Silylated 5-fluorouracil

In MeCN/Cl(CH2)2Cl in the presence of SnCU silylated co-hydroxy-acetals such as 1422 react, via cations such as 1423, with silylated 5-fluorouracil 1424 to afford, after aqueous work-up, 84% of the nucleoside analogue 1425 and MeOSiMe3 13 a [7] (Scheme 9.5). 

This type of nucleoside includes numerous simple derivatives of heterocyclic compounds. Only a few examples are given. Condensation of the chloro-methyl ethers 1053 with silylated 5-fluorouracil gave the two mono- and one disubsituted derivatives 1054,1055, and 1056, respectively (86MI3). 

The best solvent, temperature, and Lewis acid conditions for the Sn reactions of CRS)-l-(2-mtrobenzenesulfonyl)- and (7 5 )-l-(4-nitrobenzenesulfonyl)-3-methoxy-l,2,3,5-tetrahydro-4,l-benzoxazepines with silylated 5-fluorouracil and uracil129 proved to be SnCL at 50 °C in MeCN. The more nucleophilic silylated uracil reacts faster at its N(3) atom giving mainly the cyclic 0,N-acetal (by C-OMe cleavage). The silylated 5-fluorouracil, on the other hand, reacts at its less sterically hindered N(l) atom and gives mainly an acyclic product (by ring C-0 cleavage). Calculations at the HF/6-31G level of theory support the experimental observations. 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

For the preparation of /V-2-methacryIoyloxyethyl-5-fluorouracil (MAOFU), which is a typical polymerizable monomer containing 5-FU, the silylated 5-FU (1) was allowed to react with 2-bromoethyl methacrylate in acetonitrile at refluxing temperature the decomposition of the silylated compound followed in a manner similar to that described previously [27]. MAOFU was obtained in 20% yield. When no solvent was used, the yield was extremely low, as is the reaction of silylated uracil with 2-bromoethyl methacrylate [27],... 

Condensation of 2-(benzyloxy)ethanol with a mixture of the hydrate and methyl hemiacetal of methyl glyoxalete 638 gave a hemiacetal, which was converted directly with methanesulfonyl chloride to a-chloro ether 639. It condensed with silylated uracil, 5-fluorouracil, and A -acetylcytosine,... 

---