Allyl Moiety Research Articles

Iridium-catalyzed asymmetric ring-opening reactions of azabenzonorbornadiene with carboxylic acid nucleophiles

Iridium-catalyzed asymmetric ring-opening reaction of N-substituted azabenzonorbornadienes with various carboxylic acids has been developed. The ring-opening reaction offered trans-1,2-dihydronaphthalene products containing an allylic carboxylate moiety in moderate yields (up to 89 %) with high enantioselectivities (up to 96 %). The trans-configuration of the products was confirmed by X-ray crystallography.

Mechanistic Study of the Pd/TOMPP-Catalyzed Telomerization of 1,3-Butadiene: Influence of Aromatic Solvents on Bis-Phosphine Complex Formation and Regioselectivity

A study of the influence of reaction conditions on the Pd/TOMPP-catalyzed (TOMPP = tris(2-methoxyphenyl)phosphine) telomerization of 1,3-butadiene with phenols revealed that the composition of the reaction medium strongly influences the regioselectivity of the telomer products. Mechanistic studies show this effect to be related to the stability of the key catalytic intermediate cis-[Pd((1–3η)-octa-2,7-dien-1-yl)(TOMPP)2]+ (E), which mainly depends on the solvent composition. The crotyl analogue cis-[Pd((1–3η)-but-2-en-1-yl)(TOMPP)2]BF4 (4) was synthesized as a model for E and was fully characterized, including by an X-ray crystal structure determination. Comparison of the crystal structures of 4 and [Pd((1–3,7,8η)-octa-2(E),7-dien-1-yl)(TOMPP)]BF4 (1), an analogue of intermediate C, shows that the difference in regioselectivity for nucleophilic attack of these complexes is not reflected in the structure of the allyl moiety. Furthermore, Pd/TOMPP-catalyzed n/iso equilibration reactions of telomers show that all product formation routes in the Pd-catalyzed telomerization mechanism are reversible. Telomer product equilibration studies resulted in complete conversion to 1,3,7-octatriene, with the selectivity changing over time in favor of formation of the Z isomer of octatriene.

Experimental and Theoretical Studies of Selective Thiol–Ene and Thiol–Yne Click Reactions Involving N-Substituted Maleimides

A combination of experimental and computational methods has been used to understand the reactivity and selectivity of orthogonal thiol-ene and thiol-yne ″click″ reactions involving N-allyl maleimide (1) and N-propargyl maleimide (2). Representative thiols methyl-3-mercaptopropionate and β-mercaptoethanol are shown to add exclusively and quantitatively to the electron poor maleimide alkene of 1 and 2 under base (Et3N) initiated thiol-Michael conditions. Subsequent radical-mediated thiol-ene or thiol-yne reactions can be carried out to further functionalize the remaining allyl or propargyl moieties in near quantitative yields (>95%). Selectivity, however, can only be achieved when base-initiated thiol-Michael reactions are carried out first, as radical-mediated reactions between equimolar amounts of thiol and N-substituted maleimides give complex mixtures of products. CBS-QB3 calculations have been used to investigate the energetics and kinetics of reactions between a representative thiol (methyl mercaptan) with N-allyl and N-propargyl maleimide under both base-initiated and radical-mediated conditions. Calculations help elucidate the factors that underlie the selective base-initiated and nonselective radical-mediated thiol-ene/yne reactions. The results provide additional insights into how to design selective radical-mediated thiol-ene/yne reactions.

Theoretical study on thermal decomposition kinetics of allyl formates in the gas phase

The study of the kinetics and mechanisms of the gas-phase thermal decarboxylation of allyl formate and 2-methylallyl formate was carried out by means of electronic structure calculations using Density Functional Theory (DFT) functionals: B3LYP, B3PW91, MPW1PW91 and PBEPBE. Two possible molecular mechanisms were investigated: a concerted [1,5] hydrogen shift through a six-centered cyclic transition state, and a [1,3] hydrogen shift mechanism through a four-centered cyclic transition state. Calculation results suggest these reactions to be unimolecular and proceed in a concerted mechanism through a six-membered cyclic transition state (TS) geometry. Despite the similar activation energies, differences were found when comparing the two elimination processes. In the case of allyl formate, the reaction shows small predominance of the change in the terminal allyl moiety bond order and the COester bond breaking. Conversely, for 2-methylallyl formate, the process is highly controlled by the new CO double bond development leading to carbon dioxide formation. Moreover, in the 2-methylallyl formate decomposition, the α-carbonyl hydrogen transfer to the terminal allyl carbon to produce 2-methyl propene is at a very early stage in the TS compared to allyl formate.

Combining Spontaneous Polymerization and Click Reactions for the Synthesis of Polymer Brushes: A “Grafting Onto” Approach

Two novel benzofulvene monomers bearing propargyl or allyl groups have been synthesized by means of readily accessible reactions, and were found to polymerize spontaneously by solvent removal, in the apparent absence of catalysts or initiators, to give the corresponding polybenzofulvene derivatives bearing clickable propargyl or allyl moieties. The clickable propargyl and allyl groups were exploited in appropriate click reactions to develop a powerful and versatile "grafting onto" synthetic methodology for obtaining tailored polymer brushes.

Allyl-containing polyaryl ethers with perfluorinated mono- and biphenylene fragments

A method for the synthesis of fluorinated allyl-containing bisphenol based on 4,4′-[(2,3,5,6-tetrafluoro-1,4-phenylene)bis(oxy)]diphenol has been elaborated. Curable aromatic polyethers have been prepared via polycondensation of the synthesized bisphenol with decafluorobiphenyl. The influence of bases, namely K2CO3 and NaH, on the molecular weights of polymers has been studied, and the conditions of their curing at allyl moieties have been found. Mechanical, physicochemical, and dielectric properties of allylcontaining polymers are dependent on the method of their preparation and curing.

Efficient Anodic Allylation and Benzylation of Carbons Using Allyl and Benzyl Trimethylsilanes

An easy process for allylation and benzylation of different carbon materials, primarily of glassy carbon, in acetonitrile solutions containing tetraalkyammonium salts is described. The method relies on the capability of C(sp(2)) zones of glassy carbon (graphite and fullerene-like inclusions) to be anodically charged at potentials >1.5 V versus Ag/AgCl to form electrophilic centers reacting with substituted trimethylsilanes RSiMe3. Great propensity of the trimethylsilyl group (TMS(+)) to act as a cationic leaving group facilitates electrophilic reactions of the charged anodic surface with R-carrying silylated precursors, permitting efficient grafting of a large variety of R groups. The present preliminary work focuses only on the efficient grafting of benzyl and allyl moieties.

Bioinspired Water-Enhanced Mechanical Gradient Nanocomposite Films That Mimic the Architecture and Properties of the Squid Beak

Inspired by the water-enhanced mechanical gradient character of the squid beak, we herein report a nanocomposite that mimics both the architecture and properties of this interesting natural material. Similar to the squid beak, we have developed nanocomposites where the degree of cross-linking is controlled along the length of the film. In this study, we utilized tunicate cellulose nanocrystals as the nanofiller that are functionalized with allyl moieties. Using photoinduced thiol-ene chemistry, we have been able to cross-link the CNC nanofiller. In the dry state where strong CNC interactions can occur, only a small mechanical contrast is observed between the cross-linked and uncross-linked samples. However, when the films are exposed to water, which "switches off" the noncovalent CNC interactions, a significant mechanical contrast is observed between the same films. For example, at 20 wt % CNC (in the dry film), an increase in wet modulus from 60 to 300 MPa (∼500% increase) is observed after photoirradiation. Furthermore, we show that the wet modulus can be controlled by altering the UV exposure time which allows access to mechanical gradient films.

Efficient [2+2] photocycloadditions under equimolar conditions by employing a continuous UV-flow reactor

Abstract The [2 + 2] photocycloaddition between maleimide and various alkenes was optimized in a simple custom-made UV flow reactor. While complete maleimide conversion is only achieved with excesses of at least 10 eq. of alkene and reaction times of 12–24 h in batch, complete reactions with yields in the range >98% could be obtained in 5 min in the flow reactor under strictly equimolar conditions. Functional alkenes carrying allyl, alcohol, amine and ether moieties were successfully conjugated in good yields under optimized reaction conditions. As is demonstrated, the reaction gains in flow most characteristics of a high-efficient reaction, making the process highly valuable for upscaled synthesis of maleimide conjugates.

Controlled-Length Efficient Synthesis of Heterobifunctionalized Oligo Ethylene Glycols

A set of heterobifunctional oligo ethylene glycols have been synthesized in a straightforward and stepwise manner starting from inexpensive, commercially available, tetraethylene glycol. Introduction of terminal allyl moieties followed by reductive ozonolysis allowed controlled elongation. Mono-allyl derivatives were used for the elongation with a functionalized moiety and for successive introduction of different functional groups on the chain terminal.

Amphidinolide B: total synthesis, structural investigation, and biological evaluation.

The total syntheses of amphidinolide B1 and the proposed structure of amphidinolide B2 have been accomplished. Key aspects of this work include the development of a practical, non-transition-metal-mediated method for the construction of the C13-C15 diene, the identification of α-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy, and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B2 and diastereomers thereof display potent antitumor activities with IC50 values ranging from 3.3 to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B2 is over 12-fold more potent than the C8,9-epimer and C18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity.

Photochemistry of 1-allyl-4-aryltetrazolones in solution; structural effects on photoproduct selectivity

The photochemistry of tetrazolones derived from the carbocyclic allylic alcohols cyclohex-2-enol and 3-methylcyclohex-2-enol and from the natural terpene alcohol nerol was investigated in solution with the aim of assessing the effect of solvent and of structural constraints imposed by bulky allylic moieties on photoproduct selectivity and stability. Photolysis of tetrazolones derived from nerol and cyclohex-2-enol afforded the corresponding pyrimidinones as major products through a pathway that appears to be similar to that proposed for other 1-allyl-4-phenyl-1,4-dihydro-5H-tetrazol-5-ones derived from acyclic and unhindered allylic alcohols previously investigated but photolysis of the tetrazolone derived from the bulkier 3-methylcyclohex-2-enol 4c leads to formation of a benzimidazolone, indicating that, in this case, cyclization of the biradical formed upon extrusion of N(2) involves the phenyl substituent and not the allylic moiety. Theoretical calculations (DFT(B3LYP)/3-21G*) were conducted to support the interpretation of the experimental results and mechanistic proposals. Laser flash photolysis experiments were conducted with the aim of clarifying the nature of the intermediate involved in the primary photocleavage process.

Highly practical iron-catalyzed C–O cleavage reactions

Facile iron-catalyzed cleavage of various allyl, cinnamyl and benzyl C–O linkages has been effected in the presence of ethylmagnesium chloride. The protocol is operationally simple (xylene–THF, r.t., 1 h), requires low catalyst loading (1 mol% FeCl2) and tolerates halides, esters, amines, ethers and olefins. The allyl moiety is converted to volatile hydrocarbons which renders laborious product separation unnecessary.

Some transformations of tacrolimus, an immunosuppressive drug

Transformations of the macrocyclic lactone tacrolimus (1), an important immunosuppressive drug produced by Streptomyces species, are described. These transformation products are primarily of interest as reference substances for drug impurity analyses. Upon action of acid (p-toluenesulfonic acid in toluene), tacrolimus is dehydrated by loss of water from the β-hydroxyketone moiety with partial inversion of configuration at C-8, resulting in formation of 5-deoxy-Δ5,6-tacrolimus and 5-deoxy-Δ5,6-8-epitacrolimus. The structure of the latter was determined by single-crystal X-ray crystallography. The same products are formed upon action of free radicals (iodine in boiling toluene), along with formation of 8-epitacrolimus. The latter is converted by p-toluenesulfonic acid to 5-deoxy-Δ5,6-8-epitacrolimus. Treatment of tacrolimus with weak base (1,5-diazabicyclo[4.3.0]nonene) gives, in addition to 8-epitacrolimus, the open-chain acid corresponding to 5-deoxy-Δ5,6-tacrolimus, a rare non-cyclic derivative of tacrolimus. Strong base (t-butoxide) causes pronounced degradation of the molecule. Thermolysis of tacrolimus leads to ring expansion by an apparent [3,3]-sigmatropic rearrangement of the allylic ester moiety with subsequent loss of water from the β-hydroxyketone moiety. 1H and 13C NMR spectra of the obtained compounds, complicated by the presence of amide bond rotamers and ketal moiety tautomers, were assigned by extensive use of 2D NMR techniques.

Effect of Cross-Link Density on Photoplasticity of Epoxide Networks Containing Allylic Dithioether Moieties

A new diepoxide monomer (ADTDE) containing an allylic dithioether moiety has been synthesized to extend the suite of monomers that form networks exhibiting radical-mediated photoplasticity. These cross-linked polymers show permanent shape change under load and stress relax only when under the stimulus of visible or UV radiation. The Lewis base-catalyzed reaction of the epoxide groups in ADTDE with tri- and tetrafunctional thiols was monitored by differential scanning calorimetry and infrared spectroscopy. These curing systems were found to be more efficient than anionic, cationic, or anhydride polymerizations. The dynamic mechanical thermal analysis of ADTDE with the tetrathiol showed that the network was rubbery at room temperature which is considered ideal for the demonstration of photoplasticity. The photoinduced creep behavior was shown to be controlled by the presence of active free radicals in the matrix—on cessation of irradiation, the creep was terminated. The stress relaxation of the stretched ne...

Identification of novel chromenone derivatives as interleukin-5 inhibitors

A series of (E)-5-alkoxy-3-(3-phenyl-3-oxoprop-1-enyl)-4H-chromen-4-ones (4) and (E)-5-alkoxy-3-(3-hydroxy-3-phenylprop-1-enyl)-4H-chromen-4-ones (5) were synthesized and evaluated for their IL-5 inhibitory activity. Propenone analogs 4 possess some of the structurally important characteristics of isoflavone 2 and chalcone 3 previously known as potent IL-5 inhibitor. However, the inhibitory activity of 4 was weak and therefore this structural hybridization appears to be ineffective for the design of IL-5 inhibitor. Meanwhile the potent activity profile of compounds 5 was discovered. This enhanced activity of 5 compared to 4 could be due to the effective location of hydroxyl group of allylic alcohol moiety of 5 in the 3D structure. The electron withdrawing substituents at position 4 of phenyl ring of 5 enhances the activity possibly due to an increase in the strength of hydrogen bonding property of hydroxyl group of allylic alcohol moiety.

1,2]- and [1,4]-Wittig rearrangements of α-alkoxysilanes: effect of substitutions at both the migrating benzylic carbon and the terminal sp2 carbon of the allyl moiety

Substituted α-alkoxysilanes can be deprotonated by alkyllithium bases and made to undergo Wittig rearrangements to afford the [1,4]- and [1,2]-rearranged products in varying ratios. Substitution at the benzylic migrating carbon and/or at the allylic carbon of the allyl moiety impacts the rearrangement reaction, influencing the reactivity as well as the [1,4]-/[1,2]-selectivity. Diastereomeric α-alkoxysilanes show different reactivities with the syn diastereomer being the more reactive isomer.

Synthesis and SAR studies of 3-allyl-4-prenyloxyaniline amides as potent 15-lipoxygenase inhibitors

15-Lipoxygenases are one of the nonheme iron-containing proteins with ability of unsaturated lipid peroxidation in animals and plants. The critical role of the enzymes in formation of inflammations, sensitivities and some of cancers has been demonstrated in mammalians. Importance of the 15-lipoxygenases leads to development of mechanistic studies, products analysis and synthesis of their inhibitors. In this work new series of the 3-allyl-4-allyoxyaniline amides and 3-allyl-4-prenyloxyaniline amides were designed, synthesized and their inhibitory potency against soybean 15-lipoxygenase were determined. Among the synthetic amides, 3-allyl-4-(farnesyloxy)-adamantanilide showed the most potent inhibitory activity by IC50 value of 0.69μM. SAR studies showed that in spite of prenyl length increases, the effects of the amide size and its electronic properties on the inhibitory potency became predominant. The SAR studies was also showed that the orientation of allyl and prenyloxy moieties toward Fe core of the SLO active site pocket is the most suitable location for enzyme inhibition.

Flame retardancy and thermal decomposition of flexible polyurethane foams: Structural influence of organophosphorus compounds

In this study the structural effect of different phosphorus compounds on the flame retardant (FR) properties of flexible polyurethane foams (FPUF) was investigated. A series of organophosphorus compounds (phosphonates, phosphates and phosphoramidates) with systematical structure variations were synthesized and incorporated into the flexible foam during its polymerization process. The flame-retarding efficiency of these phosphorus compounds was subsequently evaluated by subjecting their corresponding flame-retarded foams to standard fire tests such as limiting oxygen index (LOI), BKZ-vertical burning test and UL 94-horizontal burning test for foamed materials. It was observed that the synthesized phosphonates and analogous phosphoramidates were more effective than the corresponding phosphates. The presence of an allyl moiety within the molecular structure further improved the FR efficacy of the phosphonate and phosphoramidate compounds, whereas a benzyl group reduced the flame retardant efficiency significantly. The thermogravimetric (TGA) analysis and pyrolysis combustion flow calorimetry (PCFC) results for the FPUF indicated that the most effective FRs might act predominantly in gas phase and exhibit lower condensed phase action (i.e. catalyze the decomposition of FPUF to happen at lower temperatures). Mass spectrometric analysis of FRs indicates that phosphonate and phosphoramidate derivatives appear to support the phosphoryl radical formation more than the investigated phosphate compounds.

Synthesis and Characterization of Thiol-Ene Functionalized Siloxanes and Evaluation of their Crosslinked Network Properties.

Three types of linear thiol-functionalized siloxane oligomers and three types of ene-functionalized oligomers were synthesized and subsequently photopolymerized. Within each type of thiol-functionalized oligomer, the ratio of mercaptan repeat units to non-reactive phenyl repeat units was varied to manipulate both the crosslink density and the degree of secondary interactions through pi-pi stacking. Similarly, the repeat units of the three ene-functionalized oligomers are composed of allyl-functional monomers, benzene-functional monomers, and octyl-functional monomers in varying ratios of benzene:octyl but with a constant fraction of allyl moieties. The structural composition of the siloxane oligomers plays a pivotal role in the observed material properties of networks formed through thiol-ene photopolymerization. Networks with a high concentration of thiol functionalities exhibit higher rubbery moduli, ultimate strengths, and Young's moduli than networks with lower thiol concentrations. Moreover, the concentration of functionalities capable of participating in secondary interactions via hydrogen bonding or pi-pi stacking directly impacts the network glass transition temperature and elasticity. The combination of low crosslink density and high secondary interactions produces networks with the greatest toughness. Finally, the fraction of octyl repeats correlates with the hydrophobic nature of the network.