Ulrich Lüning

How To Synthesize Macrocycles Efficiently by Using Virtual Combinatorial Libraries

The selection of different diimines 4 a-c by alkaline earth ions from a virtual combinatorial library (VCL) is described. The products were stabilized by reduction to the diamines 6 a-c; this allowed easy analysis. The library can be directed toward different target molecules 6 a-c upon addition of alkaline earth ions with different radii. Competition experiments show the possibility of synthesizing the macrocycles 6 a, 6 b, and 6 c simultaneously when using Mg(2+), Ca(2+), and Ba(2+) as template ions. The scope of this thermodynamically controlled, reversible approach for macrocycle syntheses is illustrated.

Heterodimers for molecular recognition by fourfold hydrogen bonds

Abstract DAAD hydrogen bond donor (D) and acceptor (A) arrays 1 were synthesized and the recognition of the complementary ADDA substrates 2 and heterodimer formation by four hydrogen bonds was measured by 1 H NMR titrations. The binding energy of a sterically not crowded dimer is in accordance with the value calculated from increments.

Four Hydrogen Bonds − DDAA, DADA, DAAD and ADDA Hydrogen Bond Motifs

Receptor molecules containing four hydrogen-bond acceptor or donor sites based on aminopyridines, aminonaphthyridines and urea subunits have been synthesized and their association has been investigated. DDAA (13a−c) and DADA (18a−b) arrays may form homodimers, while DAAD (24a−d) with ADDA (25a−b) may form heterodimers. While most parent heterocycles were only slightly soluble in standard organic solvents, substitution was able to enhance the solubility in most cases. The naphthyridine 24d, bearing a substituent derived from lysine, possesses potential anchor groups for a covalent connection. Binding studies were carried out in chloroform and monitored by 1H NMR, and the binding constants Kass for the heterodimers DAAD·ADDA (24·25) were compared to the binding of smaller (ADD, 26) or mismatching (DADD, 27) counterparts, showing that the matching heterodimer is formed with a selectivity of > 50. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2002)

A New Quadruply Bound Heterodimer DDAD·AADA and Investigations into the Association Process

DDAD·AADA heterodimers based on the structures 8 and 9 have been synthesised and characterised. Solubility problems have been overcome through the introduction of a 2,6-dimethylphenyl substituent (8c), and association constants Kass have been determined by 1H NMR titrations. The Kass values obtained could be confirmed by osmometry, as could the association constants for other heterodimers. The Kass value increases when the acidity of participating N−H hydrogen atoms is enhanced. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

On the Mechanism and Stereoselectivity of the Copper(I)-Catalyzed Cyclopropanation of Olefins − A Combined Experimental and Density Functional Study

The mechanism of copper(I)-catalyzed olefin cyclopropanation with diazomethanes has been studied at the BP86/AE1 level of density-functional theory. For the model system Cu(diazabutadiene)+ + ethene + diazomethane, copper carbene complexes are confirmed as viable intermediates, with rate-determining barriers of the order of 25 kcal/mol (energies including zero-point corrections) or 14 kcal/mol (when entropic contributions are included). For another model system, Cu(2,9-dimethyl-1,10-phenanthroline)+ + styrene + diazoacetate, very small anti/syn selectivities (resulting in trans/cis-cyclopropanes) have been found both computationally and experimentally. Cu(carbene) complexes with macrocyclic phenanthroline-based ligands 1 (aryl bridgeheads and ether linkages) and 2 (calix[6]arene) have been optimized at the BP86/SDD level. A qualitative explanation for the trans selectivity observed with 1, based on the tilted, cleft-like conformation of 1·(CuCHCO2Me)+, is put forward. Similar conformations are found in structures of related acyclic mono- and diarylphenanthrolines (either free or complexed with Cu2+ or Pd2+), which have been determined by X-ray crystallography. The observed cis selectivity of 2 is probably related to the fact that in 2·(CuCHCO2Me)+ the calixarene macrocycle effectively blocks one hemisphere of the catalyst.

Concave reagents - 23. Synthesis of a calix[6]arene bridged by a 1,10-phenanthroline

Abstract 3 , the first calix[6]arene A,D-bridged by a 1,10-phenanthroline, was synthesized by reaction of p - tert -butylcalix[6]arene ( 1 ) with 2,9-bis(bromomethyl)-1,10-phenanthroline ( 2 ). The basicity of 3 was investigated qualitatively and quantitatively. Preliminary complexation studies indicate that 3 is a suitable ligand for Cu + .

CONCAVE ACIDS AND BASES

The selectivity of an enzyme is largely determined by the geometry of the active site which is usually embedded in a concave region of the protein (cavity or cleft). Similar geometries for standard reagents of organic chemistry can be generated when functional groups like pyridine, 1,10-phenanthroline or benzoic acid are placed into concave structures, e.g. bimacrocycles. In this review, the concept of concave reagents and catalysts, their syntheses and characterization, and their behavior in model reactions will be presented. The bimacrocyclic concave reagents may be used as acids in protonations and as bases in base catalyses. To facilitate the recovery of the concave acids and bases, their fixation to polymers is also described.

The AAAA·DDDD Hydrogen Bond Dimer. Synthesis of a Soluble Sulfurane as AAAA Domain and Generation of a DDDD Counterpart

Sulfurane 5b with solubility enhancing substituents has been synthesized to be used as an AAAA recognition site in quadruple hydrogen bond heterodimers. A complementary DDDD partner [4b + H+] has been generated from a DDAD domain 4b by protonation. The association constant for the heterodimer complex formation has been determined by NMR titration in chloroform.

Imidyl radicals. 3. Stereoselectivity of radical additions ofN-haloimides to cyclic alkenes

The addition of N-haloimides (1–5) to alkenes 9via imidyl radicals 6–8 introduces a halogen atom and an imidyl moiety to vicinal C-atoms of a carbon chain. With cyclic alkenes, the trans/cis-stereoselectivity depends on the nature of the imidyl unit, on the halogen atom, and on the alkene and varied between 58 : 42 and >95 : <5. Temperature dependend studies showed higher trans/cis-selectivities at elevated temperatures, which may be caused by different conformations of the adduct radicals 10–12, each of them exhibiting a different stereoselectivity.

The first supramolecular ion triplet complex

A neutral tritopic macrocycle 1 was obtained by condensation of a diacid dichloride 2 with a diamine 3. 1 contains three binding sites: two for anions by hydrogen bonding and one for cations by ether oxygen atoms. The selective binding of LiCl and CaCl2 has been studied by NMR and MS techniques. 1 is the first host to form a supramolecular complex with an ion triplet: 1·CaCl2.