1,721,100 research outputs found
Kinetic Evidence of an Arm-Off Mechanism in Complexes of Hemilabile Hybrid Ligands. Oxidative Addition of Methyl Iodide to the Rhodium(I) Complex [Rh(2,6-bis(benzylthiomethyl)pyridine)(CO)]PF6 via Competitive Pathways
No full textInvolvement of alkoxyl radical intermediates in the photolysis of 1-alkylcycloalkanols in the presence of bis(pyridine) iodonium tetrafluoroborate - Comparison with the (diacetoxyiodo)benzene/I-2 system
No full textThe product distributions observed after visible light irradiation of a series of 1-alkylcycloalkanols (1-3) and bis(pyridine)iodonium tetrafluo-. roborate (IPy2BF4), have been compared with those observed after irradiation of the same substrates in the presence of (diacetoxy)iodobenzene (DIB) and I-2, i.e. under bona fide conditions for alkoxyl radical generation. The observation of very similar product distributions with the two systems strongly supports the previous hypothesis that alkoxyl radical intermediates are formed after photolysis of substrates 1-3 in the presence Of IPy2BF4. (c) 2006 Elsevier B.V. All rights reserved
Tuning Reactivity and Selectivity in Hydrogen Atom Transfer from Aliphatic C-H Bonds to Alkoxyl Radicals: Role of Structural and Medium Effects
No full textHydrogen atom transfer (HAT) is a fundamental reaction that takes part in a wide variety of chemical and biological processes, with relevant examples that include the action of antioxidants, damage to biomolecules and polymers, and enzymatic and biomimetic reactions. Moreover, great attention is currently devoted to the selective functionalization of unactivated aliphatic C-H bonds, where HAT based procedures have been shown to play an important role. In this Account, we describe the results of our recent studies on the role of structural and medium effects on HAT from aliphatic C-H bonds to the cumyloxyl radical (CumO(•)). Quantitative information on the reactivity and selectivity patterns observed in these reactions has been obtained by time-resolved kinetic studies, providing a deeper understanding of the factors that govern HAT from carbon and leading to the definition of useful guidelines for the activation or deactivation of aliphatic C-H bonds toward HAT. In keeping with the electrophilic character of alkoxyl radicals, polar effects can play an important role in the reactions of CumO(•). Electron-rich C-H bonds are activated whereas those that are α to electron withdrawing groups are deactivated toward HAT, with these effects being able to override the thermodynamic preference for HAT from the weakest C-H bond. Stereoelectronic effects can also influence the reactivity of the C-H bonds of ethers, amines, and amides. HAT is most rapid when these bonds can be eclipsed with a lone pair on an adjacent heteroatom or with the π-system of an amide functionality, thus allowing for optimal orbital overlap. In HAT from cyclohexane derivatives, tertiary axial C-H bond deactivation and tertiary equatorial C-H bond activation have been observed. These effects have been explained on the basis of an increase in torsional strain or a release in 1,3-diaxial strain in the HAT transition states, with kH(eq)/kH(ax) ratios that have been shown to exceed one order of magnitude. Medium effects on HAT from aliphatic C-H bonds to CumO(•) have been also investigated. With basic substrates, from large to very large decreases in kH have been measured with increasing solvent hydrogen bond donor (HBD) ability or after addition of protic acids or alkali and alkaline earth metal ions, with kinetic effects that exceed 2 orders of magnitude in the reactions of tertiary alkylamines and alkanamides. Solvent hydrogen bonding, protonation, and metal ion binding increase the electron deficiency and the strength of the C-H bonds of these substrates deactivating these bonds toward HAT, with the extent of this deactivation being modulated by varying the nature of the substrate, solvent, protic acid, and metal ion. These results indicate that through these interactions careful control over the HAT reactivity of basic substrates toward CumO(•) and other electrophilic radicals can be achieved, suggesting moreover that these effects can be exploited in an orthogonal fashion for selective C-H bond functionalization of substrates bearing different basic functionalities
Reaction Pathways of Alkoxyl Radicals. The Role of Solvent Effects on C-C Bond Fragmentation and Hydrogen Atom Transfer Reactions
No full textThis Account describes the results of our recent mechanistic studies on unimolecular C–C bond fragmentation (beta-scission and O-neophyl rearrangement) and bimolecular hydrogen atom transfer (HAT) reactions of alkoxyl radicals. Particular attention has been devoted to the study of solvent effects on these reactions by means of time-resolved techniques such as laser flash photolysis. Information has been provided on the effect of ring-substituents and of the solvent on the spectral properties of arylcarbinyloxyl radicals and on their reactivity in beta-scission and O-neophyl rearrangement reactions, showing that a change in solvent can influence the fragmentation reactivity and selectivity. Detailed information has been also obtained on the role of substrate structure and of the solvent on HAT reactions to the cumyloxyl radical, showing the importance of solvent hydrogen bond interactions with the substrate and/or the radical on these processes, and providing a general mechanistic description of the kinetic solvent effects observed in HAT reactions from C-H bonds and expanding the previously available one for HAT from phenolic O-H bonds. The possible application of these findings to synthetically useful C-H functionalization procedures is discussed
Electronic control over site-selectivity in hydrogen atom transfer (HAT) based C(sp3)-H functionalization promoted by electrophilic reagents
No full textThe direct functionalization of C(sp3)-H bonds represents one of the most investigated approaches to develop new synthetic methodology. Among the available strategies for intermolecular C-H bond functionalization, increasing attention has been devoted to hydrogen atom transfer (HAT) based procedures promoted by radical or radical-like reagents, that offer the opportunity to introduce a large variety of atoms and groups in place of hydrogen under mild conditions. Because of the large number of aliphatic C-H bonds displayed by organic molecules, in these processes control over site-selectivity represents a crucial issue, and the associated factors have been discussed. In this review article, attention will be devoted to the role of electronic effects on C(sp3)-H bond functionalization site-selectivity. Through an analysis of the recent literature, a detailed description of the HAT reagents employed in these processes, the associated mechanistic features and the selectivity patterns observed in the functionalization of substrates of increasing structural complexity will be provided
Structural effects on the beta-scission reaction of alkoxyl radicals. Direct measurement of the absolute rate constants for ring opening of benzocycloalken-1-oxyl radicals
No full textThe absolute rate constants for beta-scission of a series of benzocycloalken-1-oxyl radicals and of the 2-(4-methylphenyl)-2-butoxyl radical have been measured directly by laser flash photolysis. The benzocycloalken-1-oxyl radicals undergo ring opening with rates which parallel the ring strain of the corresponding cycloalkanes. In the 1-X-indan-1-oxyl radical series, ring opening is observed when X = H, Me, whereas exclusive C-X bond cleavage occurs when X = Et. The factors governing the fragmentation regioselectivity are discussed
Tuning Hydrogen Atom Abstraction from the Aliphatic C-H Bonds of Basic Substrates by Protonation. Control Over Selectivity by C-H Deactivation
No full textA kinetic study on the effect of acetic (AcOH) and trifluoroacetic acid (TFA) on hydrogen abstractions from
the C–H bonds of basic substrates by the cumyloxyl radical (CumO*) was carried out in acetonitrile. With
tetrahydropyran no significant effect on kH was observed after acid addition. With the more basic
tertiary amines acid addition led to greater than 4-orders of magnitude decreases in kH. Protonation at
nitrogen decreases the degree of overlap between the alpha-C–H sigma* orbital and the lone-pair leading to an
increase in the strength of the C–H bond and a destabilization of the radical formed after abstraction.
Evidence that C–H deactivation extends up to the gamma-C–H bonds and for the reversibility of this approach
was also provided. With TFA no reaction was observed up to [amine] = [TFA], pointing towards
stoichiometric protonation. At [amine] > [TFA], kH values that are very similar to those measured in the
absence of added acid were obtained. With the weaker acid, AcOH, no reaction was observed up to
[AcOH]/[amine] = 4, and a curved plot was observed with increasing [amine], as a result of the acid–
base equilibrium between AcOH and the amine. With 1,4-dimethylpiperazine, a quantitative evaluation
of the C–H deactivation determined by sequential protonation of one or both nitrogen centers was
obtained. These observations show that protonation provides an extremely efficient, precise and
tunable method for the deactivation of the C–H bonds of basic substrates allowing moreover for careful
control over the hydrogen abstraction selectivity. The implications of this approach are discussed
Hydrogen Atom Transfer from 1,n-Alkanediamines to the Cumyloxyl Radical. Modulating C-H Deactivation Through Acid-Base Interactions and Solvent Effects
No full textA time-resolved kinetic study on the effect of trifluoroacetic acid (TFA) on the hydrogen atom transfer (HAT) reactions from 1,n-alkanediamines (R2N(CH2)nNR2, R = H, CH3; n = 1−4), piperazine, and 1,4-dimethylpiperazine to the cumyloxyl radical (CumO•), has been carried out in MeCN and DMSO. Very strong deactivation of the α-C−H bonds has been observed following nitrogen protonation and the results obtained have been explained in terms of substrate
basicity, of the distance between the two basic centers and of the solvent hydrogen bond acceptor ability. At [substrate] ≤ 1/2 [TFA] the substrates exist in the doubly protonated form HR2N+(CH2)nN+R2H, and no reaction with CumO• is observed. At 1/2 [TFA] < [substrate] ≤ [TFA], HAT occurs from the C−H bonds that are α to the nonprotonated nitrogen in R2N(CH2)nN+R2H. At [substrate] > [TFA], HAT occurs from the α-C−H bonds of R2N(CH2)nNR2, and the mesured kH values are very close to those obtained in the absence of TFA. Comparison between MeCN and DMSO clearly shows that in the monoprotonated diamines R2N(CH2)nN+R2H remote C−H deactivation can be modulated through solvent hydrogen bonding
Kinetic Solvent Effects on the Reactions of the Cumyloxyl Radical with Tertiary Amides. Control Over the Hydrogen Atom Transfer Reactivity and Selectivity Through Solvent Polarity and Hydrogen Bonding
No full textA laser flash photolysis study on the role of solvent effects on hydrogen atom transfer (HAT) from the C−H bonds of N,Ndimethylformamide (DMF), N,N-dimethylacetamide (DMA), N-formylpyrrolidine (FPRD), and N-acetylpyrrolidine (APRD) to the cumyloxyl radical (CumO•) was carried out. From large to very large increases in the HAT rate constant (kH) were measured on going from MeOH and TFE to isooctane (kH(isooctane)/kH(MeOH) = 5−12; kH(isooctane)/kH(TFE) > 80). This behavior was explained in terms of the increase in the extent of charge separation in the amides determined by polar solvents through solvent−amide dipole−dipole interactions and hydrogen bonding, where the latter interactions appear to play a major role with strong HBD solvents such as TFE. These interactions increase the electron deficiency of the amide C−H bonds, deactivating these bonds toward HAT to an electrophilic radical such as CumO•, indicating that changes in solvent polarity and hydrogen bonding can provide a convenient method for deactivation of the C−H bond of amides toward HAT. With DMF, a solvent-induced change in HAT selectivity was observed, suggesting that solvent effects can be successfully employed to control the reaction selectivity in HAT-based procedures for the functionalization of C−H bonds
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