Showing papers on "Nucleophile published in 1987"

Chirale Alkoxytitan(IV)‐Komplexe für enantioselektive nucleophile Additionen an Aldehyde und als Lewis‐Säuren in Diels‐Alder‐Reaktionen

Abstract: Chiral Alkoxytitanium(iv) Complexes for Enantioselective Nucleophilic Additions to Aldehydes and as Lewis Acids in Diels-Alder Reactions A Number of chiral 1,2-1,3 and 1,4-diols were prepared and used as alkoxy ligands on Ti for enantioselective nucleophilic transfer of methyl, butyl, cyclopropyl, allyl, alkinyl, and phenyl groups to aromatic aldehydes, as well as for the enantioselective[4+2]cycloaddition of acrylate to cyclopentadiene. The 1,2-diols were pinane diol 7 and 1,2:5.6-diacetonide-protected mannitol 9 (Scheme 3) and tartrates. The 1,3-diols were obtained from the yeast-reduction products of 2-oxocyclopentane- and 2-oxocyclohexanecarboxylates and excess MeLi, BuLi, or PhLi (or the corresponding Grignard reagents; see4–6.) As 1,4-diols, we used the products 2 and 3 from tartrate acetals and methyl or Pheny1 Grignard reagents, the bis(benzaldehyde) acetal 8 of d-mannitol and o,o'-binaphthol (22). These diols were attached to the Ti-atom by azeotropic removal of i-PrOH from a mixture with [TiCi(i-PrO)3]. Addition of various organometallic reagents R-metal (metal = Li, BR3, MgX, MnC1, CuLiR) was followed by combination with aldehydes at – 75., a warm up period, quenching with aqueous KF solution, and workup (for results see Tables 1–6 and Formulae17–20). The enantiomeric excess of the secondary alcohols obtained varies greatly, certain combinations of chiral ligands, nucleophilic groups, and aldehyde substrates give rise to values as high as 90% ee; see e.g. Table 4. The Ti-complexes of the general formula [Ti(R*O)2Ci2] or [Ti(R*O)2(i-PrO)CI] induced the Diels-Alder addition of methyl acrylate to cyclopentadience to take place at –30.. The best enantioselectivity (50% ee) was observed with the binaphthol derivative (Table 7). The structures of the complexes involved in these reactions are unknown. The substitution on C(2) of the dioxolanes 2 and 3 (derived from tartaric acid) has a pronounced effect on the selectivities of both reactions studied here (Tables 2, 3, and 7). This remote effect (1,6-distance between the stereogenic acetal-C-atom and the Ti-centers) must be caused by conformational changes in the vicinity of the reactive site, i.e. the TiC bond in the nucleophilic addition reactions and the Ti-acrylate-oxygen complexation in the Diels-Alder reaction.

Carbon-carbon bond-forming reactions of zinc homoenolate of esters. A novel three-carbon nucleophile with general synthetic utility

Abstract: Reactions d'addition sur les composes carbonyles, allylation, arylation, vinylation et acylation en presence ou non de catalyseurs

Unsaturated Molecules Containing Main Group Metals

Abstract: Molecules in which there are neighboring electrophilic and nucleophilic centers are unusually reactive. Oligomerization can be prevented only by bulky groups attached to the main group metal atom that would act as electron pair acceptor, or to the basic non-metal atom. The basic and the acid centers behave as a single unit in chemical reactions; the system is similar to a “double bond” whose π-electron density is largely concentrated at one atom. The unsaturated nature of these molecules can be seen in (for example) their addition reactions with hydrogen compounds of non-metals, or in reactions that are distantly related to cycloadditions at homopolar double bonds. The selection of suitable reaction partners leads to polycyclic, cage-like molecules containing metal atoms. If these atoms possess lone pairs (as is usual in the lower oxidation states of the third and fourth main groups), these can be utilized to form bonds to further (Lewis acid) metal centers. In some cases large assemblies can be built up from polycyclic systems in this way; a characteristic of these assemblies is a one-dimensional array of metal atoms. Commonly occurring structural features of the polycyclic species are tetrahedra, trigonal bipyramids and cubes.

Modeling chemical reactivity. 7. The effect of a change in rate-limiting step on the stereoselectivity of electrophilic addition to allylic alcohols and related chiral alkenes

Abstract: The stereoselectivities of electrophilic additions to acyclic allylic alcohols with and without internal nucleophiles have been assessed with use of previously developed chemical reactivity modeling techniques. Reactions normally assumed to proceed via onium-type intermediates have been investigated. The diastereofacial selectivity of attack by I/sub 2/, Br/sub 2/, PhSeCl, Hg(OAc)/sub 2/, and related electrophiles, known to be opposite for substrates containing an internal nucleophile compared with those without, is explained in terms of a change in the rate-limiting step for the reaction. Specifically, where intramolecular nucleophilic attack is possible, cyclizations proceed via a transition state that resembles a (reactant-like) ..pi.. complex, whereas reactions that involve intermolecular addition of the nucleophile are governed by one that resembles an onium ion, e.g., iodonium. Calculations show that these two extremes should exhibit opposite diastereofacial selectivity of attack on the acyclic allylic ..pi.. bond by the electrophile, in agreement with available experimental results.

Transition metal complexes with terminal carbyne ligands

Abstract: Publisher Summary This chapter discusses the chemistry of molecular carbyne complexes; there is also much interest in them as models for species that are possibly present on metal surfaces in catalytic reactions. Surfacebound methine (CH) is a proposed intermediate in the Fischer–Tropsch synthesis, and alkylidyne groups are suggested as intermediates in heterogeneously catalyzed alkyne metathesis reactions. X-Ray structure determinations of carbyne complexes show that they have very short metal–carbon bond lengths consistent with a metal–carbon triple bond. In certain cases, ∞-protons of an alkylidene ligand may be abstracted by a base to give alkylidyne compounds. Addition of electrophiles to terminal isonitrile (CNR) ligands gives aminocarbyne complexes; the analogous reaction of terminal thiocarbonyl (CS) ligands gives thiocarbynes. Fischer and Himmelreich reported the abstraction of oxygen from an anionic carbamoyl compound with SOCl 2 to give an aminocarbyne compound. Reactions of cationic carbyne compounds with nucleophiles proceed exclusively by nucleophilic attack at the carbyne carbon atom, thus providing a synthetically useful route to certain carbene complexes. The field of transition-metal carbyne chemistry has matured to the point where a great deal is known about the structure, bonding, and reactivity of the carbyne ligand.

Photochemistry of 3- and 4-nitrophenyl azides: detection and characterization of reactive intermediates

Abstract: Irradiation of nitro-substituted aromatic azides initiates a complex series of chemical reactions that lead to different products depending on the details of the experiment. There is evidence that four reactive intermediates participate in product-determining reactions. These are the singlet nitrene, the triplet nitrene, the triplet azide, and the ring-expanded dehydroazepine. The chemical and physical properties of each of these species is modified by the nitro substituent. The reactivity of the singlet nitrene with nucleophilic amines is increased, the lifetime of the dehydroazepine is shortened, and the triplet nitrene becomes a powerful single-electron acceptor. Nitro-substituted aromatic azides are widely used in photolabeling experiments. The findings of this study suggest that they may be inappropriate choices as photolabeling agents in many circumstances.

Catalytic mechanism and inhibition of tRNA (uracil-5-)methyltransferase: evidence for covalent catalysis.

Abstract: tRNA (Ura-5-)methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine (AdoMet) to the 5-carbon of a specific Urd residue in tRNA. This results in stoichiometric release of tritium from [5-3H]Urd-labeled substrate tRNA isolated from methyltransferase-deficient Escherichia coli. The enzyme also catalyzes an AdoMet-independent exchange reaction between [5-3H]-Urd-labeled substrate tRNA and protons of water at a rate that is about 1% that of the normal methylation reaction, but with identical stoichiometry. S-Adenosylhomocysteine inhibits the rate of the exchange reaction by 2-3-fold, whereas an analogue having the sulfur of AdoMet replaced by nitrogen accelerates the exchange reaction 9-fold. In the presence (but not absence) of AdoMet, 5-fluorouracil-substituted tRNA (FUra-tRNA) leads to the first-order inactivation of the enzyme. This is accompanied by the formation of a stable covalent complex containing the enzyme, FUra-tRNA, and the methyl group of AdoMet. A mechanism for catalysis is proposed that explains both the 5-H exchange reaction and the inhibition by FUra-tRNA: the enzyme forms a covalent Michael adduct with substrate or inhibitor tRNA by attack of a nucleophilic group of the enzyme at carbon 6 of the pyrimidine residue to be modified. As a result, an anion equivalent is generated at carbon 5 that is sufficiently reactive to be methylated by AdoMet. Preliminary experiments and precedents suggest that the nucleophilic catalyst of the enzyme is a thiol group of cysteine. The potent irreversible inhibition by FUra-tRNA suggests that a mechanism for the "RNA" effects of FUra may also involve irreversible inhibition of RNA-modifying enzymes.

Mechanistic studies on the phosphoramidite coupling reaction in oligonucleotide synthesis. I. Evidence for nucleophilic catalysis by tetrazole and rate variations with the phosphorus substituents

Abstract: Tetrazole catalyzed reactions of a series of phosphoramidites, 5'-O-DMTdT-3'-O-P(OR1)NR2(2) (1a-h), with 3'-O-SiButPh2-6-N-benzoyl-dA (2a) in acetonitrile solution have been studied. It is found that the coupling rate depends very much on whether tetrazole is added before or after 2a, and that dialkylammonium tetrazolide salts are inhibitors. These and other facts are evidence that the reactions are subjected to nucleophilic catalysis by tetrazole, in addition to acid catalysis. The rate variations with phosphorus substituents of 1a-h are NEt2 greater than NPri2 greater than N(CH2CH2)O greater than NMePh, and OMe greater than OCH2CH2CN greater than OCHMeCH2CN greater than OCMe2CH2CN much greater than OC6H4Cl. The inhibitor properties of dialkylammonium tetrazolides have practical consequences for the efficiency of DNA syntheses, when in situ prepared phosphoramidites are used; the same would apply for segmented, simultaneous syntheses or syntheses where recycling is performed.

New method for the classification of nucleophiles in the palladium-catalyzed substitution of allylic acetates

Abstract: Les reactions avec divers nucleophiles ont lieu avec les deux composes suivants: l'acetate du cyclopentene-2ol et l'acetate du methano-4,7 indenol-1 (hexahydro-«3a,4,5,6,7,7a»)

Optisch aktive Alkohole aus 1,3-Dioxan-4-onen: eine praktikable Variante der enantioselektiven Synthese unter nucleophiler Substitution an Acetal-Zentren†

Abstract: Optically Active Alcohols from 1,3-Dioxan-4-ones. A Practical Version of Enantioselective Synthesis with Nucleophilic Substitution at Acetal Centers Secondary alcohols in enantiomeric excesses above 90% are accessible from 2-substituted 6-methyl-1,3-dioxan-4-ones (Scheme 4). The dioxanones are prepared from aldehydes and readily available (R)-or (S)-3-hydroxybutanoic acid. Treatment of the dioxanones with silyl nucleophiles or triisopropoxy(methyl)titanium in the presence of [Cl3TiX] yields the corresponding 3-alkoxy acids in diastereoselectivities ≥ 95%. The ‘chiral auxiliary’ is removed from the alkoxy acids by treatment with LiN(i-Pr)2 to give the secondary alcohols with ≤ 90% ee. cis/trans-Mixtures (9:1) of the dioxanones furnish products of the same configurational purity as those obtained from pure cis-isomers. In comparison with other variants of enantioselective synthese with nucleophilic substitution at acetal centers, the following advantages of the dioxanone method are noteworthy: (i) (R)- and (S)-3-hydroxybutanoic acids are both readily available; (ii) reactions are not sensitive to changes in conditions; (iii) the ‘chiral auxiliary’ is removed simply by base elimination, no oxidation is required; (iv) no chromatographic purification steps are necessary. The overall reaction described here is an enantioselective nucleophilic addition to aldehydes with concomitant dehydration of enantiomerically pure 3-hydroxybutanoic to crotonic acid.

The N.C.A. nucleophilic 18F‐fluorination of 1,N‐disubstituted alkanes as fluoroalkylation agents

Abstract: This systematic study describes the preparation of bifunctional n.c.a. 18F-fluoroalkanes using amino-polyether (APE) supported nucleophilic substitution. With the APE (Kryptofix® 2.2.2.) potassium carbonate complex in acetonitrile n.c.a. 18F− is introduced into disubstituted alkanes ( X(CH2)nX, n = 1–3, X = Br, OMes, OTos) in high yields within 10–15 min. The substitution yield increases in the sequence of leaving groups Br < OMes < OTos and with increasing alkyl chain length. At substrate concentrations of 0.025 M of bistosyloxyethane a radiochemical yield of 82 ± 8% of [1-18F]-fluoroethyltosylate is obtained. This compound appears optimal as fluoroalkylation agent with respect to size, stability and ease of its preparation.

Polar effects in free-radical reactions. Solvent and isotope effects and effects of base catalysis on the regio- and chemoselectivity of the substitution of protonated heteroaromatic bases by nucleophilic carbon-centered radicals

Abstract: Les substitutions des pyridine, quinaldine, lepidine et cyano-3 et -4 pyridines protonees par les radicaux Ph, Me, n-Pr, i-Pr, t-Bu, α-tetrahydrofuryle, dioxannyle et benzyle sont modifiees selon la nature du solvant

Linear solvation energy relationships. Part 37. An analysis of contributions of dipolarity–polarisability, nucleophilic assistance, electrophilic assistance, and cavity terms to solvent effects on t-butyl halide solvolysis rates

Abstract: Solvolysis/dehydrohalogenation rates of t-butyl chloride in 21 hydrogen bond donor (HBD) and non-HBD solvents are well correlated (r= 0.9973, s.d. = 0.24) by the equation: log k=–14.60 + 0.48λH2/100 + 5.10π*+ 4.17α+ 0.73β where δH2 is the solvent cohesive energy density, and π*, α, and β are the solvatochromic parameters that scale solvent diplority–polarizability, HBD acidity (electrophilicity), and hydrogen-bond acceptor basicity (nucleophilicity). In the corresponding equation over the same solvent set for t-butyl bromide, the terms in δH2 and α are smaller still, and the terms in δH2 and β are not statistically significant. It is shown that a trifluoroethanol (TFE)–ethanol plot, wherein ButCl and 1-adamantyl chloride (1-AdCl) solvolysis rates are compared, can be interpreted as evidence for electrophilic assistance of 1-AdCl in TFE rather than the more usual interpretation of nucleophilic assistance to ButCl in EtOH–H2O.

Nucleophilic additions to thionolactones. New synthetic technology for the construction of medium and large ring ethers

Abstract: Reaction d'oxepannethione-2 avec des alkyllithiums puis avec l'iodomethane; obtention d'alkyl-2 methylthio-2 oxepannes (le groupe methylthio est ensuite elimine par Ph 3 SnH-AIBN). Application aux thioolactones suivantes: oxocannethione-2, oxonannethione-2, oxacycloheptadecannethione-2 et perhydro pyranno [3,2-b] oxocinne- et -oxoninnethiones

Synthesis of high performance aromatic polymers via nucleophilic nitro displacement reaction

Abstract: Nucleophilic displacement reaction of activated aromatic nitro groups with various nucleophiles is a useful and versatile method for the synthesis of aromatic compounds such as ethers, thioethers and other functionalized intermediates and polymers. Various strong electron withdrawing groups can activate aromatic nitro groups. Effective activating groups include cyano, nitro, sulfone and carbonyl groups such as ester, ketone, anhydride, imide, etc. The reaction of activated nitro compounds with bisphenols and bisthiophenols yields bisethers and bisthioethers from which various aromatic polymers containing ether and sulfide groups can be derived. In many cases, nitro displacement reactions are essentially quantitative so that high molecular weight polymers are directly prepared by the displacement reaction of difunctional nitro compounds with bisphenols or bisthiophenols. Another type of unique nitro displacement occurs in the presence of catalytic amount of a nucleophile at higher temperatures resulting de-nitro coupling of two molecules of nitro compound to form substituted diarylethers.

The chemistry of N-substituted benzotriazoles. Part 1.1-(Chloromethyl)benzotriazole

Abstract: The N-chloromethyl group of 1-(chloromethyl)benzotriazole undergoes nucleophilic substitution by carbon, nitrogen, phosphorus, oxygen, and sulphur nucleophiles. α-Lithiation was achieved in high yield in 1-phenylthiomethyl-, 1-phenylsulphinylmethyl-, and 1-(phenylstilphonylmethyl)benzotriazoles and the lithio derivatives reacted with a variety of electrophiles. New benzotriazolium salts were prepared by quaternization of the N-3 nitrogen with methyl iodide.

Fast halogen abstractions from alkyl halides by alkyl radicals. Quantitation of the processes occurring in and a caveat for studies employing alkyl halide mechanistic probes

Abstract: : Reactions of nucleophilic tin anionoids with alkyl halides are broadly applied for formation of tin-carbon bonds. The mechanisms of these reactions have been studied by the use of alkyl halide mechanistic probes. This report demonstrates how qualitative mechanistic probes can give misleading information about the extent of electron transfer processes in reactions of nucleophiles with alkyl halides. Second order rate constants for halogen atom transfer (k sub RX) in benzene at 50 C were determined for reactions of octyl radical with tert-butyl, iopropyl and cyclohexyl iodides and bromides and with ethyl iodide, n-butyl bromide, tert-butyl chloride, and carbon tetrachloride using two methods. In Method A, an alkyl iodide and tributylstannane were allowed to compete for octyl radical in radical chain reactions; in Method B, an alkyl halide competed with 1-(oxononoxy)-2(1H)-pyridine (1) for octyl radical. The values of k sub RX were calculated from the product distributions, the reactant ratios and the known rate constants for reaction of tributylstannane or 1 with octyl radical. The possibility that rearranged products can be formed in reactions of alkyl halide mechanistic probes with nucleophiles via a sequence involving radical chain isomerization that converts the probe halide into a rearranged halide followed by nucleophilic attack on the isomerized halide is discussed as are possible chain terminating reactions. The conclusion is reached that the percentage of rearranged substitution products formed in reactions of alkyl halide mechanistic probes with nucleophiles can give misleading information about the number of radical initiating events.

Nucleophilic ring opening of aziridine-2-carboxylates with Wittig reagents; an enantioefficient synthesis of unsaturated amino acids

Abstract: Reaction of N-tosyl- or N-acyl aziridine-(2S)-carboxylate esters with carbonyl stabilized Wittig reagents provides an isolable phosphorus ylide resulting from opening of the aziridine ring; this ylide reacts with carbonyl compounds to provide a novel synthesis of optically pure unsaturated amino acids, exemplified by enantioefficient syntheses of the naturally occuring (2S)-γ-methyleneglutamic acid and (E)-(2S)-4-ethylideneglutamic acid

Electronic and steric factors determining the asymmetric epoxidation of allylic alcohols by titanium-tartrate complexes (the Sharpless epoxidation)

Abstract: The structure and epoxidation properties of titanium-tartrate asymmetric epoxidation catalysts have been studied by using the frontier orbital approach. It is suggested that an important factor determining the dimeric structure of these titanium-tartrate epoxidation catalysts is electronic, as one of the LUMOs, located at the titanium atom, is oriented so it facilitates nucleophilic trans coordination to the titanium of the carbonyl group in the tartrate. Coordination of a peroxide to titanium-tartrate is analyzed. From the frontier orbitals at the equatorial peroxygen, four possible orientations of the allylic alcohol are possible. Analysis of the preferred orientation of a hydroxyl and a methoxy group at the equatorial site at the titanium atom, and of an alkene around the peroxygen, led to a spiro orientation of the alkene part of the allylic alcohol at the peroxygen as the most probable. The preferred orientation of the allylic alcohol at the titanium atom is discussed in relation to electronic as well as steric interactions with the tartrate. The orientation and reactivity of the alkene part of the allylic alcohol can be traced to two two-electron interactions: one is the peroxygen lone pair electron interaction with the T* orbital of the alkene part of the allylic alcohol and the other is the interaction of the titanium-peroxygen antibonding orbital with the K orbital of the alkene. Epoxidation of alkenes, and especially asymmetric epoxidation, is a fundamental and important organic reaction type. The asymmetric epoxidation was pioneered by Herbst, who used chiral monoperoxycamphoric acid to produce chiral epoxides with an enantiomeric excess of 5% or less;' later Pirkle and Rinaldi were able to improve the enantiomeric excess to 9%.* Catalytic epoxidation with hydrogen peroxide and tert-butyl hydrogen peroxide catalyzed by chiral phase-transfer agents such as benzyl guinidinium salts was investigated by Hummelen and Wynberg, with moderate ~ u c c e s s . ~ The first transition metal catalyzed asymmetric epoxidation was reported independently by Sharpless et aL4 and Yamada et al.,5 the first with vanadium and the second molybdenum complexes. Further examples of molybdenumcatalyzed epoxidations were reported by Otsuka et a1.,6 who described the treatment of squalene with a mixture of tert-butyl hydroperoxide, chelated molybdenum oxide, and the chiral inducing agent (+)-diisopropyl tartrate. By this method it was possible to obtain (S)-2,3-squalene epoxide in 14% enantiomeric excess. The real breakthrough in asymmetric epoxidation came when Sharpless et al. treated a mixture of commercially available titanium tetraisoproxide, tert-butyl hydroperoxide, and (+)or (-)-diethyl tartrate with allylic alcohol^.^ With (-)-diethyl tartrate the oxidant approaches the allylic alcohol from the top side of the plane shown in 1, whereas the bottom side is open for the (+)-diethyl tartrate reagent, giving rise to the corresponding optically active epoxy alcohols, 2. This asymmetric epoxidation, now known as the Sharpless epoxidation, has already shown its power in the synthesis of natural products.8 ' Aarhus University. 1 Baker Laboratory. o ( ) D i e t h y l t a r t r a t e