Showing papers in "Angewandte Chemie in 1988"

Supramolecular Chemistry—Scope and Perspectives Molecules, Supermolecules, and Molecular Devices (Nobel Lecture)

Abstract: Supramolecular chemistry is the chemistry of the intermolecular bond, covering the structures and functions of the entities formed by association of two or more chemical species. Molecular recognition in the supermolecules formed by receptor-substrate binding rests on the principles of molecular complementarity, as found in spherical and tetrahedral recognition, linear recognition by coreceptors, metalloreceptors, amphiphilic receptors, and anion coordination. Supramolecular catalysis by receptors bearing reactive groups effects bond cleavage reactions as well as synthetic bond formation via cocatalysis. Lipophilic receptor molecules act as selective carriers for various substrates and make it possible to set up coupled transport processes linked to electron and proton gradients or to light. Whereas endoreceptors bind substrates in molecular cavities by convergent interactions, exoreceptors rely on interactions between the surfaces of the receptor and the substrate; thus new types of receptors, such as the metallonucleates, may be designed. In combination with polymolecular assemblies, receptors, carriers, and catalysts may lead to molecular and supramolecular devices, defined as structurally organized and functionally integrated chemical systems built on supramolecular architectures. Their recognition, transfer, and transformation features are analyzed specifically from the point of view of molecular devices that would operate via photons, electrons, or ions, thus defining fields of molecular photonics, electronics, and ionics. Introduction of photosensitive groups yields photoactive receptors for the design of light-conversion and charge-separation centers. Redox-active polyolefinic chains represent molecular wires for electron transfer through membranes. Tubular mesophases formed by stacking of suitable macrocyclic receptors may lead to ion channels. Molecular self-assembling occurs with acyclic ligands that form complexes of double-helical structure. Such developments in molecular and supramolecular design and engineering open perspectives towards the realization of molecular photonic, electronic, and ionic devices that would perform highly selective recognition, reaction, and transfer operations for signal and information processing at the molecular level.

Molecular Architecture and Function of Polymeric Oriented Systems: Models for the Study of Organization, Surface Recognition, and Dynamics of Biomembranes

Abstract: The Part and the Whole. The principle of self-organization for the creation of functional units is not an invention of modern natural sciences. It was already a basic idea of the ancient philosophies in Asia and Europe: only the mutuality of the parts creates the whole and its ability to function. Translated into the language of chemistry this means: the self-organization of molecules leads to supramolecular systems and is responsible for their functions. Thermotropic and lyotropic liquid crystals are such functional units, formed by self-organization. As highly oriented systems, they exhibit new properties. The importance of lyotropic liquid crystals for the life sciences has been known for a long time. They are a prerequisite for the development of life and the ability of cells to function. In materials sciences this concept of function through organization led to the development of new liquid-crystalline materials. From the point of view of macromolecular chemistry, this review tries to combine these two different fields and especially hopes to stimulate their interaction and joint treatment. To exemplify this, the molecular architecture of polymeric organized systems will be discussed. Polymeric liquid crystals combine the ability to undergo spontaneous self-organization–typical of liquid-crystalline phases–with the polymer-specific property of stabilizing these ordered states. As new materials, polymeric liquid crystals have already been investigated intensively. As model systems for biomembranes as well as for the simulation of biomembrane processes, they so far have been little discussed. The intention of this review article is to show that polymer science is able to contribute to the simulation of cellular processes such as the stabilization of biomembranes, specific surface recognition, or even the “uncorking” of cells. Polymer science, having an old tradition as an inter-disciplinary field, can no longer restrict itself to common plastics. Attempts to reach new horizons have already begun. The borderland between liquid crystals and cells will certainly play an important role. Basic requirements to work in this frontier area between organic chemistry, membrane biology, life science, and materials science will be the delight in scientific adventures as well as the courage to go ahead. The most important prerequisite will be the willingness to cooperate with disciplines which so far have not really accepted each other. From this point of view, this review does not aim at giving defined answers. It wants instead to encourage the scientific venture: too often we cling to painfully acquired knowledge, fearing adventures.

Structure and Reactivity of Lithium Enolates. From Pinacolone to Selective C‐Alkylations of Peptides. Difficulties and Opportunities Afforded by Complex Structures

Abstract: The chemistry of lithium enolates is used to demonstrate that complex structures held together by noncovalent bonds (“supramolecules”) may dramatically influence the result of seemingly simple standard reactions of organic synthesis. Detailed structural data have been obtained by crystallographic investigations of numerous Li enolates and analogous derivatives. The most remarkable features of these structures are aggregation to give dimers, tetramers, and higher oligomers, complexation of the metal centers by solvent molecules and chelating ligands, and hydrogen-bond formation of weak acids such as secondary amines with the anionoid part of the enolates. The presence in nonpolar solvents of the same supramolecules has been established by NMR-spectroscopic, by osmometric, and by calorimetric measurements. The structures and the order of magnitude of the interactions have also been reproduced by ab-initio calculations. Most importantly, supramolecules may be product-forming species in synthetic reactions of Li enolates. A knowledge of the complex structures of Li enolates also improves our understanding of their reactivity. Thus, simple procedures have been developed to avoid complications caused by secondary amines, formed concomitantly with Li enolates by the common methods. Mixtures of achiral Li enolates and chiral Li amides can give rise to enantioselective reactions. Solubilization by LiX is observed, especially of multiply lithiated compounds. This effect is exploited for alkylations of N-methylglycine (sarcosine) CH2 groups in open-chain oligopeptides. Thus, the cyclic undecapeptide cyclosporine, a potent immunosuppressant, is converted into a THF-soluble hexalithio derivative (without epimerization of stereogenic centers) and alkylated by a variety of electrophiles in the presence of either excess lithiumdiisopropyl amide or of up to 30 equivalents of lithium chloride. Depending on the nature of the LiX additive, a new stereogenic center of (R) or (S) configuration is created in the peptide chain by this process. A structure-activity correlation in the series of cyclosporine derivatives thus available is discussed.

Supramolekulare Chemie – Moleküle, Übermoleküle und molekulare Funktionseinheiten (Nobel-Vortrag)†

Abstract: Supramolekulare Chemie ist die Chemie der intermolekularen Bindung und beschaftigt sich mit Strukturen und Funktionen von Einheiten, die durch Assoziation von zwei oder mehr chemischen Spezies gebildet werden. Molekulare Erkennung in Ubermolekulen, die bei der Rezeptor/Substrat-Bindung entstehen, beruht auf dem Prinzip der molekularen Komplementaritat, wie es bei der Erkennung spharischer, tetraedrischer und linearer Substrate durch Rezeptoren, Corezeptoren, Metallorezeptoren und amphiphile Rezeptoren vorgefunden wird. Supramolekulare Katalyse mit Rezeptoren, die reaktive Gruppen tragen, bewirkt Bindungsspaltungen und -knupfungen durch Cokatalyse. Lipophile Rezeptoren konnen als selektive Carrier fur verschiedenartige Substrate verwendet werden, und sie ermoglichen den Aufbau von Transportsystemen, die mit einem Elektronen- oder Protonengradienten oder mit einem Photoprozes gekoppelt sind. Wahrend Endorezeptoren Substrate durch „konvergente Wechselwirkungen” in Molekulhohlraumen binden, werden bei Exorezeptoren die Substrate durch Wechselwirkungen zwischen den Ausenflachen von Rezeptor und Substrat gebunden. Demgemas lassen sich neue Typen von Rezeptoren, z. B. die Metallonucleate, entwickeln. In polymolekularen Aggregaten konnen Rezeptoren, Carrier und Katalysatoren zu molekularen und supramolekularen Funktionseinheiten fuhren, die strukturell organisierte und funktionell integrierte chemische Systeme sind („supramolekulare Architektur”). Erkennungs-, Translokations- und Transformationsprozesse mit molekularen Funktionseinheiten werden unter dem Gesichtspunkt analysiert, ob sie durch Photonen, Elektronen oder Ionen ausgelost werden konnen. Auf diese Weise lassen sich die Gebiete der molekularen Photonik, Elektronik und Ionik definieren. Fuhrt man photosensitive Gruppen ein, ergeben sich photoaktive Rezeptoren, die sich zur Lichtumwandlung und Ladungstrennung eignen. Redoxaktive, langkettige Polyolefine – „molekulare Drahte” – konnen Elektronen, z. B. durch Membranen, ubertragen. Tubulare Mesophasen, die durch Stapelung geeigneter makrocyclischer Rezeptoren entstehen, konnen Ionenkanale bilden. Bei acyclischen Liganden gibt es das Phanomen der molekularen Selbstorganisation, was zu Komplexen mit doppelt-helicaler Struktur fuhrt. Derartige Entwicklungen im Bereich des „molekularen und supramolekularen Designs und Engineerings” lassen auf photonische, elektronische und ionische molekulare Funktionseinheiten hoffen, die hochselektive Erkennungs-, Umwandlungs- und Ubertragungsprozesse – Verarbeitung von Signalen und Informationen auf molekularer Ebene – ausfuhren konnen.

Zeolites: Catalysts for Organic Syntheses

Abstract: Zeolites have proved to be valuable technical catalysts in petrochemistry and in oil processing. The characteristic properties of zeolites, such as acidity, shape-selectivity and thermal stability also enable them to be used for highly selective synthesis in the fields of chemical intermediates and fine chemicals. This interesting area of application has grown continuously in recent years. The present article summarizes the various standard types of reaction involved in organic syntheses which can be catalyzed by zeolites; these include, inter alia, electrophilic and nucleophilic substitution reactions, isomerization of double bonds and carbon skeletons, as well as addition, elimination and hydrogenation reactions.

Contributions to Organo‐Nickel Chemistry

Abstract: One hundred years of organonickel chemistry have generated a wealth of new knowledge and a history of examples of accidental discoveries which have finally led to industrial applications. The historical development is associated with the names of Mond, Sabatier, Reppe and Ziegler and, with the methods and techniques available today, many of the original discoveries and unsolved problems are attracting renewed attention. For example, 70 years were to go by before a synthesis first conceived by Sabatier could finally be realized. The path leading from nickel-catalyzed hydrogenation to highly enantioselective homogeneous catalysts is one of the contributions to organonickel chemistry which is described here.

Two‐Dimensional NMR Spectroscopy: Background and Overview of the Experiments [New Analytical Methods (36)]

Abstract: An exact knowledge of the structure, dynamics, and reactions of molecules provides the key to understand their functions and properties. NMR spectroscopy has developed, through the introduction of two-dimensional methods, into the most important method for the investigation of these questions in solution. A great variety of different techniques is available. However, for their successful application not only the appropriate equipment is required, but also the right choice of experiments and optimum measurement parameters, as well as a careful evaluation of the spectra. This contribution describes the necessary background for modern NMR spectroscopy. With the aid of the so-called product operator formalism it is possible to understand pulsed Fourier transform NMR spectroscopy both qualitatively and quantitatively. Very few, readily understandable assumptions are sufficient for confident application of these methods. This article attempts to introduce in a simple manner this formalism as well as phase cycles necessary for the understanding of pulse sequences, and to train the reader through the discussion of several 2D NMR techniques. An overview of the most important techniques is given in the second part of this article.

Complexation of Neutral Molecules by Cyclophane Hosts

Abstract: Since the discovery of the crown ethers by Pedersen twenty years ago, the chemistry of synthetic hosts for the selective complexation of organic and inorganic guests has seen an extraordinarily rapid development. This article discusses in particular the contributions provided by synthetic cyclophanes as hosts to the understanding of molecular complexation of neutral organic guest molecules in aqueous and organic solvents. In aqueous solution, cyclophanes form stoichiometric complexes with neutral aromatic guests which can approach enzyme-substrate complexes in their stability. Efficient molecular complexation is also observed in organic environments. Here, as a result of large solvation effects, the strength of complexation is strongly dependent on the nature of the organic solvent. Electron donor-acceptor interactions can contribute significantly to the stability of complexes formed between cyclophane hosts and aromatic guests. Force-field calculations together with computer graphics are powerful tools in the design of water-soluble, optically active hosts for chiral recognition of complexed racemic guests. Simple and selective functionalization of the cyclophane framework leads to stable, bioorganic catalysts. Like enzymes, these catalysts bind their substrates in a rapid equilibrium prior to the reaction steps. As a perspective, some fascinating research objectives in the field of molecular recognition and catalysis which can be targeted with designed cyclophane hosts are shown.

“Proton Sponges” and the Geometry of Hydrogen Bonds: Aromatic Nitrogen Bases with Exceptional Basicities

Abstract: Certain aromatic diamines (the “proton sponges”) are found to have exceptionally high basicity constants: this is due to spatial interaction of the basic centers, which are in close proximity. The two factors which are most important in causing this effect are, on the one hand, the extreme steric strain in these systems and the destabilizing effect of the overlap of the nitrogen lone pairs of the neutral diamines and, on the other, the strong NċHċN hydrogen bonds which are formed on monoprotonation and which lead to a considerable relaxation of the steric strain. By the systematic variation of the structures of such aromatic diamines we have been able to study these effects as a function of steric factors, in particular of the geometry and the bond length of the NċHċN hydrogen bonds, by means of X-ray structural analysis. The hydrophobic shielding of the basic centers and the NċHċN hydrogen bonds, which was characteristic of the “proton sponge” compounds studied previously, is indeed responsible for the extremely low rate of protonation and deprotonation of these compounds; however, it apparently has no influence on their high thermodynamic basicity. The recent synthesis and basicity determination of a new type of “proton sponge” with no hydrophobic shielding whatever show that not only very strong but also kinetically active bases are accessible using the “proton sponge” concept. Their unusual properties, which are discussed here as the result of steric interactions between two basic centers, provide examples of the fact that cooperative steric interactions of reactive structural elements can lead to properties which cannot be derived from an isolated consideration of the various functional groups. Such “proximity effects” are certainly of general importance in chemistry and biochemistry; the study of their structure-function relationships is worthy of closer consideration.

Vitamin B12: Experiments Concerning the Origin of Its Molecular Structure

Abstract: Following the chemical synthesis of vitamin B12, a search was begun for a potentially biomimetic “dark” variant of the photochemical A/D-secocorrin → corrin cycloisomerization, the central ring-closure step in one of the two cobyric acid syntheses. Significantly, not just one but a whole family of such variants was discovered. According to what is currently known, one of these variants can indeed be regarded as a chemical model for the reaction path followed by Nature in the biosynthetic construction of the corrin ring. These chemical studies of vitamin B12 biosynthesis had revealed that the A/D-ring junction, regarded as the main obstacle to a chemical vitamin B12 synthesis at the outset, is in fact a structural element that is formed readily and in a variety of ways from structurally appropriate precursors. More recent investigations have shown that the same holds for other specific structural elements of the vitamin B12 molecule, including the characteristic arrangement of double bonds in the corrin chromophore, the special dimension of the macrocyclic ring of the corrin ligand, the specific attachment of the nucleotide loop to the propionic acid side chain of ring D, and the characteristic constitutional arrangement of the side chains around the ligand periphery (which vitamin B12 shares with all uroporphinoid cofactors). All these outwardly complex structural elements are found to “self-assemble” with surprising ease under structurally appropriate preconditions; the amount of “external instruction” required for their formation turns out to be surprisingly small in view of the complexity and specificity of these structural elements. We view these findings as steps on the way toward a chemical rationalization of the vitamin B12 structure. The goal is to arrive experimentally at a perception of the biomolecule's intrinsic potential for structural self-assembly. This potential, together with the specific type of reactivity related to the biological function, is considered to be responsible for the biomolecule having been chosen by natural selection. The chemical rationalization of the structure of biomolecules is an objective of organic natural product chemistry. The field of natural product synthesis provides appropriate conceptual and methodological tools to approach this objective experimentally.

Carbon Dioxide as an Alternative C1 Synthetic Unit: Activation by Transition‐Metal Complexes

Abstract: The carbon dioxide molecule has been of limited importance as a synthetic unit in organic chemistry. When it is coordinated to transition metals, however, completely new possibilities arise; CO2 can bond to metal complexes in a variety of ways and can enter into insertion and coupling reactions, or become catalytically attached to other substrates. The formation of CC bonds between carbon dioxide and unsaturated hydrocarbons under conditions of homogeneous catalysis makes available new synthetic routes to industrially interesting organic compounds.

Molekulare Architektur und Funktion von polymeren orientierten Systemen – Modelle für das Studium von Organisation, Oberflächenerkennung und Dynamik bei Biomembranen

Abstract: Der Teil und das Ganze. Nicht erst die moderne Naturwissenschaft hat die Selbstorganisation fur den Aufbau von Funktionseinheiten entdeckt, schon in den alten Philosophien Asiens und Europas ist sie ein Grundgedanke: Erst die Gemeinsamkeit der Teile schafft das Ganze und seine Funktionsfahigkeit. Ubersetzt in die Sprache der Chemie bedeutet dies: Die Selbstorganisation von Molekulen fuhrt zu supramolekularen Systemen. Thermotrope und lyotrope Flussigkristalle sind solche Funktionseinheiten, die sich durch Selbstorganisation bilden und als hochorientierte Systeme neue Eigenschaften aufweisen. Die Bedeutung lyotroper Flussigkristalle ist in den Biowissenschaften seit langem bekannt. Sie sind eine Voraussetzung fur die Entstehung des Lebens und die Funktionsfahigkeit von Zellen. In den Materialwissenschaften hat das Konzept Funktion durch Organisation in den letzten Jahren bereits zur Entwicklung neuer flussigkristalliner Materialien gefuhrt. Aus der Sicht der Makromolekularen Chemie soll am Beispiel der molekularen Architektur von Polymersystemen versucht werden, diese beiden Bereiche gemeinsam zu betrachten und besonders zu ihrer gemeinsamen Bearbeitung anzuregen. Polymere Flussigkristalle vereinigen die Fahigkeit zur spontanen Selbstorganisation, die den flussigkristallinen Zustand auszeichnet, mit polymerspezifischen Eigenschaften, die eine Stabilisierung von Ordnungszustanden zulassen. Als neue Materialien wurden auch diese bereits intensiv untersucht. Als Modellsysteme fur Biomembranen und zur Simulation von Biomembranprozessen hingegen wurden sie bisher nur wenig diskutiert. Intention dieses Beitrags ist es, zu zeigen, das die Makromolekulare Chemie helfen kann, Zellprozesse wie die Stabilisierung von Biomembranen, die spezifische Oberflachenerkennung oder gar die „Entkorkung” von Zellen zu simulieren. Von jeher interdisziplinar arbeitend, kann sich die Polymerwissenschaft schon lange nicht mehr an den klassischen Massenkunststoffen festhalten. Der Aufbruch zu neuen Forschungsbereichen hat begonnen. Die Verbindung von Flussigkristall- und Biomembranforschung scheint uns besonders wichtig. Eine der Grundvoraussetzungen, dieses Grenzgebiet zwischen Organischer Chemie und Membranbiologie oder, allgemeiner, zwischen Biowissenschaften und Materialwissenschaften zu bearbeiten, wird die Bereitschaft zu einer engen Kooperation mit Nachbardisziplinen sein, die sich bisher oft fremd gegenuberstanden. Dieser Beitrag ist weit davon entfernt, definitive Antworten zu geben; er soll aber Mut machen zum wissenschaftlichen Wagnis, denn oft halten wir aus Angst vor dem Abenteuer am muhsam erworbenen Wissen zu fest.

Transition Metals in the Synthesis and Functionalization of Indoles [New Synthesis Methods (72)]

Abstract: The use of transition-metal complexes as reagents for the synthesis of complex organic compounds has been under development for at least several decades, and many extraordinary organic transformations of profound potential have been realized. However, adoption of this chemistry by the practicing synthetic organic chemist has been inordinately slow, and only now are transition-metal reagents beginning to achieve their rightful place in the arsenal of organic synthesis. Several factors contributed to the initial reluctance of synthetic organic chemists to use organometallic reagents. Lacking education and experience in the ways of elements having d electrons, synthetic chemists viewed organometallic processes as something mysterious and unpredictable, and not to be discussed in polite society. Organometallic chemists did not help matters by advertising their latest advances as useful synthetic methodology, but restricting their studies to very simple organic systems lacking any serious functionality (e.g., the “methyl, ethyl, butyl, futile” syndrome). Happily, things have changed. Organometallic chemists have turned their attention to more complex systems, and more recently trained organic chemists have benefited from exposure to the application of transition metals. This combination has set the stage for major advances in the use of transition metals in the synthesis of complex organic compounds. This review deals with one aspect of this area, the use of transition metals in the synthesis of indoles.

Struktur und Reaktivität von Lithiumenolaten, vom Pinakolon zur selektiven C‐Alkylierung von Peptiden – Schwierigkeiten und Möglichkeiten durch komplexe Strukturen

Abstract: Am Beispiel der Li-Enolate last sich zeigen, das komplexe, durch nicht-kovalente Bindungen zusammengehaltene Gebilde („Ubermolekule”) das Ergebnis von scheinbar einfachen Standardreaktionen der organisch-chemischen Synthese beeinflussen konnen. Kristallographische Untersuchungen zahlreicher Li-Enolate und analoger Derivate ergaben eine Fulle detaillierter Strukturinformationen. Auffalligste Merkmale der Strukturen sind die Aggregation zu Dimeren, Tetrameren und zum Teil noch hoheren Oligomeren, die Komplexierung der Metallzentren mit Solvensmolekulen und Chelatbildnern sowie die Wasserstoff-bruckenbindung schwacher Sauren (z. B. sekundarer Amine) mit anionoiden Komponenten der Li-Enolate. Durch NMR-spektroskopische, osmometrische und calorimetrische Messungen ist die Anwesenheit derselben Ubermolekule in unpolaren Losungsmitteln (Kohlen-wasserstoffen und Ethern) wie in den Kristallen nachgewiesen worden. Mit ab-initio-Berechnungen wurden auser den Strukturen auch die Grosenordnung der Wechselwirkungen qualitativ reproduziert. Wichtig fur die Praxis der organischen Synthese mit Li-Enolaten ist schlieslich, das Ubermolekule auch produktbildende Spezies sein konnen. Die Reaktivitat von Li-Enolaten ist besser zu verstehen, wenn ihre komplexen Strukturen berucksichtigt werden. So kann der storende Einflus von sekundaren Aminen, den Nebenprodukten bei der ublichen Enolaterzeugung, durch Deprotonierung vermieden werden; in Mischungen aus achiralen Li-Enolaten und chiralen Li-Amiden finden enantioselektive Reaktionen statt; durch Zusatz von LiX werden die Eigenschaften von Li-Enolaten drastisch verandert; vor allem vielfach lithiierte Verbindungen konnen durch LiX auch solubilisiert werden. Offenkettige Oligopeptide lassen sich an der CH2-Gruppe von N-Methylglycin(Sarkosin)-Einheiten alkylieren. In Gegenwart von uberschussigem Lithiumdiisopropylamid oder von bis zu 30 Aquivalenten LiCl wird das cyclische Undecapeptid Cyclosporin, ein potentes Immunsuppressivum, uber ein in Tetrahydrofuran losliches Hexalithium-Derivat (ohne Epimerisierung stereogener Zentren) mit Elektrophilen umgesetzt. Dabei entsteht, je nach Art des LiX-Zusatzes, selektiv ein neues stereogenes Zentrum mit (R)- oder (S)-Konfiguration in der Peptidkette. Die so zuganglichen Abkommlinge des Cyclosporins sind Musterbeispiele fur das Studium von Struktur-Wirkungs-Beziehungen.

Natural Fats and Oils—Renewable Raw Materials for the Chemical Industry

Abstract: Since last century, the supply of raw materials for the chemical industry has undergone a radical change. Whereas at the beginning of the nineteenth century the demand for basic chemicals was satisfied entirely by renewable raw materials, from about 1850 the chemical industry came to rely increasingly upon coal. In the 1940's, mineral oil started to become increasingly important, and during the past thirty years it has remained by far as the most important source of raw materials. Renewable raw materials are likely to become important again in the future, as the choice of raw materials is now of great significance not only for economic reasons by influencing competitiveness, but also because this choice largely determines the properties of the derivatives produced and their ecological effects. Following the two oil crises of the 1970's, there is also now a growing awareness of the limits of raw material resources, and against the continuing background of agricultural surpluses, chemists are again showing an increasing interest in renewable raw materials. Since the end of the seventies, the Bundesministerium fur Forschung und Technologie (Ministry of Research and Technology of the Federal Republic of Germany) has supported research projects on renewable raw materials in universities and in industry. For the chemical industry the use of natural products as raw materials opens up a wider spectrum of synthetic methods and finished products, some of which are not accessible by petrochemical routes.

Tetrahedrane and Cyclobutadiene

Abstract: Tetra-tert-butyltetrahedrane—a useless molecule? In the first part of this progress report an attempt is made to answer this provoking question in order that the reader can evaluate why it is worthwhile to track such an esoteric molecule. An account of the unusual properties of tetra-tert-butyltetrahedrane, the only tetrahedrane unequivocally identified so far, and the most highly strained saturated hydrocarbon of all, is followed by a summary of attempts to synthesize the parent compound. The emphasis in these two sections is on our own research achievements. Since any discussion of the tetrahedranes must necessarily include the corresponding cyclobutadienes, it was found appropriate to organize the article at the same time as a final account of the cyclobutadiene problem. Masamune[8c] characterized his excellent report in 1980 in the journal Tetrahedron as a comma in the history of cyclobutadiene. Meanwhile, the significant questions have been answered. The time is now ripe to replace the comma by a full stop.

Enzymic Baeyer–Villiger Oxidations by Flavin‐Dependent Monooxygenases

Abstract: There has recently been a revival of interest in microbial biochemistry. Part of this resurgence is due to the increased presence of man-made organic compounds in the biosphere and the resultant interest in microorganisms which can degrade these xenobiotic molecules. Also, advances in genetic engineering have raised the possibility of utilizing the chemical machinery of bacteria for commercial profit and social benefit. The Baeyer-Villiger reaction is a useful transformation in organic synthesis which provides chemists with a gentle means of converting ketones into esters or lactones. The reaction, however, suffers from the problems of low yield and the need, in some cases, to utilize harsh conditions. There exist bacteria, capable of growth on aliphatic molecules, that contain enzymes which can catalyze Baeyer-Villiger reactions. These enzymes, known as monooxygenases, are involved in the breakdown of acyclic and alicyclic ketones to provide simpler carbon units for further catabolism. The gamut of reactions catalyzed by some of these enzymes is remarkable. This diversity, plus their availability in pure form in quantity by genetic engineering raises the possibility that these biocatalysts can be useful as reagents in organic synthesis.

Electron Transfer and Charge Transfer: Twin Themes in Unifying the Mechanisms of Organic and Organometallic Reactions

Abstract: The broad varieties of organic and organometallic reactions merge into a common unifying mechanism by considering all nucleophiles and electrophiles as electron donors (D) and electron acceptors (A), respectively. Comparison of outer-sphere and inner-sphere electron transfers with the aid of Marcus theory provides the thermochemical basis for the generalized free energy relationship for electron transfer (FERET) in Equation (37) and its corollaries in Equations (43) and (44) that have wide predictive applicability to electrophilic aromatic substitutions, olefin additions, organometallic cleavages, etc. The FERET is based on the conversion of the weak nucleophile–electrophile interactions extant in the ubiquitous electron donor—acceptor (EDA) precursor complex [D, A] to the radical ion pair [D⊕, A⊖], for which the free energy change can be evaluated from the charge-transfer absorption spectra according to Mulliken theory. FERET analysis thus indicates that the charge-transfer ion pairs [D⊕, A⊖] are energetically equivalent to the transition states for nucleophile/electrophile transformations. The behavior of such ion pairs can be directly observed immediately following the irradiation of the charge-transfer bands of various EDA complexes with a 25-ps laser pulse. Such studies confirm the radical ion pair [Arene⊕, NO2] as a viable intermediate in electrophilic aromatic nitration, as presented in the electron-transfer mechanism between arenes and the nitryl cation (NO) electrophile.

Phosphaalkynes—Syntheses, Reactions, Coordination Behavior [New Synthetic Methods (73)]†

Abstract: Organophosphorus compounds have been applied in two ways in chemical synthesis. They can either be used as a reagent in a step of the synthesis (for example, in the Wittig reaction) or they can be incorporated directly into the target molecule. This second application, in particular, has expanded greatly in the last few years with the preparation of low-coordination phosphorus compounds. These include the phosphaalkynes, which are of great interest to organic and inorganic chemists. Phosphaalkynes have been employed in the synthesis of heterocyclic compounds, phosphaarenes and their valence isomers, and polycyclic compounds. Further applications have been the use of phosphaalkynes as new ligand systems in complex chemistry and their cyclooligomerization with organometallic reagents. While the chemical properties of phosphaalkynes have little in common with those of nitriles, they are in many ways very similar to those of the isoelectronic acetylenes.