1,2-Shifts stereochemistry

A proton can be (numerically) represented by a series of topological and physicochemical descriptors, which account for the influence of the neighborhood on its chemical shift. Fast empirical procedures for the calculation of physicochemical descriptors are now easily accessible [45. Geometric descriptors were added in the case of some rigid substructures, as well as for rr-systems, to account for stereochemistry and 3D effects. 

Proton chemical shift data from nuclear magnetic resonance has historically not been very informative because the methylene groups in the hydrocarbon chain are not easily differentiated. However, this can be turned to advantage if a polar group is present on the side chain causing the shift of adjacent hydrogens downfteld. High resolution C-nmr has been able to determine position and stereochemistry of double bonds in the fatty acid chain (62). Broad band nmr has also been shown useful for determination of soHd fat content. 

The main appHcation of nmr in the field of pyrazolines is to determine the stereochemistry of the substituents and the conformation of the ring. For pyrazolones, nmr is useful in estabUshing the stmcture of the various tautomeric forms. Table 2 summarizes the chemical shifts of a few representative derivatives. 

Nucleophilic substitution in cyclohexyl systems is quite slow and is often accompanied by extensive elimination. The stereochemistry of substitution has been determined with the use of a deuterium-labeled substrate (entry 6). In the example shown, the substitution process occurs with complete inversion of configuration. By NMR amdysis, it can be determined that there is about 15% of rearrangement by hydride shift accon any-ing solvolysis in acetic acid. This increases to 35% in formic acid and 75% in trifiuoroacetic acid. The extent of rearrangement increases with decreasing solvent... 

The stereochemistry of addition is usually anti for alkyl-substituted alkynes, whereas die addition to aryl-substituted compounds is not stereospecific. This suggests a termo-iecular mechanism in the alkyl case, as opposed to an aryl-stabilized vinyl cation mtermediate in the aryl case. Aryl-substituted alkynes can be shifted toward anti addition by including bromide salts in the reaction medium. Under these conditions, a species preceding the vinyl cation must be intercepted by bromide ion. This species can be presented as a complex of molecular bromine with the alkyne. An overall mechanistic summary is shown in the following scheme. 

These are suprafacial sigmatropic shifts of order [1,5] and should occur with retention of configuration at the migrating carbon. This stereochemical course has been established for the 1,5-alkyl shift that converts 16 to 17. The product which is isolated, 18, results from a subsequent 1,5-hydrogen shift, but this does not alter the stereochemistry at the migrating... 

The following rearrangement was devised and carried out to prove the stereochemistry of [1,5] sigmatropic hydrogen shifts. Explain how the observed result confirms the predictions of orbital symmetry. 

The silicon- and sulfur-substituted 9-allyl-9-borabicyclo[3.3.1]nonane 2 is similarly prepared via the hydroboration of l-phenylthio-l-trimethylsilyl-l,2-propadiene with 9-borabicy-clo[3.3.1]nonane36. The stereochemistry indicated for the allylborane is most likely the result of thermodynamic control, since this reagent should be unstable with respect to reversible 1,3-borotropic shifts. Products of the reactions of 2 and aldehydes are easily converted inlo 2-phenylthio-l,3-butadienes via acid- or base-catalyzed Peterson eliminations. 

Thia-[2,3]-Wittig sigmatropic rearrangement of lithiated carbanions 47, obtained by deprotonation of the S-allylic sulfides 46, affords the thiols 48 or their alkylated derivatives 49. The corresponding sulfonium ylides 51, prepared by deprotonation of the sulfonium salts 50 also undergoes a [2,3]-sigmatropic shift leading to the same sulfides 49 [36,38] (Scheme 13). As far as stereochemistry is concerned, with crotyl (R R =H,R =Me) and cinnamyl (R, R =H,R =Ph) derivatives, it has been shown that the diastereoselectivity depends on the nature of the R substituent and on the use of a carbanion or an ylide as intermediate. 

During the course of the development of our group s alkylation/reductive decyanation strategy, a very reliable method for distinguishing between syn-and anfz-l,3-diols was discovered [17,18]. The acetonide methyl groups reliably display diagnostic C-NMR chemical shifts, allowing for stereochemistry to be determined simply by inspection (Fig. 1). Evans later extended the C-NMR chemical correlation to polypropionate chains [19,20]. 

The NOESY spectrum and H-NMR chemical shift assignments of 7-hydroxyfrullanolide are shown. Interpret the NOESY spectrum. What conclusions can you draw about the stereochemistry at C-6 and C-10 ... 

Cerniglia CE, JR Althus, EE Evans, JP Freeman, RK Mitchum, SK Yang (1983) Stereochemistry and evidence for an arene oxide-NIH shift pathway in the fungal metabolism of naphthalene. Chem-Biol Interactions 44 119-132. 

The stereochemistry, however, is sensitive to the concentration of chloride ion, shifting to anti when chloride is present.103... 

NMR provides one of the most powerful techniques for identification of unknown compounds based on high-resolution proton spectra (chemical shift type integration relative numbers) or 13C information (number of nonequivalent carbon atoms types of carbon number of protons at each C atom). Structural information may be obtained in subsequent steps from chemical shifts in single-pulse NMR experiments, homo- and heteronuclear spin-spin connectivities and corresponding coupling constants, from relaxation data such as NOEs, 7) s 7is, or from even more sophisticated 2D techniques. In most cases the presence of a NOE enhancement is all that is required to establish the stereochemistry at a particular centre [167]. For a proper description of the microstructure of a macromolecule NMR spectroscopy has now overtaken IR spectroscopy as the analytical tool in general use. 

Oxostephasunoline (4) was isolated from the roots of Stephania japonica(4). The UV spectrum of oxostephasunoline (4) showed an absorption maximum at 286 nm, and the IR spectrum depicted bands at 3550,3500, and 1670 cm, indicating the presence of a hydroxyl group and a y-lactam. The mass spectrum (Table VI) exhibited the most abundant ion peak at m/z 258, and the H-NMR spectrum (Table II) revealed the presence of three methoxyl and one N-methyl group. The downfield shift (53.06) of the JV-methyl resonance indicated that oxostephasunoline (4) was a y-lactam, which was further supported by the IR band at 1670 cm 1, significant features of the mass spectrum (Table VI), and the 13C-NMR spectrum (Table III). On exhaustive H-NMR analysis similar to the case of stephasunoline (17), the structure of oxostephasunoline (4) including the stereochemistry was practically proved (4). 

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