Mitsunobu Macrolactonization
- Page ID
- 15018
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The following is a standard procedure for a Mitsunobu macrolactonization.
Procedure

Notes:
- PhMe is the most common solvent for this reaction. Other useful ones are: PhH, THF and CH2Cl2.
- Very dilute conditions and slow addition of the diazo compound are critical to avoid formation of the diolide (dimerization of the seco-acid).
- Slow addition of the seco-acid to the azo/phosphine mixture can also prevent diolide formation.
- If addition of the azo compound onto the acid occurs, other diazo compounds can be used: DEAD (1972-28-7), DBAD (212-796-9), ADDP (10465-81-3) depending on the bulkiness needed.
- Changing the triphenylphosphine to a less bulky phosphine (PBu3, PMe3) can accelerate slow reactions.