Chiral Brønsted Acid from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric Reduction of Indoles

Kai Yang; Yixian Lou; Chenglan Wang; Liang-Wen Qi; Tongchang Fang; Feng Zhang; Hetao Xu; Lu Zhou; Wangyang Li; Guan Zhang; Peiyuan Yu; Qiuling Song

doi:10.1002/anie.201913656

Chiral Brønsted Acid from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric Reduction of Indoles

Angew Chem Int Ed Engl. 2020 Feb 17;59(8):3294-3299. doi: 10.1002/anie.201913656. Epub 2020 Jan 9.

Authors

Kai Yang¹, Yixian Lou², Chenglan Wang², Liang-Wen Qi³, Tongchang Fang¹, Feng Zhang¹, Hetao Xu¹, Lu Zhou¹, Wangyang Li¹, Guan Zhang⁴, Peiyuan Yu³, Qiuling Song^{1

2

4}

Affiliations

¹ Key Laboratory of Molecule Synthesis and Function Discovery, Fujian Province University, College of Chemistry at Fuzhou University, Fuzhou, Fujian, 350108, China.
² Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, 310000, P. R. China.
³ Department of Chemistry and Shenzhen Grubbs Institute, Southern University of Science and Technology, Shenzhen, 518055, China.
⁴ Institute of Next Generation Matter Transformation, College of Materials Science Engineering at Huaqiao University, 668 Jimei Boulevard, Xiamen, Fujian, 361021, China.

PMID: 31782876
DOI: 10.1002/anie.201913656

Abstract

A new chiral Brønsted acid, generated in situ from a chiral phosphoric acid boron (CPAB) complex and water, was successfully applied to asymmetric indole reduction. This "designer acid catalyst", which is more acidic than TsOH as suggested by DFT calculations, allows the unprecedented direct asymmetric reduction of C2-aryl-substituted N-unprotected indoles and features good to excellent enantioselectivities with broad functional group tolerance. DFT calculations and mechanistic experiments indicates that this reaction undergoes C3-protonation and hydride-transfer processes. Besides, bulky C2-alkyl-substituted N-unprotected indoles are also suitable for this system.

Keywords: Brønsted acid; asymmetric catalysis; boron; heterocycles; water.

Abstract

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