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 -tris-O-TBDMS-be ta-D-ribofuranosyl)-6-chloropurine (2) with LDA, subsequent quenching of its lithiated species with Bu3SnCl (or TMSCl) results in the format ion of 2-substituted products. Under optimized reaction conditions, wh ere LTMP was us ed as a lithiating agent, -ribofuranosyl)-6-chloro-2-( tributylstannyl)purine (11) was formed in quantitative yield. Several experiments carried out to verify the reaction mechanism suggested tha t 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-sub stituted purine nucleosides. This chemistry was briefly applied to the synthesis of the 2-fluoro analogue of neplanocin A.