Thomas Burgemeister

Chiral recognition of allenic hydrocarbons by 1H NMR

Abstract The syntheses of the allenes (±)- 1 , (±)- 4 and (±)- 6 as well as of the enriched samples (-)- 1 , (-)- 4 and (-)- 6 are described. 1H NMR shifts and splittings induced by a mixture of the achiral salt Ag(fod) and the optically active complex (+)-Yb(hfbc)3 are given. This procedure is recommended by the magnitude of such splittings as a means of determining the enantiomeric purity of 1,3-disubstituted allenic hydrocarbons. The results for (-)- 1 and (-)- 5 represent the first application of this absolute method.

Synthesis and NMR studies of chiral 4-oxazolidinones and rhodanines

Sterically hindered N-(o-tolyl) and N-(o-chlorophenyl) substituted 2-thioxo-4-oxazolidinones 1 and-thiazolidinones (rhodanines) 2 forming enantiomers by partial rotation around the CN bond are synthesized. Their chirality is proven by the presence of diastereotopic protons (or carbon atoms) detected by 1H or 13C NMR (1c, 2c). In the presence of (S)-(+)-1-(9-anthryl)-2,2,2-trifluoroethanol as an auxilliary the enantiomers showed 1H shift differences of 0.01 ppm for otherwise isochronous nuclei.

Tumor-inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes. V. Synthesis and evaluation of enantiomeric [1,2-bis-(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) complexes

SummaryThe enantiomeric [1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) complexes were synthesized and tested on the hormone-sensitive human MCF7 breast cancer cell line and on the P388 leukemia of the mouse. They showed a strong and comparable activity on both tumor models.

Crystal structures and solution conformations of the meso-forms of 2,3,11,12-tetraphenyl-[18] crown-6

The X-ray crystal stuctures of the achiral cis-anti-cis and trans-syn-trans diastereoisomers of 2,3,11,12-tetraphenyl-[18]-crown-6 and their sodium iodide 1:1 complexes are presented. In the free ligands, the vicinal phenyl groups assume a diaxial- antiperiplanar orientation in the cis-anti-cis isomer and a diequatorial-synclinal one in the trans-syn-trans isomer. The vicinal coupling constants of the benzylic protons in the diphenylethanediyl groups in the three meso-forms, derived from 13C satellites, suggest similar conformations in the solid state and in deuteriotrichloromethane solution. Conformational changes of the crown ethers from the free ligand to their complexes are discussed in the context of previously determined complex association constants.

Konfigurations‐ und konformationsisomere paratrope, rotationsdynamische Tetraepoxy[32]annulene(6.2.6.2) und diatrope Tetraoxa[30]porphyrin(6.2.6.2)‐Dikationen : Nachweis eines Tetraepoxy[31]annulen(6.2.6.2)‐Radikalkations

Configurational and Conformational Isomeric Paratopic, Rotational Dynamics Tetraepoxy[30]annulenes(6.2.6.2) and Diatropic Tetraoxa[30]porphyrin(6.2.6.2) Dications: Detection of a Tetraepoxy[31]annulene(6.2.6.2)Radical Cation The synthesis of tetraepoxy[32]annulenes(6.2.6.2) (4) by a cyclizing twofold Wittig reaction of (E,E,E)-5,5′-(hexa-1,3,5-triene-1,6-diyl)bis[furan-2-carbaldehyde] (6) and the corresponding bis-phosphonium salt 7 is described (Scheme 1). Contrary to the configuration of the educts, the obtained annulenes 4a and 4b are (Z,E,E,E,Z,E,E,E)- and (E,Z,E,E,E,Z,E,E)-configurated, respectively. The 1H-NMR spectra establish the paratropic, antiaromatic character of 4. The annulenes 4 are highly dynamic systems, the (E)-ethenediyl bridges rotate around the adjacent σ-bonds, these rotations are frozen at −80°. The McMurry condensation of dialdehyde 6 yields the (E,E,Z,E,E,E,Z)-4,5-dihydrotetraepoxy[32]annulene(6.2.6.2) (13a), where the configuration of the dialdehyde 6 – beside the hydrogenated double bond – is retained. As result of an intramolecular McMurry reaction of 6, (Z,E,Z,Z)-dioxa[16]annulene(6.2) 14 is formed. By oxidation of the [32]annulenes(6.2.6.2) 4a and 4b, a mixture of the four stereoisomeric tetraoxa[30]porphyrin(6.2.6.2) dications 5a/5a′/5b/5c is obtained; the configuration of the isomers is determined by COSY, NOESY, and NOE experiments. The Δδ values (26.81, 25.83, and 21.11 ppm) underline the diatropic, aromatic character of the dications 5, the Soret bands are shifted bathochromically to 550 nm, and the Q-bands are in the NIR region (896 – 1039 nm). The dihydroannulene 13a is dehydrogenated by p-chloroanil (tetrachloro-1,4-benzoquinone) to give the annulenes 4a and 4b, its oxidation with DDQ (=4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile) results in the same mixture of dications 5. Entirely different results are obtained by reaction of the dihydroannulene 13a with DDQ. Here, the (E,E,E,Z,E,E,E,Z) tetraoxa[30]porphyrin(6.2.6.2) dication 5c – formed only in traces from 4a/4b – is the main product. Beside 5c, a by-product (3%) can be isolated, which turns out (ESR, conductivity) to be the (E,E,E,Z,E,E,E,Z)-tetraoxa[31]porphyrin(6.2.6.2) radical cation 16, obviously the intermediate in the oxidation sequence of the annulene to the dication. This result leads to the conclusion that the reaction of the dihydro compound 13a with p-chloroanil and DDQ follows different reaction mechanisms. For all isolated stereoisomeric tetraepoxy annulenes and tetraoxaporphyrin dications, the ΔHf values are calculated by the semiempiric AM1 method. The results are in agreement with the experimental observations. All data confirm the antiaromaticity of the tetraepoxy[32]annulenes(6.2.6.2) 4 and the aromaticity of the tetraoxa[30]porphyrin(6.2.6.2) dications.

A NOVEL APPROACH TO 4-BENZYLISOQUINOLINES

Abstract The reaction of quinone methides with 3.4-dihydroisoquinoline or isoquinoline leads to benzylisoquinoline derivatives. NMR and ms investigations as well as chemical degradation prove that benzylation takes place at C-4 of the isoquinoline nucleus. Spectroscopic data are given for all new compounds.

Synthesis, structural studies, and biological evaluation of some purine substituted 1-aminocyclopropane-1-carboxylic acids and 1-amino-1-hydroxymethylcyclopropanes

Abstract The novel purine derivatives of 1-aminocyclopropane-1-carboxylic acid (8 and 9) and 1-amino-1-hydroxymethylcyclopropane (12 and 13) with methylene spacer between the base and the cyclopropane ring were prepared by multistep synthetic route involving alkylation of adenine and 6-(N-pyrrolyl)purine with 2-hydroxymethyl-1-aminocyclopropane-1-carboxylic acid derivative 3 as a key reaction. All novel compounds were racemic. The N-9 substitution of the purine ring and the Z-configuration of the cyclopropane ring in 4–13 were deduced from their 1H and 13C NMR spectra by analyses of chemical shifts, H-H coupling constants and connectivities in two-dimensional homo- and heteronuclear correlation spectra. An unequivocal proof of the stereostructure of 1, 4 and 5 was obtained by their X-ray structure analysis. The novel compounds were evaluated on cytostatic and antiviral activities in several cell lines. The 6-(N-pyrrolyl)purine derivative of 1,2-aminocyclopropane alcohol 12 exhibited a more pronounced inhibitory activity against the proliferation of cervical carcinoma (HeLa) and human fibroblast (WI-38) cells than other types of tumor cell lines. None of the compounds showed inhibitory activities against cytomegalovirus, varicella-zoster virus or other viruses.

Tetraoxa [24] porphyrinogen(4.0.4.0)/tetraoxa[22]porphyrin(4.0.4.0) dication a further isomer of the aromatic 22π-tetraoxaporphyrins

Abstract While the antiaromatic tetraoxa[24]porphyrinogen(2.2.2.2) 1 ( trans , cis , trans , cis ) and the corresponding aromatic dication 1 2+ have been published recently, the synthesis of the title compounds is described for the first time. Beside the cis , trans , cis , trans -tetraoxa[24]porphyrinogen(4.0.4.0) 2b the isomeric porphyrinogens 2a ( trans , cis , cis , trans ) and 2c ( all - trans in the cisoid conformation) could be isolated. The tetraoxa[22]porphyrin(4.0.4.0) dication is an aromatic 22π-system, it exists only in the cis , trans , cis , trans -configuration. The dication 2b 2+ can be reduced with tetrakis-N,N-dimethylaminoethene to give pure porphyrinogen 2b . The electrochemistry of the system 2/ 2b 2+ and AM1 calculations are described.

Sterically hindered N-aryl pyrroles: chromatographic separation of enantiomers and barriers to racemization

The novel N-aryl-2,5-dimethylpyrrole-3-carbaldehydes (1)–(7) have been synthesized by condensation of hexane-2,5-dione with the appropriate aniline and subsequent Vilsmeier–Haack formylation of the pyrrole ring. Diastereoisomeric association complexes of these racemic pyrroles were studied by 1H n.m.r. spectroscopy chemical shifts and the splittings induced by the optically active auxiliary compound (+)-Eu(hfbc)3. Separation of the enantiomers of (6) was achieved by liquid chromatography on triacetylcellulose. The barrier to partial rotation about the C–N bond in (6) was determined and their lower limits in (2) and (4) were estimated by variable temperature 1H n.m.r. spectroscopy.

Chemical evidence for the existence of peralkylated niobocene in a fulvenoid form by its reaction with sulfur

Abstract Completely reduced Cp 2 ∗ NbCl 2 (Cp ∗ = η 5 -C 5 Me 5 ) solutions (two equipvalents of NaHg) which were previously supposed to contain two isomers A and B of decamethylniobocene react with sulfur to give products 1–4 . Their 1 H and 13 C NMR spectroscopy investigations allow for the first time a clear assignment of the structures of A and B . As 1 and 2 are identical with the previously reported Cp ∗ 2 Nb(η-S 2 )L derivatives (L = H ( 1 ), SH ( 2 )) a bent niobocene structure follows for isomer A . Products 3 and 4 are in agreement with structures involving a η 1 :η 5 -tetramethylfulvene ligand which in the case of 4 is slightly modified by sulfur insertion into the CH 2 Nb bond. Thus the structure of isomer B may be derived from bent niobecene by a hydride migration from one CH 3 group to Nb.