We report studies delineating the speciation, kinetics, and deoxygenation catalysis of phosphine-modified mixtures of B(C6F5)3 (BCF) and R3SiH. Combinations of BCF, a tertiary silane, and PAr3 generate the [H–B(C6F5)3–][R3Si–PAr3+] ion pair with conversions that depend on the silane and the phosphine. Smaller silanes enhance the ionization of the Si–H, as judged by heteronuclear NMR spectroscopy. Kinetic studies indicate that from BCF·PPh2(p-tol), formation of the borohydride/silyl phosphonium ion pair is α [Et3SiH]1[PPh2(p-tol)]0. DFT calculations confirmed the intermediacy of the weakly coordinated BCF···H–SiEt3 adduct en route to the silyl phosphonium. For the catalytic deoxygenation of anisole with Et3SiH, phosphine additives slow the reaction relative to phosphine-free conditions. In situ monitoring confirmed the presence of [H–B(C6F5)3–][Et3Si–PAr3+] at early times, but this slowly converts to [H–B(C6F5)3–][H3C–PAr3+], which is catalytically inactive. These data are reconciled by invoking a competitive demethylation of a key PhOMe(SiEt3)+ oxonium ion intermediate by H–B(C6F5)3– (productive) or phosphine (nonproductive).

Claisen rearrangements of allyl aryl ethers to generate enones bearing all carbon quaternary centers are accelerated by Ph3PAuNTf2 under mild conditions in good yields. Multiple C–C bond containing variants of the allyl fragment are viable, including alkylidenecyclopropanes, allenes, and alkynes, which generate all-carbon stereogenic centers substituted with vinyl cyclopropanes, 1,3-butadienyl, and allenyl substituents, respectively, for subsequent synthetic manipulation. With allyl phenyl ethers, the product of the [3,3] rearrangements can be trapped by a tandem [4 + 2] cycloaddition to generate complex molecular scaffolds from readily available, achiral starting materials.

A set of B(C6F5)3-catalyzed methods for diversification of unsaturated carbohydrate derived substrates is disclosed. Lewis acid cyclization, allylic alcohol hydrosilylation, and selective silyl group exchange is achieved with this single versatile catalyst. Allylic polyols and highly enriched (Z)-triols are obtained in high yields under a single-step protocol.Keywords: chemoselective deoxygenation; unsaturated polyols;

Results of kinetic experiments and quantum chemical computations on a series of platinum-promoted polycyclization reactions are described. Analyses of these results reveal a reactivity model that reaches beyond the energetics of the cascade itself, incorporating an ensemble of pre-cyclization conformations of the platinum–alkene reactant complex, only a subset of which are productive for bi- (or larger) cyclization and lead to products. Similarities and differences between this scenario, including reaction coordinates for polycyclization, for platinum- and enzyme-promoted polycyclization reactions are highlighted.

We report a functional synthetic model for studying the noncovalent networks (NCNs) required for complex protein functions. The model [2]-catenane is self-assembled from dipeptide building blocks and contains an extensive network of hydrogen bonds and aromatic interactions. Perturbations to the catenane cause compensating changes in the NCNs structure and dynamics, resulting in long-distance changes reminiscent of a protein. Key findings include the notion that NCNs require regions of negative cooperativity, or “frustrated” noncovalent interactions, as a source of potential energy for driving the response. We refer to this potential energy as latent free energy and describe a mechanistic and energetic model for responsive systems.

A B(C6F5)3-catalyzed method for the selective conversion of unsaturated carbohydrates to cyclopentanes and cyclopropanes is disclosed. Catalyst activation of tertiary silanes generates the ion pair [(C6F5)3B–H][ROSi2] whose components synergistically activate C–O bonds for diastereoselective C–C bond formation. Sila-THF cations are invoked as key intermediates facilitating carbocyclizations. Complex chiral synthons are thereby obtained in a single pot.

This paper reports the binding properties of tetrameric pseudo-peptide receptors for protonated cytidines. The receptors, which were isolated from a dynamic combinatorial chemistry (DCC) experiment, bind the analytes with affinities that depend on the presence or absence of excess acid, and with a stoichiometry that is both concentration and temperature dependent.

In situ generated benzyne reacts at room temperature with (triphos)Pt–CH3+ to form a five-coordinate π-complex (2) that is isolable and stable in solution. Thermolysis of 2 at 60 °C generates (triphos)Pt(o-tolyl)+ (3), which is the product of formal migratory insertion of CH3– onto the coordinated benzyne. The reaction of 2 with the acid Ph2NH2+ yields toluene at room temperature over the course of 8 h, while the same reaction with 3 only proceeds to 40% conversion over 2 days. These data indicate that the protonolysis of 2 does not proceed by CH3 migration onto benzyne to form 3 followed by protodemetalation. Instead, the data suggest either that protonation of 2 is first and is followed by H migration to yield a PtIVPh(Me) dication or that this latter species is generated by direct protonolysis of coordinated benzyne prior to reductive elimination of toluene.

A discontinuity exists between the importance of the cation–olefin reaction as the principal C–C bond forming reaction in terpene biosynthesis and the synthetic tools for mimicking this reaction under catalyst control; that is, having the product identity, stereochemistry, and functionality under the control of a catalyst. The main reason for this deficiency is that the cation–olefin reaction starts with a reactive intermediate (a carbocation) that reacts exothermically with an alkene to reform the reactive intermediate; not to mention that reactive intermediates can also react in nonproductive fashions. In this Account, we detail our efforts to realize catalyst control over this most fundamental of reactions and thereby access steroid like compounds. Our story is organized around our progress in each component of the cascade reaction: the metal controlled electrophilic initiation, the propagation and termination of the cyclization (the cyclase phase), and the turnover deplatinating events. Electrophilic Pt(II) complexes efficiently initiate the cation–olefin reaction by first coordinating to the alkene with selection rules that favor less substituted alkenes over more substituted alkenes. In complex substrates with multiple alkenes, this preference ensures that the least substituted alkene is always the better ligand for the Pt(II) initiator, and consequently the site at which all electrophilic chemistry is initiated. This control element is invariant. With a suitably electron deficient ligand set, the catalyst then activates the coordinated alkene to intramolecular addition by a second alkene, which initiates the cation–olefin reaction cascade and generates an organometallic Pt(II)-alkyl. Deplatination by a range of mechanisms (β-H elimination, single electron oxidation, two-electron oxidation, etc.) provides an additional level of control that ultimately enables A-ring functionalizations that are orthogonal to the cyclase cascade. We particularly focus on reactions that combine an initiated cyclization reaction with a turnover defining β-hydride elimination, fluorination, and oxygenation. These latter demetalation schemes lead to new compounds functionalized at the C3 carbon of the A-ring (steroid numbering convention) and thus provide access to interesting potentially bioactive targets. Progress toward efficient and diverse polycyclization reactions has been achieved by investing in both synthetic challenges and fundamental organometallic reactivity. In addition to an interest in the entrance and exit of the metal catalyst from this reaction scheme, we have been intrigued by the role of neighboring group participation in the cyclase phase. Computational studies have served to provide nuance and clarity on several key aspects, including the role (and consequences) of neighboring group participation in cation generation and stabilization. For example, these calculations have demonstrated that traversing carbonium ion transition states significantly impacts the kinetics of competitive 6-endo and 5-exo A-ring forming reactions. The resulting nonclassical transition states then become subject to a portion of the strain energy inherent to bicyclic structures, with the net result being that the 6-endo pathway becomes kinetically favored for alkene nucleophiles, in contrast to heteroatom nucleophiles which progress through classical transition states and preferentially follow 5-exo pathways. These vignettes articulate our approach to achieving the desired catalyst control.

Assaying a solid-phase library of histidine-containing β-hairpin peptides by a reactive tagging scheme in organic solvents selects for catalysts that reproduce the strategies used by His-based enzyme active sites to accelerate acyl- and phosphonyl-transfer reactions. Rate accelerations (krel) in organic solvents of up to 2.4 × 108 are observed.

Application of a tridentate NHC containing pincer ligand to Pt catalyzed cascade cyclization reactions has allowed for the catalytic, diastereoselective cycloisomerization of biogenic alkene terminated substrates to the their polycyclic counterparts.

The combination of the N-based pincer ligand PyBOX with Pt2+ leads to new catalysts for the enantioselective cycloisomerization of dienyl- and trienyl-ols. The mechanistic combination of electrophilic cyclization followed by rapid protodemetalation is surprising and leads to a powerful construct for developing new reactions.Keywords: cycloisomerization; electrophilic catalysis; platinum; protodemetalation

An enantioselective ring-expanding cycloisomerization of 1,5-enynes bearing a cyclopropylidene moiety has been developed. This methodology provides a new approach to bicyclo[4.2.0]octanes, a structural motif present in many biologically active natural products.

A reactive tagging methodology was used to select the species most reactive to an acylation reagent from a solid phase library of beta hairpin peptides. Hits bearing an electron-rich aromatic residue across strand from a reactive histidine were found to competitively become N-acylated. In addition to displaying rapid N-acylation rates the hit peptide was additionally deacylated in the presence of a nucleophile, thus closing a putative catalytic cycle. Variants of the hit peptide were studied to elucidate both the magnitude (up to 18000-fold over background, kcat/kuncat = 94000000, or 45-fold over Boc-histidine methyl ester) and mechanism of acyl transfer catalysis. A combination of CH–π, cation–π and HisH+–O interactions in the cationic imidazole transition state is implicated in the rate acceleration, in addition to the fidelity of the beta hairpin fold. Moreover, NMR structural data on key intermediates or models thereof suggest that a key feature of this catalyst is the ability to access several different stabilizing conformations along the catalysis reaction coordinate.

A method for the selective transamidation of the 3-oxo sub-family of N-acyl homoserine lactones (3-oxo-AHLs) under physiologically relevant conditions has been developed. The reaction has the potential to serve as a strategy for selective knockdown of key autoinducers in a multicellular environment.

Herein we describe the screening and subsequent optimization of peptide catalysts for ester activation. A combinatorial methodology using dye-tagged substrate analogs is described for determining which components of a His-containing helical library display acyl transfer activity. We found that helical peptides display high activity, and amino acids that reinforce this propensity are advantaged. Through this approach two new structural motifs have been discovered that are capable of activating esters in organic solvents. Unlike most acyl transfer catalysts functioning in organic solvents, these catalysts are histidine- rather than N-alkyl histidine-based. Longer peptides with localization of reactive groups on the C-terminal end of the peptide were found to further enhance catalytic activity up to ∼2800-fold over background.

Reaction of a complex Pt organometallic species with electrophilic halogen sources in the presence of X– ligands changes the mechanism of reductive elimination from a concerted reductive coupling type to an SN2 type reductive elimination. In the absence of the added X– ligand the reductive elimination is stereoretentive; in its presence, the process is stereoinvertive. This selectivity hinges on the reactivity of a key five-coordinate Pt(IV) intermediate with the X– ligand.

(Xylyl-phanephos)Pt2+ in combination with XeF2 mediates the consecutive diastereoselective cation-olefin cyclization/fluorination of polyene substrates. Isolated yields were typically in the 60–69% range while enantioselectivities reached as high as 87%. The data are consistent with a stereoretentive fluorination of a P2Pt-alkyl cation intermediate.

In light of diminishing petroleum feedstocks, there is significant interest in developing carbohydrate defunctionalization reactions. In this context we have examined the use of iridium pincer catalysts for the hydrosilylative reduction of sugars, and we report herein complete reduction of silyl-protected glucose to a mixture of hexane isomers.

Quantum chemical calculations are used to explore the origins of regioselectivity for proton-, Pt(II)- and Pd(II)-promoted cyclizations of 1,5-hexadienes, 5-aminoalkenes, and allylic acetimidates. The strain associated with achieving carbonium ion-like transition state geometries is shown to be a key factor in controlling 5-exo vs. 6-endo selectivity.

While investigating the gold(I)-catalyzed intramolecular hydroarylation of allenes, the structure of a digold-vinyl intermediate was verified. Instead of the previously proposed geminally diaurated binding mode for the digold when L = PPh3, an alternative σ–π-diauration mode was observed with the bulkier ligand L = P(o-Tol)3. Reactivity studies indicate the σ–π-mode has a disproportionate effect on protonolysis reactivity.

A series of phosphine–Pt2+-catalysts is reported, which enable the oxidative cascade cyclization of poly-alkene substrates. When the terminus is appropriately arranged and a catalyst reoxidation mediator is included, several polycyclic all carbon skeletons can be obtained. In one example, a chiral P2Pt+2 catalyst provides up to 79% ee.

Thiourea catalysts accelerate aminolysis of N-acyl homoserine lactones (AHLs), molecules integral to bacterial quorum sensing. The catalysts afford rate enhancement of up to 10 times the control in CD3CN. Mild catalysis in other polar aprotic solvents is still observed, while the activity is attenuated in polar protic solvents.

Oxidatively induced halogenation and oxygenation reactions of complex Pt(II) organometallic complexes provide a route to a catalytic cation–olefin cyclization/oxygenation sequence. The evidence suggests the involvement of a Pt(III) intermediate, which reacts homolytically to generate an organic free radical that can be intercepted by O2 followed by the Russell breakdown of the resulting alkyl peroxy radicals or by CuX2 (X = Br, Cl) to yield the X–R product.

Gold(I) catalysts effectively promote the Cope rearrangement of acyclic 1,5-dienes bearing a terminal cyclopropylidene. When this methodology is applied to cyclic substrates an unexpected transformation occurs, resulting in the formation of a tricyclic compound incorporating a bicyclo[4.2.0]oct-1-ene core, a portion of which is found in a number of natural products. Density functional theory calculations (M06 and M06-2X) reveal insight into the mechanism and thermodynamics of this unique transformation.

Under acidic conditions (50 equiv of TFA), combinations of hydrazide A-B monomers self-assemble into octameric [2]-catenanes with high selectivity for [132]2, where 1 is a d-Pro-X (X = Aib, Ac4c, Ac6c, l-4-Cl-PhGly)-derived monomer and 2 is an l-Pro′-l-arylGly (Pro′ = Pro, trans-F-Pro, trans-HO-Pro, aryl = naphthyl, phenyl)-derived monomer. Five different combinations of monomers were studied by X-ray crystallography. In each case, the unique aryl glycine unit is located in the core of the structure where the aryl ring templates a CH−π–CH sandwich. Analysis of metrical parameters indicates that this core region is highly conserved, while the more peripheral zones are flexible. 1H NMR spectroscopy indicate that the solid-state structures are largely retained in solution, though several non-C2-symmetric compounds have a net C2-symmetry that indicates accessible dynamic processes. Catenane dynamic processes were additionally probed through H/D exchange, with the core being inflexible relative to the peripheral structure. Mass spectrometry was utilized to identify the constitutional isomerism in the minor asymmetric [1523] catenanes.

Mechanistic investigation of gold(I)-catalyzed intramolecular allene hydroalkoxylation established a mechanism involving rapid and reversible C–O bond formation followed by turnover-limiting protodeauration from a mono(gold) vinyl complex. This on-cycle pathway competes with catalyst aggregation and formation of an off-cycle bis(gold) vinyl complex.

Using dynamic combinatorial chemistry, mixtures of dipeptide monomers were combined to probe how the structural elements of a family of self-assembled [2]-catenanes affect their equilibrium stability versus competing non-catenated structures. Of particular interest were experiments to target the effects of CH−π interactions, inter-ring hydrogen bonds, and β-turn types on [2]-catenane energetics. The non-variant core of the [2]-catenane was shown only to adopt type II′ and type VIII turns at the β-2 and β-4 positions, respectively. Monomers were designed to delineate how these factors contribute to [2]-catenane equilibrium speciation/stability. Dipeptide turn adaptation studies, including three-component dynamic self-assembly experiments, suggested that stability losses are localized to the mutated sites, and that the turn types for the core β-2 and β-4 positions, type II′ and type VIII, respectively, cannot be modified. Mutagenesis studies on the core Aib residue involved in a seemingly key CH−π–CH sandwich reported on how CH−π interactions and inter-ring hydrogen bonds affect stability. The interacting methyl group of Aib could be replaced with a range of alkyl and aryl substituents with monotonic affects on stability, though polar heteroatoms were disproportionately destabilizing. The importance of a key cross-ring H-bond was also probed by examining an Aib for l-Pro variant. Inductive affects and the effect of CH donor multiplicity on the core proline−π interaction also demonstrated that electronegative substituents and the number of CH donors can enhance the effectiveness of a CH−π interaction. These data were interpreted using a cooperative binding model wherein multiple non-covalent interactions create a web of interdependent interactions. In some cases, changes to a component of the web lead to compensating effects in the linked interactions, while in others, the perturbations create a cascade of destabilizing interactions that lead to disproportionate losses in stability.

The electrophilic fluorination of several (triphos)Pt-aryl+ establishes the first example of aryl–F coupling from a Pt center.

Mixtures of dipeptide monomers create stereochemically and constitutionally complex dynamic libraries of potential receptors. When (−)-cytidine was utilized as guest an 84-membered cyclic host was amplified (70–175 fold) from a nearly undetectable initial concentration. Only the specified diastereomeric combination of the two chiral building blocks yielded a dynamic library from which the macrocyclic receptor could be amplified.

A Pd(II)-catalyzed homo-coupling of Au(I)-aryls is reported. The reaction is driven by a Pd(0)/Au(I) redox reaction that generates a gold mirror and Pd(II), and illustrates one of the challenges for developing dual catalytic Au–Pd systems.

The photoreduction of glucosyl halides to generate glucosyl radicals has been investigated to probe the nature of the photoredox cycle. Amine (the reductant) and catalyst concentration affect the reaction rate at low concentrations but exhibit saturation at higher concentrations. Water and hydrophobic catalysts were found to significantly increase the conversion efficiency.

The oxidative addition of secondary electrophiles to Pd(0) is significantly accelerated by anomeric effects. In contrast to cyclohexyl bromide, acetobromo-α-d-glucose undergoes invertive oxidative addition to tris(triethylphosphine)palladium(0) to generate a stable, isolable organometallic complex, Pd(PEt3)2(Br)(AcO-β-glucose), which has been fully characterized but is prone to β-acetoxy elimination.

A high-yielding fluorination of (triphos)Pt–R+ has been achieved using an array of F+ sources, with XeF2 yielding R–F in minutes. The C–F coupling proved to be a stereoretentive process that proceeds via a concerted reductive elimination from a putative dicationic Pt(IV) center. The larger the steric congestion of the (triphos)Pt–Csp3+ complexes, the more efficient the fluorination, seemingly a result of sterically accelerated C–F reductive elimination along with simultaneous deceleration of its competing processes (β-H elimination).

In traditional Wacker processes, Pd(II) becomes reduced to Pd(0) after C−O bond formation and β-H elimination and must be reoxidized to the electrophilic Pd(II) state via a stoichiometric oxidant such as benzoquinone, CuCl2, or O2. We report herein a Pt-catalyzed Wacker-type process that regenerates the electrophilic Pt2+ state by H− abstraction from a [Pt]-H using an oxocarbenium ion generated from an acetal or ketal under acidic conditions.

Thiol−thioester exchange was found to readily generate libraries of cyclic thiodepsipeptides under thermodynamic control, which will enable their use in a variety of dynamic combinatorial chemistry assays. The kinetic determinants of macrocycle formation and the role of amino acid structure on the reaction dynamics are discussed.

Cationic gold(I) phosphite catalysts activate allenes for epoxide cascade reactions. The system is tolerant of numerous functional groups (sulfones, esters, ethers, sulfonamides) and proceeds at room temperature in dichloromethane. The cyclization pathway is sensitive to the substitution pattern of the epoxide and the backbone structure of the A-ring. It is capable of producing medium-ring ethers, fused 6-5 bicyclic, and linked pyran-furan structures. The resulting cycloisomers are reminiscent of structures found in numerous polyether natural products.

The resting state of the gold(I)-catalyzed hydroarylation of 1 changes in the presence of Ag+, with silver free catalysts resting at the dinuclear gold structure 5 and Ag+ containing solutions resting at a heteronuclear species like 6. Adventitious Ag+ (typically from LAuCl activation) can therefore intercept key organogold intermediates and effect the catalysis even when it does not effect the reaction in Au free control experiments.

trans-Ir(PMe3)2(CO)Cl reacts with acetobromo-α-d-glucose in the presence of AIBN to give a 1.3:1 ratio of the retentive and invertive oxidative addition products, each of which were characterized by crystallography. Reaction with α-d-glucopyranosyl bromide tetrabenzoate gave a 2:1 α:β ratio, while acetobromo-α-d-mannose gave a 5:1 ratio of retentive to invertive products.

In situ generated [(PPP)Pt][BF4]2 (PPP = triphos) catalyzes the cycloisomerization of 1,6-enyne-ols by initiative π-activation of the alkyne. This generates an isolable cationic Pt-alkenyl species, which subsequently participates in turnover-limiting protonolysis with in situ generated acid. This latter reactivity contrasts cationic Pt-alkyls, which are more difficult to protonolyze. Mechanistic studies on isolated Pt-alkenyls and deuterium labeling helped to elucidate the mechanistic details.

Carbonylruthenium tetrakis(pentafluorophenyl)porphyrin Ru(TPFPP)(CO) was utilized for the aerobic oxidation of alcohols. The in situactivation of the catalyst with mCPBA provided a species capable of catalyzing the oxidation of alcohols with molecular oxygen. The choice of solvent and additive was crucial to obtaining high activity and selectivity. Secondary aromatic alcohols were oxidized in the presence of the ruthenium porphyrin and tetrabutyl ammonium hydroxide in the solvent bromotrichloromethane, enabling high yields to be achieved (up to 99%). Alternatively, alcohols could be oxidized in perfluoro(methyldecalin) with the ruthenium porphyrin at higher temperatures (140 °C) and elevated oxygen pressures (50 psi).

Reaction of (dppe)MCl2 (dppe = 1,2-bis(diphenylphosphino)ethane) with 2-(N-phenyliminomethyl)phenol leads to air-stable (dppe)M(N,O) chelates (M = Pd, 1a; M = Pt, 1b). The N-4-methylphenyl derivative of 1a has been characterized by X-ray analysis. The N,O ligands are kinetically labile and exchange occurs in solution in the presence of other salicylaldimines. In the presence of anilines, a metal-mediated imine exchange process occurs. Hammett analysis reveals that the platinum complexes are sensitive to the electronics at N but not at O. Electron donating groups on the N-aryl ring stabilize the metal complex.

Functionalisation of the second coordination sphere of a molecularly imprinted Pd complex was achieved by localising within the polymeric cavity a crown-ether receptor capable of altering the catalytic activity of the reactive site.

We report herein an efficient synthesis of a series of chelating bis(aryloxide) ligands that can be diverged at a late stage to generate a variety of structures. Based on structural differences between linked and unlinked analogs of six-coordinate acid–base adducts of (ArO)2TiCl2(dmpe), a hypothesis predicted that a difference between the two structure types would be apparent when the compounds shuttled between four- and six-coordinate structures. Comparing their efficiencies in the Lewis acid accelerated Diels–Alder reaction, however, did not support this notion.We report an efficient synthesis of a series of chelating bis(aryloxide) ligands that can be diverged at a late stage to generate a variety of structures. Based on structural differences between linked and unlinked analogs of six-coordinate acid–base adducts of (ArO)2TiCl2(dmpe), a hypothesis predicted that a difference between the two structure types would be apparent when the compounds shuttled between four- and six-coordinate structures. Comparing their efficiencies in the Lewis acid accelerated Diels–Alder reaction, however, did not support this notion.

When diphosphine rhodium(I) hydrogenation catalysts are incorporated into organic polymers that contain a permanent pore structure, they can be utilized in fluorous biphase solvent systems, where reaction rates increase with the fluorous content of the solvent.

Equimolar mixtures of NMRP and ATRP initiators lead to polystyrene that is unimodal by GPC; the mechanism of action most consistent with the data suggests that under the reaction conditions, TEMPO and Cl end groups scramble rapidly relative to the propagation rate, and result in a single type of polymer chain.

While investigating the gold(I)-catalyzed intramolecular hydroarylation of allenes, the structure of a digold-vinyl intermediate was verified. Instead of the previously proposed geminally diaurated binding mode for the digold when L = PPh3, an alternative σ–π-diauration mode was observed with the bulkier ligand L = P(o-Tol)3. Reactivity studies indicate the σ–π-mode has a disproportionate effect on protonolysis reactivity.

Carbonylruthenium tetrakis(pentafluorophenyl)porphyrin Ru(TPFPP)(CO) was utilized for the aerobic oxidation of alcohols. The in situactivation of the catalyst with mCPBA provided a species capable of catalyzing the oxidation of alcohols with molecular oxygen. The choice of solvent and additive was crucial to obtaining high activity and selectivity. Secondary aromatic alcohols were oxidized in the presence of the ruthenium porphyrin and tetrabutyl ammonium hydroxide in the solvent bromotrichloromethane, enabling high yields to be achieved (up to 99%). Alternatively, alcohols could be oxidized in perfluoro(methyldecalin) with the ruthenium porphyrin at higher temperatures (140 °C) and elevated oxygen pressures (50 psi).

A reactive tagging methodology was used to select the species most reactive to an acylation reagent from a solid phase library of beta hairpin peptides. Hits bearing an electron-rich aromatic residue across strand from a reactive histidine were found to competitively become N-acylated. In addition to displaying rapid N-acylation rates the hit peptide was additionally deacylated in the presence of a nucleophile, thus closing a putative catalytic cycle. Variants of the hit peptide were studied to elucidate both the magnitude (up to 18000-fold over background, kcat/kuncat = 94000000, or 45-fold over Boc-histidine methyl ester) and mechanism of acyl transfer catalysis. A combination of CH–π, cation–π and HisH+–O interactions in the cationic imidazole transition state is implicated in the rate acceleration, in addition to the fidelity of the beta hairpin fold. Moreover, NMR structural data on key intermediates or models thereof suggest that a key feature of this catalyst is the ability to access several different stabilizing conformations along the catalysis reaction coordinate.

Herein we describe the screening and subsequent optimization of peptide catalysts for ester activation. A combinatorial methodology using dye-tagged substrate analogs is described for determining which components of a His-containing helical library display acyl transfer activity. We found that helical peptides display high activity, and amino acids that reinforce this propensity are advantaged. Through this approach two new structural motifs have been discovered that are capable of activating esters in organic solvents. Unlike most acyl transfer catalysts functioning in organic solvents, these catalysts are histidine- rather than N-alkyl histidine-based. Longer peptides with localization of reactive groups on the C-terminal end of the peptide were found to further enhance catalytic activity up to ∼2800-fold over background.

Thiourea catalysts accelerate aminolysis of N-acyl homoserine lactones (AHLs), molecules integral to bacterial quorum sensing. The catalysts afford rate enhancement of up to 10 times the control in CD3CN. Mild catalysis in other polar aprotic solvents is still observed, while the activity is attenuated in polar protic solvents.

Using mass spectrometry coupled with LC analysis we report evidence of diastereomer dependent fragmentation and oligomerization reactions in the ionization of acyl-hydrazone-based libraries of cyclic oligomers. These effects can significantly affect the accuracy of MS-based quantitations, but also provide a venue for examining ionization effects in dynamic combinatorial libraries (DCLs).

A diastereoselective, gold-catalyzed cascading cycloisomerization of alkylidene cyclopropane bearing 1,5-enynes that terminates in a cyclo-addition of aldehydes has been developed. This diastereoselective reaction provides convergent access to novel polycyclic molecular structures (18 examples), and tolerates a diverse scope of aldehydes. Mechanistic studies reveal that the catalytic cycle rests at a digold off-cycle intermediate, one of which was isolated.

This paper reports the binding properties of tetrameric pseudo-peptide receptors for protonated cytidines. The receptors, which were isolated from a dynamic combinatorial chemistry (DCC) experiment, bind the analytes with affinities that depend on the presence or absence of excess acid, and with a stoichiometry that is both concentration and temperature dependent.

A series of phosphine–Pt2+-catalysts is reported, which enable the oxidative cascade cyclization of poly-alkene substrates. When the terminus is appropriately arranged and a catalyst reoxidation mediator is included, several polycyclic all carbon skeletons can be obtained. In one example, a chiral P2Pt+2 catalyst provides up to 79% ee.

The electrophilic fluorination of several (triphos)Pt-aryl+ establishes the first example of aryl–F coupling from a Pt center.

A Pd(II)-catalyzed homo-coupling of Au(I)-aryls is reported. The reaction is driven by a Pd(0)/Au(I) redox reaction that generates a gold mirror and Pd(II), and illustrates one of the challenges for developing dual catalytic Au–Pd systems.

Quantum chemical calculations are used to explore the origins of regioselectivity for proton-, Pt(II)- and Pd(II)-promoted cyclizations of 1,5-hexadienes, 5-aminoalkenes, and allylic acetimidates. The strain associated with achieving carbonium ion-like transition state geometries is shown to be a key factor in controlling 5-exo vs. 6-endo selectivity.

Mixtures of dipeptide monomers create stereochemically and constitutionally complex dynamic libraries of potential receptors. When (−)-cytidine was utilized as guest an 84-membered cyclic host was amplified (70–175 fold) from a nearly undetectable initial concentration. Only the specified diastereomeric combination of the two chiral building blocks yielded a dynamic library from which the macrocyclic receptor could be amplified.

A method for the selective transamidation of the 3-oxo sub-family of N-acyl homoserine lactones (3-oxo-AHLs) under physiologically relevant conditions has been developed. The reaction has the potential to serve as a strategy for selective knockdown of key autoinducers in a multicellular environment.