Synthesis of Lasofoxifene, Nafoxidine and Their Positional Isomers via the Novel Three-Component Coupling Reaction

Molecules

Kenya Nakata¹  Yoshiyuki Sano¹ 

[1] Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan

关键词: three-component coupling reaction;    diversity oriented synthesis;    lasofoxifene;    nafoxidine;    inv-lasofoxifene;    inv-nafoxidine;   

DOI  :  10.3390/molecules15106773

来源: mdpi

【 摘 要 】

A Lewis acid-mediated three-component coupling reaction was successfully applied for the synthesis of lasofoxifene (1), nafoxidine (2), and their positional isomers, inv-lasofoxifene (3) and inv-nafoxidine (4). In the presence of HfCl₄, the desired one-pot coupling reaction among 4-pivaloyloxybenzaldehyde (5), cinnamyltrimethylsilane (6), and anisole proceeded to afford the corresponding 3,4,4-triaryl-1-butene 7 in high yield. The iodocarbocyclization of the coupling product and the successive elimination of hydrogen iodide forming the olefin part, followed by the migration of the double-bond afforded the common synthetic intermediate of lasofoxifene (1) and nafoxidine (2) via a very concise procedure. Additionally, the syntheses of their positional isomers inv-lasofoxifene (3) and inv-nafoxidine (4) were also achieved through very convenient protocols.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.