Accessing Fluorinated Tertiary Homoallylamines via Photocatalytic Defluorinative Aminoalkylation of Fluoroalkyl-Substituted Alkenes
Wenhui Xiong, Guangyu Sun, Meijuan Zhou, Mandi Lu, Ming Joo Koh, Tao Yang
Abstract
Due to their appealing physiological attributes, tertiary aliphatic amines are pervasive in a myriad of biologically active molecules. In particular, amines featuring homoallylic substituents serve as versatile synthetic building blocks. Therefore, there is a growing demand for the development of practical and modular methods for the rapid assembly of sp 3 -rich complex amines from readily accessible chemical feedstock. Here, we disclose a multicomponent, reductive photocatalytic protocol that merges secondary alkylamines, carbonyl compounds, and fluoroalkyl-substituted alkenes, yielding fluorinated tertiary aliphatic homoallylamines. This defluorinative aminoalkylation protocol involves the addition of alkyl-substituted α-amino radicals, generated from reduction of in situ -generated iminium ions by a photocatalyst, to fluoroalkyl-substituted alkenes and subsequent fluoride elimination, reliably furnishing gem -difluoroalkene and monofluoroalkene motifs that are not easily accessible through alternative methods. Utility of the method was demonstrated by its broad functional group compatibility, the derivatization of complex alkylamines, and the synthesis of drug analogues.