Carbene-Like Reactivity in an Iron Azametallacyclobutene Complex: Insights from Electronic Structure.

Herein we describe our investigation into the electronic structure of the first isolated monometallic iron azametallacyclobutene complex. Computational analysis through density functional theory calculations reveals electron delocalization throughout the four atoms of the ring system, in line with experimental observations and supporting the classification of this complex as a conjugated metallacycle. The results of this study also point to significant contribution from an imine-substituted iron carbene resonance structure to the overall bonding picture for the azametallacyclobutene. Accordingly, this complex participates in carbene-like reactivity in the presence of an isocyanide substrate to generate a ketenimine product. The related reaction with carbon monoxide leads to the isolation of a five-membered metallacycle that is analogous to the proposed intermediate in ketenimine formation, and confirms the α-carbon as the site of reactivity.

Copper(I) Complexes Containing PCP Ligand Catalyzed Hydrogenation of Carbon Dioxide to Formate under Ambient Conditions.

The five new copper(I) complexes [Cu2(µ-Cl)2(κ1-PCPt-Bu)] (1), [Cu2(µ-Br)2(κ1-PCPt-Bu)] (2), [Cu2(µ-I)2(κ1-PCPt-Bu)] (3), [Cu2(µ-CN)2(κ1-PCPt-Bu)] (4), and [Cu4(µ3-SCN)4(κ1-PCPt-Bu)2]·CH2Cl2 (5) bearing a 1,3-bis[(di-tert-butylphosphino)methyl]benzene ligand were synthesized and characterized spectroscopically, and the molecular structures of 1, 3, and 5 were determined by single-crystal X-ray diffraction techniques. Structural studies for 1 and 3 revealed their binuclear structures with Cu···Cu separations of 2.609(3) and 2.6359(19) Å, respectively. However, 5 has a tetranuclear cubane structure with an 18-electron configuration at each copper without any metal-metal bonds. The two copper centers in 1 and 3 are bonded to one bridging PCPt-Bu ligand in a κ1-manner and two bridging (pseudo)halido ligands in a µ2-bonding mode to generate a nonplanar Cu2(µ-X)2 framework. The four copper centers in 5 are at the vertices of a tetrahedron. Each copper center has pseudo-tetrahedral coordination provided by two bridging PCPt-Bu ligands in a κ1-manner and the four bridging thiocyanate groups in a µ3-manner. These complexes were used as catalysts for the hydrogenation of CO2 to formate in the presence of DBU as a base to produce valuable energy-rich chemicals, and therefore it is a promising, safe, and simple strategy to conduct reactions under ambient pressure at room temperature. Among all of the five copper(I) complex based catalysts, 3 displayed the best catalytic performance with turnover number (TON) values of 38-8700 in 12-48 h of reaction at 25-80 °C. The outstanding catalytic performance of [Cu2(µ-I)2(κ1-PCPt-Bu)] (3) makes it a potential candidate for realizing the large-scale production of formate by CO2 hydrogenation.

Indolylthio Glycosides As Effective Building Blocks for Chemical Glycosylation.

The S-indolyl (SIn) anomeric moiety was investigated as a new leaving group that can be activated for chemical glycosylation under a variety of conditions including thiophilic and metal-assisted pathways. Understanding of the reaction pathways for the SIn moiety activation was achieved via the extended mechanistic study. Also reported is how the new SIn donors fit into selective activation strategies for oligosaccharide synthesis.

Detection and Characterization of Mononuclear Pd(I) Complexes Supported by N2S2 and N4 Tetradentate Ligands.

Palladium is a versatile transition metal used to catalyze a large number of chemical transformations, largely due to its ability to access various oxidation states (0, I, II, III, and IV). Among these oxidation states, Pd(I) is arguably the least studied, and while dinuclear Pd(I) complexes are more common, mononuclear Pd(I) species are very rare. Reported herein are spectroscopic studies of a series of Pd(I) intermediates generated by the chemical reduction at low temperatures of Pd(II) precursors supported by the tetradentate ligands 2,11-dithia[3.3](2,6)pyridinophane (N2S2) and N,N'-di-tert-butyl-2,11-diaza[3.3](2,6)pyridinophane (tBuN4): [(N2S2)PdII(MeCN)]2(OTf)4 (1), [(N2S2)PdIIMe]2(OTf)2 (2), [(N2S2)PdIICl](OTf) (3), [(N2S2)PdIIX](OTf)2 (X = tBuNC 4, PPh3 5), [(N2S2)PdIIMe(PPh3)](OTf) (6), and [(tBuN4)PdIIX2](OTf)2 (X = MeCN 8, tBuNC 9). In addition, a stable Pd(I) dinuclear species, [(N2S2)PdI(µ-tBuNC)]2(ClO4)2 (7), was isolated upon the electrochemical reduction of 4 and structurally characterized. Moreover, the (tBuN4)PdI intermediates, formed from the chemical reduction of [(tBuN4)PdIIX2](OTf)2 (X = MeCN 8, tBuNC 9) complexes, were investigated by EPR spectroscopy, X-ray absorption spectroscopy (XAS), and DFT calculations and compared with the analogous (N2S2)PdI systems. Upon probing the stability of Pd(I) species under different ligand environments, it is apparent that the presence of soft ligands such as tBuNC and PPh3 significantly improves the stability of Pd(I) species, which should make the isolation of mononuclear Pd(I) species possible.

Improved Oxidative C-C Bond Formation Reactivity of High-Valent Pd Complexes Supported by a Pseudo-Tridentate Ligand.

There is a large interest in developing oxidative transformations catalyzed by palladium complexes that employ environmentally friendly and economical oxidizing reagents such as dioxygen. Recently, we have reported the isolation and characterization of various mononuclear PdIII and PdIV complexes supported by the tetradentate ligands N,N'-dialkyl-2,11-diaza[3.3](2,6)pyridinophane (RN4, R = tBu, iPr, Me), and the aerobically induced C-C and C-heteroatom bond formation reactivity was investigated in detail. Given that the steric and electronic properties of the multidentate ligands were shown to tune the stability and reactivity of the corresponding high-valent Pd complexes, herein we report the use of an asymmetric N4 ligand, N-mehtyl-N'-tosyl-2,11-diaza[3.3](2,6)pyridinophane (TsMeN4), in which one amine N atom contains a tosyl group. The N-Ts donor atom exhibits a markedly reduced donating ability, which led to the formation of transiently stable PdIII and PdIV complexes, and consequently the corresponding O2 oxidation reactivity and the subsequent C-C bond formation were improved significantly.

Synthesis of Phostones via the Palladium-Catalyzed Ring Opening of Epoxy Vinyl Phosphonates.

The reaction of epoxy aldehydes with tetraethyl methylenediphosphonate gave γ,δ-epoxy vinyl phosphonates. The palladium-catalyzed addition of primary alcohols gave the monoprotected diols as single diastereoisomers. The trans- and cis-epoxides lead to opposite ( syn and anti) diastereoisomers of the addition products. The alkene of the vinyl phosphonates was subjected to hydrogenation, and the resulting saturated phosphonates underwent base-catalyzed cyclization to give phostones with a very high diastereoselectivity in the formation of the new chiral center at the phosphorus atom.

Regioselective photoreactions within a series of mixed co-crystals containing isosteric dihalogenated resorcinols with 4-stilbazole.

The formation and photoreactivity of a series of mixed co-crystals containing 4-stilbazole along with both 4,6-dichlororesorcinol and 4,6-dibromoresorcinol at various ratios is reported. In all cases, the quantitative [2 + 2] cycloaddition reaction yields an identical head-to-tail photoproduct, namely rctt-1,3-bis(4-pyridyl)-2,4-bis(phenyl)cyclobutane. The selectivity in the cycloaddition reaction occurred due to a shorter distance observed between two carbon-carbon double bonds that were found between and not within the hydrogen-bonded assemblies.

Isolation of Amine Derivatives of (ZnSe)34 and (CdTe)34. Spectroscopic Comparisons of the (II-VI)13 and (II-VI)34 Magic-Size Nanoclusters.

The spectroscopically observed magic-size nanoclusters (ZnSe)34 and (CdTe)34 are isolated as amine derivatives. The nanoclusters [(ZnSe)34( n-octylamine)29±6(di- n-octylamine)5±4] and [(CdTe)34( n-octylamine)4±3(di- n-pentylamine)13±3] are fully characterized by combustion-based elemental analysis, UV-visible spectroscopy, IR spectroscopy, and mass spectrometry. Amine derivatives of both (ZnSe)34 and (CdTe)34 are observed to convert to the corresponding (ZnSe)13 and (CdTe)13 derivatives, indicating that the former are kinetic products and the latter thermodynamic products, under the conditions employed. This conversion process is significantly inhibited in the presence of secondary amines. The isolation of the two new nanocluster derivatives adds to a total of nine of 12 possible isolated derivatives in the (II-VI)13 and (II-VI)34 families (II = Zn, Cd; VI = S, Se, Te), allowing comparisons of their properties. The members of these two families exhibit extensive spectroscopic homologies. In both the (II-VI)13 and (II-VI)34 families, linear relationships are established between the lowest-energy nanocluster electronic transition and the band gap of the corresponding bulk semiconductor phase.

Glycosyl nitrates in synthesis: streamlined access to glucopyranose building blocks differentiated at C-2.

In an attempt to refine a CAN-mediated synthesis of 1,3,4,6-tetra-O-acetyl-α-d-glucopyranose (2-OH glucose) we unexpectedly discovered that this reaction proceeds via the intermediacy of glycosyl nitrates. Improved mechanistic understanding of this reaction led to the development of a more versatile synthesis of 2-OH glucose from a variety of precursors. Also demonstrated is the conversion of 2-OH glucose into a variety of building blocks differentially protected at C-2, a position that is generally hard to protect regioselectively in the glucopyranose series.

Oxidative C-C Bond Formation Reactivity of Organometallic Ni(II), Ni(III), and Ni(IV) Complexes.

The use of the tridentate ligand 1,4,7-trimethyl-1,4,7-triazacyclononane (Me3tacn) and the cyclic alkyl/aryl C-donor ligand -CH2CMe2-o-C6H4- (cycloneophyl) allows for the synthesis of isolable organometallic NiII, NiIII, and NiIV complexes. Surprisingly, the five-coordinate NiIII complex is stable both in solution and the solid state, and exhibits limited C-C bond formation reactivity. Oxidation by one electron of this NiIII species generates a six-coordinate NiIV complex, with an acetonitrile molecule bound to Ni. Interestingly, illumination of the NiIV complex with blue LEDs results in rapid formation of the cyclic C-C product at room temperature. This reactivity has important implications for the recently developed dual Ni/photoredox catalytic systems proposed to involve high-valent organometallic Ni intermediates. Additional reactivity studies show the corresponding NiII species undergoes oxidative addition with alkyl halides, as well as rapid oxidation by O2, to generate detectable NiIII and/or NiIV intermediates and followed by C-C bond formation.

S-Benzimidazolyl (SBiz) Imidates as a Platform for Oligosaccharide Synthesis via Active-Latent, Armed-Disarmed, Selective, and Orthogonal Activations.

This article describes the development of S-benzimidazolyl (SBiz) imidates as versatile building blocks for oligosaccharide synthesis. The SBiz imidates have been originally developed as a new platform for active-latent glycosylations. This article expands upon the utility of these compounds. The application to practically all common concepts for the expeditious oligosaccharide synthesis including selective, chemoselective, and orthogonal strategies is demonstrated. The strategy development was made possible thanks to our enhanced understanding of the reaction mechanism and the modes by which SBiz imidates interact with various promoters of glycosylation.

Extending the S-benzimidazolyl (SBiz) platform: N-alkylated SBiz glycosyl donors with the universal activation profile.

This article describes the development of alkylated S-benzimidazolyl (SBiz) imidates as versatile building blocks for chemical glycosylation. The SBiz imidates have been originally developed as a new platform for active-latent glycosylations and its utility was further extended to other common strategies for oligosaccharide synthesis. This article expands upon the utility of these compounds. We developed a general protocol for the synthesis of a series of N-alkylated SBiz glycosides from N-protected SBiz aglycones by Lewis acid-mediated coupling with glucose pentaacetate. The N-alkylated SBiz moiety was found to be stable under strong basic conditions which allowed us to obtain both armed and disarmed N-alkylated SBiz donors. These donors showed good reactivity at a variety of activation conditions, and generally provided high yields in glycosylations.

Mononuclear Rhodium(II) and Iridium(II) Complexes Supported by Tetradentate Pyridinophane Ligands.

The tetradentate ligands N,N'-dialkyl-2,11-diaza[3,3](2,6)pyridinophane (RN4, where R = Me or tBu) were employed to synthesize and fully characterize [(RN4)MI(COD)]+ complexes (M = Rh or Ir; COD = cyclooctadiene). Interestingly, these complexes exhibit accessible oxidation potentials and can generate detectable [(RN4)MII(COD)]2+ complexes, which were characterized by electron paramagnetic resonance and high-resolution electrospray ionization mass spectrometry. Moreover, a rare mononuclear [(MeN4)RhII(COD)]2+ complex was isolated and crystallographically characterized, allowing for a direct comparison with its rhodium(I) analogue. The detailed characterization of such paramagnetic rhodium(II) and iridium(II) complexes enables further investigation of their redox reactivity.

Cadmium Bis(phenyldithiocarbamate) as a Nanocrystal Shell-Growth Precursor.

Cadmium bis(phenyldithiocarbamate) [Cd(PTC)2] is prepared and structurally characterized. The compound crystallizes in the monoclinic space group P21/n. A one-dimensional polymeric structure is adopted in the solid state, having bridging PTC ligands and 6-coordinate pseudo-octahedral Cd atoms. The compound is soluble in DMSO, THF, and DMF and insoluble in EtOH, MeOH, CHCl3, CH2Cl2, and toluene. {CdSe[n-octylamine]0.53} quantum belts and Cd(PTC)2 react to deposit epitaxial CdS shells on the nanocrystals. With an excess of Cd(PTC)2, the resulting thick shells contain spiny CdS nodules grown in the Stranski-Krastanov mode. Stoichiometric control affords smooth, monolayer CdS shells. A base-catalyzed reaction pathway is elucidated for the conversion of Cd(PTC)2 to CdS, which includes phenylisothiocyanate and aniline as intermediates, and 1,3-diphenylthiourea as a final product.

Coordination Chemistry of Bifunctional Chemical Agents Designed for Applications in 64Cu PET Imaging for Alzheimer's Disease.

Positron emission tomography (PET) is emerging as one of the most important diagnostic tools for brain imaging, yet the most commonly used radioisotopes in PET imaging, 11C and 18F, have short half-lives, and their usage is thus somewhat limited. By comparison, the 64Cu radionuclide has a half-life of 12.7 h, which is ideal for administering and imaging purposes. In spite of appreciable research efforts, high-affinity copper chelators suitable for brain imaging applications are still lacking. Herein, we present the synthesis and characterization of a series of bifunctional compounds (BFCs) based on macrocyclic 1,4,7-triazacyclononane and 2,11-diaza[3.3](2,6)pyridinophane ligand frameworks that exhibit a high affinity for Cu2+ ions. In addition, these BFCs contain a 2-phenylbenzothiazole fragment that is known to interact tightly with amyloid ß fibrillar aggregates. Determination of the protonation constants (pKa values) and stability constants (log ß values) of these BFCs, as well as characterization of the isolated copper complexes using X-ray crystallography, electron paramagnetic resonance spectroscopy, and electrochemical studies, suggests that these BFCs exhibit desirable properties for the development of novel 64Cu PET imaging agents for Alzheimer's disease.

Conformationally superarmed S-ethyl glycosyl donors as effective building blocks for chemoselective oligosaccharide synthesis in one pot.

A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete ß-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning.

Aromatic Cyanoalkylation through Double C-H Activation Mediated by Ni(III).

Herein we report an atom- and step-economic aromatic cyanoalkylation reaction that employs nitriles as building blocks and proceeds through Csp(2)-H and Csp(3)-H bond activation steps mediated by Ni(III). In addition to cyanomethylation with MeCN, regioselective α-cyanoalkylation was observed with various nitrile substrates to generate secondary and tertiary nitriles. Importantly, to the best of our knowledge these are the first examples of C-H bond activation reactions occurring at a Ni(III) center, which may exhibit different reactivity and selectivity profiles than those corresponding to analogous Ni(II) centers. These studies provide guiding principles to design catalytic C-H activation and functionalization reactions involving high-valent Ni species.

Isolated Organometallic Nickel(III) and Nickel(IV) Complexes Relevant to Carbon-Carbon Bond Formation Reactions.

Nickel-catalyzed cross-coupling reactions are experiencing a dramatic resurgence in recent years given their ability to employ a wider range of electrophiles as well as promote stereospecific or stereoselective transformations. In contrast to the extensively studied Pd catalysts that generally employ diamagnetic intermediates, Ni systems can more easily access various oxidation states including odd-electron configurations. For example, organometallic NiIII intermediates with aryl and/or alkyl ligands are commonly proposed as the active intermediates in cross-coupling reactions. Herein, we report the first isolated NiIII-dialkyl complex and show that this species is involved in stoichiometric and catalytic C-C bond formation reactions. Interestingly, the rate of C-C bond formation from a NiIII center is enhanced in the presence of an oxidant, suggesting the involvement of transient NiIV species. Indeed, such a NiIV species was observed and characterized spectroscopically for a nickelacycle system. Overall, these studies suggest that both NiIII and NiIV species could play an important role in a range of Ni-catalyzed cross-coupling reactions, especially those involving alkyl substrates.

2,3-Di-O-picolinyl building blocks as glycosyl donors with switchable stereoselectivity.

2-O-Picolinyl protected glycosyl donors lead to the formation of 1,2-trans glycosides with complete stereoselectivity. This is due to the participatory effect of the picolinyl nitrogen that is able to block the bottom face of the ring via a six-membered cyclic intermediate. Herein we demonstrate that if the nitrogen atom of the O-picolinyl moiety is temporarily blocked by coordination to the metal center (Pd), it becomes unavailable to participate in glycosylation and hence the stereoselectivity of 2-O-picolinyl-assisted glycosylations can be "switched".

Structure-activity studies of non-steroid analogues structurally-related to neuroprotective estrogens.

Estrone and 17ß-estradiol are phenolic steroids that are known to be neuroprotective in multiple models of neuronal injury. Previous studies have identified the importance of their phenolic steroid A-ring for neuroprotection and have identified ortho substituents at the C-2 and C-4 positions on the phenol ring that enhance this activity. To investigate the importance of the steroid ring system for neuroprotective activity, phenolic compounds having the cyclopent[b]anthracene, cyclopenta[b]phenanthrene, benz[f]indene, benz[e]indene, indenes linked to a phenol, and a phenolic spiro ring system were prepared. New synthetic methods were developed to make some of the cyclopent[b]anthracene analogues as well as the spiro ring system. Compounds were evaluated for their ability to protect HT-22 hippocampal neurons from glutamate neurotoxicity and their activity relative to a potent neuroprotective analogue of 17ß-estradiol was determined. An adamantyl substituent placed ortho to the phenolic hydroxyl group gave neuroprotective analogues in all ring systems studied.