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(Parallel) kinetic resolution of 3,3-disubstituted indolines via organocatalyzed reactions with azodicarboxylates

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Abstract

A novel kinetic resolution (KR) method has been developed for 3,3-disubstituted indolines, whose catalytic asymmetric synthesis remains a significant challenge in organic synthesis. The key to the success of this KR protocol lies in the utilization of chiral phosphoric acid-catalyzed triazane formation reaction with azodicarboxylates, which enables the enantioselective synthesis of various substituted indolines bearing C3-quaternary stereocenters with good to high enantioselectivities (with s-factors up to 70). Moreover, an intriguing parallel kinetic resolution (PKR) has been developed by combining triazane formation and dehydrogenation reactions using different azodicarboxylates. Experimental studies have provided insight into the mechanism of this PKR reaction, demonstrating stereoselectivity in both triazane formation and dehydrogenation steps, favoring the opposite enantiomers. The large-scale synthesis and diverse derivatizations of the products, particularly the imine group-containing 3H-indoles, demonstrate the value of these (P)KR methods.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (22171186, 22222107), ShanghaiTech University Start-up Funding, and Analytical Instrumentation Center (# SPSTAIC10112914), SPST, ShanghaiTech University. The authors thank Mr. Huanchao Gu for the assistance with X-ray crystallographic analysis.

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  1. School of Physical Science and Technology, Shanghai Tech University, Shanghai, 201210, China

    Qianwen Jiang, Dekun Zhang, Mengyao Tang, Hua Liu & Xiaoyu Yang

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  1. Qianwen Jiang
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  2. Dekun Zhang
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Correspondence to Xiaoyu Yang.

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Supporting information The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Jiang, Q., Zhang, D., Tang, M. et al. (Parallel) kinetic resolution of 3,3-disubstituted indolines via organocatalyzed reactions with azodicarboxylates. Sci. China Chem. 67, 973–980 (2024). https://doi.org/10.1007/s11426-023-1810-9

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