[155632-33-0] · C22H23N2O2PS · (MW 428.494)
(reagent for mediating Mitsunobu-like processes;1 a convenient alternative to DEAD-triphenylphosphine system)
Physical Data: mp 169-172 °C (CH2Cl2-MeCN; decomposition).
Solubility: soluble in DMSO, CH2Cl2, CHCl3; limited solubility in THF, toluene, Et2O.
Form Supplied in: not commercially available. White solid.
Analysis of Reagent Purity: 1H-NMR, 31P-NMR, elemental analysis.
Preparative Methods: the title reagent can be prepared in quantitative yield by addition of DEAD (1 equiv) to a solution of 3,3-dimethyl-1,2,5-thiadiazolidine-1,1-dioxide (1 equiv)2 and triphenylphosphine (1 equiv) in THF at room temperature.1 3,3-Dimethyl-1,2,5-thiadiazolidine-1,1-dioxide can be prepared in high yield by reaction of sulfamide and 1,2-diamino-2-methylpropane in anhydrous pyridine.
Purification: preparation of the reagent as above affords material of high purity with no need for further purification. Recrystallization can be achieved from CH2Cl2-MeCN.
Handling, Storage, and Precautions: the compound is hydrolytically unstable to acid, decomposing on silica gel to triphenylphosphine oxide and 3,3-dimethyl-1,2,5-thiadiazolidine-1,1-dioxide, but can be stored in the solid state at room temperature, under nitrogen, for several months without significant degradation. 1H-NMR experiments in CDCl3 may be misleading for purity check due to presence of DCl/HCl/H2O.
Triphenylphosphonium 3,3-dimethyl-1,2,5-thiadiazolidine 1,1-dioxide (1) can be conveniently utilized as a stable source of [Ph3P+] in the promotion of Mitsunobu-like processes. By analogy with the betaine generated by reaction of DEAD and triphenylphosphine, protonation of zwitterionic species 1 by an acidic component HX generates ion pair 2 which on subsequent reaction with an alcohol (ROH) affords oxyphosphonium species (3) and 3,3-dimethyl-1,2,5-thiadiazolidine-1,1-dioxide (4). Finally, SN2 displacement reaction, occurring with Walden inversion of the alcohol stereochemistry, leads to the coupled product R-X and triphenylphosphine oxide (TPPO) (
Reagent 1 has been utilized to promote the couplings of alcohols and carboxylic acids,1 phenols,3-7 phthalimide,1 thiazolidinedione,8 and sulphonamides.9 The compound has gained popularity as a preparatively useful reagent on Mitsunobu-like reactions on solid support, where advantages over conventional methodology have unfolded (e.g. convenient addition of one reagent rather than two, cleaner products).3-5,8,9 Suitable solvents for the reaction include dichloromethane and toluene, and although the reagent is not usually soluble at the start of the process, a homogenous solution is obtained as the reaction proceeds (excluding resin in solid-phase syntheses). Cyclic sulfamide (4) is not extracted into Et2O facilitating the isolation of coupled products. Illustrative examples of the above mentioned utilities are shown in
Merck Sharp & Dohme Research Laboratories, Harlow, Essex, UK