Molybdenum-Catalyzed Regio- and Enantioselective Amination of Allylic Carbonates: Total Synthesis of (S)-Clopidogrel

Abstract

The first molybdenum-catalyzed highly regio-and enantioselective allylic amination of both aryl-and alkyl-substituted branched allylic carbonates has been developed. A wide variety of amines, including drugs and complex bioactive molecules, underwent successful amination with excellent reaction outcomes (up to 96% yield, >99% ee, and >20:1 b/l). The reaction could be scaled up and has been applied to the total synthesis of chiral drug molecule (S)-clopidogrel (Plavix).

Thermal/photochemical micro-flow probe system for direct C–H bond functionalization of biologically active molecules

“…Our developed protocols enabled an 83% yield of the isolated product clopidogrel (details in ESI †). 61,62…”

Green Chemistry Approach toward the Regioselective Synthesis of α,α-Disubstituted Allylic Amines

“…On the other hand, group 6 metals, especially molybdenum, are also known to catalyze allylic substitution reactions, but there is still no example of these reactions utilizing secondary and/or tertiary allylic electrophiles with amines to form carbon–nitrogen bonds . Based on this background, during the course of our research on group 6 (Mo and W) metal-catalyzed allylic substitutions to form carbon–heteroatom bonds (Scheme , left side), we examined the reaction of readily available tertiary allylic alcohol derivatives, with various amines, and successfully obtained the challenging α,α-disubstituted allylic amines (Scheme , right side) …”