Aminierende reduktive Kupplung aromatischer Aldehyde mit niervalenten Titan-Reagenzien zu 1,2-Diarylethylendiaminen

Preparation of 1,2-Diarylethylenediamines by Aminative Reductive Coupling of Aromatic Aldehydes with Low-Valent Titanium Reagents In a novel McMurry- Type one-pot reaction, aromatic aldehydes and secondary amines are poupled of give the N, N, N′, N′-tetraalkyl-1,2-diarylethylendiamines 1–22 (Table 3). To this end, a lithium dialkylamide is added to an aromatic aldehyde to give the adduct B which is then treated with 1 equiv. of TiC1₄ to yield a coloured suspension of a reagent synthetically equivalent to a iminium salt ( C/D in Scheme 4). After treatment with a low-valent Ti reagent which is prepared by reduction of TiC1₄ with either K or, preferably, Mg, the coupling products are isolated in 23 to 81% yield as a 1:1 mixture of the diastereoisomers (meso- and rac-form). These are separated either by chromatography or by crystallization and characterized.     

Präparative chromatographische Enantiomerentrennung von synthetisch nützlichen cyclischen Acetalen

Preparative Chromatographic Resolution of Synthetically Useful Cyclic Acetals Racemic cyclic acetals derived from aldehydes and glycine, glycolic acid, thioglycolic acid, formylacetic acid, and acetoacetic acid (oxazolidinones 4 – 13 , dioxolanones 14 , 15 , oxathiolanone 16 , dioxinones 17 – 23 ) are resolved by preparative high-pressure liquid chromatography on silica gel coated with the polymer from N-acryloylphenylalanine ethyl ester (Chiraspher®). The separation factors α range from1,1 to 2,4. Use of a Prepbar®-chromatography system allows injection of several grams at a time. The enantiomeric acetals thus obtained are fully characterized. First application to amino-acid synthesis are mentioned.     

Synthesis of Hexadentate Hexahydro-1,3,5-triazine-Based Ligands and their Copper(I) Complexes

Summary.  Hexadentate ligands were formed by the reaction of primary dimethylaminoethyl- or methoxyethylamines with formaldehyde. The resulting N, N′, N″-functionalized hexahydro-1,3,5-triazines contain pending amino or ether functionalities which are able to coordinate to metals in addition to the ring nitrogen atoms. Both ligands were reacted with CuBr, and novel tricopper clusters were isolated and characterized by X-ray structure analysis. In these compounds a ring nitrogen atom, the pending amino or ether functionality, and two bridging bromine atoms coordinate each of the copper atoms. Received January 22, 2002; accepted (revised) March 22, 2002     

Perfluoralkyljod-verbindungen: Darstellungen und eigenschaften von CF3JO,CF3JOF2 und CF3JO2

Perfluoroalkyl iodine compounds: preparations and properties of CF₃IO, CF₃IOF₂, and CF₃IO₂. The trifluoromethyl iodine compounds CF₃IO, CF₃IOF₂, and CF₃IO₂ are formed from the reactions of CF₃I, CF₃IF₂ or CF₃IF₄ with ozone or silicon dioxide respectively. Their preparartions, properties, ¹⁹F-nmr spectra, and ir spectra are described.     

Enantioselective Preparation of 2‐Aminomethyl Carboxylic Acid Derivatives: Solving the β2‐Amino Acid Problem with the Chiral Auxiliary 4‐Isopropyl‐5,5‐diphenyloxazolidin‐2‐one (DIOZ). Preliminary Communication

Multigram amounts of suitably protected β²‐amino acids with 17 of the 20 proteinogenic side chains are prepared by diastereoselective reactions of Li, B, or Ti enolates of the corresponding 3‐acyl‐4‐isopropyl‐5,5‐diphenyloxazolidin‐2‐ones (acyl‐DIOZ; 1 ) with appropriate electrophiles (amidomethylation, hydroxyalkylation, (benzyloxycarbonyl)methylation) in yields of 55–90% and with diastereoselectivities of 80 to >97% (Scheme). The primary products 2 – 8 thus obtained are converted to protected β²‐amino acids by standard procedures (Table 1). Many of the DIOZ derivatives are highly crystalline compounds (31 X‐ray crystal structures in Table 2). The chiral auxiliary DIOZ, readily prepared in either enantiomeric form, is recovered with high yield.     

Synthese monodisperser linearer und cyclischer Oligomere der (R)-3-Hydroxybuttersäure mit bis zu 128 Einheiten

Monodisperse Linear and Cyclic Oligo[(R)-3-hydroxybutanoates] Containing up to 128 Monomeric Units Using benzyl ester/(tert-butyl)diphenylsilyl ether protection, (COCl)₂/pyridine esterification conditions, and a fragment-coupling strategy (with H₂/Pd-C debenzylation and HF · pyridine desilylation), linear oligomers of (R)-3-hydroxybutanoic acid (3-HB) containing up to 128 3-HB building blocks (mol. weight > 11 000 Da) are assembled (Schemes 1,2,5, and 6). In contrast to the previously employed protecting-group combination, and due to the low-temperature esterifying conditions, this procedure leads to monodisperse oligomers: all steps occur without loss of single 3-HB units. The product oligomers with two, one, and no terminal protecting groups (mostly prepared in multi-gram amounts) are characterized by all standard spectroscopic methods, especially by mass spectroscopy (Figs. 2 and 3), by their optical activity, and by elemental analyses. Cyclization of the oligo[(R)-3-hydroxybutanoic acids] with up to 32 3-HB units, using thiopyridine activation and CuBr₂ for the ring closure, produces oligolides consisting of up to 128 ring atoms (Scheme 7). Mixed oligolides containing 3-HB and (R)-3-hydroxypentanoic units are prepared from the corresponding linear trimers, using Yamaguchi's method for the ring closure (Scheme 8 and Fig.4 (X-ray crystal structures of two folded conformers)). Comparisons of melting points (Table 1), of [α] values (Tables 2 and 3), of ¹H-NMR coupling constants (Table 3), and of molecular volume/hydroxyalkanoate unit (Table 4) of linear and cyclic oligomer derivatives and of the high-molecular-weigh polymer show that the monodisperse oligomers appear to be surprisingly good models for the polymer. Besides this insight, our synthesis is supplying the samples to further test the role of P(3-HB) (ca. 140 units) as a component of complexes forming channels through cell-wall phospholipid bilayers.     

Stir bar sorptive extraction based on restricted access material for the direct extraction of caffeine and metabolites in biological fluids

A biocompatible stir bar sorptive extraction (SBSE) device was prepared using an alkyl-diol-silica (ADS) restricted access material (RAM) as the SBSE coating. The RAM-SBSE bar was able to simultaneously fractionate the protein component from a biological sample, while directly extracting caffeine and its metabolites, overcoming the present disadvantages of direct sampling in biological matrices by SBSE, such as fouling of the extraction coating by proteins. Desorption of the analytes was performed by stirring the bar in a water/ACN mixture (3/1, v/v) and subsequently reconcentrating the sample solution in water to enable HPLC-UV analysis to be performed. The limit of detection, based on a signal to noise ratio of 3, for caffeine was 25 ng/mL in plasma. The method was confirmed to be linear over the range of 0.5-100 microg/mL of caffeine with an average linear coefficient (R2) value of 0.9981. The injection repeatability and intra-assay precision of the method were evaluated over ten injections, resulting in a %RSD of approximately 8%. The RAM-SBSE device was robust (>50 extraction in plasma without significant signal loss) and simple to use, providing many direct extractions and subsequent determination of caffeine and its metabolites in biological fluids. In contrast to existing sample preparation methods for the analysis of caffeine and selected metabolites in biological fluids, this feasibility study using a biocompatible SBSE approach was advantageous in terms of simplifying the sample preparation procedures.     

Perfluoralkyljod-verbindungen: das trifluormethyljod-bis-trifluoracetat CF3J(OCOCF3)2

CF₃I(OCOCF₃)₂ is formed from the reactions of CF₃IF₂ or CF₃IO with trifluoroacetic anhydride at low temperature. During the reaction of CF₃IF₂ with (CF₃CO)₂O CF₃IF(OCOCF₃) is formed as an intermediate product. The preparation, the ¹⁹F-nmr spectra and the thermal decomposition are described.     

Preparation,Structure, and Reactivity of Thioxo and Imino Derivatives of the Triolide (and Pentolide) from (R)-3-Hydroxybutanoic Acid

Reaction of the triolide 1 from (R)-3-hydroxybutanoic acid with Lawesson's reagent 5 leads to the mono-, di-, and trithio derivatives 6–8 which can be isolated in pure form (20–40% yields), and which have crystal structures very similar to the parent triolide 1 (Fig. 1). Similarly, pentolide 3 is converted to mixtures of various thio derivatives, three of which are separated ( 10–12 ) by HPLC and fully characterized. The X-ray structures of the mono- and of one of the dithiopentolides ( 10, 12 ) differ remarkably from each other (Fig. 3). Reduction of the thiotriolides 6–8 (NaBH₄, R₃SnH, Cl₃SiH, Raney-Ni) gives 12-membered rings containing up to three ether groups (chiral crown ethers, 15, 17–19 ) in poor yields. The thiotriolides react spontaneously and in yields of up to 96% with ammonia, certain primary amines, and hydroxylamine to give imine and oxime derivatives with intact 12-membered-ring backbones ( 20, 22–24, 30 , see crystal structures in Figs. 4–7). The rigid structure of all the derivatives of triolide 1 puts the C?O, C?S, and C?NR O-, S-, and N-atoms in juxtaposition (a feature reminiscent of the side chains in the iron-binder enterobactin, Fig. 6). Imines containing PPh₂ groups are prepared ( 30, 33, 35 ) from the thiotriolides and tested as chiral ligands for Pd^II-catalyzed 1,3-diphenyallylations (→ 37 , enantiomer ratio up to 77:23). The reactions described demonstrate that multiple reactions of the triolide 1 from (R)-3-hydroxybutanoic acid which proceed through tetrahedral intermediates are possible without ring opening – the skeleton is remarkably stable, and this might be exploited as a template for bringing up to three pendent substituents into close proximity to allow a study of their interactions and cooperative properties. Also, the di- and trithio derivatives 7 and 8 could be used for cross-linking in molecules containing primary NH₂ groups.