Synthesis by Mitsunobu reaction

In 1992, Parker and Fokas reported the short step (11 steps) synthesis of racemic dihydroisocodeine, which completes a formal synthesis of codeine and morphine [58]. The key feature of their synthesis are (1) a construction of an aryl ether moiety (connection of the A and C rings) by Mitsunobu reaction, (2) a tandem radical cyclization of aryl bromide possessing the C-ring precursor to generate the A-B-C-E ring of morphine, and (3) a hydroamination for the construction of the D-ring by the reaction of a tosylamide with Li/NH3. In 2006, they reported the chiral version of the synthesis of dihydrocodeinone [59]. 

Walker et al. have described by tliis method a seven-step synthesis of 4-thio-2-deox-y-i3-eri f/7ro-pentosc (37) from 2-dcoxy-D-erir/ira-pentosc via dithioacetals 35 and 36, involving inversion at C-4 by Mitsunobu reaction and final cyclization of the dithioacetal, accompanied by further inversion at C-4. Secrist et al.- have synthesized 39 from the ribose derivative 38 using the same method. Similarly, Imbach et al. have prepared 1,4-dithio-D-ribofuranosides 39 from L-lyxose and from D-ribose,and 1,4-dithio-L-lyxofuranosides 40 from D-ribose. Mackenzie... 

Scheme 1. Synthesis of azocellulose polymers by Mitsunobu reaction...

Caras-Quintero, D., and P. Bauerle. 2002. Efficient synthesis of 3,4-ethylenedioxythiophenes (EDOT) by Mitsunobu reaction. Chem Commun 2690-2691. 

Amino-2 -deoxynucleosides 190 involving all the main nucleobases have been prepared by Mitsunobu reactions involving iV-hydroxyphthalimide the products are of relevance in the synthesis of antisense oligonucleotides (see Vol.26, p.242).2 ... 

The synthesis of 6-azidomethyl-S,6,7,8-tetrahydropterin 108 has been carried out from 106 via the intermediate 107 using the Mitsunobu reaction with diphenylphosphoryl azide followed by deprotection <95MI09 %CA(124)232123>. 

Scheme 21 shows the synthesis of a dihydrofuran derivative 86. Synthesis of this compound was described by Nam et al. [68] utilizing a furanone compound 87 synthesized by Kim et al. [61] via a similar synthetic approach as described in Scheme 17. The lactone was reduced using lithium aluminum hydride to give the diol 88 and intramolecular etherification using the Mitsunobu reaction afforded the dihydrofuran 86 in moderate yield (47%).

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