Mario Waser

Asymmetric cyclopropanation of chalcones using chiral phase-transfer catalysts

Graphical abstract

Design of chiral urea-quaternary ammonium salt hybrid catalysts for asymmetric reactions of glycine Schiff bases

Bifunctional chiral urea-containing quaternary ammonium salts can be straightforwardly synthesised in good yield and with high structural diversity via a scalable and operationally simple highly telescoped sequence starting from trans-1,2-cyclohexanediamine. These novel hybrid catalysts were systematically investigated for their potential to control glycine Schiff bases in asymmetric addition reactions. It was found that Michael addition reactions and the herein presented aldol-initiated cascade reaction can be carried out to provide enantiomeric ratios up to 95 : 5 and good yields under mild conditions at room temperature.

Enantioselective Spirocyclopropanation of para-Quinone Methides Using Ammonium Ylides

The use of Cinchona alkaloid-based chiral ammonium ylides allows for the first highly enantioselective and broadly applicable spirocyclopropanation reactions of para-quinone methides. This strategy provides a straightforward protocol toward the chiral spiro[2.5]octa-4,7-dien-6-one skeleton, which is a frequently found structural motif in important biologically active molecules.

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

Summary New bifunctional chiral ammonium salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as the Belliotti (S)-PD172938 and arylated analogues with hypnotic sedative activity, obtained in good overall total yield (50%) and high enantiomeric purity (95% ee). The synthetic routes developed herein are particularly convenient in comparison with the current methods available in literature and are particularly promising for large scale applications.

Asymmetric organocatalysis in natural product syntheses.

1 Introduction.- 2 Enamine Catalysis.- Aldol Reactions.- Mannich Reactions.- a-Heterofunctionalizations.- Conjugate Additions.- Dienamine Catalysis.- Combined Enamine-Catalyzed Approaches and Cascade Reactions.- Synopsis.- 3 Iminium Catalysis.- Pericyclic Reactions.- Conjugate Additions.- Iminium-Catalyzed Organocascade Reactions.- Synopsis.- 4 Combined Iminium-Enamine Catalyzed Approaches.- Cascade Reactions Using a Single Organocatalyst.- Organocascade Catalysis Using a Combination of Different Catalysts.- Synopsis.- 5 Singly Occupied Molecular Orbital (SOMO) Catalysis.- Friedel-Crafts Reactions.- Epoxide Formation.- Synopsis.- 6 Asymmetric Phase-Transfer Catalysis.- Asymmetric a-Alkylations.- Phase-Transfer Catalyzed Michael Additions.- Alkylative Dearomatization-Annulation Reaction.- Synopsis.- 7 Chiral Bronsted Acids and Hydrogen Bonding Donors.- Chiral Phosphoric Acids.- Chiral Diols.- Chiral (Thio)-Ureas.- Bifunctional Bronsted Acid-Base Active (Thio)-Ureas.- Synopsis.- 8 Chiral Bronsted and Lewis Bases.- Cinchona Alkaloids.- Phosphine Catalysis.- Carbene Catalysis.- Synopsis.- 9 Asymmetric Oxidations and Reductions.- Organocatalytic Oxidations.- Organocatalytic Reductions.- Synopsis.- 10 Conclusions.

Asymmetric Synthesis of 2,3-Dihydrobenzofurans by a [4+1] Annulation Between Ammonium Ylides and In Situ Generated o-Quinone Methides

Abstract A highly enantio‐ and diastereoselective [4+1] annulation between in situ generated ammonium ylides and o‐quinone methides for the synthesis of a variety of 2,3‐dihydrobenzofurans has been developed. The key factors controlling the reactivity and stereoselectivity were systematically investigated by experimental and computational means and the energy profiles obtained provide a deeper insight into the mechanistic details of this reaction.

Towards Tartaric-Acid-Derived Asymmetric Organocatalysts

Tartaric acid is one of the most prominent naturally occurring chiral compounds. Whereas its application in the production of chiral ligands for metal-catalysed reactions has been exhaustively investigated, its potential to provide new organocatalysts has been less extensively explored. Nevertheless, some impressive results, such as the use of TADDOLs as chiral H-bonding catalysts or of tartrate-derived asymmetric quaternary ammonium salt catalysts, have been reported over the last decade. The goal of this article is to provide a representative overview of the potential and the limitations of tartaric acid or TADDOLs in the creation of new organocatalysts and to highlight some of the most spectacular applications of these catalysts, as well as to summarize case studies in which other classes of chiral backbones were better suited.

Identification of the best-suited leaving group for the diastereoselective synthesis of glycidic amides from stabilised ammonium ylides and aldehydes

In comparison to the use of sulfur ylides, the use of ammonium ylides for the synthesis of epoxides is significantly less developed. As a part of our systematic investigations concerning the use of amide-stabilised ammonium ylides for the synthesis of glycidic amides we have focused on the identification of the best-suited amino leaving group for this purpose. Whereas tertiary amines like quinuclidine or cinchona alkaloids were found to be not suited for epoxide formation, trimethylamine was found to be the leaving group of choice, yielding trans-glycidic amides in excellent yields of > 90%.

Bifunctional Ammonium Salt Catalyzed Asymmetric α-Hydroxylation of β-Ketoesters by Simultaneous Resolution of Oxaziridines

Chiral bifunctional urea-containing ammonium salts were found to be very efficient catalysts for asymmetric α-hydroxylation reactions of β-ketoesters with oxaziridines under base-free conditions. The reaction is accompanied by a simultaneous kinetic resolution of the oxaziridine and a plausible and so far unprecedented bifunctional transition-state model has been obtained by means of DFT calculations.

An Organocatalytic Biomimetic Strategy Paves the Way for the Asymmetric Umpolung of Imines

Just like Nature: A recently developed enantioselective organocatalytic biomimetic transamination provides an elegant approach towards chiral amines. In the presence of an asymmetric phase-transfer catalyst, the intermediate anionic species undergoes an asymmetric C-C bond-forming reaction in a powerful and broadly applicable asymmetric umpolung strategy.