Pot Economy in the Total Synthesis of Estradiol Methyl Ether by Using an Organocatalyst
Yujiro Hayashi1, Seitaro Koshino1, Kanna Ojima1
1Department of Chemistry, Graduate School of Science, Tohoku University, 6-3 Aramaki-Aza Aoba, Aoba-ku, Sendai, 980-8578, Japan.
Abstract:
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.
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