Conformation, lanthanide-induced shifts

A study195 based on the NMR lanthanide-induced shifts (LIS) for a series of cis- and trans-3-substituted, and 3,3-disubstituted thietane oxides concluded that all cis-substituted oxides (5c R = CH3, t-Bu and aryl) exist exclusively in the diequatorial conformation. The trans-3-substituted isomers (185) prefer the equatorial oxygen conformation (R = CH3,86% t-Bu, 65-75% aryl, 75%), which means an axial preference for the substituents (e.g. 185d), at least when they are bound to a shift reagent (equation 75). 

Computer simulation of lanthanide-induced shifts in the 2-formyl and 2-acetyl derivatives of furan, thiophene, selenophene, and tellurophene108 indicate a nearly equipopulated mixture of trans and cis conformers of the furan, and a preponderance of the cis for the thiophene, selenophene, and tellurophene derivatives. This difference is due to an interaction between the ring heteroatom and the carbonyl oxygen lone pair electrons. 

Hofer, O., The Lanthanide Induced Shift Technique Applications in Conformational Analysis, 9, 111. 

Lanthanide-induced Shift Technique - Applications in Conformational Analysis/Hb/er 9 111... 

Conformational Analysis, Applications of the Lanthanide-induced Shift... 

Lanthanide-induced Shift Technique— Applications in Conformational... 

This technique (see Section 4.1.1.4.) is well suited to the exploration of double-bond configurations. This is because these compounds arc often rigid and therefore there are no conformational rearrangements to complicate lanthanide induced shift (LIS) interpretations. However, if present, mobile groups within a molecule must be taken into consideration. 

Early work on the experimentally established conformational preferences in solution for a variety of other 2-substituted heterocycles is summarized in Table 30. Most of these conclusions have been deduced either from dipole moment measurements in benzene or by the use of lanthanide induced shifts for chloroform solutions. The aforementioned MO studies correctly predict the preferred conformations, (63, R = H) or (64, R = H), of pyrrole-2-carbaldehyde, thiophene-2-carbaldehyde and furfural in the gas phase. 

An improved lanthanide-induced shift analysis technique that employs Yb(fod)3 was used to investigate the conformation of a number of lactones including 3,4-dihydrocoumarin (fod = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octadione). These studies indicate that both C-2 and C-3 are displaced from planarity to give a puckered conformation to the lactone ring <1997J(P2)1279>. 

A lanthanide-induced shift analysis of tetrahydrothiopyran 1-oxide based on calculated geometrical parameters indicated that the equilibrium mixture contained ca. 45% of the equatorial conformer in CDCI3 solution. However, the conformational equilibrium is solvent dependent, with the equatorial conformer predicted to be favored by polar solvents. The calculated dipole moments for the equatorial and axial conformers are 4.39 and 4.17 D respectively, which compare favorably with the experimental value of 4.19 D <1994J(P2)2329>. 

Lanthanide-induced Shift Technique—Applications in Conformational Analysis... 

The goodness of fit between observed and calculated shifts needs to be assessed, and methods of performing significance testing of lanthanide-induced shifts have been evaluated and reviewed . Complexities arise when fitting lanthanide shift data for compounds with conformationally mobile groups . Procedures for fitting free and hindered rotation have been described . Reviews of the utilization of lanthanide-induced shifts for conformational analysis have been published , and studies to further refine the utilization of lanthanide-induced shift data for such analyses continue . ... 

X-Ray crystallography has also established that dihydrothiazine imines have similar conformations. For example, compounds 36 and 38 were found to have half-chair conformations (cf. Scheme 1-IV), once again with the sulfur-heteroatom bond quasi-axial. Adduct 37 was correlated with 36 by lanthanide-induced shift H-NMR experiments, and the data have been interpreted as supporting this same type of conformation. ... 

Barriers for interconversion between BC-3 and its enantiomer, BC-7, have been calculated. Passage through either a BC-5 or a BC-1 conformation, are calculated to be 5.0 kcal mol and 6.7 kcal mol , respectively. The small barriers allow for a rapid pseudorotation between BC-3 and BC-7, even at low temperatures, and account for the symmetric spectra. NMR results on oxocane-2,2,7,7-d4 have allowed a definitive assignment for the H and C chemical shifts. Lanthanide-induced shift reagents provide compelling proof, that the lowest energy conformations are BC-3 and BC-7. 

Determination of Absolute Configuration and Solution Conformation. Abraham et have employed H and C lanthanide induced shifts produced by Yb(fod)3 as an experimental probe of the solution conformations of cyclopen-tanol and cis- and trans-cyclopentane-l,2-diol. Analysis of the LIS was undertaken in conjunction with molecular mechanics and ab initio calculations of structure. 

More recently, Abraham and coworkers [18] reexamined the conformational behaviour of thiane-l-oxide (3) by analysis of lanthanide-induced shifts (LIS) in the appropriate NMR spectra. Their results compare reasonably well with those obtained by Barbarella et al. [17], suggesting the applicability of the LIS method to sulfoxide conformational analysis. 

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