Organocatalysis by Neutral Multidentate Halogen‐Bond Donors

Kniep, Florian; Jungbauer, Stefan H.; Zhang, Qi; Walter, Sebastian M.; Schindler, Severin; Schnapperelle, Ingo; Herdtweck, Eberhardt; Huber, Stefan M.

doi:10.1002/anie.201301351

Cited by 291 publications

(178 citation statements)

References 75 publications

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“…Although the utilization of halogen bonding (XB) in solid-state crystal engineering has been extensively explored [3][4][5][6][7] , its application in solution-phase molecular recognition and self-assembly remains underdeveloped, despite the obvious analogy with the ubiquitous hydrogen bond 8 . It is only very recently that seminal applications of XB to the fields of molecular recognition and assembly 9,10 , anion binding [11][12][13][14][15][16] and membrane transport 17 , catalysis 18 , structural biology 19 and medicinal chemistry 20 have resulted in an explosion of interest in this non-covalent intermolecular interaction.…”

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confidence: 99%

Halogen bonding in water results in enhanced anion recognition in acyclic and rotaxane hosts

et al. 2014

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Halogen bonding (XB), the attractive interaction between an electron-deficient halogen atom and a Lewis base, has undergone a dramatic development as an intermolecular force analogous to hydrogen bonding (HB). However, its utilization in the solution phase remains underdeveloped. Furthermore, the design of receptors capable of strong and selective recognition of anions in water remains a significant challenge. Here we demonstrate the superiority of halogen bonding over hydrogen bonding for strong anion binding in water, to the extent that halide recognition by a simple acyclic mono-charged receptor is achievable. Quantification of iodide binding by rotaxane hosts reveals the strong binding by the XB-rotaxane is driven exclusively by favourable enthalpic contributions arising from the halogen-bonding interactions, whereas weaker association with the HB-rotaxanes is entropically driven. These observations demonstrate the unique nature of halogen bonding in water as a strong alternative interaction to the ubiquitous hydrogen bonding in molecular recognition and assembly.

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Halogen bonding in water results in enhanced anion recognition in acyclic and rotaxane hosts

et al. 2014

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“…Isothermal calorimetric titrations yielded binding strengths of ΔG° = -24.7 kJ/mol and ΔG° = -28.3 kJ/mol for the adducts of m-12 and p-12 to chloride in tetrahydrofuran, respectively, which is in accordance with their different catalytic activity. 23 In contrast to the cationic halogen-bond donor 8a mentioned above, the entropic contribution is almost negligible in these cases. A prototypical thiourea organocatalyst {N,N′-bis[3,5-bis(trifluoromethyl)phenyl]thiourea} gave a corresponding binding strength to chloride of ΔG° = -31.7 kJ/mol, albeit with a markedly higher entropic contribution (TΔS° = 13.3 kJ/mol).…”

Section: Methodsmentioning

confidence: 88%

“…In contrast, the bi-or tridentate neutral halogen-bond donors m-12, p-12 and 13 gave yields of the product 16 of 14%, 37%, and 91%, respectively. 23 Equally importantly, the non-iodinated analogues of these compounds did not lead to any product formation in all three cases. Thus, the catalytic activity of the multidentate halogen-bond donors relies on the presence of iodine substituents.…”

Section: Methodsmentioning

confidence: 97%

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Multidentate Halogen-Bond Donors as Lewis Acidic Activators or Catalysts in Halide Abstraction Reactions

Jungbauer

Schindler

Kniep

et al. 2013

Synlett

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Although halogen bonds share many similarities with hydrogen bonds, they have so far found virtually no application in organic synthesis. This account summarizes our efforts to use multidentate halogen-bond donors (halogen-based Lewis acids) in formal halide abstraction reactions. Following a first proof-ofprinciple study, we recently reported the first halogen-bond-based organocatalytic carbon-carbon bond-forming reaction.Hydrogen bonds are ubiquitous in Nature. As arguably the most important type of non-covalent interactions, they are crucial for various processes of life, for example, the specific binding of substrates in enzyme pockets. 1 Mimicking Nature, hydrogen-bond donors such as thiourea derivatives have, in the last 15 years, been established as potent non-covalent organocatalysts. 2 Although it has been known for a long time 3 that certain halogen substituents form similar non-covalent interactions with Lewis bases (LB; Figure 1, a), these so-called 'halogen bonds' 4 have so far found very little use in synthetic organic chemistry. Figure 1Halogen bonding: a) general definition (X = F, Cl, Br, I; LB = Lewis base); b) charge-transfer interaction; c) electrostatic potential (red = negative potential, blue = positive potential) of CF 3 I (violet = iodine, grey = carbon, cyan = fluorine) illustrating the σ-hole (in blue) on the iodine substituent Traditionally, halogen bonds have predominantly been described as n→σ* charge-transfer interactions (Figure 1, b), 5 while in recent years, the electrostatic contribution to the overall interaction energy has been more in focus. 6 The latter is often visualized by the 'σ-hole', a region of positive electrostatic potential on the halogen substituent ( Figure 1, c). 6a Strong halogen-bond donors (halogenbased Lewis acids) R-X are obtained for X = I > Br > Cl, and very electron-withdrawing (or highly polarizable) 7a R substituents. In contrast to hydrogen bonds, halogen bonds invariably feature a high directionality, with an R-X···LB angle of approximately 180°. 4,7b,c In the last two decades, halogen bonds have mostly found applications in the solid state, especially for crystal engineering. 8 With few exceptions, 9 studies in solution have only started to appear in the last few years. 10 In addition to fundamental investigations, 11 further examples include trans-membrane anion transport, 12 catenanes and rotaxanes, 13 and anion receptors. 14 In the field of organocatalysis, there are only two reports in which the involvement of halogen bonds has been postulated (Scheme 1). 15 In both cases, it was shown that typical halogen-bond donors (a perfluoroiodoalkane or iodine trichloride) acted as catalysts. The exact mode of activation was not elucidated, however, and it cannot be ruled out that traces of acid are responsible for part of the observed activity. Similar Stefan M. Huber (3 rd from left) studied chemistry at the FriedrichAlexander University of Erlangen-Nuremberg, Germany. He obtained his PhD in 2007 in the group of Prof. Robert Weiss, working on...

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“…4) [46]. Association constants with tetrabutylammonium chloride and bromide were determined by isothermal titration calorimetry (ITC) in THF solvent.…”

Section: CLmentioning

confidence: 99%

Anion Recognition in Solution via Halogen Bonding

Taylor

2014

Topics in Current Chemistry

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An overview of the interactions between anions and electron-deficient, covalently bound halogens is presented. It might be anticipated that species such as halides and oxoanions would be good acceptors of halogen bonds because of their relatively high charge densities and nucleophilicities. The stabilities of the trihalide anions X3 (-) provide a clear indication that this is indeed the case. The thermodynamics of formation of the trihalides, and of analogous complexes between anions and monodentate haloorganics in organic solvent, are discussed in detail. Although the incorporation of multiple interacting groups to achieve high guest affinity has been a key principle of supramolecular chemistry for decades, it is only recently that multidentate halogen bond donors capable of anion recognition have been reported. This contribution highlights the range of architectures that have been employed as the basis for multidentate halogen bond donor design. Examples of selective and high-affinity anion recognition through halogen bonding, including implementations in polar, protic media, are discussed.

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Organocatalysis by Neutral Multidentate Halogen‐Bond Donors

Cited by 291 publications

References 75 publications

Halogen bonding in water results in enhanced anion recognition in acyclic and rotaxane hosts

Halogen bonding in water results in enhanced anion recognition in acyclic and rotaxane hosts

Multidentate Halogen-Bond Donors as Lewis Acidic Activators or Catalysts in Halide Abstraction Reactions

Anion Recognition in Solution via Halogen Bonding

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