Azodicarboxylic acid, diethyl ester, oxidation

This method is unusually mild, using neutral conditions and low temperatures (20 °C and less). It tolerates a number of functional groups in the components (e.g. acetals, esters, alkenes, etc.)- The alcohol, the carboxylic acid and triphenylphosphine are treated dropwise in an inert solvent (dichloromethane, THF, ether) with diethyl azodicarboxylate (DEAD). The ester is formed rapidly. However, tedious chromatography is frequently required to remove the by-products, triphenylphosphane oxide and hydrazo ester. The main value of the reaction lies in the clean inversion of configuration at a secondary carbinol center and in its selectivity towards primary hydroxy groups (vide infra). Inversions are usually performed with benzoic or p-nitrobenzoic acid. The benzoates are purified and saponified with aqueous base to furnish the inverted alcohols in overall yields of ca. 50%. Elimination is the main side reaction. Thus, from (44) 75% of the desired Sn2 product (45) is formed, along with 25% of the elimination product (46) (equation 19). The mechanism of the reaction has been clarified to the point that betaine (47) is the pri-... 

The corresponding 3a-hydroxy lactone 42 was synthesized from 68 using the Mitsunobu procedure (diethyl azodicarboxylate/triphenylphosphine/formic acid) for inversion of the hydroxy function in position 3.73 The resulting 3oc-formyloxy ester 73, upon hydrolysis afforded the 3a-alcohol 74. Asymmetric dihydroxylation of 74 yielded 24-epityphasterol (75) as the main product. Baeyer-Villiger oxidation of 75 led to 2-deoxy-24-epibrassinolide (42) and its isomeric lactone 76 in a 1 0.6 ratio.74... 

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