Synlett 2006(18): 3182-3184  
DOI: 10.1055/s-2006-951517
LETTER
© Georg Thieme Verlag Stuttgart · New York

Effective Synthesis of Tamoxifen Using Nickel-Catalyzed Arylative Carboxylation

Kazuya Shimizua, Masanori Takimotob, Miwako Mori*c, Yoshihiro Sato*a
a Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
b Organometallic Chemistry Laboratory, RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
c Health Sciences University of Hokkaido, Ishikari-Tobetsu 061-0293, Japan
Fax: +81(11)7064982; e-Mail: mori@pharm.hokudai.ac.jp;
Further Information

Publication History

Received 2 May 2006
Publication Date:
25 October 2006 (online)

Abstract

Tamoxifen was synthesized using a nickel-catalyzed arylative carboxylation developed by our group. The key compound, tetrasubstituted alkene, was synthesized from disubstituted alkyne using a catalytic amount of Ni(0) and DBU in the presence of Ph2Zn under an atmosphere of carbon dioxide. The reaction proceeded smoothly in a regio- and stereoselective manner, and the resultant tetrasubstituted alkene was converted into tamoxifen.