Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032, China.
Future Med Chem. 2009 Aug;1(5):875-88. doi: 10.4155/fmc.09.62.
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.
氟代手性胺是药物化学中非常重要的构建模块，因为氟降低了胺官能团的碱性，从而提高了药物分子的生物利用度。最近，基于 N-叔丁基亚磺酰亚胺的氟代手性胺的立体选择性合成由于高立体选择性、广泛的底物范围和易于实验操作而受到了极大的关注。本文总结了过去十年中该领域的发展，包括三氟甲基化、二氟甲基化、偕二氟甲基化和单氟甲基化手性胺的合成。通过两种主要策略实现了基于 N-叔丁基亚磺酰亚胺的氟代手性胺的立体选择性合成。一种是氟代 N-叔丁基亚磺酰亚胺及其衍生物的立体选择性加成或不对称还原。另一种策略是氟代试剂对 N-叔丁基亚磺酰亚胺的不对称加成，其发展缺乏新的高效和原子经济性的氟代试剂。
