Shifts Of Protons Research Articles

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.

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

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.

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 studiesof 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

Molecular Dynamic, Hirshfeld Surface, Computational Quantum and Spectroscopic analysis of 4-Hydroxy-1-Naphthaldehyde

aims: Computational Quantum and Spectroscopic analysis of 4-Hydroxy-1-Naphthaldehyde Background: Known also as 4-Hydroxynaphthalene-1-carbaldehyde, 4-hydroxy-1-naphthaldehyde (4H1NA) is a crucial precursor of many coordinating agents. A commercial compound called 4-hydroxy-1-naphthaldehyde (4H1NA) can be used to make a number of different sensors. In the development of many chemosensors, they operate effectively as a functionalized fluorescent backbone. Objectives: Molecular Dynamic, Hirshfeld Surface, Computational Quantum analysis of Naphthalde-hyde. Methods: The methods employed in the analysis of the compound involve the DFT calculations, using the DFT method and B3LYP/6-311++G (d, p) basis set with respect to its FTIR, NMR, and UV-Visible spectrum. The NMR chemical shifts of carbon and protons in CDCl3 were determined by the GIAO method. For the molecule of reference, HOMO-LUMO and Donor-Acceptor interactions were also taken into consideration. Investigations also looked into E.L.F., Fukui activity, and non-linear optical properties. Results: The investigation of compounds at their atomic level was analyzed using computational methods so that chemical, medicinal, and environmental research make use of them to make the molecule more in an improved form with distinguished properties. Strong interaction has been produced as a result of electron transfer from the oxygen atoms lone pair LP (2) to the anti-bonding orbital *(C3-C5) with a significant stabilization energy of 42.61kcal/mol. The attributes of the NLO molecule were calculated and found to be superior to those of the urea molecule, with linear and first-order hyperpolarizability situations. Our findings imply that the reference molecule can be a heavier contender for NLO as a surface material and could be considered a vital substance for medical purposes in the drug industry due to its maximum electrophilicity index. Conclusion: A commercial compound called 4-hydroxy-1-naphthaldehyde (4H1NA) can be used to make several different sensors. The compound has good structural and optical properties. They can be employed for a variety of optical limiting applications because of their unusual optical characteristic, which exhibits third-order non-linear behavior.

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction.

Treatment of various (R)-N-(2,2,3,3-tetrafluoropent-4-en-1-ylidene)-1-phenylethylamine derivatives with 2.4 equiv of DBU in toluene at room temperature to 50 °C for 24 h led to a smooth [1,3]-proton shift reaction with a high chirality transfer, affording the corresponding rearranged products in acceptable yields. Without purification, these products were subjected to acid hydrolysis and the subsequent N-Cbz protection, providing the optically active tetrafluoroethylenated amides in moderate three-step yields.

Solvents Influence 1H NMR Chemical Shifts and Complete 1H and 13C NMR Spectral Assignments for Florfenicol

Florfenicol (FFC) is an important and widely used veterinary drug, and its structure has been characterized by nuclear magnetic resonance (NMR) spectroscopy. The study aimed to investigate the influences of solvent type, solvent concentration, and temperature on the chemical shifts of the 1H NMR of FFC. The results showed that different types of solvents significantly affected the chemical shifts, especially the chemical shifts of 2-H, 3-H, 5-H, and the active protons. When DMSO-d 6 is used as the solvent, there is no significant difference in the chemical shifts of FFC with a concentration ranging from 20 to 250 mmol/L; however, as the temperature increases, the chemical shifts of the active protons move to a higher field. Besides, the NMR spectroscopic data and structural analysis of FFC were refined by 1H, 13C, distortionless enhancement by polarization transfer-135 (DEPT-135), 1H–1H correlation spectroscopy (1H–1H COSY), phase-sensitive gradient heteronuclear singular quantum correlation (gHSQC), and heteronuclear multiple bond correlation (gHMBC) NMR spectroscopy using DMSO-d 6 as a solvent. The study will help with qualitative and quantitative analysis of FFC in the future.

Surface reconstruction and cleavage of phyllosilicate clay edge by density functional theory

Phyllosilicate materials (e.g., smectite) have been proposed to act as a waste barrier within long-term deep geological repositories. Aside from longevity, these clay materials must also limit the mobility of radionuclides, which is achieved through intermolecular interaction involving clay basal planes and edge surfaces. We aim to contribute to the fundamental knowledge of clay edges by investigating surface reconstruction in a dehydrated context. Using density functional theory, surface reconstruction, charge redistribution, and formation energies have been explored for pyrophyllite edges resulting from thirteen terminations. Three primary reconstruction mechanisms were identified: (1) the displacement of Al into the tetrahedral layer, (2) proton shift, and (3) sub-surface reconstruction involving sub-surface -OH or apical O and surface Si. Reduction in overall relative bond deficiency and charge redistribution to becoming more bulk-like were found to be the main driving force for reconstruction. Formation energies were also determined with dispersion correction for dehydrated and hydrated surfaces. The presence of water terminating agents reduced energetic costs by approximately one order of magnitude and the inclusion of dispersion correction resulted in indistinguishable formation energies between different hydrated surfaces. Linear regression models were also explored to predict surface formation energies based on relative bond deficiency and charge. These models were able to identify the key contributions to the surface energy; however, due to the small dataset they were not found to be predictive.

Theoretical study of an N-heterocyclic carbene-catalyzed annulation reaction between an enal and a β-silyl enone: Mechanism and origin of stereoselectivity

In this study, the mechanism and origin of the stereoselectivity of an N-heterocyclic carbene (NHC)-catalyzed transformation reaction between an enal and a β-silyl enone are systematically investigated using density functional theory (DFT) at the M06-2X level. Multiple pathways are proposed and studied to identify the most energetically favorable mechanism for the reaction. The calculation results show that the most energetically favorable pathway comprises the following processes: nucleophilic addition of NHC to the Si-face of the enal to form a zwitterionic intermediate, two sequential CsHCO3-assisted intramolecular proton shifts to produce an enolate intermediate, Michael-type addition of the enolate intermediate to the β-silyl enone, ring closure to construct a six-membered ring intermediate, and the dissociation of NHC to release the final product. The reaction between the enolate intermediate and the β-silyl enone is identified as the stereoselectivity-determining step, preferentially generating an RS-configured product. Subsequent atoms-in-molecules (AIM) and noncovalent interaction (NCI) analyses verify that the main factor for inducing stereoselectivity is the higher number of noncovalent intermolecular interactions in the low-energy transition state.