Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• -prenylation of 3-O-methoxymethyl-4′-O-methyl-5-O-prenyl-7-O-benzylkaempferol (8) via para-Claisen–Cope rearrangement catalyzed by Eu(fod)3 in the presence of NaHCO3, and the glycosylation of icaritin (3) are the key steps. Keywords: Claisen–Cope rearrangement; flavonol; icariin; prenylation; regioselectivity

• developed procedure [19]. In order to methylate exclusively the 4′-OH in kaempferol, we initially attempted to use methoxymethyl (MOM) as 7-OH protecting group, but this method could not provide an ideal yield in the 4′-OH selective methylation and in subsequent Claisen–Cope rearrangement. The resulting

• efficient method for the preparation of C-isopentenyl. In the case of flavonoids, control of the regioselectivity of ortho (C6)/para (C8)-rearranged products is still remained a challenging issue [20]. Once the prenyl ether 8 was obtained, attention was fastened on the para-Claisen–Cope rearrangement to