Showing papers in "Accounts of Chemical Research in 2004"
TL;DR: The contributions of this laboratory to converting enzymatic enamines, and in some cases imines, into a versatile catalytic asymmetric strategy powered by small organic molecules are summarized.
Abstract: Enamines and imines have long been recognized as key intermediates in enzyme catalysis, particularly within a class of enzymes organic chemists would very much like to emulate, the aldolases. Here we summarize the contributions of this laboratory to converting enzymatic enamines, and in some cases imines, into a versatile catalytic asymmetric strategy powered by small organic molecules.
1,192 citations
TL;DR: Sterically less encumbered ligand designs have been developed to improve reaction rates, and metallocene and nonmetallocene chiral lanthanide complexes have been synthesized for enantioselective hydroamination.
Abstract: Organolanthanides are highly efficient catalysts for inter- and intramolecular hydroamination of various C−C unsaturations such as alkenes, alkynes, allenes, and dienes. Attractive features of organolanthanide catalysts include very high turnover frequencies and excellent stereoselectivities, rendering this methodology applicable to concise synthesis of naturally occurring alkaloids and other polycyclic azacycles. The general hydroamination mechanism involves turnover-limiting C−C multiple bond insertion into the Ln−N bond, followed by rapid protonolysis by other amine substrates. Sterically less encumbered ligand designs have been developed to improve reaction rates, and metallocene and nonmetallocene chiral lanthanide complexes have been synthesized for enantioselective hydroamination.
935 citations
TL;DR: After a long and difficult search, stable carbenes are finally isolated, characterized, and in the chemist's hands, and the experiments of decades have finally resulted in successful enantioselective benzoin condensations and enantiOSElective intramolecular Stetter reactions.
Abstract: The coenzyme thiamine (vitamin B1), a natural thiazolium salt, is involved in many enzymatic catalyses. Since it has been proposed that the catalytically active species of these reactions is a nucleophilic carbene, many chemists have tried to perform enzyme mimetic asymmetric carbene catalysis. After a long and difficult search, stable carbenes are finally isolated, characterized, and in the chemist's hands. The experiments of decades have finally resulted in successful enantioselective benzoin condensations and enantioselective intramolecular Stetter reactions as important examples of carbene catalyzed asymmetric nucleophilic acylation processes.
922 citations
TL;DR: The changes of some interesting properties in different colloidal semiconductor nanoparticles, such as the electronic relaxation rates as spherical nanoparticles change to nanorods, and the changes in the structure or size of very small nanoparticles upon adsorbing strongly bound molecules are described.
Abstract: As the size of material becomes equal to or falls below the nanometer length scale that characterizes the motion of its electrons and thus its properties, the latter become sensitive not only to the size but also to the shape and composition of the particles. In this Account, we describe the changes of some interesting properties in different colloidal semiconductor nanoparticles, such as the electronic relaxation rates as spherical nanoparticles change to nanorods, and the changes in the structure or size of very small nanoparticles upon adsorbing strongly bound molecules. We have also determined and explained the difference in the interfacial crossing rates of electrons and holes in a composite nanostructure.
847 citations
TL;DR: The key features that have opened up this new field have been ultrahigh-resolution FT-ICR mass analysis, specifically, the capability to resolve species differing in elemental composition by C(3) vs SH(4) (i.e., 0.0034 Da), thereby extending to >900 Da the upper limit for unique assignment of elemental composition based on accurate mass measurement.
Abstract: Ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry has recently revealed that petroleum crude oil contains heteroatom-containing (N,O,S) organic components having more than 20 000 distinct elemental compositions (CcHhNnOoSs). It is therefore now possible to contemplate the ultimate characterization of all of the chemical constituents of petroleum, along with their interactions and reactivity, a concept we denote as “petroleomics”. Such knowledge has already proved capable of distinguishing petroleum and its distillates according to their geochemical origin and maturity, distillation cut, extraction method, catalytic processing, etc. The key features that have opened up this new field have been (a) ultrahigh-resolution FT-ICR mass analysis, specifically, the capability to resolve species differing in elemental composition by C3 vs SH4 (i.e., 0.0034 Da); (b) higher magnetic field to cover the whole mass range at once; (c) dynamic range extension by external mass filtering; and ...
683 citations
TL;DR: Contributions from this laboratory to the revitalized interest in asymmetric enamine catalysis are summarized in this Account.
Abstract: The chemistry of preformed enamines, especially their use as enolate equivalents, has been a well-investigated area of research since the early 1950s. However, enamine catalysis, the catalysis of carbonyl transformations via enamine intermediates by using primary and secondary amines as catalysts, has only been fully appreciated as a powerful strategy for asymmetric synthesis since the beginning of this century. Contributions from this laboratory to the revitalized interest in asymmetric enamine catalysis are summarized in this Account.
643 citations
TL;DR: The direct catalytic asymmetric addition of unmodified carbonyl compounds to preformed or in situ-generated imines has emerged as a promising new route to optically enriched alpha- and beta-amino acid derivatives, beta-lactams, and 1,2- and gamma-aminos alcohols.
Abstract: The direct catalytic asymmetric addition of unmodified carbonyl compounds to preformed or in situ-generated imines has emerged as a promising new route to optically enriched alpha- and beta-amino acid derivatives, beta-lactams, and 1,2- and gamma-amino alcohols. The direct catalytic asymmetric Mannich reactions are mediated by small organometallic and organic amine catalysts that can achieve levels of selectivity similar to those possible with natural enzymes. The different small-molecule catalysts described here are complementary in their applications. They also complement each other in syn or anti selectivity of the direct asymmetric Mannich reaction. In this Account, we highlight the recent developments in and contributions to this research.
641 citations
TL;DR: The development and application of chiral phase-transfer catalysis (PTC) for the enantioselective synthesis of optically active alpha-amino acid derivatives using achiral Schiff base esters developed in the author's laboratory and by others is reviewed.
Abstract: The development and application of chiral phase-transfer catalysis (PTC) for the enantioselective synthesis of optically active α-amino acid derivatives using achiral Schiff base esters developed in the author's laboratory and by others is reviewed. Phase-transfer catalysts derived from the Cinchona alkaloids have been exploited as inexpensive and attractive organocatalysts in the chiral PTC process. The recent evolution and use of these and other catalytic systems is described.
634 citations
TL;DR: These studies demonstrate the potential of modified cinchona alkaloids as broadly useful chiral organic catalysts for asymmetric synthesis.
Abstract: Insights into the role played by modified cinchona alkaloids in the Sharpless asymmetric dihydroxylation inspired studies of modified cinchona alkaloids as chiral organic catalysts that lead to the development of highly enantioselective alcoholyses for the desymmetrization, kinetic resolution, and dynamic kinetic resolution of cyclic anhydrides, cyanation of ketones, and 1,4-addition of thiols to cylic enones. These studies demonstrate the potential of modified cinchona alkaloids as broadly useful chiral organic catalysts for asymmetric synthesis.
511 citations
TL;DR: Significant milestones in achieving controlled free radical homopolymerization and block copolymerization of water-soluble and amphiphilic monomers including nonionic, cationic, anionic, and zwitterionic species are recounted.
Abstract: Reversible addition−fragmentation chain transfer (RAFT) polymerization has been the focus of intensive research over the past few years since this methodology allows the synthetic tailoring of macromolecules with complex architectures including block, graft, comb, and star structures with predetermined molecular weight, terminal functionality, and narrow molecular weight distribution. In this paper we recount significant milestones in achieving controlled free radical homopolymerization and block copolymerization of water-soluble and amphiphilic monomers including nonionic, cationic, anionic, and zwitterionic species. It is shown that under aqueous conditions, control of homopolymerization and further blocking to extend the molecular weight or to produce precisely structured block copolymers require not only careful selection of reagents (initiator, chain transfer agent, and monomer) but also regulation or elimination of hydrolysis of the ω-terminal thiocarbonylthio functionality. The technological potent...
506 citations
TL;DR: O-Alkyl N-anthracenylmethyl derivatives of Cinchona alkaloids can function as enantioselective phase-transfer catalysts, resulting in the development of a new highly selective catalyst and opening up the potential of further expanding the range of alpha-amino acid derivatives that can be prepared.
Abstract: O-Alkyl N-anthracenylmethyl derivatives of Cinchona alkaloids can function as enantioselective phase-transfer catalysts. By employing these catalysts in the asymmetric alkylation of glycine imines, one can generate a range of α-amino acid derivatives with high levels of enantiomeric excess. It is also possible to generate the catalysts in situ from commercially available chiral amines, which offers the opportunity to evaluate libraries of related structures. This latter approach has been successfully applied to a series of biphenyl quaternary ammonium salts resulting in the development of a new highly selective catalyst and opening up the potential of further expanding the range of α-amino acid derivatives that can be prepared.
TL;DR: This Account summarizes the efforts at optimizing (salen)CrIIIX catalysts for the selective formation of polycarbonates from alicyclic and aliphatic epoxides with CO2.
Abstract: The design of efficient metal catalysts for the selective coupling of epoxides and carbon dioxide to afford completely alternating copolymers has made significant gains over the past decade. Hence, it is becoming increasingly clear that this “greener” route to polycarbonates has the potential to supplement or supplant current processes for the production of these important thermoplastics, which involve the condensation polymerization of diols and phosgene or organic carbonates. On the basis of the experiences in our laboratory, this Account summarizes our efforts at optimizing (salen)CrIIIX catalysts for the selective formation of polycarbonates from alicyclic and aliphatic epoxides with CO2. An iterative catalyst design process is employed in which the salen ligand, initiator, cocatalyst, and reaction conditions are systematically varied, with the reaction rates and product selectivity being monitored by in situ infrared spectroscopy.
TL;DR: Computational studies have led to models to understand some classic and contemporary asymmetric reactions involving organocatalysts, and Quantitative predictions for several new catalysts and reactions are provided.
Abstract: Computational studies have led to models to understand some classic and contemporary asymmetric reactions involving organocatalysts. The Hajos−Parrish−Eder−Sauer−Wiechert reaction and intermolecular aldol reactions as well as Mannich reactions and oxyaminations catalyzed by proline and other amino acids, and Diels−Alder reactions catalyzed by MacMillan's chiral amine organocatalysts have been studied with density functional theory. Quantitative predictions for several new catalysts and reactions are provided.
TL;DR: The reaction of sulfur ylides with carbonyl compounds to give epoxides is an important synthetic method and the recent advances in rendering this process both asymmetric and catalytic are charts.
Abstract: The reaction of sulfur ylides with carbonyl compounds to give epoxides is an important synthetic method. This Account charts the recent advances in rendering this process both asymmetric and catalytic. Two catalytic methods have been developed: the first involving the reaction of a sulfide with an alkyl halide in the presence of a base and aldehyde and the second involving the reaction of a sulfide with a diazo compound or diazo precursor in the presence of a metal catalyst and aldehyde. These catalytic methods coupled with suitable chiral sulfides provide a new catalytic asymmetric epoxidation process for the preparation of epoxides. The scope of the two catalytic processes is discussed together with the factors that influence both relative and absolute stereochemistry. The application of these methods in target-orientated synthesis is also reviewed.
TL;DR: "planar-chiral" derivatives of 4-(dimethylamino)pyridine (DMAP) are developed, a highly versatile nucleophilic catalyst that are effective in a diverse array of processes, including the Staudinger synthesis of beta-lactams, the acylation of silyl ketene acetals, and the kinetic resolution of amines.
Abstract: Whereas chiral Lewis acid catalysis has been intensively investigated, chiral Lewis base (nucleophilic) catalysis has been comparatively neglected. We have developed “planar-chiral” derivatives of 4-(dimethylamino)pyridine (DMAP), a highly versatile nucleophilic catalyst, that are effective in a diverse array of processes, including the Staudinger synthesis of β-lactams, the acylation of silyl ketene acetals, and the kinetic resolution of amines.
TL;DR: The structural features of the Cu(2+) binding sites have now been characterized and are providing important clues about the normal function of the prion protein and perhaps how metals or loss of protein function play a role in disease.
Abstract: A conformational change of the prion protein is responsible for a class of neurodegenerative diseases called the transmissible spongiform encephalopathies that include mad cow disease and the human afflictions kuru and Creutzfeldt−Jakob disease. Despite the attention given to these diseases, the normal function of the prion protein in healthy tissue is unknown. Research over the past few years, however, demonstrates that the prion protein is a copper binding protein with high selectivity for Cu2+. The structural features of the Cu2+ binding sites have now been characterized and are providing important clues about the normal function of the prion protein and perhaps how metals or loss of protein function play a role in disease. The link between prion protein and copper may provide insight into the general, and recently appreciated, role of metals in neurodegenerative disease.
TL;DR: Chiral ketones have been shown to be effective organocatalysts for asymmetric epoxidation of olefins with broad substrate scope and the stereochemical outcome of the reaction can be rationalized by a spiro transition state model.
Abstract: Chiral ketones have been shown to be effective organocatalysts for asymmetric epoxidation of olefins with broad substrate scope. High enantioselectivity has been obtained for a wide variety of trans and trisubstituted olefins, as well as a number of cis olefins, with encouragingly high ee's for some terminal olefins. The stereochemical outcome of the reaction can be rationalized by a spiro transition state model.
TL;DR: A variety of directly linked porphyrin arrays including linear, windmill, gridlike, cyclic, and box architectures are developed, which exhibit an exceptionally low HOMO-LUMO gap as a result of a fully conjugated pi electronic system over a coplanar platform.
Abstract: On the basis of the Ag(I)-promoted coupling reaction of Zn(II) 5,15-diaryl porphyrin that gave a meso−meso-linked diporphyrin, we developed a variety of directly linked porphyrin arrays including linear, windmill, gridlike, cyclic, and box architectures. Electronic and excitonic interactions are thus fine tuned by placing porphyrin chromophores in well-defined arrangements. Photoexcited-state dynamics of these porphyrin arrays, as revealed by various ultrafast laser-based measurements, are pertinent to photosynthetic light-harvesting antenna in terms of very efficient excitation energy hopping over many porphyrins and lack of a defect that acts as energy sink. The conformational flexibility of a meso−meso-linked diporphyrin has also been used for the fine tuning of excitonic interactions as demonstrated by strapped meso−meso diporphyrins and reversible switching of energy transfer in a triporphyrin. Triply linked porphyrin arrays have also been explored, which exhibit an exceptionally low HOMO−LUMO gap as...
TL;DR: The discovery of short peptide sequences that function as asymmetric catalysts for a variety of reactions is documented and the evolution of the project from an exercise in rational design to an endeavor that combines combinatorial screening with various mechanism-based experiments is presented.
Abstract: The discovery of short peptide sequences that function as asymmetric catalysts for a variety of reactions is documented. The evolution of the project from an exercise in rational design to an endeavor that combines combinatorial screening with various mechanism-based experiments is presented. The specific development of catalysts for enantioselective acylation, phosphorylation, conjugate addition, and Morita-Baylis-Hillman reactions is described.
TL;DR: Two principal approaches have been implemented to create a new type of catalysis and high catalytic efficiency: one is the creation of a highly viable acidic function within acid-base catalysts; the other is thecreation of rather complicated but more cooperatively arranged hydrogen-bond networks that would be expected to stabilize a transition state, thereby promoting new reactivity and selectivity.
Abstract: Proper design of acid-base catalysis has been shown to be effective for achieving high reactivity and selectivity in the asymmetric direct aldol reaction during the development of diamine-Bronsted acid types of catalyst. In this study, two principal approaches have been implemented to create a new type of catalysis and high catalytic efficiency: one is the creation of a highly viable acidic function within acid-base catalysts; the other is the creation of rather complicated but more cooperatively arranged hydrogen-bond networks that would be expected to stabilize a transition state, thereby promoting new reactivity and selectivity.
TL;DR: Six well-characterized photoreceptor families function in Nature to mediate light-induced signal transduction: the rhodopsins, phytochromes, xanthopins, cryptochromes, phototropins, and BLUF proteins.
Abstract: Six well-characterized photoreceptor families function in Nature to mediate light-induced signal transduction: the rhodopsins, phytochromes, xanthopsins, cryptochromes, phototropins, and BLUF proteins. The first three catalyze E/Z isomerization of retinal, phytochromobilin, and p-coumaric acid, respectively, while the last three all have a different flavin-based photochemistry. For many of these photoreceptor proteins, (many of) the details of the conversion of the light-induced change in configuration of their chromophore into a signaling state and eventually a biological response have been resolved. Some members of the rhodopsins, the xanthopsins, and the phototropins are so well characterized that they function as model systems to study (receptor) protein dynamics and (un)folding.
TL;DR: This Account describes work done in these laboratories that has used synthetic, physical organic, and biological chemistry to understand the roles played by the nucleobases, sugars, and phosphates of DNA in the molecular recognition processes central to genetics.
Abstract: This Account describes work done in these laboratories that has used synthetic, physical organic, and biological chemistry to understand the roles played by the nucleobases, sugars, and phosphates of DNA in the molecular recognition processes central to genetics. The number of nucleobases has been increased from 4 to 12, generating an artificially expanded genetic information system. This system is used today in the clinic to monitor the levels of HIV and hepatitis C viruses in patients, helping to manage patient care. Work with uncharged phosphate replacements suggests that a repeating charge is a universal feature of genetic molecules operating in water and will be found in extraterrestrial life (if it is ever encountered). The use of ribose may reflect prebiotic processes in the presence of borate-containing minerals, which stabilize ribose formed from simple organic precursors. A new field, synthetic biology, is emerging on the basis of these experiments, where chemistry mimics biological processes as complicated as Darwinian evolution.
TL;DR: Simulations are underway in an attempt to understand some of the peculiarities of the polysiloxanes, known to exhibit some intriguing physical properties, in particular very high permeability to gases.
Abstract: Poly(dimethylsiloxane) [−Si(CH3)2O−] is by far the most studied of the polysiloxanes and is known to exhibit some intriguing physical properties, in particular very high permeability to gases. Simulations are underway in an attempt to understand some of these peculiarities. In addition, other symmetrically substituted polysiloxanes exhibit mesophases that are not understood at all. In the case of cross-linked polysiloxanes, there have been many important developments, including (i) elastomers undergoing strain-induced crystallization through control of chain stiffness or stereochemical structure, (ii) model elastomers (including dangling-chain networks), (iii) possible thermoplastic elastomers, (iv) bimodal network chain-length distributions, and (v) cross linking in solution. Interesting elastomeric composites include those with (i) in-situ-generated ceramiclike particles, (ii) ellipsoidal fillers, (iii) claylike-layered fillers, (iv) polyhedral oligomeric silsesquioxane (POSS) particles, (v) porous fill...
TL;DR: It is shown here how the tuning of the properties of quinonoid metal complexes can be pursued by using appropriate molecular synthetic techniques, focusing on metal polyoxolene complexes exhibiting intramolecular electron transfer processes involving either the ligand and the metal ion or the two dioxolene moieties of a properly designed ligand thus inducing electronic bistability.
Abstract: The peculiar redox-active character of quinonoid metal complexes makes them extremely appealing to design materials of potential technological interest We show here how the tuning of the properties of these systems can be pursued by using appropriate molecular synthetic techniques In particular, we focus our attention on metal polyoxolene complexes exhibiting intramolecular electron transfer processes involving either the ligand and the metal ion or the two dioxolene moieties of a properly designed ligand thus inducing electronic bistability The transition between the two metastable electronic states can be induced by different external stimuli such as temperature, pressure, light, or pH suggesting the use of these systems for molecular switches
TL;DR: This Account describes how polymerization depends on the dye structure and DNA sequence and also summarizes the interesting optical properties exhibited by these chiral, helical materials.
Abstract: Symmetrical cationic cyanine dyes assemble in cooperative fashion into helical supramolecular polymers using DNA as a template. The dyes assemble into cofacial dimers within the minor groove of the DNA and assembly of one dimer facilitates assembly of additional dimers directly adjacent to the first. Growth of the polymer ceases when the end of the DNA is reached or when the DNA sequence blocks dimerization of the dye. Thus, this process can be thought of as a supramolecular analogue of a chain polymerization. This Account describes how polymerization depends on the dye structure and DNA sequence and also summarizes the interesting optical properties exhibited by these chiral, helical materials.
TL;DR: This Account presents the evolution of dithiane chemistry in the laboratory and presents 1,3-dithiane linchpins as convenient acyl anion equivalents for multicomponent linchpin couplings.
Abstract: Umpolung-based strategies play a significant role in organic synthesis. Particularly important are 1,3-dithiane linchpins, which serve as convenient acyl anion equivalents. The general synthetic accessibility and impressive reactivity of 1,3-dithianes have thus led to widespread application. Since the late 1970s, dithianes have featured prominently in our program directed toward the synthesis of complex natural and unnatural products, both for effective union of advanced fragments and for multicomponent linchpin couplings. In this Account, we present the evolution of dithiane chemistry in our laboratory.
TL;DR: The structural and physical characteristics of the glycosaminoglycans responsible for their interaction with proteins important in cell-cell communication are examined.
Abstract: Glycosaminoglycans are of critical importance in intercellular communication in organisms. This ubiquitous class of linear polyanions interacts with a wide variety of proteins, including growth factors and chemokines, which regulate important physiological processes. The presence of glycosaminoglycans on cell membranes and in the extracellular matrix also has resulted in their exploitation by infectious pathogens to gain access and entry into animal cells. This Account examines the structural and physical characteristics of these molecules responsible for their interaction with proteins important in cell-cell communication.
TL;DR: A summary of qualitative and quantitative elements of a fluorescent intercalator displacement (FID) assay useful for establishing the DNA binding selectivity, affinity, stoichiometry, and binding site size and distinguishing modes of DNA binding is provided in this paper.
Abstract: A summary of the qualitative and quantitative elements of a fluorescent intercalator displacement (FID) assay useful for establishing the DNA binding selectivity, affinity, stoichiometry, and binding site size and distinguishing modes of DNA binding is provided.
TL;DR: The quantitative effect of cosolvents on the water solubility of hydrophobic substrates can be correlated with the effect on reaction rates to determine the geometries of transition states for Diels-Alder reactions, the benzoin condensation and alkylations of phenoxide ions and aniline.
Abstract: The quantitative effect of cosolvents on the water solubility of hydrophobic substrates can be correlated with the effect on reaction rates to determine the geometries of transition states for Diels-Alder reactions, the benzoin condensation, and alkylations of phenoxide ions and aniline. Some of these reactions have transition states with packing of hydrophobic surfaces and some do not. Methods were devised to sort out the effect of the cosolvents on solvation of hydrophobic surfaces and the effect on solvation of polar groups. The result is a set of geometries for these reactions that is consistent with theory.
TL;DR: The potential of a bottom-up approach to Transformations of rationally synthesized molecular compounds to materials constitute an important new direction in both structural inorganic chemistry and materials chemistry and enable possible pathways for the rational design of materials.
Abstract: A variety of complex inorganic solids with open-framework and other fascinating architectures, involving silicate, phosphate, and other anions, have been synthesized under hydrothermal conditions. The past few years have also seen the successful synthesis and characterization of several molecular compounds that can act as precursors to form open-framework and other materials, some of them resembling secondary building units (SBUs). Transformations of rationally synthesized molecular compounds to materials constitute an important new direction in both structural inorganic chemistry and materials chemistry and enable possible pathways for the rational design of materials. In this article, we indicate the potential of such a bottom-up approach, by briefly examining the transformations of molecular silicates and phosphates. We discuss stable organosilanols and silicate secondary building units, phosphorous acids and phosphate secondary building units, di- and triesters of phosphoric acids, and molecular phosphate clusters and polymers. We also examine the transformations of metal dialkyl phosphates and molecular metal phosphates.