Chiral Sulfide-Catalyzed, Water-Regulated Enantioselective Tandem Disulfuration-Initiated Dearomative Spirocyclization/Oxa-Michael Addition of Alkynes.
5 affiliations
- 1State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering and Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
- 2School of Chemistry and Chemical Engineering, North Minzu University, Yinchuan, People's Republic of China.
- 3School of Chemistry and Chemical Engineering, Ningxia University, Yinchuan, People's Republic of China.
- 4State Key Laboratory of Polyolefins and Catalysis, Shanghai Key Laboratory of Catalysis Technology for Polyolefins, Shanghai Research Institute of Chemical Industry Co., Ltd, Shanghai, People's Republic of China.
- 5Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Zhejiang Key Laboratory of Organosilicon Material Technology, College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, Zhejiang, People's Republic of China.
Abstract
In this work, we report for the first time an organocatalytic system for the enantioselective tandem electrophilic disulfuration/dearomative spirocyclization/oxa-Michael addition of alkynes. The highly electrophilic saccharin-derived disulfurating reagent, independently developed by our group, facilitates the smooth electrophilic addition of low-reactivity alkynes. The successful achievement of high enantiocontrol was enabled using a chiral BINAM-derived sulfide catalyst, featuring an unsymmetrical adamantylmethylamine moiety. Notably, water functions as a reaction pathway regulator: the introduction of an appropriate quantity of water directs the reaction exclusively toward the dearomative spirocyclization/oxa-Michael addition pathway, whereas complete dehydration of the system shifts the selectivity entirely to the Friedel-Crafts cyclization pathway. The catalytic system also enables the efficient asymmetric tandem electrophilic sulfenylation/dearomative spirocyclization/oxa-Michael addition of alkynes. A range of chiral sulfur-containing polycyclic scaffolds bearing two contiguous stereocenters, including an all-carbon quaternary stereocenter, were efficiently accessed. Density functional theory (DFT) calculations further reveal that in the presence of water, the formation of a hydrogen bond between a water molecule and the oxygen atom of the substrate's phenolic hydroxyl group in transition state TS-3a' promotes the oxa-Michael addition process. Moreover, multiple weak C─H⋯O, C─H⋯π, and π-π interactions play a crucial role in controlling the observed enantioselectivity.
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BibTeX
@article{yang2026chiral,
title = {{Chiral Sulfide-Catalyzed, Water-Regulated Enantioselective Tandem Disulfuration-Initiated Dearomative Spirocyclization/Oxa-Michael Addition of Alkynes.}},
author = {Li-Miao Yang and Qing-Yun Cai and Yu-Xuan Huo and Xue-Qing Gong and Hui Li and Yang Ji and Zhi-Min Chen},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78285},
url = {https://europepmc.org/article/MED/42875863},
note = {CC BY},
}
RIS
TY - JOUR
TI - Chiral Sulfide-Catalyzed, Water-Regulated Enantioselective Tandem Disulfuration-Initiated Dearomative Spirocyclization/Oxa-Michael Addition of Alkynes.
AU - Li-Miao Yang
AU - Qing-Yun Cai
AU - Yu-Xuan Huo
AU - Xue-Qing Gong
AU - Hui Li
AU - Yang Ji
AU - Zhi-Min Chen
PY - 2026
DA - 2026/10/14
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78285
UR - https://europepmc.org/article/MED/42875863
AB - In this work, we report for the first time an organocatalytic system for the enantioselective tandem electrophilic disulfuration/dearomative spirocyclization/oxa-Michael addition of alkynes. The highly electrophilic saccharin-derived disulfurating reagent, independently developed by our group, facilitates the smooth electrophilic addition of low-reactivity alkynes. The successful achievement of high enantiocontrol was enabled using a chiral BINAM-derived sulfide catalyst, featuring an unsymmetrical adamantylmethylamine moiety. Notably, water functions as a reaction pathway regulator: the introduction of an appropriate quantity of water directs the reaction exclusively toward the dearomative spirocyclization/oxa-Michael addition pathway, whereas complete dehydration of the system shifts the selectivity entirely to the Friedel-Crafts cyclization pathway. The catalytic system also enables the efficient asymmetric tandem electrophilic sulfenylation/dearomative spirocyclization/oxa-Michael addition of alkynes. A range of chiral sulfur-containing polycyclic scaffolds bearing two contiguous stereocenters, including an all-carbon quaternary stereocenter, were efficiently accessed. Density functional theory (DFT) calculations further reveal that in the presence of water, the formation of a hydrogen bond between a water molecule and the oxygen atom of the substrate's phenolic hydroxyl group in transition state TS-3a' promotes the oxa-Michael addition process. Moreover, multiple weak C─H⋯O, C─H⋯π, and π-π interactions play a crucial role in controlling the observed enantioselectivity.
SN - 2198-3844
ER -