Olaf Schupp

A new multicomponent synthesis of 1,2,3,4-tetrahydroquinolines

Abstract The synthesis of a variety of differently substituted 1,2,3,4-tetrahydroquinolines by a new three-component reaction involving an imine (Ar-NCHR), an α-branched and enolizable aldehyde (R 1 R 2 CHCHO), and a nucleophile (ROH, ArSH, ArNH 2 , H 2 O) is described. The in situ generation of the imine (that allows a four-component process), and the reactions of an enantiomerically pure imine and/or aldehyde were also studied. A short discussion of the reaction mechanism is reported.

Cis- and trans-isoshinanolone from Dioncophyllum thollonii: absolute configuration of two `known', wide-spread natural products

Abstract From the rare West African liana, Dioncophyllum thollonii (Dioncophyllaceae), the known acetogenic tetralones, cis - and trans -isoshinanolone, were isolated. Exemplarily on this material, a new ruthenium-catalyzed oxidative degradation procedure, related to the well-established stereoanalysis of 1,3-dimethyltetrahydroisoquinolines, was elaborated. The method allows to unambiguously attribute the absolute configuration of these natural products, which likewise occur in several other plant species. For the rapid discrimination between the four possible stereoisomeric forms of isoshinanolone (i.e. the cis - and trans -diastereomers and their enantiomers), an HPLC-analytical procedure on a chiral stationary phase has been developed.

Acetogenic isoquinoline alkaloids: CXXI. Use of on-line high-performance liquid chromatography–nuclear magnetic resonance spectrometry coupling in phytochemical screening studies: rapid identification of metabolites in Dioncophyllum thollonii

Abstract Exemplarily for a root extract of the West African liana Dioncophyllum thollonii a strategy for the rapid identification of secondary metabolites in plant extracts is presented, based upon on-line coupling of high-performance liquid chromatography with nuclear magnetic resonance detection. For a first overview, an on-flow experiment was performed, which allowed the identification of the naphthylisoquinoline alkaloid dioncophylline A. A second alkaloid, 5′-O-demethyldioncophylline A, was identified by subsequent application of stop-flow two-dimensional HPLC–NMR ROESY experiments. In the case of coeluting compounds, the design of appropriate time-slice experiments allowed the characterization of the diastereomeric tetralones trans- and cis-isoshinanolone. Thus, through consequent use of all different experimental modes available in HPLC–NMR, a phytochemical screening of plant extracts can be realized in a fast and reliable way. The NMR detection allows the characterization of diastereomeric compounds even in the case of far-reaching chromatographic coelution.

Novel concepts in directed biaryl synthesis: XV. Chiral rhenium complexes [(η5-C5H5)Re(NO)(PPh3)(R,R-lactone)]+BF4− of lactone-bridged biaryls as ligands: s☆☆☆

Abstract The preparation is reported of the first series of (racemic) chiral rhenium complexes with “axially prostereogenic” biaryl lactone ligands, which a

Stereoselective one-pot synthesis of β-lactams by Lewis acid promoted condensation of silylketene thioacetals with imines

Abstract A series of silylketene thioacetals derived from 2-pyridylthioesters have been prepared and the (E) (Z) configuration of some of them has been determined by NMR spectroscopy. In the presence of Lewis acids these compounds stereoselectively react with imines to afford β-lactams in a convenient one-pot procedure. An enantioselective β-lactam synthesis promoted by a chiral Lewis acid is also described.

Synthesis and ring-opening reactions of cationic ruthenium biaryl thionolactone complexes☆☆☆

The preparations of novel thionolactone-bridged configuratively labile biaryls and their [Cp(R3P)2Ru]+-complexes are described. The dynamics of helimerization of these complexes and their reactivity towards nucleophiles have been investigated. Hydride transfer reagents lead to a cleavage of the thionolactone bridge to give the corresponding thiolate complexes, apparently via intermediate exothiolactolate ruthenium complexes. A similar lactolate analog is formed upon addition of a mild S-nucleophile.

The influence of aluminum trichloride on a configuratively labile lactone-bridged biaryl: quantum chemical calculations and optical spectroscopy

Semiempirical and ab initio calculations on the binding properties of the AlCl3 complex of 1,3-dimethylbenzo [b][naphtho[1,2-d]pyran-6-one are reported. Compounds of this type are key intermediates in the stereoselective synthesis of axially chiral biaryl systems. Semiempirical (MNDO, PM3) and ab initio (STO-3G, 3-21G) calculations give important information about conformational changes that occur by complexing the free lactone with AlCl3: the calculations predict a significant influence on the lengths of the (CO)exo and (CO)endo bonds, and a distinct planarization of the heterocyclic lactone part of the complexed benzonaphthopyranone. IR and Raman spectroscopy was applied in order to confirm the theoretical predictions. The good agreement of results obtained by semiempirical frequency calculations with the experimental data supports the assignment of vibrational bands affected on coordination. The highest shift caused by coordination (−152 cm−1) is observed for v(CO).

Enantioselective Organic Syntheses Using Chiral Transition Metal Complexes, 9 Atropo-Diastereoselective Ring Opening of Biaryl Thionolactones Using [CpRu{(S,S)-CHIRAPHOS}]+ as a Chiral Auxiliary

The substitution-labile thiophene complex [CpRu{(S,S)-CHIRAPHOS}(SC4H4)]BF4 (2) [(S,S)-CHIRAPHOS = (2S,3S)bis(diphenylphosphanyl)butane], prepared from [CpRu{(S,S)-CHIRAPHOS}Cl] (1), thiophene, and AgBF4, reacted with the biaryl-thionolactones 3a–f to give the corresponding S-coordinated complexes 4a–f in high yields. The structure of 4c, which crystallized as the pure (S,S,P) diastereoisomer, was determined by X-ray crystallography. Coordination of the ruthenium fragment caused an elongation of the C=S bond, a contraction of the C–O bond within the lactone ring and a flattening of that ring. Single hydride transfer with LiBEt3H converted 4a–f into the thiolactolate complexes 5a–f in good yields and diastereoselectivities. An X-ray structure determination of the major isomer of 5a revealed it to be the (S,S,S,P) diastereoisomer. Protonation with NH4PF6 converted 5a–f into the corresponding ring-opened thioaldehyde complexes 6a–f. Alkylation of 5a with methyl iodide resulted in Ru–S cleavage to give the oxothioacetal 7a and [CpRu{(S,S)-CHIRAPHOS}I] (8). Full reduction of 4a–f with LiAlH4 produced the thiolate complexes 9a–f in high yields and 6–74% de. Methylation at sulfur converted 9a–c into the corresponding thioether complexes 10a–c, which were cleaved to 8 and the free methyl thioethers 11a–c without isomerization of the biaryl axis.

Determination of the absolute stereostructure of a helical biaryl lactone by multiple scattering X-Ray Experiments

Abstract The elucidation of the absolute configuration of a lactone-bridged biaryl was performed by multiple scattering X-ray experiments. This helical, but configuratively unstable compound shows spontaneous deracemization by crystallization. For the rapid stereochemical correlation with the examined crystal, an analytical device was developed, by chromatography on a chiral HPLC phase.

Unexpected ring-expansion of axially prostereogenic biaryl lactones by methylenephosphoranyl-substituted imido complexes of molybdenum and tungsten

Abstract Transition-metal-substituted phosphorus ylides M(NtBu)2(CHPPh3Cl, with M  Mo, W, have been shown to be useful C-nucleophiles for the selective CO bond cleavage of benzocoumarin-type “axially prostereogenic” biaryl lactones. The reaction of the metallo-ylide with the lactone leads to an eight-membered metallacycle as established by spectroscopic data and confirmed by an X-ray diffraction study of one of the products.