Facile Synthesis of Chiral α-Difluoromethyl Amines from N-(tert-Butylsulfinyl)aldimines

摘要

Fluorinated amines are important synthetic building blocks in the design of antimetabolites and drugs because fluorine causes minimal structural changes and maximal shifts in electron distribution.[1], [2] Fluorine lowers the basicity of amines and improves oral absorption, suppresses metabolism, and thus increases the bioavailability of a target drug.[3]-[5] Among the fluorinated amines, -difluoromethyl amines are of particular interest as the CF2H functionality is isosteric to a carbinol (CH2OH) unit and also, as a lipophilic group, it shares much of the dipolar nature of the latter.[6], [7] Therefore, -difluoromethyl amines can be regarded as more lipophilic bioisosteres of corresponding -aminocarbinols (or -amino alcohols), which may feature some significant properties within biologically active molecules.