Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

Abstract

The 5’-alkynylation of uridine-derived aldehydes is described. The addition of alkynyl Grignard reagents on the carbonyl group is significantly influenced by the 2’,3’-di-O-protecting groups (R1): O-alkyl groups led to modest diastereoselectivities (65:35) in favor of the 5’R-isomer, whereas O-silyl groups promoted higher diastereoselectivities (up to 99:1) in favor of the 5’S-isomer. A study related to this protecting group effect on the diastereoselectivity is reported.

Direct Access to Unique C‐5’‐Acyl Modified Nucleosides through Liebeskind–Srogl Cross‐Coupling Reaction

“…In contrast the C‐5’ position has been significantly less studied despite its potential importance for biological activity, both at the nucleos(t)ide [6] and oligonucleotide levels [7] . Aside from the multi‐step downstream nucleobase introduction via Vorbrüggen glycosylation, [8] the introduction of 5’ functional groups usually involves a 5’‐aldehyde which is submitted either to an olefination and subsequently functionalized (Figure 1a) [9] or to a nucleophilic addition reaction (Figure 1b) [6c,7a,b,10] . The reduction of a C‐5’ ketone obtained from Weinreb amides has also been described with success (Figure 1c) [3c,6a,11] .…”

Synthesis of β-Methyl Alcohols: Influence of Alkyl Chain Length on Diastereoselectivity and New Attractants of Rhynchophorus ferrugineus

“…The second factor is the polar effect that stabilizes a transition state with maximum separation between the nucleophile (Nu – ) and a large group (L). Although the stereoselective synthesis in the Felkin–Anh model has been explored extensively, − to the best of our knowledge, the influence of steric alkyl chain length has not been studied for diastereoselectivity. Here, we investigate the effect of alkyl chain lengths on the diastereoselective synthesis of β-methyl alcohols via the Felkin–Anh model.…”