Synthesis of fluorinated chiral amines using N-tert-butylsulfinyl imines

Abstract

Fluorinated chiral amines are highly important building blocks in medicinal chemistry since fluorine decreases the basicity of the amine functionality and, thus, improves the bioavailability of a drug molecule. Recently, stereoselective synthesis of fluorinated chiral amines based on the use of N-tert-butylsulfinyl imines has attracted much attention due to the high stereoselectivity, broad substrate scope and easy experimental handing. In this article, we summarize developments in the field over the last decade, including the synthesis of trifluoromethylated, difluoromethylated, gem-difluoromethylenated and monofluoromethylated chiral amines. Stereoselective synthesis of fluorinated chiral amines based on the use of N-tert-butylsulfinyl imines has been accomplished by two major strategies. One is the stereoselective addition or asymmetric reduction of fluorinated N-tert-butylsulfinyl imines and their derivatives. The other strategy is the asymmetric addition of fluorinated reagents to N-tert-butylsulfinyl imines, the development of which is lacking new efficient and atom-economic fluorinated reagents.