Applications of Mitsunobu Reaction in total synthesis of natural products

Abstract

The Mitsunobu Reaction allows the conversion of primary and secondary alcohols to esters, phenyl ethers, thioethers and some other compounds. The nucleophile employed should be acidic, since one of the reagents, diethylazodicarboxylate (DEAD) must be protonated during the course of the reaction, preventing from the formation of unwanted side products. In this review, we try to focus on the scope and preparative synthetic applications of Mitsunobu reaction as a key step in the total synthesis of biologically active natural products.

Synthesis and Antiviral Evaluation of 3′-Fluoro-5′-norcarbocyclic Nucleoside Phosphonates Bearing Uracil and Cytosine as Potential Antiviral Agents

“…The latter was synthesized from alcohol (±)- 3 obtained according to our previously described procedure [ 6 ]. The azide with trans-configuration was obtained in good yield using a Mitsunobu reaction [ 7 ] in the presence of diphenylphosphorylazide (DPPA), triphenylphosphine and diisopropyl azodicarboxylate (DIAD). From azido derivative (±)- 4 , the required amine (±)- 5 was obtained after reduction with LiAlH 4 in 84% yield.…”

Estimation of the helical twisting power of chiral inducers by time-dependent density functional theory (TD-DFT) for electrochemical polymerization in cholesteric liquid crystals

“…Here, the Mitsunobu reaction is considered to be highly efficient for the nucleophilic substitution (S N 2) reaction to form a phenolic ester or ether. Because the Mitsunobu reaction often provides a high enantiomeric excess yield, the absolute configuration at the stereogenic center is inverted (100%, Walden inversion) for forming a purely asymmetric chiral product [32]. The difficulty that is associated with this reaction is the subsequent purification process.…”