Shifts Of Protons Research Articles

Biopolymer-Levan Characterization in Bacillus Species Isolated from Traditionally Fermented Soybeans (Thua Nao).

Bacterial levans are biopolymers composed of fructose units linked by β-2,6 glycosidic bonds that are degradable, nontoxic and flexible, representing a green technology with significant applications across various industries. Fermented soybeans are a common source of bacteria-producing polysaccharides. In this study, Bacillus siamensis KKSB4, Bacillus velezensis KKSB6 and Bacillus amyloliquefaciens KKSB7 isolated from traditionally fermented soybean (Thua-nao), along with B. velezensis strain 5.18 isolated from Jerusalem artichoke were investigated for their levansucrase activity and subsequent levan production. B. siamensis KKSB4, B. amyloliquefaciens KKSB7 and B. velezensis strain 5.18 exhibited the highest enzyme activity at 30% sucrose, whereas B. velezensis KKSB6 demonstrated optimal activity at 20% sucrose. Characterization of the levans using Fourier transform infrared spectroscopy (FTIR) revealed the peak at 3310.02, 1122.42, 1011.14, and 923.89 cm-1, corresponding to the O-H group in fructose, C-O-H stretching, C-O-C stretching vibrations, and pyranose ring structures, respectively. 13C NMR spectrum of levan aligned with the reference spectrum of B. siamensis, showing proton shifts at H3 (4.19 ppm), H4 (4.10 ppm), H5(3.96 ppm), H6a (3.89 ppm), H1a (3.76 ppm), H1b (3.67 ppm), and H6b (3.56 ppm). All strains produced high molecular weight levans (107-108 Da) with thermal stability, exhibiting melting temperatures exceeding 200 °C. The levans also demonstrated high water and oil holding capacities of over 100%, attributed to their large molecular complexes. Additionally, they exhibited antioxidant activity by scavenging DPPH radicals and oxidizing ABTS, particularly B. siamensis KKSB4 and B. velezensis KKSB6, although low FRAP activity was observed. Furthermore, the levans were produced by B. siamensis KKSB4 and B. velezensis KKSB6 promoted the growth of Streptococcus thermophilus DKT-3, suggesting its potential prebiotic properties. This work highlights B. siamensis KKSB4 and B. velezensis KKSB6 is an outstanding candidate for levan production with diverse functional properties.

On the Role of Hydrogen Migrations in the Taxadiene System.

Taxa-4,11-diene is made by the taxa-4,11-diene synthase (TxS) from Taxus brevifolia. The unique reactivity of the taxane system is characterised by long distance hydrogen migrations in the biosynthesis. This study demonstrates that selective long range hydrogen migrations also play a role in the high energy process of the EI-MS fragmentation of taxa-4,11-diene. A TxS enzyme variant was generated that produces cyclophomactene, a compound that is formed through a concerted process involving a long range proton shift and a ring closure that can also be described as the addition of a methylcarbinyl cation to an olefin. Based on a previous computational study the cyclisation mechanism towards taxa-4,11-diene was suggested to involve two long distance proton migrations instead of one direct transfer. A substrate analog with a shifted double bond was converted with TxS to obtain experimental evidence for this proposal.

β-Cyclodextrin modified imidazole probe specific recognition of organic acids based on nuclear magnetic resonance.

Supramolecular interactions play an important role in molecular recognition. Cyclodextrins (CDs) are excellent hosts that are frequently utilized in the identification of chemical compounds. Proper modifications to CD can give it the ability to accurately recognize specific molecules. In this research, CD was modified with the allylimidazole moiety to generate a synergistic effect. Remarkably, the newly formed cation probe exhibits selective recognition of 1-adamantanecarboxylic acid from six guest molecules, which cannot be achieved by CD or allylimidazole alone. The recognition is evidenced by the retention of hydrogen-deuterium exchange (HDX) properties in the formed complexes and a change in the chemical shift of protons (H-4, H-5) in the allylimidazol backbone. Wavefunction analysis was employed to demonstrate that the mechanism of molecular recognition is the electrostatic interaction between host and guest molecules as well as the hydrogen bond formed by the guest molecule with the imidazole moiety H-2. This work reports an intramolecular synergistic strategy to specifically identify 1-adamantanecarboxylic acid, which could inspire probe design for various analysts.

Synthesis, Protonation and Aromatic Characteristics of a Series of 1,10-Phenanthroline-Fused Porphyrinoids.

A series of porphyrin analogues with fused 1,10-phenanthroline units were synthesized. The proton NMR spectra for phenanthroline-fused heteroporphyrins showed significantly upfield shifted meso-proton resonances compared to related porphyrinoid systems and the peaks corresponding to alkyl substituents directly attached to these macrocycles were also observed further upfield. These results indicate that the presence of the phenanthroline unit leads to reduced diatropicity, but the internal NH resonance was also further upfield, a result that is inconsistent with this interpretation. A phenanthrene-fused carbaporphyrin gave an unexpectedly upfield singlet for the internal C-H at nearly -9 ppm, while the NH protons appeared at -6.8 ppm. These unusual chemical shifts again imply enhanced diatropicity but the reduced downfield shifts for the external protons indicates that the aromatic ring current has been significantly reduced. Similar results were obtained for phenanthroline-fused oxybenzi- and oxypyriporphyrins. Detailed analyses of the spectroscopic properties for these systems are reported and protonation studies were conducted. The conjugation pathways and aromatic properties were computationally analyzed using nucleus independent chemical shifts (NICS) and anisotropy of induced current density plots.

Tetra-azolium Salts Induce Significant Cytotoxicity in Human Colon Cancer Cells In vitro.

Azolium salts are the organic salts used as stable precursors for generating N-Heterocyclic Carbenes and their metal complexes. Azolium salts have also been reported to have significant biological potential. Hence, in the current study, four tetra-dentate azolium salts were derived from bis-azolium salts by a new synthetic strategy. The tetra azolium salts have been synthesized by reacting the imidazole or methyl imidazole with dibromo xylene (meta, para)/ 1-bromo methyl imidazole or dibromo ethane resulting in the mono or bis azolium salts namely I-IV. V-VII have been obtained by reacting I with II-IV, resulting in the tetra azolium salts. Each product was analyzed by various analytical techniques, i.e., microanalysis, FT-IR, and NMR (1H & 13C). Salts V-VII were evaluated for their antiproliferative effect against human colon cancer cells (HCT-116) using MTT assay. Four chemical shifts for acidic protons between 8.5-9.5 δ ppm in 1H NMR and resonance of respective carbons around 136-146 δ ppm in 13C NMR indicated the successful synthesis of tetra azolium salts. Salt V showed the highest IC50 value, 24.8 μM among all synthesized compounds. Tetra-azolium salts may play a better cytotoxicity effect compared to mono-, bi-& tri-azolium salts.

Anilines Formation via Molybdenum-Catalyzed Intermolecular Reaction of Ynones with Allylic Amines.

The multi-substituted anilines are widely found in organic synthesis, medicinal chemistry and material science. The quest for robust and efficient methods to construct a diverse array of these compounds using readily accessible starting materials under simple reaction conditions is of utmost importance. Here, we report an unprecedented and efficient approach for the synthesis of 2,4-di and 2,4,6-trisubstituted anilines. With a simple molybdenum(VI) catalyst, a wide range of 2,4-di and 2,4,6-trisubstituted anilines were efficiently prepared in generally good to excellent yields from readily accessible ynones and allylic amines. The synthetic potential of this methodology was further underscored by its applications in several synthetic transformations, gram-scale reactions, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this aniline formation might involve a cascade of aza-Michael addition, [1,6]-proton shift, cyclization, dehydration, 6π-electrocyclization, and aromatization. This novel strategy provided a robust, simple, and modular approach for the syntheses of various valuable di- or trisubstituted anilines, some of which were otherwise challenging to access.

Anilines Formation via Molybdenum‐Catalyzed Intermolecular Reaction of Ynones with Allylic Amines

AbstractThe multi‐substituted anilines are widely found in organic synthesis, medicinal chemistry and material science. The quest for robust and efficient methods to construct a diverse array of these compounds using readily accessible starting materials under simple reaction conditions is of utmost importance. Here, we report an unprecedented and efficient approach for the synthesis of 2,4‐di and 2,4,6‐trisubstituted anilines. With a simple molybdenum(VI) catalyst, a wide range of 2,4‐di and 2,4,6‐trisubstituted anilines were efficiently prepared in generally good to excellent yields from readily accessible ynones and allylic amines. The synthetic potential of this methodology was further underscored by its applications in several synthetic transformations, gram‐scale reactions, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this aniline formation might involve a cascade of aza‐Michael addition, [1,6]‐proton shift, cyclization, dehydration, 6π‐electrocyclization, and aromatization. This novel strategy provided a robust, simple, and modular approach for the syntheses of various valuable di‐ or trisubstituted anilines, some of which were otherwise challenging to access.

The Adaptative Modulation of the Phosphinito-Phosphinous Acid Ligand: Computational Illustration Through Palladium-Catalyzed Alcohol Oxidation.

The phosphinito-phosphinous acid ligand (PAP) is a singular bidentate-like self-assembled ligand exhibiting dissymmetric but interchangeable electronic properties. This unusual structure has been used for the generation of active palladium hydride through alcohol oxidation. In this paper, we report the first theoretical highlight of the adaptative modulation ability of this ligand within a direct H-abstraction path for Pd and Pt catalyzed alcohol oxidation. A reaction forces study revealed rearrangements in the ligand self-assembling system triggered by a simple proton shift to promote the metal hydride generation via concerted six-center mechanism. We unveil here the peculiar behavior of the phosphinito-phosphinous acid ligand in this catalysis.

Mechanistic studies on phosphine-catalyzed [4 + 3] annulation of β′-acetoxy allenoate with 1C,3N-dinucleophile

The mechanism and role of catalyst on the PPh3-catalyzed [4 + 3] annulation reaction have been systematically investigated using density functional theory (DFT) method. Based on the calculations, the possible mechanism contains six steps: nucleophilic addition of PPh3 to allenoate to give Z-configured intermediate, cleavage of CO bond for forming phosphonium diene, nucleophilic addition of phosphonium diene with anionic 1C,3N-dinucleophile, intramolecular [1,5]-proton shift, ring-closure, and dissociation of catalyst. Non-covalent interaction (NCI) analysis shows that the O⋯P interaction would be the key for leading to the Z-configured pathway more favorable and electron localization function (ELF) analysis indicates that the implication of PPh3 can significantly lower the energy barrier involved in CO cleavage process, which mainly because the addition of PPh3 reduces the electron density of CO bond and thus facilities the cleavage of CO bond. This theoretical study would provide some clues for understanding the role of catalyst in a catalytic reaction.

Determination of solid-state acidity of lyophilized trehalose containing citrate, phosphate, and histidine buffers using UV/VIS diffuse reflectance and solid-state NMR spectroscopy

Changes in the protonation state of lyophilized proteins can impact structural integrity, chemical stability, and propensity to aggregate upon reconstitution. When a buffer is chosen, the freezing/drying process may result in dramatic changes in the protonation state of the protein due to ionization shift of the buffer. In order to determine whether protonation shifts are occurring, ionizable probes can be added to the formulation. Optical probes (dyes) have shown dramatic ionization changes in lyophilized products, but it is unclear whether the pH indicator is uniform throughout the matrix and whether the change in the pH indicator actually mirrors drug ionization changes. In solid-state NMR (SSNMR) spectroscopy, the chemical shift of the carbonyl carbon in carboxylic acids is very sensitive to the ionization state of the acid. Therefore, SSNMR can be used to measure ionization changes in a lyophilized matrix by employing a small quantity of an isotopically-labeled carboxylic acid species in the formulation. This paper compares the apparent pH of six trehalose-containing lyophilized buffer systems using SSNMR and UV-Vis diffuse reflectance spectroscopy (UVDRS). Both SSNMR and UVDRS results using two different ionization probes (butyric acid and bromocresol purple, respectively) showed little change in apparent acidity compared to the pre-lyophilized solution in a sodium citrate buffer, but a greater change was observed in potassium phosphate, sodium phosphate, and histidine buffers. While the trends between the two methods were similar, there were differences in the numerical values of equivalent pH (pHeq) observed between the two methods. The potential causes contributing to the differences are discussed.

Sonochemical synthesis, characterization, and ADMET studies of Fe (II) and Cu (II) nano-sized complexes of trimethoprim

Nanoparticles exhibit distinct physical and chemical characteristics and are becoming increasingly significant in the production of innovative nanodevices for many applications in physics, biology, biomedicine, and pharmaceuticals. The aim of this research work is to synthesize Fe (II) and Cu (II) nano-sized complexes of trimethoprim (TMP) using the sonication method, characterize them using physical and spectroscopic methods, and carry out ADMET studies on the synthesized complexes. The spectroscopic and physical studies showed a change in colour and an increase in melting point due to coordination. The novel compounds were slightly soluble in water. The XRD tests revealed that the new nanocomplexes were crystalline. The Fe (II) nanocomplexes had a size of 57.56 nm and the Cu (II) nanocomplexes had a size of 69.88 nm. These values were found using Debye-Scherrer’s equation. The FTIR results of the TMP, Fe (II), and Cu (II) nanometal complexes showed a shift of the amino group band from 3317 to 3295 and 3202 cm?1 and the azomethine band from 1633 to 1625 and 1592 cm?1 in the complexes. In the complexes, the proton NMR spectra revealed an upfield shift of the amine proton. The carbon-13 NMR spectra showed that CH2 was involved in coordination with the metal ions. The spectra studies indicated that TMP coordinated with the metal ions through the methylene and amino groups. A trigonal bipyramid structure was proposed for the complexes. The results of the Rule of 5 studies indicated that the test compounds had a good drug-likeness prediction, with only one violation. The ADMET prediction showed that all of the compounds demonstrated improved pharmacokinetic characteristics and adhered to the RO5 requirement. These findings highlight the therapeutic potential of Fe (II) and Cu (II) nano-sized TMP complexes as bioactive compounds that warrant further investigation for pharmaceutical applications.

Dihedral Angles and Photoluminescence Quantum Yields: An NMR Analysis.

The synthesis of two different series of donor-acceptor (D-A) molecules is reported, consisting of a series of four structurally related donors and two different acceptors. The subtle differences in the electron density of these D-A-D and D-A compounds are clearly reflected in the different chemical shifts of certain donor protons in the 1H NMR spectra. These shifts show a cosine squared correlation of the dihedral angle between the donor units and the neighbouring phenyl unit of the acceptor. This correlation is also related to optical properties such as the photoluminescence quantum yield, which shows a similar trend due to the different degree of charge transfer during excitation and relaxation processes. In this way, it is possible to directly correlate a molecular structural parameter with a material property on a purely experimental basis, which should be applicable to many donor-acceptor systems.

The reaction of 1-alkyl-3-phenylpropynones with aromatic aldehydes: an update

1-Alkyl-3-phenylprop-2-yn-1-ones smoothly react with aromatic aldehydes in the presence of triphenylphosphine (acetonitrile, room temperature, 24 h) to regio- and stereo- selectively afford (Z)-2-benzylideneoxacyclopentan-3-ones in yields up to 93%. The proposed mechanism for the transformation involves 1,3-H proton shift from the alkyl group at the intermediate β-phosphoniovinylide species.

A Lipophilic Salt Form to Enhance the Lipid Solubility and Certain Biopharmaceutical Properties of Lapatinib.

Lapatinib (LTP) commercially available as lapatinib ditosylate (LTP-DTS) salt is the only drug approved for the treatment of HER-positive metastatic breast cancer. A low and pH-dependent solubility results in poor and variable oral bioavailability, thus driving significant interest in molecular modification and formulation strategies of the drug. Furthermore, due to very high crystallinity, LTP and LTP-DTS have low solubility in lipid excipients, making it difficult to be delivered by lipid-based carrier systems. Thus, the present work reports a new salt form of LTP with a docusate counterion to enhance the pharmaceutical properties of the drug (LTP-DOC). NMR spectra showed a downfield shift of the methylene singlet proton from 3.83 and 4.41 ppm, indicating a lowering of electron density on the adjacent nitrogen atom and confirming the formation of amine-sulfonyl salt through the specified basic nitrogen center located adjacent to the furan ring. PXRD diffractograms of LTP-DOC indicated a reduced crystallinity of the prepared salt. The dissolution, equilibrium solubility, lipid excipient solubility, partitioning coefficient, distribution coefficient, tabletability, and in vitro cytotoxicity of the lipophilic salt of LTP were investigated. The equilibrium solubility data showed that LTP-DOC possesses a pH-independent solubility profile in the pH range of 3.5 to 7.4 with a 3.14 times higher permeability coefficient than commercial ditosylate salt. Furthermore, the prepared LTP-DOC salts showed twice higher log P than the free base and 8 times higher than LTP-DTS. The prepared LTP-DOC was found to have 4- to 9-fold higher solubility in lipid excipients like Capmul MCM C8 and Maisine CC compared to the ditosylate salt. The LTP-DOC salt was tabletable and showed approximately 1.2 times lower dissolution than commercial ditosylate salt, indicating extended-release behavior. A cytotoxicity study of LTP-DOC salt showed an approximately 2.5 times lower IC50 value than the LTP-free base and 1.7 times lower than commercial ditosylate salt with an approximately 3 times higher selectivity index. The investigations strongly indicate a high translational potential of the prepared salt form in maintaining solubility-lipophilicity interplay, enhancing the drug's bioavailability, and developing lipidic formulations.

Sonochemical synthesis and characterization of Fe(II) and Cu(II) nano-sized complexes of sulfamethoxazole

Nanoparticle drug delivery systems are precisely designed technologies that utilize nanoparticles to deliver therapeutic drugs to specific targets and regulate their release. In recent times, nanoparticles have garnered significant interest owing to their potential for efficient drug delivery. This work is aimed at synthesizing Fe(II) and Cu(II) nano-sized complexes of sulfamethoxazole (SMX) using the sonication method. The physical and spectroscopic studies showed a colour change from white to grey, and a decrease in melting points suggested the formation of the metal complexes. The nanometal complexes were insoluble in water. XRD analysis showed that the crystallite sizes of Fe(II) and Cu(II) nanometal complexes were determined to be 76.08 nm and 37.13 nm, respectively, using the Debye-Scherrer equation. The FTIR results of the SMX, Fe(II), and Cu(II) nanometal complexes showed a shift of the amine band from 3243 to 3191 cm^-1 and the sulfone band from 1154 to 1092 cm^-1 in both complexes. The proton NMR showed a shift of the amine proton from 6.100 ppm to 6.035 ppm in the spectra of the Cu(II) complex. The amine chemical shift was absent in the spectra of the Fe(II) complex, showing deprotonation. The carbon-13 NMR spectra showed a similar chemical shift. The spectra studies indicated that SMX coordinated with the metal ions through the amino and sulfone groups. A tetrahedral structure was proposed for the complexes. SMX coordinated as a bidentate ligand to Fe(II) and Cu(II) ions.

Persimmon leaf polyphenols as potential ingredients for modulating starch digestibility: Effect of starch-polyphenol interaction

The interaction mode between persimmon leaf polyphenols (PLP) and corn starch with different amylose content and its effect on starch digestibility was studied. Results of iodine binding test, TGA, and DSC revealed that PLP interacted with starch and reduced the iodine binding capacity and thermal stability of starch. High amylopectin corn starch (HAPS) interacted with PLP mainly via hydrogen bonds, since the FT-IR of HAPS-PLP complex showed higher intensity at 3400 cm−1 and an obvious shift of 21 cm−1 to shorter wavelength, and the chemical shifts of protons in 1H NMR and the shift of C-6 peak in 13C NMR of HAPS moved to low field with the addition of PLP. Results of 1H NMR also showed the preferential formation of hydrogen bonds between PLP and OH-3 of HAPS. Different from HAPS, PLP formed V-type inclusion complex with high amylose corn starch (HAS) because XRD of HAS-PLP complex showed characteristic feature peaks of V-type inclusion complex and C-1 signal in 13C NMR of PLP-complexed HAS shifted to low field. Interaction with PLP reduced starch digestibility and HAS-PLP complex resulted in more resistant starch production than HAPS-PLP complex. To complex PLP with starch might be a potential way to prepare functional starch with slower digestion.

Accurate Prediction of 1H NMR Chemical Shifts of Small Molecules Using Machine Learning

NMR is widely considered the gold standard for organic compound structure determination. As such, NMR is routinely used in organic compound identification, drug metabolite characterization, natural product discovery, and the deconvolution of metabolite mixtures in biofluids (metabolomics and exposomics). In many cases, compound identification by NMR is achieved by matching measured NMR spectra to experimentally collected NMR spectral reference libraries. Unfortunately, the number of available experimental NMR reference spectra, especially for metabolomics, medical diagnostics, or drug-related studies, is quite small. This experimental gap could be filled by predicting NMR chemical shifts for known compounds using computational methods such as machine learning (ML). Here, we describe how a deep learning algorithm that is trained on a high-quality, “solvent-aware” experimental dataset can be used to predict 1H chemical shifts more accurately than any other known method. The new program, called PROSPRE (PROton Shift PREdictor) can accurately (mean absolute error of <0.10 ppm) predict 1H chemical shifts in water (at neutral pH), chloroform, dimethyl sulfoxide, and methanol from a user-submitted chemical structure. PROSPRE (pronounced “prosper”) has also been used to predict 1H chemical shifts for >600,000 molecules in many popular metabolomic, drug, and natural product databases.

Effects of Electron-Withdrawing and Electron-Donating Groups on Aromaticity in Cyclic Conjugated Polyenes.

Determining the aromaticity of various fluorinated benzenes is challenging as easily obtained experimental aromaticity [Δδ(Houter - Hinner)] necessitates the chemical shifts of inner and outer protons. This issue was addressed in porphyrinoids by replacing the electron-withdrawing (E.W.) groups at the meso-positions of porphyrins and allyliporphyrins. Electronic effects on aromaticity in porphyrinoids have not been thoroughly examined in the literature. In porphyrins, the effect of E.W. groups is minimal, making it difficult to establish a clear relationship between the aromaticity strength and E.W. groups. Conversely, in allyliporphyrins, stronger E.W. groups, such as indandione (IND) derivatives, significantly reduce the aromaticity of the parent structure. The IND derivatives disrupted the aromatic pathway of allyliporphyrin more effectively than those attached to porphyrins. This is attributed to the absence of β-carbons in allyliporphyrins. The effect of electron-donating (E.D.) groups on porphyrins and allyliporphyrins was further investigated. Contrary to the initial assumption that the E.D. groups might enhance aromaticity owing to their ability to increase electron density, as the strength of the E.D. groups increased, the aromaticity of the porphyrinoids decreased. Despite the modest reduction in aromaticity, any form of electron perturbation reduces aromaticity. The aromaticity of various fluorinated benzenes is expected to parallel our observations of porphyrinoids as representative aromatic polyenes.

Magnetic field dependence of the para-ortho conversion rate of molecular hydrogen in SABRE experiments

The use of parahydrogen – the isomer of molecular hydrogen with zero nuclear spin – is important for promising and actively developing methods for spin hyperpolarization of nuclei called parahydrogen induced polarization (PHIP). However, the dissolved parahydrogen in PHIP experiments quickly loses its spin order, resulting in the formation of orthohydrogen and reduction of the overall nuclear polarization of the substrate. This process is due to the difference of chemical shifts of hydride protons, as well as spin–spin couplings between nuclei, in the intermediate catalytic complexes, and it has not been rigorously explained so far. We proposed a new experimental technique based on magnetic field cycling for measuring the rate of molecular hydrogen para–ortho conversion in solution and applied it for non-hydrogenative PHIP Signal Amplification By Reversible Exchange (SABRE) experiments. The para–ortho conversion rate was measured over a wide range of magnetic field from 0.5 mT to 9.4 T. It was found that the conversion rate strongly depends on the magnetic field in which the reaction occurs, as well as on the concentrations of reactants. The rate decreases with increasing the concentration of pyridine ligand and increases with increasing the concentration of iridium catalyst. The model, which takes into account the reversible exchange of molecular hydrogen with the catalyst, nuclear spin–spin interaction of hydride protons with nuclei of ligands within catalytic complex and nuclear Zeeman interactions, qualitatively describes the experimental data. Two types of complexes with different spin system symmetry contribute to the molecular hydrogen conversion. In asymmetric complexes possessing hydride protons with different chemical shifts due to the presence of chlorine anion ligand the para–ortho conversion rate increases with magnetic field, while for symmetric complexes this mechanism is not operable. In the magnetic field where level anti-crossing occurs the resonant feature for the rate of para–ortho conversion is found. The results of this work can be utilized for finding the optimal conditions for obtaining the maximum hyperpolarization in the experiments employing parahydrogen.

Acidic Hydrogen-Tethered Electron-Deficient Acceptors for Phosphine-Catalyzed Annulations

AbstractNucleophilic phosphine-catalyzed annulations are recognized as practical and powerful tools for synthesizing various cyclic compounds. Phosphine acceptors play a key role in nucleophilic phosphine catalysis. The design and synthesis of new phosphine acceptors that are able to introduce new zwitterionic intermediates with new reactivities into phosphine-catalyzed annulations is highly desirable. We recently applied proton-shift principles in the design of new phosphine acceptors, and we synthesized several new acceptors. With the use of these acceptors, we have developed several novel phosphine-catalyzed annulation reactions. In this account, we present a brief introduction to the design and application of a series of acidic-hydrogen-tethered electron-deficient acceptors for phosphine-catalyzed annulation reactions, categorized according to the type of atom (N–H, O–H, C–H) to which the acidic hydrogen is bound.1 Introduction2 Phosphine Acceptors Tethered with an Acidic N–H Group3 Phosphine Acceptors Tethered with an Acidic O–H Group4 Phosphine Acceptors Tethered with an Acidic C–H Group5 Conclusions