A convenient method for the assignment of the absolute configuration to cyclic amines

We have assigned the absolute configuration to trans-2,5-dimethylpyrrolidine and trans-2,6-dimethyl-piperidine through radical chlorination in ω-1 position of optically active amines, 2 and 5, of known absolute configuration, followed by cyclization. CD curves of 1f and 4g derivatives indicate that the reaction is stereospecific. The absolute configuration of trans-2,5-dimethyl-Δ³-pyrròline has also been determined.     

Baker's yeast-induced asymmetric reduction of α-ketosulfides: synthesis of optically active 1-(benzothiazol-2-ylsulfanyl)-2-alkanols, 2-alkanols,and thiiranes

1-(Benzothiazol-2-ylsulfanyl)-2-alkanols 3 were prepared in very high enantiomeric excess by baker's yeast-induced asymmetric reduction of 1-(benzothiazol-2-ylsulfanyl)-2-alkanones 1. Conversion of 3 into optically active simple 2-alkanols 4 and thiiranes 2 by reductive desulfurization and base treatment, respectively, is also described. The absolute configuration of the new compounds synthesized has been established by chemical correlation and specific rotation comparison.     

Die absolute konfiguration des (+)-corynolins

From Corydalis incisa (+)-corynoline (2) was isolated together with (±)-corynoline (2'), which has been reported to be the major alkaloid. Optical resolution of 2' was achieved by resolving the corresponding diastereomeric esters with (-)-menthoxyacetic acid. The quaternary hydroxide of (+)-corynoline-O-acetate (3) was subjected to Emde degradation to afford the hydromethine base (5), the methiodide of which was converted by further Emde degradation into the optically active nitrogenfree product (6). This product was identical with the nitrogen-free product resulting from Emde degradation of (+)-14-epicorynoline (1), whose absolute configuration has been determined by means of an X-ray analysis. This result shows the absolute configuration of (+)-corynoline (2) to be 11S, 13R and 14R.     

Enantioselective epoxidation of isoflavones by Jacobsen's Mn(III)salen catalysts and dimethyldioxirane oxygen-atom source

The catalytic enantioselective epoxidation of the isoflavones 1a–f has been performed by the Mn(III)salen complexes (R,R)-3 and (S,S)-3 as catalysts and dimethyldioxirane as the oxygen-atom source to afford optically active isoflavone epoxides 2a–f. The absolute configuration of the nonracemic epoxides 2 have been determined by X-ray diffraction analysis. Our present results constitute the first examples of the preparation of optically active isoflavone epoxides.     

Pavinane and isopavinane alkaloids: Correlation of absolute configurations by synthesis

(?)-Caryachine (9) and (?)-Reframoline (10) have been synthesised from a common intermediate; this confirms the absolute configuration in the isopavinane series deduced previously by application of the aromatic chirality rule. This also represents the first synthesis of an optically active pavinane alkaloid.     

Asymmetric synthesis of aerothionin, a marine dimeric spiroisoxazoline natural product, employing optically active spiroisoxazoline derivative

Successful first synthesis of optically pure (+)- and (−)-aerothionins (1) from the racemic spiroisoxazoline derivative 8 has been accomplished. The absolute configuration of natural (+)-1 was determined by comparison of (+)- and (−)-8 with related derivatives.     

One step synthesis of aziridines by the Michael type addition of free sulfimides: Preparation and absolute configuration of optically active acylaziridines

The Michael type additions of diphenyl N-unsubstituted sulfimide (free sulfimide) to various electrophilic olefins were carried out. The reaction with cis- and trans-dibenzoylethylene, dimethyl-fumarate, dimethylmaleate, benzalacetophenone and benzalacetone gave mainly the corresponding trans-2-acylaziridines and trans-enaminoketones. However, phenyl vinyl sulfone or acrylonitrile afforded not the corresponding aziridine but diphenyl-N-2-cyano or N-2-phenylsulfonylethylsulfimide, a simple Michael adduct When optically active (+)-(R)-o-methoxyphenyiphenyl free sulfimide was treated with such an α,β-unsaturated carbonyl compound as benzalacetopbenone, an optically active 2-acylazindine, i.e., (-)-trans-2-benzoyl-3-phenylaziridine was obtained in ca 30% optical purity and its absolute configuration was assigned as (2R,3S) upon chemical transformation to the configuration-ally known 2-phenyl-2-benzoylamino-1-ethanol or by comparing its CD spectrum with that of (1R,2R)-1-phenyl-2-benzoyl-cyclopropane. Meanwhile, (-)-(S)-o-methoxyphenylphenyl free sulfimide was found to react with benzalacetophenone to afford (+)-trans-2-benzoyl-3-phenylaziridine of 25% optical purity. Effects of solvent and temperature on both die distribution of the products ratio and the optical yield were examined.     

Stereochemical studies—VIII Unequivocal determination of the absolute configuration in biaryl systems

According to the reaction sequences shown in Figs 1-5, the absolute configuration of optically active biaryl derivatives such as biphenyl, binaphthyl, bianthryl and bianthroaquinonyl have been clearly established, based on the standard compound (R)-(+)-I, in the binaphthyl system, whose absolute configuration was unequivocally determined by the anomalous X-ray diffraction method.     

Sedum alkaloids—VII : Structure and synthesis of (+)-4-hydroxysedamine and (+)-4-hydroxyallosedamine

The structures of (+)-4-hydroxysedamine ¹ and (+)-⁴-H-hydroxyallosedamine ², two new minor alkaloids from Sedum itacre, are reported 1 and 2 were synthesized, and their absolute configuration established, via the optically pure tetrahydro 1,3-oxazines 17 and 18.     

Prostaglandin chemistry—VIII : Synthesis of optically active 7-oxoprostaglandins

Regiospecific α-acylation of β-alkenylated enolates generated by conjugate addition of lithium organocuprates to α,β-unsaturated ketones is described. Several new 7-oxoprostaglandin analogues, 7-oxoprostaglandin E₁ (18), 11-deoxy-7-oxoprostaglandin E₁ (23), and their 15-epi enantiomers 17 and 22, were synthesized by conjugate addition-acylation method. From optically active 4(R) -t - butyldimethylsiloxycyclopent - 2 - en - 1 - one (R-11), 7-oxoprostaglandin E₁ (18) was synthesized. Determination of the absolute configuration of 11-deoxy-7-oxoprostaglandin E₁ (23) and its 15-epi enantiomer (22) on the basis of CD study is described. Successful acylation of β-alkenylated lithium copper enolates with reactive acylating agents such as thiol esters and N-acyl imidazole as well as acyl halides is described.     

Asymmetric oxidation and determination of the configurations of an optically pure sulfoxide and an I-menthoxysulfonium salt of 1,9-bis(methylthio)dibenzothiophene by x-ray crystallographic analysis

1,9-Bis(methylthio)dibenzothiophene (1a) was treated with one equivalent of bromine and pyridine in the presence of l-menthol and then with aqueous sodium hydroxide to give optically active 1-(methylsulfinyl)-9-(methylthio)dibenzothiophene (2a) enriched by the S isomer (ee: 57%). The configuration of optically pure sulfoxide (2a) was determined by X-ray crystallographic analysis to be the S configuration at the sulfinyl sulfur atom. On the other hand, 1-(methyl-l-menthoxysulfonio)-9-(methylthio)dibenzothiophene tetrafluoroborate (4a) was isolated as an intermediate of this asymmetric oxidation in an optically pure form, as yellow crystals. The absolute configuration of this sulfonium salt (4a) was verified by X-ray crystallographic analysis as the R configuration. Optically pure sulfonium salt (4a) also gave partially optically active sulfoxide (2a) with net inversion on its hydrolysis. It was suggested that the hydrolysis reaction of the sulfonium salt (4a) accordingly proceeds, not only via a sulfurane having a simple S_N2 type of geometry but also by a front side attack ofhydroxide anion, with respect to the l-menthoxy group, on sulfur, and the sequential elimination of the l-menthoxy group from the tetracoordinated intermediate. © 1996 John Wiley & Sons, Inc.     

Stereochemie von Metallocenen, 36. Mitt.:

The two optically active methylbenchrotrenecarboxylic acids (1 a and1 b) with absolute configurations established by the X-ray method were chemically correlated with several o-and m-disubstituted benchrotrenes. Curtius degradation of the carboxylic acids1 afforded amino methylbenchrotrenes (4) which were also obtained by reduction of the active aminobenchrotrenecarboxylic acids (2). From the amines4 by diazotation and methylation methoxy methylbenchrotrenes (5) were accessible which in turn were prepared by reduction of the active methoxybenchrotrene carboxylic acids (3). The m-isomer3 b was transformed by Curtius degradation into m-methoxy aminobenchrotrene (6 b). Thereby the absolute configurations of some sixty optically active benchrotrene derivatives are now established.     

Anreicherung der Enantiomeren,Circulardichroismus und absolute Konfiguration vonN,N,N′,N′-Tetramethyldithiooxamid

(+)- and (?)-1 (N,N,N′,N′-Tetramethyldithiooxamide) were enriched by semipreparative liquid chromatography on triacetylcellulose. According to¹HNMR in the presence of an optically active auxiliary, the sample of (+)₃₆₅-1 had an enantiomeric purity of 0,50±0,01, thus permitting to calculate the CD spectrum for the pure enantiomer. The CD and UV spectra are discussed in terms of qualitative MO theory. Thereby, the absolute configuration of (+)₃₆₅-1 is determined to be (R).     

High Syn Selectivity of a SE′ Reaction: Acylation of an Optically Active 1,1-Disilyl-2-alkene. Preliminary communication

The disilane/disilylmethane rearrangement of an optically active disilanyl sulfide 9B was used to prepare an optically active disilylalkene 10 whose absolute configuration was established by X-ray analysis of the bromo derivative 13 (P2₁, a = 7.847 (3) Å, b = 9.487 (3) Å, c = 20.010 (8) Å, β = 82.28° (3), Z = 2). Acylation of 10 furnished an optically active ketone 14 , which was degraded to 16 , a compound of known absolute configuration. The enantiomeric excess of 10 was determined by alkylation with an optically active lithium compound and that of 14 by an optically active NMR.-shift reagent. The S_E′ reaction 10 → 14 was thus shown to proceed with 94% (97% syn/3% anti) stereoselectivity.     

Preparation of optically active bridged biphenyls via a stereoselective synthesis of their mono (tricarbonylchromium) complexes. Chiroptical properties and absolute chiralities of the complexes and ligands12

Reaction of the mono(tricarbonylchromium) complex 3 of diphenic acid anhydride with chiral amines gave the optically active imides 9-11. 10 and 11, from (S)-(?) and (R)(+)-phenylalaninol, respectively were separated by chromatography into exo- and endo-diastereomers (a and b) with opposite metallocene chiralities but with the same axial chirality. The (S)-(?) amino-alcohol induces (S)_a-chirality and vice versa. The absolute configurations of the metallocene and axial-chiral parts of the biphenyl system were deduced from the circular dichroism spectra, the former [(R)_m or (S)_m] by comparison with the CD of benchrotrenes of known absolute configuration, the latter [(R)_a or (S)_a] by applying the exciton model of coupled oscillators to the optically stable biphenyl ligands [i.e. the imides (?)- and (+)-8 easily accessible from 10 and 11 by photochemical decomplexation]. (R)_m-(S)_a for the complex (+)-10a (exo) and (S)_m-(S)_a for the endo-isomer (?)-10b, and vice versa for the complex 11. The parent ligands have the configurations (S)_a(?)-8 and (R)_a(+)-8, respectively.Photochemical cleavage of the optically active bis(tricarbonylchromium) complex (?)-13 of the biphenyl lactone 12 at ?60°C afforded optically labile 12 with a half-life time of racemization of ca 10 min at ?20°. On the basis of its CD the configuration (R)_a is tentatively proposed for 12.The work described represents the first example of the preparation of optically-active biphenyls via benchrotrene precursors.     

D3-trishomocubanetrione synthesis and optical resolution

A large-scale synthesis for the title compound rac-1 based on 11-oxahexacyclo-[5.4.1.0^2,6.0^3,10.0^4,8.0^9,12] dodecan-5-one (12) as the key intermediate and an efficient procedure for the optical resolution of rac-1 via the diastereomeric ketals with (R,R)-2,3-butandiol are reported. The absolute configuration is established by correlating the optically pure (+)-trione ([α]_D +949°) with (-)-trishomocubane.     

手性硫代磷酸及其衍生物的研究(Ⅻ)─杀虫剂O－甲基S－丙基O－苯基硫代磷酸酯光学异构体的合成及其绝对构型

以奎宁和番木鳖碱为拆分试剂,成功地拆分了外消旋的O-甲基O-苯基硫代磷酸2.拆分的酸(+)-2和(-)-2在甲醇钠存在下与溴丙烷反应,分别得到旋光活性的(-)-O-甲基S-丙基O-苯基硫代磷酸酯1和(+)-1.通过化学相关法确定了1的绝对构型为(-)-(S)和(+)-(R).     

Stereoselective oxidation of gem-disulphides with aspergillus niger

A strain of Aspergillus niger was used to prepare optically active gem-disulphide S-oxides 2 and 3 and the (s)-meso-disulphoxide 4. The structural assignment was made by intercorrelating the senses of NMR non-equivalence in pseudoasymmetric disulphoxides 4 and 5 of established configurations with the configurationally related monosulphoxides 2 and 3. The enantiomeric composition and absolute configurations were determined using the chiral solvent NMR method. The stereoselectivity in the microbial oxidation was found to be independent of the configuration of the incipient chiral centre at carbon.     

Diastereomeric process-based chiral resolution of helical quinone derivatives using (−)-menthyl chloroformate

Diastereomeric resolution of helically distorted polycondensed bisphenols (1,1′-bibenzo[c]phenanthrene-2,2′-diols: HEBPOLs) 2a–b was conducted utilizing (1R)-(?)-menthyl chloroformate as a chiral resolving agent. Subsequent manipulation produced highly optically pure [>99% enantiomeric excess (ee)] quinone derivatives (P) and (M)-1a–b in very good yields. The absolute configuration of each product was confirmed based on circular dichroism (CD) spectra and X-ray crystal structure analysis.     

Chemo-enzymatic synthesis of the active enantiomer of the anorressant 2-benzylmorpholine

Baker's yeast reduction of (Z)-α-bromocinnamaldehyde 1 in the presence of absorbing resins allows the easy preparation of the corresponding saturated bromo-alcohol 2 in high yields and enantiomeric excess. The absolute configuration is assigned through conversion into the (R)-phenyl oxirane 3 and 1-phenyl-2-propanol 4 of (S) absolute configuration. The (R)-epoxide is transformed into 6, the pharmacologically active enantiomer of the appetite suppressant 2-benzylmorpholine, to which the (R) configuration is assigned.