Use of carbohydrate derivatives for studies of phosphorus stereochemistry. Part V. Preparation and some reactions of tetrahydro-1,3,2-oxazaphosphorine-2-ones and -2-thiones

Abstract

The configurations at phosphorus in pairs of tetrahydro-1,3,2-oxazaphosphorines, epimeric at phosphorus and prepared by treatment of methyl 6-deoxy-2,3-di-O-methyl-6-methylamino-α-D-glucopyranoside (1) with phosphonic dihalides, have been established by spectroscopic methods. Treatment of the glucopyranoside derivative (1) with phosphoric or phosphorothioic trichloride afforded 2-chlorotetrahydro-1,3,2-oxazaphosphorine derivatives which on treatment with sodium alkoxides (aryloxides) under mild conditions were converted, with inversion of configuration at phosphorus, into the corresponding 2-alkoxy-(aryloxy-) derivatives. All displacement reactions of the exocyclic substituent at phosphorus occurred with inversion of configuration. With sodium alkoxides under more vigorous conditions the tetrahydro-1,3,2-oxazaphosphorines underwent endocyclic P–N fission as well as P–O fission, both reactions occurring with inversion of configuration. Acid-catalysed endocyclic fission reactions also occurred with inversion of configuration at phosphorus. Methyl 2,3-di-O-methyl-α-D-glucopyranoside cyclic (R)-4(O),6(N)-NP-dimethylphosphonamidothioate was degraded to (R)-ethyl methylphosphonothioic acid by successive treatment with sodium ethoxide and dilute hydrochloric acid.