FORMATION OF RADICALS IN THE MITSUNOBU REACTION

The first step of the Mitsunobu reaction, involving the reaction of triphenylphosphine with diisopropyl (or diethyl) azodicarboxylate, results in the formation of a radical cation. The EPR spectra of the N-centered radicals reveal hyperfine coupling to two nitrogen nuclei, a phosphorus nucleus, and one or two protons from the alkyl CH (or CH2) groups. The radical is relatively persistent, slowly decomposing at room temperature over a period of about 6 h. When the reaction was carried out in the presence of neopentyl alcohol (1 equiv), the radical still formed. However, in the presence of benzoic acid (1 equiv) or neopentyl alcohol/benzoic acid, no EPR signal was observed. This suggests that the order of addition of reagents in the Mitsunobu reaction may influence the outcome in some cases. A new mechanism, involving single electron transfer, is proposed for the formation of the Morrison-Brunn-Huisgen betaine.