolonium cation, while a sulfur ylide acts as the equivalent of the α-carbinol anion. The resulting isoxazoline N -oxides undergo catalytic reductive cleavage to aldols under mild conditions at room temperature and under 1 atm hydrogen pressure. The efficiency of the method was demonstrated by the synthesis of a series of polysubstituted β-hydroxyketones that are difficult to synthesize using the classical aldol reaction. The developed approach allows for the regiodivergent assembly of aldols by selecting a nitroalkene isomer with the appropriate position of the C , C double bond.

Nitrogen-containing heterocycles are present in most approved drugs, reflecting the significance of their synthetic strategies. By utilizing oxadiazolone as a nitrenoid (nitrene-like) precursor, we have developed a general strategy for the annulation with nucleophilic heterocycles to access various polycyclic aminoheterocycles. We have discovered that 2-pyrryl-substituted substrates undergo a rearrangement, which indicates a spirocyclization-migration pathway. Given their fluorescence and biological activity as kinase hinge binders, these fragment-like aminoheterocycles represent potential starting points for applications in chemical biology and drug discovery.

Mesoionic compounds are the starting material for the synthesis of unique anionic N-heterocyclic carbenes. Herein, mesoionic imidazolium pyrrolides synthesized from pyrrole-2-carbaldehyde via various N -alkyl-4-pyrroyl-imidazoles are described. These were converted into nine new 4-(pyrrol-2-yl)-substituted imidazolium salts and transformed into the mesoionic title compounds using an anion exchange resin. The DFT-calculated (B3LYP/6-311++G**) CREF values indicate a great potential for the formation of anionic N-heterocyclic carbenes by deprotonation, which were generated and reacted with selenium to obtain selenoureas. The 77 Se NMR shifts investigated under systematic variation of conditions are dependent on the substitution pattern (Δδ Se = 133 ppm) and the steric demand of the substituents. Solvent dependencies of the 77 Se NMR shifts were investigated applying toluene- d 8 , THF- d 8 , CDCl 3 , CD 2 Cl 2 , pyridine- d 5 CN, AcOD, and MeOD. The influences of the referencing method on the d 6 , DMSO- d 6 , CD 3 = ca. 80 ppm. In addition, we observed a temperature dependence of both the selenoureas and the reference reagent Ph 77 Se shifts using external or internal Me 2 Se or Ph 2 Se shift difference of the analyte caused by interaction with internally added Ph 2 and solvent can add up to Δδ Se . The negative charge of deprotonated selenoureas shifts the values by an additional -20 ppm.2 Se 2 as well as a 77 Se shift difference of the analyte caused by interaction with internally added Ph 2 Se 2 . The negative charge of deprotonated selenoureas shifts the values by an additional -20 ppm.

We recently described the development and application of a new bioorthogonal conjugation, the triazinium ligation. To explore the wider application of this reaction, in this work, we introduce a general method for synthesizing C 3 -substituted triazinium salts based on the Liebeskind-Srogl cross-coupling reaction and catalytic thioether reduction. These methods enabled the synthesis of triazinium derivatives for investigating the effect of different substituents on the ligation kinetics and stability of the compounds under biologically relevant conditions. Finally, we demonstrate that the combination of a coumarin fluorophore attached to position C 3 with a C 5 -(4-methoxyphenyl) substituent yields a fluorogenic triazinium probe suitable for no-wash, live-cell labeling. The developed methodology represents a promising synthetic approach to the late-stage modification of triazinium salts, potentially widening their applications in bioorthogonal reactions.

A palladium-catalyzed regioselective [8 + 3] cycloaddition of tropsulfimides and tropones with vinylidenecyclopropane-diesters (VDCP-diesters) has been disclosed in this paper, affording decahydro-1 H -cyclohepta[ b ]pyridine derivatives bearing an allene moiety or decahydro-1 H -cyclohepta[ b ]pyran derivatives having a conjugated diene unit in moderate to good yields. The reactions proceed through a zwitterionic allenyl palladium species derived from VDCP-diesters. The substrate scopes have been investigated and the plausible reaction mechanisms have also been proposed according to the previous work, the first captured zwitterionic Pd-allenyl intermediate, and control experiments.

Trinitromethyl and N -amino groups were innovatively incorporated into the framework of 1,2,4-triazole, resulting in 1-amino-5-nitro-3-(trinitromethyl)-1,2,4-triazole ( 2 ). Ammonium and hydrazinium salts of 1-amino-5-nitro-3-(dinitromethyl)-1,2,4-triazole were synthesized by acidification, extraction, and neutralization with bases from the potassium salt. All of the newly prepared energetic compounds were comprehensively characterized by using infrared spectroscopy, elemental analysis, nuclear magnetic resonance spectroscopy, and single crystal X-ray diffraction. Compound 2 exhibits favorable properties such as positive oxygen balance (OB CO2 = 5.8%), high density (1.88 g cm -1 ), good detonation performances ( v D = 8937 m s -1 , P = 35.5 GPa), and appropriate friction sensitivity (FS = 144 N). The potassium salt 3 ), while the ammonium salt and hydrazinium salt also display good thermal decomposition temperatures of 183 and 176 °C, respectively. Among these compounds, the ammonium salt exhibits the lowest mechanical sensitivities (FS = 144 N, IS = 6 J).-1 ), while the ammonium salt and hydrazinium salt also display good thermal decomposition temperatures of 183 and 176 °C, respectively. Among these compounds, the ammonium salt exhibits the lowest mechanical sensitivities (FS = 144 N, IS = 6 J).

Development of robust d -methylthiolating reagents represents an attractive synthetic method to access deuterated molecules in the field of drug discovery. Here, we report a straightforward strategy to prepare electrophilic 3 -methylthiolating reagents represents an attractive synthetic method to access deuterated molecules in the field of drug discovery. Here, we report a straightforward strategy to prepare electrophilic S arylsulfonothioates in one-step without column purification. These reagents exhibit good radical reactivity toward silver-catalyzed vicinal thiosulfonylation of alkenes or 1,6-enynes on water. As a result, simultaneous incorporation of both SCD d 3 arylsulfonothioates in one-step without column purification. These reagents exhibit good radical reactivity toward silver-catalyzed vicinal thiosulfonylation of alkenes or 1,6-enynes on water. As a result, simultaneous incorporation of both SCD 3 and ArSO 2 units into unsaturated carbon-carbon bonds with 100% atom economy has been established. Moreover, the ATRA adducts with >99% D incorporation can serve as nucleophilic d 3 -methylthiolating synthons via retro-Michael addition under mild basic conditions, providing a good alternative in trideuteromethylthiolating alkyl iodides to access corresponding trideuteromethyl sulfides with high efficiency.

The addition of C-H bonds to isocyanates catalyzed by transition metals is a highly auspicious methodology for providing synthetically and biologically important amides. However, the substrates are limited to C(sp 2 )-H bonds. In this work, an efficient manganese(I)-catalyzed direct addition reaction of C(sp 3 )-H bonds of 8-methylquinolines to aryl isocyanates has been developed, leading to the synthesis of various α-quinolinyl amide compounds in moderate to high yields. The reaction has a broad range of substrates and a good functional group tolerance. A possible mechanism is proposed based on the experimental results.

The ability of sodium hypophosphite to generate the phosphorus-centered radical, which can activate the carbon-halogen bond via the halogen atom transfer (XAT) is described. The hydroalkylation of nonactivated alkenes with methyl bromoacetate was performed using sodium hypophosphite as reducing agent under photocatalytic conditions. The key phosphorus centered radical is formed from the hypophosphite anion by hydrogen atom abstraction.

An efficient and high-selectivity approach for the divergent synthesis of β-sulfinyl alkenylsulfones and ( E )-vinyl sulfones from alkynes and TsCN is described. A series of disulfurized products were constructed under mild conditions in the absence of transition metals. This transformation featured excellent regio- and stereoselectivity, good functional group compatibility, and broad substrate scope. The copper(I)-catalyzed sulfonation of alkynes with TsCN that affords ( E )-vinyl sulfones in good to excellent yields was also developed.

This study demonstrates the rearrangement of C2-spirooxindoles to the 2-hydroxyhemi-indigo and chromenoindole. The N -H-spirooxindole exhibits double proton translocation and its conversion to the ( Z )-2-hydroxyhemi-indigo photoswitch with trifluoroacetic acid, while the N -methyl-spirooxindole undergoes structural rearrangement to the chromenoindole. The mechanism of the reactions was proposed, and the structure of the products was confirmed by one-dimensional (1D) and two-dimensional (2D) NMR spectra and X-ray structure analysis. The photoswitching performance of ( Z )-2-hydroxyhemi-indigo, which allows the stabilization of the E -switched form by intramolecular hydrogen bonding, has been studied in solvents of different polarities. It was found that in the less polar solvents, the E -switched metastable isomer is characterized by high stability.

N -Acetyllactosamine is a common saccharide motif found in various biologically active glycans. This motif usually works as a backbone for additional modifications and thus significantly influences glycan conformational behavior and biological activity. In this work, we have investigated the type-2 N -acetyllactosamine scaffold using the complete series of its monodeoxyfluorinated analogs. These glycomimetics have been studied by molecular mechanics, quantum mechanics, X-ray crystallography, and various NMR techniques, which have provided a comprehensive and complete insight into the role of individual hydroxyl groups in the conformational behavior and lipophilicity of N -acetyllactosamine.

A powerful synthetic strategy for the asymmetric synthesis of enantiomerically enriched γ-functionalized α-amino acid derivatives based on the highly stereoselective proline-catalyzed Mannich-type reaction of pre-prepared or in situ -generated γ-pyrone-derived aldimines with carbonyl compounds and subsequent transformations of multifunctional reaction products has been developed. A significant positive nonlinear effect was detected for the key organocatalytic reaction. The developed strategy was applied for facile gram-scale preparation of ( S )-γ-oxonorvaline, used for site-specific modification of proteins, and both enantiomers of amycolatolide A recently isolated from the lichen-derived actinomycete Amycolatopsis sp. YIM 130923.

Deuteration of amine compounds has been widely of concern because of its practical role in organic reaction mechanisms and drug research; however, only limited deuteration label methods are accessible with D 2 O as a deuterium source. Herein, we propose a convenient deuteration protocol, including preparing D 2 by the AlGa activation method, using PtRu nanowires as catalysts, and utilizing the elementary step in the couple reaction involving an imine unit, to realize the rapid preparation of a secondary amine with a diversified deuteration label. The self-coupling between nitriles not only provides a symmetric secondary amine with four α-D atoms but also produces high-valued ND 3 in an atomic-economic way.

The radical 1,3-hydro-di/monofluoromethylation of N,N' -cyclic azomethine imines with HCF 2 SO 2 Na/H 2 CFSO 2 Na via photoredox catalysis is described. This reaction exhibits broad functional group compatibility, providing the desired products in good yields. However, CF 3 SO 2 Na failed to produce the trifluoromethyl product. DFT calculations revealed that the transition state activation energy for radical trifluoromethylation was significantly higher and the isotropic charge repulsion makes it difficult for the CF 3 radical to transfer electrons.

Hydrofluoroalkylation of alkenes with organozinc reagents under photocatalytic conditions is described. The fluorinated alkyl radicals were generated from organozincs by the single electron oxidation of the carbon-zinc bond. The radical addition step is followed either by hydrogen atom transfer for unactivated olefins or by a reduction/protonation sequence for strongly accepting arylidenemalononitriles.

Herein, we report radical chlorination of cubane-1,4-dicarboxylic acid leading preferentially to one monochlorinated cubane dicarboxylate (ca. 70%) that is accompanied by four dichlorinated derivatives (ca. 20% in total). The exact positions of the chlorine atoms have been confirmed by X-ray diffraction of the corresponding single crystals. The acidity constants of all dicarboxylic acids in water were determined by capillary electrophoresis (3.17 ± 0.04 and 4.09 ± 0.05 for monochlorinated and ca. 2.71 ± 0.05 and 3.75 ± 0.05 for dichlorinated cubanes). All chlorinated derivatives as well as the parent diacid showed high thermal stability (decomposition above 250 °C) as documented by differential scanning calorimetry. The probable reaction pathways leading to individual isomers were proposed, and the energies of individual transition states and intermediates were obtained using density functional theory calculations (B3LYP-D3BJ/6-311+G(d,p)). The relative strain energies for all newly prepared derivatives as well as for hypothetical hexahalogenated (fluorinated, chlorinated, brominated, and iodinated) derivatives of cubane-1,4-dicarboxylic acids were predicted using wavefunction theory methods. The hexafluorinated derivative was identified as the most strained compound (57.5 kcal/mol), and the relative strain decreased as the size of halogen atoms increased (23.7 for hexachloro, 16.7 for hexabromo, and 4.0 kcal/mol for the hexaiodo derivative).

Rational design and development of organic reactions are lofty goals in synthetic chemistry. Quantitative description of the properties of molecules and reactions by physical organic parameters plays an important role in this regard. In this Article, we report an energy scale, namely, electrophile-arene affinity (EAA), for evaluating the thermodynamics of electrophilic dearomatization reactions, a class of important transformations that can rapidly build up molecular complexity and structural diversity by converting planar aromatic compounds into three-dimensional cyclic molecules. The acquisition of EAA data can be readily achieved by theoretically calculating the enthalpy changes (Δ H ) of the hypothetical reactions of various (cationic) electrophiles with aromatic systems (taking the 1-methylnaphthalen-2-olate ion as an example in this study). Linear correlations are found between the calculated Δ H values and established physical organic parameters such as the percentage of buried volume %V Bur (steric effect), Hammett's σ or Brown's σ + (electronic effect), and Mayr's E (reaction kinetics). Careful analysis of the Δ H values leads to the rational design of a dearomative alkynylation reaction using alkynyl hypervalent iodonium reagents as the electrophiles.

Chiral oxygen-containing heterocyclic compounds are of great interest for the development of pharmaceuticals. Monoterpenes and their derivatives are naturally abundant precursors of novel synthetic chiral oxygen-containing heterocyclic compounds. In this study, acid catalyzed reactions of salicylic aldehydes with (-)-8-acetoxy-6-hydroxymethyllimonene, readily accessible from α-pinene, leads to the formation of chiral polycyclic products of various structural types. Three of the six isolated chiral heterocyclic products obtained from salicylic aldehyde contain previously unknown polycyclic ring types. Having carried out the reaction in the presence of Brønsted or Lewis acids (Amberlyst 15, trifluoromethanesulfonic acid, trifluoroacetic acid and boron trifluoride etherate) or aluminosilicates (montmorillonite K10, halloysite nanotubes), we found that the nature of products depends on the catalyst as well as the reaction conditions (reaction time, reactant ratio, presence or absence of solvent). Detailed mechanistic insight on the complex cascade reactions for product formation is provided with extensive experimental and quantum mechanical computational studies.

N -Acyl/sulfonyl-α-functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) are significant structural motifs in organic synthesis and drug discovery. However, the one-pot approach enabling direct difunctionalization of THIQs remains challenging. Herein we report a photomediated one-pot three-component strategy to access N -acyl/sulfonyl-α-functionalized THIQs. This method features the use of oxygen (from air) as the green oxidant, high atom and step economy, and decent structural diversity. The synthetic applicability of the method was further demonstrated via the facile construction of valuable bioactive molecules. Mechanistic studies indicated that oxidation with singlet oxygen and the acceptor-less dehydrogenation were involved in the photoredox process.

Advanced analogs of piperidine and smaller homologues of tropane─3-substituted 6-azabicyclo[3.1.1]heptanes─were synthesized on a large scale using readily available bulk reagents. The key step of the approach involved the double alkylation reaction of malonate with cis -2,4-bis(mesyloxymethyl)azetidine-1-carboxylate, in turn easily prepared on up to 1 kg scale. After hydrolysis, N -Boc-6-azabicyclo[3.1.1]heptane-3,3-dicarboxylic acid was obtained (up to 400 g in a single run), which was used as a common intermediate for the preparation of all the title building blocks. In particular, Pb(OAc) 4 -mediated oxidative decarboxylation of this intermediate gave 2,6-methanopiperidone derivative (up to 400 g scale), while monodecarboxylation gave N -Boc-6-azabicyclo[3.1.1]heptane-3-carboxylic acids as an easily separatable mixture of cis and trans diastereomers (up to 100 g scale). Further functional group transformations gave diastereopure cis - and trans - N -Boc-monoprotected diamines and amino alcohols. Molecular structure analysis using exit vector parameters (EVP) revealed that cis isomers of 3-substituted 6-azabicyclo[3.1.1]heptanes are three-dimensional analogs of common 1,4-disubstituted piperidine chair conformer, whereas trans isomers can be considered as unusual " boat " piperidines.

Inherently chiral compounds, such as calixarenes, are chiral due to a nonplanar three-dimensional (3D) structure. Determining their conformation is essential to understand their properties, with nuclear magnetic resonance (NMR) spectroscopy being one applicable method. Using alignment media to measure residual dipolar couplings (RDCs) to obtain structural information is advantageous when classical NMR parameters like the nuclear Overhauser effect (NOE) or J -couplings fail. Besides providing more accurate structural information, the alignment media can induce different orientations of enantiomers. In this study, we examined the ability of polyglutamates with different side-chain moieties─poly-γ-benzyl-l-glutamate (PBLG) and poly-γ- p -biphenylmethyl-l-glutamate (PBPMLG) ─to enantiodifferentiate the inherently chiral phenoxathiin-based thiacalix[4]arenes. Both media, in combination with two solvents, allowed for enantiodiscrimination, which was, to the best of our knowledge, proved for the first time on inherently chiral compounds. Moreover, using the experimental RDCs, we investigated the calix[4]arenes conformational preferences in solution, quantitatively analyzed the differences in the alignment of the enantiomers, and discussed the pitfalls of the use of the RDC analysis.

Herein, we report a mild and general protocol for chemoselective deacetylation of mixed acetyl- and benzoyl-protected carbohydrates under mild acidic conditions. The protocol allows quick access to partially protected carbohydrates, which serve as versatile synthetic intermediates during the total synthesis of various mono- and oligosaccharide targets. The applicability of the developed protocol was successfully demonstrated on a range of carbohydrate substrates of various configurations and substitution patterns featuring functionalized aliphatic and aromatic aglycones. The protocol has shown excellent compatibility with the widely used O -anomeric protecting groups, prespacer aglycones, and thioglycoside glycosyl donors.

N-protected sulfilimines are prepared by imination of sulfides with a combination of 2,2,2-trichloroethyl sulfamate (H 2 NTces), (diacetoxyiodo)benzene (PIDA), and a catalytic amount of iron triflate. The reaction proceeds at room temperature, and after only 3 h a wide range of acyclic and cyclic N Tces-sulfilimines with various functional groups and (hetero)aryl substituents can be obtained. By subsequent oxidation followed by deprotection, the products are converted into N H-sulfoximines.

A three-component reaction of 1-(1 H -indol-1-yl)isoquinolines or 1-(pyridin-2-yl)-1 H -indoles, DABCO·(SO 2 ) 2, and thianthrenium salts under synergistic photoredox and palladium catalysis is accomplished. This direct C-H bond sulfonylation of indoles with the insertion of sulfur dioxide under mild conditions works efficiently, giving rise to a wide range of 2-sulfonated indoles in moderate to good yields under mild conditions. In this protocol, the generality of aryl/alkyl thianthrenium salts is demonstrated as well. A photoredox radical process combined with palladium catalysis is proposed.