Practical Access to Key Intermediates of Crizotinib, Lorlatinib, and Pibrentasvir Enabled by Oxa-Spirocyclic Ligands

Jingyuan Song1,2; Menglong Zhao1,2; Renwei Xiao1,2; Gen-Qiang Chen3; Xumu Zhang1,2

2023-11-09

10.1021/acs.oprd.3c00089

Org. Process Res. Dev.   影响因子和分区

1083-6160

1520-586X

Optically active secondary alcohols are key building blocks for a variety of chiral drugs, and transition-metal-catalyzed asymmetric hydrogenation represents one of the most efficient and direct methods for the preparation of chiral secondary alcohols. We herein report a practical and efficient asymmetric hydrogenation catalyzed by a chiral iridium complex bearing (R)-O-SpiroPAP as the ligand, producing intermediates of crizotinib, ensartinib, lorlatinib, and pibrentasvir in up to 99% yield with up to 99% ee and >20:1 dr. The synthetic potential of the current catalytic system was demonstrated by experiments on the gram and kilogram scales.

asymmetric hydrogenation chiral alcohols pharmaceutical intermediates tridentate ligands

SCI ; EI

英语

通讯

20234915155974

Catalysis ; Hydrogenation ; Iridium compounds ; Transition metals

Metallurgy and Metallography:531 ; Physical Chemistry:801.4 ; Chemical Reactions:802.2

CHEMISTRY

2-s2.0-85178148251

人工提交

在线出版

1.Medi-X Pingshan, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis
2.Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China
3.Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen 518000, China

Jingyuan Song,Menglong Zhao,Renwei Xiao,et al. Practical Access to Key Intermediates of Crizotinib, Lorlatinib, and Pibrentasvir Enabled by Oxa-Spirocyclic Ligands[J]. Org. Process Res. Dev.,2023,27(12):2280−2285.

Jingyuan Song,Menglong Zhao,Renwei Xiao,Gen-Qiang Chen,&Xumu Zhang.(2023).Practical Access to Key Intermediates of Crizotinib, Lorlatinib, and Pibrentasvir Enabled by Oxa-Spirocyclic Ligands.Org. Process Res. Dev.,27(12),2280−2285.

Jingyuan Song,et al."Practical Access to Key Intermediates of Crizotinib, Lorlatinib, and Pibrentasvir Enabled by Oxa-Spirocyclic Ligands".Org. Process Res. Dev. 27.12(2023):2280−2285.