2026-10-11T13:39:39Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34028289 2026-09-30T00:03:38Z category_1 category_4 category_21 category_24 category_873 portal_63 item_type_6 month_year_09_2026

Aluminum Cation-Catalyzed C2–H Activation and Enantioselective Michael Addition of Indoles Ching-Pei Hsu (10686521) Chu-Chiao Wen (25139562) Chao-An Liu (8978849) Li-Hui Hong (25139565) Wan-Chi Liao (25139568) Yi-Hung Liu (1425700) Wei-Chih Chen (1755193) Ching-Wen Chiu (1858801) Biophysics Biochemistry Biotechnology Evolutionary Biology Chemical Sciences not elsewhere classified unique catalytic reactivity observed complete suppression mechanistic studies suggest far less common enantioselective michael addition assisted concerted metalation amine basic site supported aluminum cations cycle aluminum complex lewis acid catalysts aluminum cation catalyst furnishing alkylated indoles aluminum cation group catalysts based catalysts substituted indoles rds ). longer essential induce stereoselectivity group metals future development excellent enantioselectivity determining step catalyzed systems also consistent While C–H functionalization reactions are widely achieved using precious metal-based catalysts, such transformations are far less common for earth-abundant main-group metals. In this work, we demonstrate that prolinol-supported tetracoordinate aluminum cations can activate the C2–H bond of 3-substituted indoles and facilitate an enantioselective Michael addition to enones, furnishing alkylated indoles with good to excellent enantioselectivity. In contrast to transition-metal-catalyzed systems, the use of specially designed chelating enone substrates is no longer essential for the aluminum cation catalyst to induce stereoselectivity. Mechanistic studies suggest that the ligand-assisted concerted metalation-deprotonation of the C2–H bond is the rate-determining step (RDS). Stoichiometric NMR experiments provide direct evidence for an on-cycle aluminum complex, further supporting the proposed C2–H activation pathway. These findings are also consistent with the observed complete suppression of the C2–H activation when the amine basic site of the ligand was blocked or other Lewis acid catalysts were used. Our findings highlight the unique catalytic reactivity of prolinol-supported aluminum cations and provide a foundation for the future development of main-group catalysts for enantioselective C–H functionalization of heterocycles. 2026-09-29T00:00:00Z Text Journal contribution 10.1021/acs.joc.6c01197.s001 https://figshare.com/articles/journal_contribution/Aluminum_Cation-Catalyzed_C2_H_Activation_and_Enantioselective_Michael_Addition_of_Indoles/34028289 CC BY-NC 4.0