Citation: Zhiqian Chang, Xiaochun He, Xuemei Zhang, Zhong Lian. Stereoconvergent synthesis of chiral sulfonyl phthalide containing two chiral centers from Z/E mixed alkenes via copper catalysis[J]. Chinese Chemical Letters, ;2026, 37(5): 111405. doi: 10.1016/j.cclet.2025.111405 shu

Stereoconvergent synthesis of chiral sulfonyl phthalide containing two chiral centers from Z/E mixed alkenes via copper catalysis

Zhiqian Chang ^{a, b, 1,} ,
Xiaochun He ^{b, 1} ,
Xuemei Zhang ^{b, *,} ,
Zhong Lian ^{b, *,}

a.
College of Pharmacy, North China University of Science and Technology, Tangshan 300072, China
b.
Department of Dermatology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China

changzq@ncst.edu.cn

xuemeizhang@scu.edu.cn

lianzhong@scu.edu.cn

Received Date: 4 March 2025
Revised Date: 19 May 2025
Accepted Date: 3 June 2025
Available Online: 10 June 2025

Figures(7)

Chiral phthalides are present in numerous natural products and bioactive molecules. Synthesizing phthalides from alkenes is an effective strategy. However, the challenges of facial-selectivity in the addition to Z/E mixed alkenes and diastereoselectivity at vicinal stereogenic centers have prevented the achievement of a highly selective stereoconvergent synthesis of chiral sulfonyl phthalides from Z/E alkene mixtures. Therefore, we have developed an efficient methodology for the stereoconvergent synthesis of chiral sulfonyl phthalides, using the Cu/PyBim catalytic system. This method enables the asymmetric construction of sulfonyl phthalides with multiple stereocenters for the first time. It exhibits broad applicability across various terminal and internal alkene substrates, and accommodates a diverse array of aryl, alkyl, and nitrogen radical precursors, all under exceptionally mild reaction conditions. The experimental results indicate that the reaction utilizes a Curtin-Hammett kinetic control strategy, leading to the stereoconvergent synthesis of Z/E internal alkene substrates with significant enantioselectivity and diastereoselectivity in the asymmetric construction of chiral sulfonyl phthalides.
- Sulfur dioxide,
- Stereoconvergent synthesis,
- Copper catalysis,
- Chiral sulfonyl phthalide,
- Asymmetric radical reaction
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