Synthesis of W‐Phos Ligand and Its Application in the Copper‐Catalyzed Enantioselective Addition of Linear Grignard Reagents to Ketones

作者：Luo Wenjun; Zhang LiMing; Zhang ZhanMing; Zhang Junliang

来源：Angewandte Chemie, 2022, 134(29).

DOI：10.1002/ANGE.202204443

• Alcohols
• Asymmetric Catalysis
• Copper
• Grignard Reagents
• Ketones

The asymmetric catalytic addition of linear Grignard reagents to ketones has been a long‐standing challenge in organic synthesis. Herein, a novel family of PNP ligands (W‐Phos) was designed and applied in copper‐catalyzed asymmetric addition of linear Grignard reagents to aryl alkyl ketones, allowing facile access to versatile chiral tertiary alcohols in good to high yields with excellent enantioselectivities (up to 94?% yield, 96?% ee). The process can also be used to synthesize chiral allylic tertiary alcohols from more challenging α,β‐unsaturated ketones. Notably, the potential utility of this method is demonstrated in the gram‐scale synthesis and modification of various densely functionalized medicinally relevant molecules.(#br)A novel family of PNP ligands (W‐Phos) was designed and applied in the copper‐catalyzed asymmetric addition of linear Grignard reagents to ketones, allowing ready access to versatile chiral tertiary alcohols in high yields and with excellent enantioselectivities.

• 单位
  中国科学院; 复旦大学; 金属有机化学国家重点实验室