Catalytic Activation of Imines by Chalcogen Bond Donors in a Povarov [4+2] Cycloaddition Reaction.

Recently, chalcogen bonding has been investigated in more detail in organocatalysis and the scope of activated functionalities continues to increase. Herein, the activation of imines in a Povarov [4+2] cycloaddition reaction with bidentate cationic chalcogen bond donors is presented. Tellurium-based Lewis acids show superior properties compared to selenium-based catalysts and inactive sulfur-based analogues. The catalytic activity of the chalcogen bonding donors increases with weaker binding anions. Triflate, however, is not suitable due to its participation in the catalytic pathway. A solvent screening revealed a more efficient activation in less polar solvents and a pronounced effect of solvent (and catalyst) on endo : exo diastereomeric ratio. Finally, new chiral chalcogen bonding catalysts were applied but provided only racemic mixtures of the product.

Preorganization: A Powerful Tool in Intermolecular Halogen Bonding in Solution.

Preorganization is a powerful tool in supramolecular chemistry which has been utilized successfully in intra- and intermolecular halogen bonding. In previous work, we had developed a bidentate bis(iodobenzimidazolium)-based halogen bond donor which featured a central trifluoromethyl substituent. This compound showed a markedly increased catalytic activity compared to unsubstituted bis(iodoimidazolium)-based Lewis acids, which could be explained either by electronic effects (the electron withdrawal by the fluorinated substituent) or by preorganization (the hindered rotation of the halogen bonding moieties). Herein, we systematically investigate the origin of this increased Lewis acidity via a comparison of the two types of compounds and their respective derivatives with or without the central trifluoromethyl group. Calorimetric measurements of halide complexations indicated that preorganization is the main reason for the higher halogen bonding strength. The performance of the catalysts in a series of benchmark reactions corroborates this finding.

Carbonyl Activation by Selenium- and Tellurium-Based Chalcogen Bonding in a Michael Addition Reaction.

In the last years the use of chalcogen bonding-the noncovalent interaction involving electrophilic chalcogen centers-in noncovalent organocatalysis has received increased interest, particularly regarding the use of intermolecular Lewis acids. Herein, we present the first use of tellurium-based catalysts for the activation of a carbonyl compound (and only the second such activation by chalcogen bonding in general). As benchmark reaction, the Michael-type addition between trans-crotonophenone and 1-methylindole (and its derivatives) was investigated in the presence of various catalyst candidates. Whereas non-chalcogen-bonding reference compounds were inactive, strong rate accelerations of up to 1000 could be achieved by bidentate triazolium-based chalcogen bond donors, with product yields of >90 % within 2 h of reaction time. Organotellurium derivatives were markedly more active than their selenium and sulphur analogues and non-coordinating counterions like BArF 4 provide the strongest dicationic catalysts.

Chalcogen Bonding Catalysis of a Nitro-Michael Reaction.

Chalcogen bonding is the non-covalent interaction between Lewis acidic chalcogen substituents and Lewis bases. Herein, we present the first application of dicationic tellurium-based chalcogen bond donors in the nitro-Michael reaction between trans-ß-nitrostyrene and indoles. This also constitutes the first activation of nitro derivatives by chalcogen bonding (and halogen bonding). The catalysts showed rate accelerations of more than a factor of 300 compared to strongly Lewis acidic hydrogen bond donors. Several comparison experiments, titrations, and DFT calculations support a chalcogen-bonding-based mode of activation of ß-nitrostyrene.

A halogen-bonding-catalysed Nazarov cyclisation reaction.

Various neutral, mono- and dicationic halogen bond donors were screened for their ability to act as catalysts in a Nazarov cyclisation reaction. Using a highly preorganized dicationic catalyst with a noncoordinating counterion proved essential for high activity.

Chalcogen Bonding: An Overview.

In the last few decades, "unusual" noncovalent interactions like anion-π and halogen bonding have emerged as interesting alternatives to the ubiquitous hydrogen bonding in many research areas. This is also true, to a somewhat lesser extent, for chalcogen bonding, the noncovalent interaction involving Lewis acidic chalcogen centers. Herein, we aim to provide an overview on the use of chalcogen bonding in crystal engineering and in solution, with a focus on the recent developments concerning intermolecular chalcogen bonding in solution-phase applications. In the solid phase, chalcogen bonding has been used for the construction of nano-sized structures and the self-assembly of sophisticated self-complementary arrays. In solution, until very recently applications mostly focused on intramolecular interactions which stabilized the conformation of intermediates or reagents. In the last few years, intermolecular chalcogen bonding has increasingly also been exploited in solution, most notably in anion recognition and transport as well as in organic synthesis and organocatalysis.

Catalytic Carbon-Chlorine Bond Activation by Selenium-Based Chalcogen Bond Donors.

Chalcogen bonding is a noncovalent interaction based on electrophilic chalcogen substituents, which shares many similarities with the more well-known hydrogen and halogen bonding. Herein, the first application of selenium-based chalcogen bond donors in organocatalysis is described. Cationic bifunctionalized organoselenium compounds activate the carbon-chlorine bond of 1-chloroisochroman in a benchmark reaction. While imidazolium-based derivatives showed no noticeable activation, benzimidazolium backbones yielded potent catalysts. In all cases, syn-isomers were markedly more active, presumably due to bidentate coordination, which was confirmed by DFT calculations. Comparison experiments with the corresponding non-selenated as well as the non-cationic reference compounds clearly indicate that the catalytic activity can be ascribed to chalcogen bonding. The rate acceleration by the catalyst-compared to the non-selenated derivative-was about 10 fold.

Carbon-Halogen Bond Activation by Selenium-Based Chalcogen Bonding.

Chalcogen bonding is a little explored noncovalent interaction similar to halogen bonding. This manuscript describes the first application of selenium-based chalcogen bond donors as Lewis acids in organic synthesis. To this end, the solvolysis of benzhydryl bromide served as a halide abstraction benchmark reaction. Chalcogen bond donors based on a bis(benzimidazolium) core provided rate accelerations relative to the background reactivity by a factor of 20-30. Several comparative experiments provide clear indications that the observed activation is due to chalcogen bonding. The performance of the chalcogen bond donors is superior to that of a related brominated halogen bond donor.