Citation: Ya-Ling Li, Jia-Wei Ke, Yue Liu, Dong-Mei Yao, Jing-Dong Zhang, You-Cai Xiao, Fen-Er Chen. Asymmetric conjugated addition of aryl Grignard reagents for the construction of chromanones bearing quaternary stereogenic centers in batch and flow[J]. Chinese Chemical Letters, ;2025, 36(6): 110377. doi: 10.1016/j.cclet.2024.110377 shu

Asymmetric conjugated addition of aryl Grignard reagents for the construction of chromanones bearing quaternary stereogenic centers in batch and flow

Ya-Ling Li ^a ,
Jia-Wei Ke ^a ,
Yue Liu ^a ,
Dong-Mei Yao ^a ,
Jing-Dong Zhang ^a ,
You-Cai Xiao ^{a, *,} ,
Fen-Er Chen ^{a, b, *,}

a.
Province Key Laboratory of Drug-Targeting and Drug Delivery System of the Ministry of Education and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
b.
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China

xiaoliguo1987@scu.edu.cn

Received Date: 15 April 2024
Revised Date: 21 August 2024
Accepted Date: 27 August 2024
Available Online: 7 September 2024

Figures(7)

The asymmetric conjugate additions of aryl Grignard reagents to trisubstituted enones by chiral P, N ligand L6 with low catalyst loading (0.25–1.0 mol%) are disclosed. Chiral 2-ester chromanone and its analogs bearing a quaternary stereogenic centers at C2 position were produced in high to excellent yields, enantioselectivities and high turnover number. The notable features of this reaction include its broad substrate scope, complete 1, 4-addition regioselectivities, applicability to both batch and flow for large scale synthesis. This report develops an efficient strategy to apply aryl Grignard reagents in asymmetric 1, 4-conjugation reactions and provides a direct method to incorporate quaternary chiral centers toward the synthesis of biologically relevant chromanone derivatives.
- Cyclic enones,
- Aryl grignard reagents,
- Chiral P, N ligand,
- Tetra-substituted chromanones,
- Asymmetric conjugation
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