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3d-Metals have been identified as economic and sustainable alternatives to palladium, the frequently used metal in transition-metal-catalyzed cross-couplings. However, cobalt has long stood behind its neighboring elements, nickel and copper, in asymmetric radical couplings, owing to its high catalytic activity in the absence of ligands. Here, we disclose an asymmetric metallaphotoredox catalysis (AMPC) strategy for the dynamic kinetic resolution (DKR) of racemic heterobiaryls, which represents the first example of visible-light-induced, asymmetric radical couplings for the construction of axial chirality. This success can also be extended to the reductive cross-coupling variant featuring on more easily available feedstocks. The keys to these successes are the rational design of a sustainable AMPC system by merging asymmetric cobalt catalysis with organic photoredox catalysis and, perhaps more importantly, the identification of an efficient chiral polydentate ligand.

A photoredox/cobalt dual catalytic procedure has been developed that allows benzoylation of olefins. Here the photoredox catalyst effects the decarboxylation of α-ketoacids to form benzoyl radicals. After addition of this radical to styrenes, the cobalt catalyst abstracts a H-atom. Hydrogen evolution from the putative cobalt hydride intermediate allows a Heck-like aroylation without the need for a stoichiometric oxidant. Mechanistic studies reveal that electronically different styrenes lead to a curved Hammett plot, thus suggesting a change in product-determining step in the catalytic mechanism.

Grignard addition is one of the most important methods used for syntheses of alcohol compounds and has been known for over a hundred years. However, research on asymmetric catalysis relies on the use of organometallic nucleophiles. Here, we report the first visible-light-induced cobalt-catalyzed asymmetric reductive Grignard-type addition for synthesizing chiral benzyl alcohols (50 examples, up to 99% yield, and 99% ee). This methodology has the advantages of mild reaction conditions, good functionality tolerance, excellent enantiocontrol, the avoidance of mass metal wastes, and the use of precious metal catalysts. Kinetic realization studies suggested that migratory insertion of an aryl cobalt species into the aldehyde was the rate-determining step of the reductive addition reaction.

A dual catalytic decarboxylative allylation and benzylation method for the construction of new C(sp3)–C(sp3) bonds between readily available carboxylic acids and functionally diverse carbonate electrophiles has been developed. The new process is mild, operationally simple, and has greatly improved upon the efficiency and generality of previous methodology. In addition, new insights into the reaction mechanism have been realized and provide further understanding of the harnessed reactivity.

Organic molecules bearing acetoxy moieties are important functionalities in natural products, drugs, and agricultural chemicals. Synthesis of such molecules via transition metal-catalyzed C-O bond formation can be achieved in the presence of a carefully chosen directing group to alleviate the challenges associated with regioselectivity. An alternative approach is to use ubiquitous carboxylic acids as starting materials and perform a decarboxylative coupling. Herein, we report conditions for a photocatalytic decarboxylative C-O bond formation reaction that provides rapid and facile access to the corresponding acetoxylated products. Mechanistic investigations suggest that the reaction operates via oxidation of the carboxylate followed by rapid decarboxylation and oxidation by Cu(OAc)2.

While the divinyl cyclopropane Cope rearrangement is well-known, and has been broadly applied in synthesis, examples of the aryl vinyl cyclopropane Cope rearrangement are less common and generally limited in scope or reaction yield. The aryl vinyl cyclopropane Cope rearrangement gives access to the benzocycloheptene scaffold, which is present in a variety of naturally occurring and medicinally relevant products. Herein we report a method to obtain either of two regioisomeric benzocycloheptene products via an aryl vinyl cyclopropane Cope rearrangement, featuring additive-controlled regioselectivity. Mechanistic studies indicate a dynamic equilibration of cyclopropane stereoisomers, followed by rearrangement of the cis diastereomer.

A dual catalytic decarboxylative allylation and benzylation method for the construction of new C(sp3)–C(sp3) bonds between readily available carboxylic acids and functionally diverse carbonate electrophiles has been developed. The new process is mild, operationally simple, and has greatly improved upon the efficiency and generality of previous methodology. In addition, new insights into the reaction mechanism have been realized and provide further understanding of the harnessed reactivity., A dual catalytic decarboxylative allylation and benzylation method for the construction of new C(sp3)–C(sp3) bonds between readily available carboxylic acids and functionally diverse carbonate electrophiles has been developed.

A dual-catalytic strategy for the synthesis of enamides and enecarbamates directly from easily accessible and inexpensive amino acids has been realized. This mild and efficient protocol makes use of an organic photoredox catalyst and a cobaloxime catalyst to achieve decarboxylative elimination using hydrogen evolution to drive the oxidation. Thus, the reaction occurs without a stoichiometric oxidant or the forcing conditions previously employed in attempts to achieve similar eliminations.

Benzylic alkylation of enolates and acetylides has been achieved through the use of a decarboxylative benzylation strategy. Previous research in this area is often limited by the need for extended conjugation in the electrophiles that are coupled. Herein, we report that the use of 1,1'-bis(diphenylphosphino)ferrocene (dppf) ligand allows the coupling of simple benzyl electrophiles with enolates, while the use of XPhos ligand promotes the decarboxylative couplings of propiolates.

A method where an allyl alcohol is formed from a Tsuji-Trost allylation between a vinyl epoxide and an acyl containing nucleophile is described. Subsequently, a retro-Claisen condensation is utilized as a means of through-space anion relay. The anion relay results in the formation of a reactive carbanion and simultaneously activates an allylic alcohol toward intramolecular Tsuji-Trost cyclopropanation. Hence, in one pot, Tsuji-Trost allylation, retro-Claisen activation, and Tsuji-Trost cyclopropanation are combined to access synthetically useful vinyl cyclopropanes from vinyl epoxides using a mild and operationally simple procedure.

The (DIOP)rhodium-catalyzed hydroformylation of butadiene has been shown to give among the highest selectivities for formation of adipaldehyde, which is useful for the synthesis of nylon. Herein, isomerizing hydroformylation is shown to be a mechanism that is partially responsible for this selectivity and density functional theory studies are used to reveal the detailed pathway for the requisite alkene isomerization.

Decarboxylative elimination of easily accessible N-acyl amino acids to provide enamide and enecarbamate building blocks has been realized through the combination of an organophotoredox catalyst and copper acetate as the terminal oxidant. This operationally simple process utilizes inexpensive and readily available reagents without preactivation of the carboxylic acid. Enamides and enecarbamates are now accessible directly from N-acyl amino acids consequently improving upon the utility of Kochi’s oxidative decarboxylation of carboxylic acids.

A palladium-catalyzed decarboxylative coupling of enol carbonates with diarylmethyl electrophiles that are derived from secondary benzylic alcohols has been developed. This method allows the generation of a variety of β-diaryl ketones through an efficient and highly stereospecific coupling. In addition, detailed mechanistic insight into the coupling suggests that the reaction is a rare example of an intramolecular decarboxylative coupling that proceeds without crossover between reactants.

An interceptive decarboxylative allylation protocol has been developed utilizing pyrone as a C4 synthon. This palladium-catalyzed transformation difunctionalizes the pyrone moiety by in situ generation and activation of both the electrophile and nucleophile via a double decarboxylation pathway. Ultimately, allyl carbonates react smoothly with 2-carboxypyrone under mild reaction conditions to generate synthetically useful acyclic dienoic esters, forming carbon dioxide as the sole byproduct.

A new strategy to access conjugated allenynes via a decarboxylative coupling of propargyl esters of propiolates has been developed. In this process, allenyl-palladium intermediates are coupled with acetylides that are generated in situ to form the conjugated allenynes. Finally, the coupling is demonstrated to be highly stereospecific, providing a route to enantioenriched allenes.

Aminodecarboxylation of unactivated alkyl carboxylic acids has been accomplished utilizing an organic photocatalyst. This operationally simple reaction utilizes readily available carboxylic acids to chemoselectively generate reactive alkyl intermediates that are not accessible via conventional two-electron pathways. The organic radical intermediates are efficiently trapped with electrophilic diazo compounds to provide aminated alkanes.

A new method is developed for the synthesis of spirooxindoles from amines and isatins via C–H functionalization. The reaction leverages the tert-amino effect to form an enolate–iminium intermediate via [1,5]-hydride shift followed by cyclization. Interestingly the hydride migrates to the N atom of a C═N, which is atypical for hydride additions to imines.

A variety of ester enolate equivalents are generated in situ and undergo α-allylation in high yields via palladium-catalyzed decarboxylative allylation. The transformations are complete within very short reaction times under ambient conditions. Synthesis of α-allylated acyl derivatives provides access to other carboxylic acid and alcohol derivatives via acyl group substitution or reduction.

A novel process for continuous hydroformylation in CO2-expanded liquids (CXLs) is demonstrated using bulky phosphite ligands that are effectively retained in the stirred reactor by a nanofiltration membrane. The reactor is operated at 50°C with a syngas pressure of 0.6 MPa to avoid CO inhibition of reaction rate and selectivity. The nanofiltration pressure is provided by ∼3.2 MPa CO2 that expands the hydroformylation mixture and increases the H2/CO ratio in the CXL phase resulting in enhanced turnover frequency (∼340 h−1), aldehydes selectivity (>90%) and high regioselectivity (n/i ∼8) at nearly steady operation. The use of pressurized CO2 also reduces the viscosity in the CXL phase, thereby improving the mass-transfer properties. Constant permeate flux is maintained during the 50 h run with Rh leakage being less than 0.5 ppm. This technology concept has potential applications in homogeneous catalytic processes to improve resource utilization and catalyst containment for practical viability. © 2013 American Institute of Chemical Engineers AIChE J, 59: 4287–4296, 2013

Aminodecarboxylation of unactivated alkyl carboxylic acids has been accomplished utilizing an organic photocatalyst. This operationally simple reaction utilizes readily available carboxylic acids to chemoselectively generate reactive alkyl intermediates that are not accessible via conventional two-electron pathways. The organic radical intermediates are efficiently trapped with electrophilic diazo compounds to provide aminated alkanes.

We report the first example of a palladium-catalyzed decarboxylative dearomatization reaction that occurs via Pd-π-benzyl intermediates. In fact, the Pd-catalyzed decarboxylative cross-coupling reaction of benzyl enol carbonates can lead to either the dearomatized alicyclic ketones or α-monoarylated ketone products depending on the catalyst and ligand employed.

The palladium(0)-catalyzed, ligand-controlled, regioselective addition of diaryl acetonitrile pronucleophiles to propargylic carbonates is reported. Selective formation of either terminal 1,3-dienyl or propargylated products is proposed to arise from a change in reaction mechanism controlled by the denticity of the coordinating ligand.

We report the first example of a palladium-catalyzed decarboxylative dearomatization reaction that occurs via Pd-π-benzyl intermediates. In fact, the Pd-catalyzed decarboxylative cross-coupling reaction of benzyl enol carbonates can lead to either the dearomatized alicyclic ketones or α-monoarylated ketone products depending on the catalyst and ligand employed.

This is the peer reviewed version of the following article: Lang, S. B., O'Nele, K. M., Douglas, J. T. and Tunge, J. A. (2015), Dual Catalytic Decarboxylative Allylations of α-Amino Acids and Their Divergent Mechanisms. Chem. Eur. J., 21: 18589–18593. doi:10.1002/chem.201503644, which has been published in final form at http://doi.org/10.1002/chem.201503644. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Enantioenriched benzyl esters of propiolic acids undergo highly stereospecific decarboxylative coupling to provide 1,1-diarylethynyl methanes. This sp–sp3 coupling does not require strongly basic conditions or preformed organometallics and produces CO2 as the sole byproduct. Ultimately, this method results in the successful transfer of stereochemical information from secondary benzyl alcohols to generate enantioenriched tertiary diarylmethanes.

Using palladium-catalyzed decarboxylation, several cascade reactions of allyl and prenyl nitroalkanoates that lead to nitro-containing chemical building blocks are described. A nitronate Michael addition/Tsuji-Trost allylation cascade was developed, leading to functionally dense chemical building blocks. Likewise, a Tsuji-Trost/decarboxylative protonation sequence was developed for the synthesis of orthogonally functionalized 2° nitroalkanes. The latter method provides rapid access to the indolizidine core.

The palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium π-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively added to the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening.

By employing polymer bound bulky phosphite ligands (synthesized in house) in conjunction with polyimide membranes with appropriate molecular weight cutoff (MWCO), homogeneous Rh complexes were effectively retained in solution. Batch filtration of toluene-based solutions of various phosphorus ligands at constant pressure revealed that Rh complexed with polymer bound bidendate ligands (average molecular weight from 7000 to 10,000) were most effectively retained in solution with Rh leakage in the permeate being on the order of tens of ppb. Continuous filtration of toluene-based solutions containing dissolved polymer bound phosphite ligand at constant pressure and cell hold-up revealed that the Rh and P concentrations in the permeate were steady after several hours at less than 100 ppb. The higher initial concentrations of Rh and P in the permeate suggests the removal of perhaps unbound Rh and P from the initial mixture and also from the fraction of the polymers that are smaller than the MWCO of the membrane. Continuous 1-olefin hydroformylation with Rh complexed with polymer bound bidentate ligand (JanaPhos) was demonstrated at 50 °C in a stirred reactor fitted with a nanofiltration membrane. The catalyst complex was dissolved in a toluene-based reaction mixture and the feed solution (containing the substrate) and syngas were added continuously to maintain a constant flow rate and reactor pressure (3.0 MPa). At optimized conditions, the continuous run reached a steady state characterized by nearly 50% 1-olefin conversion, >98% aldehydes selectivity and a n/i ratio of 3.5, all of which remained constant even after 22 h. The Rh concentrations in the effluent were steady at approximately 20 ppb even after 22 h. The makeup Rh cost required to offset this loss during continuous processing ($0.004/lb aldehyde) exceeds the economic viability criterion ($0.013/lb aldehyde).

Catalytic Tsuji-Trost allylation has become a ubiquitous method for allylation of active methylene compounds.[1] While monoallylation products are typically formed, bisallylation of malonates and related ketone enolates leads to 1,6-dienes.[2] Given the utility of these 1,6-heptadienes in metal-catalyzed cycloisomerization reactions,[3] it would be beneficial if one could perform controlled bisallylation of less stabilized carbon nucleophiles. Unfortunatly, the one-pot bisallylation of other carbon nucleophiles is not well documented and usually requires harsh reaction conditions.[4] Moreover, the addition of two different allyl electrophiles to form unsymmetric 1,6-dienes in a one-pot operation is exceedingly rare.[5] Herein, we describe the development of an unsymmetric bisallylation of carbon nucleophiles and introduce catalytic deacylative allylation as a new strategy for tandem in situ generation and coupling of nucleophiles with allyl electrophiles (eq. 1).1 (1) We initiated our pursuit of a 3-component catalytic bisallylation reaction with the investigation of the deacylative allylation of nitroalkanes. Palladium-catalyzed allylation of nitroalkanes is a well-known, albeit non-trivial, process.[6,7] For example, monoallylation of nitromethane and primary nitroalkanes is complicated by competing bisallylation, so excess nitroalkane is often required to achieve monoallylation.[6] To begin, it was expected that we could take advantage of the ease of Tsuji-Trost allylation of highly stabilized nitroacetone nucleophiles to form allylated nitroketones (eq. 2).[8] Ballini and others have shown that simple nitroalkanes can be generated by deacylation of related nitroacetone derivatives.[9,10] Indeed performing Tsuji-Trost reactions in the presence of methanol and base proceeded with deacylation to selectively afford the monoallylated nitroalkanes (eq. 2). Similar treatment of the cyclic nitroketones likewise provided clean monoallylated products containing a pendant ester (eq. 3). Thus, clean one-pot monoallylation of nitroalkanes is possible using a deacylative Tsuji-Trost reaction.[8,11] (2) (3) Like most other deacylative (retro-Claisen) reactions,[12] our monoallylation reactions simply use the acyl group as an activating group that can be readily removed. However, we hypothesized that an allyl alcohol could deacylate the intermediate α-nitroketone to generate a nitronate anion and simultaneously generate an allyl acetate electrophile (eq. 1). Such a process would allow selective 3-component bisallylation using nitroacetones, an allyl acetate or carbonate, and an allylic alcohol (Scheme 1). Because allyl alcohols are relatively nonreactive toward palladium catalysts, the nitroacetone is expected to undergo rapid, selective Tsuji-Trost allylation with the allylic acetate. The resulting product nitroketone can undergo further allylation only via a deacylative allylation protocol. Ultimately, it was anticipated that these kinetically distinct steps could be combined to afford a 3-component unsymmetric bisallylation reaction. Scheme 1 Proposed bisallylation via deacylative allylation. The proposed coupling hinged on the hypothesis that an allyl alcohol could decacylate an α-nitroketone to generate an allyl acetate and a nitronate anion in situ. To begin, a model allylated nitroacetone was synthesized via Tsuji-Trost allylation and treated under a variety of reaction conditons. We were pleased to find that various primary allyl alcohol derivatives participated in Pd(PPh3)4-catalyzed deacylative allylation when 1 equivalent of Cs2CO3 base was added (Table 1). The allylation worked well for 2-hexenol as well as for cinnamyl alcohol, providing the linear allylation products 2b and 2c respectively. However, the coupling of cinnamyl alcohol did require a higher palladium catalyst loading of 10 mol % to achieve high yield. The higher catalyst concentration promotes the desired C-allylation of the intermediate nitronate at the expense of problematic vinylogous Hass-Bender oxidation of cinnamyl acetate to cinnamaldehyde.[7b,13] When crotyl alcohol was the coupling partner, a decrease in linear to branched selectively (3.8:1) was observed (entry 5, Table 1). A similar drop in regioselectivity was noted in the decarboxylative allylation of nitroacetates with crotyl alcohol derivatives.7b While the primary alcohol derivatives provided products in good to excellent yields, the deacylative allylation appears to have a steric limitation as a secondary allylic alcohol provided the desired product in poor yield (entry 6, Table 1). Table 1 Deacylative allylation scope Having demonstrated the requisite deacylative allylation, we turned our attention to the 3-component bisallylation of an α-nitroketone. Indeed treatment of α-methyl nitroacetone with an allyl carbonate (or acetate) and allyl alcohol selectively produced the desired nitroalkyl 1,6-diene 2c in high yield (eq. 4). Importantly, attempts to make the same product directly from nitroethane gave rise to a complex mixture of allylated products. Thus, deacylative allylation provides a unique avenue to unsymmetrically substituted 1,6-dienes. (4) Since the allyl carbonate provided a higher yield than the allyl acetate (eq 5), subsequent exploration of the reaction scope focused on coupling of allyl carbonate derivatives (Table 2).[14] A comparison of 2c (derived from allyl alcohol) and 2c′ (derived from cinnamyl alcohol) suggests that the allyl carbonate and alcohol partners can be reversed with little or no change in yield. With regard to the nitroketone substrate, α-phenyl and alkyl ketones were viable coupling partners (e.g. 2g and 2h, Table 2). Notably, an α-substituent with a base sensitive methyl ester moiety survived the reaction conditions leading to the functionalized products 2i–k. Importantly, the fact that the methyl ester remains intact shows that acyl substitution of nitroacetones by allyl alcohols is more facile than acyl substitution of esters. Lastly, a cyclic α-nitroketone provides the ring-opened nitroalkane with a pendant carboxylic acid (eq. 5). The carboxylic acid could be obtained in good yield, however it was necessary to convert it to the methyl ester to effect complete purification. Table 2 3-component unsymmetric bisallylation (5) While the bisallylation reactions described above utilize secondary nitroketones, trisallylation of a primary nitroketone is possible using 2 equivalents of an allyl carbonate and 1.3 equivalents of allyl alcohol (eq. 6). Thus, deacylative allylation allows the selective synthesis of 2m from 4 reactant molecules via the formation of 3 new C–C bonds in 81% yield. (6) In addition to the deacylative allylations of nitroketones, preliminary studies suggest that deacylative allylation will also allow intermolecular allylations of activated ketones (Table 3). We and others have previously developed decarboxylative allylations of ketones which proceed via formation of ketone enolates via C–C cleavage.1c–f While these reactions have significant utility, their use is somewhat hampered by the need to incorporate the electrophile and nucleophile in the same molecular entity prior to decarboxylative coupling. The allylations in Table 3 suggest that deacylative allylation may allow similar reactions to take place in an intermolecular fashion. Finally, ketone substrates that participate in deacylative allylation also allow selective 3-component coupling to form unsymmetric heptadienes (eq. 7). Table 3 Deacylative allylation of nitrophenyl acac. (7) In closing, we have developed deacylative allylation as a synthetic strategy for directly utilizing inexpensive, readily available allyl alcohols in electrophilic allylation reactions. Not only does deacylative allylation allow selective monoallylation of nitronates, but it also can be used in tandem with Tsuji-Trost allylation of stabilized nitronates to allow controlled synthesis of unsymmetric 1,6-dienes via 3-component coupling. Precise control of the kinetics of the couplings obviates many possible side reactions (e.g. homoallylation, allylation of alkoxide intermediates), leading to a highly selective bisallylation. Similar strategies are expected to allow the selective multi-component allylations of a wide variety of acyl pronucleophiles using allyl alcohols.

Syntheses of enantioenriched sulfides and sulfones via substitution of tertiary mesylate with thiolate nucleophile with modest to excellent success.

Palladium-catalyzed decarboxylative alpha-allylation of nitriles readily occurs with use of Pd(2)(dba)(3) and rac-BINAP. This catalyst mixture also allows the highly regiospecific alpha-allylation of nitriles in the presence of much more acidic alpha-protons. Thus, the reported method provides access to compounds that are not readily available via base-mediated allylation chemistries. Lastly, mechanistic investigations indicate that there is a competition between C- and N-allylation of an intermediate nitrile-stabilized anion and that N-allylation is followed by a rapid [3,3]-sigmatropic rearrangement.

Phenols provide a useful template for diversification via sequential hydroarylation reactions. Specifically, a protocol has been developed that begins with the hydroarylation of cinnamic acids by 3,5-dimethoxyphenol to produce dihydrocoumarins. This activated ester undergoes facile ring-opening with amines to form a C-N bond and regenerate a phenol. The resulting phenol can be further functionalized via a second hydroarylation reaction. Thus, in 3-4 steps, a phenol is coupled with a cinnamic acid, an amine, and a cinnamic or propiolic acid.

An interceptive decarboxylative allylation protocol has been developed utilizing pyrone as a C4 synthon. This palladium-catalyzed transformation difunctionalizes the pyrone moiety by in situ generation and activation of both the electrophile and nucleophile via a double decarboxylation pathway. Ultimately, allyl carbonates react smoothly with 2-carboxypyrone under mild reaction conditions to generate synthetically useful acyclic dienoic esters, forming carbon dioxide as the sole byproduct.

This is the peer reviewed version of the following article: Lang, S. B., O'Nele, K. M., Douglas, J. T. and Tunge, J. A. (2015), Dual Catalytic Decarboxylative Allylations of α-Amino Acids and Their Divergent Mechanisms. Chem. Eur. J., 21: 18589–18593. doi:10.1002/chem.201503644, which has been published in final form at http://doi.org/10.1002/chem.201503644. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Enantioenriched benzyl esters of propiolic acids undergo highly stereospecific decarboxylative coupling to provide 1,1-diarylethynyl methanes. This sp-sp(3) coupling does not require strongly basic conditions or preformed organometallics and produces CO2 as the sole byproduct. Ultimately, this method results in the successful transfer of stereochemical information from secondary benzyl alcohols to generate enantioenriched tertiary diarylmethanes.

A combination of photoredox and palladium catalysis has been employed to facilitate the room temperature decarboxylative allylation of recalcitrant α-amino and phenylacetic allyl esters. This operationally simple process produces CO2 as the only byproduct and provides direct access to allylated alkanes. After photochemical oxidation, the carboxylate undergoes radical decarboxylation to site-specifically generate radical intermediates which undergo allylation. A radical dual catalysis mechanism is proposed. Free phenylacetic acids were also allylated utilizing similar reactions conditions.

HuR, an RNA binding protein, binds to adenine- and uridine-rich elements (ARE) in the 3'-untranslated region (UTR) of target mRNAs, regulating their stability and translation. HuR is highly abundant in many types of cancer, and it promotes tumorigenesis by interacting with cancer-associated mRNAs, which encode proteins that are implicated in different tumor processes including cell proliferation, cell survival, angiogenesis, invasion, and metastasis. Drugs that disrupt the stabilizing effect of HuR upon mRNA targets could have dramatic effects on inhibiting cancer growth and persistence. In order to identify small molecules that directly disrupt the HuR-ARE interaction, we established a fluorescence polarization (FP) assay optimized for high throughput screening (HTS) using HuR protein and an ARE oligo from Musashi RNA-binding protein 1 (Msi1) mRNA, a HuR target. Following the performance of an HTS of ∼6000 compounds, we discovered a cluster of potential disruptors, which were then validated by AlphaLISA (Amplified Luminescent Proximity Homogeneous Assay), surface plasmon resonance (SPR), ribonucleoprotein immunoprecipitation (RNP IP) assay, and luciferase reporter functional studies. These compounds disrupted HuR-ARE interactions at the nanomolar level and blocked HuR function by competitive binding to HuR. These results support future studies toward chemical probes for a HuR function study and possibly a novel therapy for HuR-overexpressing cancers.

The retro-Claisen activation is applicable to primary and secondary benzyl alcohols and hetarylmethyl alcohols.

The method utilizes an aldehyde to activate nitriles toward α-allylation and prevent multiple allylations.

The palladium-catalyzed decarboxylative allylation of esters (I) leading to desired products (II) is reported.

Organoselenides catalyze the oxidation of halides by H2O2. Furthermore, these selenides catalyze the transfer of oxidized halogens from N-halosuccinimides to olefins and ketones. Thus, organoselenides catalyze oxidative halogenation reactions including halolactonization, α-halogenation of ketones, and allylic halogenation. The ability of selenium to undergo reversible 2e− oxidation–reduction chemistry facilitates halogenation through selenium-bound halogen intermediates.

CO2-expanded liquids (CXLs) are demonstrated to be effective reaction media for the catalytic hydroformylation of 1-octene. The performance of several rhodium catalysts, Rh(acac)(CO)2, Rh(acac)[P(OPh)3]2, Rh(acac)(CO)[P(OAr)3], and two phosphorous ligands, PPh3 and biphephos, was compared in neat organic solvents and in CXLs wherein more than 50% of the solvent volume is replaced with dense CO2 at relatively mild temperatures (30–90°C) and pressures ( 10), and aldehyde selectivity (∼90%) at the optimum CO2 content were either comparable to or better than values reported with other media and catalysts. Furthermore, the operating pressure (3.8 MPa) and temperature (60°C) for the CXL process are significantly milder than those reported for industrial hydroformylation processes. © 2006 American Institute of Chemical Engineers AIChE J, 2006