Epoxidation of amides

Tabic 9. Diastereoselectivities in the Epoxidation of Amides of Allylic Amines... 

As an application of the modified conditions, the asymmetric synthesis of (7 )-fiuoxetine was demonstrated (Scheme 35.28). Fluoxetine is an antidepressant drug and currently marketed as a racemate. Asymmetric epoxidation of amide 101 under Shibasaki s conditions provided epoxide 102 in 91% yield and 99% ee. Subsequent regionselec-tive reduction with Red-Al in the presence of a crown ether afforded the (3-hydoxyl amide 103, which was converted into (/ )-fluoxetine 104 in two steps. °... 

SCHEME 35.28. Using the asyimnetric epoxidation of amide 101 under ShibasaM s conditions for the asymmetric synthesis of (R)-fluoxetine. 

Winstein showed that carboxamides display a strong syn directing effect, as demonstrated in the epoxidation of amide 21, furnishing cis-epoxide 22 as the only observed diastereomer (Equation 8) [63]. The directing effect of carboxamide substituents was studied by Sable, who found that triol 24 is converted diastereoselectively into epoxide 25 (syn to the amide group), despite the presence of one allylic and two homoallylic hydroxyl substituents on the opposite face (Equation 9) [64],... 

---

See also in sourсe #XX -- [ ]

---