Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

An approach to highly regiodivergent epoxide openings (REOs) is presented. The very popular kinetic resolutions of epoxides and openings of meso-epoxides constitute subclasses of such REOs. REOs are attractive for parallel resolutions, double asymmetric reactions of enantiomerically enriched epoxides, and for semisynthetic applications in the functionalization of natural products. They have been notoriously difficult to realize by means of S_N2 mechanisms. Our titanocene-catalyzed radical REO addresses this issue by decoupling epoxide opening and radical trapping and is firmly based on a mechanistic study of the reductive epoxide opening.

Many biologically active substances are composed of sesquiterpene units linked to aromatic structures, especially substituted phenols. Here, we describe an efficient synthetic approach to this class of natural product from commercially available substances in a short sequence. The key transformations involve allylic substitution reactions using a palladium or copper catalyst and titanocene-catalyzed epoxypolyene cyclization reactions via radicals. The polycyclic core structures are accessed with high chemo- and stereocontrol. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Sterische Einflüsse bestimmen die katalytische reduktive Epoxidringöffnung. Das ergab eine Kombination aus experimentellen und theoretischen Studien, die interessante Merkmale der Katalysatorstruktur, der Substratbindung, des Übergangszustands (siehe Bild) und der Reaktionsenergien aufdeckten. Auf dieser Grundlage können hoch selektive Bedingungen für die Ringöffnung vorgeschlagen werden.

Conceptually novel homolytic substitutions (S_H2) of ClCp₂Ti−O bonds with benzylic, secondary and tertiary alkyl radicals are described. The intermediates and crucial transition structures were studied by DFT methods. The resulting atom economical radical tandem reaction can be utilized for the synthesis of structurally complex tetrahydrofurans from simple starting materials and is therefore of interest for natural product synthesis. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

A catalyzed synthesis of cyclopropanes and cyclobutanes via radical chemistry is described. The method that generally proceeds in high yields uses epoxides as radical precursors and titanocene(III) complexes as the electron transfer catalysts (see scheme). The key to the success of the transformation is constituted by the chemoselectivity of radical reduction. Electrophilic enol radicals generated through cyclization are reduced rapidly whereas their precursors, nucleophilic alkyl radicals, remain unaffected.

A radical merry-go-round. An electron is transferred from a titanocene(III) complex to the substrate and finally back to the catalyst in a novel atom-economical tandem reaction. Complex structures can be readily accessed (see scheme). The unprecedented mechanism involving a homolytic cleavage of a TiO bond is supported by DFT calculations.

Over the last few decades the use of radicals in synthesis has witnessed an explosive growth through introduction of efficient chain and electron-transfer reactions. Strained heterocycles, in particular, have emerged as a highly versatile and readily available class of radical precursors. The generation of carbinyl radicals of heterocycles has resulted in many elegant applications of heteroatom-centered radicals, such as β fragmentations, cyclizations, and intramolecular hydrogen atom abstractions. Direct electron transfer to strained heterocycles has been realized through the use of arene radical anions. The method combines the virtues of radical and organometallic chemistry to yield useful functionalized organolithium compounds. Epoxides have been opened with high regioselectivity by titanocene(III) reagents in either stoichiometric or catalytic quantities to yield β-titanoxy radicals. This development has resulted in many new applications in natural product synthesis.

Vom Titanocen(III)-Komplex auf das Substrat und schließlich zurück zum Katalysator wird ein Elektron wie auf einem Karussell in einer neuen atomökonomischen Tandemreaktion übertragen. Komplexe Strukturen ähnlich der hier gezeigten sind einfach zugänglich. Der beispiellose Mechanismus, der eine homolytische Spaltung einer Ti-O-Bindung einschließt, wird durch DFT-Rechnungen untersucht.

In den vergangenen Jahrzehnten ist die Zahl der Anwendungen von Radikalen in der Synthese durch die Einführung effizienter Ketten- und Elektronentransfer-Reaktionen sprunghaft angestiegen. Insbesondere gespannte Heterocyclen haben sich als nützliche und leicht zugängliche Radikalvorstufen erwiesen. Die Erzeugung von Carbinylradikalen der Heterocyclen hat viele elegante Anwendungen von Heteroatom-zentrierten Radikalen ermöglicht, z. B. β-Fragmentierungen, Cyclisierungen und intramolekulare Wasserstoffatomabstraktionen. Mit aromatischen Radikalanionen gelingt der direkte Elektronentransfer auf gespannte Heterocyclen. Die folgende Ringöffnung vereint die Vorzüge von metallorganischer Chemie und Radikalchemie bei der Synthese funktionalisierter Organolithiumreagentien. Epoxide werden mit hoher Regioselektivität durch stöchiometrische oder katalytische Mengen an Titanocen(III)-Reagentien zu β-Titanoxyradikalen geöffnet. Dadurch sind zahlreiche neue Anwendungen in der Naturstoffsynthese denkbar.

The generation and addition reactions of metal bound radicals derived from normal and meso epoxides by electron transfer from titanocene(III) reagents is described. The control of enantioselectivity and diastereoselectivity of these transformations is investigated by variation of the ligands of the metal complex. The reaction can lead to unprecedented and highly selective reactions, in which synthetically useful alcohols may be prepared. The synthesis presented also circumvents the use of toxic metals. Another advantage is that there is no loss of two functional groups as usually observed in reductive radical chain reactions.

Intramolecular CC bond formation based on a titanocene-catalyzed epoxide ring opening selectively leads to tri- and tetrasubstituted olefins (see scheme). This represents an excellent method for the otherwise difficult synthesis of such compounds.

Die intramolekulare Knüpfung von C-C-Bindungen auf Basis einer Titanocen-katalysierten Epoxidringöffnung führt selektiv zu tri- und tetrasubstituierten Alkenen (siehe Schema). Damit steht eine effiziente Synthesemethode für diese bislang nur schwer zugänglichen Verbindungsklassen zur Verfügung.