Synthesis of α-chloropolyfluoroalkyl ethers and acetals based on them

α-Chloropolyfluoroalkyl ethers were synthesized by the reaction of polyfluorinated alcohols H(CF₂CF₂) _n CH₂OH (n=1?3) with aliphatic aldehydes (ethanal, propanal, butanal) and hydrogen chloride. Yield of α-chloroethers decreases from 71 to 61% as the number of carbon atoms in the starting reactants increases. α-Chloropolyfluoroalkyl ethers react with polyfluorinated alcohols (n = 1?3) to form acetals in yield of up to 40–61%, and with methanol and ethanol, up to 98%.     

Hyperfine coupling constants of β-phosphorylated nitroxides: Subtle interplay between steric strain,hyperconjugation, and dipole-dipole interactions

Solvent effects in β-phosphorylated nitroxides show that nitrogen and phosphorus hyperfine coupling constants a_N and a_P, increase and decrease with increasing polarity, polarizity, and Hydrogen Bond Donor effects of solvents, respectively. In a series of articles, it was shown that the driving interaction controlling the change in a_P is the maximization of the N^+?—O^– … ???⁺PO^– dipole – dipole interaction. In this work, we show that the steric strain in spiro β-phosphorylated nitroxides affords the opposite trend for a_P, that is, a_P increases with increasing solvent properties features.     

Studies on the syntheses and properties of Schiff base type crown ethers

Eight bis-,two tris-and two mono-crown ethers of Schiff base type have been pre-parcd by the reaction of 4'-formylbenzo-15-crown-5 with diamincs.Conductivity measurementsshow that the bis-crown ethers form 1:1 complexes(crown cther unit:metal ion)with sodiumion and 2:1 complexes with potassium,rubidium and ammonium ion,respectively.     

Competition between n,π- and n,σ-orbital interactions in chlorinated ethers R-O-chcir 1

Using the AM-1 method, we have studied CH₂=CH-O-CHClR¹ molecules (R¹=H, Me). We have shown that the sc conformation with respect to the bond is preferred. We have systematized the¹³Cl NQR data on the degree of manifestation of the generalized anomeric effect in R-OCHClR¹ [R=Me, Ph, Vyn, R²C(=O)] molecules. We have established that enhancement of n, conjugation in the R-O fragment leads to weakening of the n, interaction in the O-C-Cl triad.Deceased.     

Effect of steric factors on the keto-cis-trans-enol equilibrium of α-acetylcycloalkaneacetic esters

Summary With the aid of atomic models the structures of -acetylcyclohexane-, -acetylcyclopentane-, and -acetyl-cyclobutane-acetic esters were examined, and an explanation is proposed for the observed proportions of the tautomeric forms.     

Electronic and steric effects on the photo-induced C→E ring-opening of structurally modified furylfulgides

The ultrafast C→E ring-opening reactions of four selectively modified furylfulgides have been studied by means of ultrafast broadband transient absorption spectroscopy after femtosecond laser excitation at λ = 500 nm. A large difference in the dynamics was found in the case of benzannulation at the furyl moiety as an example for an electronic effect by extension of the conjugated π-electron system compared to furylfulgides carrying sterically different alkyl substituents at the central cyclohexadiene (CHD) ring. The measured very similar spectro-temporal absorption maps for the furylfulgides with a methyl or isopropyl group at the CHD ring or an intramolecular alkyl bridge from the CHD to the furyl moiety showed two distinctive excited-state absorptions with slightly different decay times. The first time constant (τ(1) = 0.39-0.57 ps) was assigned to the rapid departure of the excited wavepacket from the Franck-Condon region. The slightly longer second decay time of τ(2) = 0.66-0.92 ps, depending on the compound, was attributed to the electronic deactivation and ring-opening through a conical intersection to the S(0) state. In contrast, the benzannulation at the furyl moiety was found to lead to a bi-phasic excited-state decay with τ(2) = 4.7 ps and a much slower additional contribution of τ(3) = 17.4 ps, ≈25 times longer compared to the normal furylfulgides. The drastic change is attributed to a trapping of excited molecules in a local potential energy minimum en route to the conical intersection.     

Influence of steric parameters on the synthesis of tetramates from α-amino-β-alkoxy-esters and Ph3PCCO

α-Aminoesters react with Ph₃PCCO in a domino addition–Wittig cyclization sequence affording enantiomerically pure tetramates. In the case of β-oxo functionalized α-aminoesters, e.g., esters of serine, threonine or β-hydroxyornithine the yields of this reaction depend heavily on the bulkiness of the β-OR group and on the configuration of β-carbon atom C-3. Smaller residues and 2R/3R-configured aminoesters give better yields. The alkoxycarbonyl group of the ester moiety and the residue on the N-atom are less important. These findings can be accounted for by assuming an early puckered transition state for the intramolecular ring-closing Wittig reaction. The addition of sub-stoichiometric amounts of benzoic acid or N-hydroxysuccinimide (for acid-sensitive compounds) is advantageous in some cases as it accelerates the formation of the intermediate amide ylides.     

Synthesis and structures of α-lithiated vinyl ethers

The structures of α-lithiated vinyl ethers were explored on the basis of a combined computational and NMR study. Calculations (M06/6-31 + G(d)) on free energies of aggregate formation for a series of α-lithiated vinyl ethers indicated that the tetramer is generated preferentially in both the gas phase and THF solution, except for cyclohexylidene derivatives. (1-(Methoxymethoxy)vinyl)lithium, (2,2-difluoro-1-(methoxymethoxy)vinyl)lithium, and (1-butoxyvinyl)lithium were prepared in NMR tubes by the deprotonation of alkyl/alkoxylalkyl vinyl ethers or by the transmetalation of tin compounds. The NMR spectra of these lithium species in THF solution showed that in each species one aggregate is primarily present at 173 K, which is consistent with the preference of the tetramer.     

Oxetane ethers are formed reversibly in the lithium-catalyzed Friedel–Crafts alkylation of phenols with oxetanols: Synthesis of dihydrobenzofurans,diaryloxetanes, and oxetane ethers

Studies on the mechanism and intermediate products in the Friedel–Crafts reaction between oxetanols and phenols are presented. The formation of O-alkylated intermediates is identified using ¹H NMR spectroscopy, in a reversible formation of the kinetic oxetane ether products. An interesting relationship between the electronic nature of the nucleophile and the degree of O-alkylation is uncovered. For phenols substituted with an electron withdrawing group such as CN, oxetane ethers are the only products isolated regardless of reaction time. Increasing the electron rich nature of the phenol leads to an increased proportion of the thermodynamic C-alkylated Friedel–Crafts products after just 1?h and as the sole product/s after extended reaction times. These studies have enabled a more complete catalytic cycle to be proposed. Using the same lithium catalyst and carefully selected reaction times, several examples of oxetane ethers are successfully isolated as novel bioisosteres for ester groups.     

Conformational, steric and electronic effects on the site- and chemoselectivity of the metal-catalyzed reaction of N-bis(trimethylsilyl)methyl, N-(2-indolyl)methyl α-diazoamides

The Rh(II)- and Cu(II)-catalyzed reactions of N-bis(trimethylsilyl)methyl, N-(2-indolyl)methyl α-diazoamides are investigated to delineate how conformational, steric and electronic factors influence the site- and chemoselectivity of the metallocarbenoid reaction. The N-bis(trimethylsilyl)methyl (N-BTMSM) group is found to be essential in promoting the metallocarbenoid reaction at the N-(2-indolyl)methyl moiety as well as providing subtle but effective conformational influence about the amide N-C(α) sigma bond in diazoamides carrying an N-C(α) alkoxymethyl side-chain, to afford excellent site- and chemoselectivity. In general, the metal-catalyzed reactions are found to favor metallocarbenoid addition to the indole C(2)-C(3) double bond over C-H insertion to give cyclopropanated products (tetracyclic γ-lactams); however, chemoselectivity is also affected by steric effects, as revealed in the N-[2-(3-methylindolyl)]methyl diazoamides, and to some extent by the nature of the catalyst employed, as seen in the N-C(α)-alkoxymethyl diazoamides. The tetracyclic γ-lactams are found to rearrange to give good to high yields of the tricyclic indole derivatives under the metallocarbenoid reaction conditions or under acidic conditions. The propensity of the tetracyclic γ-lactams to undergo rearrangement is found to be dependent on the nature of the α-substituent on the original diazo carbon and the indole N-substituent.     

Molecular complexes of crown ethers. part 2: Complexes between crown ethers and π acceptors

The intermolecular charge transfer (CT) complexes of four crown ethers (CE), viz. B15C5, B18C6, DB18C6 and DB24C8 (as donors), and three acceptors, i.e. tetracyanoethylene (TCNE) 7,7,8,8-tetracyanoquinodimethane (TCNQ) and chloranil were studied in the UV-Visible region in 1,2-dichloroethane (DCE) at 298.2 K. Solid complexes were also prepared and the ratio of the donor to the acceptor was 1:1. Results indicate that the _max of the CT band decreases whileK _c (formation equilibrium constant) increases following the systematic change of the electron affinity of the acceptors. TheK _c values suggest that the phenyl group in CE plays a major role in the formation of a CT complex.     

Effect of noncovalent complexations on coordination interactions in a tricomponent system ofβ-cyclodextrin,copper chloride and hexamethylene tetramine

This study reveals that the noncovalent complexation betweenβ-CD and Cu（HMTA）²⁺ makes a positive contribution to the coordination interaction between Cu²⁺ and HMTA in a tricomponent system.Besides,mono- and binuclear complexes:[β-CDCu]⁺ and[Cu·β-CDCu]⁺ were observed under the condition of ESI-MS.     

Effects of ionic strength, temperature and conformation on affinity interactions of β₂-glycoprotein I monitored by capillary electrophoresis

We have used CE to evaluate the interaction between β?-glycoprotein I (β?gpI) and heparin. β?gpI is a human plasma protein involved in the blood coagulation cascade. It is of interest to functionally characterize the interactions of β?gpI because the exact function is not entirely known and because circulating autoantibodies against β?gpI are associated with an increased risk of thrombotic events. The effect of the ionic strength, temperature, and conformation of the protein on the interaction between β?gpI and heparin has been studied. The CE procedure for this study is simple, fast, and automatic. β?gpI and heparin were allowed to interact during electrophoresis at different ionic strength buffers and at different capillary temperatures. To mimic perturbation of the conformation of β?gpI, different denaturing agents (SDS, ACN, and urea) were added to the BGE. While simple 1:1 binding isotherms were obtained at 22 °C, the data strongly suggest that at physiological temperature the binding stoichiometry is not 1:1 and/or that cooperative interactions begin to play a role. We found that (i) the K(D)-values differed by a factor of 60 at the ionic strengths studied (ii) β?gpI was resistant to denaturation with SDS and ACN, but was partially denatured by urea, and (iii) the K(D) for the β?gpI-heparin interaction in the presence of urea was ten times higher than the K(D) determined at the same conditions without urea added. Therefore, we conclude that the interaction between β?gpI and heparin is dependent on electrostatic interactions and on the conformation of β?gpI.     

Electrochemical synthesis of copper nanoparticles on nafion–graphene nanoribbons and its application for the synthesis of diaryl ethers

Electrochemical synthesis of copper nanoparticles on nafion–graphene nanoribbons support for the synthesis of diaryl ethers via Ullmann type coupling is reported. The catalyst showed excellent performance for C–O cross coupling reactions under ligand free condition. The catalyst was characterized by various techniques such as SEM, TEM, XRD, EDX, BET, TGA, and UV spectrophotometry. It was recycled several times without significant loss in its catalytic activity.     

Syntheses of chiral β- and γ-amino ethers, morpholines, and their homologues via nucleophilic ring-opening of chiral activated aziridines and azetidines

Lewis acid catalyzed quaternary ammonium salt mediated highly regioselective ring-opening of chiral activated aziridines and azetidines with alcohols to nonracemic β- and γ-amino ethers has been developed. The reaction mainly proceeds via an S(N)2 pathway, and the partial racemization of the starting substrate was effectively controlled by using quaternary ammonium salts. β- and γ-amino ethers are obtained with high enantio- and diastereospecificity (ee up to >99%, de up to 99%). The methodology was further extended to synthesize morpholines and their homologues with high enantiospecificity (ee up to 90%) when halo alcohols were employed as the nucleophiles.     

A new approach to the synthesis of cyclic ethers via the intermolecular allylation of α-acetoxy ethers and ring-closing metathesis

A concise synthesis of the isolaurepinnacin skeleton 6 was achieved via the intermolecular allylation of the α-acetoxy ether 3 followed by ring-closing metathesis. This methodology was successfully applied to the convergent synthesis of the oxocene 15, an advanced synthetic intermediate for the total synthesis of laurencin.     

Selectivity in DNA replication. Interplay of steric shape, hydrogen bonds, π-stacking and solvent effects

Our dispersion-corrected DFT computations reveal key factors behind the intrinsic affinity of a DNA template-primer complex to select the correct nucleotide.     

Suzuki–Miyaura reactions of the bis(triflates) of 1,3- and 1,4-dihydroxythioxanthone. Electronic and steric effects on the site-selectivity

The palladium(0)-catalyzed Suzuki cross-coupling reactions of the bis(triflates) of 1,3- and 1,4-dihydroxythioxanthone afforded various aryl-substituted thioxanthones. While the Suzuki reactions of the bis(triflate) derived from 1,3-dihydroxythioxanthone proceeded by site-selective attack in favor of position 3, the reactions of the bis(triflate) of 1,4-dihydroxythioxanthone proceeded in favor of position 1. The site-selectivity is controlled by steric and electronic parameters.     

A theoretical study on the importance of steric effects,electronic properties,interaction and solvation energies in the ‘host–guest’ chemistry of protonated azacryptands and halide anions

It is well known that the selectivity of a receptor for an anion depends on the compatibility of the cavity size of the receptor and the size of the anion. In this work the macrobicyclic [H₆L(X)]⁵⁺ (X⁻=F, Cl, Br); are studied theoretically and compared with [H₆L′(F)]⁵⁺ having a smaller cavity size. It was shown that the ideal match between the sizes of the protonated azacryptand and the fluoride ion exists in the [H₆L′(F)]⁵⁺ complex but the [H₆L]⁶⁺ is a better receptor than [H₆L′]⁶⁺ in solution. Thus the results clearly indicate that in some special cases a better receptor is not one whose cavity size has better compatibility with the anion size.