Ammonium Salt Catalysts Research Articles

Chiral Quaternary Ammonium Salt‐Catalyzed Enantioselective Addition Reactions of Hydantoins

AbstractWe herein report a protocol for the asymmetric 1,4‐addition of hydantoins to various Michael acceptors by utilizing Cinchona alkaloid‐based chiral quaternary ammonium salt catalysts. Various products were obtained with moderate to good enantioselectivities and accompanying computational investigations helped to identify key interactions responsible for the observed selectivity. DFT calculations along with non‐covalent interaction plots reveal the presence of numerous stabilizing non‐classical hydrogen bonding interactions along with other non‐covalent interactions between the chiral quaternary ammonium salt and hydantoin molecule in the C−C bond forming transition states leading to the formation of the products. In addition, a first proof‐of‐concept for an analogous a‐sulfanylation reaction, albeit with poor selectivity, is reported as well.

Controlled ring-opening copolymerization of epoxides and cyclic anhydrides through bifunctional thiourea–quaternary ammonium salt catalysts

Bifunctional thiourea–quaternary ammonium salt catalysts exhibited significantly higher activity over a two-component system with a similar structure at a low catalyst loading for the ring-opening copolymerization of epoxides and cyclic anhydrides.

Towards an asymmetric β-selective addition of azlactones to allenoates.

We herein report the asymmetric organocatalytic addition of azlactones to allenoates. Upon using chiral quaternary ammonium salt catalysts, i.e., Maruoka's binaphthyl-based spirocyclic ammonium salts, the addition of various azlactones to allenoates proceeds in a β-selective manner with moderate levels of enantioselectivities (up to 83:17 er). Furthermore, the obtained products can be successfully engaged in nucleophilic ring opening reactions, thus giving highly functionalized α-amino acid derivatives.

Enantioselective β-Selective Addition of Isoxazolidin-5-ones to Allenoates Catalyzed by Quaternary Ammonium Salts.

The enantioselective addition of isoxazolidin-5-ones to the β-carbon of allenoates has been carried out by using a novel spirobiindane-based quaternary ammonium salt catalyst. This protocol, which proceeds under classical liquid-solid phase-transfer conditions, gives access to unprecedented highly functionalized β2,2-amino acid derivatives with good enantioselectivities and in high yields, and further manipulations of these products have been carried out as well.

(Thio)urea Containing Chiral Ammonium Salt Catalysts.

(Thio)-urea-containing bifunctional quaternary ammonium salts emerged as powerful non-covalently interacting organocatalysts over the course of the last decade. The most commonly employed catalysts in this field are either based on Cinchona alkaloids, α-amino acids, or trans-cyclohexane-1,2-diamine. Our group has been heavily engaged in the design and use of such catalysts, i. e. trans-cyclohexane-1,2-diamine-based ones for around 10 years now, and it is therefore the intention of this short personal account to provide an overview of the, at least in our opinion, most significant and pioneering achievements in this field by looking on catalyst design and asymmetric method development, with a special focus on our own contributions.

Asymmetric Hydroboration of Ketones by Cooperative Lewis Acid–Onium Salt Catalysis: A Quantum Chemical and Microkinetic Study to Combine Theory and Experiment

We apply microkinetic modeling in homogeneous catalysis and show how it can be used to reveal important details of a complex mechanism and how this can lead to a direct comparison between theory and experiment. While regularly used in heterogeneous catalysis, its applications to organic chemistry or homogeneous catalysis are still comparatively scarce. This approach is exemplarily applied to the mechanism of the asymmetric hydroboration of acetophenone with a highly active cooperative Lewis acid–ammonium salt catalyst. In combination with density functional theory, it is a gateway to shed light into important mechanistic details. In our study, it reveals that the counterion of the ammonium salt of the catalyst facilitates the hydride transfer step of the cycle. Chloride replacing iodide speeds up the main reaction but simultaneously has the same effect on a side reaction that consumes the product. This observation is confirmed by experimental measurements of both the main catalytic cycle and the side reaction. A sensitivity analysis showed that the transition from the product complex to the hydride transfer is rate-limiting and that it determines the enantioselectivity. Based on this insight, an enantioselective kinetic model was applied, from which the difference of the Gibbs free energy barriers of the two pathways forming the two enantiomers can be extracted. The barriers are in fairly good agreement with the ones calculated by DFT, which reveal that the asymmetric backbone interacts with the reactant sterically to favor asymmetric product formation.

Enantioselective Bifunctional Ammonium Salt-Catalyzed Syntheses of 3-CF3S-, 3-RS-, and 3-F-Substituted Isoindolinones.

We herein report the ammonium salt‐catalyzed synthesis of chiral 3,3‐disubstituted isoindolinones bearing a heteroatom functionality in the 3‐position. A broad variety of differently substituted CF3S‐ and RS‐derivatives were obtained with often high enantioselectivities when using Maruoka's bifunctional chiral ammonium salt catalyst. In addition, a first proof‐of‐concept for the racemic synthesis of the analogous F‐containing products was obtained as well, giving access to one of the rare examples of a fairly stable α‐F‐α‐amino acid derivative.

Highly Active Cooperative Lewis Acid—Ammonium Salt Catalyst for the Enantioselective Hydroboration of Ketones

AbstractEnantiopure secondary alcohols are fundamental high‐value synthetic building blocks. One of the most attractive ways to get access to this compound class is the catalytic hydroboration. We describe a new concept for this reaction type that allowed for exceptional catalytic turnover numbers (up to 15 400), which were increased by around 1.5–3 orders of magnitude compared to the most active catalysts previously reported. In our concept an aprotic ammonium halide moiety cooperates with an oxophilic Lewis acid within the same catalyst molecule. Control experiments reveal that both catalytic centers are essential for the observed activity. Kinetic, spectroscopic and computational studies show that the hydride transfer is rate limiting and proceeds via a concerted mechanism, in which hydride at Boron is continuously displaced by iodide, reminiscent to an SN2 reaction. The catalyst, which is accessible in high yields in few steps, was found to be stable during catalysis, readily recyclable and could be reused 10 times still efficiently working.

A Remarkably Efficient Phase-Transfer Catalyzed Amination of α-Bromo-α, β-Unsaturated Ketones in Water

Tandem conjugate addition–alkylation reaction of various amines with α-bromo-α, β-unsaturated ketones resulted in near-quantitative conversions into the corresponding aziridines when the reaction was carried out in the presence of 10 mol% of phase-transfer, PT catalysts in water. Some chiral quaternary ammonium salts derived from Cinchona alkaloids were investigated as water-stable PT catalysts. The scope and limitations of the reaction have also been investigated. The catalytic performances were significantly improved in comparison with the corresponding ordinary quaternary ammonium salt catalysts, and excellent yields (81%–96%) were obtained. Although an increase in the rate of aziridination has been accomplished, no stereoselectivity was observed. The positive values of the protocol have been confirmed.

Conversion of dilute CO2 to cyclic carbonates at sub-atmospheric pressures by a simple indium catalyst

A simple indium halide with an ammonium salt catalyst can catalyze effectively the cycloaddition of epoxide and dilute CO2. A detailed mechanistic investigation is conducted using kinetics, isotope labeling, and in situ NMR and IR experiments.

Kinetic Resolution of α-Nitrolactones by Catalytic Asymmetric Hydrolysis or Ester–Amide Exchange Reaction

Abstract C 1-Symmetric chiral ammonium salt catalysts induced a kinetic resolution of racemic α-nitrolactones through an asymmetric ester–amide exchange reaction. The corresponding amides were obtained with high enantioselectivities and high S (= k fast/k slow) values. This reaction system is a useful approach for obtaining carbocyclic quaternary α-nitroamides as chiral building blocks.

Ammonium Salt-Catalyzed Ring-Opening of Aryl-Aziridines with β-Keto Esters.

We herein report an ammonium salt‐catalyzed protocol for the regioselective ring opening of aryl‐aziridines with β‐keto esters. The reaction gives access to a variety of highly functionalized target molecules with two consecutive stereogenic centers and can be rendered enantioselective (up to e.r. = 91:9) by using bifunctional chiral ammonium salt catalysts.

Enantioselective Acetalization by Dynamic Kinetic Resolution for the Synthesis of γ-Alkoxybutenolides by Thiourea/Quaternary Ammonium Salt Catalysts: Application to Strigolactones.

Although acetalization is a fundamental transformation in organic synthesis, intermolecular asymmetric acetalization remains an unsolved problem. In this study, a thiourea-ammonium hybrid catalyst was shown to promote the O-alkylation of enols with a racemic γ-chlorobutenolide through dynamic kinetic resolution to give chiral acetals with good enantioselectivity. The catalyst simultaneously activates both the nucleophile and electrophile in a multifunctional manner. This method was applied to the asymmetric synthesis of several strigolactones. DFT calculations suggest that hydrogen-bonding interactions between the chlorine atom of the γ-chlorobutenolide and the tosylamide hydrogen atom of the catalyst, as well as other types of noncovalent catalyst-substrate interactions, are crucial for achieving high stereoselectivity.

Enantioselective Acetalization by Dynamic Kinetic Resolution for the Synthesis of γ‐Alkoxybutenolides by Thiourea/Quaternary Ammonium Salt Catalysts: Application to Strigolactones

AbstractAlthough acetalization is a fundamental transformation in organic synthesis, intermolecular asymmetric acetalization remains an unsolved problem. In this study, a thiourea‐ammonium hybrid catalyst was shown to promote the O‐alkylation of enols with a racemic γ‐chlorobutenolide through dynamic kinetic resolution to give chiral acetals with good enantioselectivity. The catalyst simultaneously activates both the nucleophile and electrophile in a multifunctional manner. This method was applied to the asymmetric synthesis of several strigolactones. DFT calculations suggest that hydrogen‐bonding interactions between the chlorine atom of the γ‐chlorobutenolide and the tosylamide hydrogen atom of the catalyst, as well as other types of noncovalent catalyst–substrate interactions, are crucial for achieving high stereoselectivity.

Mario Waser

Abstract“My group focusses on the design of bifunctional chiral ammonium salt catalysts and on the development of catalytic asymmetric methods to access fluorinated amino acids and peptides.” Find out more about this author's research at https://doi.org/10.1002/ejoc.202000295.

Bifunctional Thiourea-Ammonium Salt Catalysts Derived from Cinchona Alkaloids: Cooperative Phase-Transfer Catalysts in the Enantioselective Aza-Henry Reaction of Ketimines.

An efficient enantioselective aza-Henry reaction of aryl α-ketoester-derived ketimines has been realized by using bifunctional thiourea-ammonium salt phase-transfer catalysts, which were derived from quinine. A variety of aryl α-ketoester-derived N-Ts ketimines were investigated, and the corresponding products were obtained in high to excellent yields (up to 99%) with good to high enantioselectivities (up to >99% ee).

Highly efficient conversion of CO2 to cyclic carbonates with a binary catalyst system in a microreactor: intensification of "electrophile-nucleophile" synergistic effect.

An intensification of the “electrophile–nucleophile” synergistic effect was achieved in a microreactor for the coupling reaction of CO2 and epoxides mediated by the binary Al complex/ternary ammonium salt catalyst system. The microreactor technology is proven to be a powerful tool for the preparation of cyclic carbonates with an improved reaction rate and a wide substrate scope.

CO2 Fixation with Epoxides under Mild Conditions with a Cooperative Metal Corrole/Quaternary Ammonium Salt Catalyst System.

The cooperative catalytic activity of several metal corrole complexes in combination with tetrabutyl‐ammonium bromide (TBAB) has been investigated for the reaction of epoxides with CO2 leading to cyclic carbonates. It was found that the use of just 0.05 mol % of a manganese(III)corrole with 2 mol % TBAB exhibits excellent catalytic activity under an atmosphere of CO2.

Catalytic Enantioselective γ‐Selective Additions of 2‐Allylazaarenes to Activated Ketones

AbstractReported herein is the first example of 2‐allylazaarenes in asymmetric catalysis. Highly γ‐selective allylation was demonstrated for activated ketones, including isatins and trifluoromethyl ketones. In the presence of either an amino‐acid‐based tertiary amine or quaternary ammonium salt catalyst, two series of tertiary hydroxy‐containing moieties were installed at the remote δ‐position of azaarenes in good chemical yields, excellent enantioselectivities, and E/Z ratios. The success of current γ‐selective reactions should provide inspiration for expansion to other allylazaarene derivatives and would open up new paradigms for the synthesis of chiral γ‐ and/or δ‐functionalized azaarenes.

Catalytic Enantioselective γ-Selective Additions of 2-Allylazaarenes to Activated Ketones.

Reported herein is the first example of 2-allylazaarenes in asymmetric catalysis. Highly γ-selective allylation was demonstrated for activated ketones, including isatins and trifluoromethyl ketones. In the presence of either an amino-acid-based tertiary amine or quaternary ammonium salt catalyst, two series of tertiary hydroxy-containing moieties were installed at the remote δ-position of azaarenes in good chemical yields, excellent enantioselectivities, and E/Z ratios. The success of current γ-selective reactions should provide inspiration for expansion to other allylazaarene derivatives and would open up new paradigms for the synthesis of chiral γ- and/or δ-functionalized azaarenes.