Synthesis of 2‘,3‘-Didehydro-2‘,3‘-dideoxynucleosides by Reaction of 5‘-Protected Nucleoside 2‘,3‘-Dimesylates with Telluride Dianion:  A General Route from Cis Vicinal Diols to Olefins

Abstract

2',3'-Dimesylates of 5'-protected nucleosides are converted into the corresponding 2',3'-didehydro-2',3'-dideoxy compounds by treatment with telluride dianion in the form of the sodium or lithium salt. The method is well-suited to the preparation of unsaturated nucleosides that can be converted into compounds that are believed to be useful in the treatment of AIDS. The deoxygenation is general for vicinal dimesylates that have, or may adopt, a synperiplanar conformation. With straight chain compounds the reaction is stereospecific. In some cases, similar, but slower, deoxygenations can be performed with selenide dianion.

New Telluride-Mediated Elimination for Novel Synthesis of 2′,3′-Didehydro-2′,3′-dideoxynucleosides

“…In this reaction, dimethyl ditelluride is first reduced to methyl telluride monoanion. Via a S N 2 reaction, this strong telluride nucleophile attacks the R-2′-position of 2,2′-anhydronucleosides by substituting the 2-oxide as the intramolecular leaving group, which leads to formation of a substitution (or addition) intermediate (11). This intermediate undergoes elimination to give 2′,3′-olefin (12, d4N) and 1′,2′-olefin (13).…”

Synthesis of some monocyclic-N-acetyl 4′-aza-D-nucleosides

“…Thus, selective protection of the 5'-hydroxyl group of 17 with TBDMSCl gave the corresponding silyl ether which upon treatment with methanesulfonyl chloride gave fully protected intermediate dimesylate 29. The dimesylate upon reaction with freshly prepared telluride dianion [30] in tetrahydrofuran at room temperature for 16 h afforded the silyl-protected 2',3'-didehydro-3'-deoxy-4'-aza-thymidine 30. The silyl group in 30 was then removed using Et 3 N.3HF to afford 2',3'-didehydro-3',4'-dideoxy-4'-(acetamido)-D-thymidine 31 in 65% yield.…”

Why is RCM Favoured Over Dimerisation? Predicting and Estimating Thermodynamic Effective Molarities by Solution Experiments and Electronic Structure Calculations

“…Dienes 1 a-f are all commercially available and most cycloalkenes 3 are either commercially available (3 a-d and E-and Z-3 f) or known in the literature (3 e). [14] In addition, many of the dimers, products of cross-metathesis, are known (linear dimer 4 a [15] and cyclic dimers 5 c-f). [16] The experimental approach was described in our previous Communication, and utilises non-invasive 1 H NMR analysis to quickly quantify reaction outcomes without processing the reaction mixture.…”