Efficient sialylation with phenyltrifluoroacetimidates as leaving groups

[reaction: see text] Sialylation with N-phenyltrifluoroacetimidates as leaving groups and a catalytic amount of TMSOTf as promoter compares favorably with the previous protocols for direct sialylation and expand in essence the scope of the Schmidt glycosylation reaction.     

Direct studies on 5-coordinate intermediates formed during substitution at tetrahedral Fe sites: role of bound nucleophile in labilisation of leaving group

The substitution reactions of the tetrahedral Fe sites in [FeCl(4)](-), [Fe(2)S(2)Cl(4)](2-), [Fe(4)S(4)Cl(4)](2-) and [{MoFe(3)S(4)Cl(3)}(2)(micro-SEt)(3)](3-) with 4-RC(6)H(4)S(-) (R = MeO, Me, H, Cl or NO(2)) all involve rapid binding of the thiolate to a Fe site and formation of a kinetically and spectroscopically detectable intermediate. Kinetic studies allow calculation of the rate of Fe-Cl dissociation from the 5-coordinate site of the intermediate (k(2)(R)). The rate of Fe-Cl dissociation from the intermediate exhibits a marked dependence on the nature of the bound thiolate with log(10)(k(2)(R)) increasing in a linear manner with the calculated NBO charge on the sulfur atom of the coordinated thiolate. This behaviour indicates that Fe-Cl bond dissociation at the 5-coordinate intermediate involves a process in which Fe-thiolate bond shortening occurs prior to movement of the Fe-Cl bond.     

Indium-mediated radical cyclization of iodoalkenes and iodoalkynes with and without allylic and propargylic leaving groups

Upon treatment with In and I₂, mono-substituted alkenes having an iodine substituent at the δ-position of the tether gave the corresponding iodinated cyclic compounds, whereas di- and tri-substituted alkenes gave the corresponding hydroxylated cyclic compounds. Alkenes bearing leaving groups at the allylic position were transformed only to the corresponding vinyl substituted cyclic compounds. On the other hand, alkynes bearing good leaving groups at the propargylic position gave allenic products selectively.     

Stereoselective O-glycosylation reactions using glycosyl donors with diphenylphosphinate and propane-1,3-diyl phosphate leaving groups

Glycosyl donors having a diphenylphosphinate and a propane-1,3-diyl phosphate leaving group were easily prepared by the addition of the anomeric hydroxyl group of 2,3,4,6-tetra-O-benzyl-α,β-d-glucopyranose to diphenylphosphinic and propane-1,3-diyldioxyphosphoryl chlorides. These glycosyl donors were selectively glycosylated with a number of primary and secondary oxygen nucleophiles in the presence of trimethylsilyl triflate (TMSOTf). The use of 1,3-diyl phosphate resulted in the stereoselective formation of β-O-linked glycosides.     

Polymer-supported triazole and benzotriazole leaving groups. Three new examples and a comparison of their efficiency

Three polymer-supported heterocyclic (triazole 4 and benzotriazoles 2, 8) leaving groups are described. The loading of 8 was clearly superior to those of 2 and 4. The efficiency of 8 was higher than those of previously reported benzotriazole resins 9a,b in the C-acylation of ketones.     

Photoactivation of amino-substituted 1,4-benzoquinones for release of carboxylate and phenolate leaving groups using visible light

Upon exposure to visible light, 2-pyrrolidino-substituted 3,6-dimethyl-1,4-benzoquinones photocyclize to give benzoxazolines with quantum yields of 0.07-0.10 in CH2Cl2, 0.02-0.04 in CH3CN, and <0.01 in 30% aq CH3CN. With carboxylate or phenolate leaving groups incorporated via coupling to a 5-hydroxymethyl group of the quinones, the photocyclizations give benzoxazolines that eliminate the leaving groups in a dark reaction. Lifetimes for elimination of 4-YC6H4OH in 30% phosphate buffer in CD3CN (pD 7) at 17 degrees C are 13.1, 0.54, and 0.13 h for Y = H, CF3, and CN, respectively, and the linear equation log k (h(-1)) = 0.998(-pKa) + 8.80 gives a best fit to the data. Carboxylate leaving groups are rapidly eliminated upon photolysis of the quinones in aq CH3CN to produce an o-quinone methide intermediate that is trapped by 4 + 2 cycloaddition with unreacted starting material or with added 3-(dimethylamino)-5,5-dimethyl-2-cyclohexen-1-one. The ortho-quinone methide is observed at 339 and 455 nm by conventional absorption spectroscopy and gives a pseudo-first-order fit of the decay kinetics with tau1/2 = 34.9 min in 30% phosphate buffer in CH3CN at 20 degrees C.     

The substituent effects of the leaving groups on the aminolysis of phenyl acetates: DFT studies

The density functional theory B3LYP/6-31G(d, p) method is employed to study the mechanism of aminolysis reaction of p-substituted phenyl acetates (CH₃C(O)OC₆H₄X, X = H, NH₂, and NO₂) with ammonia in the gas phase. Two reaction pathways are considered: the concerted process and the stepwise pathway through neutral intermediates. The substituent effects of the leaving groups on the reactivity of phenyl acetates are discussed. The solvent effect of acetonitrile on the title reaction is also assessed by the polarizable continuum model (CPCM model) at B3LYP/6-31++G(d, p) level of theory. The calculated results show that the activation barriers of the concerted pathways are lower than those of the rate-controlling steps of the stepwise processes for all the three aminolysis reactions. This aminolysis of phenyl acetates is more favorable for X = NO₂ than for X = H and NH₂ in the gas phase and in acetonitrile.     

Diazeniumdiolate ions as leaving groups in anomeric displacement reactions: a protection-deprotection strategy for ionic diazeniumdiolates

Diazeniumdiolate ions [R2N-N(O)=N-O-] are of growing interest pharmacologically for their ability to generate up to two molar equivalents of bioactive nitric oxide (NO) spontaneously on protonating the amino nitrogen. Accordingly, their stability increases as the pH is raised. Here we show that the corresponding beta-glucosides [R2N-N(O)=N-O-Glc] decreased in stability with pH; when R2N was diethylamino, the rate equation was kobs = ko + kOH- [OH-], where ko = 7.8 x 10-7 s-1 and kOH- = 5.3 x 10-3 M-1 s-1. The primary products were 1,6-anhydroglucose and the regenerated R2N-N(O)=N-O- ion. The results were qualitatively similar to those of beta-glucosyl fluoride and p-nitrophenoxide, whose hydrolyses have been rationalized as proceeding via a glycal oxide intermediate. This chemistry offers a convenient strategy for protecting heat- and acid-sensitive diazeniumdiolate ions during manipulations that would otherwise destroy them. As an example, a poly(urethane) film that generated NO in physiological buffer at a surface flux comparable to that of the mammalian vascular endothelium was prepared by glucosylating the ionic diazeniumdiolate group attached to the diol monomer before reacting it with the bis-isocyanate, then removing the saccharide with base when the protecting group was no longer needed.     

A new insight into using chlorine leaving group and nucleophile carbon kinetic isotope effects to determine substituent effects on the structure of SN2 transition states

Chlorine leaving group k(35)/k(37), nucleophile carbon k(11)/k(14), and secondary alpha-deuterium [(kH/kD)alpha] kinetic isotope effects (KIEs) have been measured for the SN2 reactions between para-substituted benzyl chlorides and tetrabutylammonium cyanide in tetrahydrofuran at 20 degrees C to determine whether these isotope effects can be used to determine the substituent effect on the structure of the transition state. The secondary alpha-deuterium KIEs indicate that the transition states for these reactions are unsymmetric. The theoretical calculations at the B3LYP/aug-cc-pVDZ level of theory support this conclusion; i.e., they suggest that the transition states for these reactions are unsymmetric with a long NC-C(alpha) and reasonably short C(alpha)-Cl bonds. The chlorine isotope effects suggest that these KIEs can be used to determine the substituent effects on transition state structure with the KIE decreasing when a more electron-withdrawing para-substituent is present. This conclusion is supported by theoretical calculations. The nucleophile carbon k(11)/k(14) KIEs for these reactions, however, do not change significantly with substituent and, therefore, do not appear to be useful for determining how the NC-C(alpha) transition-state bond changes with substituent. The theoretical calculations indicate that the NC-C(alpha) bond also shortens as a more electron-withdrawing substituent is placed on the benzene ring of the substrate but that the changes in the NC-C(alpha) transition-state bond with substituent are very small and may not be measurable. The results also show that using leaving group and nucleophile carbon KIEs to determine the substituent effect on transition-state structure is more complicated than previously thought. The implication of using both chlorine leaving group and nucleophile carbon KIEs to determine the substituent effect on transition-state structure is discussed.     

Eine formal nucleophile Substitution an Bilatrienen-abc

Reaction of Aetiobiliverdine-IV- with cyanide ion in dimethylsulfoxide yieldsvia nucleophilic addition and oxidation the 10-cyano derivative exclusively. Its structure was established from its spectroscopic properties.