A Bulky Diamine Ligand Promoted Cross-Coupling with Difluoroalkyl Bromides via Iron Catalysis.

A Bulky Diamine Ligand Promoted Cross-Coupling with Difluoroalkyl Bromides via Iron Catalysis.
Angew Chem Int Ed Engl. 2018 Apr 17;:
Authors: Zhang X, An L, Xiao YL, Zhang S
Abstract
Although iron-catalyzed cross-coupling of Grignard reagents with alkyl halides has been well established, the adoption of the reaction for fluoroalkylations has not been reported because traditional catalytic systems often lead to defluorination reactions. Here, we describe our investigation of an iron-catalyzed cross-coupling between arylmagnesium and difluoroalkyl bromides with steric modified N,N,N',N'-tetramethyl-ethane-1,2-diamine (TMEDA) (L4) as a ligand. The use of a bulky diamine ligand (L4), in which a butylene is substituted at one carbon atom of ethylene backbone in TMEDA, enables the iron-catalyzed difluoroalkylation under mild reaction conditions with a wide range of difluoroalkyl bromides including vulnerable bromodifluoromethane, thus providing a general and cost-efficient route for application in medicinal chemistry.
PMID: 29667283 [PubMed - as supplied by publisher]

Source: Angewandte Chemie - April 17, 2018 Category: Chemistry Authors: Zhang X, An L, Xiao YL, Zhang S Tags: Angew Chem Int Ed Engl Source Type: research