Oligo Tröger's bases--new molecular scaffolds

Oligo Tr?ger's bases are compounds containing two or more Tr?ger's base subunits (1,5-methanodiareno[b,f][1,5]diazocines) sharing one or more arene parts. Due to their interesting molecular shapes, these compounds are studied as chiral molecular tweezers, clips, cavitands, clefts, calixes, etc. This review includes all available data on oligo Tr?ger's bases, and introduces their preparation and properties to a wide audience.     

calix-Tris-Tröger's bases--a new cavitand family

The first members of a new cavitand family, represented by calix-shaped tris Tr?ger's base diastereoisomers, are prepared via step-by-step synthesis as well as one-pot mixed troegeration.     

Synthesis and Properties of Chiral Molecular Clefts Related to Tröger's Base

The chiral cavities present in 2,3:6,7-dibenzo-9-oxabicyclonona-2,6-diene, dibenzobicyclo[b,f][3.3.1]nona-5a, 6a-diene-6,12-dione, bicyclo[3.3.1]nonane and dibenzobicyclo[b,f],diazocines are reminiscent of Tröger's base, which has been widely used as a molecular cleft in supramolecular chemistry. The synthetic methodology to provide key derivatives for elaboration into new supramolecular structures, efficient resolution methods, the introduction of additional recognition groups and applications in supramolecular chemistry of these structurally related molecular clefts are reviewed.     

Synthesis of functionalized chiral carbocyclic cleft molecules complementary to Tröger's base derivatives

The synthesis of optically pure functionalized cleft molecules derived from dibenzobicyclo[b,f][3.3.1]nona-5a,6a-diene-6,12-dione is reported. These clefts are reminiscent of Tr?ger's base but contain clefts with different dimensions and additional carbonyl (or alcohol) groups that may be utilized in molecular recognition studies. The 2,8-dimethyl and 2,8-dibromo derivatives were synthesized via an intramolecular Friedel-Crafts acylation and were resolved by chiral HPLC. The 2,8-dinitro derivative was prepared by regiospecific nitration of dibenzobicyclo[b,f][3.3.1]nona-5a, 6a-diene-6,12-dione. The dibromo and dinitro derivatives allow direct access to a range of functionalized molecular clefts. Palladium-catalyzed coupling of the dibromo derivative afforded the disubstituted phenyl, anisole, and acetylene derivatives, while reduction of the dinitro derivative and acetylation provided amino-dione and amide-hydroxyl derivatives. X-ray crystal structures of the dimethyl 12, dibromo 13, di(p-methoxyphenyl) 16, dinitro 18, and dimethyl dinitro 22 derivatives show cleft angles between the planes between the aromatic rings of 84-104 degrees. The synthetic route, structural features, and potential for molecular recognition studies of this class of clefts are compared with those of the more widely studied Tr?ger's base cleft molecules.     

Synthesis and resolution of naphthyl-Tröger's base

A naphthyl analogue of Tröger's base {8H,16H-7,15-methanodinaphtho[2,1-b][2′,1′-f][1,5]-diazocine (NTB)} was prepared and successfully resolved using (−)- and (+)-di-p-toluoyl-tartaric acid. Enantiomers obtained show extremely high specific rotations related to (i) the rigid [1,5]-diazocine skeleton with molecular asymmetry and (ii) the presence of condensed aromatic rings, similar to helicenes.     

Sequential Alkylation of Tröger's Base. An Approach to New Chiral Ligands

Heterocycles derived from Tröger's base were shown to complex with metal salts in 2:1 ligand:salt ratios as monodentate or bidentate ligands depending on structure.     

(1)H and (13)C NMR studies of asymmetrically substituted bis- and tris-Tröger's bases

The (1)H and (13)C NMR spectra of two stereoisomeric bis-Tr?ger's bases and four stereoisomeric tris-Tr?ger's bases asymmetrically substituted on the external aromatic rings were recorded and the corresponding signals assigned. The relative configuration of the stereogenic units has been unequivocally determined on the basis of homoallylic couplings and NOE experiments.     

Metallomacrocycles incorporating a hemilabile Tröger's base derived ligand

Tr?ger's base, a chiral molecule with a rigid 90 degrees backbone, has been incorporated into a novel hemilabile phosphinoalkyl thioether ligand. Using the Weak Link Approach, this ligand has been reacted with Cu(CH3CN)4PF6 and [Rh(COE)2Cl]x (COE = cyclooctene) to form metallomacrocycles. Upon reaction of the ligand with Cu(I), which prefers a tetrahedral coordination geometry, a bimetallic macrocycle was formed. Alternatively, owing to the steric restrictions imposed by the 90 degrees backbone of the ligand and the square-planar geometry of Rh(I), when the ligand was reacted with [Rh(COE)2Cl]x, the formation of bimetallic closed macrocycles was not observed, and instead a mixture of tri- and tetrametallic closed macrocycles is formed. Introducing pyridine to the Cu(I) complex causes the weak thioether-Cu bonds to break, generating a large bimetallic open macrocycle. Upon reaction of the mixture of Rh(I) metallomacrocycles with CO and Cl-, the cyclic structure of these complexes becomes flexible enough that the dimeric bimetallic macrocycle forms, along with tri- and tetrameric open complexes. The mixture of differently sized Rh(I) macrocyclic complexes has been analyzed using gel permeation chromatography, and the tetramer has been characterized by a single-crystal X-ray diffraction study. These are the first examples of metallomacrocycles containing a Tr?ger's base derivative.     

Stepwise Replication of a Tröger's Base Analogue

Redox-controlled covalent templating and macrocyclization underlie a novel scheme for stepwise exponential self-replication. This process has been demonstrated by using Tr?ger's base analogue 1 as the template.     

Photophysical and biological investigation of novel luminescent Ru(II)-polypyridyl-1,8-naphthalimide Tröger's bases as cellular imaging agents

The synthesis and photophysical properties of 1 and 2, two Ru(II)-polypyridyl based-1,8-naphthalimide Tr?ger's bases, are described; these were found to stabilize double stranded DNA, undergo rapid cellular uptake, displaying good luminescence without affecting cell viability even after 24 hours of incubation.     

Overcoming regioselectivity issues inherent in bis-Tröger's base preparation

[structure: see text] Bis-Tr?ger's base derivatives are a new family of molecular tweezers. A major drawback to their study is a lack of commercially available precursors, ortho-nitrocarboxylic acids. A reverse synthetic strategy starting from known dinitrodicarboxylic acids, which circumvents this problem, is presented. Via this methodology regioisomeric bis-TB derivatives can be prepared selectively, using only common aromatic amines that are typically commercially available.     

The synthesis and characterization of all diastereomers of a linear symmetrically fused Tris-Tröger's base analogue: new chiral cleft compounds

The synthesis and characterization of all diastereomers of a linear symmetrically fused tris-Tr?ger's base analogue are described. The diastereomers are unambiguously assigned as syn-anti 1 a, anti-anti 1 b, and syn-syn 1 c isomers, by using X-ray diffraction analysis and NMR spectroscopy. For the first time, the anti-anti and the syn-syn diastereomers of a linear symmetrically fused tris-Tr?ger's base analogue have been synthesized. Molecules 1 a and 1 c are new cleft compounds and analysis of compound 1 a in the solid state shows inclusion of one molecule of CH(2)Cl(2) in the larger aromatic cleft, whereas in isomer 1 c disordered solvent molecules are trapped in the extended aromatic cleft. Furthermore, in the solid state, isomer 1 c forms infinite open channels along one of the crystallographic axes and perpendicular to this axis there are infinitely extending "wedged-ravines". Importantly, each of the diastereomers 1 a-c is resistant to inversion at the stereogenic nitrogen atoms under strongly and weakly acidic conditions in the range from room temperature (RT) to 95 degrees C. This observed configurational stability at the stereogenic nitrogens of 1 a-c is unique for analogues of Tr?ger's base in general to date. Finally, the ratio of cleft compounds 1 a and 1 c significantly increased relative to cavity compound 1 b when ammonium chloride was used as an additive in the Tr?ger's base condensation to 1 a-c suggesting a templating effect of the ammonium ion.     

New chiral molecular tweezers with a bis-Tröger's base skeleton

A convenient synthesis of 5alpha,8alpha,14alpha,17alpha-5,17:8,14-dimethano-5,8,14,17-tetraaza-5,6,7,8,13,14,17,18-octahydrodibenzo[e,e']benzo[1,2-a:3,4-a']dicyclooctene derivatives is described, and the compounds have been fully characterized by NMR; in some cases, the molecular structure has been determined by X-ray crystallography. These compounds represent the first examples of a new class of molecular tweezers.     

Tröger's Base Derivatives—New Life for Old Compounds

Synthetic Tröger's base derivatives are reviewed, including their properties and applications. The rigid V-shaped Tröger's base framework and its inherent chirality have promoted the preparation of diverse receptor systems. Heterocyclic Tröger's base derivatives exhibit affinity for DNA. Metal complexes of Tröger's base are used as catalysts. New applications continue to emerge as synthetic methods are developed.     

Dynamic processes in [16]annulene: Möbius bond-shifting routes to configuration change

Density functional and ab initio methods have been used to study the mechanisms for key dynamic processes of the experimentally known S4-symmetric [16]annulene (1a). Using BH&HLYP/6-311+G** and B3LYP/6-311+G**, we located two viable stepwise pathways with computed energy barriers (Ea = 8-10 kcal/mol) for conformational automerization of 1a, in agreement with experimental data. The transition states connecting these conformational minima have M?bius topology and serve as starting points for non-degenerate pi-bond shifting (configuration change) via M?bius aromatic transition states. The key transition state, TS1-2, that connects the two isomers of [16]annulene (CTCTCTCT, 1 --> CTCTTCTT, 2) has an energy, relative to the S4 isomer, that ranged from 6.9 kcal/mol (B3LYP/6-311+G**) to 16.7 kcal/mol (BH&HLYP/6-311+G**), bracketing the experimental barrier. At our best level of theory, CCSD(T)/cc-pVDZ(est), this barrier is 13.7 kcal/mol. Several other M?bius bond-shifting transition states, as well as M?bius topology conformational minima, were found with BH&HLYP energies within 22 kcal/mol of 1a, indicating that many possibilities exist for facile thermal configuration change in [16]annulene. This bond-shifting mechanism and the corresponding low barriers contrast sharply with those observed for cis/trans isomerization in acyclic polyenes, which occurs via singlet diradical transition states. All M?bius bond-shifting transition states located in [16]- and [12]annulene were found to have RHF --> UHF instabilities with the BH&HLYP method but not with B3LYP. This result appears to be an artifact of the BH&HLYP method. These findings support the idea that facile thermal configuration change in [4n]annulenes can be accounted for by mechanisms involving twist-coupled bond shifting.     

Reaction of Schiff bases anions with α,ω-dihaloalkanes: Synthetic route to cyclic α-aminoacid derivatives.

Addition-elimination versus substitution reactions.     

A Facile Synthetic Route to L-Phosphinothricin

Phosphinothricin, the active ingredient of the well known broad-spectrum herbicideglufosinate-ammonium, is a naturally occurring amino acid possessing the uniquemethylphosphinate moiety, and its strong herbicidal activity has been attributed to anability to inhibit glutamine synthetase in plants and bacteria1. Further research showedthat L-enantiomer of phosphinothricin was the carrier of the activity, whereas the D formonly had a small action2, therefore the stereoselective synthesis of L-pho…     

Diastereoselective self-assembly of double-stranded helicates from Tröger's base derivatives

[structure: see text]. Several ligands based on the rigid, V-shaped structure of Tr?ger's base bearing 2,2'-bipyridine and 2-pyridylmethanimine moieties have been synthesized. These ligands undergo diastereoselective self-assembly to dinuclear double-stranded D2d-symmetric helicates upon coordination to copper(I) and silver(I) ions as elucidated by NMR techniques and ESI mass spectrometric methods.