Alkenyl Substituents Research Articles

Iron-Catalyzed Cross-Dehydrogenative Coupling of para-Quinone Methides with Formamides: In Situ Activation of C(sp2)-H Bonds.

A novel and straightforward method for the iron-catalyzed regioselective cross-dehydrogenative coupling of para-quinone methides (p-QMs) with formamides has been developed, facilitated by the in situ activation of the C(sp2)-H bonds of the formyl and alkenyl substituents via a radical strategy. This method does not require the preactivation of the substrates, and it can accommodate a wide range of p-QMs and formamides under the optimized reaction conditions, resulting in the formation of the expected C-7 acetamides-functionalized para-quinone methides with moderate to good yields. The control experiments revealed that the reaction follows the fundamental equation of second-order kinetics. Additionally, an exploration of the Hammett effect was undertaken to elucidate the impact of the substituents for the reaction. In combination with the DFT calculation, a plausible reaction mechanism was proposed through meticulously controlled experiments.

HYDROGEN SULFIDE CORROSION INHIBITORS AND BIOCIDES BASED ON FUNCTIONALLY SUBSTITUTED ALKENILPHENOL DERIVATIVES

The article presents the results of gravimetric anticorrosion studies of 1-alkenyl-2-propargyloxy- and 1-alkenyl-2-propargyloxy-3-aminomethylbenzenes on Ct.3 steel in water- salt and hydrocarbon media saturated with hydrogen sulfide (500 mg/L), as well as the study of their bactericidal properties against sulfate-reducing bacteria. The dependence of the protective properties of these compounds on their structure was revealed. It has been established that 1-propenyl-2-propargyl-3-diethylaminomethylphenol has the best properties. At the concentration 50 and 100 mg / L in an aggressive, saturated H2S environment, 3% aqueous solution of NaCl and kerosene (9:1 vol), the degree of protection of St.3 steel against corrosion is 94.7 and 97.5%, (at 250C) and 88.0 and 94.6% (at 400C), respectively.The studied compounds also have bactericidal properties, especially compounds containing in the structures, in addition to the alkenyl and propargyl substituents, also a morpholinomethyl fragment. At its concentration 50 and 100 mg/L, the degree of protection is 96–100%.

Gold‐Catalyzed Tandem Oxidation‐Migration of 3‐Propargyl Indoles: Synthesis of α‐Indol‐3‐yl α,β‐Unsaturated Carbonyls

Abstractα‐Indol‐3‐yl α,β‐unsaturated carbonyl compounds are synthesized from 3‐propargyl indoles, obtained by direct propargylation of indoles, via a gold‐catalyzed tandem oxidation‐1,2‐indole migration reaction in the presence of pyridine N‐oxides. Fine‐tuning of the catalyst and oxidant enables the reaction of 3‐propargyl indoles bearing different substituents. The order of oxidation and indole migration is determined by the terminal or internal nature of the alkyne moiety. In addition, the process can be coupled with additional reactions, allowing an increase in molecular complexity or the design of more elaborated tandem reactions. In this sense, indole derivatives bearing an alkenyl substituent at the alkyne position evolve through a gold‐catalyzed tandem oxidation‐1,2‐indole migration‐Nazarov cyclization producing α‐indolyl cyclopentenones.

Ionic plastic crystals and ionic liquids containing quaternary cations with alkenyl substituents: chemical phase transformations by bromine vapor

Quaternary ammonium salts with vinyl or allyl substituents were synthesized, which underwent bromine addition reactions under bromine vapor, resulting in transformations between ionic plastic crystals, ionic liquids, and ordinary ionic crystals.

Cyclizations of Alkenyl(Alkynyl)-Functionalized Quinazolinones and their Heteroanalogues: a Powerful Strategy for the Construction of Polyheterocyclic Structures.

Quinazolin-4-one, its heteroanalogues, and derivatives represent an outstandingly important class of compounds in modern organic, medicinal, and pharmaceutical chemistry, as these molecular structures are noted for their wide synthetic and pharmacological potential. In the last years, ever-increasing research attention has been paid to quinazolinone derivatives bearing alkenyl and alkynyl substituents on the pyrimidinone nucleus. The original structural combination of synthetically powerful endocyclic amidine (or amidine-related) and exocyclic unsaturated moieties provides a driving force for cyclizations, which offer an efficient toolkit to construct a variety of fused pyrimidine systems with saturated N- and N,S-heterocycles. In this connection, the present review article is mainly aimed at systematic coverage of the progress in using alkenyl(alkynyl)quinazolinones and their heteroanalogues as convenient bifunctional substrates for regioselective annulation of small- and medium-sized heterocyclic nuclei. Much attention is paid to elucidating the structural and electronic effects of reagents on the regio- and stereoselectivity of the cyclizations as well as to clarifying the relevant reaction mechanisms.

Phosphine-Catalyzed (3 + 2) Annulation of γ-Substituted Cinnamic Aldehyde-Derived Morita-Baylis-Hillman Carbonates through Remote Activation.

A series of γ-substituted Morita-Baylis-Hillman (MBH) carbonates were synthesized and subjected to phosphine-catalyzed annulations with electrophilic exocyclic alkenes, giving various valuable spirocyclopentenes in moderate to excellent yields with moderate to excellent diastereoselectivities. A large scope of MBH carbonates bearing γ-hydrogen, alkenyl, and alkynyl substituents was well tolerated. The annulation unprecedentedly involves β-, γ-, and δ-carbons of MBH carbonates.

Transition-Metal-Free Cross-Coupling of Acetals and Grignard Reagents To Form Diarylmethyl Alkyl Ethers and Triarylmethanes

AbstractWe herein report a transition-metal-free cross-coupling reaction of acetals and Grignard reagents. The method provides a modular preparation of diarylmethyl alkyl ethers, triarylmethanes, and 1,1-diarylalkanes that constitute the core structures of many bioactive molecules and synthetic motifs. A series of readily accessible acetals bearing aryl, alkenyl, and alkyl substituents efficiently coupled with commercially available aryl, alkyl, and allylic magnesium bromides to give the products in high yields. In addition to acyclic and cyclic acetals, ketal and orthoester also serve as viable substrates to afford sterically hindered tertiary ether and ketal respectively. A sequential difunctionalization of acetals led to the rapid synthesis of triarylmethanes and diarylalkanes.

Unexplored Vinylic-Substituted 5-Benzylidenethiazolidine-2,4-diones: Synthesis and DFT/NMR Stereochemical Assignment.

By exploring an efficient and versatile method for the 6-functionalization of its scaffold, we investigated the opening of a new chemical space around benzylidenethiazolidine-2,4-dione (BTZD). The 6-chloro- and 6-formyl BTZD obtained in two steps starting from 5-lithioTZD were selected as key intermediates and involved in a Pd-catalyzed cross-coupling or Wittig olefination. A variety of aryl, heteroaryl, or alkenyl substituents was successfully introduced on the vinylic position of BTZD, and particular attention was paid to elucidate the stereochemistry of the benzylidene derivatives by using a combined DFT/NMR study.

Design and Synthesis of Novel Phenylahistin Derivatives Based on Co-Crystal Structures as Potent Microtubule Inhibitors for Anti-Cancer Therapy.

Phenylahistin is a naturally occurring marine product with a diketopiperazine structure that can bind to the colchicine site of microtubulin as a possible anticancer agent. To develop more potent microtubule inhibitors, novel phenylahistin derivatives were designed and synthesized based on the co-crystal complexes of phenylahistin derivatives and microtubulin. We established a focused library of imidazole-type molecules for the introduction of different groups to the C-ring and A-ring of phenylahistin. Structure-activity relationship studies indicated that appropriate hydrocarbon substituents and unsaturated alkenyl substituents at the 1-position of the imidazole group are important for improving the activity of such compounds. In addition, this study found that propylamine groups could maintain the activity of these compounds, as exemplified by compound 16d (IC50 = 5.38 nM, NCI-H460). Compound 15p (IC50 = 1.03 nM, NCI-H460) with an allyl group exhibited potent cytotoxic activity at the nanomolar level against human lung cancer cell lines. Immunofluorescence assay indicated that compound 15p could efficiently inhibited microtubule polymerization and induced a high expression of caspase-3. 15p also displayed good pharmacokinetic characteristics in vitro. Additionally, the growth of H22 transplanted tumors was significantly inhibited in BALB/c mice when 15p alone was administered at 4 mg/kg, and the tumor inhibition rate was as much as 65%. Importantly, the continuous administration of 15p resulted in a lower toxicity than that of docetaxel (10 mg/kg) and cyclophosphamide (20 mg/kg). Overall, the novel allyl-imidazole-diketopiperazine-type derivatives could be considered safe and effective potential agents for cancer treatment.

SYNTHESIS OF SALTS OF N-ALLYLTRICHLOROACETAMIDINIUM HEXAHALOGENOTELLURATE

Amidines with a trichloromethyl group exhibit the properties of inotropic agents, which are used as scaffolds in synthesizing aza-hete­rocycles and ligands for complex formation. Functionalized amidines show anticancer, and antidiabetic activity, and are antihypertensive and antiparasitic agents. The synthesis of new functional derivatives of such amidines is definitely an urgent task. The introduction of an alkenyl substituent and several nucleophilic centers in the amidine creates prerequisites for electrophilic cyclization. This work aims to study the reactions of N-allyl-N-methyl-N'-(trimethylsilyl)-2,2,2-trichloroethanimidamide with tellurium halides.
 The starting N-allyl-N-methyl-N'-(trimethylsilyl)-2,2,2-trichloroethanimidamide was synthesized from N-allyl-N-methyl-­2,2,2-­trichloroethanimidamide by the action of trimethylsilyl chloride in the presence of triethylamine base. The reaction of N-­allyl-­N-methyl-N'-(trimethylsilyl)-2,2,2-trichloroethanimidamide with tellurium dioxide in hydrohalic acid was carried out while cooling to 0°C. Elemental analysis confirms that the electrophilic reagent is in its acidic form in the complex. The 1H NMR spectra of the obtained complexes indicate the absence of EVC - the spin pattern of the proton signals of the allylic substituent, characteristic of the starting compounds, is preserved, but the signals are shifted by 0.3–0.6 ppm. The absence of proton signals of the trimethyl salt substituent indicates the removal of imide protection under these conditions. The presence of a broade­ned singlet in a weak field indicates the pre­sence of acidic protons. Apparently, protonation does not take place on the alkenyl multiple bonds, but, presumably, on the imide nitrogen atom. Based on elemental analysis, the composition of the formed complex was determined: N-allyl-N-methyl-2,2,2-trichloroethanimidamidine: hexahalogenotelluric acid as 1:0.5, which contains 4 or 3 water molecules. So the interaction of N-allyl-N-methyl-N'-(trimethylsilyl)-2,2,2-trichloroethanimidamide with tellurium tetrahalides in a strongly acidic environment, tellurium- or proton-induced cyclization does not occur, but hexahalogeno­tellurate N-allyl-N-methyl-2,2,2-trichloro­etha­neimidamidinium regardless of the polarity of the solvent.

Electrochromic materials containing pyridinium salt and benzoate moieties with dual-colored and long-life performance

This study aimed to develop dual-colored electrochromic materials by combining two electrochromic active moieties (pyridinium quaternary salt and benzoate) in one molecule. Four star-shaped 4,4'-([4,4′-bipyridine]-2,6-diyl) dibenzoates with various alkyl, alkenyl, and aryl N-substituents were designed and their electrochemical/electrochromic performance studied. Electrochromic devices based on 4,4'-([4,4′-bipyridine]-2,6-diyl) dibenzoates exhibited dual-colored electrochromic behavior, good switching stability, and low power consumption. Compared to the compounds with alkenyl and aryl substituents, those with alkyl substituents showed longer lifetimes and better switching stabilities. Good electrochromic properties and low power consumption make this type of material a candidate for application in the fields of electronic paper, smart windows, and displays.

The effects of introducing terminal alkenyl substituents into the 2,2'-bipyridine domain in [Cu(N^N)(P^P)]+ coordination compounds.

The N^N chelating ligands 6,6'-bis(but-3-en-1-yl)-2,2'-bipyridine (1), 6-(but-3-en-1-yl)-6'-methyl-2,2'-bipyridine (2), 6,6'-bis(pent-4-en-1-yl)-2,2'-bipyridine (3) and 6-(pent-4-en-1-yl)-6'-methyl-2,2'-bipyridine (4) have been prepared, characterized, and incorporated into the heteroleptic [Cu(N^N)(P^P)][PF6] complexes in which P^P is either POP (bis(2-(diphenylphosphanyl)phenyl)ether) or xantphos (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane). The eight coordination compounds have been fully characterized, including the single crystal structures of [Cu(1)(xantphos)][PF6], [Cu(1)(POP)][PF6]·CH2Cl2, [Cu(2)(xantphos)][PF6], [Cu(2)(POP)][PF6] and [Cu(3)(POP)][PF6]·0.5Et2O. The [Cu(N^N)(P^P)]+ cations exhibit a partially reversible or irreversible Cu+/Cu2+ oxidation at more positive potentials than the benchmark [Cu(bpy)(P^P)]+ and [Cu(Me2bpy)(P^P)]+ complexes consistent with the increase in steric hindrance of the terminal alkenyl substituents. When excited in the region of the metal-to-ligand charge transfer (MLCT) absorption, solutions of the [Cu(N^N)(P^P)][PF6] complexes are weak emitters with λmaxem in the range 565-578 nm. However, powdered samples achieve photoluminescence quantum yields in the range of 28.5 to 62.3%, with the highest PLQY found for [Cu(3)(POP)][PF6] with an excited-state lifetime, τ, of 16.1 μs. For [Cu(3)(POP)][PF6], the excited state lifetime was measured in MeTHF at 293 and 77 K, and the increase in τ from 1.77 to 59.4 μs upon cooling supports thermally activated delayed fluorescence (TADF) at ambient temperatures.

Innovative Strategies for the Construction of Diverse 1'-Modified C-Nucleoside Derivatives.

Modified C-nucleosides have proven to be enormously successful as chemical probes to understand fundamental biological processes and as small-molecule drugs for cancer and infectious diseases. Historically, the modification of the glycosyl unit has focused on the 2'-, 3'-, and 4'-positions as well as the ribofuranosyl ring oxygen. By contrast, the 1'-position has rarely been studied due to the labile nature of the anomeric position. However, the improved chemical stability of C-nucleosides allows the modification of the 1'-position with substituents not found in conventional N-nucleosides. Herein, we disclose new chemistry for the installation of diverse substituents at the 1'-position of C-nucleosides, including alkyl, alkenyl, difluoromethyl, and fluoromethyl substituents, using the 4-amino-7-(1'-hydroxy-d-ribofuranosyl)pyrrolo[2,1-f][1,2,4]triazine scaffold as a representative purine nucleoside mimetic.

Construction of N-Heterocycles Fused with a Highly Substituted Benzene Ring by a Benzyne-Mediated Cyclization/Functionalization Cascade Reaction and Its Application to the Total Synthesis of Marine Natural Products.

This account summarizes the development of a benzyne-mediated cyclization/functionalization protocol for the versatile construction of highly substituted benzene derivatives fused with an N-heterocyclic ring such as indolines, indoles, and related nitrogen-containing heterocycles. The protocol comprises sequential reactions initiated by generating a benzyne species and subsequent cyclization via addition of magnesium amide to the benzyne, followed by trapping of the resultant magnesium compound in situ with various electrophiles. The substituent scope was expanded by conducting a transmetalation on a copper species to introduce alkyl, aryl, and alkenyl substituents. The utility of the sequential reaction was demonstrated in the synthesis of a carbazole natural product (heptaphylline), pyrrolo[4,3,2-de]quinoline alkaloids (batzellines), and pyrrolo[2,3-c]carbazole alkaloids (dictyodendrines).

α,α'-C-H Bond Difunctionalization of Unprotected Alicyclic Amines.

A simple one-pot procedure enables the sequential, regioselective, and diastereoselective introduction of the same or two different substituents to the α- and α'-positions of unprotected azacycles. Aryl, alkyl, and alkenyl substituents are introduced via their corresponding organolithium compounds. The scope of this transformation includes pyrrolidines, piperidines, azepanes, and piperazines.

Palladium-Catalyzed Aminocyclization-Coupling Cascades: Preparation of Dehydrotryptophan Derivatives and Computational Study.

Dehydrotryptophan derivatives have been prepared by palladium-catalyzed aminocyclization-Heck-type coupling cascades starting from o-alkynylaniline derivatives and methyl α-aminoacrylate. Aryl, alkyl (primary, secondary, and tertiary), and alkenyl substituents have been introduced at the indole C-2 position. Further variations at the indole benzene ring, as well as the C-2-unsubstituted case, have all been demonstrated. In the case of C-2 aryl substitution, the preparation of the o-alkynylaniline substrate by Sonogashira coupling and the subsequent cyclization–coupling cascade have been performed in a one-pot protocol with a single catalyst. DFT calculations have revealed significant differences in the reaction profiles of these reactions relative to those involving methyl acrylate or methacrylate, and between the reactions of the free anilines and their corresponding carbamates. Those calculations suggest that the nature of the alkene and of the acid HX released in the HX/alkene exchange step that precedes C–C bond formation could be responsible for the experimentally observed differences in reaction efficiencies.

Synthesis of 3-Iodomethyl Sultams

A method for the synthesis of iodomethyl-substituted five-membered sultams has been developed. The sultams were synthesized by intramolecular iodoamination of alkenyl sulfamides. The method allows synthesis of N- and C-substituted sultams. NH-Sultams were prepared by acidic cleavage of the corresponding tert-butyl sultams that are readily available. Varying the length of alkenyl substituent at sulfamide it was shown that only five- and six-membered sultams could be prepared by this method. Neither four- nor seven-membered sultams were detected. The simple practical procedure and available starting materials make the variously substituted sultams readily available.

Syntheses of Tetrasubstituted [10]Cycloparaphenylenes by a Pd-catalyzed Coupling Reaction. Remarkable Effect of Strain on the Oxidative Addition and Reductive Elimination.

A small library of tetrasubstituted [10]cycloparaphenylene ([10]CPP) derivatives bearing alkyl, alkenyl, alkynyl and aryl substituents was constructed by a Pd-catalyzed cross-coupling reaction starting from tetratriflate [10]CPP 5 e, which was readily available in high yields on a >2 g scale. The CPP skeleton increases the reactivity of aryl triflate for oxidative addition to the Pd species, and 5 e is 10 times more reactive than its linear paraphenylene analogue, as determined by competition experiments. Theoretical calculations suggest that the accumulation of the small strain relief from each paraphenylene unit not involved in the reaction is responsible for the observed enhanced reactivity.

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol.

A general procedure for the synthesis of 2-substituted tetrahydro-1,3-thiazepines by MW-assisted cyclization of 4-thioamidobutanols is presented. The acyclic precursors were prepared in high overall yields by an expeditious three-step diacylation/thionation/deprotection sequence from 4-aminobutanol. Microwave-assisted ring closure of 4-thioamido alcohols promoted by trimethylsilyl polyphosphate (PPSE) in solvent-free conditions allowed for the synthesis of several hitherto unreported seven-membered iminothioethers bearing 2-aryl, alkenyl, aralkyl and alkyl substituents. The cyclodehydration reaction is likely to involve an SN2-type displacement and affords good to excellent yields of the desired heterocycles in very short reaction times.

Catalytic Systems for Production of 1-Hexene by Selective Ethylene Trimerization

New chromium complexes with diphosphine ligands have been obtained by the reaction of chromium(III) hexahydrate and diphosphines in acetone. The structure of chromium(III) complex 4 containing water molecule and 1,2-bis(diphenylphosphino)benzene as ligands and that of two chromium(III) complexes (12 and 13) with 1,2-bis(diphenylphosphino)benzene ligands containing alkenyl substituents in the ortho-position of one of the phenyl groups at the phosphorous atom have been determined using X-ray diffraction analysis. The catalytic properties of the obtained complexes in the composition of catalytic systems for ethylene trimerization have been studied. It has been shown that the obtained series of catalytic systems manifests high activity in the process of ethylene trimerization to 1-hexene, with the process selectivity exceeding 94%. The highest value of productivity amongst known selective catalytic systems for trimerization was achieved using a chromium complex 13 bearing the 2-methylprop-1-enyl group at the ortho-position of one of the phenyl groups. The influence of temperature, pressure, the nature of the solvent and the composition of the catalytic system on the parameters of the process of ethylene trimerization to form 1-hexene has been determined.