STEREOCHEMISTRY OF BASE-CATALYZED RING-OPENING OF 1,3,2-OXATHIAPHOSPHOLANES - ABSOLUTE-CONFIGURATION OF 2-(N-[(R(C))-1-(ALPHA-NAPHTHYL)ETHYL]AMINO)-2-THIONO-1,3,2-OXATHIA-PHOSPHOLANES AND O,S-DIMETHYL N-[(R(C))-1-(ALPHA-NAPHTHYL)ETHYL]PHOSPHORAMIDOTHIOATES

Pure diastereoisomers of 2-{[(R(c))-1-(alpha-naphthyl)ethyl]amino}-2-thiono-1,3,2-oxathiaphospholane (1) and O,S-dimethyl N-[(R(c))-1-(alpha-naphthyl)ethyl]phosphoramidothioate (2) were obtained, and both ''slow''-migrating isomers of 1 and 2 were studied by X-ray crystallography which demonstrated their (R(p),R(c)) absolute configuration. Therefore, the absolute configuration of both ''fast''-migrating isomers of 1 and 2 must be (S(p),R(c)). In (R(p),R(c))-1 oxathiaphospholane, the ring adopts the open-envelope conformation with the C2 atom in the flap position; the S1-P-O1 angle is 97-degrees. DBU-assisted methanolysis of (R(p),R(c))-1 (''slow'') followed by S-methylation, gave (S(p),R(c))-2 (''fast''). This result is interpreted in terms of an ''adjacent'' type mechanism or the regio- and stereoselective 1,3,2-oxathiaphospholane ring-opening process. Suggestions are presented regarding the absolute configuration at the phosphorus atom in diastereoisomers of 5'-O-protected nucleoside 3'-O-(2-thiono-1,3,2-oxathiaphospholanes), which are synthons for stereocontrolled synthesis of oligo(nucleoside phosphorothioate)s.