Nucleophilic substitution at the anomeric position of 1,2- O-isopropylidenefuranose derivatives. A novel stereoselective synthesis of cyclic phosphates analogous to cAMP

Abstract

1,2- O-Isopropylidenefuranose derivatives were treated with various nucleophiles in the presence of either BF 3·OEt 2 or trimethylsilyl trifluoromethanesulfonate (TMSOTf) leading to substitution products in a regio- and stereoselective manner. In particular, nucleophilic substitution of 1,2- O-isopropylidenefuranose derivatives when treated with allyltrimethylsilane was controlled by steric and electronic factors (similar to Woerpel’s stereoelectronic model). On the other hand, when 1,2- O-isopropylidenefuranose derivatives were treated with trimethylsilane, in the presence of bis- O-trimethylsilyl-5-iodouracil or bis- O-trimethylsilyl-thymidine, substitution products were generated in high regio- and stereoselectivities via an unusual nucleophilic substitution with opening of the furanose ring. Based on these results, a stereoselective method for the synthesis of neutral cyclic phosphates analogous to cAMP was developed.