3- tetrahydropyran conformational analysis

This article deals with the conformational analysis of substituted oxanes (tetrahydropyranes) and derivatives in which ring methylenes are replaced by further oxygen atoms (di-, tri-, tetroxanes, pentoxanes, and O ) or by carbonyl group(s) (oxanones, Meidrum s acid derivatives) and, if conforma-tionally of interest, systems incorporating these rings in polycyclic structures... 

From a study of a range of 2-substituted tetrahydropyrans it was concluded that the effects of an electronegative substituent were to deshield C-2 by about 30 p.p.m. and C-3 to a much reduced extent (ca. 4 p.p.m.), but to cause small upheld shifts in the signals from C-4, C-5 and C-6 (740MR(6)233). The influence of a 2-substituent on the chemical shift of C-4 can be used for quantitative conformational analysis provided suitable reference compounds are available. A comparatively large shielding of the C-4 signal indicates a preference of the 2-substituent for the axial position. 

Recently, only the conformational analysis of 4-hydroxy-tetrahydro-pyran 38 and of 2-(hydroxymethyl)-tetrahydropyran 39 was published (98JCS(P2)1751). The low temperature i I NMR study of 38 gave 8.5%... 

Eliel EL, Hargrave KD, Pietrusiewicz KM, Manoharan M (1982) Conformational analysis. 42. Monosubstituted tetrahydropyrans. J Am Chem Soc 104 3635-3643... 

AS is -2.7 calK mol for the conversion of the axial (oC) conformer to the equatorial (/9) conformer in an 85s 15 mixture of trichlorofluoromethane-trichlorodeuteromethane. Conformational energies of C-2 carbon-substituted tetrahydropyrans form the basis of an important paper on the conformational analysis of such compounds. The values obtained will be of use in the field of -glycosides. An exception to the Imbach criteria for determining the anomeric configuration of D-ribofuranosyl nucleosides has... 

With the conformational analysis in mind, our investigation commenced with the stereoselective formation of 2,3-trani-2,6-tran5-tetrahydropyrans. To determine the feasibility of the oxa-conjugate addition reaction for the stereoselective synthesis of 2,3-frans-2,6-trans-tetrahydropyrans, allyl alcohol (Z)-2.38a was prepared by dithiane coupling of (Z)-2.36 with (5)-glycidyl benzyl ether (2.37a) and subsequently subjected it to the tandem oxidation/oxa-conjugate addition reaction... 

The cyclic dimer, tetramer, and hexamer can be crystallized in acetonitrile, and also in chloroform (the former two oligomers). X-ray analysis of the crystals of the cyclic dimer47 disclosed that it consisted of a pair of different enantiomers of 53 and that all of the four substituents attached to the two tetrahydropyran rings occupied the axial position as illustrated in Fig. 54s). Such a conformation is in... 

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. 

The X-ray crystallographic analysis of thyrsiferol 18-acetate (5) revealed a strained tetrahydropyran ring C in a twist-boat conformation so as to avoid 1,3-diaxial interactions between the methyl groups at Cio and Cl 5. Initial biological studies of the natural product by Munro et al did not reveal any significant pharmacological activity [4]. 

The absolute configuration, i.e. S,S), of a tetrahydropyran (17) that is present in civet Viverra civetta) has been determined, using a chiral shift reagent [Eu(hfc)3] and 360 MHz n.m.r. spectroscopy in comparison with a synthetic sample of (+)-(5,5)-(17) and its methyl ester.X-Ray analysis was applied to the determination of the conformation of the violet form of cunaniol acetate (18), which was shown to have an undistorted chair form with both substituents equatorial. An e.p.r. spectral study has shown that the radical which is formed from several stereoisomeric 2,4-disubstituted tetrahydropyrans is the same, namely the cis-2-alkoxy-4-methyltetrahydropyran-2-yl radical. 

According to NBO analysis, the key component of anomeric effect is the negative hyperconjugative interaction between the lone pair of X and the low-lying a C-Y orbital. When both X and Y have at least one lone pair, a more balanced description also involves n <7 c.x donation in the opposite direction. For the 2-alkoxy-substituted tetrahydropyrans, the overall conformational profile originates from the combination of n c-o hyperconjugative interactions, responsible for both the endo- and exo-anomeric effects (Figure 6.56). 

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