Pot Economy in the Total Synthesis of Estradiol Methyl Ether by Using an Organocatalyst

Enantioselective total synthesis of estradiol methyl ether has been accomplished in a pot‐economical manner using five reaction vessels and four purifications. The key reaction is a diphenylprolinol silyl ether mediated domino Michael/aldol reaction to afford bicyclo[4.3.0]nonane derivatives, contai...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2017-09, Vol.56 (39), p.11812-11815
Main Authors: Hayashi, Yujiro, Koshino, Seitaro, Ojima, Kanna, Kwon, Eunsang
Format: Article
Language:English
Subjects:
17β-Estradiol
Aldehydes
asymmetric synthesis
Chlorides
domino reactions
Economics
Enantiomers
Friedel-Crafts reaction
organocatalysis
Oxidation
Sex hormones
Steroid hormones
Steroids
Synthesis
total synthesis
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Summary:Enantioselective total synthesis of estradiol methyl ether has been accomplished in a pot‐economical manner using five reaction vessels and four purifications. The key reaction is a diphenylprolinol silyl ether mediated domino Michael/aldol reaction to afford bicyclo[4.3.0]nonane derivatives, containing the A, C, and D rings of steroids, as a single isomer with excellent enantioselectivity. Six reactions such as oxidation, hydrogenation, formation of acid chloride, Friedel–Crafts reaction, deprotection, and reduction can be carried out in the last one‐pot sequence. Pot luck: Estradiol methyl ether was synthesized using only five reaction vessels and four purification steps. The key step involved a diphenylprolinol silyl ether mediated Michael reaction. The last one‐pot sequence of the reaction involves six reactions, and highlights the pot‐economical aspect of the synthesis. TMS=trimethylsilyl.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201706046