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We present a new class of room-temperature stable diazoalkenes featuring a 1,2,3-triazole backbone. Dinitrogen of the diazoalkene moiety can be thermally displaced by an isocyanide and carbon monoxide. The latter alkylidene ketenes are typically considered as highly reactive compounds, traditionally only accessible by flash vacuum pyrolysis. We present a new and mild synthetic approach to the first structurally characterized alkylidene ketenes by a substitution reaction. Density functional theory calculations suggest the substitution with isocyanides to take place via a stepwise addition/elimination mechanism. In the case of carbon monoxide, the reaction proceeds through an unusual concerted exchange at a vinylidene carbon center. The vinylidene ketenes react with carbon disulfide via a four-membered thiete intermediate to give vinylidene thioketenes under release of COS. We present spectroscopic as well as structural data for the complete isoelectronic series (R2C═C═X; X = N2, CO, CNR, CS) including 1J(13C-13C) data. As N2, CO, and isocyanides belong to the archetypical ligands in transition-metal chemistry, this process can be interpreted in analogy to coordination chemistry as a ligand exchange reaction at a vinylidene carbon center.

Highlights A general layered 2D materials-derived atomic substitution conversion strategy is proposed to achieve the synthesis of large-size ultrathin nonlayered 2D materials.Using low-melting-point CdI2 flakes via a simple hot plate assisted vertical vapor deposition method as precursor, large-size ultrathin CdS flakes were successfully converted from layered to nonlayered nanostructures through a facile low-temperature chemical sulfurization process.The size and thickness of CdS flakes can be controlled by the CdI2 precursor. The growth mechanism is ascribed to the chemical substitution reaction from I to S atoms between CdI2 and CdS, which has been evidenced by experiments and theoretical calculations. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00692-6., Nonlayered two-dimensional (2D) materials have attracted increasing attention, due to novel physical properties, unique surface structure, and high compatibility with microfabrication technique. However, owing to the inherent strong covalent bonds, the direct synthesis of 2D planar structure from nonlayered materials, especially for the realization of large-size ultrathin 2D nonlayered materials, is still a huge challenge. Here, a general atomic substitution conversion strategy is proposed to synthesize large-size, ultrathin nonlayered 2D materials. Taking nonlayered CdS as a typical example, large-size ultrathin nonlayered CdS single-crystalline flakes are successfully achieved via a facile low-temperature chemical sulfurization method, where pre-grown layered CdI2 flakes are employed as the precursor via a simple hot plate assisted vertical vapor deposition method. The size and thickness of CdS flakes can be controlled by the CdI2 precursor. The growth mechanism is ascribed to the chemical substitution reaction from I to S atoms between CdI2 and CdS, which has been evidenced by experiments and theoretical calculations. The atomic substitution conversion strategy demonstrates that the existing 2D layered materials can serve as the precursor for difficult-to-synthesize nonlayered 2D materials, providing a bridge between layered and nonlayered materials, meanwhile realizing the fabrication of large-size ultrathin nonlayered 2D materials. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00692-6.

Novel 1,2-diamines based on the mefloquine scaffold prepared in enantiomerically pure forms resemble 9-amino-Cinchona alkaloids. Most effectively, 11-aminomefloquine with an erythro configuration was obtained by conversion of 11-alcohol into azide and hydrogenation. Alkylation of a secondary amine unit was needed to arrive at diastereomeric threo-11-aminomefloquine and to introduce diversity. Most of the substitution reactions of the hydroxyl group to azido group proceeded with net retention of the configuration and involved actual aziridine or plausible aziridinium ion intermediates. Enantiomerically pure products were obtained by the resolution of either the initial mefloquine or one of the final products. The evaluation of the efficacy of the obtained vicinal diamines in enantioselective transformations proved that erythro-11-aminomefloquine is an effective catalyst in the asymmetric Michael addition of nitromethane to cyclohexanone (up to 96.5:3.5 er) surpassing epi-aminoquinine in terms of selectivity.

The electron-rich nature of aminoaromatic compounds and the electrophilic character of fluoroalkyl RF radicals allow for a special match in substitution reactions. We herein present visible light photocatalyzed fluoroalkylation reactions of aniline derivatives, with a study of the reaction mechanisms. The examples evaluated make use of different photocatalysts, such as polypyridyl complexes of Ir or Ru transition metals, organic dyes such as Rose Bengal, phthalocyanine-metal organocatalysts, or visible-light activated complexes. Different visible light sources that span from the blue region of the electromagnetic spectrum to low power red light irradiation sources deliver the excited photocatalysts that ensue into the production of fluoroalkyl RF radicals. In turn, many sources of RF radicals can be employed, such as fluoroalkyl halides, Togni’s reagents, Umemoto’s reagent, etc. All these protocol variants demonstrate the expansion of the methodology and the versatility of photocatalytic techniques applied to a special family of organic compounds such as aminoaromatic substrates, which has been studied by different groups. Contributions from our own laboratory will be given.

The dynamic parallel kinetic resolution (DPKR) of an α-ferrocenyl cation intermediate under the influence of a chiral conjugate base of a chiral phosphoric acid catalyst has been demonstrated in an SN1 type substitution reaction of a racemic ferrocenyl derivative with a nitrogen nucleophile. The present method provides efficient access to a ferrocenylethylamine derivative in a highly enantioselective manner, which is potentially useful as a key precursor of chiral ligands for metal catalysis. The mechanism of the present intriguing resolution system was elucidated by control experiments using the enantio-pure precursor of relevant α-ferrocenyl cation intermediates and the hydroamination of vinylferrocene. Further theoretical studies enabled the elucidation of the origin of the stereochemical outcome as well as the efficient DPKR. The present DPKR, which opens a new frontier for kinetic resolution, involves the racemization process through the formation of vinylferrocene and the chemo-divergent parallel kinetic resolution of the enantiomeric α-ferrocenyl cations generated by the protonation/deprotonation sequence of vinylferrocene., The dynamic parallel kinetic resolution (DPKR) of an enantiomeric α-ferrocenyl cation using a chiral phosphate anion of an acid catalyst was accomplished by the combination of the PKR and the racemization through the formation of vinylferrocene.

This highlight review overviews our recent advances on enantioselective propargylic substitution reactions catalyzed by transition metal complexes including cooperative and hybrid catalysts for the...

Graphical AbstractNVP-2 (1), a potent and selective inhibitor of cyclin-dependent kinase 9 (CDK9), showed potent antitumor activity in preclinical studies. In this work, we designed and adopted a convergent synthetic route to efficiently synthesize NVP-2 (1). The key intermediate (7) was synthesized from malononitrile (2) and 1-bromo-2-(2-bromoethoxy)ethane (3) by successive cyclization, reduction, nucleophilic substitution with 2-bromo-6-fluoropyridine, and Suzuki–Miyaura reaction with (5-chloro-2-fluoropyridin-4-yl)boronic acid. Another key intermediate (11) was synthesized from (S)-1-methoxypropan-2-ol (8) by reaction with TsCl, electrophilic substitution reaction with tert-butyl ((1r,4r)-4-aminocyclohexyl)carbamate, and then by deprotection of Boc. Finally, a substitution reaction by the key intermediates (7) and (11) to afford the target product NVP-2 (1). The reaction conditions of the whole synthesis process were simple and mild, free of harsh conditions such as the microwave reaction and dangerous reagents in the original patent, and realized the efficient synthesis of NVP-2. In addition, we analyzed the binding mode of NVP-2 in the active pocket of CDK9 to provide reasonable design ideas for subsequent discovery of novel CDK9 inhibitors.

Methyl 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate and (2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)(pyrrolidin-1-yl)methanone are boric acid ester intermediates with benzene rings. In this paper, the title compounds are obtained by a three-step substitution reaction. The structures of the compounds are confirmed by FTIR, 1H and 13C NMR spectroscopy, and mass spectrometry. At the same time, single crystals of the title compounds are measured by X-ray diffraction and subjected to crystallographic and conformational analyses. The molecular structures are further calculated using density functional theory (DFT), which were compared with the X-ray diffraction value. The results of the conformational analysis indicate that the molecular structures optimized by DFT are consistent with the crystal structures determined by single crystal X-ray diffraction. In addition, the molecular electrostatic potential and frontier molecular orbitals of the title compounds are further investigated by DFT, and some physicochemical properties of the compounds are revealed.

Due to an intrinsically polar π-bond with a narrow π-π* gap, silenes (silicon-carbon doubly bonded compounds) should receive remarkable attention as a member of π-conjugation units. We report herei...

The SN2 reaction exhibits the classic Walden inversion, indicative of the stereospecific backside attack of the nucleophile on the stereogenic center. Observation of the inversion of the stereocenter provides evidence for an SN2-type displacement. However, this maxim is contingent on substitution proceeding on a discrete stereocenter. Here we report an SN2 reaction that leads to enantioenrichment of product despite starting from a racemic mixture of starting material. The enantioconvergent reaction proceeds through a dynamic Walden cycle, involving an equilibrating mixture of enantiomers, initiated by a chiral aminocatalyst and terminated by a stereoselective SN2 reaction at a tertiary carbon to provide a quaternary carbon stereocenter. A combination of computational, kinetic, and empirical studies elucidates the multifaceted role of the chiral organocatalyst to provide a model example of the Curtin-Hammett principle. These examples challenge the notion of enantioenriched products exclusively arising from predefined stereocenters when operating through an SN2 mechanism. Based on these principles, examples are included to highlight the generality of the mechanism. We anticipate the asymmetric SN2 dynamic kinetic resolution to be used for a variety of future reactions.

Iridium/Bronsted acid cooperative catalyzed asymmetric allylic substitution reactions at the C5 position of indolines have been reported for the first time. The highly efficient protocol allows rapid access to various C5-allylated products in good to high yields (48-97%) and enantioselectivities (82% to >99% ee) with wide functional group tolerance. The transformations allow not only the formation of C5-allylindoline derivatives but also the synthesis of C5-allylindole analogues in good yields and excellent stereoselectivities via an allylation/oxidation reaction sequence.

The development of transition metal-catalyzed enantioselective propargylic substitution reactions has gained much progress in recent years, however, no successful example with phosphorus-centered nucleophiles has yet been reported until now. Herein, we report the first successful example of ruthenium-catalyzed enantioselective propargylic substitution reactions of propargylic alcohols with diarylphosphine oxides as phosphorus-centered nucleophiles. This synthetic approach provides a new method to prepare chiral phosphorus-containing organic compounds.

Compared with the ever-growing list of nonprochiral nucleophiles in Ir-catalyzed asymmetric allylic substitution reactions, prochiral nucleophiles are less studied. We present a new prochiral nucleophile, namely, deconjugated butyrolactam, for Ir-catalyzed asymmetric allylic alkylation (AAA). This reaction provides access to I±-allyl deconjugated butyrolactams with a moderate to good dr and an excellent er. This is the first AAA reaction of deconjugated butyrolactams. Allyl transposition through Cope rearrangement appears to proceed stereospecifically to form I³-allyl conjugated butyrolactams. © 2021 American Chemical Society.

In recent years, carbon dots (CDs) have attracted great research interest in the field of nanochemosensors due to their fascinating optical properties. However, synthesis of CDs with novel recognition groups in a convenient method is still an area to be explored urgently. In this work, we reported a simple strategy to prepare fluorescent CDs with carbon-carbon double bonds (C═C) as the characteristic structure for phenylephrine (PHE) identification and detection. The itaconic acid and polyethylenimine (PEI) were selected as precursors to fabricate highly emissive CDs under the hydrothermal cross-linking and carbonization process. The fluorescence of designed CDs at 465 nm can be effectively quenched by bromine aqueous solution due to the electrophilic addition reaction with the double bonds. On the other hand, the presence of PHE can inhibit fluorescence quenching by bromine-consumption of a substitution reaction. Inspired by the novel findings, a convenient assay for PHE determination was established using the fluorescence of C═C bond functional CDs as an output signal and bromine as a bridge. The method demonstrated here provided a unique way to develop CD-based nanosensors.

The review summarizes the existing methods of the synthesis of 2-aminochromanes. N,O-acetals in which the dihydropyran ring is spiroannulated or condensed with any carbo- or heterocyclic fragment at the b or c bond are not considered in the review because of the wide variety of methods for their preparation. The main attention is paid to (4+2) annulation processes with the participation of o-quinone methide precursors, salicylic aldehydes and their imino derivatives, as well as substitution reactions in chroman-2-ols and conjugated addition to electron-deficient 4H-chromenes.

The reaction of P,S-phosphoramidite bearing (Ra)-BIPHEN H2 core and exocyclic amino sulfide as the new ligand with [Pd(ppp-allyl)Cl]2 in the presence of AgBF4 yielded a cationic metallochelate [Pd(ppp-allyl)(L)]BF4. This new chiral inducer provided up to 90% ee in the Pd-mediated allylic substitution reaction of (E)-1,3-diphenylallyl acetate with various C- and N-nucleophiles. In the Pd-catalyzed amination of 2-diethoxyphosphoryl-1-phenylallyl acetate with aniline, ee values up to 57% were achieved.

The development of high-fidelity mechanisms for chemically reactive systems is a challenging process that requires the compilation of rate descriptions for a large and somewhat ill-defined set of reactions. The present unified combination of modeling, experiment, and theory provides a paradigm for improving such mechanism development efforts. Here we combine broadband rotational spectroscopy with detailed chemical modeling based on rate constants obtained from automated ab initio transition state theory-based master equation calculations and high-level thermochemical parametrizations. Broadband rotational spectroscopy offers quantitative and isomer-specific detection by which branching ratios of polar reaction products may be obtained. Using this technique, we observe and characterize products arising from H atom substitution reactions in the flash pyrolysis of acetone (CH3C(O)CH3) at a nominal temperature of 1800 K. The major product observed is ketene (CH2CO). Minor products identified include acetaldehyde (CH3CHO), propyne (CH3CCH), propene (CH2CHCH3), and water (HDO). Literature mechanisms for the pyrolysis of acetone do not adequately describe the minor products. The inclusion of a variety of substitution reactions, with rate constants and thermochemistry obtained from automated ab initio kinetics predictions and Active Thermochemical Tables analyses, demonstrates an important role for such processes. The pathway to acetaldehyde is shown to be a direct result of substitution of acetone's methyl group by a free H atom, while propene formation arises from OH substitution in the enol form of acetone by a free H atom.

The title IrIIIcomplex, [Ir(C11H8N)2Cl(C25H22P2)], was synthesized from the substitution reaction between the (ppy)2Ir(μ-Cl)2Ir(ppy)2(ppy = deprotonated 2-phenylpyridine, C11H8N−) dimer and 1,1-bis(diphenylphosphanyl)methane (dppm, C25H22P2) under an argon gas atmosphere for 20 h. The IrIIIatom is coordinated by two C,N-bidentate ppy anions, a unidentate dppm ligand and a chloride anion in a distorted octahedral IrC2N2PCl arrangement. The N donor atoms of the ppy ligands are mutuallytranswhile the C atoms arecis. Intramolecular aromatic π–π stacking between the phenyl rings of ppy and dppm, and C—H...Cl interactions are observed. In the crystal, C—H...Cl and C—H...π contacts link the molecules into a three-dimensional network. A Hirshfeld surface analysis was carried out to further quantify the intermolecular interactions, and indicated that H...H contacts (63.9%) dominate the packing.

In Surface-Aligned-Reactions (SAR), the degrees of freedom of chemical reactions are restricted and therefore the reaction outcome is selected. Using the inherent corrugation of a Cu(110) substrate the adsorbate molecules can be positioned and aligned and the impact parameter, the collision miss-distance, can be chosen. Here, substitution reaction for a zero impact parameter collision gives an outcome which resembles the classic Newton’s cradle in which an incident mass ‘knocks-on’ the same mass in the collision partner, here F + CF3 → (CF3)′ + (F)′ at a copper surface. The mechanism of knock-on was shown by Scanning Tunnelling Microscopy to involve reversal of the CF3 umbrella as in Walden inversion, with ejection of (F)′ product along the continuation of the F-reagent direction of motion, in collinear reaction. Collision geometries are hard to control, making transition states in chemical reaction hard to study. Here the authors show that a linear transition state leads to formation of reaction product ‘knocked-on’ along the continuation of the direction of reagent approach.

Introduction Carbonic anhydrase-IX (CA-IX) is markedly overexpressed in many types of solid tumors promoting tumorigenicity and tumor growth. We synthesized novel 68Ga-labeled imidazothiadiazole sulfonamide (IS) derivatives ([68Ga]Ga-DO3A-IS1 and [68Ga]Ga-DO2A-IS2), and evaluated their utility as positron emission tomography (PET) probes targeting CA-IX. Methods [67/68Ga]Ga-DO3A-IS1 and [67/68Ga]Ga-DO2A-IS2 were synthesized from corresponding precursors by ligand substitution reaction in acetate buffer. Cell binding assays were performed using HT-29 cells, which highly express CA-IX, and MDA-MB-231 cells, which show lower-level expression of CA-IX, and a biodistribution assay with model mice bearing the HT-29 or MDA-MB-231 tumor was performed. [68Ga]Ga-DO3A-IS1 was further evaluated by PET/CT. Results To evaluate their fundamental properties, [67Ga]Ga-DO3A-IS1 and [67Ga]Ga-DO2A-IS2 were synthesized by conjugation with 67Ga, which has a much longer decay half-life and can be utilized more easily than 68Ga. [67/68Ga]Ga-DO3A-IS1 and [67/68Ga]Ga-DO2A-IS2 were prepared from corresponding precursors with preferable yield and purity. [67Ga]Ga-DO3A-IS1 and [67Ga]Ga-DO2A-IS2 showed significantly greater binding to HT-29 cells than MDA-MB-231 cells in vitro and the binding of [67Ga]Ga-DO2A-IS2 to HT-29 cells was much greater than that of [67Ga]Ga-DO3A-IS1, suggesting multivalent interactions. [67Ga]Ga-DO3A-IS1 and [67Ga]Ga-DO2A-IS2 showed significant selectivity for the HT-29 tumor in vivo, while tumor uptake of [67Ga]Ga-DO3A-IS1 was greater than that of [67Ga]Ga-DO2A-IS2. PET/CT of [68Ga]Ga-DO3A-IS1 showed selectivity for the HT-29 tumor, although [68Ga]Ga-DO3A-IS1 could not be used to visualize the HT-29 tumor clearly because of its strong background signals. Conclusion These results indicate that 68Ga-labeled IS derivatives may be useful 68Ga-PET probes targeting CA-IX with further structural modifications.

3-Aryloxindole derivatives were synthesized through a Friedel–Crafts-type cyclization. The reaction was catalyzed by a trimethylsilyl tricyanopalladate complex generated in situ from trimethylsilyl cyanide and Pd(OAc)2. Wide varieties of diethyl phosphates derived from N-arylmandelamides were converted almost quantitatively into oxindoles. When N,N-dibenzylamide was used instead of an anilide substrate, a benzo-fused δ-lactam was obtained. An oxindole product was subjected to substitution reactions to afford 3,3-diaryloxindoles with two different aryl groups.

Keeping Z -olefins intact with iridium Transition metal catalysis offers a versatile means of modifying carbon centers adjacent to carbon-carbon double bonds. However, in the course of these reactions, the double bond tends to get weakened, allowing its substituents to swivel back and forth. Thus, if two large groups start out on the same side of the bond axis (a geometry known as a Z -olefin), they end up on opposite sides in the product. Jiang et al. report a chiral iridium catalyst that prevents this swiveling just long enough to substitute the adjacent carbon enantioselectively (see the Perspective by Malcolmson). Science , this issue p. 380 ; see also p. 345

The regioselectivity (r.s.) and enantiospecificity (e.s.) of the substitution reactions of secondary propargylic alcohol derivatives using reagents derived from ArMgBr and Cu salts were studied. First, the picolinate, 3-methylpicolinate, and diethylphosphonate derivatives of Ph(CH2 )2 CH(OH)C≡CTMS were reacted with PhMgBr/CuCN in ratios of 2.5:2.7-2.5:0.25. The use of 2.5:0.25 ratio in THF/DME (6:1) at 0 °C for 1 h afforded the α-substitution product from the phosphate with ≥98 % r.s. and 99 % e.s. CuBr⋅Me2 S gave similar selectivity. The reaction system was then applied to phosphates derived from R1 CH(OH)C≡CR2 and ArMgBr to obtain synthetically sufficient r.s. and e.s. values with R2 =TMS, Ph, whereas iPr was borderline in terms of size as an R1 substituent. The presence of a substituent at the o-position of Ar marginally affected the selectivity. We also found that the use of PhMgBr/Cu(acac)2 in a 2:1 ratio in THF produced the γ-substitution products (allenes) with high r.s. and e.s.

The development of efficient methods, particularly catalytic and enantioselective processes, for the construction of all-carbon quaternary stereocentres is an important (and difficult) challenge in organic synthesis due to the occurrence of this motif in a range of bioactive molecules. One conceptually straightforward and potentially versatile approach is the catalytic enantioconvergent substitution reaction of a readily available racemic tertiary alkyl electrophile by an organometallic nucleophile; however, examples of such processes are rare. Here we demonstrate that a nickel-based chiral catalyst achieves enantioconvergent couplings of a variety of tertiary electrophiles (cyclic and acyclic α-halocarbonyl compounds) with alkenylmetal nucleophiles to form quaternary stereocentres with good yield and enantioselectivity under mild conditions in the presence of a range of functional groups. These couplings, which probably proceed via a radical pathway, provide access to an array of useful families of organic compounds, including intermediates in the total synthesis of two natural products, (–)-eburnamonine and madindoline A.

A detailed study for the synthesis of dinickel(II)-thiolate and dinickel(II)-hydrosulfide complexes and the complete characterization of the relevant intermediates involved in the C-S bond cleavage of thiolates are presented. Hydrated Ni(II) salts mediate the hydrolytic C-S bond cleavage of thiolates (NaSR/RSH; R = Me, Et, nBu, tBu), albeit inefficiently, to yield a mixture of a dinickel(II)-hydrosulfide complex, [Ni2(BPMP)(μ-SH)(DMF)2]2+ (1), and the corresponding dinickel(II)-thiolate complexes, such as [Ni2(BPMP)(μ-SEt)(ClO4)]1+ (2) (HBPMP is 2,6-bis[[bis(2-pyridylmethyl)amino]methyl]-4-methylphenol). A systematic study for the reactivity of thiolates with Ni(II) was therefore pursued which finally yielded 1 as a pure product which has been characterized in comparison with the dinickel(II)-dichloride complex, [Ni2(BPMP)(Cl)2(MeOH)2]1+ (3). While the reaction of thiolates with anhydrous Ni(OTf)2 in dry conditions could only yield [Ni2(BPMP)(OTf)2]1+ (5) instead of the expected dinickel(II)-thiolate compound, the C-S bond cleavage could be suppressed by the use of a chelating thiol, such as PhCOSH, to yield [Ni2(BPMP)(SCOPh)2]1+ (6). Finally, with the suitable choice of a monodentate thiol, a dinickel(II)-monothiolate complex, [Ni2(BPMP)(SPh)(DMF)(MeOH)(H2O)]2+ (7), was isolated as a pure product within 1 h of reaction, which after a longer time of reaction yielded 1 and PhOH. Complex 7 may thus be regarded as the intermediate that precedes the C-S bond cleavage and is generated by the reaction of a thiolate with an initially formed dinickel(II)-solvento complex, [Ni2(BPMP)(MeOH)2(H2O)2]3+(4). Selected dinickel(II) complexes were explored further for the scope of substitution reactions, and the results include the isolation of a dinickel(II)-bis(thiolate) complex, [Ni2(BPMP)(μ-SPh)2]1+ (8).

We synthesized cinnamoyl amide type chiral P,olefin ligand (S)-4. We successfully obtained separable diastereomers of 4d and demonstrated Pd-catalyzed asymmetric allylic substitution reactions of indoles using (S,aS)-4d as a chiral ligand with high enantioselectivities (up to 98% ee).

While primary aliphatic amines are ubiquitous in natural products, they are traditionally considered inert to substitution chemistry. This review highlights historical and recent advances in the field of aliphatic deamination chemistry which demonstrate these moieties can be harnessed as valuable C(sp3) synthons. Cross-coupling and photocatalyzed transformations proceeding through polar and radical mechanisms are compared with oxidative deamination and other transition metal catalyzed reactions.

A nucleophilic substitution reaction of N3P3Cl2(2,2′-dioxybiphenyl)2 (1) with 2-(1H-pyrazol-3-yl) phenol (2) was performed in order to synthesize molecules that may exhibit different photophysical properties on the cyclotriphosphazene scaffold. Bis-geminal phenol-pyrazole (3) and mono-spiro phenoxy-pyrazole (4) cyclotriphosphazene derivatives were obtained as a result of an effective single substitution reaction. The structures of the new cyclotriphosphazene derivatives (3 and 4) were illuminated by various spectroscopic techniques such as mass spectrometry (MALDI-TOF), 1H, 31P NMR, and elemental analysis, and also confirmed by single crystal X-ray diffraction. After the structural analysis, their photophysical properties in solution and the solid phase were examined by UV-Vis absorption and fluorescence spectroscopies. At the same time, the functionality of the excited state intramolecular proton transfer (ESIPT) mechanism and crystallization-enhanced emission (CEE), which are an important point, and their relationship with different substitution modes on the cyclotriphosphazene ring were investigated by steady-state fluorescence, time resolved-fluorescence and 3-D fluorescence measurements in solution and the crystalline state. The proton transfer properties of compounds 3 and 4 can lead to highly efficient ESIPT or inhibited-ESIPT and efficient crystallization-enhanced emission (CEE) via changing of the substitution mode. The phenol-pyrazole modified cyclotriphosphazenes (3 and 4) are the first examples where the ESIPT mechanism is active and inactive.

The imine umpolung is a relatively new and interesting strategy, especially in catalytic asymmetric synthesis. A significant development in organo- and transition metal-catalyzed umpolung of imines took place only in the recently concluded decade. A majority of the reports on the asymmetric umpolung of imines involve the initial generation of 2-azaallyl anion intermediates with the chiral catalysts, which serve as a significant driving force for the umpolung addition/substitution reactions. A variety of organocatalysts such as bifunctional cinchona alkaloids including squaramides and thioureas, chiral BINOL derived phosphoric acids, phase transfer catalysts (PTCs), phosphines, and transition metal-complexes of iridium, copper and palladium have been employed to achieve the excellent level of asymmetric induction in such types of umpolung reactions. The asymmetric imine umpolung strategy has been applied successfully to synthesize synthetic amino-acid derivatives and other useful chiral amines, including drugs and potentially bioactive molecules. This review summarizes all the significant recent development in catalytic umpolung reactions of imines involving a 2-azaallyl anion intermediate.

The copper-catalyzed substitution reaction of 5-(TBDPS-oxy)-1-(TMS)pent-1-yn-3-yl phosphate with [3-(cyclopentyloxy)-4-methoxyphenyl]MgBr, followed by several transformations, afforded the tumor necrosis factor inhibitor possessing a Ph-acetylene moiety. The inhibitor was also synthesized from 5-(TBDPS-oxy)-1-(Ph)pent-1-yn-3-yl phosphate. Furthermore, the substitution of 4-(TMS)but-3-yn-2-yl and 4-methyl-1-(TMS)pent-1-yn-3-yl phosphates with (2-fluoro-[1,1'-biphenyl]-4-yl)MgBr gave the corresponding substitution products, which were transformed to flurbiprofen and its i-Pr analogue. The copper-catalyzed substitutions in these syntheses proceeded in a regio- and stereoselective manner.

The cyclocondensation reaction of triphenylene-1,2-diquinone with 1,2-diamino-4-nitrobenzene results in two regioisomers, and is succeeded by a nucleophilic substitution reaction with alkyl mercaptans. The synthesis of unsymmetrically substituted phenazines, separation and characterization of their regioisomers are rare in discotic liquid crystal chemistry. Here, we report for the first time the synthesis of two regioisomers of phenanthro[a]phenazine via a simple SNAr substitution reaction. Separation of these regioisomers was achieved successfully via column chromatography and they were well characterized by spectroscopic analysis. Both the regioisomers were found to be mesomorphic. This study throws a lot of light on the SNAr strategy for functionalizing diverse π-conjugated systems for various applications.

Alkoxide-mediated enolization of 1-arylpropan-2-ones and their fluorinated derivatives, followed by α-functionalization with nucleophilic addition and substitution reactions, has been accomplished in the environmentally friendly eutectic mixture choline chloride/urea, under aerobic conditions. The usefulness of this new protocol has also been exemplified through the synthesis of a small selection of building-block like molecules through Pd-catalyzed α-arylation reactions.

Metal-catalyzed C–H functionalization is one of the most effective methods to form a C–C bond. We herein report a highly regiospecific, site-selective, and C–H chemoselective substitution reaction of phenols with alkenyl diazo compounds catalyzed by commercially available and low-cost In(OTf)3. The reactions of aryl or alkyl substituted vinyldiazoacetates provided the corresponding phenol-allylation products in different regioselective and site-selective manners.

The azepinoindole framework present in natural alkaloids such as subincanadine F, ibogaine and catharanthine was formed in a novel acid-promoted cyclization-rearrangement of tryptamine-derived N-sulfonyl enamines. The latter were conveniently prepared via a cesium carbonate mediated formal vinylic substitution reaction of 2-bromoallyl sulfones (allenyl sulfone surrogate) and tryptamine sulfonamides. The azepinoindole forming cyclization-rearrangement involves the initial generation of a six-membered tetrahydro-β-carboline derivative. The steric bulk of the N-sulfonyl group on tryptamine plays an important role in deciding the reaction outcome.

In industries and academic laboratories, several late transition metal-catalyzed prerequisite reactions are widely performed during single and multistep synthesis. However, besides the desired products, these reactions lead to the generation of numerous chemical waste materials, by-products, hazardous gases, and other poisonous materials, which are discarded in the environment. This is partly responsible for the creation of global warming, resulting in climate adversities. Thus, the development of environmentally benign, cheap, easily accessible, and earth-abundant metal catalysts is desirable to minimize these issues. Certainly, iron is one of the most important metals belonging to this family. The field of iron catalysis has been explored in the last two-three decades out of its rich chemistry depending on its oxidation states and ligand cooperation. Moreover, this field has been enriched by the promising development of iron-catalyzed reactions namely, C-H bond activation, including organometallic C-H activation and C-H functionalization via outer-sphere pathway, cross-dehydrogenative couplings, insertion reactions, cross-coupling reactions, hydrogenations including hydrogen borrowing reactions, hydrosilylation and hydroboration, addition reactions and substitution reactions. Thus, herein an inclusive overview of these reaction have been well documented.

The automated reaction mechanisms and kinetics (AutoMeKin) program evolved from a transition state search using chemical dynamics simulations (TSSCDS). It combines a series of empirical, semi-empirical and ab initio calculation methods to provide a two-step transition state search process from low-level calculation to high-level calculation. However, in this process, with the lack of solution keywords, low-level calculation has the problem of low accuracy or high computational cost. To address this problem, the gau_xtb interface that combines the high efficiency of xTB and the comprehensiveness of Gaussian09 was incorporated into the AutoMeKin2020 in this work and after adding some keywords, the AMK-gau_xtb software was obtained. Meanwhile, to adapt to the interface, the MD sampling results used Quadratic Synchronous Transit 3 (QST3) for the low-level transition state search. As an application, the reaction in which the nitroso group is replaced by hydroxide anion during the alkaline hydrolysis of 2,4,6-trinitrotoluene (TNT) in the water phase was studied with AMK-gau_xtb. The results of Intrinsic Reaction Coordinate (IRC) calculations revealed that the reactions on the front side and back side are different, with higher energy barriers obtained for the reactions on the front side. In addition, the hydrogen atom of the hydroxide anion has a slightly higher energy barrier for motion toward the inside of the benzene ring than for motion out of the benzene ring. Examination of the transition state structures of the low-level and high-level results showed that all reactions involve the stretching and restoration of the benzene ring. This process will lead to the incorrect identification of several transition states by the gau_xtb-based low-level calculation, while high-level calculation eliminates these incorrect results. The results of this research showed that AMK-gau_xtb has high efficiency and high fault tolerance, and has potential for use in large-scale system transition state searches.

In this paper, a high sensitivity and accuracy biosensor for CEA detection based on atom transfer radical polymerization (ATRP) with β-cyclodextrin (β-CD) and 2-bromoisobutyryl bromide (BIBB) as a macroinitiator is reported for the first time. Carcinoembryonic antigen (CEA), as a tumor-associated antigen, can be of great significance in the diagnosis of illness. Herein, thiolated CEA-aptamer 1 (Apt 1) at the 5′-terminal is first immobilized on amino magnetic beads (MBs) via a cross-linking agent to specifically recognize the antigen of CEA. After the sandwich-type structure formed, β-CD, with a bridging effect, is linked to the carboxylation CEA-aptamer 2* (Apt 2*) and BIBB via esterification reaction and substitution reaction, respectively. Remarkably, the combination of β-CD and the initiators BIBB can provide a large number of active sites for monomers and significantly amplify the fluorescent signal. Under optimum experimental conditions, the proposed biosensor for detecting CEA has a strong linear relationship in the wide detection range of 1.0 × 10−15–1.0 × 10−7 g mL−1 (R2 = 0.9989), and it is capable of detecting as low as 6.76 ag mL−1 CEA. Furthermore, the fluorescence biosensor exhibits splendid analytical performance in practical sample analysis. More importantly, the excellent sensitivity with outstanding anti-interference properties of this proposed biosensor makes it of great potential in the field of bioanalytical applications.

The sterically demanding iminophosphonamido chlorosilylene [Ph2P(DipN)2]SiCl (Dip = 2,6-diisopropylphenyl) was synthesized and fully characterized using NMR spectroscopy and X-ray crystallography. Substitution reactions of [Ph2P(DipN)2]SiCl with N- and Fe-nucleophiles led to the unexpected formation of the corresponding silaimine derivatives. This process involves the ring-opening rearrangement of three-coordinated silylene intermediates that proceeds via intramolecular N–P bond cleavage.