Allylic Phosphonates Research Articles

Palladium-Catalyzed Ligand-Enabled Cyclization of Substituted Aliphatic Carboxylic Acids with Allylic Electrophiles.

A palladium-catalyzed cyclization of the β-C(sp3)-H bond of aliphatic carboxylic acids with allylic electrophiles providing five-membered γ-lactones in good to excellent yields is demonstrated. An acetyl-protected aminoethyl phenyl thioether ligand is used to promote the C-H activation reaction. A diverse range of allylic electrophiles such as allyl alcohols, allyl acetates, allyl sulfones, allyl phosphonate, allyl amine, and allyl ester have been utilized for this reaction. A feasible reaction mechanism has been proposed to account for the present cyclization reaction.

Nickel-Catalyzed Suzuki-Miyaura Coupling in Water for the Synthesis of 2-Aryl Allyl Phosphonates and Sulfones.

An operationally simple and green protocol using a NiSO4·6H2O/cationic 2,2'-bipyridyl ligand system as a water-soluble catalyst for the coupling of arylboronic acids with (2-haloallyl)phosphonates and (2-haloallyl)sulfones in water under air was developed. The reaction was performed at 120 °C with arylboronic acids (2 mmol) and (2-haloallyl)phosphonates or sulfones (1 mmol) in the presence of 5 mol % of the Ni catalytic system in a basic aqueous solution for 1 h, giving the corresponding 2-aryl allyl phosphonates or sulfones in good to excellent yields. This reaction features the use of an abundant transition metal as a catalyst in water and exhibits high functional group tolerance, rendering it an eco-friendly procedure.

Lewis acid-catalyzed phosphinoylation and halogenation of α,β-unsaturated ketones: access to γ-halo allylic phosphonates

A Lewis acid-catalyzed phosphinoylation and halogenation of α,β-unsaturated ketones to synthesize γ-halo allylic phosphonates is described.

Naked-Eye Thiol Analyte Detection via Self-Propagating, Amplified Reaction Cycle.

We present an approach for detecting thiol analytes through a self-propagating amplification cycle that triggers the macroscopic degradation of a hydrogel scaffold. The amplification system consists of an allylic phosphonium salt that upon reaction with the thiol analyte releases a phosphine, which reduces a disulfide to form two thiols, closing the cycle and ultimately resulting in exponential amplification of the thiol input. When integrated in a disulfide cross-linked hydrogel, the amplification process leads to physical degradation of the hydrogel in response to thiol analytes. We developed a numerical model to predict the behavior of the amplification cycle in response to varying concentrations of thiol triggers and validated it with experimental data. Using this system, we were able to detect multiple thiol analytes, including a small molecule probe, glutathione, DNA, and a protein, at concentrations ranging from 132 to 0.132 μM. In addition, we discovered that the self-propagating amplification cycle could be initiated by force-generated molecular scission, enabling damage-triggered hydrogel destruction.

Synthesis of chiral allylic phosphonates via asymmetric reductive cross-coupling of α-bromophosphonates and vinyl bromides

Synthesis of chiral allylic phosphonates via asymmetric reductive cross-coupling of α-bromophosphonates and vinyl bromides

Mechanism of the phosphine‐catalyzed [3 + 3] annulation with MBH carbonates as the potential dipoles

AbstractThe [3 + 3] cylcloaddition/annulation is an important complementary for construction of six‐membered ring. With addition of organophosphine to the Morita‐Baylis‐Hillman (MBH) carbonate, a potential C3 synthon can be furnished. In this work, the catalytic mechanisms for using this synthon as the nucleophilic or electrophilic dipole to react with the cyclohexa‐2,5‐dienone‐substituted benzenesulfonamide are studied by the density functional theory method. The computational results reveal that the nucleophilic addition of the amide anion to the allylic phosphonium is more favorable than the electrophilic addition of alkenyl in the benzenesulfonamide with the allylic phosphorus ylide. Namely, the allylic phosphonium adduct, rather than the allylic phosphorus ylide that is generated by deprotonation of the allylic phosphonium, is more likely to act as the potential dipole. The global reactivity index calculations indicate that species involved in the favored pathway have better reactivities (both in nucleophilicity and electrophilicity), especially the significantly higher nucleophilicity of the amide anion.

Syntheses and utilizations of pyrroline and tetrahydropyridine nitroxide-based phosphonate esters, a phosphate ester and a bisphosphonate

Five- and six-membered cyclic nitroxide-based allylic phosphonate esters, α-ketophosphonate esters were obtained from the corresponding paramagnetic allyl bromides and acyl chlorides respectively via the Arbuzov reactions. The α-hydroxyphosphonate esters were accessed by Pudovik reactions from the corresponding paramagnetic ketones and aldehydes. The β-ketophosphonate esters were obtained from the appropriate 1-alkynylphosphonate esters via PdCl2-catalyzed hydration. The synthesis of an allylic phosphate ester and a paramagnetic geminal bisphosphonate was also reported.

Total Syntheses and Absolute Configuration Assignment of (+)-Sootepdienone, (-)-Jambolanin C, (-)-Jambolanin I, and (-)-Gibberodione.

Total syntheses of the sesquiterpenes (+)-sootepdienone, (-)-jambolanin C, (-)-jambolanin I, and (-)-gibberodione have been accomplished in 10 steps each from R-(+)-pulegone, allowing assignment of the absolute configuration of the natural products. A key step in the synthetic pathways involves the one-carbon ring expansion of a cyclic allylic phosphonate to a substituted cycloheptenone by a tandem oxidative cleavage/intramolecular Horner-Wadsworth-Emmons reaction.

Synthesis of α-Aminophosphonic Acid Derivatives Through the Addition of O- and S-Nucleophiles to 2H-Azirines and Their Antiproliferative Effect on A549 Human Lung Adenocarcinoma Cells

This work reports a straightforward regioselective synthetic methodology to prepare α-aminophosphine oxides and phosphonates through the addition of oxygen and sulfur nucleophiles to the C–N double bond of 2H-azirine derivatives. Determined by the nature of the nucleophile, different α-aminophosphorus compounds may be obtained. For instance, aliphatic alcohols such as methanol or ethanol afford α-aminophosphine oxide and phosphonate acetals after N–C3 ring opening of the intermediate aziridine. However, addition of 2,2,2-trifluoroethanol, phenols, substituted benzenthiols or ethanethiol to 2H-azirine phosphine oxides or phosphonates yields allylic α-aminophosphine oxides and phosphonates in good to high general yields. In some cases, the intermediate aziridine attained by the nucleophilic addition of O- or S-nucleophiles to the starting 2H-azirine may be isolated and characterized before ring opening. Additionally, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549) and non-malignant cells (MCR-5) was also screened. Some α-aminophosphorus derivatives exhibited very good activity against the A549 cell line in vitro. Furthermore, selectivity towards cancer cell (A549) over non-malignant cells (MCR-5) has been detected in almost all compounds tested.

γ-Substituted Allenic Amides in the Phosphine-Catalyzed Enantioselective Higher Order Cycloaddition with Azaheptafulvenes.

Racemic γ-substituted allenes undergo enantioselective higher order [8 + 2]-cycloaddition with azaheptafulvenes using a chiral amino acid derived amidophosphine as catalyst, providing the corresponding azaazulenoid cycloadducts with excellent levels of regio-, diastereo-, and enantioselectivities. In this reaction, the activated allylic phosphonium ylide intermediate participates as the C2-component of the reaction, in contrast to the conventional reactivity of this type of zwitterionic intermediates as C3-components in cycloaddition reactions.

Phosphine‐Catalyzed Activation of Alkylidenecyclopropanes: Rearrangement to Form Polysubstituted Furans and Dienones

AbstractWe report a phosphine‐catalyzed ring opening of electron‐deficient alkylidenecyclopropanes (ACPs) to generate allylic phosphonium zwitterions that resemble the well‐studied phosphine‐allene adducts but exhibit distinct properties. The potent reactivity of these intermediates has been demonstrated in three types of substrate‐controlled phosphine‐catalyzed rearrangements of alkylidenecyclopropylketones, which chemoselectively afford tri‐ and tetrasubstituted furans, and trisubstituted dienones in good yields.

Phosphine-Catalyzed Activation of Alkylidenecyclopropanes: Rearrangement to Form Polysubstituted Furans and Dienones.

We report a phosphine-catalyzed ring opening of electron-deficient alkylidenecyclopropanes (ACPs) to generate allylic phosphonium zwitterions that resemble the well-studied phosphine-allene adducts but exhibit distinct properties. The potent reactivity of these intermediates has been demonstrated in three types of substrate-controlled phosphine-catalyzed rearrangements of alkylidenecyclopropylketones, which chemoselectively afford tri- and tetrasubstituted furans, and trisubstituted dienones in good yields.

Synthesis of Benzothiophene-Fused Oxa[6.6.5]tricyclic Skeletons through a Cinchonidine- or NaOH-Promoted Quadruple Domino Sequence.

Two base-promoted quadruple domino reactions between thioaurones and allylic phosphonium salts have been developed to synthesize benzothiophene-fused oxa[6.6.5]tricyclic skeletons in moderate to good yields with excellent stereoselectivity and broad functional-group tolerance. This is a simple and useful protocol for the rapid construction of the umbrella-like oxa[6.6.5]tricyclic skeleton.

Substrate Self-Assisted Secondary Bond Activation of Allylic Alcohol in a Tsuji-Trost Reaction Revealed by NMR Methods.

The first experimental evidence for the palladium-catalyzed secondary bond activation of allylic alcohols in a Tsuji-Trost reaction was provided by NMR methods, such as variable-temperature 1H NMR, diffusion-ordered spectroscopy (DOSY), Job's method, 1H NMR titration, and nuclear Overhauser enhancement spectroscopy (NOESY). The experimental results revealed that the substrate self-assisted activation of allylic alcohols is probably performed via a 1:1 binding six-membered-ring complex, which are formed by the formation of the secondary bonds, the hydrogen bond and P···O noncovalent bond between allylic alcohol and phosphonium ylide.

Asymmetric Vinylogous Aldol-type Reactions of Aldehydes with Allyl Phosphonate and Sulfone

SummaryTwo catalytic asymmetric vinylogous aldol-type reactions of aldehydes with allyl phosphonate and allyl sulfone have been uncovered in good to high yields for the first time. The bulky ligand—(R)-DTBM-SEGPHOS—was found to be the key to perfectly control both regio- and enantioselectivities. Transformations of the vinylogous products (including Horner-Wadsworth-Emmons and Julia olefinations) were successfully realized by virtue of the phosphonate and sulfone moieties. Moreover, the present methodology was successfully applied in the asymmetric synthesis of natural products.

Catalytic Asymmetric Vinylogous Aldol-Type Reactions of Aldehydes with Allyl Phosphonate and Allyl Sulfone

Two catalytic asymmetric vinylogous aldol-type reactions of aldehydes with allyl phosphonate and allyl sulfone have been uncovered in good to high yields for the first time. The bulky ligand — (R)-DTBM-SEGPHOS was found to be the key to perfectly control both regio- and enantioselectivities. Transformations of the vinylogous products (including Horner-Wadsworth-Emmons olefination and Julia olefination) were successfully realized by virtue of the phosphonate and the sulfone moieties. Moreover, the present methodology was successful applied in the asymmetric synthesis of natural products.

Facile access to functionalized chiral secondary benzylic boronic esters via catalytic asymmetric hydroboration.

Allylic and homoallylic phosphonates bearing an aryl or heteroaryl substituent at the γ- or δ-position undergo rhodium-catalyzed asymmetric hydroboration by pinacolborane to give functionalized chiral secondary benzylic boronic esters in yields up to 86% and enantiomer ratios up to 99 : 1. Compared to minimally-functionalized terminal and 1,1-disubstituted vinyl arenes, there are relatively few reports of efficient catalytic asymmetric hydroboration (CAHB) of more highly functionalized internal alkenes. Phosphonate substrates bearing a variety of common heterocyclic ring systems, including furan, indole, pyrrole and thiophene derivatives, as well as those bearing basic nitrogen substituents (e.g., morpholine and pyrazine) are tolerated, although donor substituents positioned in close proximity of the alkene can influence the course of the reaction. Stereoisomeric (E)- and (Z)-substrates afford the same major enantiomer of the borated product. Deuterium-labelling studies reveal that rapid (Z)- to (E)-alkene isomerization accounts for the observed (E/Z)-stereoconvergence during CAHB. The synthetic utility of the chiral boronic ester products is illustrated by stereospecific C-B bond transformations including stereoretentive electrophile promoted 1,2-B-to-C migrations, stereoinvertive SE2 reactions of boron-ate complexes with electrophiles, and stereoretentive palladium- and rhodium-catalyzed cross-coupling protocols.

Castor‐oil derived nonhalogenated reactive flame‐retardant‐based polyurethane foams with significant reduced heat release rate

ABSTRACTNational Fire Protection Association encounters one structural fire every 66 s. Rigid polyurethane foam is one of the principal components used in constructional and household applications. In this work, a reactive flame retardant (FR) was synthesized using a facile one‐step thiol–ene reaction by reacting mercaptenized castor oil (MCO) and diethyl allyl phosphonate (DEAP). The obtained MCO–DEAP polyol was used for the preparation of polyurethanes having different weight percentages of phosphorus (P). Addition of FR polyol showed no adverse effect on the cellular structure of the foams and maintained the compressive strength. All the foams showed closed cell content greater than 95%. Horizontal burning test (HBT) was performed before and after the migration test to understand the stability of the FR within the foams. Foams showed no relative weight loss before and after the migration test and maintained equivalent results for HBT. For 1.5 wt % P foams, low extinguishing time of 3 s and weight loss of 4% was observed. The cone calorimeter test showed a reduction in the peak heat release rate from 313 to 158 kW m−3, the total heat release from 18 to 8 MJ m−2, and O2 consumption from 12 to 6 g. Our results suggest that MCO–DEAP polyol could act as an essential FR for rigid PU foam ensuring fire safety. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47276.

Sustainable flame-retardant polyurethanes using renewable resources

Renewable bio resources such as soybean, orange peel, and castor along with a novel phosphorous based polyol were used to prepare highly flame-retardant polyurethane foams. Diethyl allyl phosphonate (DEAP) and thioglycerol (TG) were used to synthesize phosphorous (P) based flame retardant polyol (DEAP-TG). Polyurethane (PU) foams having a various weight percentage of phosphorous were prepared using a varying amount of DEAP-TG (as a phosphorous source) and other bio-based polyols. Use of DEAP-TG polyol in polyurethane foams showed improved compressive strength without affecting closed cell content and morphology of the foams. The horizontal burning test showed a drastic reduction in self-extinguishing time and weight loss for the PU foams containing DEAP-TG polyol. For example, castor oil and DEAP-TG based PU foam which contains 1.5 wt% P showed significant reduction in self-extinguishing time (from 94s to 1.7s) and weight loss (from 48.5% to 3%) compared to neat castor oil based foams. Cone calorimeter data also showed a significant reduction in peak heat release rate, total heat release, total smoke release, and overall smoke production rate for the foam containing 1.5 wt% P compared to 0 wt% P in the foam. The improved flame retardancy was due to the formation of a protective char layer over the surface of the foam due to decomposition of a phosphorus compound. Our research provides a green alternative to prepare industrial grade flame-retardant polyurethane foams.

Ring Expansion, Ring Contraction, and Annulation Reactions of Allylic Phosphonates under Oxidative Cleavage Conditions.

Oxidative cleavage of cycloalkenylalkylphosphonates 1 followed by treatment with base gives rise to homologated cycloalkenones 2 in good to excellent yields. Subjecting cycloalk-2-enylphosphonates 3 to identical conditions provides the one-carbon ring-contracted compounds 4 in excellent yields. Oxidative cleavage of γ,δ-unsaturated ketophosphonates 6 followed by treatment with base affords 2-cyclopenten-1-ones 7 in good overall yields. This method may offer a practical alternative to existing methods for effecting one-carbon ring expansion, ring contraction, and annulation reactions.