Triphenylphosphine-dialkyl azodicarboxylate

Intermolecular and intramolecular nucleophilic substitution of an alcoholic hydroxy group by the triphenylphosphine/dialkyl azodicarboxylate redox system is widely used in the synthesis and transformation of natural products and is known in organic chemistry as the Mitsunobu reaction.1951 This reaction starts with formation of the zwitterionic phosphonium adduct 19 (Scheme 9) from triphenylphosphine and diethyl (or diisopropyl) azodicarbox-... 

This class of compound is represented by 2,3-disubstituted-l,2,3-benzoxadiazoles and new caged structures. 2,3-Disubstituted-l,2,3-benzoxadiazoles 128 were prepared in high yield when the Huisgen zwitterion, formed between dialkyl azodicarboxylates 127 and triphenylphosphine, was reacted with 3-methoxy 4,6-disubstituted-l,2-benzoqui-nones 126 (Equation 23 Table 6) <20050L5139>. 

Reaction of 4,6-disubstituted-3-methoxy-l,2-benzoquinones with dialkyl azodicarboxylates and triphenylphosphine gives dihydro-1,2,3-benzoxadiazoles 99 in good yield (64—94%) (Scheme 25). A multistep mechanism leading to the zwitterionic intermediates 98, which then cyclise to the products 99, has been proposed (05OL5139). An N,N-diphenyl-2,3-dihydro-l,2,3-benzoxadiazole has been obtained (40% yield) by reaction of 3,5-di-f-butyl-l,2-benzoquinone with W-phenyliminophosphorane (PhN - PPhg) (see also Section 3.1.3.2) (02SC2779). 

Formylchromones (116) react under Mitsonobu conditions (triphenylphosphine and dialkyl azodicarboxylate). The zwitterionic intermediate generated can add once or twice to form a third ring, that is, to give chromeno[2,3-c]-pyrazolines or chromeno[2,3-c]-tetrazepines. 

The Mitsunobu reaction, discovered by Oyo Mitsunobu (1934-2003) in 1967, is one of the most important among modern synthetic reactions. It allows the replacement of the OH group of primary and secondary alcohols with a variety of nucleophiles, with clean inversion of stereochemistry and under mild conditions. The key reagents are triphenylphosphine and a dialkyl azodicarboxylate the latter is very often diethyl azodicarboxylate (DEAD). In addition, a key requirement is that the nucleophile should be acidic (for reasons you ll see below) carboxylic acids, phenols, thiols, imides, and activated carbon acids are all appropriate nucleophiles. 

Preparation of Mixed Carbonates. The reaction of (Me2N)3P with alcohols and dialkyl azodicarboxylates proceeds smoothly at rt to provide mixed dialkyl carbonate esters in moderate to good yields (eq 17). An advantage of the method over the chloroformate method is the neutrality of the conditions employed. It should be noted that the related system Triphenylphosphine-Diethyl AzodicarboxyUite converts alcohols into amines. 

Esterification of dialkyl phosphates is carried out with diethyl azodicarboxylate and triphenylphosphine (equation 46). This condensation is applicable to phosphorylation of pyrimidine nucleosides. The trichloromethanephosphonic acid derivative (69 equation 47) serves as a phosphorylating agent of ribonucleosides, affording the 2 - and 3 -monophosphates. ° Ethyl vinyl ether assisted the dimeric condensation of diethyl hydrogen phosphate giving tetraethyl pyrophosphate (equation 48). ... 

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