Enantioselective synthesis of (R)-Cinacalcet via cobalt-catalysed asymmetric Negishi cross-coupling

Abstract

A novel enantioselective synthesis of (R)-cinacalcet with 99% enantiomeric excesses (ee) has been achieved. The main strategies of the approach include a gram-scale cobalt-catalysed asymmetric cross-coupling of racemic ester with arylzinc reagent, Hoffman-type rearrangement of acidamide, the amidation of chiral amine, and improving the ee of chiral amide from 87% to 99% via recrystallization.

Keywords: (R)-Cinacalcet; asymmetric synthesis; chiral drug; cobalt; enantioselective Negishi cross-coupling.