Citation: Ruihua Liu, Jiashu Chen, Nan Zhou, Cong Shi, Hongyun Qin, Wenlong Shan, Zemin Wang, Chenxia Gao, Chao Liu, Bokan Wang, Chao Xie, Xiangqian Li, Yuxi Lin, Jiqiang Zhu, Pan Xing, Dayong Shi. Dual photocatalytic access to antiviral alkenyl phosphonates via radical 1,4-difunctionalization across ordinary alkenes and arylacetylenes[J]. Chinese Chemical Letters, ;2026, 37(8): 112156. doi: 10.1016/j.cclet.2025.112156 shu

Dual photocatalytic access to antiviral alkenyl phosphonates via radical 1,4-difunctionalization across ordinary alkenes and arylacetylenes

Ruihua Liu ^a ,
Jiashu Chen ^a ,
Nan Zhou ^a ,
Cong Shi ^a ,
Hongyun Qin ^a ,
Wenlong Shan ^a ,
Zemin Wang ^a ,
Chenxia Gao ^a ,
Chao Liu ^a ,
Bokan Wang ^c ,
Chao Xie ^a ,
Xiangqian Li ^a ,
Yuxi Lin ^a ,
Jiqiang Zhu ^a ,
Pan Xing ^a ,
Dayong Shi ^{a, b, *,}

a.
State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China
b.
Shandong Lead High Biotechnology Co., Ltd., Ji'nan 250031, China
c.
Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China

shidayong@sdu.edu.cn

Received Date: 8 July 2025
Revised Date: 7 November 2025
Accepted Date: 21 November 2025
Available Online: 22 November 2025

Figures(6)

The radical-mediated 1,2-difunctionalization of alkenes or alkynes has emerged as an efficient strategy for augmenting molecular diversity and complexity. Nevertheless, developing remote 1,4-difunctionalization reactions through radical cascade additions involving two intermolecular unsaturated bonds confronts complex chemo-, regio-, and stereoselectivity challenges. Here, we report a photocatalytic strategy that enables the first radical 1,4-difunctionalization across simple alkenes and arylacetylenes, leveraging the distinct reactivity between alkyl phosphites and different carbon radicals, by employing 1 mol% fac-Ir(ppy)₃ as the photocatalyst and quinuclidine as the base. Mechanistic studies reveal that the photoexcited Ir(Ⅲ)* synergistically governs two processes: (1) Single-electron transfer (SET) activation of Rf-X to generate fluoroalkyl radicals, and (2) triplet energy transfer (TEnT)-mediated stereo-control of the constructed alkenyl phosphonates to achieve high Z/E selectivity. This method enables the efficient synthesis of various δ-fluoroalkyl-substituted alkenyl phosphonates with high Z/E selectivity under mild conditions. Furthermore, some products exhibit a synergistic inhibitory effect on porcine epidemic diarrhea virus (PEDV), effectively blocking viral adsorption and replication while preventing PEDV-induced cell apoptosis in vitro.
- Radical 1,4-difunctionalization,
- Dual photocatalytic,
- Alkenyl phosphonates,
- Z/E selectivity,
- Alkenes,
- Arylacetylenes
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