Synthèse énantiospécifique des acides (+)-(2R)- et (−)-(2S)-éthyl-6-dihydro-3,4-méthyl-2-oxo-4–2H pyranecarboxylique-5

Enantiospecific Synthesis of (+)-(2R)- and (?)-(2S)-6-Ethyl-3,4-dihydro-2-methyl-4-oxo-2H-pyran-5-carboxylic Acid The two enantiomers (?)-(2S)- and (+)-(2R)-6-ethyl-3,4-dihydro-2-methyl-4-oxo-2H-pyran-5-carboxylic acid ((S)- and (R)- 7 ) have been synthesized from (+)-(3S) and (?)-(3R)-3-hydroxybutanoates, respectively (Scheme 1). By reduction and decarboxylation, the tetrahydro-2H-pyranols (2R, 4R, 6S)- and (2S, 4S, 6R)- 13 , respectively, were obtained with an enantiomeric excess of ≥ 93%.     

Proof of the Absolute Configuration of (−)-(S)-2-Hydroxy-β-ionone by correlation with ursolic acid and with (−)-trans-verbenol

(?)-(S)-2-Hydroxy-β-ionone ( 33 ), (+)-(2 S, 6 S)-2-hydroxy-α-ionone ( 34 ), and their acetates 35 and 36 have been synthesized from (+)-(S)-6-methylbicyclo [4.3.0]-non-1-ene-3, 7-dione ( 3 ). The key intermediate (+)-(1 R, 3 S, 6 S)-2, 2, 6-trimethyl-7-oxobicyclo [4.3.0]non-3-yl acetate ( 7 ) was correlated with a degradation product of the pentacyclic triterpene ursolic acid ( 16 ). Compound 33 was also synthesized by an alternative route starting from (?)-trans-verbenol ( 42 ).     

Stereospezifische Synthese von (+)-(3R, 4R)-4-Methyl-3-heptanol,das Enantiomere eines Pheromons des kleinen Ulmensplintkäfers (Scolytus multistriatus)

Stereospecific Synthesis of (+)-(3R, 4R)-4-Methyl-3-heptanol, the Enantiomer of a Pheromone of the Smaller European Elm Bark Beetle (Scolytus multistriatus) Reduction of 2 with actively fermenting baker's yeast gave (?) -3. Stereospecific alkylation [3] of (?) -3 with propyl iodide furnished ethyl (+)-(2R, 3R)-2-propyl-3-hydroxypentanoate ((+) -4 , 58%) which was converted to the tetrahydropyranyl ether (?) -5 , then the alcohol 6 , the p-toluenesulfonate 7 and the thiophenyl ether 8 to give the title compound (+) -1. The latter consisted of 97% of the threo- and 3% of the erythro-isomer. The above synthesis also correlates the absolute configuration of (?)-(R) -3 with that of (+)-(R)-citronellic acid (see [2]).     

Synthese und Bestimmung des Chiralitätssinns von (+)-(R)-1-Azabicylo[3.3.1]nonan-2-on

Synthesis and Determination of the Chirality Sense of (+)-(R)-1-Azabicyclo[3.3.1]nonan-2-one Optically active (+)-(R)-1-azabicyclo[3.3.1]nonan-2-one ((+)- 1 ) of known absolute configuration is synthesized in the following way: Resolution of (±)-piperidin-3-ethanol ((±)- 2 ) by fractional recrystallization of its diastereoisomeric salts with (+)-3-bromocamphor-8-sulfonic acid from EtOH gave a less soluble salt that yielded(+)- 2 . The chirality sense of (+)- 2 was shown to be (R) by chemical correlation with the enantiomers of 3-oxocyclopentaneacetic acid ((±)- 8 ) of known absolute configuration. This correlation was effected by a Beckmann rearrangement of the oxime (R)-9 to the pyridone (S)- 10 followed by a direct reduction with LiAlH₄ to give the enantiomer (?)-(S)- 2 that was characterized as its benzyloxycarbonyl derivative (?)-(S)- 3 . The alcohol (+)-3 was converted via (+)- 4 into the nitrile (+)-5 which gave by hydrogenolysis and hydrolysis the (R)-configurated hydrochloride (+)- 6 which was cyclized to the bicyclic (5R)-lactam (+)- 1 in 67% yield by heating with 2 equiv. of dibutyltin(IV) oxide in toluene. The nonplanar amide function in (+)- 1 with the substituents at the N-atomarranged in a trigonal pyramid causes two rather intense Cotton effects at 242 (Δ?_max = +19.5) and 211 nm(Δ?_max = ?17.9) in the CD spectrum. If the molecules of (+)- 1 do exist mainly in the chair-twistboat conformation, the amide chromophore is pyramidally deformed in a sense defined by the absolute configuration at C(5). Therefore, the CD spectrum of the (5R)-lactam (+)- 1 can be used to test theories describing the chiroptical properties of distorted amides.     

Synthèse énantiospécifique de la (+)-(R)-éthyl-6-dihydro-2,3-méthyl-2-4H-pyranone-4, phéromone de la mite Hepialus hecta L

Enantiospecific Synthesis of (+)-(R)-6-Ethyl-2,3-dihydro-2-methyl-4H-pyran-4-one, Sex-pheromonal Component of the Male Swift Moth Hepialus hecta L . A new synthesis of (+)?(R)-6-ethyl-2,3-dihydro-2-methyl-4H-pyran-4-one ((R)- 8 ), sex-pheromonal component of the male swift moth Hepialus hecta L., has been performed from (?)-(R)-1-(1,3-dithian-2-yl)propan-2-ol with an enantiomeric excess of ? 97%.     

Biosynthese der Verrucarine und Roridine. Teil 5. Synthese von zwei Diastereoisomerenpaaren des [1,8-14C]-α-Bisabolols und Versuche zu deren Einbau in Verrucarol Verrucarine und Roridine, 32. Mitteilung [1]

The diastereoisomeric (+)-[1,8-¹⁴C]-(1'R,6R, S)-α-bisabolol ( 2a ) and (?)-[1,8-¹⁴C]-(1′S, 6R, S)-α-bisabolol ( 2b ) were synthesized by reaction of the Grignard compound of [1,6-¹⁴C]-5-bromo-2-methyl-2-pentene ( 12 ) with (+)-(R)- and (?)-(S)-4-acetyl-1-methyl-1-cyclohexene, ( 6a ) and ( 6b ) respectively. For the preparation of compound 12, cyclopropyl methyl ketone was treated with [¹⁴C]-methyl magnesium iodide to form the carbinol 11, which was cleaved by HBr. Compounds 6a and 6b were synthesized from (+)-(R)- and (?)-(S)-limonene, ( 4a ) and ( 4b ), via the derivatives 5a , 6a and 5b , 6b respectively. - This synthesis established the absolute configuration at C(1′) of the natural α-bisabolols: (R) for (+)-α-bisabolol and (S) for (?)-α-bisabolol. - Feeding experiments with cultures of Myrothecium roridum and radioactive (+)-(1′R, 6R, S)- and (?)-(1′S, 6R, S)-α-bisabolol ( 2a ) and ( 2b ) gave negative results. These findings indicate that bisabolane derivatives are not intermediates in the biosynthesis of verrucarol (3).     

Helix-sense-selective polymerization of phenyl[bis(2-pyridyl)]methyl methacrylate and chiral recognition ability of the polymer

A novel monomer, phenyl[bis(2-pyridyl)]methyl methacrylate (PB2PyMA), was synthesized. The solvolysis rate of PB2PyMA measured in CDCl₃–CD₃ OD [1/1 (v/v)] by ¹H-NMR spectroscopy at 35°C was much smaller than those of triphenylmethyl methacrylate (TrMA) and diphenyl-2-pyridylmethyl methacrylate (D2PyMA). PB2PyMA was anionically polymerized with the complexes of organolithiums with (?)-sparteine (Sp), (S,S)-(+)-and (R,R)?(-)-2,3-dimethoxy-1,4-bis(dimethylamino)butanes[(+)-and (?) -DDB], and (S)-(+)-1-(2-pyrrolidinylmethyl) pyrrolidine (PMP) in toluene at low temperature. The polymers obtained with Sp and DDB complexes showed low optical activity. PMP complexes, particularly that with N,N′-diphenylethylenediamine monolithium amide, were effective in synthesizing a polymer of high optical rotation ([α]²⁵₃₆₅ ～ +1350°) which was comparable to those of poly(TrMA) and poly(D2PyMA) with one-handed helical structure. The optical rotation of poly(PB2PyMA) in a mixture of CHCl₃ and 2,2,2-trifluoroethanol (9/1, v/v) slowly decreased with time. Optically active poly(PB2PyMA) coated on macroporous silica gel was able to resolve racemic compounds as a chiral stationary phase for high-performance liquid chromatography. © 1993 John Wiley & Sons, Inc.     

Preparation and Absolute Configuration of (−)-(E)-α-trans-Bergamotenone

The synthesis, absolute configuration, and olfactive evaluation of (?)-(E)-α-trans-bergamotenone (= (?)-(1′S,6′R,E)-5-(2′,6′-dimethylbicyclo[3.1.1]hept-2′-en-6′-yl)pent-3-en-2-one; (?)- 1 ), as well as its homologue (?)- 19 are reperted. The previously arbitrarily attributed absolute configuration of 1 and of (?)-α-trans-bergamotene (= (?)-(1 S,6R)-2,6-dimethyl-6-(4-methylpent-3-enyl)bicyclo[3.1. 1]hept-2-ene; (?)- 2 ), together with those of the structurally related aldehydes (?)- 3a,b and alcohols (?)- 4a,b , have been rigorously assigned.     

Photochemische Umsetzung von optisch aktiven 2-(1′-Methylallyl)anilinen mit Methanol

Photochemical Reaction of Optically Active 2-(1′-Methylallyl)anilines with Methanol It is shown that (?)-(S)-2-(1′-methylallyl)aniline ((?)-(S)- 4 ) on irradiation in methanol yields (?)-(2S, 3R)-2, 3-dimethylindoline ((?)-trans- 8 ), (?)-(1′R, 2′R)-2-(2′-methoxy-1′-methylpropyl)aniline ((?)-erythro- 9 ) as well as racemic (1′RS, 2′SR)-2-(2′-methoxy-1′-methylpropyl) aniline ((±)-threo- 9 ) in 27.1, 36.4 and 15.7% yield, respectively (see Scheme 3). By deamination and chemical correlation with (+)-(2R, 3R)-3-phenyl-2-butanol ((+)-erythro- 13 ; see Scheme 4) it was found that (?)-erythro- 9 has the same absolute configuration and optical purity as the starting material (?)-(S)- 4 . Comparable results are obtained when (?)-(S)-N-methyl-2-(1′-methylallyl)aniline ((?)-(S)- 7 ) is irradiated in methanol, i.e. the optically active indoline (+)-trans- 10 and the methanol addition product (?)-erythro- 11 along with its racemic threo-isomer are formed (cf. Scheme 3). These findings demonstrate that the methanol addition products arise from stereospecific, methanol-induced ring opening of intermediate, chiral trans, -(→(?)-erythro-compounds) and achiral cis-spiro [2.5]octa-4,6-dien-8-imines (→(±)-threo-compounds; see Schemes 1 and 2).     

Circulardichroismus. 62. Mitteilung. Chiroptische Eigenschaften einiger Trimethylcyclohexen-Derivate: Die Jonone,Irone und Abszisinsäuren

The absolute configuration of (+)-α-ionone 3 (R), the absolute configurations at C(6) of (+)-cis-α-irone 5 (6S) and (?)-trans-α-irone 6 (6R), and the absolute configurations of (+)-cis-abscisic acid 10 (S) and (+)-trans-abscisic acid 11 (S) are deduced from the CD.-spectra.     

Über die Konstitution von Loroglossin. Vorläufige Mitteilung

The Constitution of Loroglossine. Loroglossine, a characteristic constituent of orchids, is shown to be bis-[4-(β-D -glucopyranosyloxy)-benzyl]-(2 R, 3 S)-2-isobutyl-tartrate ( 1 ). Hydrolysis and esterification gave 1 mol-equiv. of dimethyl (+)-2-isobutyl-erythro-tartrate ((+)-3) and 2 mol.-equiv. of a glucoside which, after acetylation, gave 4 , identical with a synthetic sample. The erythro configuration of (+)- 3 by oxidation of isobutyl-maleic acid with osmium tetroxide and subsequent esterification. The absolute configuration of (+)- 3 was based on Horeau experiments and NMR. data of the diastereomeric mixture of its esters 7 and 8 with S (+)- and R (?)-α-phenylbutyric acid respectively.     

Synthesis of (R)- and (R)-4-methyl-6-2′-methylprop-1′-enyl-5,6-dihydro-2H-pyran (Nerol oxide) and Natural Occurrence of its Racemate

Following a known procedure, a mixture of (?)-(2S,3R)- and (+)-(2R,3R)-2,3-epoxy-citronellols ( 5 ) was prepared from (?)-(R)-linalool ( 3 ) via epoxy alcohol 4 and then reduced to (?)-(R)-3-hydroxy-citronellol ( 6 ). Sensitized photooxygenation of (?)-(R)-diol 6 led in part to (?)-(R)-triol 8 which was cyclodehydrated by dilute acid to a mixture of diastereoisomeric tetrahydropyran-4-ols 9 and 10 . Dehydration of hydroxy ethers 9 and 10 afforded (?)-(S)-nerol oxide ( 11 ) and (+)-(R)-nerol oxide ( 12 ), respectively, with an optical purity of 91%. Nerol oxide isolated from Bulgarian rose oil (0.038%) proved to be racemic. These results shed some light on the formation of nerol oxide in plants.     

Die Konstitution des Loroglossins. 163. Mitt. über organische Naturstoffe

The Constitution of Loroglossine Loroglossine, a characteristic constituent of orchids, is shown to be bis[4-(β-D -glucopyranosyloxy)-benzyl]-(2R, 3S)-2-isobutyl-tartrate (1) . Base catalysed hydrolysis and esterification with diazomethane gave 1 mol-equiv. of dimethyl (+)-2-isobutyl-erythro-tartrate ((+)- 3 ) and 2 mol-equiv. of a glucoside which after acetylation formed 4 identical with a synthetic sample. The structure of (+)- 3 follows from the synthesis of (±)- 3 by osmium tetroxide oxidation of isobutyl-maleic acid anhydride and subsequent esterification. The absolute configuration of (+)- 3 was based on Horeau experiments and NMR. data of the diastereomeric mixture of its esters 15 and 16 and pure 15 with (S)-(+)- and (R)-(?)-α-phenyl-butyric acid, respectively.     

(R)-(+)-[VCD(+)945]-4-Ethyl-4-methyloctane, the simplest chiral saturated hydrocarbon with a quaternary stereogenic center

Enantiopure (R)-(+)-[VCD(+)945]-4-ethyl-4-methyloctane, the simplest chiral saturated hydrocarbon with a quaternary stereogenic center, was synthesized by the use of MαNP acid method, and its absolute configuration was first unambiguously determined by the ¹H NMR anisotropy, X-ray crystallography, and VCD methods.     

Synthesis and absolute configuration of clemastine and its isomers (author's transl)]

Synthesis and Absolute Configuration of Clemastine and its Isomers. Condensation of 4-chloro-α-methylbenzhydrylalkohol ( 1 ) with 2-(2-chloroethyl)-1-methylpyrrolidine ( 2 ) gave an isomeric mixture of 2-[2-(p-chloro-α-methyl-=-phenylbenzyloxy)ethyl]-1-methylpyrrolidine ( 3 ) and 4-(p-chloro-=-phenylbenzyloxy)-1-methyl-hexahydroazepin ( 4 ). The separation of the four possible optically active isomers of 3 is described and their absolute configuration established by degradation to (R)- and (S)-1-methyl-2-pyrrolidineethanol ( 6 ), respectively, and by an X-ray cristallographic analysis of the quarternary methiodide of the isomer 3-A . Clemastine (3-A) is (+)-(2R)-2-[2-((αR)-(p-chloro-α-methyl-α-phenylbenzyloxy)ethyl)]-1-methylpyrrolidine.     

Die Stereochemie der Irone

The 6 R configuration of (+)-cis-γ-irone [(+)- 4 ] was established by chemical correlation with (—)-camphor. (+)-cis-γ-irone [(+)- 4 ] was converted into (+)-cis-α-irone [(+)- 1 ], (?)-trans-α-irone [(minus;;)- 2 ], and (+)-β-irone [(+)- 3 ], which therefore also have the 6 R configuration. The 2 S configurations of (+)-cis-α-irone [(+)- 1 ] and (+)-trans-α-irone [(+)- 2 ] were determined by comparison of their circular dichroism with that of R-α-ionone [(+)- 5 ]. The 2 S configuration of (+)-cis-γ-irone [(+)- 4 ] was established by chemical correlation with (+)-cis-α-irone [(+)- 1 ].     

(+)-(1S, 3S, 6S, 8S)-und (−)-(1R, 3R, 6R, 8R)-4, 9-Twistadien: Synthese und Bestimmung der absoluten Konfiguration

(+)-(1S, 3S, 6S, 8S)-and (?)-(1R, 3R, 6R, 8R)-4, 9-Twistadiene: Synthesis and Absolute Configuration A synthesis and the determination of the absolute configuration of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-4, 9-twistadiene ((+)- and (?)- 4 , respectively) is described. Their chiroptical properties are compared with those of saturated twistane ((+)- and (?)- 5 ) as well as with those of the unsaturated and saturated 2, 7-dioxatwistane analogs (+)- and (?)- 9 , and (+)- and (?)- 10 , respectively, which also are compounds of known absolute configurations.     

Optically active organoaluminum based inclusion compounds. Synthesis and characterization of (S)-(−)-α-[(C6H5)CH(CH3)N(CH3)3][Al2R6I] (R=CH3, C2H5)

The optically active quaternary ammonium salt (S)-(?)-α-[(C₆H₅)CH(CH₃)N(CH₃)₃I] reacts with AlR₃ to afford optically active organoaluminum based inclusion compounds, liquid clathrates, of the formula (S)-(?)-α-[(C₆H₅)CH(CH₃)N(CH₃)₃][Al₂R₆I] (R=CH₃, C₂H₅). Specific rotation ([α] ₂₅ ^D ) for the Al(CH₃)₃ compound was determined to be ?13.19° while that for the Al(C₂H₅)₃ analog was determined to be ?14.30°. There are 13.8 toluene molecules per anionic moiety for the trimethylaluminum based liquid clathrate while there are 15.0 toluene molecules per anion for the corresponding triethylaluminum inclusion compound.     

Absolute Configuration of 3-Substituted 1-Azabicyclo[2.2.1]heptanes

The l-azabicyclo[2.2.1]heptan-3-exo-ol ( 2 ) was resolved by fractional crystallisation of its hydrogen tartrate salts. The enantiomers (+)- and (?)- 2 were oxidised to the ketones (?)- 4 and (+)- 4 , respectively (Scheme). CD spectroscopy suggested that (?)- 4 possesses the (1R,4S)-configuration. This absolute configuration was confirmed by single-crystal X-ray diffraction of the derivative (+)-(1R,4R)-3-(1,3-dithian-2-ylidene)-1-azabicyclo [2.2.1]-heptane ((+)- 5 ).     

The Preparation of Optically Pure 7-Oxabicyclo [2.2.1]hept-2-ene Derivatives. The CD Spectrum of (+)-(1R)-7-Oxabicyclo [2.2.1]hept-5-en-2-one

(?)-1-Camphanoyloxyacrylonitrile (=(?)-1-cyanovinyl camphanate; 1 ) obtained from the commercially available (?)-camphanoyl chloride and 2-oxo-propiononitrile added to furan at 20° in the presence of Cu (BF₄)₂ · 6H₂O or ZnI₂ and gave a mixture of 2-cyano-7-oxabicyclo [2.2.1]hept-5-en-2-yl camphanates ( 2–5 ) from which isomer 5 could be obtained pure by crystallization. The latter was transformed into (+)-(1R)-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 6 ) in high yield and optical purity. Adducts 2–4 were recycled into 1 +furan by heating in toluene, and (?)-camphanic acid was recovered after saponification of 5 . The absolute configuration of 6 was deduced from its CD spectrum which showed two 1200-cm_?1 Franck-Condon series for its n→π transition.