Magnus Rueping

Unifying metal and Brønsted acid catalysis--concepts, mechanisms, and classifications.

Asymmetric catalysis is a key feature of modern synthetic organic chemistry. Traditionally, different combinations of ligands and metals are used to perform highly enantioselective reactions. Since the renaissance of organocatalysis in the early 2000s, tremendous improvement in the field of metal-free catalysis has been achieved. Recently, the combination of transition metals and organocatalysts has allowed the development of new protocols enabling transformations that could not previously be realized. This article aims to present the latest contributions in the field of combined chiral Brønsted acid and metal catalyzed reactions, highlighting the advantages of these catalytic systems as well as describing the uncertainties regarding the molecular structure of the catalytically active species and the reaction mechanisms.

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

Summary The development of efficient Friedel–Crafts alkylations of arenes and heteroarenes using only catalytic amounts of a Lewis acid has gained much attention over the last decade. The new catalytic approaches described in this review are favoured over classical Friedel–Crafts conditions as benzyl-, propargyl- and allyl alcohols, or styrenes, can be used instead of toxic benzyl halides. Additionally, only low catalyst loadings are needed to provide a wide range of products. Following a short introduction about the origin and classical definition of the Friedel–Crafts reaction, the review will describe the different environmentally benign substrates which can be applied today as an approach towards greener processes. Additionally, the first diastereoselective and enantioselective Friedel–Crafts-type alkylations will be highlighted.

Oxygen Switch in Visible-Light Photoredox Catalysis: Radical Additions and Cyclizations and Unexpected C–C-Bond Cleavage Reactions

Visible light photoredox catalyzed inter- and intramolecular C-H functionalization reactions of tertiary amines have been developed. Oxygen was found to act as chemical switch to trigger two different reaction pathways and to obtain two different types of products from the same starting material. In the absence of oxygen, the intermolecular addition of N,N-dimethyl-anilines to electron-deficient alkenes provided γ-amino nitriles in good to high yields. In the presence of oxygen, a radical addition/cyclization reaction occurred which resulted in the formation of tetrahydroquinoline derivatives in good yields under mild reaction conditions. The intramolecular version of the radical addition led to the unexpected formation of indole-3-carboxaldehyde derivatives. Mechanistic investigations of this reaction cascade uncovered a new photoredox catalyzed C-C bond cleavage reaction.

Modulating the Acidity: Highly Acidic Brønsted Acids in Asymmetric Catalysis

Recently, chiral highly acidic Brønsted acids have emerged as powerful catalysts for enantioselective C-C and C-X bond-forming reactions. Their strong acidity renders them valuable tools for the activation of imines, carbonyl compounds, and other weakly basic substrates. As a result, new perspectives are opened and highly stereoselective transformations based on the concept of chiral contact-ion-pair catalysis can be realized. This Minireview gives an overview of the design and application of these new organocatalysts and presents recent results in this rapidly growing field.

Direct Catalytic Trifluoromethylthiolation of Boronic Acids and Alkynes Employing Electrophilic Shelf‐Stable N‐(trifluoromethylthio)phthalimide

A new and safe method for the synthesis of N-(trifluoromethylthio)phthalimide, a convenient and shelf-stable reagent for the direct trifluoromethylthiolation, has been developed. N-(Trifluoromethylthio)phthalimide can be used as an electrophilic source of F3 CS(+) and reacts readily with boronic acids and alkynes under copper catalysis. The utility of CF3 S-containing molecules as biologically active agents, the mild reaction conditions employed, and the high tolerance of functional groups demonstrate the potential of this new methodology to be widely applied in organic synthesis as well as industrial pharmaceutical and agrochemical research and development.

N-Trifluoromethylthiophthalimide: A Stable Electrophilic SCF3-Reagent and its Application in the Catalytic Asymmetric Trifluoromethylsulfenylation†

Cinchona alkaloid catalysts in combination with air- and moisture-stable N-trifluoromethylthiophthalimide as electrophilic SCF3 source enabled the catalytic enantioselective trifluoromethylsulfenylation. Thus, a series of α-SCF3 esters that bear a quaternary carbon stereogenic center were obtained with excellent yield and enantioselectivity. Moreover, the products can be readily converted into valuable α-SCF3 β-hydroxyesters.

Chiral Organic Contact Ion Pairs in Metal-Free Catalytic Asymmetric Allylic Substitutions

Chiral contact ion-pair catalysis with particular focus on metal-free processes is gaining in interest. As a result, new perspectives are opened, and highly stereoselective transformations, traditionally performed under metal catalysis, can be realized. Herein, we report the development of an unprecedented asymmetric Brønsted acid-catalyzed allylic alkylation. The concept relies on chiral contact ion-pair catalysis, in which the chiral organic counteranion of an allylic carbocation induces high enantioselectivities and allows access to biologically relevant chromenes in good yields and with excellent enantioselection.

Advances in catalytic metal-free reductions: from bio-inspired concepts to applications in the organocatalytic synthesis of pharmaceuticals and natural products

This review focuses on recent advances in catalytic metal-free transfer hydrogenations. In recent years dihydropyridines have been widely used as reducing agents in organocatalytic reductions. Analogous to natures co-factor nicotinamide adenine dinucleotide (NADH), Hantzsch esters serve as efficient hydride donors. In combination with chiral organocatalysts, including chiral secondary amines, hydrogen bond donors or Bronsted acids, efficient catalytic asymmetric reductions have been developed which provide a diverse set of biologically active compounds, synthetic building blocks and natural products. These recent advances in developing green and sustainable reductions employing organocatalytic strategies are promising and important alternatives to conventional metal- and bio-catalyzed reductions.

Dual Catalysis: Combination of Photocatalytic Aerobic Oxidation and Metal Catalyzed Alkynylation Reactions—CC Bond Formation Using Visible Light

A new dual catalytic system for efficient C[BOND]H functionalization was developed. The appropriate choice of two metal catalysts allows the oxidative alkynylation of tertiary amines under mild and sustainable reaction conditions.

Light‐Mediated Heterogeneous Cross Dehydrogenative Coupling Reactions: Metal Oxides as Efficient, Recyclable, Photoredox Catalysts in CC Bond‐Forming Reactions

Let there be light: A heterogeneous photocatalytic system based on easily recyclable TiO(2) or ZnO allows cross dehydrogenative coupling reactions of tertiary amines. The newly developed protocols have successfully been applied to various C-C and C-P bond-forming reactions to provide nitro amines as well as amino ketones, nitriles and phosphonates.