Use of carbohydrate derivatives for studies of phosphorus stereochemistry. Part IV. Ring-opening reactions of 1,3,2-dioxaphosphorinan-2-ones and related compounds with grignard reagents and with sodium methoxide

Abstract

The 1,3,2-dioxaphosphorinan-2-one ring in methyl 2,3-di-O-methyl-α-D-glucopyranoside (R)- and (S)-4,6-alkyl-(or aryl-)phosphonates is opened by Grignard reagents by attack at phosphorus with inversion of configuration and with preponderant cleavage of the bond between phosphorus and O-6 of the glucopyranoside unit. By contrast, in the corresponding 1,3,2-dioxaphosphorinan-2-thiones the stereochemistry at phosphorus and the nature of the P-substituent determines whether the P–O(4) or the P–O(6) bond is cleaved preponderantly and whether the cleavage occurs with inversion or retention of configuration. Ring opening of the foregoing dioxaphosphorinans with sodium methoxide results first in the preponderant formation of glucopyranoside 4-[methyl alkyl-(or aryl-)phosphonates (phosphonothioates)]. Migration of the P-substituent from O-4 to O-6 then occurs. The stereochemistry of the ring-opening and migration reactions is discussed. The stereochemistry of the ring-opening reaction, with Grignard reagents, of the 1,3,2-oxathiaphosphorinan ring in methyl 2,3-O-methyl-6-thio-α-D-glucopyranoside (S)- and (R)-4,6-methylphosphonothioates and the corresponding ethyl phosphorothioates is also described. The 2-methyl-1,3,2-oxathiaphosphorinan-2-ones with sodium methoxide in methanol undergo P–O bond fission with inversion of configuration, in contrast to the corresponding 2-ethoxy-derivatives which undergo P–S cleavage with probable retention of configuration at phosphorus. On storage in methanol containing sodium methoxide methyl 2,3-di-O-methyl-6-thio-α-D-glucopyranoside 6-(methyl methylphosphonothioate) is converted with preponderant inversion of configuration into the corresponding 4-(methyl methylphosphonates).