13964-48-2Relevant articles and documents
Fluorinated Pyrimidines. Part 4. Synthesis, Properties and Stereochemical Conversion of the cis and trans Isomers of 6-Alkoxy-5-fluoro-5,6-dihydrouracils
Visser, Gerard W. M.,Wedzinga, Rinny,Klok, Robert P.,Herscheid, Jacobus D. M.
, p. 231 - 236 (2007/10/02)
The reaction of 6-acetoxy-5-fluoro-5,6-dihydrouracil with ROH (R=Me, Et, Pr, Pri, Bu, But) under acidic conditions has been investigated using 18F as a tracer.The quantitative replacement of the OAc-group proceeded predominantly with cisoid (gauche) stereochemistry, but upon prolonged heating the amount of the trans compound increased.This isomerization did not originate from epimerization at C5.The trans compounds-apart from being more stable towards substitution and elimination than the corresponding cis compounds-gave invariably substitution products with inversion of configuration, while the cis compounds mainly retained their configuration.Within the concept of the unifying ion-pair mechanism it is proposed that the trans compound reacts via an intimate protonated intermediate and the cis compound via a solvent-separated protonated intermediate.As a result, it was not the gauche attraction between the fluorine atom and the incoming nucleophile, but the poor ?-donor ability of the C-F bond that was the determining factor in the cisoid stereochemistry of 5-fluoro-5,6-dihydrouracil adducts.
