A New Entry to 2-Substituted Purine Nucleosides Based on Lithiation-Mediated Stannyl Transfer of 6-Chloropurine Nucleosides

In spite of exclusive lithiation at the 8-position of 9-(2,3,5-tris- O -TBDMS-β- d -ribofuranosyl)-6-chloropurine ( 2 ) with LDA, subsequent quenching of its lithiated species with Bu 3 SnCl (or TMSCl) results in the formation of 2-substituted products. Under optimized reaction conditions, where LTMP was used as a lithiating agent, 9-(2,3,5-tris- O -TBDMS-β- d -ribofuranosyl)-6-chloro-2-(tributylstannyl)purine ( 11 ) was formed in quantitative yield. Several experiments carried out to verify the reaction mechanism suggested that an anionic stannyl (or silyl) transfer from the 8- to the 2-position had been involved. Manipulation of the 2-tributylstannyl group in 11 and in its adenine counterpart ( 22 ) has disclosed a new entry to 2-substituted purine nucleosides. This chemistry was briefly applied to the synthesis of the 2-fluoro analogue of neplanocin A.