The site-selective formation of carbon-carbon bonds through direct functionalizations of otherwise unreactive carbon-hydrogen bonds constitutes an economically attractive strategy for an overall streamlining of sustainable syntheses. In recent decades, intensive research efforts have led to the development of various reaction conditions for challenging C-H bond functionalizations, among which transition-metal-catalyzed transformations arguably constitute thus far the most valuable tool. For instance, the use of inter alia palladium, ruthenium, rhodium, copper, or iron complexes set the stage for chemo-, site-, diastereo-, and/or enantioselective C-H bond functionalizations. Key to success was generally a detailed mechanistic understanding of the elementary C-H bond metalation step, which depending on the nature of the metal fragment can proceed via several distinct reaction pathways. Traditionally, three different modes of action were primarily considered for CH bond metalations, namely, (i) oxidative addition with electronrich late transition metals, (ii) σ-bond metathesis with early transition metals, and (iii) electrophilic activation with electrondeficient late transition metals (Scheme 1). However, more recent mechanistic studies indicated the existence of a continuum of electrophilic, ambiphilic, and nucleophilic interactions. Within this continuum, detailed experimental and computational analysis provided strong evidence for novel C-H bond metalationmechanisms relying on the assistance of a bifunctional ligand bearing an additional Lewis-basic heteroatom, such as that found in (heteroatom-substituted) secondary phosphine oxides or most prominently carboxylates (Scheme 1, iv). This novel insight into the nature of stoichiometric metalations has served as stimulus for the development of novel transformations based on cocatalytic amounts of carboxylates, which significantly broadened the scope of C-H bond functionalizations in recent years, with most remarkable progress being made in palladiumor ruthenium-catalyzed direct arylations and direct alkylations. These carboxylate-assisted C-H bond transformations were mostly proposed to proceed via a mechanism in which metalation takes place via a concerted base-assisted deprotonation. To mechanistically differentiate these intramolecular metalations new acronyms have recently been introduced into the literature, such as CMD (concerted metalationdeprotonation), IES (internal electrophilic substitution), or AMLA (ambiphilic metal ligand activation), which describe related mechanisms and will be used below where appropriate. This review summarizes the development and scope of carboxylates as cocatalysts in transition-metal-catalyzed C-H functionalizations until autumn 2010. Moreover, experimental and computational studies on stoichiometric metalation reactions being of relevance to the mechanism of these catalytic processes are discussed as well. Mechanistically related C-H bond cleavage reactions with ruthenium or iridium complexes bearing monodentate ligands are, however, only covered with respect to their working mode, and transformations with stoichiometric amounts of simple acetate bases are solely included when their mechanism was suggested to proceed by acetate-assisted metalation.

Carboxylate-assisted transition-metal-catalyzed C-H bond functionalizations: mechanism and scope.

Practical methodologies for the synthesis of indoles.

Palladium-catalyzed amination reactions of aryl halides have undergone rapid development in the last 12 years, largely driven by the implementation of new classes of ligands. Biaryl phosphanes have proven to provide especially active catalysts in this context. This Review discusses the application of these catalysts in C-N cross-coupling reactions in the synthesis of heterocycles and pharmaceuticals, in materials science, and in natural product synthesis.

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Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

8.4.5. Nitromercuration Reactions 3878 9. Hydroamination of Alkenes and Alkynes under Microwave Irradiation 3878 * To whom correspondence should be addressed. Phone: +49 241 8

Hydroamination: direct addition of amines to alkenes and alkynes.

: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

The regioselective functionalization of terminal alkenes and alkynes is of utmost importance for the synthesis of a wide variety of organic products. Based on the original observation by Vladimir Markovnikov-the pioneer of this field of research-in the 19th century, the possible regioisomeric products are classified as Markovnikov or anti-Markovnikov products. Contrary to traditional belief, it is nowadays possible to control the regiochemistry of various additions of nucleophiles to alkenes and alkynes by applying different transition-metal catalysts. Recent developments in this area of selective functionalization of alkenes and alkynes are reviewed.

Catalytic Markovnikov and anti-Markovnikov functionalization of alkenes and alkynes: recent developments and trends.

The base-catalyzed hydroamination of olefins offers a simple and elegant access to various primary, secondary, and tertiary amines. Particular focus is placed on developments in the area of hydroamination of non-activated olefins. Advantages and disadvantages of the methodology compared to other synthetic methods are presented. Special attention is paid to potential industrial applications of this chemistry.

Base-Catalyzed Hydroamination of Olefins: An Environmentally Friendly Route to Amines

In the past decade alkynes have become attractive starting materials for the synthesis of a variety of indole derivatives. This review summarizes the development of diverse homogeneous catalytic methods for the synthesis of indoles from alkynes and different N nucleophiles such as arylhydrazines, aniline derivatives, aryl isonitriles and nitroarenes.

Catalytic Synthesis of Indoles from Alkynes

Reaktionen zur selektiven Veredelung von Alkenen zahlen zu den wichtigsten Methoden in der Organischen Synthese. Durch die Entwicklung von Ubergangsmetallkatalysatoren in den letzten Jahrzehnten konnen heute alle Arten von Selektivitat bei einer Vielzahl von Transformationen effizient gesteuert werden. Auch 100 Jahre nach dem Tod von Vladimir Markownikow – dem Pionier auf diesem Gebiet – ist die regioselektive Funktionalisierung von Alkenen und Alkinen immer noch ein wichtiges Forschungsziel: Besonders die Anti-Markownikow-Addition von Sauerstoff- und Stickstoff-Nucleophilen an aliphatische Alkene und Alkine verfugt uber groses industrielles Potenzial. In diesem Aufsatz werden neuere Entwicklungen auf diesem Gebiet beschrieben. Eine Auswahl aktueller Beispiele zeigt, wie die Regioselektivitat durch die Wahl des Katalysators gesteuert werden kann.

Katalytische Markownikow‐ und Anti‐Markownikow‐Funktionalisierung von Alkenen und Alkinen

The N-alkylation of amines in the presence of different ruthenium catalysts generated in situ was investigated. Among the various catalysts tested, the combination of [Ru3(CO)12] and N-phenyl-2-(dicyclohexylphosphanyl)pyrrole showed the best performance. By applying this novel catalyst, a variety of functionalized alcohols and amines were converted into the corresponding secondary amines in high yield.

Annegret Tillack

Papers

Catalytic Markovnikov and anti-Markovnikov functionalization of alkenes and alkynes: recent developments and trends.

Base-Catalyzed Hydroamination of Olefins: An Environmentally Friendly Route to Amines

Catalytic Synthesis of Indoles from Alkynes

Katalytische Markownikow‐ und Anti‐Markownikow‐Funktionalisierung von Alkenen und Alkinen

An Improved Ruthenium Catalyst for the Environmentally Benign Amination of Primary and Secondary Alcohols