Oct 24, 2014

Room-temperature enantioselective C–H iodination via kinetic resolution

  • Ling Chu,
  • Kai-Jiong Xiao,
  • and Jin-Quan Yu
Science 24 October 2014: 451-455.
Palladium catalysis produces benzylamine derivatives of interest in medicinal chemistry.

 

Abstract

Asymmetric carbon-hydrogen (C–H) activation reactions often rely on desymmetrization of prochiral C–H bonds on the same achiral molecule, using a chiral catalyst. Here, we report a kinetic resolution via palladium-catalyzed enantioselective C–H iodination in which one of the enantiomers of a racemic benzylic amine substrates undergoes faster aryl C–H insertion with the chiral catalysts than the other. The resulting enantioenriched C–H functionalization products would not be accessible through desymmetrization of prochiral C–H bonds. The exceedingly high relative rate ratio (kfast/kslow up to 244), coupled with the subsequent iodination of the remaining enantiomerically enriched starting material using a chiral ligand with the opposite configuration, enables conversion of both substrate enantiomers into enantiomerically pure iodinated products.
Simultaneous measurements of structural and optical properties are used to study optically excited vanadium dioxide.
The complex interplay among several active degrees of freedom (charge, lattice, orbital, and spin) is thought to determine the electronic properties of many oxides. We report on combined ultrafast electron diffraction and infrared transmissivity experiments in which we directly monitored and separated the lattice and charge density reorganizations that are associated with the optically induced semiconductor-metal transition in vanadium dioxide (VO2). By photoexciting the monoclinic semiconducting phase, we were able to induce a transition to a metastable state that retained the periodic lattice distortion characteristic of the semiconductor but also acquired metal-like mid-infrared optical properties. Our results demonstrate that ultrafast electron diffraction is capable of following details of both lattice and electronic structural dynamics on the ultrafast time scale.

Oct 22, 2014

Chemistry prize winners pushed microscopes past supposed limit.
For more than 100 years, microscopists thought they would never get a clear close-up look at living organisms in visible light micrographs. The stumbling block was the so-called Abbe diffraction limit, a supposed physical law that stated optical images could never reach a resolution finer than half a wavelength of light. But beginning in the late 1990s, Eric Betzig of the Howard Hughes Medical Institute, Stefan Hell of the Max Planck Institute for Biophysical Chemistry, and William Moerner of Stanford University found a way to blast through that limit by using fluorescence to coax objects to reveal details through their own light. The techniques netted them this year's Nobel Prize in chemistry. 
Syntheses of two natural products reveal a surprising divergence in the plausible biosynthetic precursors of their class.
Cycloaddition is an essential tool in chemical synthesis. Instead of using light or heat as a driving force, marine sponges promote cycloaddition with a more versatile but poorly understood mechanism in producing pyrrole–imidazole alkaloids sceptrin, massadine, and ageliferin. Through de novo synthesis of sceptrin and massadine, we show that sponges may use single-electron oxidation as a central mechanism to promote three different types of cycloaddition. Additionally, we provide surprising evidence that, in contrast to previous reports, sceptrin, massadine, and ageliferin have mismatched chirality. Therefore, massadine cannot be an oxidative rearrangement product of sceptrin or ageliferin, as is commonly believed. Taken together, our results demonstrate unconventional chemical approaches to achieving cycloaddition reactions in synthesis and uncover enantiodivergence as a new biosynthetic paradigm for natural products. 

Intramolecular Iron-Mediated C–H Bond Heterolysis with an Assist of Pendant Base in a [FeFe]-Hydrogenase Model

Publication Date (Web): September 22, 2014 (Article)
DOI: 10.1021/ja5078014
 
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Although many metalloenzymes containing iron play a prominent role in biological C–H activation processes, to date iron-mediated C(sp3)–H heterolysis has not been reported for synthetic models of Fe/S-metalloenzymes. In contrast, ample precedent has established that nature’s design for reversible hydrogen activation by the diiron hydrogenase ([FeFe]-H2ase) active site involves multiple irons, sulfur bridges, a redox switch, and a pendant amine base, in an intricate arrangement to perform H–H heterolytic cleavage. In response to whether this strategy might be extended to C–H activation, we report that a [FeFe]-H2ase model demonstrates iron-mediated intramolecular C–H heterolytic cleavage via an agostic C–H interaction, with proton removal by a nearby pendant amine, affording FeII–[tiebar above startFe′II–CH–tiebar above endS] three-membered-ring products, which can be reduced back to 1 by Cp2Co in the presence of HBF4. The function of the pendant base as a proton shuttle was confirmed by the crystal structures of the N-protonated intermediate and the final deprotonated product in comparison with that of a similar but pendant-amine-free complex that does not show evidence of C–H activation. The mechanism of the process was backed up by DFT calculations.
 
Publication Date (Web): September 30, 2014 (Article)
DOI: 10.1021/ja507665a
 
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We prepared bifunctional MgII porphyrin catalysts 1 for the solvent-free synthesis of cyclic carbonates from epoxides and CO2. The activities of 1d, 1h, and 1i, which have Br, Cl, and I counteranions, respectively, increased in the order 1i < 1h < 1d. Catalysts 1d and 1jm, which bear four tetraalkylammonium bromide groups with different alkyl chain lengths, showed comparable but slightly different activities. Based on the excellent catalyst 1d, we synthesized MgII porphyrin 1o with eight tetraalkylammonium bromide groups, which showed even higher catalytic activity (turnover number, 138,000; turnover frequency, 19,000 h–1). The catalytic mechanism was studied by using 1d. The yields were nearly constant at initial CO2 pressures in the 1–6 MPa range, suggesting that CO2 was not involved in the rate-determining step in this pressure range. No reaction proceeded in supercritical CO2, probably because the epoxide (into which the catalyst dissolved) dissolved in and was diluted by the supercritical CO2. Experiments with 18O-labeled CO2 and D-labeled epoxide suggested that the catalytic cycle involved initial nucleophilic attack of Br on the less hindered side of the epoxide to generate an oxyanion, which underwent CO2 insertion to afford a CO2 adduct; subsequent intramolecular ring closure formed the cyclic carbonate and regenerated the catalyst. Density functional theory calculations gave results consistent with the experimental results, revealing that the quaternary ammonium cation underwent conformational changes that stabilized various anionic species generated during the catalytic cycle. The high activity of 1d and 1o was due to the cooperative action of the MgII and Br and a conformational change (induced-fit) of the quaternary ammonium cation.

Oct 21, 2014

Investigations on the Role of Proton-Coupled Electron Transfer in Hydrogen Activation by [FeFe]-Hydrogenase

Publication Date (Web): October 6, 2014 (Article)
DOI: 10.1021/ja508629m
 
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Proton-coupled electron transfer (PCET) is a fundamental process at the core of oxidation–reduction reactions for energy conversion. The [FeFe]-hydrogenases catalyze the reversible activation of molecular H2 through a unique metallocofactor, the H-cluster, which is finely tuned by the surrounding protein environment to undergo fast PCET transitions. The correlation of electronic and structural transitions at the H-cluster with proton-transfer (PT) steps has not been well-resolved experimentally. Here, we explore how modification of the conserved PT network via a Cys → Ser substitution at position 169 proximal to the H-cluster of Chlamydomonas reinhardtii [FeFe]-hydrogenase (CrHydA1) affects the H-cluster using electron paramagnetic resonance (EPR) and Fourier transform infrared (FTIR) spectroscopy. Despite a substantial decrease in catalytic activity, the EPR and FTIR spectra reveal different H-cluster catalytic states under reducing and oxidizing conditions. Under H2 or sodium dithionite reductive treatments, the EPR spectra show signals that are consistent with a reduced [4Fe-4S]H+ subcluster. The FTIR spectra showed upshifts of νCO modes to energies that are consistent with an increase in oxidation state of the [2Fe]H subcluster, which was corroborated by DFT analysis. In contrast to the case for wild-type CrHydA1, spectra associated with Hred and Hsred states are less populated in the Cys → Ser variant, demonstrating that the exchange of −SH with −OH alters how the H-cluster equilibrates among different reduced states of the catalytic cycle under steady-state conditions.

Oct 6, 2014

Hot molecules—off the beaten path

  • Arthur G. Suits and
  • David H. Parker
Science 3 October 2014: 30-31.
Highly excited carbon dioxide dissociates unexpectedly to form molecular oxygen [Also see Report by Lu et al.]
Absorption of high-energy ultraviolet light can break apart CO2 into C and O2 . [Also see Perspective by Suits and Parker]
Photodissociation of carbon dioxide (CO2) has long been assumed to proceed exclusively to carbon monoxide (CO) and oxygen atom (O) primary products. However, recent theoretical calculations suggested that an exit channel to produce C + O2 should also be energetically accessible. Here we report the direct experimental evidence for the C + O2 channel in CO2 photodissociation near the energetic threshold of the C(3P) + O2(X3Σg) channel with a yield of 5 ± 2% using vacuum ultraviolet laser pump-probe spectroscopy and velocity-map imaging detection of the C(3PJ) product between 101.5 and 107.2 nanometers. Our results may have implications for nonbiological oxygen production in CO2-heavy atmospheres.

Colloidal nanoparticle biosensors have received intense scientific attention and offer promising applications in both research and medicine. We review the state of the art in nanoparticle development, surface chemistry, and biosensing mechanisms, discussing how a range of technologies are contributing toward commercial and clinical translation. Recent examples of success include the ultrasensitive detection of cancer biomarkers in human serum and in vivo sensing of methyl mercury. We identify five key materials challenges, including the development of robust mass-scale nanoparticle synthesis methods, and five broader challenges, including the use of simulations and bioinformatics-driven experimental approaches for predictive modeling of biosensor performance. The resultant generation of nanoparticle biosensors will form the basis of high-performance analytical assays, effective multiplexed intracellular sensors, and sophisticated in vivo probes.

Spin-Selective Charge Recombination in Complexes of CdS Quantum Dots and Organic Hole Acceptors

Publication Date (Web): September 17, 2014 (Article)
DOI: 10.1021/ja507301d

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This paper describes the mechanisms of charge recombination on both the nanosecond and microsecond time scales in a donor–acceptor system comprising thiol-modified bis(diarylamino)4,4′-biphenyl (TPD) molecules attached to a CdS quantum dot (QD) via the thiolate linker. Transient absorption measurements, in conjunction with EPR and magnetic field effect studies, demonstrate that recombination on the nanosecond time scale is mediated by radical pair intersystem crossing (RP-ISC), as evidenced by the observation of a spin correlated radical ion pair, the formation of the localized 3*TPD state upon charge recombination, and the sensitivity of the yield of 3*TPD to an applied magnetic field. These experiments show that the radical spins of the donor–acceptor system have weak magnetic exchange coupling (|2J| < 10 mT) and that the electron donated to the QD is trapped in a surface state rather than delocalized within the QD lattice. The microsecond-time scale recombination is probably gated by diffusion of the trapped electron among QD surface states. This study demonstrates that magneto-optical studies are useful for characterizing the charge-separated states of molecule–QD hybrid systems, despite the heterogeneity in the donor–acceptor geometry and the chemical environment of the radical spins that is inherent to these systems.
Publication Date (Web): September 22, 2014 (Article)
DOI: 10.1021/ja5059444

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Oxidation of small organic molecules in a fuel cell is a viable method for energy production. However, the key issue is the development of suitable catalysts that exhibit high efficiencies and remain stable during operation. Here, we demonstrate that amine-modified ZnO nanorods on which ultrathin Au nanowires are grown act as an excellent catalyst for the oxidation of ethanol. We show that the modification of the ZnO nanorods with oleylamine not only modifies the electronic structure favorably but also serves to anchor the Au nanowires on the nanorods. The adsorption of OH species on the Au nanowires that is essential for ethanol oxidation is facilitated at much lower potentials as compared to bare Au nanowires leading to high activity. While ZnO shows negligible electrocatalytic activity under normal conditions, there is significant enhancement in the activity under light irradiation. We demonstrate a synergistic enhancement in the photoelectrocatalytic activity of the ZnO/Au nanowire hybrid and provide mechanistic explanation for this enhancement based on both electronic as well as geometric effects. The principles developed are applicable for tuning the properties of other metal/semiconductor hybrids with potentially interesting applications beyond the fuel cell application demonstrated here.

Sep 29, 2014

Carbon monoxide reveals new possibilities for substrate binding in nitrogenase [Also see Report by Spatzal et al.]

The structure of an inhibitor bound to nitrogenase reveals rearrangements in the active-site metallocluster. [Also see Perspective by Hognom]


The mechanism of nitrogenase remains enigmatic, with a major unresolved issue concerning how inhibitors and substrates bind to the active site. We report a crystal structure of carbon monoxide (CO)–inhibited nitrogenase molybdenum-iron (MoFe)–protein at 1.50 angstrom resolution, which reveals a CO molecule bridging Fe2 and Fe6 of the FeMo-cofactor. The μ2 binding geometry is achieved by replacing a belt-sulfur atom (S2B) and highlights the generation of a reactive iron species uncovered by the displacement of sulfur. The CO inhibition is fully reversible as established by regain of enzyme activity and reappearance of S2B in the 1.43 angstrom resolution structure of the reactivated enzyme. The substantial and reversible reorganization of the FeMo-cofactor accompanying CO binding was unanticipated and provides insights into a catalytically competent state of nitrogenase.

Water's place in Au catalysis

  • Gregory M. Mullen and
  • C. Buddie Mullins
Science 26 September 2014: 1564-1565.
Water plays a key role in gold-catalyzed CO oxidation [Also see Report by Saavedra et al.]
Adsorbed water enables proton-transfer steps that lower the activation barrier for carbon monoxide oxidation. [Also see Perspective by Mullen and Mullins]
We provide direct evidence of a water-mediated reaction mechanism for room-temperature CO oxidation over Au/TiO2 catalysts. A hydrogen/deuterium kinetic isotope effect of nearly 2 implicates O-H(D) bond breaking in the rate-determining step. Kinetics and in situ infrared spectroscopy experiments showed that the coverage of weakly adsorbed water on TiO2 largely determines catalyst activity by changing the number of active sites. Density functional theory calculations indicated that proton transfer at the metal-support interface facilitates O2 binding and activation; the resulting Au-OOH species readily reacts with adsorbed Au-CO, yielding Au-COOH. Au-COOH decomposition involves proton transfer to water and was suggested to be rate determining. These results provide a unified explanation to disparate literature results, clearly defining the mechanistic roles of water, support OH groups, and the metal-support interface.

Spectroscopy in the laboratory elucidates key steps in ozone’s atmospheric reaction with unsaturated hydrocarbons.
Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the troposphere, proceeds through energized Criegee intermediates that undergo unimolecular decay to produce OH radicals. Here, we used infrared (IR) activation of cold CH3CHOO Criegee intermediates to drive hydrogen transfer from the methyl group to the terminal oxygen, followed by dissociation to OH radicals. State-selective excitation of CH3CHOO in the CH stretch overtone region combined with sensitive OH detection revealed the IR spectrum of CH3CHOO, effective barrier height for the critical hydrogen transfer step, and rapid decay dynamics to OH products. Complementary theory provides insights on the IR overtone spectrum, as well as vibrational excitations, structural changes, and energy required to move from the minimum-energy configuration of CH3CHOO to the transition state for the hydrogen transfer reaction.

Synthesis and detection of a seaborgium carbonyl complex

The radioactive superheavy element seaborgium can form a carbonyl compound during its short lifetime [Also see Report by Even et al.]
A special apparatus enables synthesis of a compound with carbon bonds to a short-lived element produced via nuclear reaction. [Also see Perspective by Loveland]
Experimental investigations of transactinoide elements provide benchmark results for chemical theory and probe the predictive power of trends in the periodic table. So far, in gas-phase chemical reactions, simple inorganic compounds with the transactinoide in its highest oxidation state have been synthesized. Single-atom production rates, short half-lives, and harsh experimental conditions limited the number of experimentally accessible compounds. We applied a gas-phase carbonylation technique previously tested on short-lived molybdenum (Mo) and tungsten (W) isotopes to the preparation of a carbonyl complex of seaborgium, the 106th element. The volatile seaborgium complex showed the same volatility and reactivity with a silicon dioxide surface as those of the hexacarbonyl complexes of the lighter homologs Mo and W. Comparison of the product’s adsorption enthalpy with theoretical predictions and data for the lighter congeners supported a Sg(CO)6 formulation.

Mechanisms of Hydride Abstractions by Quinones

Publication Date (Web): September 8, 2014 (Article)
DOI: 10.1021/ja507598y
 
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The kinetics of the hydride abstractions by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) from 13 C–H hydride donors (acyclic 1,4-dienes, cyclohexa-1,4-dienes, dihydropyridines), tributylstannane, triphenylstannane, and five borane complexes (amine–boranes, carbene–boranes) have been studied photometrically in dichloromethane solution at 20 °C. Analysis of the resulting second-order rate constants by the correlation log k2(20 °C) = sN(E + N) ( J. Am. Chem. Soc. 2001, 123, 9500) showed that the hydride abstractions from the C–H donors on one side and the Sn–H and B–H hydride donors on the other follow separate correlations, indicating different mechanisms for the two reaction series. The interpretation that the C–H donors transfer hydrogen to the carbonyl oxygen of DDQ while Sn–H and B–H hydride donors transfer hydride to a cyano-substituted carbon of DDQ is supported by quantum-chemical intrinsic reaction coordinate calculations and isotope labeling experiments of the reactions of D8-cyclohexa-1,4-diene, Bu3SnD, and pyridine·BD3 with 2,5-dichloro-p-benzoquinone. The second-order rate constants of the reactions of tributylstannane with different quinones correlate linearly with the electrophilicity parameters E of the quinones, which have previously been derived from the reactions of quinones with π-nucleophiles. The fact that the reactions of Bu3SnH with quinones and benzhydrylium ions are on the same log k2 vs E (electrophilicity) correlation shows that both reaction series proceed by the same mechanism and illustrates the general significance of the reactivity parameters E, N, and sN for predicting rates of polar organic reactions.
 

Molecular Catalysis of H2 Evolution: Diagnosing Heterolytic versus Homolytic Pathways

Publication Date (Web): September 4, 2014 (Article)
DOI: 10.1021/ja505845t
 
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Molecular catalysis of H2 production from the electrochemical reduction of acids by transition-metal complexes is one of the key issues of modern energy challenges. The question of whether it proceeds heterolytically (through reaction of an initially formed metal hydride with the acid) or homolytically (through symmetrical coupling of two molecules of hydride) has to date received inconclusive answers for a quite simple reason: the theoretical bases for criteria allowing the distinction between homolytic and heterolytic pathways in nondestructive methods such as cyclic voltammetry have been lacking heretofore. They are provided here, allowing the distinction between the two pathways. The theoretical predictions and the diagnosing strategy are illustrated by catalysis of the reduction of phenol, acetic acid, and protonated triethylamine by electrogenerated iron(0) tetraphenylporphyrin. Rather than being an intrinsic property of the catalytic system, the occurrence of either a heterolytic or a homolytic pathway results from their competition as a function of the concentrations of acid and catalyst and the rate constants for hydride formation and H2 evolution by hydride protonation or dimerization.
 

Oxygen Insertion into Metal Carbon Bonds: Formation of Methylperoxo Pd(II) and Pt(II) Complexes via Photogenerated Dinuclear Intermediates

Publication Date (Web): September 8, 2014 (Article)
DOI: 10.1021/ja5055143
 
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Platinum(II) and palladium(II) complexes [M(CH3)(L)]SbF6 with substituted terpyridine ligands L undergo light-driven oxygen insertion reactions into metal methyl bonds resulting in methylperoxo complexes [M(OOCH3)(L)]SbF6. The oxygen insertion reactions occur readily for complexes with methyl ligands that are activated due to steric interaction with substituents (NH2, NHMe or CH3) at the 6,6″-positions on the terpyridine ligand. All complexes exhibit attractive intermolecular π···π or M···M interactions in the solid state and in solution, which lead to excited triplet dinuclear M–M complexes upon irradiation. A mechanism is proposed whereby a dinuclear intermediate is generated upon irradiation that has a weakened M–C bond in the excited state, resulting in the observed oxygen insertion reactions.
 

Sep 17, 2014

Mechanism of the Reactions of Alcohols with o-Benzynes

Publication Date (Web): September 4, 2014 (Article)
DOI: 10.1021/ja502595m
 
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We have studied reactions of secondary and primary alcohols with benzynes generated by the hexadehydro-Diels–Alder (HDDA) reaction. These alcohols undergo competitive addition vs dihydrogen transfer to produce aryl ethers vs reduced benzenoid products, respectively. During the latter process, an equivalent amount of oxidized ketone (or aldehyde) is formed. Using deuterium labeling studies, we determined that (i) it is the carbinol C–H and adjacent O–H hydrogen atoms that are transferred during this process and (ii) the mechanism is consistent with a hydride-like transfer of the C–H. Substrates bearing an internal trap attached to the reactive, HDDA-derived benzyne intermediate were used to probe the kinetic order of the alcohol trapping agent in the H2-transfer as well as in the alcohol addition process. The H2-transfer reaction is first order in alcohol. Our results are suggestive of a concerted H2-transfer process, which is further supported by density functional theory (DFT) computational studies and results of a kinetic isotope effect experiment. In contrast, alcohol addition to the benzyne is second order in alcohol, a previously unrecognized phenomenon. Additional DFT studies were used to further probe the mechanistic aspects of the alcohol addition process.
 

Sep 16, 2014

Decoupled catalytic hydrogen evolution from a molecular metal oxide redox mediator in water splitting

  • Benjamin Rausch,
  • Mark D. Symes,
  • Greig Chisholm,
  • and Leroy Cronin
Science 12 September 2014: 1326-1330.
A silicotungstic acid cluster can store protons and electrons during water electrolysis and later rapidly release hydrogen.

 

Abstract

The electrolysis of water using renewable energy inputs is being actively pursued as a route to sustainable hydrogen production. Here we introduce a recyclable redox mediator (silicotungstic acid) that enables the coupling of low-pressure production of oxygen via water oxidation to a separate, catalytic hydrogen production step outside the electrolyzer that requires no post-electrolysis energy input. This approach sidesteps the production of high-pressure gases inside the electrolytic cell (a major cause of membrane degradation) and essentially eliminates the hazardous issue of product gas crossover at the low current densities that characterize renewables-driven water-splitting devices. We demonstrated that a platinum-catalyzed system can produce pure hydrogen over 30 times faster than state-of-the-art proton exchange membrane electrolyzers at equivalent platinum loading.

Isotope Effects, Dynamic Matching, and Solvent Dynamics in a Wittig Reaction. Betaines as Bypassed Intermediates

Publication Date (Web): September 11, 2014 (Communication)
DOI: 10.1021/ja506497b


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The mechanism of the Wittig reaction of anisaldehyde with a stabilized ylide was studied by a combination of 13C kinetic isotope effects, conventional calculations, and molecular dynamics calculations in a cluster of 53 THF molecules. The isotope effects support a cycloaddition mechanism involving two sequential transition states associated with separate C–C and P–O bond formations. However, the betaine structure in between the two transition states is bypassed as an equilibrated intermediate in most trajectories. The role of the dynamics of solvent equilibration in the nature of mechanistic intermediates is discussed.