Chair conformation tetrahydropyran

Typical carbon-oxygen bond distances m ethers are similar to those of alcohols (—142 pm) and are shorter than carbon-carbon bond distances m alkanes (—153 pm) An ether oxygen affects the conformation of a molecule m much the same way that a CH2 unit does The most stable conformation of diethyl ether is the all staggered anti conformation Tetrahydropyran is most stable m the chair conformation—a fact that has an important bearing on the structures of many carbohydrates... 

X-Ray analysis of hexahydrofuro[2,3- ]pyran derivative 39 shows that the tetrahydropyran ring assumes a chair conformation with the C(7a)-0(1) bond found in the axial position <1998T8753>. This conformation agrees with that obtained by analysis of the NMR spectrum of 39. 

In 3-bromo-7-methoxy-2-tetrahydropyran-2-ylpyrazolo[l,5-( ]pyrimidine 66, the pyrimidine and pyrazole rings make a dihedral angle of 3.8°. The tetrahydropyran ring is in a chair conformation and its mean plane makes an interplanar angle of 52.5° with the pyrazole ring. There is a short Br- -O intramolecular contact of 2.994 A <2004JSTC356>. 

Half-chair conformations have been established for the cis- and trans- tetrahydropyran-2-ones on the basis of IR, NMR and CD data (74JOC3890). In the case of the cis isomer, conformation (194) is preferred in order to avoid the 1,3-diaxial interactions of the 3- and 5-methyl groups, whilst a somewhat flattened conformation (195) is predicted for the trans compound. 

Formation of tetrahydropyran ring systems through 6-endo or 6-exo cyclization of substrates which lack 1,2-interactions of the type shown in equations (39) and (40), generally proceed with moderate selectivity for the diastereomer that would result from cyclization through chair conformations with equatorial substituents.7- n o, 131 b, 142,143... 

Pyranose derivatives adopt chair conformations unless an unusual combination of destabilizing interactions is present. Angyal developed a set of destabilizing interactions that can be used to estimate the relative stabilities of the two chair conformers in aqueous solution [125,126]. These values were determined before many of the A-values discussed above for cyclohexane and tetrahydropyran derivatives were measured and are formulated in terms of 1,3-diaxial... 

The most frequently used measure of the anomeric effect is based on the comparison of the stabihty of 2-substituted oxane (tetrahydropyran THP) and cyclohexane. In general, conformational properties of the oxane ring are similar to those of cyclohexane, with dominance of a chair conformation. It is further presumed that steric interactions in oxane are the same as in cyclohexane, with preference for equatorial positions of bulky substituents. The Gibbs energy of the anomeric effect, AG(AEl), can be expressed as the... 

The length of the C-O bond in ethers is generally taken as 1.43 whereas the length of an unstrained C C bond is around 1.53 This makes tetrahydro-pyran slightly less puekered than eyelohexane. In eyelohexane chemistry, conformational preferences are discussed in terms of A values for substituents (the free energy dilference between the axial and equatorial chair conformers of a monosubstituted cyclohexane). These A values for cyclohexane carmot be applied directly to tetrahydropyran, " even in the absence of an anomeric elfect, not least because they vary with the position of substitution, even with non-polar substituents which do not exert an anomeric elfect (Table 2.1). 

Glucose is an equilibrium mixture of cyclic forms (hemiacetals containing a tetrahydropyran), and a small concentration of acyclic polyhydroxyaldehyde, which is responsible for many of the observed chemical reactions. This illustrates the inherent stability of chair conformers of saturated six-membered systems. The propensity for cyclisation is a general one 5-hydroxy-aldehydes, -ketones and -acids all easily form six-membered oxygen-containing rings - lactols and lactones respectively. 

The same pattern is seen, with only one lone pair, in tetrahydropyrans, when nucleophiles like allylsilanes and allylstannanes attack axially in Lewis acid catalysed reactions in pyranyl sugars.562 The same pattern is also found in imminium ions563 as Stevens demonstrated in several syntheses. He showed that nucleophiles attack from the direction that most easily sets up an anti and axial lone pair, especially if it can create a chair conformation, as in the reduction of the imminium ion 5.143 to give monomorine-I 5.144.564... 

SThe structure of tetrahydropyran in the gaseous state has been determined by electron diffraction and microwave spectroscopy. These show that the saturated oxygen six-membered ring exists in a chair conformation with Q symmetry (see Fig. 6.5), which is somewhat flattened when compared with cyclohexane ... 

In another example, as a model study for an investigation of the conformations of certain D-glucosides and polysaccharide derivatives, the comparison of observed dipole moments with values calculated from bond-moment data was used to demonstrate that, in carbon tetrachloride solution, tetrahydropyran exists in a chair conformation, and that 2-chlorotetrahydropyran exists in that chair conformation having the C-Cl bond axially disposed. 

Tetrahydropyran, like piperidine, adopts a chair conformation. One of the interesting aspects to emerge from studies of alkoxy-substituted tetrahydropyrans is that when located at C-2, alkoxyl groups prefer an axial orientation (the anomeric effect °). The reason for this is that in an equatorial orientation there are unfavourable dipole-dipole interactions between lone pairs on the two oxygen atoms, and the energy gain, when these are relieved in a conformation with the C-2-substituent axial, more than offsets the unfavourable 1,3-diaxial interactions which are introduced at the same time. 

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