Stereoselective formation of a P–P bond in the reaction of 2-alkoxy-2-thio-1,3,2-oxathiaphospholanes with O,O-dialkyl H-phosphonates and H-thiophosphonates

Abstract

A new method for the formation of organohypophosphates containing a P–P bond under mild conditions, based on the DBU-assisted reaction of 2-alkoxy-2-thio-1,3,2-oxathiaphospholanes with O,O-dialkyl H-phosphonates or H-thiophosphonates, has been elaborated. The resulting triesters of P¹-thio- and P¹,P²-dithiohypophosphoric acids, respectively, having O-methyl or O-ethyl groups, can be selectively dealkylated to form the corresponding di- or monoesters. Appropriately protected 2′-deoxyguanosine-3′-O-(2-thio-1,3,2-oxathiaphospholane) was converted into the corresponding P¹-thio- and P¹,P²-dithiohypophosphate esters in a highly stereoselective manner (98%+ and 90%+, respectively).