Asymmetric Mannich reactions of (S)- N- tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

Ziyi Li; Li Wang; Yunqi Huang; Haibo Mei; Hiroyuki Konno; Hiroki Moriwaki; Vadim A Soloshonok; Jianlin Han

doi:10.3762/bjoc.16.217

Asymmetric Mannich reactions of (S)- N- tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

Beilstein J Org Chem. 2020 Oct 29:16:2671-2678. doi: 10.3762/bjoc.16.217. eCollection 2020.

Authors

Ziyi Li¹, Li Wang¹, Yunqi Huang¹, Haibo Mei¹, Hiroyuki Konno², Hiroki Moriwaki³, Vadim A Soloshonok^{4

5}, Jianlin Han¹

Affiliations

¹ Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, Jiangsu, China.
² Department of Biological Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
³ Hamari Chemical Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka 533-0024, Japan.
⁴ Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizábal 3, 20018 San Sebastián, Spain.
⁵ IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, Plaza Bizkaia, 48011 Bilbao, Spain.

Abstract

In the present work, arylethynes were studied as new C-nucleophiles in the asymmetric Mannich addition reactions with (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine. The reactions were conducted under operationally convenient conditions affording the corresponding Mannich adducts with up to 87% yield and 70:30 diastereoselectivity. The isomeric products can be separated using regular column chromatography to afford diastereomerically pure compounds. The purified Mannich addition products were deprotected to give the target enantiomerically pure trifluoromethylpropargylamines. A mechanistic rationale for the observed stereochemical outcome is discussed.

Keywords: C-nucleophile; CF3-aldimine; arylethynes; asymmetric Mannich reaction; fluorinated propargylamine.

Grants and funding

We gratefully acknowledge the financial support from the National Natural Science Foundation of China (No. 21761132021) and Qing Lan Project of Jiangsu Province. IKERBASQUE, Basque Foundation for Science (for V. A. Soloshonok) is also acknowledged.