Triphenylphosphine-Diethyl Azodicarboxylate compounds

Finally, a valuable example of multistep modifications of sucrose is the synthesis of Sucralose (l Ab -trideoxy-l Ab -trichloro-tya/flcm-sucrose)—a compound 650 times more sweeter than sucrose,15,326,327 which was obtained by treatment of 6-O-acetylsucrose with sulfuryl chloride in pyridine. Further reaction of this derivative with triphenylphosphine and diethyl azodicarboxylate afforded an epoxide from which a tetrachloro-derivative... 

Hydrolysis of 23 followed by debenzylation afforded demethyllasubine I (1) in 16% overall yield from 17. The configuration of the substituent at C-2 in 22 was inverted through two steps. Thus, hydrolysis of 22 followed by treatment with diethyl azodicarboxylate and triphenylphosphine in the presence of benzoic acid furnished the benzoate 24. Compound 24 was converted to demethyllasubine II (5) by sequential removal of the benzoyl and benzyl protecting groups the overall yield from 17 was 19%. 

The complex formed between diethyl azodicarboxylate and triphenylphosphine is a very useful reagent for condensation reactions. The reaction of alcohols with phthalimides, in the presence of diethyl azodicarboxylate and triphenylphosphine, resulted in the formation of the corresponding AT-alkylphthalimide in good yield. The reaction proceeds stereospecifically with complete inversion, as shown by conversion of (5 )-(+)-2-octanol to )-2-octylamine, isolated by treatment of the initially formed phthalimide with hydrazine hydrate. Condensation between alcohols and other active-hydrogen compounds using the same reagents has also been described (Scheme 1). Phosphorylation of alcohols by initial activation... 

This reaction was first reported by Mitsunobu in 1967. It is the alkylation of compounds with active protons by using primary or secondary alcohols as the alkylating agents in combination with triphenylphosphine and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD), to form molecules like esters, ethers, thioethers, and amines. Therefore, this reaction is generally known as the Mitsunobu reaction or Mitsunobu coupling. In addition, the specific reaction for forming esters by means of DEAD (or DIAD) and PPhs is generally referred to as the Mitsunobu esterification." Occasionally, the Mitsunobu reaction is also called the Mitsunobu transformation (for the conversion of alcohol into amines) or Mitsunobu cyclizafion (for the formation of cyclic compounds). Because of its intrinsic features of stereospecificity, as well as its occurrence in neutral media and at room temperature without a prerequisite activation of alcohol, this reaction has been extensively studied and used to synthesize a variety of compounds since 1970. 

The reaction of hydroxy compounds with numerous nucleophiles in the presence of diethyl azodicarboxylate/triphenylphosphine has been investigated . Epimerization with simultaneous O-acylation in the presence of the above reagents, a method initially used in steroid chemistry has been successfully applied to prostaglandin derivatives Recently, this method has been used for the preparation of prim. (lR)[l- Hi]- and -alcohols of high optical purity . 

Japanese workers have investigated the reaction between thioureas and diethyl azodicarboxylate, which in the presence of triphenylphosphine has been found to give carbodi-imides. They have now shown that the reaction in question involves (204) as an intermediate, which in the absence of triphenylphosphine could be isolated and characterized for = R = Ph. Compound (204) is easily converted into the carbodi-imide by treatment with triphenylphosphine or by refluxing in benzene. Moreover, the same workers were able to demonstrate that the formation of carbodi-imide under the first-mentioned conditions does not involve the oxidatively... 

P-Mannopyranosides with a chromo- or fluorogenic aromatic aglycone, e.g. a 4-nitrophenyl, naphthyl, or 4-methylumbelliferyl group, are valuable enzyme substrates. The 4-nitrophenyl derivative is also employed as a mannosyl donor in glycosidase-catalyzed p-mannosylation. These compounds can be prepared in 40 70% yields by reaction of the mannosyl bromide 2 [54] with sodium [202] or potassium phenolates [203, 204], Garegg has synthesized aryl P-mannosides in 50-65% yields by condensation of dicyclohexylidene-mannopyranose with phenols in the presence of diethyl azodicarboxylate and triphenylphosphine [44, 205]. Epimeriza-tion of C-2 of aryl P-D-glucopyranosides by the Lindberg protocol (Section 13.2.2) has also been described [206]. 

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