Practical Synthesis of MDM2 Antagonist RG7388. Part 2: Development of the Cu(I) Catalyzed [3 + 2] Asymmetric Cycloaddition Process for the Manufacture of Idasanutlin was written by Rimmler, Gosta;Alker, Andre;Bosco, Marcello;Diodone, Ralph;Fishlock, Dan;Hildbrand, Stefan;Kuhn, Bernd;Moessner, Christian;Peters, Carsten;Rege, Pankaj D.;Schantz, Markus. And the article was included in Organic Process Research & Development in 2016.COA of Formula: C38H32O2P2 This article mentions the following:
A concise catalytic asym. synthesis of idasanutlin was developed in which the key pyrrolidine core, containing four contiguous stereocenters, was constructed via a Ag/MeOBIPHEP promoted [3+2] cycloaddition reaction. Further development of the [3+2] cycloaddition reaction resulted in an improvement in diastereoselectivity and enantioselectivity by changing the catalyst system to Cu(I)/BINAP. While producing equivalent high quality API, the copper(I) catalyzed process not only increased the overall yield but also demonstrated benefit with respect to cycle times, waste streams and processability. The optimized copper(I) catalyzed process has been used to prepare more than 1500 kg of idasanutlin. In the experiment, the researchers used many compounds, for example, (R)-(6,6′-Dimethoxy-[1,1′-biphenyl]-2,2′-diyl)bis(diphenylphosphine) (cas: 133545-16-1COA of Formula: C38H32O2P2).
(R)-(6,6′-Dimethoxy-[1,1′-biphenyl]-2,2′-diyl)bis(diphenylphosphine) (cas: 133545-16-1) belongs to chiral phosphine ligands. The synthesis of novel trialkylphosphines can be quite difficult, thereby limiting the scope of their chiral variants. Asymmetric catalytic performance is determined not only by the metal center but also by the chiral ligand selected.COA of Formula: C38H32O2P2
Referemce:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis