A Stereospecific `2‐Aza‐divinylcyclopropane' Rearrangement

The stereochemical course of the thermal 2‐aza‐Cope rearrangement of the optically pure acyl azide (−)‐(1S)‐ 5 was investigated by determination of the absolute configuration of the rearrangement product (1R,8S)‐ 9 . The reaction proceeds by a sequence of stereospecific steps from 5 to an equilibrating mixture of exo‐ and endo‐isocyanates 6 and 7 . The endo‐isomer 7 undergoes Cope rearrangement to the putative intermediate 8 , which is trapped and characterized as the adduct 9b of butan‐1‐ol. The absolute configuration of 9b was determined by its reduction to the amide 20 , and determination of the X‐ray structure of the N‐camphanoylamide 21 derived from camphanic acid of known absolute configuration.     

Heterotricyclodecane VIII. (−)-(1S, 3R, 6R, 8R)-2, 7-Dioxaisotwistan und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twistan; Synthese und Bestimmung der absoluten Konfiguration

A synthesis and the determination of the absolute configuration of (?)-(1S, 3R′ 6R, 8R)-2, 7-dioxa-isotwistane ( 13 ) and (?)-(1R, 3R, 6R, 8R)-2, 7-dioxa-twistane ( 14 ) is described. The results for 14 are compared with those for carboeyclic (+)-twistane ( 2 ) of known chirality.     

Absolute structure determination using CRYSTALS

A study of post‐refinement absolute structure determination using previously published data was carried out using the CRYSTALS software package. We show that absolute structure determination may be carried out optimally using the analyses available in CRYSTALS, and that it is not necessary to have the separate procedures absolute structure determination and no interest in absolute structure as proposed by Flack [Chimia (2014), 68 , 26–30].     

Die absolute Konfiguration des Spermin-Alkaloides Aphelandrin

The Absolute Configuration of the Spermine Alkaloid Aphelandrine The relative configuration of aphelandrine ( 1 ) was established by X-ray structure determination. The absolute configuration of the centers 11 and 18 was determined earlier by chiroptic measurements. Therefore, structure 1 with the configurations 11S, 17S, and 18S represents the absolute configuration of aphelandrine. In the presence of base, 1 was converted to (11S, 17R, 18R) orantine ( 2 ). The ¹H-NMR coupling constants between H? C(17) and H? C(18) (part of the dihydrofuran ring) are very much dependent on the substituent pattern of the amino N-atoms N(6) and N(10).     

One‐dimensional TOCSY 1H NMR experiments on adducts of amino acid esters with cobalt(III) tetramethylchiroporphyrin. Prospects for the analysis of amino acid mixtures

Cobalt(III) tetramethylchiroporphyrin, CoCl(TMCP), is a useful chiral shift reagent for structure attribution, absolute configuration assignment and enantiomeric excess determination of amino acid methyl esters by ¹H NMR spectroscopy. However, it has two axial sites available for amine coordination, a structural feature which generates n(n + 1)/2 diastereomeric species and n² distinct spin systems from a mixture of n amino ester enantiomers, making the analysis of complex amino acid samples exceedingly difficult by classical 1‐D or 2‐D NMR methods when n > 3. The 1‐D TOCSY experiment is shown to be a powerful tool for the selective excitation and detection of every single component of a mixture of four amino acid methyl esters bound to CoCl(TMCP): those of(S)‐Leu, (S)‐Asp, (R)‐Asp and (S)‐Glu, for example. The potential utility of this methodology for the determination of amino acid enantiomers in carbonaceous meteorites or other extraterrestrial samples is suggested. Copyright © 2002 John Wiley & Sons, Ltd.     

Liquid Chromatographic Determination of Cationic Surfactants in Environmental Samples using a Continuous Post-Column Ion-Pair Extraction Detector with a Sandwich Phase Separator

Abstract

A new detection technique is described for the quantitative analysis of cationic surfactants by HPLC via post-column ion-pair formation. A new sandwich type phase separator, as part of the extraction detector, was successfully introduced. The method was used to determine ditallowdimethylammonium chloride (DTDMAC) in various environmental samples. Detection limits of DTDMAC in river water were about 2 μg/1 (60 ng absolute; S/N = 5) and 10 ng/1 (260 pg absolute; S/N = 5), using methyl orange and 9,10-dimethoxyanthracene-2-sulphonate (DAS) as ion-pairing reagents, respectively. The environmental concentration of DTDMAC found on random samples from two Belgian rivers range from 30 to 40 μg/1. The reproducibility of the determination of DTDMAC in river water was 4.2% (RSD) (n = 20).     

Configurational assignment in alkyl‐branched sugars via the geminal C,H coupling constants

The measurement of the magnitude and sign of ²J(C,H) couplings offers a reliable way to determine the absolute configuration at a carbon center in a fixed cyclic system. A decrease of the dihedral angle ? in the O—C_A—C_B—H fragment always leads to a change of the ²J(C_A,H_B) coupling to more negative values, independent of the type and position of substituents at the two carbon centers. The orientations of the two substituents at C‐3 of the epimeric pair 1 and 2 were determined unambiguously through the measurement of the geminal coupling constants between C‐3 and the hydrogen atoms at C‐2 and C‐4. In particular, ²J(C‐3,H‐2ax) with ?1.5 Hz, ? = 174° in 1 and ?6.6 Hz, ? = 47° in 2 , and ²J(C‐3,H‐4) with +1.5 Hz, ? = 175° in 1 and ?4.7 Hz, ? = 49° in 2 showed the greatest differences between the two epimers. Both couplings therefore allow the determination of the absolute configuration at C‐3. It should be noted, however, that the size of the coupling constants can be different for dihedral angles of nearly identical size, when there are different numbers of electronegative substituents on the two coupling pathways, i.e. no O‐substituent at C‐2, but one axial O‐substituent at C‐4. It becomes clear that it is not sufficient to measure the magnitude of ²J coupling constants only, but that the sign of the geminal coupling is needed to identify the absolute configuration at a chiral center. The coupling of C‐3 with H‐2eq is not useful for the determination of the configuration at C‐3, as the similarity of the dihedral angles ? (O—C‐3—C‐2—H‐2eq) (57° in 1 and 70° in 2 ) leads to identical coupling constants (?6.1 Hz) for both epimers. Copyright © 2003 John Wiley & Sons, Ltd.     

(+)-(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.     

南中国海柳珊瑚网状软柳珊瑚Subergorgia reticulata中的多氧化甾醇

Two new polyoxygenated steroids, reticulatic acid （1） and reticulatin （2）, together with a known compound 3,22,25-trihydroxy-16-24,20-24-bisepoxy-3β,16β,20S,22R,24S-cholest-5-ene （3）, were isolated from the CH2Cl2/ EtOH extract of the South China Sea gorgonian coral Subergorgia reticulata. Their structures were established on the basis of extensive spectroscopic analysis. The absolute stereochemistry of compounds 2 and 3 was determined by the X-ray crystallographic analysis and the Mosher ester determination.     

Synthesis and Optical Resolution of the Floral Odorant (±)‐2,3‐Dihydro‐2,5‐dimethyl‐1H‐indene‐2‐methanol,and Preparation of Analogues

The title compound (±)‐ 1 , a recently discovered, valuable, floral‐type odorant, has been synthesized by a straightforward procedure (Scheme 1). To determine the properties of the enantiomers of 1 , their separation by preparative HPLC and the determination of their absolute configuration by X‐ray crystallography were carried out (Figure). Furthermore, the analogues 2 – 6 were synthesized, either from differently methylated 2‐methylindan‐1‐ones (Schemes 2 and 3) or, in the case of the 2,4,6‐trimethylated homologue 6 , by a completely different synthetic approach (Scheme 4). An evaluation of (+)‐(S)‐ 1 , (−)‐(R)‐ 1 , and (±)‐ 1 showed only minor differences in terms of odor (Table).     

Synthese der enantiomeren 2-Pyrrolidinessigsäuren

Synthesis of the enantiomeric 2-pyrrolidineacetic acids. Starting from the enantiomeric Z-prolines ( 1 ) the title compounds 9 were prepared in optically pure form by using the Arndt-Eistert process. It could be shown by chemical correlation that the stereochemical determining step of the reaction sequence, the Wolff rearrangement of the N-acylated diazomethyl ketones 5 , proceeds with strict retention of configuration. Some known chiroptical methods for determination of absolute configuration were applied to the target compounds.     

2‐Amino‐1,2,3,6‐tetrahydro‐6‐oxocyclopenta[c]fluorene‐2‐carboxylic Acid (FlAib), a Completely Rigidified,Fluoren‐9‐one‐Based α‐Amino Acid

The synthesis, optical resolution, determination of absolute configuration and conformational preference, and spectroscopic characteristics of terminally protected (blocked) derivatives and short peptides of 2‐amino‐1,2,3,6‐tetrahydro‐6‐oxocyclopenta[c]fluorene‐2‐carboxylic acid (FlAib), a novel, rigid, chiral, cyclized C^α,α‐disubstituted glycine are described.     

Organic Reactions in the Solid State: Reactions of Enclathrated 3,4-Epoxycyclopentanone (=6-Oxobicyclo[3.1.0]hexan-3-one) in Tri-o-thymotide and Absolute Configuration of 4-Hydroxy- and 4-Chlorocyclopent-2-en-1-one

Several aspects of the heterogeneous actions of aqueous and gaseous HCl on the chemical behavior of 3,4-epoxycyclopentanone (=6-oxabicyclo[3.1.0]hexan-3-one; 1 ) included in the asymmetric cages of tri-o-thymotide (TOT) clathrates belonging to space groups P3₁21 are described, showing specific features strikingly at variance with those observed in liquid solutions. In a first step, the substrate underwent an acid-promoted allylic isomerization, as already observed in our previous investigations, to give optically active 4-hydroxycyclopent-2-en-1-one ( 2 ). In a consecutive step, a displacement of the OH group was accomplished by the Cl⁻ anion to afford the corresponding chloro compound 3 . Polymorphism was encountered in the preparation of TOT/ 1 clathrates. Recrystallization of TOT in the pure guest 1 yielded micro-twinned crystals belonging to the P3₁ space group (host/guest ratio 1 : 1), whereas the expected P3₁21 lattice grew from a mixture of TOT, 1 , and MeOH. The structural determination of TOT/ 1 was carried out by X-ray diffraction (Fig. 1). Kinetic measurements were achieved that shed light on some striking features of this type of heterogeneous reactions for solid-liquid and solid-gas systems. Several reactions of pure clathrate antipodes (+)-TOT/ 1 with gaseous HCl were carried out under various conditions; concentration and enantiomer-excess(ee) determinations of the products 2 and 3 allowed to establish a larger ee for 3 , thus demonstrating the influence of the host-guest diastereomeric association on the progression of the reaction. The correlation of optical activities of the host and products for the global reaction disclosed the sequence (+)-(M)-TOT/ 1 →(−)- 2 →(−)- 3 . A new way for the preparation of 2 was devised. It was further demonstrated that the X-ray structure analysis of the chiral clathrate (M)-TOT/(+)- 2 (Fig. 4) associated with chiroptical measurements was an efficient and straightforward method to determine the absolute (+)-(R)-configuration of the guest. The enantioselectivity of the TOT clathrate for 2 was established by two different methods which allowed the appraisal of an accurate revised value of the specific rotation of 2 . The enclathration of 3 occurred exclusively in the orthorhombic centrosymmetric host lattice Pbca, thus prohibiting the X-ray structural determination of the guest absolute configuration. The problem of finding a pathway to the intended enantiomer enrichment of 3 was worked out through the action of aqueous HCl on microcrystalline (+)-TOT/(−)-(S)- 2 that gave an optically active mixture of unreacted 2 with 3 as sole product. The pure optically active 3 was isolated by subsequent TLC. The resolution of 3 was achieved by GC over a chiral column and its (unknown) specific rotation measured. The absolute configuration of 3 was established by the measurement of the enantiomer purity of the optically active mixture 3 obtained after the total conversion of (−)-(S)- 2 in the presence of thionyl chloride in Et₂O, dioxane, and benzene. It was deduced that the (−)- 3 enantiomer had the (S)-configuration.     

HUG and SQUEEZE: using CRYSTALS to incorporate resonant scattering in the SQUEEZE structure‐factor contributions to determine absolute structure

The resonant‐scattering contributions to single‐crystal X‐ray diffraction data enable the absolute structure of crystalline materials to be determined. Crystal structures can be determined even if they contain considerably disordered regions because a correction is available via a discrete Fourier transform of the residual electron density to approximate the X‐ray scattering from the disordered region. However, the corrected model cannot normally account for resonant scattering from atoms in the disordered region. Straightforward determination of absolute structure from crystals where the strongly resonantly scattering atoms are not resolved has therefore not been possible. Using an approximate resonant‐scattering correction to the X‐ray scattering from the disordered regions, we have developed and tested a procedure (HUG) to recover the absolute structure using conventional Flack x refinement or other post‐refinement determination methods. Results show that in favourable cases the HUG method works well and the absolute structure can be correctly determined. It offers no useful improvement in cases where the original correction for the disordered region scattering density is problematic, for example, when a large fraction of the scattering density in the crystal is disordered, or when voids are not occupied equally by the disordered species. Crucially, however, if the approach does not work for a given structure, the statistics for the absolute structure measures are not improved, meaning it is unlikely to lead to misassignment of absolute structure.     

Crystal structure of the copper complex of the Schiff base from 1-(N,N-dimethylaminomethyl)-2-formylcymantrene and (S)-alanyl-(S)-alanine

The mechanism of stereoselective syntheses of amino acids via glycine Schiff base/metal complexes is discussed on the basis of data from the X-ray structure determination of (OC)₃Mn[η⁵-C₅H₃(CH₂NMe₂)(CHNCHMeC(O)N---CHMeCOO)Cu]. The absolute configuration of the latter complex is S (the Mn and Cu atoms are trans with respect to the Cp plane).     

Induced Helical Chirality of Perylenebisimide Aggregates Allows for Enantiopurity Determination and Differentiation of α‐Hydroxy Carboxylates by Using Circular Dichroism

We have developed a working strategy for accurate enantiomeric excess (ee) determination based on induced helical aggregation of achiral perylenebisimide (PBI) dyes. PBI dyes functionalized with boronic acid moieties were shown to be effective chirality sensors for α‐hydroxy carboxylates. Seven α‐hydroxy carboxylates tested showed strong induced Cotton effects in the perylene absorption region around λ=500 nm, which were utilized for enantiomeric excess determination and chemo‐discrimination of the analytes, with an average absolute error of 2 % in ee determination and 100 % correctness in analyte classification. Responses in the absorption spectra, which arise from the guest‐enhanced aggregation, allow the determination of the sample concentration, thus enabling analysis of samples of unknown concentration and ee. The simplicity of the strategy, the ease of sample preparation, and the accuracy demonstrated, can potentially facilitate screening procedures in asymmetric synthesis.     

New guaianolides from Berlandiera Pumila and B. Texana,and the X-ray crystal structure of pumilin

The isolation and structure determination of two new guaianolides, pumilin and its 2,3-epoxide, from Berlandiera pumila and B. texana are reported. The structure of pumilin was determined from nmr and mass spectral data, and from an X-ray single crystal study; the structure of the epoxide was found by comparison of nmr spectra. Pumilin is shown to be a Δ¹⁽¹⁰⁾-cis-guaianolide with a cyclopentenone ring attached to C1 and C5, and an α-methylene-γ-lactone ring trans-fused to C6 and C7. The absolute configuration was inferred from spectral considerations and knowledge of previous structural determinations. The cd spectrum of pumilin exhibits a negative Cotton effect, and the lactone chromophore has left-handed chirality. The cyclo-heptene ring is in the chair configuration, with the lactone a half-chair and the cyclopentenone essentially planar. Crystals are orthorhombic, a = 7.065, b = 13.652, c = 19.586 Å, space group P2₁2₁2₁, Z = 4, and the final R value is 3.9%. The crystal structure is strengthened by an O···O hydrogen bond linking the molecules into infinite chains.     

Absolute Configuration of 2-Substituted 2-Azabicyclo[2.2.1]hept-5-enes

The diastereoisomeric 2-substituted 2-azabicyclo[2.2.1]hept-5-enes 2 – 4 were prepared by aza-Diels-Alder reaction of cyclopentadiene with the corresponding methaniminium ions. Their relative configurations were deduced using ¹H, ¹H-ROESY experiments, and their absolute configurations were assigned from the crystal structure of the aziridinium derivative (?)- 5 . The absolute configuration of (+)- 1 , i.e. (1R), was assigned by CD spectroscopy.     

Stereochemical effects in mass spectrometry. 7. Determination of absolute configuration of some organic molecules by reaction mass spectrometry

It was found that in the chemical ionization (isobutane) mass spectra of some asymmetric secondary alcohols and α-amino acids, when a pair of enantiomers (such as R- and S-2-phenyIbutyric anhydride, R- and S-mandelic acid, R- and S-2-methylbutanoic acid or R- and S-α-phenyl ethyl amine) were used as reaction reagents, the relative abundances of characteristic ions formed by the stereoselective reaction between sample and reagent of the same configuration were much higher than those ions formed by the sample and a reagent of a different configuration. The absolute configuration of the sample molecule may be predicted by examination of mass spectra of the sample measured with R- and S-reagent respectively. This approach proved to be a convenient way for determination of the absolute configurations of organic molecules on a micromole level by mass Spectrometry.