10.1021/ja0524043
The study investigates the factors controlling the highly R-selective C-glycosylation of ribose derivatives by examining the stereoselective reactions of 18 ribose analogues with varying substitutions at C-2, C-3, and C-4. The researchers found that the electronic nature of the substituents, particularly the C-3 alkoxy group, dominates the selectivity of these reactions. The lowest energy conformers of the intermediate oxocarbenium ions display the C-3 alkoxy group in a pseudoaxial orientation to maximize electrostatic effects, while the C-2 substituent prefers a pseudoequatorial position. The alkyl group at C-4 has little influence on conformational preferences. The study used ribose-derived acetals, such as glycosyl fluoride 1 and acetal 10, as well as various substituted acetals like 2-deoxyribose derivatives, 2-benzyloxy acetate, and acetals with different C-4 substituents, to demonstrate that the product formation occurs through stereoelectronically preferred inside attack on the lowest energy conformer. The findings provide insights into the stereoselective synthesis of substituted tetrahydrofurans and furanosides, which are prevalent in biological systems and have therapeutic potential.
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