1.3- Oxathiane, conformations

For oxathiane 1, lone pair selectivity is controlled by steric interactions of the gem-dimethyl group and an anomeric effect, which renders the equatorial lone pair less nucleophilic than the axial lone pair. Of the resulting ylide conformations, 25a will be strongly preferred and will react on the more open Re face, since the Si face is blocked by the gem-dimethyl group (Scheme 1.9) [3, 15]. 

The synthesis of the 2-acyloxathianes 3 makes use of the fact that for stereoelectronic reasons1, electrophilic attack on conformationally locked 2-lithiated oxathianes 1 leads exclusively to equatorially substituted products 2. A subsequent oxidation step completes the synthesis. 

Only structures pertaining to the saturated 1,2-oxathiane 2,2-dioxides have been published. The preferred chair conformer is preserved in both polycyclic <1989AGE202, 1998CEJ1480, 1996CC431, 1994JOC3687> and spiro derivatives <1998EJO2073> with the sulfone oxygens in pseudoaxial and pseudoequatorial orientations. 

Ab initio calculations at the MP2 level of theory of a collection of substituted 1,3-dioxanes, 1,3-oxathianes, and 1,3-dithianes have been employed to study both the position of the conformational equilibria and the validity of the Perlin effect <2005T7349>. The 7h,c coupling constant proved to be a valuable tool in conformational analysis both twist conformers, in addition to the chair and alternative chair forms, could be readily identified simply by comparing experimental Vh,c coupling constants to the corresponding calculated values in the particular forms. In addition, the Perlin and reversed-Perlin effects of the C2-H fragments, c in 1,3-dioxanes,... 

The semi-empirical theoretical study (AMI, PM3, and force field) of 2,2,5-trimethyl- 2,2-dimethyl-5- o-propyl-, and 5- T7-butyl-2,2-dimethyl-l,3-oxathiane 47-49 afforded the correct conformational equilibria as obtained by FI NMR spectroscopic conformational analysis <2001RJC1487>. The chair conformation is adopted while the substituent at position 5 is in an equatorial position. Furthermore, there was no indication for the presence of twist conformers. 

The topological theory of atoms in molecules <2003MI190> has been employed to calculate the conformational preference of monosubstituted 1,3-oxathianes. The preferred conformer results from an energy balance between the ring and the substituent. This method has proven to be general and is a new technique for conformational analysis. 

The publication of X-ray structures from 1996 onward has continued and altogether ca. 30 structures have been published. Bond and dihedral angles for the preferred conformation of the 1,3-oxathiane rings are determined by the ring fusion and/or attached substituents thus, published structures were classified as either monocyclic (mono), spiro-substituted (spiro), bicyclic (bi), or tricyclic (tri). For each of the four groups, derivatives were found and a comparison of the experimental bond lengths for the 1,3-oxathiane ring system with representatives of the different classes are... 

Table 6 Conformations and selected bond lengths (A) for 1,3-oxathianes in the solid state...

The solid-state structure of one benzo derivative of 1,3-oxathiane 96 has been studied the heterocyclic moiety was found to adopt a half-chair conformation with the aryl substituent in an equatorial position <1998JFA4002>. 

Interestingly, during a low-temperature study of the conformational equilibria, in addition to the generally observed chair conformation of the 1,3-oxathiane ring, a significant contribution of the 2,5-twist conformer (8-9% at 180 K) was also observed (Equation 10) <2005STC369>. 

Grosu and co-workers also studied the complex configurational and conformational aspects of the unique stereochemistry of substituted spiro-l,3-oxathiane derivatives 100-102 by NMR spectroscopy <2001T8751>. 

The HF, MP2, and DFT theories were used to calculate the optimized geometries and relative energies of the chair, half-chair, sofa, twist, and boat conformers of 1,2-oxathiane (02STC149). As the most stable conformation, in agreement with experimental results, the chair conformer was identified to be at least 4.6 kcal/mol more stable than the next conformer, the 3,6-twist conformation. As a comparison, the chair conformation of 1,2-oxathiane was found to be 9.6 and 10.0 kcal/mol less stable than the chair conformers of 1,3-oxathiane and 1,4-oxathiane, respectively (02STC149). 

The stereochemistry of a few substituted 1,2-oxathianes 77-79, freshly synthesized (98TL1251), was studied (cf. Scheme 28) the conformation of the substituents at the six-membered ring is in agreement with NOE enhancements and the characteristic ax I ax vs. ax/equ and equ/equ vicinal... 

The stereochemistry, physical and chemical properties and some transformations of 1,3-oxathianes, especially alkyl substituent effects on the preferred conformers, were reviewed (99MI73, 00MI17). Also 1,3-oxathiane and its 2-substituted homologs were theoretically calculated using the semiempirical AMI and PM3 methods (98MI14) the experimental parameters are adequately reproduced. In the case of 5-alkyl substituted... 

In addition, the X-ray crystal structures of two 1,4-oxathiane derivatives were published (00AX1510, 01AX560) the di-axial conformation of the hydroxymethyl group in position 3 and of the l,9-dihydro-6//-purin-6-one group in position 6 in compound 82 is surprising (01AX560) (cf. Scheme 30). The X-ray structures of the sulfones of the isomeric 2,6-di-OEt-3-OMe-l,4-oxathianes were published (00CEJ1858) the 4,4-dioxa-... 

The methods of synthesis, the configurational and conformational aspects of the stereochemistry and the main spectral properties and reactions of 1,3-oxathiane derivatives were reviewed after submitting the manuscript (2003H1477). 

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