Synthesis of meta- and paracyclophanes containing unsaturated amino acid residues

[7.7], [8.8], [9.9] and [13.13] Paracyclophanes and [9.9] and [13.13] metacyclophanes containing two unsaturated amino acid residues have been synthesised. An X-ray crystallographic study of three of the paracyclophanes and molecular modelling of two paracyclophanes and two metacyclophanes revealed two main structural types. The ‘staggered’ structure appears to be favoured by longer hydrocarbon chains, whilst the ‘barrel’ structure appears to be more accessible to compounds containing shorter hydrocarbon chains. The [9.9] paracyclophane has been hydrogenated and deprotected to give a saturated amino acid, and an alternative approach to key aldehydes is reported.     

Electron-Rich,Lewis Acidic Diborane Meets N-Heterocyclic Aromatics: Formation and Electron Transfer in Cyclophane Boranes

Herein reported are the reactions of an electron-rich, Lewis acidic diborane with N-heterocyclic aromatics to give first members of an unprecedented family of highly charged cationic cyclophanes with diboranyl units. Tetracationic cyclophanes with 4,4‘-bipyridine/ 1,2-bis(4-pyridyl)ethylene and diboranyl units were synthesized and their redox chemistry was studied. Cyclisation of two diboranyl and two pyrazine units is accompanied by electron transfer from the diboranyl unit to the pyrazine. Our results pave the way for the integration of redox-active diboranyl units into cyclophanes and supramolecular structures.     

Polycationic Redox-Active Cyclophanes with Integrated Electron-Rich Diboron Units

Cationic cyclophanes are widely used in a variety of applications in supramolecular chemistry and materials science. In this work the authors systematically study the integration of electron-rich diboron units with B^II atoms into polycationic cyclophanes with viologen-like electron-acceptor units. They also report a first hexacationic cage-compound in which three diboron units connect two tris(4-pyridyl)triazine acceptor units. Moreover, di- and tetracationic open-structure compounds, in which one diboron unit connects two bispyridyl groups, were synthesized and the properties compared to those of the corresponding closed structures (cyclophanes). The combination of diboron electron-donor units and bi- or oligopyridyl electron-acceptor units leads to intriguing optical and redox properties.     

One-Step Synthesis of Cyclophanes as Crystalline Sponge and Their [2]Catenanes through SNAr Reactions

This work reports that cyclophanes and their [2]catenanes were synthesized by the S_NAr reactions of disubstituted adamantanes bearing halophenol units and 3,6-dichlorotetrazine in moderate yields. In the crystalline state, the cyclophanes had hexagonal structures with a cavity. The [2]catenanes were composed of two macrocycles that were singly interlocked and orthogonally arranged, indicating the construction from eight component molecules through eight C−O bonds in a one-step reaction in up to 33 % yield. The cyclophanes were assembled to afford a supramolecular organic framework in the solid state, which exhibited permanent intrinsic porosity and adsorption of leaf alcohol or aldehyde in a single-crystal to single-crystal fashion. The molecular structures of the liquid guests were determined by single-crystal X-ray analysis. The formation of catenanes and the use of cyclophane-based porous crystals in the crystalline sponge method may be largely ascribed to the solvophobic effects and the van der Waals interactions that originate in the aliphatic and bulky nature of the adamantane units.     

Syntheses and structures of isomeric [6.6]- and [8.8]cyclophanes with 1,4-dioxabut-2-yne and 1,6-dioxahexa-2,4-diyne bridges

All three isomers (ortho, meta, and para) of [8.8]cyclophane bearing 1,6-dioxahexa-2,4-diyne bridges have been synthesized and structually characterized by single-crystal X-ray crystallography to determine the conformation of the cyclophanes and their cavity dimensions. The three isomeric [6.6]cyclophanes bearing 1,4-dioxabut-2-yne bridges have also been synthesized from but-2-yne-1,4-diol ditosylate and the isomeric dihydroxybenzenes. The [6.6]orthocyclophane has been structurally characterized by single-crystal X-ray crystallography. The energy-minimized structures from the semiempirical AM1 calculations of these cyclophanes compare very well with the structures obtained by X-ray crystallography.     

Azolium-linked cyclophanes: a comprehensive examination of conformations by 1H NMR spectroscopy and structural studies

The synthesis and characterization of a series of azolium-linked cyclophanes are reported. The cyclophanes consist of two azolium groups (17 examples) or three imidazolium groups (1 example) linked to two benzenoid units (benzene, naphthalene, p-xylene, mesitylene, 1,2,3,4- and 1,2,4,5-tetramethylbenzene, 2,6-pyridine, and p-tert-butylphenol) via methylene groups. Cyclophanes containing ortho-, meta-, and para-substitution patterns in the benzenoid units were examined. The conformations of the cyclophanes were examined in solution by variable-temperature NMR studies and in the solid state by crystallographic studies. The p-cyclophanes and mesitylene-based m- and o/m-cyclophanes are rigid on the NMR time scale, as indicated by sharp (1)H NMR spectra at all accessible temperatures. The non-mesitylene-based m-cyclophanes and the o-cyclophanes are fluxional on the NMR time scale at high temperatures, but in most cases, specific conformations can be "frozen out" at low temperatures. Many structures deduced from solution studies were consistent with those in the solid state.     

Benzidine/Quinoidal‐Benzidine‐Linked,Superbenzene‐Based π‐Conjugated Chiral Macrocycles and Cyclophanes

Synthesis of fully conjugated cyclophanes containing large‐size polycyclic aromatics is challenging. Now, three benzidine‐linked, hexa‐peri‐hexabenzocoronene (superbenzene)‐based ortho‐, para‐, and meta‐cyclophanes are synthesized through intermolecular Yamamoto coupling reaction of structurally pre‐organized precursors. Subsequent oxidative dehydrogenation gave the corresponding quinoidal benzidine‐linked cyclophanes. Their geometries were confirmed by X‐ray crystallographic analysis and their electronic properties were investigated by electronic absorption, cyclic voltammetry, and DFT calculations. The quinoidal benzidine‐linked cyclophanes show thermally populated paramagnetic activity with a relatively large singlet‐triplet energy gap. Two enantiomers for the ortho‐cyclophanes ( 1‐NH and 1‐N ) were isolated and their chiral figure‐of‐eight macrocyclic structures were identified. The cage‐like cyclophanes 2‐NH and 3‐NH with concave surface can selectively encapsulate fullerene C₇₀.     

Synthesis and guest-binding study of polytopic multi(cyclophane) hosts

Novel bis(cyclophanes) bearing glucosides and pentakis(cyclophanes) bearing glucosides were prepared as water-soluble hosts by connecting two or five macrocyclic skeletons, respectively. The guest-binding affinities of the present bis(cyclophanes) and pentakis(cyclophanes) toward a hydrophobic dye, 6-p-toluidinonaphthalene-2-sulfonate, were enhanced 13- and 1200-fold, respectively, relative to that by a corresponding monocyclic cyclophane, reflecting multivalency effects in macrocycles.     

1,x-elimination reactions: extending the limits of a classical organic reaction

Alpha,omega-dibromo derivatives in which the two terminal carbon atom are separated by an unsaturated spacer unit ("pi spacer") undergo 1,x-elimination reactions (with x=6, 8, 10, and 14), using Mori's reagent (nBu3SnSiMe3/CsF). The resulting cumulenic intermediates cyclodimerize in a subsequent step yielding novel macrocyclic acetylenic and bridged aromatic compounds (cyclophanes). Thus 1,6-eliminations were carried out with dibromide 17 to yield 1,3,7,9-cyclododecatetrayne (20) and with benzylbromide 24 to provide cyclophanes 26 and 27. By 1,8-eliminations the 16-membered macrocycle 33 could be prepared from enediyne 31, the benzannelated 1,5-cyclooctadiyne 41 from dibromide 38, and a mixture of cyclophanes 45 and 46 from the precursor 43. 1,10-Eliminations were carried out successfully with dibromides 47, 50, and 53 yielding the corresponding unsaturated cyclophanes ("cyclophynes") 49, 52, and 55. The influence of the solvent on the cyclodimerization 47-->49 was investigated, with acetonitrile providing the highest yields. The heterophanes 59 a and b were obtained by 1,10-elimination of the precursor dibromides 57 a and b, and in an elimination experiment involving a 1:1 mixture of the dibromides 50 and 57 b the "mixed dimer" 60 was isolated, besides the homodimers 52 and 59 b. The method reached its limits with the 1,14-elimination of 68, 70, and 74 providing the cyclophanes 69, 71, and 75 in varying amounts. Two final debrominations with 76 and 77, which in principle could undergo 1,16- and 1,20-eliminations reactions, respectively, failed. The structures of the new cyclophanes 49, 50, 59 a, and 59 b were established by X-ray structural analysis; all other structure assignments rest on the usual spectroscopic and analytical data.     

Benzidine/Quinoidal-Benzidine-Linked,Superbenzene-Based π-Conjugated Chiral Macrocycles and Cyclophanes

Synthesis of fully conjugated cyclophanes containing large-size polycyclic aromatics is challenging. Now, three benzidine-linked, hexa-peri-hexabenzocoronene (superbenzene)-based ortho-, para-, and meta-cyclophanes are synthesized through intermolecular Yamamoto coupling reaction of structurally pre-organized precursors. Subsequent oxidative dehydrogenation gave the corresponding quinoidal benzidine-linked cyclophanes. Their geometries were confirmed by X-ray crystallographic analysis and their electronic properties were investigated by electronic absorption, cyclic voltammetry, and DFT calculations. The quinoidal benzidine-linked cyclophanes show thermally populated paramagnetic activity with a relatively large singlet-triplet energy gap. Two enantiomers for the ortho-cyclophanes ( 1-NH and 1-N ) were isolated and their chiral figure-of-eight macrocyclic structures were identified. The cage-like cyclophanes 2-NH and 3-NH with concave surface can selectively encapsulate fullerene C₇₀.     

新型丁二炔-二酰胺大环化合物的合成及与TTF和DNP在溶液中的络合行为

由三甘醇和四甘醇出发,经炔丙基烷基化、Mitsunobu反应和Eglinton偶联反应3步合成了2个含均苯四甲酸二酰亚胺结构单元以及丁二炔结构单元的大环化合物,关环产率分别为81%和85%.大环化合物及中间体的化学结构经核磁共振氢谱、碳谱、低分辨质谱、高分辨质谱或元素分析等确认.通过氘代丙酮中1HNMR实验以及氯仿中紫外滴定实验研究了这类大环化合物与客体分子四硫富瓦烯(TTF)和1,5-二甲氧基萘(DNP)在溶液中的相互作用,结果发现,大环化合物的核磁化学位移及紫外光谱均发生变化.通过得到的主-客体间的络合常数可知,此类新型大环化合物与TTF和DNP之间有一定的络合作用.     

Acetylenic cyclophanes: emerging carbon-rich compounds for molecular construction and practical applications

The preparation of simple acetylenic [2.2]parcyclophane ‘building blocks’ is described. These compounds are readily available from the commercially available [2.2]paracyclophane employing functionalization of the parent system and conversion of the resulting functional groups into triple bonds. For the incorporation of these structures into cyclophanes with ‘extended’ π-systems, coupling reactions such as the Sonogashira or the Glaser coupling are particularly valuable. Besides addition reactions the ethynyl cyclophanes can be employed to prepare novel iron, platinum, and cobalt metal complexes. By polycondensation reactions the monomeric cyclophanes can be converted into novel polymers displaying lateral π-conjugation. The application of alkynylcyclophanes in material science and nanochemistry is discussed.     

Dinuclear N-heterocyclic carbene complexes of silver(I), derived from imidazolium-linked cyclophanes

The synthesis of four new silver complexes of bidentate N-heterocyclic carbenes, derived from imidazolium-linked cyclophanes, has been achieved via a simple complexation reaction of the imidazolium-linked cyclophanes with the basic metal source Ag(2)O. The cyclophane structures contain two imidazolyl links between ortho-, meta- and mixed ortho/meta-substituted aromatic rings. The new silver carbene systems are thermally stable and have been characterised by NMR spectroscopy and X-ray crystallography. Three of the complexes have a dimeric structure of the form [L(2)Ag(2)](2+) in the solid state that is rigid on the NMR timescale in solution. The fourth complex has a neutral structure of the form [L(AgBr)(2)], the NMR studies suggesting some lability of the L-Ag bonding in solution.     

Azolium-linked cyclophanes: effects of structure, solvent, and counteranions on solution conformation behavior

This paper describes the synthesis, structural characterization, and solution behavior of some xylyl-linked imidazolium and benzimidazolium cyclophanes decorated with alkyl or alkoxy groups. The addition of alkyl/alkoxy chains to the cyclophanes allows for studies in chlorinated solvents, whereas previous solution studies of azolium cyclophanes have generally required highly polar solvents. The azolium cyclophanes may exist in a syn/syn conformation (azolium rings mutually syn, arene rings mutually syn) or a syn/anti conformation (azolium rings mutually syn, arene rings mutually anti). The preferred conformation is significantly affected by (i) binding of bromide (ion pairing) to the protons on the imidazolium or benzimidazolium rings, which occurs in solutions of bromide salts of the cyclophanes in chlorinated solvents, and (ii) the addition of alkoxy groups to the benzimidazolium cyclophanes. These structural modifications have also led to cyclophanes that adopt conformations not previously identified for similar azolium cyclophane analogues. Detailed (1)H NMR studies for one cyclophane identified binding of bromide at two independent sites within the cyclophane.     

Dimeric quinacridone cyclophanes: Synthesis,structures,and photophysical properties

Two novel quinacridone (QA) cyclophanes with intrinsic intramolecular dye-dye interactions have been designed and synthesized.X-ray crystal structures as well as detailed photophysical properties have been well demonstrated.These two dyes have a major advantage that efficient fluorescence quenching can be observed even in their dilute solutions.A comparison of photophysical properties between the dimeric QA cyclophane and its reference monomeric counterpart indicates that the dimerization is predominant for...     

Exploring structural and conformational behaviour of cyclophanes incorporating imidazole-2-thiones

New cyclophanes containing two imidazole-2-thione moieties linked by two xylylene groups have been synthesized by the reaction of imidazolium-linked cyclophanes with sulfur in the presence of K₂CO₃. The conformational behaviour of the new cyclophanes was explored by NMR spectroscopy and X-ray diffraction studies. In cyclophanes containing o-xylylene or 2,4,6-trimethyl-m-xylylene linking groups, the imidazole-2-thione groups were mutually syn in both the solid state and in solution, the cyclophanes adopting a conformation reminiscent of the cone conformation of calix[4]arenes. Cyclophanes containing p-xylylene or m-xylylene linking groups exhibited two conformations in solution, one in which the imidazole-2-thione groups are mutually syn, the other in which they are mutually anti, and these conformations did not interconvert on the NMR timescale. Both conformations co-crystallised in the m-xylylene linked cyclophane, while for the p-xylylene-linked cyclophane the anti conformation crystallised separately.     

Sterically congested macrobicycles with heteroatomic bridgehead functionality

A series of cyclophanes composed of two triarylelement caps linked by two-atom bridges has been synthesized. The bridgehead functional groups include phosphines in combination with amines, hydrosilanes, methylsilanes, and ethoxysilanes. Computational studies accurately predicted that when the bridgehead substituents are small (lone pairs or protons), an in_,in bridgehead stereochemistry is strongly favored, but larger bridgehead substituents favor the formations of in_,out stereoisomers. The X-ray structures, spectra, and reactivity of these compounds are discussed, as well as the resolution of one of the cyclophanes into pure enantiomers.     

Synthesis of [m.n]Cyclophanes: Regiochemistry Transfer from Vinyl Halides to Cyclophanes via Fischer Carbene Complexes

The double benzannulation of bis‐carbene complexes of chromium with α,ω‐diynes generates [m.n]cyclophanes in which all three rings are generated in a single reaction. This triple annulation process is very flexible allowing for the construction of symmetrical [n.n]cyclophanes and unsymmetrical [m.n]cyclophanes as well as isomers in which the two benzene rings are both meta bridged or both para bridged, and isomers that contain both meta and para bridges. The connectivity patterns of the bridges in the cyclophanes can be controlled by regioselectivity transfer from the bis‐vinyl carbene complexes in which the substitution pattern of the vinyl groups in the carbene complexes dictate the connectivity pattern in the [m.n]cyclophanes. This synthesis of [n.n]cyclophanes is quite flexible with regard to ring size and can be used with tether lengths ranging from n=2 to n=16 and thus to ring sizes with up to 40 member rings. The only limitation to regioselectivity transfer from the carbene complexes to the [m.n]cyclophanes was found in the synthesis of para,para‐cyclophanes with four carbon tethers for which the loss of fidelity occurred with the unexpected formation of meta,para‐cyclophanes.     

Specific molecular recognition by cage-type cyclophanes having a helically twisted and cylindrical internal cavity

Cage-type cyclophanes, which are constructed with two rigid 2,11,20-triaza[3.3.3]paracyclophane skeletons and three chiral bridging components, were prepared. Temperature-dependent ¹H NMR measurements in (CD₃)₂SO indicate that the molecular framework of the cage-type cyclophane having a cylindrical internal cavity is more rigid than those of the corresponding non-cage hosts. The guest-binding behavior of the cage-type hosts toward various guests was examined by electronic absorption spectroscopy and electrospray ionization (ESI) mass spectrometry. The present hosts were found to bind anionic guests, such as 1-hydroxy-2,4-dinitronaphthalene-7-sulfonate, 2-hydroxy-1-(phenylazo)naphthalene-6,8-disulfonate, 2,7-bis[(4-methyl-2-sulfophenyl)azo]-1,8-dihydroxynaphthalene-3,6-disulfonate, 8-anilinonaphthalene-1-sulfonate, 6-p-toluidinonaphthalene-2-sulfonate, naphthalene-1-sulfonate, and 3,5-bis(methoxycarbonyl)benzene-1-sulfonate, to form host-guest complexes. The computer-aided molecular modeling study reveals that the three pyridinium moieties bound to the chiral - and -valine residues in the bridging segments undergo chiral twist in the same directions. However, the twisted direction in the host bearing -valine residues is opposite to that evaluated for the host bearing -valine residues so that the former and latter cage-type cyclophanes furnish M and P-helical cavities, respectively, as reflected in their circular dichroism (CD) spectra. The chirality-based molecular recognition of the cage-type hosts toward enantiomeric guests such as bilirubin-IX and pamoic acid in aqueous media was investigated by CD spectroscopy.     

Efficient construction of biaryls and macrocyclic cyclophanes via electron-transfer oxidation of Lipshutz cuprates

An efficient method for the homocoupling of aryl halides by electron-transfer oxidation of Lipshutz cuprates (Ar2Cu(CN)Li2) with organic electron acceptors is disclosed. Thus, various types of Lipshutz cuprates are prepared by successive treatment of aryl or heteroaryl bromides with tert-butyllithium and CuCN. The electron-transfer oxidation of Lipshutz cuprates with p-benzoquinones proceeds smoothly to afford the corresponding homocoupling products in moderate to good yields. Furthermore, it can be applied to the construction of either thiophene- or benzene-fused 10-membered ring cyclophanes. For the synthesis of 10-membered cyclophanes, the linear C-Cu-C structure of Lipshutz cuprates should be maintained in the dimetallacyclic intermediates, producing the large ring cyclophanes efficiently. The X-ray analysis of the cyclophanes reveals that the difference in the bridging atoms results in the different conformations of the macrocyclic rings. Thus, the silicon-bridged cyclophane 5a adopts a D2-symmetric structure with a twisted rhombic arrangement of four thiophene rings, whereas the methylene- and oxygen-bridged cyclophanes 5b and 5c possess C2h- and C2-symmetric structures with chair- and boatlike conformations, respectively. The 1H NMR spectrum of C2-symmetric 5c is temperature-dependent, and the activation energy (DeltaG) for the conformational change is 10.1 kcal/mol.