A Simple Synthesis of Nitriles from Aldoximes

[GRAPHICS] Easily synthesized aldoximes have been converted to the corresponding nitriles under very mild conditions by a simple reaction with 1H-benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) and DBU in CH2Cl2, THF, or DMF. As an alternative reagent that eliminates the formation of hexamethylphosphoramide as a byproduct, use of 1H-benzotriazol-1-yl-4-methylbenzenesulfonate (Bt-OTs) and DBU was investigated. Reactions with this reagent also proceeded smoothly and in good yields, although in one case N-sulfonylation was observed. An attempt to gain mechanistic insight into the BOP-mediated reaction has been made using (31)p{H-1} NMR. However, no phosphorus-bearing intermediate could be readily observed. Finally, the method has been applied to the synthesis of an antiviral 4'-cyano adenosine analogue from a commercial precursor using a single saccharide protecting group.