1.3- Dithiolane, conformation

For 1,3-dithiolanes the ring is flexible and only small energy differences are observed between the diastereoisomeric 2,4-dialkyl derivatives. The 1,3-oxathiolane ring is less mobile and pseudoaxial 2- or 5-alkyl groups possess conformational energy differences (cf. 113 114) see also the discussion of conformational behavior in Section 4.01.4.3. 

Dithiolane (132) derivatives also possess non-planar skeletons the most important conformation is probably of symmetry C2 (half-chair). The dithiolane ring may be quite flexible and a minimum energy. conformation is only well defined if there is a bulky substituent at the 2-position. 

The substitution of a heteroatom for an a-sulfoxy methylene group substantially increases the preference for an axial orientation of the sulfoxide oxygen320, despite the smaller space requirement of the sulfur with its lone pairs, compared to that of a methylene group321, at least in the case of 1,3-dithiolane oxides. The substituting heteroatom, therefore, should decrease the conformation stability (i.e. lower the barrier to chair-chair interconversion). 

Conformational and electronic structure considerations are the main subjects treated in studies on dithiolanes and related open-chain species123 124 129 of the structures I and n. 

Thiosulfonium ions derived from methylation of substituted 1,2-dithianes (94a) were found to exist in undistorted chair conformation with the methyl group in axial position.254 The phenomenon was interpreted to result from minimizing electron repulsion in orthogonal position (94b) (ab initio calculation at STO-3G //STO-3G level). Unlike 1,2-dithianes, methylation of 1,2-dithiolanes and substituted thianes to form the corresponding. S -methylsulfonium hexafluorophosphate and perchlorate salts255 is non-stereoselective. 

It is interesting to note that tetrathiafulvalene (S) is not planar but rather slightly distorted into a chair conformation (71CC889). Also the five-membered ring of the 1,3-dithiolane... 

The molecular and electronic structures of cyclic disulfide cation radicals of 1,2-dithietane 6 and 1,2-dithiete 7, and radical cations of 1,2-dithiolane 2 (2a-c represent stable conformations determined in terms of the symmetry restriction of Cs, Cz, and Czv), with emphasis on the nature of a two-center three-electron (Zc-ie) sulfur-sulfur bond have been examined by ab initio molecular orbital (MO) calculations <1997JMT(418)171>. Unrestricted Hartree-Fock (UHF)/ MIDI-4(d) computations showed that this bond in organodisulfide radical cation 2 is shorter in comparison to 1,2-dithiolane 2 and possesses partial Jt-bond character (structure A), as previously implied by electron spin resonance (ESR) spectroscopy <1982JA2318>, which correlates best with the form as the most favorable conformation of the cation radical 2. Contrary to the repulsive S-S interaction in the parent 1,2-dithiolane arising from the lone pairs of electrons, the hemi-7t-bond formed by one-electron oxidation should stabilize the five-membered ring of 2, or, for example, a similar cation radical of LA 3 which is involved in diverse biochemical reactions. 

In a study related to the conformational properties of the cyclohexane-fused six-membered heterocycles, new bicyclic dithiolanes, 285-/ra r (Scheme 52) and 285-crr (not shown), were prepared along the reaction pathway, as precursors used further for the syntheses of 2-methyl substituted and unsubstituted /ra r-fused 4a,5,6,7,8,8a-hexahydro-2//,4//-1,3-benzodithiines, exemplified by structure 288-/ra ir (R=R = H) <2002JOC1910>. Thus, ditosylation of cis-Z-hydroxymethyl cyclohexanol 284, and subsequent reaction with sodium sulfide and sulfur, provided a mixture of new bicyclic products 285 and 286, albeit in very low yields, with configurational inversion at C-1. These were reduced by LiAlH4 to provide /ra r-2-mercaptomethyl cyclohexanethiol 2 l-trans. Upon acetalization or transacetalization, the desired 2SS-trans derivative was obtained. The same methodology with the precursor 2E4-trans was extended to the preparation of the r-fused bicyclic compounds 285-288. 

The first peptides with an incorporated 4-amino-l,2-dithiolane-4-carboxylic acid residue (Adt), represented by structures 319 <2000BMCL1585>, 320 <2002BMCL147>, and 321 <2005PES104>, were synthesized in order to restrict their conformational mobility and stabilize defined secondary structures, thus making them chemically more stable and biochemically active. 

The relationship between spectroscopic properties and conformation and configuration of 1,3-dithians and 1,3-dithiolans continues to attract interest, and some recent reviews contain relevant information. - Anteunis and his associates have shown that the geminal coupling constant at C(2) in 1,3-dithians and 1,3-diselenans can be predicted by an equation which takes into account the electronegativity of the heteroatoms, the bond lengths... 

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