Project description:The present study provides mechanistic details of a mild aromatic C-H activation effected by a copper(II) center ligated in a triazamacrocylic ligand, affording equimolar amounts of a Cu(III)-aryl species and Cu(I) species as reaction products. At low temperatures the Cu(II) complex 1 forms a three-center, three-electron C-H...Cu(II) interaction, identified by pulse electron paramagnetic resonance spectroscopy and supported by density functional theory calculations. C-H bond cleavage is coupled with copper oxidation, as a Cu(III)-aryl product 2 is formed. This reaction proceeds to completion at 273 K within minutes through either a copper disproportionation reaction or, alternatively, even faster with 1 equiv of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), quantitatively yielding 2. Kinetic studies of both reactions strongly implicate a rate-limiting proton-coupled electron transfer as the key C-H activation step, a mechanism that does not conform to the C-H activation mechanism in a Ni(II) analogue or to any previously proposed C-H activation mechanisms.
Project description:Electron transfer may be concerted with proton transfer. It may also be concerted with the cleavage of a bond between heavy atoms. All three events may also be concerted. A model is presented to analyze the kinetics of these all-concerted reactions for homogeneous or electrochemical reduction or oxidation processes. It allows the estimation of the kinetic advantage that derives from the increase of the bond-breaking driving force resulting from the concerted proton transfer. Application of the model to the electrochemical reductive cleavage of the O-O bond of an organic peroxide in the presence of a proximal acid group illustrates the applicability of the model and provides an example demonstrating that electron transfer, heavy-atom bond breaking, and proton transfer may be all concerted. Such analyses are expected to be useful for the invention, analysis, and optimization of reactions involved in contemporary energy challenges as well as for the comprehension of major biochemical processes, a number of which involve electron and proton transfer together with cleavage of bonds between heavy atoms.
Project description:Anthranilic acids were recently reported as superior catalysts for hydrazone and oxime formation compared to aniline, the classic catalyst for these reactions. Here, alternative proton donors were examined with varied pKa in an effort to enhance activity at biological pH. The experiments show that 2-aminobenzenephosphonic acids are superior to anthranilic acids in catalyzing hydrazone formation with common aldehyde substrates.
Project description:Functionalization of amide bond via the cleavage of a non-carbonyl, C-N ? bond remains under-investigated. In this work, a transition-metal-free single-electron transfer reaction has been developed for the C-N ? bond cleavage of N-acylazetidines using the electride derived from sodium dispersions and 15-crown-5. Of note, less strained cyclic amides and acyclic amides are stable under the reaction conditions, which features the excellent chemoselectivity of the reaction. This method is amenable to a range of unhindered and sterically encumbered azetidinyl amides.
Project description:Radical polymerization with reversible addition-fragmentation chain transfer (RAFT polymerization) has been successfully applied to generate polymers of well-defined architecture. For RAFT polymerization a source of radicals is required. Recent work has demonstrated that for minimal side-reactions and high spatio-temporal control these should be formed directly from the RAFT agent or macroRAFT agent (usually carbonothiosulfanyl compounds) thermally, photochemically or by electrochemical reduction. In this work, we investigated low-energy electron attachment to a common RAFT agent (cyanomethyl benzodithioate), and, for comparison, a simple carbonothioylsulfanyl compound (dimethyl trithiocarbonate, DMTTC) in the gas phase by means of mass spectrometry as well as quantum chemical calculations. We observe for both compounds that specific cleavage of the C-S bond is induced upon low-energy electron attachment at electron energies close to zero eV. This applies even in the case of a poor homolytic leaving group (. CH3 in DMTTC). All other dissociation reactions found at higher electron energies are much less abundant. The present results show a high control of the chemical reactions induced by electron attachment.
Project description:Development of practical methods for the production of multi-functionalized amides is one of the most important topics in both synthetic chemistry and drug discovery. Disclosed herein is a new, efficient, site-selective heteroarylation of amides via C(sp3)-H bond functionalization. Amidyl radicals are directly generated from the amide N-H bonds under mild conditions, which trigger the subsequent 1,5-HAT process. A wide scope of aliphatic amides including carboxamides, sulfonamides, and phosphoramides are readily modified at remote C(sp3)-H bonds by installing diverse heteroaryl groups. Borne out of pragmatic consideration, this protocol can be used for the late-stage functionalization of amides.
Project description:We report an enantioselective Nazarov cyclization catalyzed by chiral hydrogen-bond-donors in concert with silyl Lewis acids. The developed transformation provides access to tri-substituted cyclopentenones in high levels of enantioselectivity (up to 95% e.e.) from a variety of simple unactivated dienones. Kinetic and mechanistic studies are consistent with a reversible 4π-electrocyclization C-C bond-forming step followed by rate- and enantio-determining proton-transfer as the mode of catalysis.
Project description:A cascade reaction that involves a unique C-C bond cleavage has been discovered. This protocol affords an unusual and facile method for the synthesis of 1,3-oxazin derivatives under mild conditions.
Project description:The selective transformation of C-H bonds is a longstanding challenge in modern chemistry. A recent report details C-H oxidation via multiple-site concerted proton-electron transfer (MS-CPET), where the proton and electron in the C-H bond are transferred to separate sites. Reactivity at a specific C-H bond was achieved by appropriate positioning of an internal benzoate base. Here, we extend that report to reactions of a series of molecules with differently substituted fluorenyl-benzoates and varying outer-sphere oxidants. These results probe the fundamental rate versus driving force relationships in this MS-CPET reaction at carbon by separately modulating the driving force for the proton and electron transfer components. The rate constants depend strongly on the pKa of the internal base, but depend much less on the nature of the outer-sphere oxidant. These observations suggest that the transition states for these reactions are imbalanced. Density functional theory (DFT) was used to generate an internal reaction coordinate, which qualitatively reproduced the experimental observation of a transition state imbalance. Thus, in this system, homolytic C-H bond cleavage involves concerted but asynchronous transfer of the H+ and e-. The nature of this transfer has implications for synthetic methodology and biological systems.
Project description:The base-induced reaction of aryl diazonium salts with commercially available CF3SO2Na/CF2HSO2Na allows for the generation of the corresponding diazene radicals along with fluoromethyl radicals. The addition of fluoromethyl radicals to alkenes with subsequent diazene trapping provides the azofluoromethylation products in good to excellent yields. This metal-free method under mild reaction conditions has broad functional group compatibility and is applicable in the late-stage modification of various natural products and bioactive molecules.