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.     

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 BAr^F₄ provide the strongest dicationic catalysts.     

Activation of a Metal‐Halogen Bond by Halogen Bonding

In recent years, the non‐covalent interaction of halogen bonding (XB) has found increasing application in organocatalysis. However, reports of the activation of metal‐ligand bonds by XB have so far been limited to a few reactions with elemental iodine or bromine. Herein, we present the activation of metal‐halogen bonds by two classes of inert halogen bond donors and the use of the resulting activated complexes in homogenous gold catalysis. The only recently explored class of iodolium derivatives were shown to be effective activators in two test reactions and their activity could be modulated by blocking of the Lewis acidic sites. Bis(benzimidazolium)‐based halogen bonding activators provided even more rapid conversion, while the non‐iodinated reference compound showed little activity. The role of halogen bonding in the activation of metal‐halogen bonds was further investigated by NMR experiments and DFT calculations, which support the mode of activation occurring via halogen bonding.     

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.     

Activating Chalcogen Bonding (ChB) in Alkylseleno/Alkyltelluroacetylenes toward Chalcogen Bonding Directionality Control

Activation of a deep electron-deficient area on chalcogen atoms (Ch=Se, Te) is demonstrated in alkynyl chalcogen derivatives, in the prolongation of the (C≡)C−Ch bond. The solid-state structures of 1,4-bis(methylselenoethynyl)perfluorobenzene ( 1Se ) show the formation of recurrent chalcogen-bonded (ChB) motifs. Association of 1Se and the tellurium analogue 1Te with 4,4′-bipyridine and with the stronger Lewis base 1,4-di(4-pyridyl)piperazine gives 1:1 co-crystals with 1D extended structures linked by short and directional ChB interactions, comparable to those observed with the corresponding halogen bond (XB) donor, 1,4-bis(iodoethynyl)-perfluorobenzene. This “alkynyl” approach for chalcogen activation provides the crystal-engineering community with efficient, and neutral ChB donors for the elaboration of supramolecular 1D (and potentially 2D or 3D) architectures, with a degree of strength and predictability comparable to that of halogen bonding in iodoacetylene derivatives.     

Chalcogen Bond Mediated Enhancement of Cooperative Ion‐Pair Recognition

A series of heteroditopic receptors containing halogen bond (XB) and unprecedented chalcogen bond (ChB) donors integrated into a 3,5‐bis‐triazole pyridine structure covalently linked to benzo‐15‐crown‐5 ether motifs exhibit remarkable cooperative recognition of halide anions. Multi‐nuclear ¹H, ¹³C, ¹²⁵Te and ¹⁹F NMR, ion pair binding investigations reveal sodium cation–benzo‐crown ether binding dramatically enhances the recognition of bromide and iodide halide anions, with the chalcogen bonding heteroditopic receptor notably displaying the largest enhancement of halide binding strength of over two hundred‐fold, in comparison to the halogen bonding and hydrogen bonding heteroditopic receptor analogues. DFT calculations suggest crown ether sodium cation complexation induces a polarisation of the sigma hole of ChB and XB heteroditopic receptor donors as a significant contribution to the origin of the unique cooperativity exhibited by these systems.     

Bidentate Chiral Bis(imidazolium)‐Based Halogen‐Bond Donors: Synthesis and Applications in Enantioselective Recognition and Catalysis

Even though halogen bonding—the noncovalent interaction between electrophilic halogen substituents and Lewis bases—has now been established in molecular recognition and catalysis, its use in enantioselective processes is still very rarely explored. Herein, we present the synthesis of chiral bidentate halogen‐bond donors based on two iodoimidazolium units with rigidly attached chiral sidearms. With these Lewis acids, chiral recognition of a racemic diamine is achieved in NMR studies. DFT calculations support a 1:1 interaction of the halogen‐bond donor with both enantiomers and indicate that the chiral recognition is based on a different spatial orientation of the Lewis bases in the halogen‐bonded complexes. In addition, moderate enantioselectivity is achieved in a Mukaiyama aldol reaction with a preorganized variant of the chiral halogen‐bond donor. This represents the first case in which asymmetric induction was realized with a pure halogen‐bond donor lacking any additional active functional groups.     

Strong σ‐Hole Activation on Icosahedral Carborane Derivatives for a Directional Halide Recognition

Crystal engineering based on σ‐hole interactions is an emerging approach for realization of new materials with higher complexity. Neutral inorganic clusters derived from 1,2‐dicarba‐closo‐dodecaborane, substituted with ‐SeMe, ‐TeMe, and ‐I moieties on both skeletal carbon vertices are experimentally demonstrated herein as outstanding chalcogen‐ and halogen‐bond donors. In particular, these new molecules strongly interact with halide anions in the solid‐state. The halide ions are coordinated by one or two donor groups (μ₁‐ and μ₂‐coordinations), to stabilize a discrete monomer or dimer motifs to 1D supramolecular zig‐zag chains. Crucially, the observed chalcogen bond and halogen bond interactions feature remarkably short distances and high directionality. Electrostatic potential calculations further demonstrate the efficiency of the carborane derivatives, with V_s,max being similar or even superior to that of reference organic halogen‐bond donors, such as iodopentafluorobenzene.     

H2XP…SHY复合物中磷键与硫键的理论研究

用从头算量子化学方法MP2 与CCSD(T)研究了H₂XP和SHY (X, Y=H, F, Cl, Br)分子的P与S之间形成的磷键X―P…S与硫键Y―S…P的本质与规律以及取代基X与Y对成键的影响. 计算结果表明, 硫键比磷键强, 连接在Lewis 酸上的取代基的电负性增大导致形成的磷键或硫键增强, 键能增大, 对单体的结构和性质的影响也增大; 而连接在Lewis 碱上的取代基效应则相反. 硫键键能为8.37-23.45 kJ·mol^-1, 最强的硫键结构是Y 电负性最大而X 电负性最小的HFS…PH₃, CCSD(T)计算的键能是16.04 kJ·mol^-1; 磷键键能为7.54-14.65 kJ·mol^-1, 最强的磷键结构是X 电负性最大而Y 电负性最小的H₂FP…SH₂, CCSD(T)计算的键能是12.52 kJ·mol^-1. 对磷键与硫键能量贡献较大的是交换与静电作用. 分子间超共轭lp(S)-σ^*(PX)与lp(P)-σ^*(SY)对磷键与硫键的形成起着重要作用, 它导致单体的极化, 其中硫键的极化效应较大, 从而有一定的共价特征.     

Elucidating the Reactivity of Vicinal Dicarbenoids: From Lewis Adduct Formation to B−C Bond Activation

The reactivity of the diaminoacetylene Pip‐C≡C‐Pip (Pip=piperidyl=NC₅H₁₀) towards phenyldichloro‐ and triphenylborane is presented. In the case of the less Lewis acidic PhBCl₂, the first example of a double Lewis adduct of a vicinal dicarbenoid is reported. For the more Lewis acidic triphenylborane, coordination to the bifunctional carbene leads to a mild B?C bond activation, resulting in a syn‐1,2‐carboboration. Ensuing cis/trans isomerization yields a novel ethylene‐bridged frustrated Lewis pair (FLP). The compounds were characterized using multinuclear NMR spectroscopy, structural analysis, and mass spectrometry. Reactivity studies of both isomers with the N‐heterocyclic carbene 1,3‐dimethylimidazol‐2‐ylidene (IMe) aided in elucidating the proposed isomerization pathway. DFT calculations were carried out to elucidate the reaction mechanism. The rather low free energy of activation is consistent with the observation that the reaction proceeds smoothly at room temperature.     

“Anti‐Electrostatic” Halogen Bonding

Halogen bonding is often described as being driven predominantly by electrostatics, and thus adducts between anionic halogen bond (XB) donors (halogen‐based Lewis acids) and anions seem counterintuitive. Such “anti‐electrostatic” XBs have been predicted theoretically but for organic XB donors, there are currently no experimental examples except for a few cases of self‐association. Reported herein is the synthesis of two negatively charged organoiodine derivatives that form anti‐electrostatic XBs with anions. Even though the electrostatic potential is universally negative across the surface of both compounds, DFT calculations indicate kinetic stabilization of their halide complexes in the gas phase and particularly in solution. Experimentally, self‐association of the anionic XB donors was observed in solid‐state structures, resulting in dimers, trimers, and infinite chains. In addition, co‐crystals with halides were obtained, representing the first cases of halogen bonding between an organic anionic XB donor and a different anion. The bond lengths of all observed interactions are 14–21 % shorter than the sum of the van der Waals radii.     

Chalcogen‐Bonding Catalysis: From Neutral to Cationic Benzodiselenazole Scaffolds

Benzodiselenazoles (BDS) are emerging as privileged structures for chalcogen‐bonding catalysis in the focal point of conformationally immobilized σ holes on strong selenium donors in a neutral scaffold. Whereas much attention has been devoted to work out the advantages of selenium compared to the less polarizable sulfur donors, high expectations concerning bidentate, rigid, and neutral scaffolds have been generated with little experimental support. Here we report design, synthesis and evaluation of the necessary catalysts to confirm that i) bidentate BDS are more effective than their monodentate analogs, ii) conformationally immobilized scaffolds are more effective than more flexible ones, iii) cationic BDS scaffolds are more effective than neutral ones, and iv) in dicationic‐bidentate BDS, contributions from chalcogen‐bonding dominate possible contributions from ion‐pairing catalysis. These conclusions result from rate enhancements found for a Ritter‐type anion‐binding reaction and an X‐ray crystal structure of dicationic BDS with a triflate anion bound with highest precision in the focal point of the σ holes.     

Comparison between Hydrogen and Halogen Bonds in Complexes of 6-OX-Fulvene with Pnicogen and Chalcogen Electron Donors

Quantum chemical calculations are applied to complexes of 6-OX-fulvene (X=H, Cl, Br, I) with ZH₃/H₂Y (Z=N, P, As, Sb; Y=O, S, Se, Te) to study the competition between the hydrogen bond and the halogen bond. The H-bond weakens as the base atom grows in size and the associated negative electrostatic potential on the Lewis base atom diminishes. The pattern for the halogen bonds is more complicated. In most cases, the halogen bond is stronger for the heavier halogen atom, and pnicogen electron donors are more strongly bound than chalcogen. Halogen bonds to chalcogen atoms strengthen in the order O<S<Se<Te, whereas the pattern is murkier for the pnicogen donors. In terms of competition, most halogen bonds to pnicogen donors are stronger than their H-bond analogues, but there is no clear pattern with respect to chalcogen donors. O prefers a H-bond, while halogen bonds are favored by Te. For S and Se, I-bonds are strongest, followed Br, H, and Cl-bonds in that order.     

Enantioselective Cascade Michael Addition/Cyclization Reactions of 3‐Nitro‐2H‐Chromenes with 3‐Isothiocyanato Oxindoles: Efficient Synthesis of Functionalized Polycyclic Spirooxindoles

An unprecedented Zn(OTf)₂‐catalyzed asymmetric Michael addition/cyclization cascade of 3‐nitro‐2H‐chromenes with 3‐isothiocyanato oxindoles has been disclosed. This transformation provides an efficient access to various synthetically important polycyclic spirooxindoles in a highly stereoselective manner under mild conditions (72–99 % yields, up to >95:5 d.r. and >99 % ee). The reaction leads to the formation of three consecutive stereocenters, including 1,3‐nonadjacent tetrasubstituted carbon stereocenters, in a single operation. A bifunctional activation model of the chiral Zn(OTf)₂/bis(oxazoline) complex was proposed based on control experiments, wherein the Zn^II moiety serves as a Lewis acid and the N atom of the free NH group acts as a Lewis base by a hydrogen‐bonding interaction.     

Cyclization Triggered by Deprotonation: The Gas‐Phase Acidity of 1,8‐Chalcogen‐Bridged Naphthalenes

High‐level density functional theory computations have been used to estimate the gas‐phase (intrinsic) acidities of the complete series of 1,8‐chalcogen‐bridged naphthalene derivatives. The existence of a chalcogen? chalcogen bond in chalcogen‐bridged naphthalene derivatives plays a crucial role in the intrinsic acidity of the system. For 1,8‐naphthalenediylbis(oxy), where this bond does not exist, the para C? H group is the most acidic site, whereas for the remaining compounds, deprotonation of the ortho CH groups is the most favorable process. Deprotonation of the aromatic rings has a large effect on the strength of the bonds of the five‐membered ring. These effects depend on the nature of the heteroatoms forming the X? Y bridge, and modulate the acidity of the molecule. Also importantly, when one of the heteroatoms is oxygen, ortho and para deprotonation lead to cleavage of the X? Y bridge. This bond fission favors the formation of a CYC (Y=S, Se, Te) three‐membered ring that enhances the stability of the anion and, therefore, increases the acidity of these compounds. We have shown that, whereas this cyclization process is energetically favorable for oxygen‐containing compounds, it is not favorable for the remaining derivatives.     

Chalcogenide Derivatives of the seco‐Cubane [Sn3(μ2‐NHtBu)2(μ2‐NtBu)(μ3‐NtBu)]

A series of monochalcogenide derivatives of the seco‐cubane [Sn₃(μ₂‐NHtBu)₂(μ₂‐NtBu)(μ₃‐NtBu)] has been prepared and characterized by NMR and X‐ray crystallographic studies. These complexes exhibit different tin‐chalcogen bonding modes. In the case of the monotelluride, a terminal Sn=Te bond was observed in solution and in the solid state, whereas for the monosulfide, a μ₂ bridging mode was adopted by the sulfur atoms. The monoselenide was found to employ both bonding modes in solution, although only the terminal Sn=Se bonding mode was structurally characterized. The complexes undergo chalcogen exchange between tin atoms in solution, and this process was studied by variable temperature NMR.     

Chalcogen Bond Mediated Enhancement of Cooperative Ion-Pair Recognition

A series of heteroditopic receptors containing halogen bond (XB) and unprecedented chalcogen bond (ChB) donors integrated into a 3,5-bis-triazole pyridine structure covalently linked to benzo-15-crown-5 ether motifs exhibit remarkable cooperative recognition of halide anions. Multi-nuclear ¹H, ¹³C, ¹²⁵Te and ¹⁹F NMR, ion pair binding investigations reveal sodium cation–benzo-crown ether binding dramatically enhances the recognition of bromide and iodide halide anions, with the chalcogen bonding heteroditopic receptor notably displaying the largest enhancement of halide binding strength of over two hundred-fold, in comparison to the halogen bonding and hydrogen bonding heteroditopic receptor analogues. DFT calculations suggest crown ether sodium cation complexation induces a polarisation of the sigma hole of ChB and XB heteroditopic receptor donors as a significant contribution to the origin of the unique cooperativity exhibited by these systems.     

Polar aspects of intramolecular interactions in 2‐amino‐5‐nitro‐4‐methylpyridines and 2‐amino‐3‐nitro‐4‐methylpyridines

The dipole moments of twelve 2‐N‐substituted amino‐5‐nitro‐4‐methylpyridines ( I‐XII ) and three 2‐N‐substituted amino‐3‐nitro‐4‐methylpyridines ( XIII‐XV ) were determined in benzene. The polar aspects of intramolecular charge‐transfer and intramolecular hydrogen bonding were discussed. The interaction dipole moments, μ_int, were calculated for 2‐N‐alkyl(or aryl)amino‐5‐nitro‐4‐methylpyridines. Increased alkylation of amino nitrogen brought about an intensified push‐pull interaction between the amino and nitro groups. The solvent effects on the dipole moments of 2‐N‐methylamino‐5‐nitro‐4‐methyl‐( I ), 2‐N,N‐dimethylamino‐5‐nitro‐4‐methyl‐ ( II ) and 2‐N‐methylamino‐3‐nitro‐4‐methylpyridines ( XIII ) were different. Specific hydrogen bond solute‐solvent interactions increased the charge‐transfer effect in I , but it did not disrupt the intramolecular hydrogen bond in XIII.     

A theoretical study of imine hydrocyanation catalyzed by halogen‐bonding

A detailed theoretical study of the mechanism and energetics of an organocatalysis based on C?N activation by halogen‐bonding is presented for the hydrocyanation of N‐benzylidenemethylamine. The calculations at the level of scalar‐relativistic gradient‐corrected density functional theory give an insight in this catalytic concept and provide information on the characteristics of four different monodentate catalyst candidates acting as halogen‐bond donors during the reaction. © 2015 Wiley Periodicals, Inc.