Search

Reaction of methyl 3,3-diazido-z-cyanacrylate (7) with triphenylphosphane leads to a geminal bisphosphazide 11 and bisphosphinimine 12 respectively. The structure of methyl (E)-3-amino-z-cyan-7-(diphenylphosphinoyl)-5,5-diphenyl-4-aza-5λ5-phoepha-2,4-heptadienate (16) was established by X-ray analysis.

Since triphenylphloroglucinol (1) has been described with widely differing properties, the correct structure has been substantiated by X-ray analysis. On oxidation of 1 the dimer 5 is formed irreversibly by coupling between two phenyl groups. All three OH groups in 1 were acylated by pivaloyl chloride/AlCl3 (2). By methylation of 1 both the dimethoxy-(3) and trimethoxy-(4) derivatives are formed. On oxidation with K3[Fe(CN)6]/OH− phenol 3 yields the persistent radical 3rad, which was characterized by its ESR signal and isolated as the dimer 6. Hydroquinone reverts 6 back to 3.

Chloral-derived β-carbolines, which are structurally similar to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 5), are discussed to contribute to neuronal cell death in idiopathic Parkinson’s disease. The cytotoxicity of 1-trichloromethyl- 1,2,3,4-tetrahydro-β-carboline (TaClo, 4) to neuronal-like clonal pheochromocytoma PC12 cells was examined by the determination of lactate dehydrogenase (LDH) release. After incubation for 48 h, 4 showed a strong dose-dependent cytotoxic activity towards PC12 cells with an ED50 value of 230 μᴍ. In PC12 cells reductive dehalogenation of 4 was observed giving rise to the formation of 1-dichloromethyl-1,2,3,4-tetrahydro-β-carboline (6) as a main TaClo metabolite exhibiting a cytotoxic potential comparable to that of TaClo. An X-ray structure analysis, performed for the trifluoroacetyl derivative of 6, revealed the N-substituent of such a highly chlorinated agent to be dramatically pushed out of the β-carboline ring ‘plane’ due to the high steric demand of the huge dichloromethyl group at C(1).

Treatment of the 3,3-dimethyl-2-iminoaziridine 7 with hydrogen bromide yields similar amounts of the α-bromo amidine 10a · HBr and the α,β-unsaturated amidinium bromide 11. Ring opening reactions of the 3-tert-butyl-2-iminoaziridines 8 by nucleophiles (potassium methoxide, Pirkle's alcohol 13, and 4-nitrophenol) are sluggish affording the α-amino imidates 12, 14, and 15, respectively. Compound 15a isomerises via the Meisenheimer-type intermediate 16 to furnish the α-amino amide 17. Methyl triflate converts (R)-8 into the 2-tert-butyl-3-amino-2H-azirinium triflates (R)-18 which do not undergo racemisation as shown after hydrolysis to yield the α-amino amides (R)-20. In a similar sequence, (R)-8a and b are converted into the α-amino amides (R)-26 by the action of hydrogen halides or 4-toluenesulfonic acid hydrate followed by hydrolysis of the intermediate imidoyl derivatives (R)-24. Retention of configuration is observed after treatment of (R)-8a with hydrogen chloride and of (R)-8b with hydrogen bromide. Some racemisation found in the other cases is supposed to involve (R)-24 but not the aminoazirinium ions (R)-8 · HX. In a side reaction, 8a and b decompose into methyl isocyanide (22) and the imines 23 at low temperatures, probably under general acid catalysis. The results are not consistent with the hypothesis of an electrocyclic ring opening of 3-amino-2H-azirinium ions to afford 2-amino-1-azaallyl cations (= α-imino carbocations). – The heat of protonation of the parent compounds (E)-27, (Z)-27, 30 and the structures and energies of the resulting cations (E)-28, (Z)-28, 29, and 31 were calculated by ab initio methods. Complete geometry optimisations were performed with the RHF/6-31 + G** basis set. Energies were calculated on the RHF, MP2, MP4SDTQ, and CCSD(T) levels. According to the geometric parameters, the amidine delocalisation of the free bases is abondened in the cations (E)-28, (Z)-28, and 31 while it is considerably strengthened in 29. In accord with these geometric changes, 29 is by far the most stable protonated species followed by (E)- and (Z)-28. Azirine 31 is much higher in energy. The calculated difference in (gas phase) basicity between the two nitrogen atoms of iminoaziridines appears to exclude the ring-protonated cations as intermediates also for reactions in solution.

Several 2,6-substituted barbaralanes, viz. 1d–g, have been synthesised from Meerwein's diketone (2). Treatment of dinitrile 3 with hydrochloric acid in boiling methanol followed by hydrolysis of the intermediate Pinner salt yields the dimethyl dicarboxylate 4 which is brominated to afford the exo,exo dibromo diester 5. Reductive cyclisation of 5 gives rise to the formation of dimethyl 2,6-barbaralanedicarboxylate (1d). – Addition of (phenylethynyl)cerium(III) chloride to 2 followed by acid-induced dehydration of the resulting endo,endo diol 6 yields the bis(phenylethynyl)diene 7, which is cyclised to the bis(phynylethynyl)barbaralane 1e by allylic bromination and subsequent treatment of the exo,exo dibromide 8 with the zinc-copper couple. Likewise, the exo,exo dibromo disulphone 11, which is obtained from 2 via the bis(vinyl sulphide) 9 and the bis(vinyl sulphone) 10, is converted into the bis(phenylsulphonyl)barbaralane 1f. – Trifluoromethylation of diketone 2 with trimethyl(trifluoromethyl)silane in the presence of a source of fluoride ions affords a mixture of the O silylated endo,endo diol 12 and the oxatwistane 13. Hydrochloric acid converts the latter into the hydroxy ketone 16, which yields 12 on treatment with trimethyl(trifluoromethyl)silane and tetrabutylammonium fluoride. Desilylation of 12 to furnish the endo,endo diol 14 requires prolonged treatment with hydrofluoric acid under phase-transfer catalysis. Vigorous conditions are also necessary for the dehydration of 14 with phosphorus oxychloride in pyridine to afford the bis(trifluoromethyl)diene 15. Cyclisation of 15 to the bis(trifluoromethyl)barbaralane 1g is performed in the usual way by allylic bromination and subsequent reduction of the dibromide 17 with the zinc-copper couple. – The configurations and conformations in the crystals have been elucidated by X-ray diffraction analyses for the bicyclo[3.3.1]nonane derivatives 5, 8, and 11 as well as the barbaralanes 1f and h. In the solid state, 1f appears to exist as a single non-rearranging valence tautomer. The atomic distances found for 1h indicate the presence of equilibrating non-equivalent valence tautomers. The results are compared to those from X-ray diffraction analyses of other degenerate barbaralanes and heterobarbaralanes.

The resolution of the earlier reported racemic bridged methyl deoxyfuranosides 1 and 3 was achieved via fractional crystallization of the ephedrinium salts 2 or by column chromatography of the camphanoates 5. The absolute configurations of 1 and 3 were established by X-ray structural analysis of the (S)-α-naphthylethylammonium carboxylate (+)-4 and by correlation with the other enantiomerically pure compounds of this type. (+)-3 was converted into the 2,5-bridged altrose derivative (+)-8.

The syntheses and properties of novel, extremely strong uncharged polyaminophosphazene bases up to a high level of steric hindrance are described. Most of the systems were readily prepared in up to molar quantities and conveniently recovered from their salts. They are of appreciable to high chemical and thermal stability. Crystal structures of their salts were determined in order to parametrize a force field, which is utilized in molecular modeling studies. The latter offer a rationalization of the high conformational mobility of these systems. These bases cover a range of ca. 15 pK units in basicity and extend the range of uncharged auxiliary bases by ca. 19 pK units up to DMSOpKBH+ values of 34–35. They are proposed as a novel class of auxiliary bases for deprotonation of very low acidic compounds where chemists have been so far left to classical metalorganic bases. Depending on the basicity range and the degree of steric protection of the basic center, these systems are particularly applicable to E2 elimination or to in situ generation of highly reactive “naked” anions.

Separation and stereochemical attribution of the two enantiomers of the neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) has been achieved by applying chromatography on a chiral phase HPLC column in hyphenation with circular dichroism (CD) spectroscopy (LC-CD coupling). Assignment of the absolute configuration of TaClo and its N-methyl analog has been achieved by quantum chemical CD calculations and has finally been confirmed by single-crystal X-ray diffraction analyses of the two enantiomers of N-formyl-TaClo as obtained in enantiomerically pure form by crystallization.

A broad variety of enantiopure axially chiral 2-aminomethyl-1-(2-oxyphenyl)naphthalenes were prepared via short and efficient synthetic pathways by using the ‘lactone method’ for the regio- and stereoselective construction of the biaryl axis. Their in vitro activity against Trypanosoma cruzi, the causative agent of Chagas' disease, was evaluated. In particular, the M-configured atropisomers, with the 2-oxy function equipped with an O-triflate group, were found to exhibit good antitrypanosomal activities (down to IC50=1.6 μg/mL), combined with low levels of cytotoxicity.

The West African plant Ancistrocladus barteri (Ancistrocladaceae) was investigated chemically for the first time. Besides the known naphthylisoquinoline alkaloids N-methyldioncophylline A and 7-epi-N-methyldioncophylline A (i.e. its atropo-diastereomer), a new naphthalene-free alkaloid, belonging to the ‘Dioncophyllaceae type’, was isolated. Its structure was elucidated by spectroscopic and degradative methods and confirmed by total synthesis. The new compound, named N-methylphylline, is exactly the isoquinoline “half” of both, N-methyldioncophylline A and its atropisomer. Furthermore, the related tetrahydroisoquinoline O,N-dimethylphylline, an intermediate in the chemical synthesis of N-methylphylline, was detected as a new natural product in crude extracts of A. barteri.

The crystal structure of Pt6Cl12 (β-PtCl2) was redetermined (ah = 13.126A, ch = 8.666A, Z = 3; arh = 8.110A, α = 108.04°; 367 hkl, R = 0.032). As has been shown earlier, the structure is in principle a hierarchical variant of the cubic structure type of tungsten (bcc), which atoms are replaced by the hexameric Pt6Cl12 molecules. Due to the 60° rotation of the cuboctahedral clusters about one of the trigonal axes, the symmetry is reduced from to (). The molecule Pt6Cl12 shows the (trigonally elongated) structure of the classic M6X12 cluster compounds with (distorted) square-planar PtCl4 fragments, however without metal-metal bonds. The Pt atoms are shifted outside the Cl12 cuboctahedron by Δ = +0.046A ((Pt—Cl) = 2.315A; (Pt—Pt) = 3.339A). The scalar relativistic DFT calculations results in the full symmetry for the optimized structure of the isolated molecule with d(Pt—Cl) = 2.381A, d(Pt—Pt) = 3.468A and Δ = +0.072A. The electron distribution of the Pt-Pt antibonding HOMO exhibits an outwards-directed asymmetry perpendicular to the PtCl4 fragments, that plays the decisive role for the cluster packing in the crystal. A comparative study of the Electron Localization Function with the hypothetical trans-(Nb2Zr4)Cl12 molecule shows the distinct differences between Pt6Cl12 and clusters with metal-metal bonding. Due to the characteristic electronic structure, the crystal structure of Pt6Cl12 in space group is an optimal one, which results from comparison with rhombohedral Zr6I12 and a cubic bcc arrangement. Struktur und Bindung des hexameren Platin(II)-Dichlorids, Pt6Cl12 (β-PtCl2) Die Kristallstruktur von Pt6Cl12 (β-PtCl2) wurde neu bestimmt (ah = 13.126A, ch = 8.666A, Z = 3; arh = 8.110A, α = 108.04°; 367 hkl, R = 0.032). Wie schon fruher gezeigt, ist die Struktur im Prinzip eine hierarchische Variante des kubischen Wolframtyps (bcc), dessen Atome durch die hexameren Pt6Cl12-Molekule ersetzt sind. Wegen der 60°;-Drehung der kuboktaedrischen Cluster um eine der trigonalen Achsen ist jedoch die Symmetrie von auf () reduziert. Das Pt6Cl12-Molekul zeigt die (trigonal gestreckte) Struktur der klassischen M6X12-Clusterverbindungen mit (verzerrten) planar-quadratischen PtCl4-Fragmenten, jedoch ohne Metall-Metall-Bindungen. Die Pt-Atome liegen um Δ = +0.046A auserhalb der Cl12-Kuboktaeder ((Pt—Cl) = 2.315A; (Pt—Pt) = 3.339A). Skalar-relativistische DFT-Rechnungen ergeben fur das optimierte isolierte Molekul die vollstandige -Symmetrie mit d(Pt—Cl) = 2.381A, d(Pt—Pt) = 3.468A und Δ = +0.072A. Die Elektronenverteilung zeigt eine auswarts gerichtete Asymmetrie in der Ausdehnung des (Pt-Pt)-antibindenden HOMO senkrecht zu den PtCl4-Fragmenten, was fur die Packung der Cluster im Kristall entscheidend ist. Vergleichende Untersuchungen der Elektronen-Lokalisierungsfunktion fur das hypothetische trans-(Nb2Zr4)Cl12-Molekul zeigen die gravierenden Unterschiede zwischen Pt6Cl12 und Clustern mit Metall-Metall-Bindungen. Wegen der charakteristischen Elektronenstruktur ist die Kristallstruktur von Pt6Cl12 in optimal, wie ein Vergleich mit rhomboedrischem Zr6I12 und einer kubischen bcc-Anordnung ergibt.

CsMn2P2 entsteht bei der Reaktion von Cs4P6 mit Mn und rotem Phosphor (Nb-Ampulle; 1073 K) in Form schwarzer Plattchen. Die Verbindung ist paramagnetisch, folgt dem Curie-Weiss-Gesetz oberhalb 110 K (μ = 4.81 B.M. / CsMn2P2; θ = — 79 K) und ordnet unterhalb 110 K antiferromagnetisch. Das magnetische Moment zeigt den Wert fur MnII : MnIII = 1:1. CsMn2P2 ist isotyp mit BaZn2P2 (tI10; I4/mmm; a = 4.098(1) A, c = 14.215(4) A, d(Mn—P) = 2.387(1) A (4×), d(Cs—P) = 3.718(2) A (8×)), enthalt also keine P—P-Bindungen. Die unterschiedlichen Bereiche des Strukturtyps von BaAl4 (ThCr2Si2) werden nochmals analysiert und parametrisiert. CsMn2P2, a Manganese(II, III) Phosphide with BaZn2P2 Structure. With a Contribution to the BaAl4 Structure Type CsMn2P22is formed by the reaction of Cs4P6 with Mn and red phosphorus (Nb ampoule; 1073 K) as black platelets. The compound is paramagnetic following the Curie-Weiss law above 110 K (μ = 4.81 B.M. / CsMn2P2; θ = —79 K) and orders antiferromagnetically below 110 K. The magnetic moment corresponds with the ratio MnII : MnIII = 1:1. CsMn2P2 is isotypic with BaZn2P2 (tI10; I4/mmm; a = 4.098(1) A, c = 14.215(4) A, d(Mn—P) = 2.387(1) A (4×), d(Cs—P) = 3.718(2) A (8×)), and shows, therefore, no P—P-bonds. The different regions of the BaAl4 (ThCr2Si2) structure type are analysed and parameterized once more.

The "lactone concept" has been efficiently employed for the first atropo-enantioselective synthesis of knipholone and related natural phenylanthraquinones. Besides the regio- and stereoselective construction of the biaryl axis, another important step was the "synthetically late" introduction of the C-acetyl group, either by a Friedel-Crafts type acetylation or by an ortho-selective Fries rearrangement first tested on simplified model systems and subsequently applied to the highly atroposelective preparation of the natural products and of simplified analogs thereof for biotesting. The synthetic availability of these natural biaryls, their precursors, and their unnatural analogs permitted a broader investigation of the antiplasmodial activities of these interesting biaryls.

The atropo-enantioselective total synthesis of the axially chiral bicoumarin (+)-isokotanin A (1) is described. Key steps were the formation of a configurationally stable seven-membered biaryl lactone and its kinetic resolution by atroposelective ring cleavage. The previous assignment of the absolute configuration of (+)-isokotanin A (1) (and its synthetic precursors) was confirmed by quantum chemical CD calculations. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

The effect of different phospholipids in stabilising the tear film was investigated to determine if particular polar head groups gave greater stability than others.Purified phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS) and cardiolipin (CL) were used. These were applied to a model eye loaded with an artificial tear fluid and the tear break-up time (TBUT) was measured. Three variants of the artificial tear fluid were utilised: buffered saline alone; one with proteins and mucins; and one containing proteins, mucins and lipids.TBUT was improved by the presence of phospholipids. In particular, the best performance was with PI applied to artificial tear fluid containing proteins mucins and lipids. Use of buffered saline as the artificial tear fluid gave very short break-up times.Increase in tear film stability by phospholipids is probably not due to the charge carried by the polar head group, but more likely due to the charge distribution, and the presence of hydroxyl groups in the head group also tends to increase stability, possibly through specific interactions with proteins and mucins in the subphase.

Fused N-(di)arylamino-pyrrol-2,3-diones 1 are reacted with diphenylketene, thiosemicarbazide or 1,2-diaminobenzene to afford the 3-diphenylmethylene pyrrolones 2, the thiosemicarbazones 4 or the quinoxaline derivatives 5 as well as 6, respectively. Thermolysis of 2b,c,e,f,6b and the pyrrolo-quinoxaline 8 afford the corresponding N-deaminated products 3, 7 and 9. Rearrangements into diazapropellanes following a thermally initiated Fischer - indolization as originally expected do not occur.

3-Bromo-1-methyl-1,2,5,6-tetrahydropyridine(N−B)borane (7) was prepared from 3-bromopyridine by conversion to 3-bromo-1-methylpyridinium iodide, hydrogenation of the latter with sodium tetrahydroborate and treatment of the resulting 3-bromo-1-methyl-1,2,5,6-tetrahydropyridine (6) with borane−dimethyl sulfide. Whereas no trapping product of the possible intermediate 1-methyl-1-azacyclohexa-2,3-diene (4) could be observed on treatment of 6 with potassium tert-butoxide in the presence of furan, the subjection of 7 to the same conditions produced the hexahydroepoxyquinoline derivatives 8a−c. Treatment of 7, dissolved in styrene, with sodium bis(trimethylsilyl)amide furnished the hexahydrocyclobutapyridine derivatives 9a−c. The six-membered cycloallene 1-methyl-1-azacyclohexa-2,3-diene(N−B)borane (10) must be regarded as the key intermediate en route to 8 and 9.

The new imido compounds [(η5-C5H5)M(NR)2(η1-C5H5)] (R = tBu: M = Mo 2a, W 2b; R = Mes: M = W 2c) have been prepared and the crystal structure of 2c has been determined. Three fluxional processes can be detected by variable temperature proton NMR spectroscopic studies of these cyclopentadienyl complexes, namely: (i) rotation of the σ-C5H5 ligand about the M−Cipso-bonding axis, (ii) migration of the metal complex fragment between the carbon atoms of the σ-bonded C5H5 ligand (metallotropic migration, sigmatropic rearrangement), and (iii) the interconversion of hapticity of σ- and π-bonded C5H5 ligands.

A wide range of enol carbonate, carbamate, and ester radical cations is characterized in solution by cyclic voltammetry and EPR spectroscopy. Preparative transformations using one-electron oxidants or anodic oxidation yield benzofurans after O-CO bond cleavage. Mechanistic investigations and direct detection of radical intermediates reveal that all enol radical cations undergo exclusively O-CO bond cleavage to provide alpha-carbonyl cations and acyl (or alternatively, alkoxyacyl and aminoacyl) radicals, respectively. The kinetics of the mesolytic fragmentation and the influence of nucleophilic additives have been determined using fast-scan cyclic voltammetry.

Treatment of the cyclobutene 3 with sodium methoxide leads to the cyclopropane esters 4 and 5. Experiments with deuterated compounds supply information about the course of this reaction. The optically active epoxyoxepine (+)-2a is the starting material for the synthesis of (+)-3, (−)-4 and (+)-5. The syntheses of the functionalized cyclopropanes (+)-10a, (−)-10b and (+)-12 are also described.

The oxidation of the 1-thiochromanones 1−3 by dimethyldioxirane (DMD) produced the corresponding sulfoxides 4−6 or sulfones 7−9; their relative amounts depended on the amount of oxidant used. A low diastereoselectivity was observed in the sulfoxidation of the 2-substituted 1-thiochromanones 2 and 3, due to the small steric differentiation during the DMD attack. An unusual reactivity pattern was found in the DMD oxidation of the 1-thiochromones 10−12, in that the sulfoxides 13−15 were more reactive toward the electrophilic oxidizing agent than the corresponding sulfides. The observed anomaly may be explained in terms of transannular stabilization of the transition structure (TS) for the sulfone formation, promoted through favorable conformational effects in the sulfoxide. Higher sulfoxide/sulfone ratios were found in solvents of greater hydrogen bond donor capacity, which is in accordance with the postulated stabilizing effect.

The first total synthesis of the antimalarial alkaloid dioncophylline B (2) from Triphyophyllum peltatum (Dioncophyllaceae), and thus the first preparation of a 7,6′-coupled naphthylisoquinoline, is described. Key steps within this synthesis are the ortho-functionalization of the MOM-protected naphthalene and isoquinoline moieties 14 and 7 by directed ortho-metalation, with subsequent stannylation of the naphthalene part and bromination of the isoquinoline portion, and the regioselective intermolecular Stille coupling reaction of these building blocks. The presented synthesis opens the way for the preparation of further 7-coupled compounds of this class of alkaloids.

The absolute configuration of (+)-isoshinanolone, a wide-spread acetogenic metabolite from higher plants, has been determined by X-ray structure analysis of its new dibromide; accordingly, this natural tetralone is 3R,4R-configured, in agreement with previous degradative results. In addition, a first chiroptical on-line stereoanalysis for isoshinanolones is presented, i.a. by HPLC on a chiral phase coupled to CD spectroscopy, giving pure CD spectra of all of the four stereoisomers of isoshinanolone directly from stereoisomeric mixtures.

The photobromination of 1,1,3,3,5,5-hexamethyl-1,3,5-trisilacyclohexane (1) almost exclusively attacks CH2 groups and results in 2,2-dibromo-trisilacyclohexane (2) as well as 2,2,4,4-tetrabromo-trisilacyclohexane (3) in high yields. Starting from a mixture of C-brominated trisilacyclohexanes the isomeric 2,2,9-tribromo-1,3,3,5,5,8,8,10,10,13,13-undecamethyl-1,3,5,8,10,13-hexasilabicyclo[7.2.2]tridec-6-yne (6) had been obtained in very low yield in an attempt to establish a preparative route to adamantanes with a C4Si6 skeleton, i.e., with C bridgeheads and SiR2 bridges. By ICl-cleavage of a Si—methyl bond in 2 and subsequent substitution with Br3CLi, the trisilacyclohexane 4 with functional groups in opposite positions of the ring can be obtained. Linking the step-by-step synthesized Cl-Me2Si-C=C-SiMe2-CH2-SiMe2-Ph to the CBr3 group of 4 results after HBr-cleavage of the Si—Ph bond in (ω-bromo-octynyl)-trisilacyclohexane (12). A ring closure of 12 would result in an isomeric hexasila bicyclo[7.2.2]tridec-6-yne. The compounds were characterized by 1H, 13C, and 29Si NMR spectra. Additionally, the molecular structures of 4 and 6 were confirmed by X-ray single crystal investigations.Key words: 1,1,3,3,5,5-hexamethyl-1,3,5-trisilacyclohexane, bromination, 2,2,9-tribromo-1,3,3,5,5,8,8,10,10,13,13-undecamethyl-1,3,5,8,10,13-hexasilabicyclo[7.2.2]tridec-6-yne, carbosilane synthesis, NMR data, crystal structure investigation.

The stereoselective total synthesis of the sesquiterpene herbertenediol (3) and of its naturally occurring dimers, mastigophorenes A [(P)-1] and B [(M)-1], is described. Following the “lactone concept”, the configuration at the biaryl axis was atropo-divergently induced to be P or, optionally, M, by stereocontrolled reductive ring cleavage (diastereomeric ratio up to 97:3) of the configurationally unstable joint biaryl lactone precursor 17 using the oxazaborolidine−borane system, through dynamic kinetic resolution. Mechanistic considerations of the lactone coupling suggested interference by a methoxy group next to the halogen substituent and led to an improvement of the coupling yield from 39 to 87% (to give the lactone 37). As a new, likewise highly efficient variant of the lactone method, we report for the first time thenow nondynamickinetic resolution of a structurally related, but centrochiral “aliphatic−aromatic” lactone, (rac)-10. Its highly efficient (krel > 300) enantiomer-differentiating Corey−Ba...

Several N-alkanoyl derivatives (4-9 and 13-16) of the potent mitochondrial complex I inhibitor TaClo (1-trichlorom ethyl-1,2,3,4-tetrahydro-β-carboline, 2) have been synthesized in order to elucidate the role of hydrophobic portion in the inhibitory action. Using rat brain homogenates or submitochondrial particles, the inhibitory effects of these compounds towards NADH-ubiquinone reductase (complex I) activity indeed appeared to correlate quite strongly with their lipophilic character. An X-ray structure analysis, exemplarily performed for N-acetyl-TaClo (4), revealed the N-substituent of such chlorinated agents to be dramatically pushed out of the β-carboline ring ‘plane’ due to the high steric demand of the huge trichloromethyl group at C-1.

The oxidative cyclization of a phenolic amide to a spirolactam has long been regarded as an "impossible" reaction, because exposure of the substrates to a variety of oxidants results in formation of spirolactones with consequent loss of the amine segment. We recently communicated that this heretofore unknown transformation may be achieved by oxidation of oxazoline analogues of phenolic and indolic amides. Herein, we provide full details of our work.

The liquid odorants (R)-6 and (R)-7 and their corresponding crystalline model substances (R)-8 and (R)-13 were synthesized. Based on the X-ray analyses of (R)-8 and (R)-13, geometries for (R)-6 and (R)-7 were determined using semiempirical calculations.

2-Alkyl-1-methylquinazolinium hexafluorophosphates 9 are deprotonated by sodium or potassium hydride to afford solutions of 2-alkylidenedihydroquinazolines 10, which were investigated by NMR spectroscopy. Trapping with methanesulfonyl azide (5a) of 10 in situ or subsequent treatment with trifluoromethanesulfonyl azide (5b) gives mixtures of colourless (15) and intensely yellow N-sulfonylimino-1,4-benzodiazepines 16 along with products due to cleavage of the exocyclic double bond of 10, viz. 11 and 13. The ethylidene compound 10b yields the bicyclic products 18 and 19, apparently by complex sequences of reactions that are triggered by removal of the acidic proton at C-2 of 16b and 16f. The structures of the products are based on spectroscopic evidence and X-ray diffraction analyses performed on 15b, 16d, 16e, and 19.

Die isotypen Verbindungen LiM4[BN2]3 (M = Ca, Sr, Ba, Eu) und NaM4[BN2]3 (M = Sr, Ba) entstehen als farblose bis blasgelbe prismatische Kristalle (schwarz mit Eu) durch Umsetzung der binaren Komponenten Li3N, M3N2, EuN und BN bzw. Na, NaN3, Ba3N2 und BN in verschweisten Nb-Ampullen bei 1375 bzw. 1275 K. Die linearen [N–B–N]3–-Anionen haben Bindungslangen d(B–N) zwischen 132.6 und 136.6 pm. Schwingungsfrequenzen und Kraftkonstanten f(B–N) = 7.25–7.89 Ncm–1 weisen signifikante Verschiebungen mit Abstand und effektiver Anionenladung auf. Die kubischen Kristallstrukturen (Im3m (Nr. 229), Z = 2; LiM4[BN2]3: a(Ca) = 711.5 pm; a(Sr) = 745.6 pm; a(Eu) = 742.5 pm; a(Ba) = 788.0 pm, sowie NaM4[BN2]3: a(Sr) = 756.8 pm; a(Ba) = 791.7 pm) lassen sich als aufgefullte Varianten der β-PtHg4-Struktur beschreiben, deren Existenzbereich als Funktion von Zellvolumina und Ionenradien abgeleitet werden kann. Die Partialstruktur der Kationen wird aus zentrierten E1(E2)8-Wurfeln gebildet, die zu einem 3D-Netz [E1(E2)8/2] kondensiert sind (E1 = Li, Na; E2 = Ca, Sr, Ba, Eu). Die noch offenen Wurfellucken sind mit [N–B–N]3–-Anionen aufgefullt, wodurch zwei interpenetrierende [E1[BN2]6/2]-Netze entstehen. Periodische Knotenflachen (PNS) der Symmetrie Im3m zeigen die Regionen unterschiedlicher Wechselwirkung. Ternary Nitridoborates. 2. Synthesis, Crystal Structure, and Vibrational Spectra of New Ternary Compounds with the [N–B–N]3– Anion The isotypic compounds LiM4[BN2]3 (M = Ca, Sr, Ba, Eu) and NaM4[BN2]3 (M = Sr, Ba) are formed as colorless to pale yellow prismatic crystals (black with Eu) by reaction of the binary components Li3N, M3N2, EuN and Na, NaN3, Ba3N2 and BN in sealed niobium ampoules at 1375 and 1275 K, respectively. The linear anions [N–B–N]3– have bond lengths d(B–N) between 132.6 and 136.6 pm. Vibrational frequencies and force constants f(B–N) = 7.25–7.89 Ncm–1 reveal significant drifts related to bond length and effective anionic charge. The cubic crystal structures (Im3m (No. 229), Z = 2; LiM4[BN2]3: a(Ca) = 711.5 pm; a(Sr) = 745.6 pm; a(Eu) = 742.5 pm, a(Ba) = 788.0 pm and NaM4[BN2] structure type, and the range of existence of this cubic structure is derived from the molar volume and the ionic radii. The cations form a partial structure of centered cubes E1(E2)8 which are condensed to a [E1(E2)8/2] network (E1 = Li, Na; E2 = Ca, Sr, Ba, Eu). The remaining open cubes are filled by the [BN2]3– anions yielding two interpenetrating [E1(BN2)6/2] networks. Periodic Nodal Surfaces (PNS) of Im3m symmetry show the regions of different interactions.

2-Alkyl-1-methylquinolinium hexafluorophosphates 1 are deprotonated by sodium or potassium hydride to afford solutions of 2-alkylidenedihydroquinolines 2, which are investigated by NMR spectroscopy. 1,3-Dipolar cycloaddition of phenyl azide to 2 yields the spirocyclic products 10. While, at 80-110 °C, the [3 + 2] cycloaddition that afforded (u)-10f is reversible and accompanied by epimerisation to give (l)-10f, thermolysis of the dimethyl compounds 10b and d affords the ring-expanded products 14b and d, respectively, in good yields along with molecular nitrogen. Irradiation of 10d with light of λ > 320 nm results in the formation of similar amounts of 14d and [3 + 2] cycloreversion products, viz. 2-diazopropane (5b) and the N-phenylimine 15d. - Trapping of 2 by methanesulphonyl azide (18a) gives mixtures of the products of ring expansion (21b, d-f, 10-50 %) and [3 + 2] cycloreversion (22a, d, 10-80 %) of the apparently very labile intermediate spirocyclic cycloadducts 19. The ratio of 21 vs. 22 is significantly improved when 18a is replaced by trifluoromethanesulphonyl azide (18b), which affords the iminodihydrobenzazepines 21i-k in 50-75 % yield. The structures of the products are based on NMR evidence and X-ray diffraction analyses performed with 21b, d, and (ax,E)-21e.

Both title compounds were obtained in stereochemically pure form by refluxing 5,5-dim ethyl-1 ,3-thiazolidine-2,4-dicarboxylic acid (3) with methanolic HCl, followed by a separation of the two diastereomers 4a and 4b on silica gel. The X-ray structure analyses of these stereoisomers confirm the relative configuration to be cis for 4a and trans for 4b with respect to the two carboxymethyl substituents at C(2) and C(4). For both molecules, an envelopetype conformation of the thiazolidine ring was found with C(5)-S(1)-C(2)-N(3) being located in a plane showing a small ring torsion angle of -11.2° and -3.1° for the cis- and the rrafts-epimer, respectively. The trans-configured compound 4b adopts a nearly ideal envelope conformation with C(4) being the flap atom, while the cis-isomer 4a. apparently because of steric interactions of the C(2) and C(4) substituents, shows a twisted envelope conformation.

The synthesis of a new, suitably protected and activated binaphthalene building block representing the central structural element of all known natural dimeric naphthylisoquinoline alkaloids, is described. This functionalized fragment possesses organometallically robust O-isopropyl (instead of O-acetyl) protecting groups and bromo (instead of trifluoromethanesulfonyloxy) activation at the scheduled coupling positions. Starting from a biphenyl intermediate, the construction of the two `outer' naphthalene rings has been achieved by a Wittig reaction → cyclization sequence.

The molecular structure of the title compound 2-hexanoyl-1-tribromomethyl-1,2,3,4-tetra-hydro-β-carboline (3), a potent inhibitor of complex I of the mammalian mitochondrial respiratory chain, has been studied by single-crystal X-ray diffraction analysis. In the crystal, two heterochiral molecules of 3 (i.e., one R- and one S-configured molecule each) were found to be connected with one other in pairs via two intermolecular hydrogen bonds [O(215) ··· H(212)′ and O(215)′ ··· H(212)] to form an overall achiral ‘dimeric’ subunit

Oxidation with barium manganate of the enol of tetraacetylethane (10) affords tetraacetylethylene (7a) in good yield. Treatment of the 1,3-diketones 15a and b with iodosobenzene in the presence of boron trifluoride does not result in oxidative coupling yielding 10 and diacetyldibenzoylethane 17, respectively, as has been reported by Moriarty et al. Instead the known difluoroborylenolates 16 are formed. Oxidative coupling of the sodium enolate of 15b with iodine affords the meso-tetraketone meso-17 and diacetyldibenzoylethylene (E)-7b besides small amounts of rac-17 and the bisenol 19. In the presence of 1,4-diazabicyclo[2.2.2]octane, meso-17 and 19 tautomerise yielding identical equilibrium mixtures of meso-17, rac-17, and 19 (26:29:45). Dehydrogenation with 5,6-dichloro-2,3-dicyanobenzoquinone of meso-17 yields (E)-7b and an isomer (77:23) which was assigned structure (Z)-7b on the basis of spectroscopic evidence. – Tetraacetylethylene (7a) reacts with 1,2-dimethylenecyclohexane to afford two different [4+2]cycloadducts, viz. the spirocyclic dihydropyran 25 (30 %) and the tetraacetyloctalin 27. Whereas the latter is stable, the former isomerises to the latter on heating. Formation of both [4+2]cycloadducts and the isomerisation 25 27 are interpreted by invoking the zwitterion 26 as common intermediate. Monoolefines that cannot generate stable carbenium ions don't give [4+2]cycloadducts with 7a. In contrast, α-methylstyrene yields the oxa Diels–Alder product 30. The structures of (E)-7b, 19, 25, and 27 are established by X-ray diffraction analyses.

The deuterium-labelled 2,4,6,8-substituted barbaralanes [D5]-1a and b, and the two model barbaralanes 15 und 19 for the estimation of 13C chemical shifts in the slow-exchange limit are synthesised from bicyclo[3.3.1]nona-3,7-diene-2,6-dione (5). – The extension of Saunders′ isotopic perturbation method bridges the gap between the limiting cases “perturbation of shift equivalence in delocalised systems” and “perturbation of degeneracy” by considering the simultaneous presence of delocalised species of higher symmetry and skewed equilibria between localised molecules that are degenerate in the absence of the isotopic perturbation. An equation (Equation 7) is derived for such multi-component systems which describes the temperature dependence of the relative isotopic splittings in 13C spectra with three parameters, viz. the isotopic perturbation parameters ΔHP and ΔSP of the skewed equilibria and the enthalpy difference ΔH0 between the delocalised and localised species. – Relative isotopic splittings ΔδP/Δδ are calculated from estimated chemical shifts in the slow-exchange limit (Δδ) and isotopic splittings (ΔδP) of signals in variable-temperature 151-MHz 13C NMR spectra recorded for solutions of [D5]-1a and b in [D8]toluene and N,N′-dimethylpropylene urea. The results obtained from [D5]-1a in both solvents and from [D5]-1b in the former are compatible with either a skewed equilibrium between localised valence tautomers alone or the simultaneous presence of localised and small amounts of delocalised valence tautomers. In striking contrast, the small isotopic splittings themselves and their small temperature dependence, observed for solutions of [D5]-1b in N,N′-dimethylpropylene urea, demonstrate that one half of the solvated compound exists in the delocalised state [D5]-1b*, which is more stable by 2 kJ mol–1 than the equilibrating localised species [D5]-1b ⇌ [D5]-1b′.

Reaction of methanolic copper(II) acetate solution with oxazolidine 21 (HL7) led to the formation of the one-dimensional coordination polymer 1D-∞1[CuL27] 23. On the contrary, reaction of copper(II) acetate in methanol with pyrrolidine 24 (HL8) yielded the two-dimensional coordination polymer 2D-∞2[CuL28] 26. A common feature of 23 and 26 are the C2h-symmetric coordinatively unsaturated building blocks 22 and 25. In 1D-∞1[CuL27] 23, the cyano groups are linked to copper in a side-on fashion and the monomers 22 are oriented parallel to one another, whereas in 2D-∞2[CuL28] 26 the cyano groups are bound to copper in the end-on mode and the monomers 25 are oriented at an angle of 117° to one another. In both 1D-23 and 2D-26, copper has a distorted octahedral coordination sphere. On the other hand, reaction of methanolic copper(II) acetate solution with enantiomerically pure (5S)-pyrrolidine 27 (HL9(S)) led to the formation of the diastereomeric helical strands (M)-/(P)-1D-∞1[CuL29] 29. (M)- and (P)-29 are present in pairs in the infinite unit cell. In helical 1D-29, copper is tetragonal-pyramidally coordinated and the C2-symmetric monomers 28 (CuL29) are linked through only one cyano group. Moreover, it has been shown that the reaction of chiral racemic pyrrolidine 30 (HL10(R,S)) with copper(II) acetate via the intermediate Ci-symmetric building blocks 31 (CuL10(R)L10(S)) furnishes one-dimensional 1D-∞1[CuL10(R)L10(S)] 32. Single-crystal X-ray diffraction analyses of the supramolecular species 23, 26, 29, and 32 unequivocally establish the structures of these coordination polymers.