4- Hydroxy-tetrahydropyran, conformational

A number of pyrans, including 3-hydroxy-tetrahydropyran (both axial conformer, 29 and equatorial conformer, 30), 2-methoxy-tetrahydropyran 33, 3-methyl-tetrahydropyran 32, and several 4-substituted tetrahydropyrans, along with 2-methyl-l,3-dioxolane and the rigid cyclic ethers 7-oxabicyclo[2.2.1]heptane and 1,8-cineole, were studied extensively by NMR. These empirical results, in conjunction with the literature data for a variety of acyclic and cyclic ethers, were used to examine the reliability of O-substituent chemical shift models in these systems. The empirical data correlate well with predictions made from the model and it is concluded that ethereal oxygen substituent chemical shifts are due to both steric and electrostatic terms <1998J(P2)1751>. 

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%... 

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. 

We shall now consider the cleavage of each of the above hemi-orthoester con-formers under stereoelectronic control just as we dealt previously with the cleavage of the important orthoester conformers first, 96a will cleave to the hydroxy Z-ester 98, as shown in Eq. 25 second, 96b will not cleave and constitute the neutral conformer third, 96c will cleave to the hydroxy E-ester 99, as shown in Eq. 26. Interestingly, neither of 96a and 96c can cleave to a lactone because no ring oxygen electron pair orbital is in stereoelectronic effect with the equatorial aC-OMe bond. Thus, in instances where the tetrahydropyran ring cannot easily undergo chair inversion, lactone will not be formed. Additionally, since the Z-ester is more stable than the E-ester, hydrolysis will take place preferentially via the conformer 96a and the hydroxy Z-ester 98 will be formed. 

Three papers have reported the results of studies with simple tetrahydropyrans. 2-Hydroxytetrahydropyran has been shown to adopt a conformation placing the hydroxy-group in an axial orientation, whereas the amino-group in related 2-aminotetrahydropyrans favours an equatorial orientation. Both 3-chloro-and 3-bromo-tetrahydropyrans show a preference for the conformation in which the halogeno-group is equatorial. The conformational equilibria of the nucleoside analogues (442) have also been studied the proportion of the... 

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