Effective Synthesis of Tamoxifen Using Nickel-Catalyzed Arylative Carboxylation

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.

Key words

tetrasubstituted alkenes - nickel catalyst - zinc reagent - tamoxifen - carbon dioxide

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