Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism
Lu Qian, Cui Yu, Lan Gan, Xixia Tang, Yulei Wang, Guixia Liu, Xuebing Leng, Zhao Sun, Yinlong Guo, Xiao-Song Xue*, Zheng Huang*
*Shanghai Institute of Organic Chemistry, University of Chinese Academy
of Sciences, 345 Lingling Road, Shanghai 200032, China, Email: xuexssioc.ac.cn,
huangzh
sioc.ac.cn
L. Qian, C. Yu, L. Gan, X. Tang, Y. Wang, G. Liu, X. Leng, Z. Sun, Y. Guo, X.-S. Xue, Z. Huang, J. Am. Chem. Soc., 2024, 146, 3427-3437.
DOI: 10.1021/jacs.3c12985
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Abstract
A chiral PCNOx-pincer iridium complex enables asymmetric transfer hydrogenation of 1,1-dialkylethenes with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels of enantioselectivity can be achieved in the reactions of substrates with secondary/primary and primary/primary alkyl combinations.
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proposed mechanism
Details
The article discusses the development of a chiral PCNOx-pincer iridium complex for the enantioselective transfer hydrogenation of 1,1-dialkylethenes using ethanol. This method addresses the longstanding challenge of achieving high enantioselectivity in the hydrogenation of purely alkyl-substituted alkenes. The catalyst demonstrates high enantioselectivity for substrates with secondary/primary and primary/primary alkyl combinations, producing all-alkyl-substituted tertiary stereocenters. Mechanistic studies reveal that the active intermediate is a dihydride species, (PCNOx)Ir(H)2, which can decay to a dimeric species via a ligand-remetalation pathway. The catalyst is more effective under transfer hydrogenation conditions with ethanol than with hydrogen gas, due to faster deactivation with H2. Computational studies highlight the significant role of London dispersion interactions between the ligand and substrate in controlling enantioselectivity. The research also explores the scope of the reaction, demonstrating tolerance to various functional groups and achieving high enantioselectivity across different substrates. This work not only solves a critical problem in asymmetric alkene hydrogenation but also enhances the utility of pincer complexes in asymmetric catalysis. Future studies aim to develop more robust catalysts by preventing deactivation through ligand-remetalation.
General procedure for asymmetric transfer hydrogenation of 1,1-dialkylethenes with EtOH
In an argon filled glovebox, alkene (0.25 mmol), Ir catalyst (9.3 mg, 10 μmol, 4 mol%), NaOtBu (1.4 mg, 15 μmol, 6 mol%), EtOH (0.25 mL) and toluene (0.05 mL) were added to a 10 mL dried Schlenk tube. The tube was sealed with a Teflon plug and the mixture was stirred at room temperature for 48 h. The reaction was quenched by exposure to air and the resulting mixture was concentrated in vacuum. The residue was purified by chromatography on silica gel (PE or PE / EtOAc [10:1) to afford the corresponding product.
Iridium-Catalyzed Asymmetric Transfer Hydrogenation of 1-Aryl-1-alkylethenes with Ethanol
X. Tang, L. Qian, G. Liu, Z. Huang, Org. Lett., 2023, 25, 4950-4954.
L. Qian, X. Tang, Z. Huang, Y. Wang, G. Liu, Z. Huang, Org. Lett., 2021, 23, 8978-8983.
Key Words
cyclohexanes, reduction of alkenes, ethanol
ID: J48-Y2024