Choong Eui Song

A Highly Reactive and Enantioselective Bifunctional Organocatalyst for the Methanolytic Desymmetrization of Cyclic Anhydrides : Prevention of Catalyst Aggregation

At present, there is much interest in organocatalysts, as they tend to be less toxic and more environmentally friendly than traditional metal-based catalysts. Although much progress has been made, the development of chiral organocatalysts that are as reactive and stereoselective as some of the best transition-metal catalysts remains a considerable challenge. To attain reasonable reaction rates and stereoselectivity with organocatalysts, a large catalyst loading is often required. One way to address this difficulty is to design bifunctional or multifunctional organocatalysts with functional groups that work cooperatively to stabilize the transition state and accelerate the rate of the reaction. It has been shown that ureaor thiourea-based bifunctional organocatalysts are effective in facilitating a variety of useful organic reactions, including the methanolytic desymmetrization of cyclic anhydrides. However, we showed recently that ureaand thiourea-based organocatalysts can form hydrogen-bonded aggregates, which results in a strong dependence of reactivity and enantioselectivity on concentration and temperature. X-ray crystal structures of monofunctional and bifunctional (thio)urea derivatives show that they form aggregates through hydrogen bonding between the (thio)urea NH groups and the (thio)urea sulfur or oxygen atom in an intermolecular fashion. A recent NMR spectroscopic study also showed that the thiourea IV exists as a dimer, even in solution. Furthermore, thiourea groups tend to degrade under thermal conditions. Herein we present a thermally robust sulfonamide-based bifunctional organocatalyst I (Scheme 1), which shows unprecedented catalytic activity and excellent enantioselectivity in the methanolytic desymmetrization of meso cyclic anhydrides. A detailed mechanistic and computational approach to the design of I resulted in a catalyst that does not self-aggregate to any appreciable extent. To the best of our knowledge, I is the first quinineand sulfonamide-based bifunctional organocatalyst. The quinuclidine group of I may be able to function as a general-base catalyst to activate the nucleophile, and the sulfonamide group may be able to activate the electrophile simultaneously by hydrogen bonding. To investigate the catalytic activity and enantioselectivity of the cinchona-alkaloid-based sulfonamide catalyst I, we examined the asymmetric methanolysis of cis-1,2-cyclohexanedicarboxylic anhydride (1a) in Et2O with various amounts of I at ambient temperature. The results are summarized in Table 1, together with the results obtained with other cinchona-alkaloid-based catalysts (quinine (II), (DHQ)2AQN (III), and the quinine-based thiourea catalyst IV; Scheme 1). The desymmetrization of 1a with I (10 mol%) proceeded surprisingly fast; the reaction was complete within 1 h to Scheme 1. Structures of cinchona-alkaloid-based organocatalysts.

Enantioselective chemo- and bio-catalysis in ionic liquids

Recent developments in the enantioselective chemo- and bio-catalysis in ionic liquids are reviewed. In many cases, the use of ionic liquids provides many advantages over reactions in conventional organic solvents in terms of activity, enantioselectivity, stability and the reusability of the solvent-catalyst systems.

Catalytic asymmetric hydrogenation in a room temperature ionic liquid using chiral Rh-complex of ionic liquid grafted 1,4-bisphosphine ligandElectronic supplementary information (ESI) available: experimental details. See http://www.rsc.org/suppdata/cc/b3/b309304b/

Introduction of imidazolium ionic liquid pattern to the catalyst not only avoided catalyst leaching but also increased the stability of catalyst in ionic liquid, and thus, the Rh-complex of 1,4-bisphosphine bearing two imidazolium salt moieties was successfully immobilized in an ionic liquid and reused several times for the hydrogenation of an enamide without significant loss of catalytic efficiency.

Hydrogen bonding mediated enantioselective organocatalysis in brine: significant rate acceleration and enhanced stereoselectivity in enantioselective Michael addition reactions of 1,3-dicarbonyls to β-nitroolefins

Brine provides remarkable rate acceleration and a higher level of stereoselectivity over organic solvents, due to the hydrophobic hydration effect, in the enantioselective Michael addition reactions of 1,3-dicarbonyls to β-nitroolefins using chiral H-donors as organocatalysts.

Inhibition of TNF-α, IL-1β, and IL-6 productions and NF-κB activation in lipopolysaccharide-activated RAW 264.7 macrophages by catalposide, an iridoid glycoside isolated from Catalpa ovata G. Don (Bignoniaceae)

Abstract Catalposide, the major iridoid glycoside isolated from the stem bark of Catalpa ovata G. Don (Bignoniaceae), was found to inhibit the productions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), and the activation of nuclear factor κB (NF-κB) in RAW 264.7 macrophages activated with lipopolysaccharide (LPS). Catalposide also inhibited the expressions of TNF-α, IL-1β, and IL-6 genes and the nuclear translocation of p65 subunit of NF-κB in LPS-activated RAW 264.7 cells. Flow cytometric analysis revealed that catalposide suppressed the binding of FITC-conjugated LPS to CD14 on the surface of cells, probably resulting in the inhibitory effects on TNF-α, IL-1β, and IL-6 productions and NF-κB activation. These findings suggest that catalposide could be an attractive candidate for adjunctive therapy in Gram-negative bacterial infections.

Organocatalytic Enantioselective Decarboxylative Aldol Reaction of Malonic Acid Half Thioesters with Aldehydes

The direct asymmetric aldol reaction is one of the most powerful and fundamental tools for forming new carbon– carbon bonds and chiral hydroxy functional groups simultaneously. Inspired by nature, the development of prefunctionalized metal enolates and metal Lewis acids to mimic type II aldolases have provided a general solution to accessing enantioenriched b-hydroxy carbonyl compounds in cooperation with chiral auxiliaries and metal complexes. Specifically, the Mukaiyama aldol reaction is general in scope and is practical for controlling chemo-, stereo-, and enantioselectivity with a pregenerated silyl enol ether. However, to gain access to a variety of aldol products with defined stereochemistry, it is necessary to develop a reaction with a distinct catalytic reaction mode. Since 2000, primary and secondary amine organocatalysts have shown excellent performance, compared to chiral metal Lewis acids, for direct aldol reactions and Mukaiyama-type reactions by forming an enamine intermediate with a carbonyl compound. Recent studies by us and others using malonic acid half thioesters (2, MAHTs) as ester enolate equivalents with various electrophiles were compelling for the application of organocatalytic aldol reactions to mimic polyketide synthases. Moreover, the desired b-hydroxy thioesters 3 could readily be transformed into various functional groups. In addition, such a reaction generates only CO2 as a sole by-product. Recently, Shair et al. investigated the aldol reaction with methyl-substituted MAHT (MeMAHT) using a chiral Cu/ bis(oxazoline) catalyst. Aliphatic aldehydes underwent the aldol reaction to afford the a-methyl substituted aldol products with excellent diatereoand enantioselectivity [Eq. (1)]. However, aromatic and a,b-unsaturated aldehydes were shown to be poor substrates. Herein, we report the first organocatalytic asymmetric aldol reaction of methylsubstituted and unsubstituted MAHTs (2) with a variety of aromatic and aliphatic aldehydes to afford enantioenriched bhydroxythioesters (3) by employing a sulfonamide-based organocatalyst [Eq. (2)]. To the best of our knowledge, this is the first example of metal-free enantioselective organocatalytic aldol reaction of MAHTs (2) with aldehydes (1), as a polyketide synthase mimic, to provide b-hydroxy thioesters (3).

Scandium(III) triflate immobilised in ionic liquids: a novel and recyclable catalytic system for Friedel–Crafts alkylation of aromatic compounds with alkenes

Scandium(III) triflate catalysed Friedel–Crafts alkylation of aromatic compounds with alkenes proceeded readily in the hydrophobic ionic liquid solvents based on 1,3-dialkylimidazolium salts with easy catalyst/solvent recycling, whereas these reactions did not occur in common organic solvents, water or hydrophilic ionic liquids at all.

Practical method to recycle a chiral (salen)Mn epoxidation catalyst by using an ionic liquid

A practical recycling procedure for Jacobsen’s chiral (salen)MnIII epoxidation catalyst involving the use of the air- and moisture-stable ionic liquid [bmim][PF6] has been developed.

Efficient and practical polymeric catalysts for heterogeneous asymmetric dihydroxylation of olefins

Abstract High enantioselectivity (>99% ee) and reactivity in heterogeneous catalytic asymmetric dihydroxylation (AD) of olefins have been achieved using new polymeric cinchona alkaloids containing 1,4-bis(9- O -quininyl)phthalazine ((QN) 2 -PHAL), which can be synthesized more economically than their homogeneous analogue, 1,4-bis(9- O -dihydroquininyl)phthalazine ((DHQ) 2 -PHAL).

Hydrogenation of Arenes by Dual Activation: Reduction of Substrates Ranging from Benzene to C60 Fullerene under Ambient Conditions†

Catalytic hydrogenation of aromatic compounds is an important reaction which is useful for making key intermediates in organic chemistry and for the production of aromaticcontent-free fuels. More recently, there has been much interest in the potential for storage of molecular hydrogen, as an energy source, by catalytic hydrogenation of carboneous materials (e.g., fullerene and carbon nanotubes). Although the science of metal and metal-oxide-catalyzed arene hydrogenations have been significantly advanced since the original findings of Sabatier and Senderens, harsh conditions (high temperatures or pressures) are still required for the catalytic hydrogenation of aromatic compounds. The reduction of benzene requires harsher conditions compared to that of most other aromatic compounds because of its high stabilization energy resulting from aromaticity. The catalytic activity of heterogeneous noble metal catalysts for the hydrogenation of benzene decreases in the order of Rh>Ru>Pt>Ni>Pd. At low temperature palladium usually does not reduce a benzene ring, and palladium nanoparticles have been shown to be nearly inactive for the hydrogenation of benzene. It is well known that Lewis acids can activate aromatic compounds and that Pd/C can be used to activate molecular hydrogen. We wondered if these two types of activation could work cooperatively for the hydrogenation of arenes by the novel ionic mechanism depicted in Scheme 1. Herein we report the highly efficient catalytic hydrogenation of benzene and other hydrocarbon-based aromatic compounds, including C60 fullerene, under ambient conditions (1 bar of H2 and RT) by simultaneous activation of molecular hydrogen and the aromatic substrate with Pd/C and a Lewis acidic ionic liquid [bmim]Cl-AlCl3 (1, bmim = 1-butyl-3-methylimidazolium; x of AlCl3 = 0.67 where x is the mole fraction of AlCl3), respectively. We initially examined the hydrogenation of benzene to cyclohexane in the presence of Lewis acids and palladium (Table 1). Pd/C (Table 1, entry 1) and palladium nanoparticles (Table 1, entries 2 and 3) were ineffective as catalysts for the hydrogenation reaction. Lewis acidic ionic liquid 1 was also ineffective for the hydrogenation reaction (Table 1, entry 4). However, when Lewis acidic ionic liquid 1 and Pd/C (0.5 and 0.02 equiv, respectively) were combined, the hydrogenation reaction went to completion (Table 1, entry 6). When the amounts of 1 and Pd/C were increased to 1 and 0.1 equivalents, respectively, benzene was hydrogenated at 1 bar of H2 (Table 1, entry 7). When 1 was replaced by AlCl3 (Table 1, entry 5), a mixture of unidentified condensation products were formed by the Scholl reaction. Subsequent to our encouraging results, we focused on the hydrogenation of bicyclic and polycyclic aromatic compounds (Table 2). These aromatic substrates are more reactive to hydrogenation than benzene, therefore all of the compounds were smoothly hydrogenated to completion under ambient conditions when both 1 and Pd/C were used in combination (Table 2, entries 3, 4, 7, 10, and 12). Here again, the hydrogenation reactions were ineffective in the absence of 1, even under higher pressures of H2 (Table 2, entries 1, 5, 8, and 11). When 1 was replaced with AlCl3, various inseparable condensation products (> 99%) were formed by the Scholl Scheme 1. Concept for a new cooperative catalytic system for the double activation of an arene and molecular hydrogen.