Geometrical isomerism and 13C spectra of the β-substituted Enones R1?C(1)O?C(2)HC(3)H?R2

The ¹³C chemical shifts of the unsaturated carbons were measured in 31 cis and trans pairs of β-substituted enones R₁? C(1)O? C(2)H?C(3)H? R₂. In these polarized ethylenes the chemical shifts of the olefinic carbons are simply related by the equation δ_c=δ_t+A. The steric and electronic effects introduced by the R₁ and R₂ substituents influence the chemical shifts of C-2 and C-3 in both isomers. It is shown that the sign and magnitude of the intercept A mainly reflect the π-charge electronic density changes which arise in the cis isomer and are transmitted via the π-framework. The effect of the steric interaction on the chemical shift of C-3 in the cis isomers is postulated to be related to the symmetry of the substituents. Therefore, the differential shielding of C-3 is indicative of the conformational structure of the cis molecule.     

Configuration and conformation of substituted azetidines

Studies of compounds such as 1-cyclohexyl-2-carbomethoxy-4-methylazetidine by H-1 nmr coupling constants, nuclear Overhauser effects, C-13 steric shifts, and N-15 nmr support the revised assignment of configuration for cis/trans isomers in a series of N-alkyl substituted azetidines. The trans isomer displayed spectral characteristics consistent with a planar or nearly planar ring. The cis isomer favors a puckered ring, with major substituents at C-2 and C-4 equatorial. Compounds lacking the C-4 methyl are also puckered. Puckering angles are estimated. In contrast, trans-1-cyclohexyl-2-carboxy-4-methylazetidine (a zwitterion) prefers a puckered ring, possibly implicating the time averaged effect of nitrogen inversion on ring shape. The N-15 spectra show a large difference in chemical shift between cis and trans isomers of the azetidines, although analogous aziridines show an even larger difference.     

13C NMR spectroscopy of naturally occurring iridoid glucosides and their acylated derivatives

The ¹³C NMR spectra of twenty one iridoid glucosides and fourteen acyl iridoid glucosides of various cyclopentane oxidation states have been analysed and their carbon shifts assigned. Evidence is presented which demonstrates that ¹³C NMR spectroscopy is a valuable and reliable technique for distinguishing the sites of acylation in iridoid glucosides and confirming the predictions of the configuration at C-6 and C-8. A cis configuration of vicinal substituents is generally associated with a substantial increase in shielding, as compared with the trans analog. The ring size and C-1 configuration in the glucose moiety are also evident from the spectra.     

Carbon-13 NMR analysis of cyclobutane dimers from benzocycloalkenes

¹³C NMR Spectra for a series of 11 substituted cyclobutanes derived from photodimerization of benzocycloalkenes were recorded. Comparison of the carbon chemical shifts for the head-to-head and head-to-tail cis-syn-cis and cis-anti-cis isomers reveals shielding trends which should facilitate structural and stereochemical assignments for related compounds. The head-to-head isomers show a larger separation of cyclobutane carbon resonances than the head-to-tail isomers. The cis-syn-cis isomers relative to the cis-anti-cis isomers exhibit distinctive upfield shifts of all carbon resonances, except those of aromatic carbons ortho to alkyl-substituted aromatic carbons.     

The stereochemistry of 2,4-disubstituted γ-butyrolactones and 2,4,6-trisubstituted-5,6-dihydro-4H-1, 3-oxazines

2,4-Disubstituted butyrolactones and 2,4,6-trisubstituted-5,6 dihydro-4H-1,3-oxazines show similar features in their ¹H and ¹³C- NMR spectra. Two geminal ring hydrogens of cis isomers give rise to a complex ABXY spectra when the substituent is alkyl or aryl. In spectra of trans isomers these patterns are degenerated. When R is OMe(in 4) or OCOMe (in 6) the difference in chemical shifts of geminal protons and vicinal coupling constants cannot be used for diagnosis. In ¹³C spectra ring carbons C-2 and C-3 in lactones and C-4 and C-5 in oxazine of trans isomers show a small but consistent shift to higher fields.     

13C NMR study of some polychloro-isobutane and -isobutene compounds

The ¹³C chemical shifts and the carbon–proton coupling constants have been determined for some chlorinated isobutane and isobutene compounds. The one-bond coupling constants in isobutane derivatives showed a regular increase with an increasing number of γ-chlorine substituents. The three-bond coupling constant of the methyl carbon decreased from 4.2 to 2.0 Hz as the number of chlorine substituents in the γ-position increased. In the isobutene compounds, the vicinal coupling of C-1 was larger to protons in a group that is trans with respect to a chlorine substituent on C-1 than to those in the corresponding group cis to the chlorine. The vicinal coupling constants between atoms in geminal groups (on C-2) seem to be affected by the orientation of the chlorine substituent on C-1.     

Structural features of diastereomeric oxazolidin-2-ones

Model diastereomeric oxazolidinones containing various substituents at positions 3 and 5 were synthesized. Several individual diastereomers bearing methyl groups at positions 4 and 5 in cis-and trans orientations were isolated. The TLC and ¹H NMR spectroscopic data suggest that diastereomers, particularly those containing the aryl substituent at position 5, are substantially different in the physical and spectral properties. The configurations of some diastereomers were established by X-ray diffraction and NOESY spectroscopy. For these compounds, the reliable assignment of the characteristic ¹H NMR signals of individual groups was made, which provided evidence for the cis or trans orientation of the methyl groups at positions 4 and 5. The scope of the method as applied to the determination of the cis and trans isomers from their ¹H NMR spectra is discussed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 133–139, January, 2007.     

Synthesis and 13C NMR spectra of cis- and trans-{2-(haloaryl)-2-[(1H-imidazol)-1-yl]methyl]}-1,3-dioxolane-4-methanols

Syntheses and ¹³C nmr spectra of a number of cis and trans 2-(haloaryl)-2-[(1H-imidazol-1-yl)rnethyl]-4-(hydroxymethyl)-1,3-dioxolanes are described. The haloaryl groups are 2,4-dichloro, 2,4-difluoro-, 4-chloro-and 4-bromophenyl. In these series, some of the cis compounds become available through crystalline bromo benzoates 5 . Separations of some trans isomers are achieved through fractional crystallizations of imidazolyl benzoate nitrates 6 . Stereochemical assignments are based primarily on one major ¹³C chemical shift difference, namely that of C-4 of the 1,3-dioxolane ring, the chemical shift of the trans isomers being 1.0-2.5 ppm downfield from that of the cis isomers.     

Etude Stéréochimique par RMN 1H de Tetrahydropyrannes β-Chlorés α-Substitués

The ¹H NMR study of 2-alkyl-3-chlorotetrahydropyrans, obtained by reaction of Grignard reagents with a mixture of cis/trans-2,3-dichlorotetrahydropyrans, shows cis/trans configuration of two isomers in which the alkyl substituents are exclusively in the equatorial position. 3-Chloro-2-phenyltetrahydropyran exists in trans (eq-eq) configuration only. The ¹H NMR study of cis/trans 2-alkoxy (or aryloxy)-3-chlorotetrahydropyrans, obtained by reaction of alcohols or phenol with 2,3-dichlorotetrahydropyrans, shows the axial position of the alkoxy (or aryloxy) substituent.     

Nitrogen-15 nuclear magnetic resonance spectroscopy. Natural abundance nitrogen-15 spectra of the cis and trans isomers of secondary alkylformamides

The ¹⁵NMR chemical shifts were measured of a number of N-substituted formamides and acetamides at the natural abundance level. The ratios of the cis and trans isomers for several N-alkylformamides were also determined. Substituent effects on the ¹⁵N chemical shifts of formamides are compared with those of some other nitrogen-containing compounds. There is a consistent pattern of behavior of the one bond spin–spin coupling constants [¹J(¹⁵NH)] wherein the trans isomers of N-alkylformamides are larger than those of the cis isomers.     

12H-dibenzo[d,g][1,3,2]dioxaphosphocins: Synthesis,structures and “through-space” spin-spin coupling in their NMR spectra

A series of 12H-dibenzo[d,g][1,3,2]dioxaphosphocins has been prepared by the reactions of bisphenols with either ethyl phosphorodichloridate or phosphorus pentasulfide. The structures of a pair of cis and trans isomers in this series were elucidated by X-ray crystallography. Both isomers adopt the boat-chair conformation in the solid state with the bulky group at C-12 in the pseudo-equatorial position. Some flattening of the heterocyclic ring due to the pseudo-axial ethoxy group was observed in the cis isomer. A novel transannular cyclisation reaction was observed in the mass spectra of the cis isomers and this has allowed us to assign the configurations of all the isomers in the series. The pmr spectra of the compounds have been explained in terms of the rigid boat-chair conformation; however, as bulky groups were introduced at C-12, signs of mobility were observed for the cis isomers and an equilibrium was established with mobile boat forms. A stereospecific long-range coupling between P and the proton at C-12 could be transmitted “through space” by the antiperiplanar lone-pair electrons on the ring oxygen atoms.     

Configurationally and conformationally homogeneous cyclicN-aryl sulfimides. II.13C-and1H NMR spectra

The configuration and (in case of mobile ring systems) the preferred conformation in a series of thiane- and ofcis-andtrans-1-thiadecalin-1-N-4-chlorophenyl imides were assigned by means of¹³C- and¹H nmr spectroscopy.¹H nmr criteria known to be valid for determination of the stereochemistry of cyclic sulfoxides may be applied (with limitations) to cyclicN-aryl sulfimides, if both isomers (S–N bond equatorial and axial, respectively) are known. The assignments are easier, and unambiguous for single isomers, by comparison of¹³C nmr chemical shifts of ring carbon atoms of sulfimides and sulfides. The influence of equatorially and axially oriented sulfimide groups on the chemical shifts of neighbouring protons, and on the carbon atoms of the heterocyclic rings are discussed in detail.

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Konfigurativ und konformationell einheitliche cyclische N-Aryl-sulfimide. II.¹³C- und¹H-NMR-Spektroskopie

Zusammenfassung Die Konfiguration und (bei beweglichen Ringsystemen) die bevorzugte Konformation einer Reihe von Thian- und voncis- undtrans-1-Thiadekalin-1-N-4-chlorophenylimiden wurde durch¹³C- und¹H-NMR-Spektroskopie bestimmt. Bekannte¹H-NMR-Kriterien zur Festlegung der Stereochemie cyclischer Sulfoxide sind (mit Einschränkungen) auch bei cyclischenN-Arylsulfimiden anwendbar, wenn beide Isomere (S–N-Bindung äquatorial bzw. axial) bekannt sind. Leichter, und auch bei Vorliegen von nur einem Isomeren eindeutig, gelingt die Zuordnung durch Vergleich der¹³C-NMR-Verschiebungen der Ringkohlenstoffatome von Sulfimiden und Sulfiden. Die Einflüsse äquatorial oder axial orientierter Sulfimidgruppen auf die chemischen Verschiebungen benachbarter Wasserstoffe und der Kohlenstoffe des Heterorings werden diskutiert.

     

Stereochemistry and 13C NMR investigation of 9-halotetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones

It was shown that the halogen atom occupies the quasi-axial position in the predominant conformer of the 9-halo derivatives of tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones. When R³ = Me, the conformational equilibrium is determined by the latter substituent which is always quasi-axial. The effects of the methyl group and the halogen atoms on the ¹³C chemical shifts (SCS values) were used for the identification of cis and trans isomers. Interesting non additivity of substituent effects was found in derivatives bearing quasi-axial substituents at C-6 and C-9: and this was caused by the ring flattening.     

Investigation of the exo and endo isomers of dioxolane-type benzylidene derivatives of carbohydrates by 13C NMR spectroscopy

The absolute configurations of nine 2,3-O-benzylidene-α-L-rhamno- and α-D-mannopyranoside diasteteomeric pairs were determined and the ¹³C NMR spectra of further thirteen α-L-rhamno- and α-D-mannopyranosides, having various substituents, were completely assigned.Four ¹³C shifts were found suitable for the determination of the absolute configuration of the dioxolane skeleton. (1) The chemical shift of the acetal carbon in the endo isomers is between 103.9 and 104.7 ppm whereas for the exo isomers this region extends from 102.8 to 103.4 ppm; (2) The formation of the dioxolane ring causes a deshielding effect for the bridgehead carbons, in the exo isomers this effect is more pronounced for C-3 whereas in the endo isomers for C-2. For C-4, shielding effect was found in the exo isomers and deshielding effect in the endo ones; (3) The chemical shift of the quaternary carbon of the phenyl group is greater in the exo isomers than in the endo ones; (4) The difference between the shift of the acetal carbon and that of the quaternary carbon of the phenyl group in the exo isomers is greater than 35.4 ppm, in the endo isomers is less than 33.7 ppm.     

Structure and reactivity of α,β-unsaturated ethers. III. Cationic copolymerizations of alkenyl alkyl ethers

The relative cationic polymerizabilities of the geometrical isomers of various alkenyl alkyl ethers were studied both in copolymerizations with each other and in their respective copolymerizations with vinyl isobutyl ether as standard. Copolymerizations were carried out in methylene dichloride at ?78°C. with boron trifluoride etherate as catalyst. The cis isomers have been found to be more reactive than the corresponding trans isomers. A primary alkyl substituent on the β-cis position of vinyl ethyl ether enhances the reactivity. Yet the steric effect is noticeable when the substituents are bulky. Compounds substituted with cis-β-isobutyl and with β-dimethyl showed little tendency to homopolymerization. It was proved that the polymer ends derived from cis and from trans monomers are respectively different in character because of the restricted rotation of the end unit around the terminal carbon–carbon bond. The alternation tendency, remarkable in the copolymerization of cis monomers with vinyl ether, was explained in terms of the cis-opening mechanism.     

Multinuclear two-dimensional NMR: Assignments of natural abundance polypeptide 13C, 1H and 15N chemical shifts and demonstration of isomer interconversion

The polypeptide carbobenzoxy-glycyl-L -prolyl-L -leucyl-L -alanyl-L -proline (0.2 M in DMSO-d₆) was investigated using ¹³C, ¹H and ¹⁵N NMR in natural abundance at 4.7 tesla. The existence of cis–trans-Gly-Pro and -Ala-Pro bonds permits up to four isomers, and all four were observed (in a 60:30:7:3 ratio). ¹³C shifts of the proline β-CH₂ resonances are consistent only with the 60% form being trans–trans. The 30% form is either trans–cis or cis–trans (order as above) and was tentatively assigned as cis-trans on the basis of relaxation behavior. Refocused INEPT studies aided the ¹³C assignments. The ¹⁵N data were obtained using both NOE and INEPT excitation, with signals evident for the three major isomers. The spectra were analysed by starting from the ¹³C data, which were assigned based on known regularities in peptide spectra. A ¹³C? ¹H heteronuclear two-dimensional chemical shift correlation experiment allowed direct assignment of proton shifts for major and minor isomers. The NH proton shifts were assigned by running a homonuclear two-dimensional chemical shift correlation experiment and noting the correlation with the previously assigned α-CH protons. The ¹⁵N resonances were then assigned from a ¹⁵N? ¹H heteronuclear two-dimensional chemical shift correlation experiment, relating the ¹⁵N signals directly to the NH proton resonances. Isomer interconversion between the two major isomers was demonstrated by performing a magnetization transfer homonuclear 2D experiment. Off-diagonal intensity was noted relating the major and minor isomer alanine NH proton, as well as for the major and minor isomer leucine NH protons.     

Low-temperature 15N NMR spectra of reduced 1,3-heterocyclic systems

The ¹⁵N NMR spectra of the O-inside cis-fused conformer of perhydropyrido[1,2-c][1,3]thiazine shows a shielding of the nitrogen of 23.0 ppm relative to the trans-fused conformer. In contrast, ¹⁵N shifts for the cis-and trans-fused conformers of perhydro-oxazolo[3,4-a]pyridine and perhydrothiazolo[3,4-a]pyridine show corresponding shieldings of only 0.6 and 2.5 ppm, respectively.     

Stereochemical characterization of some mono- and diaryl substituted ethylene oxides by NMR spectroscopy

NMR spectra of several styrene, stilbene and stilbazole oxides have been determined, and chemical shifts and coupling constants have been correlated with cis-and trans-configurations. Assignments have been made for all protons, and double resonance technique and ¹³C? H coupling constants have been used in some particular cases. An explanation is proposed for the observation that chemical shifts of oxirane protons are higher for cis than for trans isomers.     

1H and 13C NMR studies of some germacrones and isogermacrones

The ¹H and ¹³C NMR spectra of the trans,trans-, cis,cis- and cis-C-3–C-4, trans-C-7–C-8-germacrones and of the cis-C-2–C-3, trans-C-7–C–8, trans-C-2–C-3, cis-C-7–C-8- and cis,cis-isogermacrones are analysed. The last two isogermacrones are new compounds. The C-2–C-3 double bond in the previously described isogermacrone is found to be of cis configuration, contrary to the hitherto accepted trans arrangement.     

13C chemical shifts and conformational analysis of S-methylthiolanium cations

The ¹³C NMR spectra of all cations obtained by methylation at sulphur of the mono-and dimethylthiolanes are reported. The methyl substituent on sulphur affects the shieldings of the adjacent carbons in a manner which allows easy identification of the cis and trans isomers. For most compounds the ¹³C pattern is consistent with a half-chair ring conformation with maximum staggering at C-3, C-4. Only with methyl groups at the 1,2-or 1,2,3-positions is the half-chair appreciably deformed. It is suggested that in these cases the preferred conformation is a quasi-envelope with C-3 at the top.