Heating of 1-N-benzyl-5-iodouracil 1   (R = Bn) in benzene or benzene/DMF (1:9/v:v) at 100 oC for 1 h in the presence of TBAF (7 equiv.) and Pd2(dba)3 afforded 5-phenyluracil coupling product 2   (70%) in addition to the reduced substrate. Cross-coupling of 1   with electron-rich furan in DMF with 3.5 equiv. of TBAF provided 5-(fur-2-yl)uracil 2   (R = Bn, Ar = fur-2-yl) in 95% yield. Coupling of 1   proceeded smoothly with other p-excessive heteroarenes such as thiophene, 2-substituted thiophenes, benzo<b>furan or pyrrole to give 5-arylated uracils of type 2   (60-90%). This direct arylation of the C-5 position of the uracil ring has a general character, hence, 5-iodouridine 1  (R = ribosyl or 2',3',5'-tri-O-acetylribosy), 2'-deoxy-5-iodouridine 1  (R = 2'-deoxyribosyl) or 1-(�,D-arabinofuranosyl)-5-iodouridine 1  (R = arabinosyl) coupled with electron-rich heteroarenes to give 5-aryluracil nucleosides of type 2   (55-90%). The 1-N-benzyl-3-N-methyl-5-iodouracil did not undergo coupling with arenes under described conditions indicating that C4-alkoxide, from the enol form of uracil, can participate in the intramolecular processes of hydrogen abstraction.

TBAF-promoted Pd-catalyzed direct arylation of 5-iodouracil nucleosides

247th National Meeting (2014)

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