A Study on the Conformation−Anomeric Effect−Stereoselectivity Relationship in Anomeric Radical Reactions, Using Conformationally Restricted Glucose Derivatives as Substrates

Abstract

We previously theorized that, since the stereoselectivity of anomeric radical reactions is significantly influenced by the kinetic anomeric effect, which can be controlled by restricting the conformation of the radical intermediate, the proper conformational restriction of the pyranose ring of the substrates would therefore make highly alpha- and beta-stereoselective anomeric radical reactions possible. This theory was based on our previous results of the anomeric radical reactions with d-xylose derivatives as the substrates. We herein report the anomeric radical deuteration reactions with the conformationally restricted 1-phenylseleno-d-glucose derivatives, 2g and 3g, restricted in a (4)C(1)-conformation by an O-cyclic diketal moiety, and 4g, 5g, 6g, 7g, and 8g, restricted in a (1)C(4)-conformation by bulky O-silyl protecting groups. The radical deuterations with Bu(3)SnD, using the (4)C(1)-restricted substrates 2g and 3g, afforded the corresponding alpha-products (alpha/beta = 98:2) highly stereoselectively, whereas the (1)C(4)-restricted substrate 6g, having a trigonal (sp(2)) carbon substituent, i.e., -CHO, at the 5-position, selectively gave the beta-products (alpha/beta = 0:100). Thus, the stereoselectivity was significantly increased by the conformational restriction and was completely inverted by changing the substrate conformation from the (4)C(1)-form to the (1)C(4)-form. On the other hand, the deuterations with the (1)C(4)-restricted substrates 4g and 5g showed that the 1,5-steric effect due to the tetrahedral carbon substituent (-CH(2)OTIPS or -CH(2)OH) at the 5-axial position dominantly prevented the hydride transfer from the beta-face competing with the kinetic anomeric effect. This study suggests that, depending on the restricted conformation of the substrates to the (4)C(1)- or the (1)C(4)-form, the alpha- or beta-products would be obtained highly stereoselectively via anomeric radical reactions of hexopyranoses.