Lithiation at the 6-Position of Uridine with Lithium Hexamethyldisilazide:  Crucial Role of Temporary Silylation

Abstract

Lithium hexamethyldisilazide (LiHMDS) can mediate silylation at the 6-position of uridine, although LiHMDS alone is not able to generate the C-6-lithiated uridine. Experimental results showed that temporary silylation of O-4 (or N-3) of the uracil ring triggers the C-6 lithiation with LiHMDS. This finding allowed us to develop an efficient intramolecular alkylation of 5‘-deoxy-5‘-iodouridine to furnish 6,5‘-C-cyclouridine