1.3- dioxane derivatives, conformational

Also, 2,2,3,6-tetra-Me-5-Cl-l,3-dioxan, due to 1,3-diaxial interactions, prefers the 2,5-twist-boat form (76BSF563) the same conformation was reported for the stereoisomeric 2-Ph-4-(2 -furyl)-5-N02-6-Me-l,3-dioxanes and 2,2,6-tri-Me-4-(2 -furyl)-5-N02-l,3-dioxanes (75MI2), for 2-Alk-2,4,4-tri-Me-l,3-dioxane derivatives (78KGS1172) and for the cis isomers of 2-OR-4-Me-l,3-dioxane (R = Et, nPr, /Pr, nBu, n-CsHn) (81DOK116). The corresponding trans isomers adopt the chair conformation with di-eq substitution. The isomeric 2-OR-4,4-di-Me-l,3-dioxanes also prefer the 1,4-twisted-boat conformer (81DOK116). 

The presence of twist-boat forms in the conformational equilibria of 1,3-dioxane derivatives due to the presence of 1,3-diaxial interactions was corroborated by force field calculations [77T2237 79T691, 79T1945]. 

The conformations of three 2,2 -disubstituted-l,3-dioxane derivatives 65-67 have been elucidated by NMR spectroscopy <1998CHE141, 1999PAC385, 2001ARK(xii)7> only the conformers with the more polar substituent in an axial position have been assessed as being in agreement with the anomeric effect. 

Toward a screening program for RhuA stereoselectivity, structurally more simplified dioxane derivatives 25-27 comprising enantiomeric and diastereomeric 3-hydroxyaldehyde geometries in a conformationally defined environment could be prepared easily from carbohydrate precursors (Scheme 2.2.5.10). First results from product analysis provide further evidence for occasionally biased fixation of... 

Haworth formulas) to form the dioxane derivative (65), rather than (64), which would have a 1,3-diaxial interaction between the aldehyde and methoxyl groups. The conformational changes involved in typical reactions of periodate-oxidized methyl a-D-glucoside are detailed in Fig. 1. 

Several values of the magnitude of the anomeric effect, AG, based on Franck s methodology (Section II.C) and calculated by us (54, 78, 98, 173, 354) for 2-substituted 5,5-dimethyl-l, 3-diheteroanes are collected in Table 19 (penultimate column) together with the appropriate values obtained by Juaristi s group (last column). The differences between these two sets of values can easily be explained as due to different methods of estimation of Fq factors (see Section II.C), different compounds studied, and different conformational probes applied. Nevertheless, except for dioxane derivative 110 (X = Y = O) the trends are the same. 

A calix[4]arene substituted at the upper-rim VIg was synthesized from calix[4]arene-0-tetra pentyloxy derivative conformationally fixed at the low rim by alkyl chains and substituted with two nitro groups and two phenolic hydroxyls at the wide rim in the opposite positions at the platform. After 0-alkylation with two equivalents of the CD-dioxane derivative and on reduction of the nitro fnnctions to the ammonium group, two CMPO functions were introduced by reaction with the active ester ae-1 (see Figure 19.3, VIg) (Griiner et al, unpublished results). However, in contrast to organic upper-rim CMPO calix[4]arenes (Schmidt, 2003), a lower separation efficiency was observed for this compound with respect to the low-rim series. This can be possibly explained by a different complexation mode. No An +/Ln2+ selectivity was observed, similarly as for the low-rim series. 

Benzyl derivatives of (1 6)-a-D-glucan, (l->6)-a-D-mannan, and (l-> 6)-a-D-galactan have been studied in 1,4-dioxane. These derivatives have complex and interesting c.d. spectra due to the ww transition of the chromophore with resolved vibrational structure. However, a conformational interpretation of these interesting spectra is not possible at this time. 

C. 1,3-Dioxanes and Derivatives 1. Conformation of the 1,3-Dioxane Ring System... 

Conformation of l,3-Dioxan-2-ones, l,3-Dioxan-4-ones, and Meldrum s Acid Derivatives... 

Pihlaja and Rossi [83ACSA(B)289] prepared l,3-dioxan-2-one and all of its methyl derivatives, recorded their C NMR spectra, and derived the methyl substituent shift parameters by a multiple linear regression analysis of the anancomeric and two equivalent chair conformers (Table X). With these values, the authors estimated the conformational equilibria for two unequally populated chair conformations (Nos. 2, 3, 9, 11, and 14 in Table X). A consistent picture of the predominance of the chair conformation and the corresponding chair chair equilibria in l,3-dioxan-2-ones was obtained in complete agreement with earlier H NMR results. 

The X-ray structures of two l,3-benzodioxin-4-one derivatives (28 in Scheme 17) were reported [83T3151 90AX(C)2416] the dioxane ring was present in a half-chair conformation with the alkoxy (phenoxy) substituent in an axial orientation. 

As in the case of the 1,2-dioxins, the 1,2-dithiins exist in various states of saturation, oxidation, and benzoannelation (cf. Scheme 1, 17-27) and they have been studied in detail both theoretically and experimentally. Not only were the conformations of the ring and attached substituents investigated, but the valence isomerism of 1,2-dithiin by both NMR and high-level ab initio molecular orbital (MO) calculations and the dithiol/disulfide equilibrium by MP2 calculations were also examined. The latter equilibrium has been applied successfully as a luminescent molecular switch (cf. Section 8.10.2.1). Finally, as a very interesting 1,2-dithiin derivative, the synthesis, structure, and reactivity of the (-l-)-camphor-derived analog 25 and its sulfoxide 26 and sulfone 27 have been reported. Both the synthesis and the antimalarial activity of the 2,3-dioxabicyclo[3.3.1]nonane pharmacophore 28, which contains the 1,2-dioxane moiety, have been reviewed recently <2006BML2991>. 

Simple calculations (MM2 and HF/6-31G ), supported by a low-temperature NMR study, reveal that 2-NMc2-l,3-dioxane and the 5,5-dimethyl derivative exist exclusively in the conformation with the dimethylamino group in axial position <2001ARK(xii)58>, and DFT calculations at the B3LYP/6-31G(d,p) level of theory show that the anomeric effect of 2-Cl in 1,3-dioxane is of stereoelectronic origin while 2-F, 2-OMe, and 2-NH2 substituents on the same molecule are not <2000MI42>. 

An enormous number of different 1,3-dioxane structures have been reported since 1996 in Figure 3, mono-, bicyclic and spiro variants are presented, while Figure 4 contains examples of tricyclic structures with the 1,3-dioxane moiety. The conformations, bond lengths, bond and dihedral angles of the 1,3-dioxane rings are determined by the ring fusion, the attached substituents, and the presence of exocyclic double bonds. Thus, published structures are classified as either monocyclic (mono), spiro-substituted (spiro), bicyclic (bi), or tricyclic (tri). The well-known Meldrum s acid derivatives (M) have been most intensively studied. 

For each of the five groups, many derivatives were found and a comparison of the experimental bond lengths for the 1,3-dioxane ring system with representatives of the different classes are presented in Tables 2 and 3. The chair proved to be the most stable conformer and was obtained in all kinds of structures, though often some were in fact twisted. In addition to twist and boat conformers, also sometimes twisted when exocyclic double bonds were present, the corresponding half-chair conformers were also obtained. 

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