Showing papers in "Angewandte Chemie in 1985"

Double Asymmetric Synthesis and a New Strategy for Stereochemical Control in Organic Synthesis

Abstract: This account examines double asymmetric induction from theoretical and practical viewpoints. In the context of four major organic reactions-the aldol, Diels-Alder, catalytic hydrogenation, and epoxidation-it is shown that a double asymmetric induction can be analyzed in terms of the single asymmetric reactions of each of the two chiral reactants. A rule which qualitatively relates the results of these single asymmetric reactions with the outcome of the double asymmetric reaction is proposed. A powerful new strategy based on this rule for the predictable creation of new chiral centers is discussed and the use of this strategy for the synthesis of sugars and macrolides is presented.

Polymerization of Propene and Butene with a Chiral Zirconocene and Methylalumoxane as Cocatalyst

Abstract: Hitherto, only atactic polypropylene could be prepared with soluble bis(cyclopentadienyl)zirconium(iv)/methylalumoxane Ziegler-Natta catalysts.".'' E ~ e n [ ~ ' has recently shown that mixtures of, e.g., 63% isotactic and 37% atactic polypropylene are formed with the sterically rigid ethylenebis( I-indeny1)titanium dichloride (mixture of meso form and ra~emate) . '~ ' If, however, the chiral ethylenebis(4,5,6,7-tetrahydro-lindeny1)zirconium dichloride 1 (Fig. 1) is used in combination with methylalumoxane ([AI(CH3)-O],) as cocatalyst, highly isotactic polypropylene is obtained. The racemate of 1 was used for this polymerization. The fraction of polymer soluble in toluene can be reduced to 0.2 wt.45, which is considerably lower than the 2-7% achievable with heterogeneous TiCI,/MgC12/AI(C2H5)3/ C,H,CO,C,H,-based catalysts.1h1

The Role of Hydrothermal Synthesis in Preparative Chemistry

Abstract: “Hydrothermal synthesis” usually refers to heterogeneous reactions in aqueous media above 100°C and 1 bar. The previously common distinction between hydrothermal conditions below and pneumatolytic conditions above the critical point is no longer made, since no discontinuities are observed upon exceeding the critical conditions. Under hydrothermal conditions, reactants otherwise difficult to dissolve go into solution as complexes, in whose formation water itself or very soluble “mineralizers” can participate. Thus, one can obtain the conditions of chemical transport reactions,[1] of which hydrothermal syntheses can be considered a special case. During recent decades in the geological sciences—in which the method is also historically rooted—it has received a strong impulse, whose effect on preparative solid state chemistry is discussed here.

Synthesis and Biological Activity of α‐Methylene‐γ‐butyrolactones

Abstract: α-Methylene-γ-butyrolactones [dihydro-3-methylene-2(3H)furanones] constitute an important group of natural products and possess wide-ranging biological activities. Progress in the synthesis of the heterocycle and the classification of the synthetic methods are not only of practical interest, but also fundamentally important as a current example for the construction of an unusual 1,4-functionality distance and an α-substituted acrylic ester moiety which is susceptible to nucleophilic attack.

Dinuclear Complexes with Predictable Magnetic Properties

Abstract: When two paramagnetic transition metal ions are present in the same molecular entity, the magnetic properties can be totally different from the sum of the magnetic properties of each ion surrounded by its nearest neighbors. These new properties depend on the nature and the magnitude of the interaction between the metal ions through the bridging ligands. If both ions have an unpaired electron (e.g. Cu2+ ions), then the molecular state of lowest energy is either a spin singlet or a spin triplet. In the former case, the interaction is said to be antiferromagnetic, in the latter case ferromagnetic. The nature and the order of magnitude of the interaction can be engineered by judiciously choosing the interacting metal ions and the bridging and terminal ligands, and, thus, by the symmetry and the delocalization of the orbitals centered on the metal ions and occupied by the unpaired electrons (magnetic orbitals). The first success in this “molecular engineering” of bimetallic compounds was in the synthesis of a Cu2+VO2+ heterobimetallic complex in which the interaction is purely ferro-magnetic. The same strategy could be utilized for designing molecular ferromagnets, one of the major challenges in the area of molecular materials. Another striking result is the possibility of tuning the magnitude of the interaction through a given bridging network by modifying the nature of the terminal ligands, which, in some way, play the role of “adjusting screws”. By careful selection of the bridging and terminal ligands, a very large antiferro-magnetic interaction can be achieved, even if the metal ions are far away from each other. Some sulfur-containing bridges are especially suitable in this respect.

Phase Behavior of Ternary Systems of the Type H2O ? Oil ? Nonionic Amphiphile (Microemulsions)

Abstract: Liquid multicomponent systems of the type H2O-oil-amphiphile-electrolyte are of growing interest, both in industry and in research. In applications technology, there are two problems to solve: 1. To prepare stable homogeneous solutions of H2O and nonpolar liquids with as little amphiphile as possible which can be diluted with H2O in all proportions without phase separation; e.g., concentrated solutions of drugs, herbicides, or insecticides. 2. To prepare stable mixtures of an aqueous, an amphiphile, and an oil phase with as little amphiphile as possible which are employed in tertiary oil recovery and in the pharmaceutical industry. Furthermore, such systems may be used for performing chemical reactions in heterogeneous liquid mixtures with continuously variable properties. In research, such systems are of interest for both experimental and theoretical studies of critical phenomena, especially near so-called tricritical points. Last but not least, their properties may stimulate further research in the field of associated solutions. In this paper we summarize the results of our studies on the phase behavior of ternary systems with nonionic amphiphiles, in particular with respect to the evolution of liquid three-phase bodies. The results suggest that the tricritical points in such systems should be regarded as kinds of pivot points from which the phase behavior evolves. If this were an approach to reality, the phase behavior would be governed in more or less good approximation by universal scaling laws, irrespective of the particular microstructure of the solutions. Finally, we discuss the effect of electrolytes on the phase behavior both in a quaternary phase tetrahedron and a pseudoternary phase prism representation. Although in practice most systems consist of mixtures of oils, amphiphiles, and electrolytes, an understanding of the phase behavior of truly ternary and quaternary systems with chemically well-defined components permits at least qualitative predictions with respect to the phase behavior of the multicomponent mixtures encountered in practice.

Polymerisation von Propen und Buten mit einem chiralen Zirconocen und Methylaluminoxan als Cokatalysator

Abstract: Mit loslichen Ziegler-Natta-Katalysatoren auf der Basis von Bis(cyclopentadienyl)zirconium(Iv)-Verbindungen und Methylaluminoxan konnte bisher nur ataktisches Polypropylen hergestellt werdenI1 •21. Kurzlich zeigte Ewen l31, das mit dem sterisch starren [Ethylenbis( -l-indenyl)]titandichlorid (Gemisch aus Mesoform und Racemat)141 Gemische aus z. B. 63% isotaktischem und 37% ataktischem Polypropylen entstehen. Wird jedoch das chirale [Ethylenbis(4,5,6,7-tetrahydroI-indenyl)]zirconiumdichlorid 1 (Abb. I) und als Cokatalysator Methylaluminoxan der Struktur [Al(CH3)-O]n verwendet, so erhalt man hoch isotaktisches Polypropylen. Fur diese Polymerisation wurde das Racemat von 1 eingesetzt. Der in Toluol losliche Anteil kann auf 0.2 Gew.-% gesenkt werden und liegt damit noch erheblich unter den Werten (2-7%), die mit heterogenen Katalysatoren auf der

Recent Developments in the Field of β‐Lactam Antibiotics

Abstract: The era of β-lactam antibiotics, which represent the most important class of drugs against infectious diseases caused by bacteria, began more than fifty years ago with the discovery of penicillin G. Further improvements by isolation and structure elucidation of new natural compounds, and systematic chemical modification of these, is a striking example of to what extent chemistry can contribute to the progress of drug therapy. The complex relationship between structure and activity requires, even today, a largely empirical approach. The minimum structural unit for antibiotic activity had to be revised several times over decades. Both the activated β-lactam ring with an acidic group and the nature and spatial arrangement of the other substituents and rings decisively affect the potency, antibacterial spectrum, pharmacokinetics, and toxicity. Totally synthetic mono- and bicyclic compounds from the series of monobactams, penems, carbapenems, 1-oxacephems, and 1-carbacephems are increasingly joining the classic groups obtained by semisynthesis from 6-amino-penicillanic acid and 7-aminophalosporanic acid.

Organocobalt Compounds in the Synthesis of Pyridines–An Example of Structure‐Effectivity Relationships in Homogeneous Catalýsis

Abstract: The cocyclization of alkynes with cyano compounds using organocobalt catalysts of the type [YCoL] has evolved into a versatile and technically useful method for synthesizing pyridine and its derivatives. An important advance came with the realization that the organo group Y remains attached to the cobalt throughout the catalytic cycle. This opened up the possibility of optimizing the catalyst by varying the controlling ligand Y.

Growth and Dissolution of Organic Crystals with “Tailor‐Made” Inhibitors—Implications in Stereochemistry and Materials Science

Abstract: When crystals of organic compounds are grown in the presence of growth inhibitors, there is a change in crystal morphology. A stereochemical correlation exists between the crystal structure, its modified morphology, and the molecular structure of the inhibitor. This correlation has been successfully exploited for the efficient resolution of conglomerates, the engineering of organic crystals with desired morphologies, the direct and relative assignment of the absolute configurations of chiral molecules and crystals, and for the design of a new model for the spontaneous generation of optical activity. In an analogous way dissolution of organic crystals in the presence of these growth inhibitors induces etch pits at preselected faces. The effect of solvent on crystal growth has been analyzed in some model systems. The experimental results are complemented by atom-atom potential energy calculations.

Doppelte Stereodifferenzierung und eine neue Strategie zur Stereokontrolle in der Organischen Synthese

Abstract: Bei der doppelten Stereodifferenzierung (doppelt asymmetrischen Synthese) wird ein chirales Substrat mit einem chiralen Reagens umgesetzt. Dieser Aufsatz befast sich mit der doppelten Stereodifferenzierung unter theoretischen und praktischen Gesichtspunkten. An vier bedeutenden organisch-chemischen Reaktionen – der Aldol- und der Diels-alder-Reaktion, der katalytischen Hydrierung und der Epoxidation – wird gezeigt, das dieses Phanomen als Funktion der einfach asymmetrischen Reaktionen eines jeden der beiden chiralen Reaktanten mit einem achiralen Partner analysiert werden kann. Es wird eine Regel vorgeschlagen, die das Ergebnis dieser einfach asymmetrischen Reaktionen und den stereochemischen Verlauf der doppelten Stereodifferenzierung qualitativ verknupft. Mit einer leistungsfahigen neuen Strategie, die auf dieser Regel aufbaut, konnen Chiralitatszentren in vorhersagbarer Weise eingefuhrt werden; die Strategie hat sich bereits bei der Synthese von Zuckern und Macroliden bewahrt.

Syntheses with Radicals—C ? C Bond Formation via Organotin and Organomercury Compounds [New Synthetic Methods (52)]

Abstract: CC bond formation is one of the most important synthetic steps in the construction of organic molecules. In the last few years it has been increasingly achieved by radical addition to alkenes. In such reactions the adduct radicals have to be trapped by an donor subsequent to the CC bond formation in order to prevent polymerization. This task can be accomplished with organotin and organomercury hydrides, the use of which has led to new synthetic methods. The occurrence of radical chain reactions in which reactions take place between radicals and nonradicals is decisive for the success of the synthesis. In these cases small amounts of radical initiators suffice and numerous functional groups may be used in the CC bond-forming reactions. The yields and selectivities of these radical reactions are often very high.

Chiral Compounds Synthesized by Biocatalytic Reductions [New Synthetic Methods (51)]

Abstract: It has been known for many decades that chiral compounds can be obtained by stereospecific biocatalytic reduction. Further significant methodological developments in this field have, however, only been made during the past ten years; they include the application of previously unused microorganisms and electron donors, the discovery of additional substrates for the known reductases, the development of methods for regenerating reduced pyridine nucleotides, and the discovery of new reductases which were sought for specific preparative purposes. Many chiral compounds can now be synthesized by microbial hydrogenation using H2 and hydrogenase-containing microorganisms as well as by electromicrobial or electroenzymatic reduction. In the two latter methods, anaerobic or aerobic organisms are supplied with electrons from electrochemically reduced, artificial mediators, e.g., methyl viologen. Reductases that do not require pyridine nucleotides and can accept electrons directly from reduced viologens are especially useful. Two examples of this type of enzyme are described which are of preparative interest. Many cells contain methyl viologen-dependent NAD(P) reductases, a large number of which have still not been characterized. A productivity number is proposed which allows different methods of bioconversion with microorganisms to be compared. The productivity numbers of compounds synthesized by the methods described in this review are often 10- to 100-fold higher than those of substances obtained by conventional techniques.

Transition Metal Polysulfides: Coordination Compounds with Purely Inorganic Chelate Ligands

Abstract: It has been long known that certain transition metal sulfides dissolve in aqueous ammonium polysulfide. Although it was assumed that they thereby formed metal polysulfides, attention was first paid to such compounds only a few years ago. In recent years a host of new complexes with polysulfido chelate ligands have been isolated and characterized. The complexes are of interest not only regarding their structure and reactivity but also in view of their potential uses; they can be used for the directed preparation of sulfur rings of a given size, and there are indications that they will find applications in catalysis.

Arene Complexes of Univalent Gallium, Indium, and Thallium

Abstract: Arene complexes of main-group metals were, until recently, rare species—in contrast to the now classical, analogous complexes of transition metals. In systematic investigations, it has been possible to prepare and structurally characterize arene complexes of the univalent elements gallium, indium, and thallium, which directly follow the d-block elements in the periodic table. This new type of compound is characterized by centric (η6) coordination of the metal to the arene; both mono- and bis(arene) complexes are known. The interaction can be explained by the perfect agreement between the HOMO/LUMO symmetry of the arene and of the low-valent metal. The electronic states of the nd10(n + 1)s2 configuration, which are partially modified by relativistic effects, play a particularly important role. The relationship to the few known complexes of the neighboring elements (SnII, PbII) becomes plausible via the isoelectronic principle. The arene/GaI, InI, TlI systems are of potential significance as homogeneous reducing agents and as agents for the activation of aromatic compounds, the purification of metals, and the separation of metals from nonaqueous media.

Synthesis of Cyclosporine and Analogues: Structural Requirements for Immunosuppressive Activity†

Abstract: Cyclosporine is a new immunosuppressive drug which was first marketed in 1983 under the trade name Sandimmune®. This compound, an innovation in selective immune modulation, was isolated from a fungal culture and characterized as a cyclic undecapeptide containing a novel amino acid together with several N-methylated amino acids. The new amino acid (4R)-4-[(E)-2-butenyl]-4,N-dimethyl-L-threonine (MeBmt) was the only unknown amino acid of cyclosporine and there had previously been no means for its isolation. For this reason and because it seemed possible that MeBmt could play a significant role in determining the pharmacological activity of cyclosporine, its synthesis in enantiomerically pure form was undertaken. The next step was the development of a total synthesis of cycloporine, which appeared attractive, not only for its intrinsic worth, but also as an important tool for investigating the relationships between structure and immunosuppressive activity. Essential for the immunosuppression are the amino acids MeBmt, Abu, Sar, and MeVal in the positions 1, 2, 3 and 11, but probably also still larger parts of the molecule. Such information could be valuable for finding new chemical leads or drugs with a new activity profile.

Organocobaltverbindungen in der Pyridinsynthese – ein Beispiel für Struktur‐Wirkungs‐Beziehungen in der Homogenkatalyse

Abstract: Die Cocyclisierung von Alkinen mit Cyanverbindungen an Organocobalt-Katalysatoren vom Typ [YCoL] hat sich in den letzten Jahren zu einer vielseitigen, auch technisch brauchbaren Synthesemethode fur Pyridin und seine Derivate entwickelt. Y ist ein Ligand wie Cyclopentadienyl, L ein Neutralligand wie Cyclooctadien. Einen entscheidenden Fortschritt brachte die Erkenntnis, das die Gruppe Y wahrend des Katalysecyclus am Cobalt gebunden bleibt. Damit eroffnete sich die Moglichkeit, die Katalysatoreigenschaften durch Variation des „steuernden Liganden Y” zu optimieren.

Phosphorus, Arsenic, Antimony, and Bismuth Multiply Bonded Systems with Low Coordination Number — Their Role as Complex Ligands

Abstract: Multiply bonded systems with low coordination number (one to three) involving phosphorus and its homologues, whether isolable or generated in situ at a metal complex, are versatile ligands that can function as two-, four-, six- or eight-electron donors to transition metal fragments and that may be coordinated in η1 (terminal), η2 (side-on), edge- or face-bridging modes The (p-p)π bonding system of the ligand is thereby rendered capable of addition and intra- or intermolecular cycloaddition reactions Some of the polycyclic species thus generated represent novel, polydentate ligands

η3‐Allylpalladium Compounds

Abstract: The use of transition-metal complexes as homogeneous catalysts for the production of organic chemicals is of considerable industrial significance. Although palladium complexes have not attained the same importance as, for example, those of rhodium or cobalt, palladium is nonetheless one of the most versatile metals for synthetic organic purposes. An understanding of the role played by the metal in these reactions is essential for their optimal utilization. This necessarily entails a detailed study of the chemistry of the palladium-carbon bond. In this article we concentrate on η3-allylpalladium complexes, which are frequently involved as intermediates in the Pd-catalyzed transformations of dienes. The study of their behavior gives a deeper insight into the individual steps of a catalytic cycle.