Practical Synthesis of MDM2 Antagonist RG7388. Part 1: A Cu(II)-Catalyzed Asymmetric [3 + 2] Cycloaddition was written by Shu, Lianhe;Gu, Chen;Fishlock, Dan;Li, Zizhong. And the article was included in Organic Process Research & Development in 2016.Computed Properties of C38H32O2P2 This article mentions the following:
An efficient asym. synthesis of MDM2 antagonist RG7388 (I) is reported. The highly functionalized chiral pyrrolidine carboxamate was assembled via a Cu(OAc)2/(R)-BINAP catalyzed asym. [3+2] cycloaddition, which gave the exo and endo adducts in a ratio of 10:1, with high enantiomeric excess for the exo isomer. A one pot hydrolysis and retro-Mannich/Mannich isomerization of the cycloaddition adducts in the presence of aqueous sodium hydroxide afforded RG7388 in high chem. and enantiomeric purities and 69% overall yield. In the experiment, the researchers used many compounds, for example, (R)-(6,6′-Dimethoxy-[1,1′-biphenyl]-2,2′-diyl)bis(diphenylphosphine) (cas: 133545-16-1Computed Properties of C38H32O2P2).
(R)-(6,6′-Dimethoxy-[1,1′-biphenyl]-2,2′-diyl)bis(diphenylphosphine) (cas: 133545-16-1) belongs to chiral phosphine ligands. Generally, the efficiency of nucleophilic phosphine catalysis often depends on the nature of the tertiary phosphine. Effective chiral catalysts for nucleophilic phosphine catalysis are scarce, seriously limiting the development of asymmetric variants. Computed Properties of C38H32O2P2
Referemce:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis