Synthesis of Chiral 2-Substituted 1,4-Benzoxazin-3-ones via Iridium-Catalyzed Enantioselective Hydrogenation of Benzoxazinones

Yu Nie; Jing Li; Jun Yan; Qianjia Yuan; Wanbin Zhang

doi:10.1021/acs.orglett.1c01701

Synthesis of Chiral 2-Substituted 1,4-Benzoxazin-3-ones via Iridium-Catalyzed Enantioselective Hydrogenation of Benzoxazinones

Org Lett. 2021 Jul 16;23(14):5373-5377. doi: 10.1021/acs.orglett.1c01701. Epub 2021 Jul 2.

Authors

Yu Nie¹, Jing Li¹, Jun Yan¹, Qianjia Yuan¹, Wanbin Zhang^{1

2}

Affiliations

¹ Shanghai Key Laboratory of Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
² College of Chemistry, Zhengzhou University, 75 Daxue Road, Zhengzhou 450052, P. R. China.

PMID: 34213913
DOI: 10.1021/acs.orglett.1c01701

Abstract

An efficient iridium-catalyzed enantioselective hydrogenation of 2-alkylidene 1,4-benzoxazin-3-ones using our developed iPr-BiphPHOX as a ligand is reported. This method showed good functional group compatibility and delivered the corresponding reduced products in excellent yields (up to 99%) with excellent enantioselectivities (up to 99% ee). The reaction proceeded very well on a gram scale with low catalyst loadings (0.1 mol %), providing the product with no erosion in enantioselectivity. Additionally, three bioactive molecules can be easily obtained from the reduced products.