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

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

doi:10.3762/bjoc.16.217

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.

Highlights

In recent years, substitution of hydrogen by fluorine atoms or fluorine-containing groups usually provides unexpected biological and physicochemical properties, which has become an established approach for the development of pharmaceuticals [1-9], agrochemicals [10-14], and advanced materials [15-19]
Arylethynes were studied as new C-nucleophiles in the asymmetric Mannich addition reactions with (S)-N-tertbutylsulfinyl-3,3,3-trifluoroacetaldimine
The results reported in this work expand our knowledge of the reactivity of imines and the origins of stereocontrol, as well as provide synthetic access to a series of trifluoromethylpropargylamine of high biological interest

Summary

Introduction

Substitution of hydrogen by fluorine atoms or fluorine-containing groups usually provides unexpected biological and physicochemical properties, which has become an established approach for the development of pharmaceuticals [1-9], agrochemicals [10-14], and advanced materials [15-19]. Arylethynes were studied as new C-nucleophiles in the asymmetric Mannich addition reactions with (S)-N-tertbutylsulfinyl-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.

Results

Conclusion