Pot Economy in the Total Synthesis of Estradiol Methyl Ether by Using an Organocatalyst.
Yujiro HayashiSeitaro KoshinoKanna OjimaEunsang KwonPublished in: Angewandte Chemie (International ed. in English) (2017)
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.