Abstract

Abstract

Abstract

Abstract

How Copper Clicks

The copper-catalyzed coupling of azides and alkynes has been termed a “click” reaction on account of its efficiency and versatility, but despite its widespread use, the mechanism remains somewhat unclear. Through a series of kinetic and isotopic labeling studies, Worrell et al. (p. 457, published online 4 April) show that, in the case of terminal alkynes (capped at one end by an H atom), two equivalents of copper participate in activating each molecule's reactivity toward azide. Surprisingly, the reaction also appears to proceed through an intermediate in which the two copper centers become equivalent and functionally exchangeable, despite initially coordinating to distinct sites on the alkyne.

1,2,3-Triazole-based polymers generated from the Cu(I)-catalyzed cycloaddition between multivalent azides and acetylenes are effective adhesive materials for metal surfaces. The adhesive capacities of candidate mixtures of azide and alkyne components were measured by a modified peel test, using a customized adhesive tester. A particularly effective tetravalent alkyne and trivalent azide combination was identified, giving exceptional strength that matches or exceeds the best commercial formulations. The addition of Cu catalyst was found to be important for the synthesis of stronger adhesive polymers when cured at room temperature. Heating also accelerated curing rates, but the maximum adhesive strengths achieved at both room temperature and high temperature were the same, suggesting that crosslinking reaches the same advanced point in all cases. Polytriazoles also form adhesives to aluminum, but copper is bound more effectively, presumably because active Cu(I) ions may be leached from the surface to promote crosslinking and adhesion. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5182–5189, 2007

4-Substituted 1-(N-sulfonyl)-1,2,3-triazoles are selectively obtained by using the Cu-catalyzed azide–alkyne cycloaddition reaction with sulfonyl azides. Performing the reaction at 0 °C in chloroform in the presence of 2,6-lutidine and CuI as the catalyst effectively prevents the ketenimine pathway and provides convenient access to N-sulfonyltriazoles in good to excellent yields.

Durch eine kupferkatalysierte Cycloaddition von Alkinen mit Sulfonylaziden werden 4-substituierte 1-(N-Sulfonyl)-1,2,3-triazole selektiv erhalten. Die im Schema gezeigte Umsetzung umgeht den Ketenimin-Reaktionsweg und führt glatt und in guten Ausbeuten zu den N-Sulfonyltriazolen.

Two catalytic cycles operate in the osmium-catalyzed olefin dihydroxylation and aminohydroxylation. Slow hydrolysis of the Os(VI) monoglycolate (or monoazaglycolate in aminohydroxylation) intermediate often results in the addition of another molecule of olefin thereby shunting the catalysis into the second catalytic cycle. As a result, both enantio- and chemoselectivity are reduced. A series of new chelating ligands were devised, which force the catalysis into the second cycle while maintaining enantiocontrol in the olefin addition step. Excellent catalytic turnover and moderate to good enantioselectivity were achieved.

Nimm drei für eine selektive Umwandlung: Hochfunktionalisierte Azetidinderivate entstehen bei einer experimentell einfachen, hoch selektiven und unter milden Bedingungen ablaufenden katalytischen Dreikomponentenreaktion mit einfach zugänglichen endständigen Alkinen (siehe Schema). Die Azetidiniminprodukte sind unter vielfältigen Reaktionsbedingungen erstaunlich stabil und lassen sich leicht weiter funktionalisieren.

Ein direkter, einfacher und effizienter Weg von endständigen Alkinen zu Amiden ist die Kupfer(I)-katalysierte Reaktion mit Sulfonylaziden (siehe Schema). Bei der Reaktion werden die Kupfer(I)-acetylide in situ erzeugt, und sie kann als formale einstufige oxidative Hydrierung einer Dreifachbindung gesehen werden.

Zweimal schwach gibt mächtig: Die HIV-1-Protease baut ihren eigenen leistungsfähigen Inhibitor zusammen, indem sie mit einem azid- und einem alkinhaltigen Fragment, die beide schwach binden, die Triazolverknüpfung erzeugt.

A powerful engine: The Cu-catalyzed azide–alkyne cycloaddition depends on rapid formation of Cu^I–acetylide complexes from terminal alkynes 2 and their ability to activate organic azides 1. A kinetics study uncovered a bimolecular dependence on the metal and an unusually fast intramolecular variant of the process. The results suggest the importance of 3 as a reactive intermediate.

Ein kräftiger Motor: Die Cu-katalysierte Azid-Alkin-Cycloaddition (siehe Schema) beruht auf der schnellen Bildung von Cu^I-Acetylid-Komplexen aus terminalen Alkinen 2 und deren Fähigkeit zur Aktivierung organischer Azide 1. Eine kinetische Studie zu dieser Reaktion ergab eine bimolekulare Abhängigkeit vom Metall. Eine ungewöhnlich schnell verlaufende intramolekulare Variante lässt auf eine Kupfer-Triazol-Spezies 3 als reaktives Intermediat schließen.

The copper(I)-catalyzed cycloaddition reaction between azides and alkynes has been employed to make metal-adhesive materials. Copper and brass surfaces supply the necessary catalytic Cu ions, and thus the polymerization process occurs selectively on these metals in the absence of added catalysts. Alternatively, copper compounds can be added to monomer mixtures and then introduced to reducing metal surfaces such as zinc to initiate polymerization. The resulting materials were found to possess comparable or superior adhesive strength to standard commercial glues, and structure-activity correlations have identified several important properties of the monomers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4392–4403, 2004

Komponenten, die Klick machen: Eine Vielzahl unterschiedlicher Dendrimere (siehe Schema) wurde mit der im Titel beschriebenen Click-Chemie-Umwandlung nahezu quantitativ erhalten. In einigen Fällen war zur Reinigung der Produkte dieses hoch effizienten Aufbaus der Triazoleinheiten der Dendrimere nur eine Filtration oder Lösungsmittelextraktion erforderlich.

Components that click: A large number of diverse dendrimers (see scheme) was prepared in almost quantitative yield by the click-chemistry transformation described in the title. In some cases filtration or solvent extraction was the only method required for purification in this highly efficient construction of the triazole units of the dendrimers.

Click and go: By using click chemistry based on a new triazole forming reaction condition (see scheme), over 100 triazole compounds generated in microtiter plates from a core structure were screened for HIV protease inhibition in situ without product isolation. Potent inhibitors, active at nanomolar concentrations, against the wild type and drug resistant mutants were identified.

A screen of over 500 diversely functionalized additives in osmium-catalyzed dihydroxylation has uncovered that electron-deficient olefins are converted into the corresponding diols much more efficiently when the pH of the reaction medium is maintained on the acidic side. Further studies have identified citric acid as the additive of choice, for it allows preparation of very pure diols in yields generally exceeding 90%. As described here, a much wider range of olefin classes can now be successfully dihydroxylated. The process is experimentally simple, in most cases involving little more than dissolving the reactants in water or a water/tert-butyl alcohol mixture, stirring them, and filtering off the pure diol product.

Hydroxyaminosäure-Derivate dienen als chirale Liganden bei der hier vorgestellten Methode zur osmiumkatalysierten Dihydroxylierung und Aminohydroxylierung von Olefinen (siehe Schema). Dies sind die ersten asymmetrischen osmiumkatalysierten Prozesse, bei denen im zweiten Katalysezyklus ein Ligand permanent am Metallzentrum verbleibt.

By simply stirring in water, organic azides and terminal alkynes are readily and cleanly converted into 1,4-disubstituted 1,2,3-triazoles through a highly efficient and regioselective copper(I)-catalyzed process (see scheme for an example).

Simple hydroxyamino acid derivatives act as chiral ligands in osmium-catalyzed dihydroxylation and aminohydroxylation of olefins (see scheme). These are the first examples of asymmetric osmium-catalyzed processes proceeding in the second catalytic cycle with resident ligands on the metal center.

In Wasser und ohne irgendwelche Liganden lassen sich Salze ungesättigter Carbonsäuren durch Aminohydroxylierung einfach und sauber in hoher Ausbeute in vicinale Hydroxyaminosäure-Derivate überführen (siehe Schema).

In water and in the absence of any ligands, salts of unsaturated carboxylic acids are readily and cleanly aminohydroxylated to provide vicinal hydroxyamino acid derivatives in high yields (see scheme).