Noncovalent Organocatalysts Research Articles

Iodonium and Telluronium Triflates Serving as Noncovalent Organocatalysts Provide Catalytic Effect in the Schiff Condensation Due to Different Reasons

AbstractSulfonium, selenonium, telluronium triflates, as well as chloronium, bromonium, and iodonium triflates have been examined in the model Schiff condensation as chalcogen‐ and halogen bond donating organocatalysts, respectively. The kinetic data indicated that the catalytic effect of the telluronium salt is provided via the decrease of enthalpy of activation of the reaction, whereas the catalytic effect of the iodonium salt – unexpectedly – is caused by the decrease of the value of the entropy of activation. In addition, it was experimentally shown that the catalytic activity of sulfonium and selenonium salts is significantly lower than that of chloronium and bromonium salts, but the latter pair of species is significantly less stable under the reaction conditions than the former pair.

Tert-Butyl 2-Amino-3-cyano-5-oxo-4-phenyl-5,7-dihydropyrano[2,3-c]pyrrole-6(4H)-carboxylate

Organocatalyzed synthesis of tert-butyl 2-amino-3-cyano-5-oxo-4-phenyl-5,7-dihydropyrano[2,3-c]pyrrole-6(4H)-carboxylate, prepared from Boc-tetramic acid and benzylidenemalononitrile, is disclosed. Two bifunctional noncovalent organocatalysts were employed, yielding the product as a racemic mixture in both cases. The structure of the new synthesized compound was confirmed by high resolution mass-spectrometry, 1H- and 13C-NMR, HSQC, and IR spectroscopy.

Sulfonium and Selenonium Salts as Noncovalent Organocatalysts for the Multicomponent Groebke-Blackburn-Bienaymé Reaction.

Sulfonium and selenonium salts, represented by S-aryl dibenzothiophenium and Se-aryl dibenzoselenophenium triflates, were found to exhibit remarkable catalytic activity in the model Groebke-Blackburn-Bienaymé reaction. Kinetic analysis and density functional theory (DFT) calculations indicated that their catalytic effect is induced by the ligation of the reaction substrates to the σ-holes on the S or Se atom of the cations. The experimental data indicated that although 10-fold excess of the chloride totally inhibits the catalytic activity of the sulfonium salts, the selenonium salt remains catalytically active, which can be explained by the experimentally found lower binding constant of the selenonium derivative to chloride in comparison with the sulfonium analogue. Both types of salts exhibit lower catalytic activity in the model reaction than dibenziodolium species.

Xenon Derivatives as Aerogen Bond-Donating Catalysts for Organic Transformations: A Theoretical Study on the Metaphorical "Spherical Cow in a Vacuum" Provides Insights into Noncovalent Organocatalysis.

Computations indicate that cationic and noncharged xenon derivatives should exhibit higher catalytic activity than their iodine-based noncovalent organocatalytic congeners. Perfluorophenyl xenonium(II) is expected to demonstrate the best balance between catalytic activity and chemical stability for use in organocatalysis. Comparing its catalytic activity with that of isoelectronic perfluoroiodobenzene indicates that the high catalytic activity of cationic noncovalent organocatalysts is predominantly attributed to the electrostatic interactions with the reaction substrates, which cause the polarization of ligated species during the reaction progress. In contrast, the electron transfer and covalent contributions to the bonding between the catalyst and substrate have negligible effects. The dominant effect of electrostatic interactions results in a strong negative correlation between the calculated Gibbs free energies of activation for the modeled reactions and the highest potentials of the σ-holes on the central atoms of the catalysts. No such correlation is observed for noncharged catalysts.

Halonium, chalconium, and pnictonium salts as noncovalent organocatalysts: a computational study on relative catalytic activity.

This theoretical study sheds light on the relative catalytic activity of pnictonium, chalconium, and halonium salts in reactions involving elimination of chloride and electrophilic activation of a carbonyl group. DFT calculations indicate that for cationic aromatic onium salts, values of the electrostatic potential on heteroatom σ-holes gradually increase from pnictogen- to halogen-containing species. The higher values of the potential on the halogen atoms of halonium salts result in the overall higher catalytic activity of these species, but in the case of pnictonium and chalconium cations, weak interactions from the side groups provide an additional stabilization effect on the reaction transition states. Based upon quantum-chemical calculations, the catalytic activity of phosphonium(V) and arsenonium(V) salts is expected to be too low to obtain effective noncovalent organocatalytic compounds, whereas stibonium(V), telluronium(IV) and iodonium(III) salts exhibit higher potential in application as noncovalent organocatalysts.

A Bifunctional N-Heterocyclic Carbene as a Noncovalent Organocatalyst for Enantioselective Aza-Michael Addition Reactions

Chiral N-heterocyclic carbenes (NHCs) have been recently established as powerful catalysts for enantioselective bond-forming processes via noncovalent interactions. The underlying HOMO-raising acti...

Tuning the Halogen Bonding Strength of Cyclic Diaryliodonium Salts

AbstractDiaryliodonium(III) salts have recently received increasing interest as a new class of strong halogen bonding noncovalent organocatalysts. Even though this utilization of their Lewis acidity has only been investigated in few studies, their high potential in comparison to classical monovalent iodine based XB donors has become very apparent. So far, only acyclic and cyclic five‐membered core structures have been used, and titration studies have shown the latter to be superior in terms of binding constants towards Lewis bases. Herein, we now compare the Lewis acidity and activity of these five‐membered iodolium salts with those of six‐membered iodininium derivatives. X‐Ray structural analyses, ITC measurements and the reaction kinetics of a Ritter‐type solvolysis reaction in wet acetonitrile (a typical halogen bond donor benchmark reaction) all demonstrate that iodolium salts are stronger halogen bond donors and catalysts than iodininium salts. Subsequently, we were able to improve the activity of both core structures significantly by introducing electron‐withdrawing substituents.

A Bidentate Iodine(III)-Based Halogen-Bond Donor as a Powerful Organocatalyst*.

In contrast to iodine(I)‐based halogen bond donors, iodine(III)‐derived ones have only been used as Lewis acidic organocatalysts in a handful of examples, and in all cases they acted in a monodentate fashion. Herein, we report the first application of a bidentate bis(iodolium) salt as organocatalyst in a Michael and a nitro‐Michael addition reaction as well as in a Diels–Alder reaction that had not been activated by noncovalent organocatalysts before. In all cases, the performance of this bidentate XB donor distinctly surpassed the one of arguably the currently strongest iodine(I)‐based organocatalyst. Bidentate coordination to the substrate was corroborated by a structural analysis and by DFT calculations of the transition states. Overall, the catalytic activity of the bis(iodolium) system approaches that of strong Lewis acids like BF3.

Iodonium salts as efficient iodine(iii)-based noncovalent organocatalysts for Knorr-type reactions.

Hypervalent iodine(iii)-derivatives display higher catalytic activity than other aliphatic and aromatic iodine(i)– or bromine(i)-containing substrates for a Knorr-type reaction of N-acetyl hydrazides with acetyl acetone to give N-acyl pyrazoles. The highest activity was observed for dibenziodolium triflate, for which 10 mol% resulted in the generation of N-acyl pyrazole from acyl hydrazide and acetyl acetone typically at 50 °C for 3.5–6 h with up to 99% isolated yields. 1H NMR titration data and DFT calculations indicate that the catalytic activity of the iodine(iii) is caused by the binding with a ketone.

Progress in Enantioselective Radical Cyclizations.

The control of stereoselectivity in radical reactions is of great importance to organic synthesis. Hence, new concepts and strategies for controlling stereochemistry of radical reactions are emerging continuously. This Review highlights the recent remarkable progress in enantioselective radical cyclization reactions. Initially, the chiral Lewis acid-catalyzed method became a field of central importance for enantioselective radical cyclizations. In recent years, significant progress has been made in enantioselective organocatalysis. In contrast to intermolecular reactions, the successful examples for enantioselective radical cyclizations are still limited. In this Review, the radical cyclizations controlled by chiral Lewis acids, chiral metallic reagents, chiral imidazolidinone catalysts, chiral non-covalent organocatalysts, and chiral thiols are summarized.

ChemInform Abstract: Asymmetric Sulfa‐Michael Addition of α,β‐Unsaturated Esters/Amides Using a Chiral N‐Heterocyclic Carbene as a Noncovalent Organocatalyst.

We report an asymmetric sulfa-Michael reaction of α,β-unsaturated amides and esters using a chiral N-heterocyclic carbene as the HOMO-raising organocatalyst. We discovered an interesting correlation between 13C NMR shifts of substrates and ee of their products. More electron-deficient Michael acceptors afforded higher enantioselectivity.

ChemInform Abstract: Highly Enantioselective Aza‐Michael Reaction Between Alkyl Amines and β‐Trifluoromethyl β‐Aryl Nitroolefins.

AbstractChiral N‐heterocyclic carbenes are used as noncovalent organocatalysts for the highly selective aza‐Michael addition between primary alkyl amines and various nitroolefins affording chiral trifluoromethylated amines.

Asymmetric Sulfa-Michael Addition of α,β-Unsaturated Esters/Amides Using a Chiral N-Heterocyclic Carbene as a Noncovalent Organocatalyst

We report an asymmetric sulfa-Michael reaction of α,β-unsaturated amides and esters using a chiral N-heterocyclic carbene as the HOMO-raising organocatalyst. We discovered an interesting correlation between ¹³C NMR shifts of substrates and ee of their products. More electron-deficient Michael acceptors afforded higher enantioselectivity.

Highly Enantioselective Aza‐Michael Reaction between Alkyl Amines and β‐Trifluoromethyl β‐Aryl Nitroolefins

AbstractThe aza‐Michael addition reaction is a vital transformation for the synthesis of functionalized chiral amines. Despite intensive research, enantioselective aza‐Michael reactions with alkyl amines as the nitrogen donor have not been successful. We report the use of chiral N‐heterocyclic carbenes (NHCs) as noncovalent organocatalysts to promote a highly selective aza‐Michael reaction between primary alkyl amines and β‐trifluoromethyl β‐aryl nitroolefins. In contrast to classical conjugate‐addition reactions, a strategy of HOMO‐raising activation was used. Chiral trifluoromethylated amines were synthesized in high yield (up to 99 %) with excellent enantioselectivity (up to 98 % ee).

Highly Enantioselective Aza-Michael Reaction between Alkyl Amines and β-Trifluoromethyl β-Aryl Nitroolefins.

The aza-Michael addition reaction is a vital transformation for the synthesis of functionalized chiral amines. Despite intensive research, enantioselective aza-Michael reactions with alkyl amines as the nitrogen donor have not been successful. We report the use of chiral N-heterocyclic carbenes (NHCs) as noncovalent organocatalysts to promote a highly selective aza-Michael reaction between primary alkyl amines and β-trifluoromethyl β-aryl nitroolefins. In contrast to classical conjugate-addition reactions, a strategy of HOMO-raising activation was used. Chiral trifluoromethylated amines were synthesized in high yield (up to 99 %) with excellent enantioselectivity (up to 98 % ee).

Noncovalent catalysis of glucose-containing imidazolium salt in solvent-free one-pot synthesis of Ortho-aminocarbonitriles

A glucose-containing imidazolium salt β-1-imidazole-2,3,4,6-tetraacetyl-D-glucopyranosyl bromide was firstly used as efficient noncovalent organocatalyst to promote the solvent-free preparation of ortho-aminocarbonitriles via a four-component condensation of aromatic aldehyde, cyclohexanone, and 2equiv of malononitrile at room temperature. Seven bonds were cleaved while four new bonds were formed and a six-membered ring was constructed in one-pot.

Highly enantioselective sulfa-Michael addition reactions using N-heterocyclic carbene as a non-covalent organocatalyst.

We report the first asymmetric sulfa-Michael addition (SMA) reactions using a chiral N-heterocyclic carbene (NHC) as a non-covalent organocatalyst. We demonstrate that a triazolium salt derived NHC functions as an excellent Brønsted base to promote enantioselective carbon-sulfur bond formation. The reaction is applicable to a wide range of thiols and electrophilic olefins. Notably, quaternary chiral centers bearing both an S atom and a CF3 group were synthesized with excellent asymmetric control. Mechanistic studies suggest that the facial discrimination is likely to be guided by non-covalent interactions: hydrogen bonding and π-π stacking.

Organocatalytic Claisen Rearrangement: Theory and Experiment

A combined computational and experimental study on the Claisen rearrangement of a 2-alkoxycarbonyl-substituted allyl vinyl ether in the presence of thioureas as potential noncovalent organocatalysts has been performed. DFT calculations employing different basis sets were utilized to predict a catalytic cycle for the thiourea-catalyzed Claisen rearrangement. The nature of the transition state in the presence and absence of thioureas was studied in detail. Critical geometrical data of the transition state that are indicators for the relative barrier height of the Claisen rearrangement are discussed. Although we did observe a significant transition state stabilization, due to endergonic conformational changes and endergonic complexation the overall effect on the barrier is small, in accordance with experimental results.