Stereoelectronic Effects of Substituents Polyhydroxylated Piperidines and Sugars

1 Stereoelectronic Effects of Substituents Polyhydroxylated Piperidines and Sugars 

A very interesting article on the stereoelectronic substituent effect appeared recently [22] in which Jensen and Bols examined the influence of the orientation of a substituent on a pyranose, piperidine, isofagomine, etc., ring upon the chemical properties and the reactivity of this six-membered ring molecule. Thus, they compared the pKa values of isofagomine 60 and its three stereoisomers 61, 62, and 63 (Fig. 5.18) [23, 24]. 

5 Armed-Disamed Concept in the Synthesis of Glycosidic Bond 

Overall, the axial OH groups decrease the base strength when compared to the corresponding deoxy derivative. A 4-OH increases basicity by 0.4 pH units when placed axially rather than equatorially. 

Jensen et al. [23], studied more than 60 different hydroxylated piperidine and hexahydropyridazines, and the measured stereoelectronic effects are summarized in Table 5.1. The value of each substituent is the basicity decreasing effect in pK units. As can be seen, the axial OH decreases the base strength of the amine by 0.5 and 0.2 units when it is in the p- and y-positirai, respectively, relative to the amine, while the equatorial OH decreases the pKa by 1.3 and 0.6 in those instances. Thus, the equatorial OH is significantly more electron-withdrawing than the axial OH. 

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