Zur Konfiguration des Vitamin-D3-Metaboliten 25, 26-Dihydroxycholecalciferol: Synthese von (25S,26)- und (25R,26)-Dihydroxycholecalciferol

Configuration of the Vitamin-D₃-Metabolite 25,26-Dihydroxycholecalciferol: Synthesis of (25S,26)- and (25R,26)-Dihydroxycholecalciferol For selective synthesis of the title compounds, (25S)- 1b and (25R)- 1b (Scheme 1), the protected cholesterol precursors (25S)- 6 and (25R)- 6 were prepared from stigmasterol-derived steroid-units 4a-d and C₅-side chain building blocks 5a–d by Grignard- or Wittig-coupling (Scheme 2), the configuration at C(25) of the target compounds being already present in the C₅-units. Conversion of the cholesterol intermediates to the corresponding vitamin-D₃ derivatives was carried out via the 7,8-didehydrocholesterol compounds (25S)- 2b and (25R)- 2b (Scheme 1), using the established photochemical-thermal transformation of the 5,7-diene system to the seco-triene system of cholecalciferol. The configuration at C(25) of the cholesterol precursors as assigned on basis of the known configuration of the C₅-units used, was found to be in agreement with the result of a single crystal X-ray analysis on compound 11 . The configuration at C(25) remained untouched on conversion of the cholesterol ring system to the seco-triene system of vitamin D₃ as evident from comparison of the lanthanide-induced CD. Cotton effects observed for (25S)- 3b and (25S) 1b . 25,26-Dihydroxycholecalciferol observed as a natural vitamin-D₃ metabolite has (25S)-configuration.     

Synthesis of the Oviposition-Deterring Pheromone (ODP) in Rhagoletis cerasi L. Preliminary communication

For the assignment of the configuration at C(8) and C(15) of the natural oviposition-deterring pheromone 1 in Rhagoletis cerasi L., the four possible stereoisomers of 1 are synthesized. By condensing the C₆ building blocks (5R)- 4 and (5S)- 4 with the boron enolates of the C₁₀ building blocks (4S)- 13 and (4R)- 13 , followed by decarboxylative dehydration, all stereoisomers of 16 are available (Scheme 5). Glucosylation of 16 followed by formation of the taurin amide gives, after deprotection, the four stereoisomers (8R,15S)- 1 , (8R,15R)- 1 , (8R,15S) -1 , and (8S,15S)- 1 (Scheme 6).     

Chiral [2H]-Labelled Methylene Groups in Trienoic- and Dienoic Fatty Acids: A Facile Approach via Asymmetric Epoxidation of [2H] Allyl Alcohols

Chiral [²H] -labelled methylene groups flanked by two double bonds within (poly)unsaturated fatty acids are readily available from trans-2,3-epoxy[2,3-²H₂] alk-4-yn-l-ols, obtained in their turn by asymmetric epoxidation of the corresponding (E)-[2,3-²H₂] alk-2-en-4-yn-l-ols (see Scheme 3). The procedure is exemplified for (8S,3Z,6Z,9Z)-[7,8-²H₂] trideca-3,6,9-trienoic acid ((8S)- 11 ) and (8R)- 11 (Scheme 4) as well as for (5S,3Z,6Z)-[4,5^?2H₂]deca-3,6-dienoic acid ((5S)- 13 ) and (5R)- 13 (Scheme 5).     

Totalsynthese von natülichem α-Tocopherol. 5. Mitteilung. Asymmetrische Alkylierung und asymmetrische Epoxidierung als Methoden zur Einführung der (R)-Konfiguration an C(2) des Chroman-Systems

Total Synthesis of Naturally Occurring α-Tocopherol. Asymmetric Alkylation and Asymmetric Epoxidation as Means to Introduce (R)-Configuration at C(2) of the Chroman Moiety Based on the reductive, stereospecific ring closure of (2R,4′R,8′R)-α-Tocophcrylquinone′ or corresponding analogues with a short, functionalized side chain ( B , Scheme 1) to 1 resp. the chroman system of 1 (C), two different approaches for the introduction of the required tertiary methyl-substituted alcohol structure in the side chain of the aromatic precursors ( A , Scheme 1) were developed. The first approach uses asymmetric alkylation in three different versions featuring (a) diastereoselective steering with chiral auxiliaries I-IV (Scheme 2) attached as esters to a-keto acids, (b) intermediate transfer of chirality in an ester enolate (from 18 , Scheme 4) derived from an optically active α-hydroxy acid, (c) enantioselective alkylation of phytenal ( 20 ) and subsequent ring closure with chirality transfer (Schemes 5–7). The second approach is based on the asymmetric epoxidation of β-metallylalcohol (Sharpless epoxidation), the corresponding epoxyalcohol being converted in situ to the (S)-or (R)-chlorodiol (S)-and (R)- 29 , respectively, for isolation (Schemes 8 and 9). Nucleophilic epoxide opening with a (3R 7R)-3,7,11-trimethyldodecyl (C₁₅**) and an ArCH2 unit in appropriate sequence is used to assemble the C-framework of the target molecule via corresponding epoxide intermediates from either chlorodiol. Combined with the use of the methoxymethyl-ether function for protection of the hydroquinone system, the epoxide approach provides a short route to 1 (Scheme 10).     

Stereoselektive Totalsynthese von natürlichem Phytol und Phytolderivaten und deren Verwendung zur Herstellung von natürlichem Vitamin K1

Steroselective Total Synthesis of Natural Phytol and Derivatives thereof; Use of these Compounds in the Synthesis of Natural Vitamin K₁ The Li₂CuCl₄-catalyzed couplings of the easily accessible bifunctional C₅ allylic acetates (E)- 18a and (E)- 18b with racemic hexahydrofarnesylmagnesium bromide ((3 RS/RS, 7 RS/SR)- 19a ) proceed with high chemo- and stereoselectivity (≥98% (E)-retention) to give the (2E, 7 RS/RS, 11 RS/SR)-phytol derivatives 1a and 1b , respectively, in yields of 72–80% (Scheme 5). The same couplings performed with optically active hexahydrofarnesylmagnesium bromide (3 R, 7 R)- 19a yielded the (E)-phytol derivatives of the natural series (7 R, 11R)- 1a and (7 R, 11 R)- 1b. Acid-catalyzed hydrolysis of(2 E, 7 R, 11 R)- 1b gave natural phytol((2 E, 7 R, 11 R)- 1c ) Friedel-Crafts alkylation of ‘menadiol monobenzoate’ 11b with (2 E, 7 R, 11 R)- 1a or (2 E, 7 R, 11 R)- 1b gave the dihydrovitamine K₁ derivative (2 E/Z, 7′ R, 11′R)- 12b ((E/Z)≈? 9:l). Conversion of configurationally pure (2 E, 7′ R, 11′ R)- 12b (yield 73%; obtained after chromatographic removal of the (Z)-isomer) into natural vitamine K₁ ((2 E,7′ R, 11′ R)- 2 ) was achieved in the usual way by saponification and oxidation with air. Some further investigations of the coupling reactions of bifunctional C₅ allylic synthons with hexahydrofarnesylmagnesium bromide (3 RS/RS, 7 RS/SR)- 19a showed the outcome of these reactions to be critically dependent on the nature of the leaving group, the double-bond geometry and the nature and concentration of the catalyst. Thus, the Li₂CuCl₄-catalyzed couplings of (3 RS/RS,7 RS/SR)- 19a with the allylic halides 29a and 29c as well as with p-toluenesulfonate 29b yielded besides the phytol derivatives 1a and 1b - also the S_N2′-type products 30a and 30b (Scheme 8, Table 2); the same result was found for the coupling with the cis-configurated allylic acetates (Z)- 18a and (Z)- 18b (Table 3). A similar loss of chemo selectivity as well as the loss of stereoselectivity in the coupling reactions of 19 with the bifunctional (E)-olefins of type 18 was observed when the Li₂CuCl₄-catalyst concentration was increased from 0.2 to 25 mol-% or upon substitution of Li₂CuCl₄ by copper (I) chloride or iodide (Table 4).     

Radical Arylation Reactions of 4, 6, 8-Trimethylazulene

The synthesis of 1- and 2-aryl-substituted (aryl = Ph, 4-NO₂? C₆H₄, and 4-MeO? C₆H₄) 4, 6, 8-trimethylazulenes ( 4 and 3 , respectively) in moderate yields by direct arylation of 4, 6, 8-trimethylazulene ( 8 ) with the corresponding arylhydrazines 13 in the presence of Cu^IIions in pyridine (see Scheme 4) as well as with 4-MeO? C₆H₄Pb(OAc)₃ ( 16 ) in CF₃COOH (see Scheme 5) is described. With 13 , also small amounts of 1, 2- and 1, 3-diarylated azulenes (see 14 and 15 , respectively, in Scheme 4) are formed. The 4-methoxyphenylation of 8 with 16 yielded also the 1, 1′-biazulene 17 in minor amounts (see Scheme 5). 4, 6, 8-Trimethyl-2-phenylazulene ( 3a ) was also obtained as the sole product in moderate yields by the reaction of sodium phenylclopentadienide ( 1a ) with 2, 4, 6-trimethylpyrylium tetrafluoroborate ( 2 ) in THF (Scheme 1). The attempted phenylation of 8 as well as of azulene ( 9 ) itself with N-nitroso-N-phenylacetamide ( 10 ) led only to the formation of the corresponding 1-(phenylazo)-substituted azulenes 12 and 11 , respectively (Scheme 3).     

Stereochemische Korrelationen zwischen (2R,4′R,8′R)-α-Tocopherol, (25S,26)-Dihydroxycholecalciferol, (–)-(1S,5R)-Frontalin und (–)-(R)-Linalol

Stereochemical Correlations between (2R,4′R,8′R)-α-Tocopherol, (25S,26)-Dihydroxycholecalciferol, (–)-(1S,5R)-Frontalin and (–)-(R)-Linalol The optically active C₅- and C₄-building units 1 and 2 with their hydroxy group at a asymmetric C-atom were transformed to (–)-(1S,5R)-Frontalin ( 7 ) and (–)-(3R)-Linalol ( 8 ) respectively; 1 and 2 had been used earlier in the preparation of the chroman part of (2R,4′R,8′R)-α-Tocopherol ( 6a , vitamin E), and for introduction of the side chain in (25S,26)-Dihydroxycholecalciferol ((25S)- 4 ), a natural metabolite of Vitamin D₃. The stereochemical correlations resulting from these converions fit into a coherent picture with those correlations already known from literature and they confirm our earlier stereochemical assignments. A stereochemical assignment concerning the C(25)-epimers of 25,26-Dihydroxycholecalciferol that was in contrast to our findings and that initiated the conversion of 1 and 2 to 7 resp. 8 for additional stereochemical correlations has been corrected in the meantime by the authors [26].     

Circular Dichroism of Tricarbonyl(diene)iron Complexes. The Octant Rule Applied to Ketones Perturbed by Remote Fe(CO)3 Groups. Crystal Structure of (±)-Tricarbonyl[(1RS,4RS,5RS,6SR)-C5,6,C-η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron

The preparation and the CD spectra of optically pure (+)-trans-μ-[(1R,4S,5S,6R,7R,8S)-C,5,6,C -η : C,7,8,C-η-(5,6,7,8-tetramethylidene-2-bicyclo [2.2.2]octanone)]bis(tricarbonyliron) ((+)- 7 ) and (+)-tricarbonyl[(1S,4S,5S,6R)-C-5,6,C-η-(5,6,7,8,-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron ((+)- 8 ), and of its 3-deuterated derivatives (+)-trans-μ-[(1R,3R,4S,5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C-η-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]-(octanone)]bis(tricarbonyliron) ((+)- 11 ) and (+)-tricarbonyl[(1S,3R,4S,5S,6R)-C-5,6,C- η-(5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone)]iron ((+)- 12 ) are reported. The chirality in (+)- 7 and (+)- 8 is due to the Fe(CO)₃ moieties uniquely. The signs of the Cotton effects observed for (+)- 7 and (+)- 8 obey the octant rule (ketone n→π*_CO transition). Optically pure (?)-3R-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone ((?)- 10 ) was prepared. Its CD spectrum showed an ‘anti-octant’ behaviour for the ketone n→π*_CO transition of the deuterium substituent. The CD spectra of the alcoholic derivatives (?)-trans-μ-[(1R,2R,4S, 5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]bis(tricarbonyliron) ((?)- 2 ) and (?)-tricarbonyl- [(1S,2R,4S,5S,6R)- C,5,6,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]iron ((?)- 3 ) and of the 3-denterated derivatives (?)- 5 and (?)- 6 are also reported. The CD spectra of the complexes (?)- 2 , (?)- 3 , (+)- 7 , and (+)- 8 were solvent and temperature dependent. The ‘endo’-configuration of the Fe(CO)₃ moiety in (±)- 8 was established by single-crystal X-ray diffraction.     

C2-Symmetrical Pyrrolidine Derivatives Chiral Auxiliaries in Radical Chemistry

Fumaramides 3b and 3c bearing the C₂-symmetrical pyrrolidine moieties (2R,5R)-2,5-bis(methoxymethyl)pyrrolidine ( 2b ) or 1,3:4,6-di-O-benzylidene-2,5-dideoxy-2,5-imino-L -idit ( 2c ), respectively, as a chiral auxiliary lead to high diastereoselectivities in radical reactions (‘tin method’;Scheme 1). Removal of the chiral auxiliaries affords the corresponding alkylated fumaric acids Scheme 2. Single-crystal X-ray structures of 3b and 3c support arguments that lead to the model of 1,4-stereoinduction.     

Full stereochemical understanding in a new (2R,3R,4R)-4-hydroxyisoleucine synthesis

We present the crystal and molecular structures of 2,3,6,7,8,8a-hexa­hydro-6,8-methano-7,7,8a-tri­methyl-3-(1-methyl-2-oxo­propyl­idene)-5H-1,4-benzoxazin-2-one, C₁₆H₂₁NO₃, (III), and 2,3,6,7,8,8a-hexa­hydro-3-(2-hydroxy-1-methyl­propyl)-6,8-methano-7,7,8a-tri­methyl-5H-1,4-benzoxazin-2-one, C₁₆H₂₅NO₃, (V). These compounds are two of the four key intermediates in our synthetic route to (2R,3R,4R)-4-hydroxy­isoleucine. The two structures provide a full understanding of the stereochemistry in successive steps. This synthesis was based on a new optically pure chiral oxazinone auxiliary derived from (1R,2R,5R)-2-hydroxy­pinan-3-one.     

Asymmetric Phase-Transfer Catalysis by Quaternary Ammonium Ions Derived from Cinchona-Alkaloid Analogs Containing 1,1′-Binaphthalene Moieties

The synthesis and catalytic properties of a new type of enantioselective phase-transfer catalysts, incorporating both the quinuclidinemethanol fragment of Cinchona alkaloids and a 1,1′-binaphthalene moiety, are described. Catalyst (+)-(aS,3R,4S,8R,9S)- 4 with the quinuclidine fragment attached to C(7′) in the major groove of the 1,1′-binaphthalene residue was predicted by computer modeling to be an efficient enantioselective catalyst for the unsymmetric alkylation of 6,7-dichloro-5-methoxy-2-phenylindanone ( 1 ; Scheme 1, Fig. 1). Its synthesis involved the selective oxidative cross-coupling of two differently substituted naphthalen-2-ols to afford the asymmetrically substituted 1,1′-binaphthalene derivative (±)- 17 in high yield (Scheme 3). Chromatographic optical resolution via formation of diastereoisomeric camphorsulfonyl esters and functional-group manipulation gave access to the 7-bromo-1,1′-binaphthalene derivative (−)-(aS)- 11 (Scheme 4). Nucleophilic addition of lithiated (−)-(aS)- 11 to the quinuclidine Weinreb amide (+)-(3R,4S,8R)- 8 afforded the two ketones (aS,3R,4S,8R)- 27 and (aS,3R,4S,8S)- 28 as an inseparable mixture of diastereoisomers (Scheme 6). Stereoselective reduction of this mixture with DIBAL-H (diisobutylaluminum hydride; preferred formation of the C(8)−C(9) erythro-pair of diastereoisomers with 18% de) or with NaBH₄ (preferred formation of the threo-pair of diastereoisomers with 50% de) afforded the four separable diastereoisomers (+)-(aS,3R,4S,8S,9S)- 29 , (+)-(aS,3R,4S,8R,9R)- 30 , (−)-(aS,3R,4S,8S,9R)- 31 , and (+)-(aS,3R,4S,8R,9S)- 32 (Scheme 6). A detailed conformational analysis, combining ¹H-NMR spectroscopy and molecular-mechanics computations, revealed that the four diastereoisomers displayed distinctly different conformational preferences (Figs. 2 and 3). These novel Cinchona-alkaloid analogs were quaternized to give (+)-(aS,3R,4S,8R,9S)- 4 , (+)-(aS,3R,4S,8S,9S)- 5 , (+)-(aS,3R,4S,8R,9R)- 6 , and (−)-(aS,3R,4S,8S,9R)- 7 (Scheme 7) which were tested as phase-transfer agents in the asymmetric allylation of phenylindanone 1 . Without any optimization work, (+)-(aS,3R,4S,8R,9S)- 4 was found to catalyze the allylation of 1 yielding the predicted enantiomer (+)-(S)- 3b in 32% ee. The three diastereoisomeric catalysts (+)- 5 , (+)- 6 , and (−)- 7 gave access to lower enantioselectivities (6 to 22% ee's), which could be rationalized by computer modeling (Fig. 4).     

Molecular Recognition of Pyranosides by a Family of Trimeric, 1,1′-Binaphthalene-Derived Cyclophane Receptors

The synthesis and carbohydrate-recognition properties of a new family of optically active cyclophane receptors, 1 – 3 , in which three 1,1′-binaphthalene-2,2′-diol spacers are interconnected by three buta-1,3-diynediyl linkers, are described. The macrocycles all contain highly preorganized cavities lined with six convergent OH groups for H-bonding and complementary in size and shape to monosaccharides. Compounds 1 – 3 differ by the functionality attached to the major groove of the 1,1′-binaphthalene-2,2′-diol spacers. The major grooves of the spacers in 2 are unsubstituted, whereas those in 1 bear benzyloxy (BnO) groups in the 7,7′-positions and those in 3 2-phenylethyl groups in the 6,6′-positions. The preparation of the more planar, D₃-symmetrical receptors (R,R,R)- 1 (Schemes 1 and 2), (S,S,S)- 1 (Scheme 4), (S,S,S)- 2 (Scheme 5), and (S,S,S)- 3 (Scheme 8) involved as key step the Glaser-Hay cyclotrimerization of the corresponding OH-protected 3,3′-diethynyl-1,1′-binaphthalene-2,2′-diol precursors, which yielded tetrameric and pentameric macrocycles in addition to the desired trimeric compounds. The synthesis of the less planar, C₂-symmetrical receptors (R,R,S)- 2 (Scheme 6) and (S,S,R)- 3 (Scheme 9) proceeded via two Glaser-Hay coupling steps. First, two monomeric precursors of identical configuration were oxidatively coupled to give a dimeric intermediate which was then subjected to macrocyclization with a third monomeric 1,1′-binaphthalene precursor of opposite configuration. The 3,3′-dialkynylation of the OH-protected 1,1′-binaphthalene-2,2′-diol precursors for the macrocyclizations was either performed by Stille (Scheme 1) or by Sonogashira (Schemes 4, 5, and 8) cross-coupling reactions. The flat D₃-symmetrical receptors (R,R,R)- 1 and (S,S,S)- 1 formed 1 : 1 cavity inclusion complexes with octyl 1-O-pyranosides in CDCl₃ (300 K) with moderate stability (ΔG⁰ ca. −3 kcal mol⁻¹) as well as moderate diastereo- (Δ(ΔG⁰) up to 0.7 kcal mol⁻¹) and enantioselectivity (Δ(ΔG⁰)=0.4 kcal mol⁻¹) (Table 1). Stoichiometric 1 : 1 complexation by (S,S,S)- 2 and (S,S,S)- 3 could not be investigated by ¹H-NMR binding titrations, due to very strong signal broadening. This broadening of the ¹H-NMR resonances is presumably indicative of higher-order associations, in which the planar macrocycles sandwich the carbohydrate guests. The less planar C₂-symmetrical receptor (S,S,R)- 3 formed stable 1 : 1 complexes with binding free enthalpies of up to ΔG⁰=−5.0 kcal mol⁻¹ (Table 2). With diastereoselectivities up to Δ(ΔG⁰)=1.3 kcal mol⁻¹ and enantioselectivities of Δ(ΔG⁰)=0.9 kcal mol⁻¹, (S,S,R)- 3 is among the most selective artificial carbohydrate receptors known.     

Stereoselective Conversion of Campholene- to Necrodane-Type Monoterpenes. Novel Access to (−)-(R,R)- and (R,S)-α-Necrodol and the Enantiomeric γ-Necrodols

Naturally occurring (?)-(R,R)-α-necrodol ((?)- 1 ) and its C(4)-epimer (?)- 2 are obtained in 84 and 44% yields, respectively, by lithium ethylenediamide (LEDA) treatment of the corresponding β-necrodols (?)- 3 and (?)- 4 (Scheme 1, Table), both readily available from (?)-campholenyl acetate ((?)- i ) by an efficient stereoselective synthesis. The thermodynamically preferred (?)-(R)-γ-necrodol ((?)- 5 ) becomes the major product (≥ 80% yield) after either prolonged treatment with LEDA or exposure of α- and β-necrodols to BF₃·Et₂O. In an alternative route, (+)- 5 is prepared starting from (+)-campholenal ((+)- ii ) via Pd-catalysed decarbonylation to (?)-(S)-1,4,5,5-tetramethylcyclopent-l-ene ((?)- 6 ) and subsequent application of an acid-catalysed CH₂O-addition/rearrangement sequence (Scheme 2).     

Polynuclear Iron and Rhodium Complexes of 7-Oxa[2.2.1]hericene (2,3,5,6-tetramethylidenebicyclo[2.2.1]heptan-7-one)

μ-Carbonyl(Rh? Rh)di(η⁵-indenyl)[(2R,3S)-C,2,3,C-η-(2,3,4,5-tetramethylidenebicyclo[2.2.1]heptan-7-one)]]-dirhodium(I)(Rh? Rh) (7) and cis-μ-[(2R,3S,5R,6S))-C,2,3,C-η:C,5,6,C-η-(2,3,5,6-tetramethylidenebicyclo[2.2.1]heptan-7-one)]bis[μ-carbonyldi(η⁵-indenyl)dirhodium(I)(Rh? Rh)] ( 8 ) have been prepared. Complex 7 reacts with Fe₂(CO)₉ in hexane/MeOH and gives cis-μ-[(2R,3S,5R,6S] ( 9 ), trans-μ-[(2R,3S,5S,6R)-C,2,3,C-η: C,5,6, C-η-(2,3,5,6-tetramethylidenebicyclo[2.2.1]heptan-7-one)-μ-carbonyldi(η⁵-indenyl)dirhodium(I)(Rh? Rh)-(tricarbonyliron) ( 10 ), and, μ-carbonyl(Rh? Rh)[(2R,3S)-C,2,3,C-η-(2,3-dimethyl-5,6-dimethylidenebicyclo-[2.2.1]hept-2-en-7-one)]di(η⁵-indenyl)dirhodium(I)(Rh? Rh) ( 11 ). Treatment of 7-oxa[2.2.1]hericene ( 4 ) with Fe₂(CO)₉ or (cyclooctene)₂Fe(CO)₃ gave a 1:2 mixture of cis-μ-[(2R,3S,5R,6S)-] ( 12 ) and trans-μ-[(2R,3S,5S,6R)-C,2,3,C-η:C,5,6,C-η-(2,3,5,6-tetramethylidenebicyclo[2.2.1]heptan-7-one)]bis(tricarbonyliron)( 13 ).     

Technical Procedures for the Syntheses of Carotenoids and Related Compounds from 6-Oxo-isophorone: Syntheses of (3R,3′R)-Zeaxanthin. Part I

Starting from the readily available, optically active (4R)-4-hydroxy-2,2,6-trimethylcyclohexanone ( 1 ), a new technical synthesis of (3R,3′R)-zeaxanthin is described. According to a 2(C₉ + C₆) + C₁₀ = C₄₀ construction scheme, the ketone 1 was first transformed with (E)-3-methylpent-2-en-4-yn-1-ol ( 5 ) into a C₁₅-intermediate which, by a three-step sequence, could be converted into the known olefinic C₁₅-Wittig salt 4 . Optimized conditions for the final Wittig reaction of 4 with the C₁₀-dialdehyde 3 are discussed. Based on 1 , the overall yield of the entire technical process is ca. 40%.     

Catalytic Enantioselective Hydrosilylation of Ketones with Rhodium-Phosphite Complexes Containing a TADDOLate and a Dihydrooxazole Unit

New types of chiral phosphorus/nitrogen ligands, capable of forming six-membered-ring metal chelates have been prepared from α,α,α′,α′-tetraaryl-1,2-dioxolane-4,5-dimethanols (TADDOLs), PCl₃, and dihydrooxazole alcohols (from amino acids) ( 7 in Scheme 1). The X-ray crystal structure of a Rh complex of one of these ligands, 8b , has been determined (Scheme 2 and Fig.). Enantioselective hydrosilylations of dialkyl and aryl alkyl ketones with Ph₂SiH₂/0.01 equiv. Rh^I⋅ 7 have been studied and found to provide secondary alcohols in enantiomer ratios of up to 97 : 3 (Scheme 3 and Table). The ligand prepared from (R,R)-TADDOL and the (R)-valine-derived (R)-α,α-dimethyl-4-isopropyl-4,5-dihydrooxazole-2-methanol gives better results than the (R,R,S)-isomer ( 7d vs. 7c in Scheme 3), and an i-Pr group on the 4,5-dihydrooxazole ring gives rise to a slightly better selectivity than a Ph group. With the (R,R,R)-ligands the hydrogen transfer occurs from the Re face of the oxo groups (Scheme 4).     

Methanofullerene Molecular Scaffolding: Towards C60-substituted poly(triacetylenes) and expanded radialenes,preparation of a C60–C70 hybrid derivative,and a novel macrocyclization reaction

The synthesis of (E)-hex-3-ene-l, 5-diynes and 3-methylidenepenta-1, 4-diynes with pendant methano[60]-fullerene moieties as precursors to C₆₀-substituted poly(triacetylenes) (PTAs, Fig. 1) and expanded radialenes (Fig. 2) is described. The Bingel reaction of diethyl (E)-2, 3-dialkynylbut-2-ene-1, 4-diyl bis(2-bromopropane-dioates) 5 and 6 with two C₆₀ molecules (Scheme 2) afforded the monomeric, silyl-protected PTA precursors 9 and 10 which, however, could not be effectively desilylated (Scheme 4). Also formed during the synthesis of 9 and 10 , as well as during the reaction of C₆₀ with thedesilylated analogue 16 (Scheme 5 ), were the macrocyclic products 11, 12 , and 17 , respectively, resulting from double Bingel addition to one C-sphere. Rigorous analysis revealed that this novel macrocyclization reaction proceeds with complete regio- and diastereoselectivity. The second approach to a suitable PTA monomer attempted N, N′-dicyclohexylcarbodiimide(DCC)-mediated esterification of (E)-2, 3-diethynylbut-2-ene-l, 4-diol ( 18 , Scheme 6) with mono-esterified methanofullerene-dicarboxylic acid 23 ; however, this synthesis yielded only the corresponding decarboxylated methanofullerene-carboxylic ester 27 (Scheme 7). To prevent decarboxylation, a spacer was inserted between the reacting carboxylic-acid moiety and the methane C-atom in carboxymethyl ethyl 1, 2-methano[60]fullerene-61, 61-dicarboxylate ( 28 , Scheme 8), and DCC-mediated esterification with diol 18 afforded PTA monomer 32 in good yield. The formation of a suitable monomeric precursor 38 to C₆₀-substituted expanded radialenes was achieved in 5 steps starting from dihydroxyacetone (Schemes 9 and 10), with the final step consisting of the DCC-mediated esterification of 28 with 2-[1-ethynyl(prop-2-ynylidene)]propane-1, 3-diol ( 33 ). The first mixed C₆₀-C₇₀ fullerene derivative 49 , consisting of two methano[60]fullerenes attached to a methano[70]fullerene, was also prepared and fully characterized (Scheme 13). The C_s-symmetrical hybrid compound was obtained by DCC-mediated esterification of bis[2-(2-hydroxy-ethoxy)ethyl] 1, 2-methano[70]fullerene-71, 71-dicarboxylate ( 46 ) with an excess of the C₆₀-carboxylic acid 28 . The presence of two different fullerenes in the same molecule was reflected by its UV/VIS spectrum, which displayed the characteristic absorption bands of both the C₇₀ and C₆₀ mono-adducts, but at the same time indicated no electronic interaction between the different fullerene moieties. Cyclic voltammetry showed two reversible reduction steps for 49 , and comparison with the corresponding C₇₀ and C₆₀ mono-adducts 46 and 30 indicated that the three fullerenes in the composite fullerene compound behave as independent redox centers.     

Bestimmung des Chiralitätssinns der enantiomeren 2,6-Adamantandiole

Determination of the Chirality Sense of the Enantiomeric 2,6-Adamantanediols The enantiomers of 2,6-adamantanediol ( 1 ) are resolved via the diastereoisomeric camphanoates. The (2R,6R)-chirality sense for (?)- 1 and (2S,6S) for (+)- 1 was determined by chemical correlation with (?)-(1R,5R)-bicyclo[3.3.1]nonan-2,6-dion ((1R,5R)- 3 ) of known absolute configuration in the following way: alkylation of the bis(pyrrolidine enamine) of (?)-(1R,5R)- 3 with CD₂I₂ and hydrolysis of the product gives the enantiomer 4 of (4,4-D₂)-2,6-adamantanedione. Reduction of 4 with LiAlH₄ leads to one enantiomer (Scheme 2) of each of the three diols 5 – 7 of known absolute configuration. The three diols are themselves configurational isomers due to the presence of the CD₂ group, but correspond otherwise entirely to the enantiomeric diols 1 . Accordingly, they can also be separated by means of their diastereoisomeric camphanoates to give the diols 5 / 6 and 7 . These samples are easily distinguished and identified by their characteristic ¹H-NMR spectra (cf. Fig. 2). This allows to identify the (2R,6R)- and (2S,6S)-enantiomer of 1 on the basis of their behavior in the resolution experiment analogous to that of the diols 5 / 6 and 7 , respectively. The diol (?)- 1 must have the (2R,6R)-configuration because it forms, like the diols 5 / 6 , with (?)-camphanic acid the diastereoisomeric ester less soluble in benzene. The diol (+)- 1 has (2S,6S)-configuration, because it forms, like 7 , with (+)-camphanic acid the diastereoisomeric ester less soluble in benzene. The bis(4-methoxybenzoate) of (?)-(2R,6R)- 1 shows chiroptical properties which are in accordance with Nakanishi's rule for two chromophores having coupled electric dipol transition moments arranged with a left-handed torsion angle.     

Technische Verfahren zur Synthese von Carotinoiden und verwandten Verbindungen aus 6-Oxo-isophoron. III. Ein neues Konzept für die Synthese der enantiomeren Astaxanthine

Technical Procedures for the Synthesis of Carotenoids and Related Compounds from 6-Oxo-isophorone. III. A New Concept for the Synthesis of the Enantiomeric Astaxanthins A new and efficient concept for the total synthesis of (3S, 3'S)- and (3R, 3'R)-astaxanthin ( 1a and 1c , resp.) in high overall yield and up to 99,2% enantiomeric purity is described. Key intermediates are the (S)- and (R)-acetals 10 and 17 , respectively (Scheme 2). These chiral building blocks were synthesized via three different routes: a) functionalization of the enantiomeric 3-hydroxy-6-oxo-isophorons⁴) 2 and 11 , respectively (Scheme 2); b) optical resolution of 3,4-dihydroxy-compound⁴) 19 (Scheme 3), and c) fermentative reductions of 6-oxo-isophorone derivatives (Schemes 4 and 5). - The absolute configurations of the two intermediates 12 and 13 (Scheme 2) have been confirmed by X-ray analysis. - The final steps leading to the enantiomeric astaxanthins are identical with those described for optically inactive astaxanthin [1].     

Structure of Tricarbonyl(diene)iron Complexes in Solution. Variable-Temperature Circular Dichroism of trans-μ-(2,3,5,6-Tetramethylidenebicyclo[2.2.2]octane)bis(tricarbonyliron) Complexes

Optically pure (?)-trans-μ-[(1R,2R,3S,4S,5S,6R)-C,2,3,C-η:C,5,6,C-η-(2,3,5,6,7-pentamethylidenebicyclo[2.2.2]octane)]bis(tricarbonyliron) ((?)- 9 ), (?)-trans-μ-[(1R,2R,3S,4S,5S,6R,7S)-C,2,3,C-η:C,5,6,C-η-(7-methyl-2,3,5,6-tetramethylidenebicyclo[2.2.2]octane)]bis(tricarbonyliron) ((?)- 10 ), and (?)-trans-μ-[(1R,2R,3S,4S,5S,6R,7R)-C,2,3,C-η:C,5,6,C-η-(2,3,5,6-tetramethylidene(7D)bicyclo[2.2.2]octane)]bis(tricarbonyliron) ((?)- 16 ) have been prepared. Their CD spectra were solvent- and concentration-independent, but temperature-dependent, in accord with the existence of equilibria between rapidly interconverting diastereoisomeric species which can be interpreted as arising from distortions of the tricarbonyl(diene)iron units from the C_s symmetry.