Nucleosides and Nucleotides. 163. Synthesis of 3‘-β-Branched Uridine Derivatives via Intramolecular Reformatsky-Type Reaction Promoted by Samarium Diiodide¹

A novel efficient method for the synthesis of 3‘-β-branched uridines starting from uridine was developed, in which a SmI 2 -promoted intramolecular Reformatsky-type reaction was effectively used. 5‘- O -(Bromoacetyl)-3‘-ketouridine derivatives 12, 26, and 27 were synthesized from uridine and were subjected to an intramolecular Reformatsky-type reaction. When 12, 26, and 27 were treated with 2.0 equiv of SmI 2 in THF at −78 °C, intramolecular carbon−carbon bond formation at the 3‘-β-position proceeded smoothly to give the corresponding 3‘,5‘-lactones 14, 28, and 29 in high yields, respectively. Treatment of 28 with NH 3 /MeOH gave the 3‘-β-branched uridine derivative 32 quantitatively, which was then deprotected to give 3‘- C -(carbamoylmethyl)uridine ( 33 ).