Development of Axially Chiral Phosphoramidite Ligands and Their Application in Pd-Catalyzed Asymmetric Synthesis of
Zhengyi Yi1, Yong Liu1, Weixin Xiao1
1Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
Abstract:
Pyrrolidinone, pyrazolone, and spiro pyrazolone derivatives possess significant and unique pharmaceutical activities. However, asymmetric synthesis of chiral spiro-pyrazolone-pyrrolidinones with potential pharmaceutical activity has not been reported thus far. Therefore, it is highly desirable to develop a concise and efficient approach to chiral spiro-pyrazolone-pyrrolidinones with high reactivity and stereoselectivity. Here, we describe a palladium-catalyzed asymmetric [2 + 3] cycloaddition of α,β-unsaturated pyrazolones with vinyloxazolidine-2,4-diones, and diverse and highly functionalized chiral spiro-pyrazolone-pyrrolidinones were synthesized in high yields (64-77%), excellent diastereoselectivity (>20:1 dr), and high to excellent enantioselectivity (84-98% ee). The results showed that our newly developed axially chiral phosphoramidite ligand significantly enhanced the reactivity and stereoselectivity of this [2 + 3] cycloaddition reaction. Further modification of the obtained chiral spiro-pyrazolone-pyrrolidinone afforded some new and valuable chiral spiro N-heterocycles.
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