Substrate‐Induced Dimerization Assembly of Chiral Macrocycle Catalysts toward Cooperative Asymmetric Catalysis

An artificial system of substrate‐induced dimerization assembly of chiral macrocycle catalysts enables a highly cooperative hydrogen‐bonding activation network for efficient enantioselective transformation. These macrocycles contain two thiourea and two chiral diamine moieties and dimerize with sulfate to form a sandwich‐like assembly. The macrocycles then adopt an extended conformation and reciprocally complement the hydrogen‐bonding interaction sites. Inspired by the guest‐induced dynamic assembly, these macrocycles catalyze the decarboxylative Mannich reaction of cyclic aldimines containing a sulfamate heading group. The imine substrate can be activated toward nucleophilic attack of β‐ketoacid by a cooperative hydrogen‐bonding network enabled by sulfamate‐induced dimerization assembly of the macrocycle catalysts. Highly efficient (>95 % yield in most cases) and enantioselective (up to 97.5:2.5 er) transformation of a variety of substrates using only 5 mol % macrocycle was achieved.     

Cooperative Catalysis of Metal and O?H⋅⋅⋅O/sp3‐C?H⋅⋅⋅O Two‐Point Hydrogen Bonds in Alcoholic Solvents: Cu‐Catalyzed Enantioselective Direct Alkynylation of Aldehydes with Terminal Alkynes

Catalyst–substrate hydrogen bonds in artificial catalysts usually occur in aprotic solvents, but not in protic solvents, in contrast to enzymatic catalysis. We report a case in which ligand–substrate hydrogen‐bonding interactions cooperate with a transition‐metal center in alcoholic solvents for enantioselective catalysis. Copper(I) complexes with prolinol‐based hydroxy amino phosphane chiral ligands catalytically promoted the direct alkynylation of aldehydes with terminal alkynes in alcoholic solvents to afford nonracemic secondary propargylic alcohols with high enantioselectivities. Quantum‐mechanical calculations of enantiodiscriminating transition states show the occurrence of a nonclassical sp³‐C? H???O hydrogen bond as a secondary interaction between the ligand and substrate, which results in highly directional catalyst–substrate two‐point hydrogen bonding.     

Enantioselective Syntheses of Heteroyohimbine Natural Products: A Unified Approach through Cooperative Catalysis

Alstonine and serpentine are pentacyclic indoloquinolizidine alkaloids (referred to as “anhydronium bases”) containing three contiguous stereocenters. Each possesses interesting biological activity, with alstonine being the major component of a plant‐based remedy to treat psychosis and other nervous system disorders. This work describes the enantioselective total syntheses of these natural products with a cooperative hydrogen bonding/enamine‐catalyzed Michael addition as the key step.     

Hydrogen‐Bonding Catalysis of Tetraalkylammonium Salts in an Aza‐Diels–Alder Reaction

A piperidine‐derived tetraalkylammonium salt with a non‐coordinating counteranion worked as an effective hydrogen‐bonding catalyst in an aza‐Diels–Alder reaction of imines and a Danishefsky diene. The hydrogen‐bonding interaction between the ammonium salt and an imine was observed as part of a ¹H NMR titration study.     

Hydrogen‐Bonding Catalysis of Alkyl‐Onium Salts

The synthetic utility of alkyl‐onium salt compounds is widely recognized in the field of organic chemistry. Among the wide variety of onium salts, quaternary ammonium, phosphonium, and tertiary sulfonium salts have been the most useful compounds in organic syntheses. These compounds have been very useful reagents in the construction of organic building blocks. In addition, onium salts are known as reliable catalysts, which are used to promote important organic transformations by serving as phase‐transfer and ion‐pair catalysts through the activation of nucleophiles. Although phase‐transfer catalysis is a major direction for onium salt catalysis, hydrogen‐bonding catalysis of alkyl‐onium salts, which is promoted via the activation of electrophiles, has recently become a relevant topic in the field of onium salt chemistry. This Minireview introduces new possibilities and future directions for alkyl‐onium salt chemistry based on its use in hydrogen‐bonding catalysis and on its overall utility.     

氢原子转移与手性氢键协同催化共轭加成—不对称质子化构建氮杂芳烃α-三级立体中心

含亚胺氮杂芳烃(如吡啶、喹啉等)是一大类结构多样的芳香杂环,广泛存在于生物活性分子、天然产物、药物、催化剂、配体及功能材料等分子结构中.因此,发展氮杂芳烃衍生物合成方法学一直备受化学家的关注.其中,利用氮杂芳烃缺电子性质直接驱动氮杂芳烃底物参与化学转换一直是这一领域的研究重点.近年来,为了克服氮杂芳烃拉电子能力较羰基弱...     

Activation of Electron‐Deficient Quinones through Hydrogen‐Bond‐Donor‐Coupled Electron Transfer

Quinones are important organic oxidants in a variety of synthetic and biological contexts, and they are susceptible to activation towards electron transfer through hydrogen bonding. Whereas this effect of hydrogen bond donors (HBDs) has been observed for Lewis basic, weakly oxidizing quinones, comparable activation is not readily achieved when more reactive and synthetically useful electron‐deficient quinones are used. We have successfully employed HBD‐coupled electron transfer as a strategy to activate electron‐deficient quinones. A systematic investigation of HBDs has led to the discovery that certain dicationic HBDs have an exceptionally large effect on the rate and thermodynamics of electron transfer. We further demonstrate that these HBDs can be used as catalysts in a quinone‐mediated model synthetic transformation.     

Solvent‐Dependent Self‐Discrimination of Bis(2‐hydroxyphenyl)diamides

Solvent‐dependent, self‐discrimination of diamides is described. Mixing a solution of (R)‐ 1 a and (S)‐ 1 a , which are valine‐derived, bis(2‐hydroxyphenyl)diamide‐bearing, multiple hydrogen‐bonding modules, in dichloromethane immediately led to the formation of a thick suspension comprising a 1:1 heterochiral aggregate of 1 a . The solubility of heterochiral 1 a was substantially lower in halogenated solvents than in ethyl acetate. A perusal of racemic crystal structures obtained from chloroform and ethyl acetate revealed a significant difference in the crystal‐packing pattern, which is likely to be the basis for the pronounced difference in solubility. Specific self‐discrimination of 1 a in an ensemble of eight structurally related molecules showcased the specific aggregation through the hydrogen‐bonding network of the bis(2‐hydroxyphenyl)diamide framework. The low solubility of heterochiral 1 a in halogenated solvent was exploited to achieve high stereoselectivity in a catalytic asymmetric reaction by using a low enantiomeric excess sample of 1 a .     

Hydrogen‐bonding interactions in the active site of a low molecular weight protein‐tyrosine phosphatase

Molecular dynamics simulation of the Michaelis complex, phospho‐enzyme intermediate, and the wild‐type and C12S mutant have been carried out to examine hydrogen‐bonding interactions in the active site of the bovine low molecular weight protein‐tyrosine phosphatase (BPTP). It was found that the S_γ atom of the nucleophilic residue Cys‐12 is ideally located at a position opposite from the phenylphosphate dianion for an inline nucleophilic substitution reaction. In addition, electrostatic and hydrogen‐bonding interactions from the backbone amide groups of the phosphate‐binding loop strongly stabilize the thiolate anion, making Cys‐12 ionized in the active site. In the phospho‐enzyme intermediate, three water molecules are found to form strong hydrogen bonds with the phosphate group. In addition, another water molecule can be identified to form bridging hydrogen bonds between the phosphate group and Asp‐129, which may act as the nucleophile in the subsequent phosphate hydrolysis reaction, with Asp‐129 serving as a general base. The structural difference at the active site between the wild‐type and C12S mutant has been examined. It was found that the alkoxide anion is significantly shifted toward one side of the phosphate binding loop, away from the optimal position enjoyed by the thiolate anion of the wild‐type enzyme in an S_N2 process. This, coupled with the high pK_a value of an alcoholic residue, makes the C12S mutant catalytically inactive. These molecular dynamics simulations provided details of hydrogen bonding interactions in the active site of BPTP, and a structural basis for further studies using combined quantum mechanical and molecular mechanical potential to model the entire dephosphorylation reaction by BPTP. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1192–1203, 2000     

Synthesis,structure and catalytic properties of bis[2‐(trifluoromethyl)phenyl]silanediol

A novel trifluoromethylaryl‐substituted disilanol, bis[(2‐trifluoromethyl)phenyl] silanediol, was prepared by hydrolysis of the precursor dichloride and fully characterized. Single‐crystal X‐ray diffraction indicates doubly linked hydrogen bonded dimers and also hydrogen bonding to tetrahydrofuran solvent. The acidity of the silanol functions is enhanced by the presence of the trifluoromethyl groups and the compound is found to be active in promoting a standard Diels–Alder reaction, increasing yields by a factor of three.     

Importance of Intermolecular Hydrogen Bonding for the Stereochemical Control of Allene–Enone (3+2) Annulations Catalyzed by a Bifunctional,Amino Acid Derived Phosphine Catalyst

The origin of stereoselectivity in the (3+2) annulation of allenes and enones catalyzed by an amino acid derived phosphine catalyst has been investigated by the use of dispersion‐corrected density functional theory. An intermolecular hydrogen bond between the intermediate zwitterion and the enone was found to be the key interaction in the two enantiomeric transition states. Additional stabilization is provided by intermolecular hydrogen‐bonding interactions between acidic positions on the catalyst backbone and the substrate. Enantioselectivity occurs because the intermolecular hydrogen bond in the transition state leading to the minor enantiomer is only possible at the expense of reactant distortion.     

Efficient Asymmetric Hydrogenation of α‐Acetamidocinnamates through a Simple,Readily Available Monodentate Chiral H‐Phosphinate

An air‐stable, simple (R_P)‐mentylbenzylphosphinate, readily available in large quantities, can efficiently induce the rhodium‐catalyzed asymmetric hydrogenation of α‐acetamidocinnamates with high enantioselectivity (up to 99.6 % ee). Intramolecular hydrogen bonding plays an important role in this asymmetric induction.     

Recent topics in dual hydrogen bonding catalysis

Dual hydrogen bonding donors have received much attention in the area of organocatalysis after the discovery of chiral thiourea derivatives that act as asymmetric catalysts. This digest focuses on recent advances in this area categorized in the following three topics: 1) enhanced hydrogen bonding donor catalysis; new scaffolds with improved reactivity and selectivity are introduced and compared with established catalysts; 2) anion binding catalysis; recent advances in terms of catalysts and their applications is addressed; 3) multiple catalysis involving dual hydrogen bonding catalysts; a relatively new field of dual hydrogen bonding donor catalysis combined with other catalysis is introduced.     

Spontaneous Stepwise Self‐Assembly of a Polyoxometalate–Organic Hybrid into Catalytically Active One‐Dimensional Anisotropic Structures

An inorganic–organic hybrid surfactant with a hexavanadate cluster as the polar head group was designed and observed to assemble into micelle structures, which further spontaneously coagulate into a 1D anisotropic structure in aqueous solutions. Such a hierarchical self‐assembly process is driven by the cooperation of varied noncovalent interactions, including hydrophobic, electrostatic, and hydrogen‐bonding interactions. The hydrophobic interaction drives the quick formation of the micelle structure; electrostatic interactions involving counterions leads to the further coagulation of the micelles into larger assemblies. This process is similar to the crystallization process, but the specific counterions and the directional hydrogen bonding lead to the 1D growth of the final assemblies. Since most of the hexavanadates are exposed to the surface, the 1D assembly with nanoscale thickness is a highly efficient heterogeneous catalyst for the oxidation of organic sulfides with appreciable recyclability.     

Enantioselective Organo‐Photocatalysis Mediated by Atropisomeric Thiourea Derivatives

Can photocatalysis be performed without electron or energy transfer? To address this, organo‐photocatalysts that are based on atropisomeric thioureas and display lower excited‐state energies than the reactive substrates have been developed. These photocatalysts were found to be efficient in promoting the [2+2] photocycloaddition of 4‐alkenyl‐substituted coumarins, which led to the corresponding products with high enantioselectivity (77–96 % ee) at low catalyst loading (1–10 mol %). The photocatalytic cycle proceeds by energy sharing via the formation of both static and dynamic complexes (exciplex formation), which is aided by hydrogen bonding.     

Iodide‐Induced Shuttling of a Halogen‐ and Hydrogen‐Bonding Two‐Station Rotaxane

The first example of utilizing halogen‐bonding anion recognition to facilitate molecular motion in an interlocked structure is described. A halogen‐bonding and hydrogen‐bonding bistable rotaxane is prepared and demonstrated to undergo shuttling of the macrocycle component from the hydrogen‐bonding station to the halogen‐bonding station upon iodide recognition. In contrast, chloride‐anion binding reinforces the macrocycle to reside at the hydrogen‐bonding station.     

Inner Workings of a Cinchona Alkaloid Catalyzed Oxa‐Michael Cyclization: Evidence for a Concerted Hydrogen‐Bond‐Network Mechanism

Cinchona alkaloids catalyze the oxa‐Michael cyclization of 4‐(2‐hydroxyphenyl)‐2‐butenoates to benzo‐2,3‐dihydrofuran‐2‐yl acetates and related substrates in up to 99 % yield and 91 % ee (ee=enantiomeric excess). Catalyst and substrate variation studies reveal an important role of the alkaloid hydroxy group in the reaction mechanism, but not in the sense of a hydrogen‐bonding activation of the carbonyl group of the substrate as assumed by the Hiemstra–Wynberg mechanism of bifunctional catalysis. Deuterium labeling at C‐2 of the substrate shows that addition of RO? H to the alkenoate occurs with syn diastereoselectivity of ≥99:1, suggesting a mechanism‐based specificity. A concerted hydrogen‐bond network mechanism is proposed, in which the alkaloid hydroxy group acts as a general acid in the protonation of the α‐carbanionic center of the product enolate. The importance of concerted hydrogen‐bond network mechanisms in organocatalytic reactions is discussed. The relative stereochemistry of protonation is proposed as analytical tool for detecting concerted addition mechanisms, as opposed to ionic 1,4‐additions.     

PyBidine–Cu(OTf)2‐Catalyzed Asymmetric [3+2] Cycloaddition with Imino Esters: Harmony of Cu–Lewis Acid and Imidazolidine‐NH Hydrogen Bonding in Concerto Catalysis

A bis(imidazolidine)pyridine (PyBidine)–Cu(OTf)₂ complex catalyzing the endo‐selective [3+2] cycloaddition of nitroalkenes with imino esters was applied to the reaction of methyleneindolinones with imino esters to afford spiro[pyrrolidin‐3,3′‐oxindole]s in up to 98 % ee. X‐ray crystallographic analysis of the PyBidine–Cu(OTf)₂ complex and DFT calculations suggested that an intermediate Cu enolate of the imino ester reacts with nitroalkenes or methyleneindolinones, which are activated by NH‐hydrogen bonding with the PyBidine–Cu(OTf)₂ catalyst.     

Rhodium‐Catalyzed Asymmetric Hydrogenation of Unprotected NH Imines Assisted by a Thiourea

Asymmetric hydrogenation of unprotected NH imines catalyzed by rhodium/bis(phosphine)‐thiourea provided chiral amines with up to 97 % yield and 95 % ee. ¹H NMR studies, coupled with control experiments, implied that catalytic chloride‐bound intermediates were involved in the mechanism through a dual hydrogen‐bonding interaction. Deuteration experiments proved that the hydrogenation proceeded through a pathway consistent with an imine.     

The Temperature‐Dependent Hydrogen‐Bonding Signature of Lipids Monitored in the Far‐Infrared Domain

Phospholipids are studied by means of Fourier transform infrared (FTIR) spectroscopy in the mid‐ and far‐infrared spectral ranges, thereby establishing the hydrogen‐bonding continuum as a function of the temperature. The well‐known mid‐infrared spectrum of the phospholipid layer clearly shows a temperature‐dependent phase transition. In the far‐infrared region (from 300 to 50 cm^?1), an alternation of the interaction between the phospholipids and water molecules is found. The hydrogen‐bonding network ensemble and bound water molecules can be monitored in this spectral region. The lipid structure is found to strongly influence the intermolecular hydrogen‐bonding interplay. Thus, studies in the far‐infrared region provide significant information—at the molecular level—about the intermolecular hydrogen‐bonding signature of self‐assembled phospholipids.