Bulky Diamine Ligand Promotes Cross‐Coupling of Difluoroalkyl Bromides by Iron Catalysis. Issue 23 (2nd May 2018)

• Record Type: Journal Article
• Authors: An, Lun; Xiao, Yu‐Lan; Zhang, Shu; Zhang, Xingang
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 23(2018)
• Page Start: 6921
• Page End: 6925
• Publication Date: 2018-05-02
• Subjects: cross-coupling -- fluoroalkylation -- Grignard reagents -- iron -- ligand design; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201802713
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Described herein is the investigation of an iron‐catalyzed cross‐coupling between arylmagnesium bromides and difluoroalkyl bromides with modified N, N, N ′, N ′‐tetramethyl‐ethane‐1, 2‐diamine (TMEDA) as a ligand. The use of this bulky diamine, in which a butylene is substituted at one carbon atom of the 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 applications in medicinal chemistry. Abstract : Ligand design : An iron‐catalyzed cross‐coupling between arylmagnesium bromides and difluoroalkyl bromides, with modified N, N, N ′, N ′‐tetramethyl‐ethane‐1, 2‐diamine (TMEDA) as a ligand, is described. The combination of iron(II) salts withL enables the difluoroalkylations with a wide range of difluoroalkyl bromides, thus providing general and cost‐efficient access to difluoroalkylated arenes that are of great interest in the life sciences.