Addition Of Electron-withdrawing Groups Research Articles

Nucleophilic Aromatic Substitution of Heteroaryl Halides with Thiols.

The nucleophilic aromatic substitution (SNAr) between heteroaryl halides (Cl, Br) and thiols proceeds smoothly in DMAc under the action of K2CO3 at rt-100 °C. For most electron-deficient heteroarenes, reaction takes place without introducing an additional electron-withdrawing group. For electron-rich heteroarenes, an additional electron-withdrawing group such as a simple ester, keto, cyano, and nitro group is required to ensure the reaction completes. The reactivity trend of heteroaryl halides is highly dependent on the electronic nature of the heteroarenes and orientation of halogens. Besides thiols, a couple of functionalized thioureas and thioamides are compatible with these conditions, providing the corresponding heteroaryl thioethers in good yields.

New Carbazole-Based Sensitizers for p-Type DSSCs: Impact of the Position of Acceptor Units on Device Performance

We report the design, synthesis, and characterization of two new carbazole-based organic dyes PC1–2 as potential sensitizers for NiO-based p-type dye-sensitized solar cells (p-DSSCs). The D-A-π-A’ configured PC1 dye comprises a thienyl unit as a π-spacer and a malononitrile as an end-capping acceptor unit, whereas in PC2, the cyanovinylene group serves as an acceptor unit and a thienyl group acts as a donor unit in a D–A–D configuration. These molecules achieved excellent solubility due to their long-branched alkyl chains. The current work encompasses their structural, photophysical, thermal, electrochemical, theoretical, and photoelectrochemical studies, establishing structure–property relationships. PC1–2 exhibit λabs and λemi in the range of 389–404 and 448–515 nm, respectively, with a band gap in the range of 2.88–2.92 eV. Electrochemical studies confirm the feasibility of electron injection, regeneration, and recombination. The introduction of an additional electron-withdrawing group (cyanovinylene group) on the dye PC1 skeleton endows it with a higher dye loading capacity, high hole injection, and a strengthened intramolecular charge transfer (ICT) effect, resulting in a redshifted ICT absorption with a higher molar extinction coefficient. Among the two new dyes, the device based on PC1 achieved the highest power conversion efficiency (PCE) of 0.027% with a short-circuit current density (JSC) of 1.29 mA·cm–2, open-circuit voltage (VOC) of 67 mV, and fill factor (FF) of 31%, whereas the device with dye PC2 performed less efficiently (PCE: 0.018%, JSC: 0.92 mA·cm–2, VOC: 68 mV, and FF: 30%). Conclusively, the study provides insights into the intricacies involved in the structural modification of carbazole-based p-type dyads for the development of highly efficient DSSCs.

Reactivity-informed design, synthesis, and Michael addition kinetics of C-ring andrographolide analogs

Andrographolide, a labdane diterpenoid lactone natural product extracted from Andrographis paniculata, has demonstrated potent biological activity and therapeutic potential against cancer, Alzheimer's disease, diabetes, and multiple sclerosis. Andrographolide is reported to significantly inhibit the NF-κB signaling pathway, which is active in immune system function and regulation of inflammatory cells. However, andrographolide use is not optimized for human systems. In order to improve upon these aspects, we designed and semi- synthesized a library of andrographolide analogues with modified electronics of the 12,13 unsaturated lactone to increase cytotoxicity via the addition of electron-withdrawing groups, thereby influencing reactivity of the compound. Reactivity of the top piece butenolide warhead was quantified via a time- resolved colorimetric ex vivo Michael addition assay using Elleman’s Method, wherein reduced-glutathione was the electron donor. The results demonstrate that the installation of an acetate ester at C14 did not result in greater Michael acceptor reactivity, whereas changing the electrophile to C14 with a C11-C12 alkene resulted in a significantly higher rate of reaction with glutathione. Further, computational studies were employed to model the Michael addition energetic pathways of andrographolide and each analog. We found the energetic pathways for all analogs were relatively consistent, suggesting that changes in sterics may play a more significant role in defining Michael addition kinetics. Through understanding the kinetic mechanisms of the Michael acceptor pharmacophore in andrographolide, we hope to further inform directed semisyntheses in order to optimize this incredibly potent natural product for clinical use.

Converting thermally activated delayed fluorescence into hybridized local and charge-transfer via an addition acceptor moiety

High-efficiency blue materials for Organic Light Emitting Diodes (OLEDs) are challenging but urgently needed, especially for solution-processed devices. Herein, based on a model compound of acridine-benzophenone, two blue materials were designed and synthesized, with the additional electron-withdrawing groups benzophenone and pentafluorobenzophenone connected to the acridine donor respectively to prepare BC and BC5F. The solution-processed OLED based on BC showed an emission peak at 486 nm, while the device with BC5F showed the electroluminescent peak at 478 nm. BC featured the thermally active delayed fluorescent (TADF) properties, but BC5F exhibited hybridized local and charge-transferring (HLCT) characteristics. This work showed that linking additional acceptors to the donor side could not only achieve deeper blue emission but also change the luminescent mechanism. Therefore, we provided a new strategy to manipulate the transition between TADF and HLCT.

Computational insight into the structural properties and redox chemistry of poly (ethylene carbonate) as electrolytes for Lithium batteries

New electrolytes with high electrochemical stability and ionic conductivity are important in the development of lithium ion batteries. Polyethylene carbonate (PEC) is a very promising candidate. Herein, the DFT modeling approach is performed to investigate the coordination structure of Li+ ion in PEC, and the redox potentials of a set of polymer models to assess the effect of polymer monomer unit composition. [Li(PEC)] [Anion] (BF4−, PF6−, ClO4−, TFSI−) are also considered. It is highlighted that the coordination shell of Li+ ion is most likely fully occupied by four carbonyl oxygen atoms of PEC. Next, the carbonate group can lead to greater oxidation stability than ester, ketone and ether group, the length and configuration of alkyl chain affect the redox potential only slightly. Furthermore, the addition of electron-withdrawing groups (-F and -CF3) can increase the oxidation stability of PEC, while the -CN group substitution shows the opposite effect, due to the ring formation or bond breaking of intramolecular structure. All these findings provide important information for understanding the ion-polymer interactions and synthesizing the promising new electrolyte molecules for high-voltage batteries.

Computational and Experimental Evaluation of Peroxide Oxidants for Amine-Peroxide Redox Polymerization.

Amine-peroxide redox polymerization (APRP) is the prevalent method for producing radical-based polymers in the many industrial and medical applications where light or heat activation is impractical. We recently developed a detailed description of the APRP initiation process through a combined computational and experimental effort to show that APRP proceeds through SN2 attack by the amine on the peroxide, followed by the rate-determining homolysis of the resulting intermediate. Using this new mechanistic understanding, a variety of peroxides were computationally predicted to initiate APRP with fast kinetics. In particular, the rate of APRP initiation can be improved by radical and anion stabilization through increased π-electron conjugation or by increasing the electrophilicity of the peroxy bond through the addition of electron-withdrawing groups. On the other hand, the addition of electron-donating groups lowered the initiation rate. These design principles enabled the computational prediction of several new peroxides that exhibited improved initiation rates over the commonly used benzoyl peroxide. For example, the addition of nitro groups (NO2) to the para positions of benzoyl peroxide resulted in a theoretical radical generation rate of 1.9 × 10-9 s-1, which is ~150 times faster than the 1.3 × 10-11 s-1 radical generation rate observed with unsubstituted benzoyl peroxide. These accelerated kinetics enabled the development of a redox-based direct-writing process that exploited the extremely rapid reactivity of an optimized redox pair with a custom inkjet printer, capable of printing custom shapes from polymerizing resins without heat or light. Furthermore, the application of more rapid APRP kinetics could enable the acceleration of existing industrial processes, make new industrial manufacturing methods possible, and improve APRP compatibility with biomedical applications through reduced initiator concentrations that still produce rapid polymerization rates.

Mechanistic understanding of humin formation in the conversion of glucose and fructose to 5-hydroxymethylfurfural in [BMIM]Cl ionic liquid.

Humin formation is one of the key issues that hinders economical 5-HMF production from hexose sugars such as glucose and fructose. In this work, the mechanism of humin formation in glucose/fructose conversion to HMF was studied in an ionic liquid system (1-butyl-3-methylimidazolium chloride, [BMIM]Cl) with CrCl3 as the catalyst. Elemental analysis, XRD, FT-IR, and TEM were applied to study the molecular structure and morphology of the solid humins. The possible intermediates to form solid humins were investigated by HPLC-MS. We synthesized furanic model compounds that mimic the experimentally identified humin intermediates to investigate the mechanism of humin growth at an early stage. The results showed that a furan compound bearing a hydroxymethyl and an electron-donating group was unstable due to three types of reactions: (1) bimolecular ether formation reactions; (2) intermolecular addition reaction; (3) furan ring opening reaction with water. The stability of a furan compound in [BMIM]Cl was increased when the hydroxymethyl group of a furan compound was protected by a methyl group, and the stability was further enhanced with an additional electron-withdrawing group (such as an aldehyde group) on the furan ring. Protecting the hydroxymethyl group of 5-HMF with a methyl group allows easy separation of the products from the [BMIM]Cl solvent through extraction.

DDIS-20. IMIPRIDONE STRUCTURE ACTIVITY RELATIONSHIP UNCOVERS ONC206 AS THE NEXT BITOPIC DRD2 ANTAGONIST FOR ONCOLOGY WITH DIFFERENTIATED RECEPTOR PHARMACOLOGY

Abstract ONC201 is the first bitopic antagonist of dopamine receptor D2 (DRD2) in oncology clinical trials, which have shown that the small molecule is well tolerated and induces durable tumor regressions in H3 K27M-mutant glioma patients. ONC201 possesses a unique tri-heterocyclic core structure that prompted a medicinal chemistry exploration following its successful clinical translation. Chemical derivatization of the ONC201 pharmacophore from an angular to a linear isomer ablated DRD2 antagonist activity and anti-cancer activity, indicating the core structure integrity is critical. A series of analogs that share the same core structure, called imipridones, were profiled for modulation of β-arrestin recruitment to GPCRs and anti-cancer efficacy. The profiled imipridones exhibited a heterogeneous spectrum of GPCR agonist/antagonist activity that was exclusive to Class A GPCRs. The addition of electron withdrawing groups to one of two peripheral benzyl rings enhanced the potency of GPCR engagement and anti-cancer effects, while derivatization of the other benzyl ring was inactivating. Among the GPCR hits identified, maximal variance in imipridone GPCR antagonism was identified for DRD2/DRD3. ONC206 emerged as the most selective and potent antagonist for DRD2/DRD3 with a Ki of ~320nM for DRD2 with complete specificity across human GPCRs and complete DRD2 antagonism. Schild analyses of ONC206 in cAMP and β-Arrestin recruitment assays revealed hallmarks of non-competitive DRD2 antagonism, unlike antipsychotics but similar to ONC201. Shotgun mutagenesis across DRD2 identified 7 residues critical for ONC206-mediated antagonism at orthosteric and allosteric sites. Six residues were critical for ONC201 and ONC206, however the impact varied between the two compounds and one allosteric residue was exclusive to ONC206. Structural mapping revealed that some ONC206-critical allosteric residue interactions are located at the interface of TM-IV and –V that mediates the DRD2 homodimer interface. Thus, ONC206 is a bitopic DRD2 antagonist that may be poised to address oncogenic DRD2 monomers or dimers.

Abstract 2749: Defining structure activity relationships for GPCR engagement and anti-cancer efficacy of imipridone small molecules

Abstract G protein-coupled receptors (GPCRs) represent the most widely exploited superfamily of drug targets for FDA-approved therapies for many diseases, however, these receptors are underexploited for oncology. ONC201 is a selective antagonist of GPCRs dopamine receptor D2 (DRD2) and DRD3 that has been shown to induce tumor regressions with a benign safety profile in high grade glioma patients. ONC201 (benzyl-2-methylbenzyl-imipridone) is the founding member of the imipridone class of small molecules that share a unique tri-heterocyclic core chemical structure. Imipridones share several chemical and biological properties that are desirable drug-like characteristics: oral administration, wide therapeutic window, chemical stability and blood brain barrier penetrance. In this study, we profiled a series of imipridones for GPCR engagement and anti-cancer efficacy. Several imipridones were screened against a large panel of human GPCRs using a β-arrestin recruitment assay. The imipridones tested resulted in GPCR agonist/antagonist activity (threshold set at >20% activity) that was heterogenous, but exclusive among Class A GPCRs that represent the largest class. Minor chemical modifications to the ONC201 chemical structure caused large shifts in agonist versus antagonist activity and selectivity for GPCRs. Specifically, switching the ONC201 imipridone core from an angular to a linear isomer resulted in loss of DRD2 antagonist activity and impaired inhibition of cancer cell viability, indicating the imipridone core structure is critical for GPCR engagement and anti-cancer effects. The addition of electron withdrawing groups (e.g. di- or tri-halogen substitution) to the methyl benzyl ring improved potency for GPCR engagement and anti-cancer effects, but not for the benzyl ring. Loss of the benzyl ring impaired anti-cancer effects. Among all of the GPCR hits identified, maximal variance in imipridone GPCR engagement was identified for DRD2/DRD3 antagonism and GPR132 agonism that were prioritized considering their known biological relevance in oncology. ONC206 (benzyl-2,4-difluoromethylbenzyl-imipridone) emerged as the most selective and potent antagonist for D2-like dopamine receptors that are overexpressed and critical for survival in several cancers. ONC212 (benzyl-4-trifluoromethylbenzyl-imipridone) was the most selective and potent agonist for tumor suppressor GPR132. Both compounds were tested in the GDSC panel of >1000 cancer cell lines and demonstrated broad spectrum nanomolar inhibition of cancer cell viability and a wide therapeutic window. GPCR target expression correlated with anti-cancer efficacy in the GDSC panel for both compounds, providing potential biomarkers of response. Thus, chemical derivatization of ONC201 has generated a class of novel GPCR-targeting agents with promising preclinical efficacy and safety profiles in oncology. Citation Format: Varun V. Prabhu, Abed Rahman Kawakibi, Neel S. Madhukar, Lakshmi Anantharaman, Sean Deacon, Neil S. Charter, Mathew J. Garnett, Ultan McDermott, Cyril H. Benes, Wolfgang Oster, Olivier Elemento, Martin Stogniew, Joshua E. Allen. Defining structure activity relationships for GPCR engagement and anti-cancer efficacy of imipridone small molecules [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2749.

Improved conversion efficiency in dye-sensitized solar cells based on porphyrin dyes with dithieno[3,2-b:2′,3′-d]pyrrole donor

Dithieno[3,2-b:2′,3′-d]pyrrole (DTP) has proved to be a powerful donor to construct novel D–π–A type porphyrin sensitizers for highly efficient dye-sensitized solar cells. Compared with the reference dye YD2−o−C8, replacing the diphenylamine donor with modified DTP unit resulted in a promotion of molar absorption coefficient from 2.11 × 105 to 3.46 × 105 M−1 cm−1, and endowed dye JY47 good light–harvesting ability. This structural modification led to an enhanced photocurrent (16.54 vs. 15.68 mA cm−2) and higher power conversion efficiency (7.95% vs. 7.76%) of JY47 based–device relative to YD2−o−C8 based–device with iodine electrolyte under the same conditions. Dye JY48 containing additional electron-withdrawing group benzothiadiazole (BTD) gave the highest PCE of 8.44%, around 1.1 times of that of YD2−o−C8, with a Jsc of 18.43 mA cm−2, a Voc of 717 mV and a FF of 0.64 under AM 1.5 G irradiation. These results demonstrate that dithieno[3,2-b:2′,3′-d]pyrrole is a promising donor to constructing highly efficient porphyrin sensitizers, besides acting generally as a π–spacer in dye-sensitized solar cells (DSSCs).

Tuning optical properties of MOF-based thin films by changing the ligands of MOFs

The preparation and development of novel optical thin films are of great importance to functional optical and opto-electric components requiring a low refractive index. In this study, a typical metal-organic framework (MOF), MIL-101(Cr), is selected as the research model. The corresponding MOF nanoparticles are prepared by a hydrothermal method and the optical thin films are successfully prepared by spin-coating. The optical properties of the corresponding MOF thin films are controlled by changing the type of functional groups on the benzene ring of the ligand (terephthalic acid) on MOFs. The functional groups are hydrogen atoms (H), electron donating groups (–NH2, –OH) and electron withdrawing groups (–NO2, –(NO2)2 or F4), respectively. It is found that the effective refractive index ( n eff) of MOF thin films decreases along with the increasing voids among MOF nanoparticles. In addition, the extinction coefficient ( k ) increases with the addition of electron donating groups, and decreases with the addition of electron withdrawing groups. Among the MOFs used in this study, the n eff of NO2-MIL-101(Cr) containing electron withdrawing groups is as low as ~1.2, and value of k is particularly low, which suggests its potential application in antireflective devices. In addition, the intrinsic refractive index ( n dense) of the dense MOF materials evaluated according to their porosity increases with the number of the functional groups, and the n dense of the two nitro-substituted MOFs is greater than that of the single nitro-substituted one, and the latter is bigger than that of hydroxyl-substituted one, which is close to that of amino-functionalized one. The diversity of ligands in MOFs makes them a promising new generation of optical materials.

Keteniminium Ions: Unique and Versatile Reactive Intermediates for Chemical Synthesis

Keteniminium ions have been demonstrated to be remarkably useful and versatile reactive intermediates in chemical synthesis. These unique heterocumulenes are pivotal electrophilic species involved in a number of efficient and selective transformations. More recently, even more reactive ‘activated’ keteniminium ions bearing an additional electron-withdrawing group on the nitrogen atom have been extensively investigated. The chemistry of these unique reactive intermediates, including representative methods for their in situ generation, will be overviewed in this review article.1 Introduction2 The Chemistry of Keteniminium Ions3 The Chemistry of Activated Keteniminium Ions4 Keteniminium Ions: Pivotal Intermediates for the Synthesis of Natural and/or Biologically Relevant Molecules5 Conclusions and Perspectives

Kinetics and Thermodynamics of Reversible Thiol Additions to Mono- and Diactivated Michael Acceptors: Implications for the Design of Drugs That Bind Covalently to Cysteines.

Additions of cysteine thiols to Michael acceptors underpin the mechanism of action of several covalent drugs (e.g., afatinib, osimertinib, ibrutinib, neratinib, and CC-292). Reversible Michael acceptors have been reported in which an additional electron-withdrawing group was added at the α-carbon of a Michael acceptor. We have performed density functional theory calculations to determine why thiol additions to these Michael acceptors are reversible. The α-EWG group stabilizes the anionic transition state and intermediate of the Michael addition, but less intuitively, it destabilizes the neutral adduct. This makes the reverse reaction (elimination) both faster and more thermodynamically favorable. For thiol addition to be reversible, the Michael acceptor must also contain a suitable substituent on the β-carbon, such as an aryl or branched alkyl group. Computations explain how these structural elements contribute to reversibility and the ability to tune the binding affinities and the residence times of covalent inhibitors.

Synthesis and Characterization of Stable Anion Exchange Membranes: The Addition of Electron-withdrawing Group

Anion exchange membranes (AEM) based on poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) were used as polymer electrolyte membrane for fuel cell applications. The membranes were prepared via bromination, quaternization and nitration reactions and their fuel cell-related properties (water uptake, ion exchange capacity, ionic conductivity) were determined. Also, the structures and thermal properties were studied with Fourier transform infrared spectroscopy (FTIR), Size exclusion chromatography (SEC) and Differential scanning calorimetry (DSC). Nitration of quaternized PPO (Q-PPO) leaded to a decrease in water uptake and ion exchange capacity of the AEM. However, Q-PPO membrane treated with nitration reaction (NO 2 -Q-PPO) exhibited a significant alkaline stability compared to quaternized PPO (Q-PPO). The results indicated that the addition of electron-withdrawing group, such as nitro, into the structure in order to improve in alkaline stability is a promising new route for preparation alkaline stable AEM membranes.

Z-Shaped Pyrrolo[3,2-b]pyrroles and Their Transformation into π-Expanded Indolo[3,2-b]indoles.

Sterically hindered 1,4-dihydropyrrolo[3,2-b]pyrroles possessing ortho-(arylethynyl)phenyl substituents at positions-2 and -5 were efficiently synthesized through a sila-Sonogashira reaction. These unique Z-shaped dyes showed relatively strong fluorescence in solution. Detailed optimization revealed that, in the presence of InCl3, these alkynes readily undergo an intramolecular double cyclization to give hexacyclic products bearing an indolo[3,2-b]indole skeleton in remarkable yields. Steady-state UV-visible spectroscopy revealed that upon photoexcitation, the prepared Z-shaped alkynes undergo mostly radiative relaxation leading to high fluorescence quantum yields. In the case of 7,14-dihydrobenzo[g]benzo[6,7]indolo[3,2-b]indoles, we believe that the substantial planarization of geometry in the excited state, is the underlying reason for the observed large Stokes shifts. The presence of additional electron-withdrawing groups makes it possible to further alter the photophysical properties. The two-photon absorption cross-section values of both families of dyes were found to be modest and the nature of the excited state responsible for two-photon absorption appeared to be strongly affected by the presence of peripheral groups. Serendipitous synthesis of unusual double-Z-shaped alkyne by Sonogashira and Glaser coupling is also reported.

Modification of D-A-π-A configuration toward a high-performance triphenylamine-based sensitizer for dye-sensitized solar cells: a theoretical investigation.

In an attempt to shed light on how the addition of a benzothiadiazole (BTD) moiety influences the properties of dyes, a series of newly designed triphenylamine-based sensitizers incorporating a BTD unit as an additional electron-withdrawing group in a specific donor-acceptor-π-acceptor architecture has been investigated. We found that different positions of the BTD unit provided significantly different responses for light absorption. Among these, it was established that the further the BTD unit is away from the donor part, the broader the absorption spectra, which is an observation that can be applied to improve light-harvesting ability. However, when the BTD unit is connected to the anchoring group a faster, unfavorable charge recombination takes place; therefore, a thiophene unit was inserted between these two acceptors, providing redshifted absorption spectra as well as blocking unfavorable charge recombination. The results of our calculations provide valuable information and illustrate the potential benefits of using computation-aided sensitizer design prior to further experimental synthesis.

Amination of Heteroaryl Chlorides: Palladium Catalysis or SNAr in Green Solvents?

The reaction of heteroaryl chlorides in the pyrimidine, pyrazine and quinazoline series with amines in water in the presence of KF results in a facile SNAr reaction and N-arylation. The reaction is less satisfactory with pyridines unless an additional electron-withdrawing group is present. The results showed that the transition-metal-free SNAr reaction not only compares favourably to palladium-catalysed coupling reactions but also operates under environmentally acceptable (“green”) conditions in terms of the base and solvent.

Aminophenoxazinones as Inhibitors of Indoleamine 2,3-Dioxygenase (IDO). Synthesis of Exfoliazone and Chandrananimycin A

A range of 2-aminophenoxazin-3-ones has been prepared by oxidative cyclocondensation of 2-aminophenols, including the natural products exfoliazone and chandrananimycin A, both synthesized for the first time. The compounds were evaluated for their ability to inhibit indoleamine 2,3-dioxygenase. Compounds containing additional electron-withdrawing carboxylate groups, such as cinnabarinic acid, showed modest inhibitory activity with a dose response.

Taming Hot CF3 Radicals: Incrementally Tuned Families of Polyarene Electron Acceptors for Air‐Stable Molecular Optoelectronics

Breakthroughs in molecular optoelectronics await the availability of new families of air-stable polyaromatic hydrocarbon (PAH) acceptors with incrementally- and predictably-tunable electron affinities and structures capable of inducing desirable solid-state morphologies in hybrid materials. Although the addition of electron withdrawing groups to PAHs has been studied for decades, producing new compounds from time to time, a generic one-step synthetic methodology applicable to potentially all PAH substrates has been, until now, an impossible dream. We herein report that at least seventeen common PAHs and polyheterocyclics can be trifluoromethylated by a new procedure to yield families of PAH(CF3)n acceptors with (i) n = 4-8, (ii) multiple isomers for particular n values, (iii) gas-phase experimental electron affinities as high as 3.32 eV and shifted from the respective PAH precursor as a linear function of n, and (iv) various solid-state morphologies, including the ability to form alternating π stacked hybrid crystals with aromatic donors.

Chemoselective synthesis of tetrasubstituted furans via intramolecular Wittig reactions: mechanism and theoretical analysis

An efficient synthesis of tetrasubstituted furans was achieved from the corresponding α,β-unsaturated ketone derivatives, acid chlorides, and Bu3P in the presence of Et3N via a chemoselective intramolecular Wittig reaction as the key step. The presence of an additional electron-withdrawing group in the α-position of Michael acceptors controlled the chemoselectivities of presumable phosphorus ylides in the intramolecular Wittig reactions, and their mechanisms were also investigated by DFT calculations.