Study of Ground State Interactions of Enantiopure Chiral Quaternary Ammonium Salts and Amides, Nitroalkanes, Nitroalkenes, Esters, Heterocycles, Ketones and Fluoroamides.

Chiral phase-transfer catalysis provides high level of enantiocontrol, however no experimental data showed the interaction of catalysts and substrates. 1 H NMR titration was carried out on Cinchona and Maruoka ammonium bromides vs. nitro, carbonyl, heterocycles, and N-F containing compounds. It was found that neutral organic species and quaternary ammonium salts interacted via an ensemble of catalyst + N-C-H and (sp2 )C-H, specific for each substrate studied. The correspondent BArF salts interacted with carbonyls via a diverse set of + N-C-H and (sp2 )C-H compared to bromides. This data suggests that BArF ammonium salts may display a different enantioselectivity profile. Although not providing quantitative data for the affinity constants, the data reported proofs that chiral ammonium salts coordinate with substrates, prior to transition state, through specific C-H positions in their structures, providing a new rational to rationalize the origin of enantioselectivity in their catalyses.

Towards a General Understanding of Carbonyl-Stabilised Ammonium Ylide-Mediated Epoxidation Reactions.

The key factors for carbonyl-stabilised ammonium ylide-mediated epoxidation reactions were systematically investigated by experimental and computational means and the hereby obtained energy profiles provide explanations for the observed experimental results. In addition, we were able to identify the first tertiary amine-based chiral auxiliary that allows for high enantioselectivities and high yields for such epoxidation reactions.

Bifunctional Ammonium Salt Catalyzed Asymmetric α-Hydroxylation of ß-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 ß-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.

Asymmetric syntheses of three-membered heterocycles using chiral amide-based ammonium ylides.

The use of carbonyl-stabilised ammonium ylides to access chiral glycidic amides and the corresponding aziridines has so far been limited to racemic trans-selective protocols. We herein report the development of an asymmetric approach to access such compounds with high levels of stereoselectivity using easily accessible chiral auxiliary-based ammonium ylides. The use of phenylglycinol as the chiral auxiliary was found to be superior to Evans or pseudoephedrine-based auxiliaries resulting in good to excellent stereoselectivities in both, epoxidation and aziridination reactions.

Towards an asymmetric organocatalytic α-cyanation of ß-ketoesters.

This communication describes the first proof of concept for an asymmetric α-cyanation of ß-ketoesters using a hypervalent iodine-based electrophilic cyanide-transfer reagent. A series of different organocatalysts has been investigated and it was found that the use of naturally occurring Cinchona alkaloids allows obtaining the target products in good yields and with moderate enantioselectivities up to er = 76:24 under operationally simple conditions.

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.

Syntheses and Applications of (Thio)Urea-Containing Chiral Quaternary Ammonium Salt Catalysts.

We herein report our efforts to obtain a new class of systematically modified bifunctional (thio)urea-containing quaternary ammonium salts based on easily obtainable chiral backbones. Among the different classes of catalysts that were successfully synthesized, those based on trans-1,2-cyclohexane diamine were found to be the most powerful for the asymmetric α-fluorination of ß-keto esters. Selectivities up to 93:7 could be obtained by using only 2 mol-% of the optimized catalyst. The importance of the bifunctional nature of these catalysts was demonstrated by control experiments using simplified monofunctional catalyst analogues, which gave almost racemic product only.

Synergistic Ammonium (Hypo)Iodite/Imine Catalysis for the Asymmetric α-Hydroxylation of ß-Ketoesters.

The synergistic use of chiral bifunctional ammonium iodide catalysts in combination with simple catalytically relevant aldimines allows for an unprecedented asymmetric α-hydroxylation reaction of ß-ketoesters using H2O2. The reaction proceeds via in situ formation of a hypervalent iodine species, which then reacts with the used aldimine to generate an activated electrophilic oxygen transfer reagent.

On the origin of the stereoselectivity in chiral amide-based ammonium ylide-mediated epoxidations.

ABSTRACT: Detailed DFT studies provide an in-depth mechanistic understanding for the use of chiral amide-based ammonium ylides in epoxidation reactions. It is shown that the used chiral auxiliary efficiently shields one face of the ylide, which thus results in an extraordinarily high stereoselectivity giving only one trans-isomer with perfect control of the absolute configuration.

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.