Regioselective functionalizations of at the positions N-1 and C-5 of pyrimidine bases

Abstract

An efficient method for the synthesis of 5-iodonium salts of the substituted pyrimidine nucleosides has been found. It has been exploited that the 5-phenyliodonium salt of the pyrimidine nucleosides cross-couples with various functionalized counter parts, i. e., vinylstannanes, alkynylstannanes, and vinylboronic acid in the presence of palladium catalyst. It has been found that alkylcuprate reagents were rapidly coupled with iodonium salt of uracil derivatives. Palladium catalyzed coupling reaction of 5-phenyliodonium triflate uracils with 2,3-dihydrofuran was carried out in DMF at room temperature afforded C-5 glycoside. Phenylsulfenylation or phenylselenenylation at the 5-position of pyrimidines were successfully achieved by the reaction of diphenyl disulfide or diphenyl diselenide with [bis(trifluoroacetoxy)-iodo]benzene in acetonitrile in good yields. A regioselective allylation at N-1 position of pyrimidine derivatives has been successfully performed by palladium catalyzed coupling of silylated pyrimidines with allyltributyltin in tetrahydrofuran at 65℃.