6380-20-7Relevant articles and documents
Coupling of Reformatsky Reagents with Aryl Chlorides Enabled by Ylide-Functionalized Phosphine Ligands
Hu, Zhiyong,Wei, Xiao-Jing,Handelmann, Jens,Seitz, Ann-Katrin,Rodstein, Ilja,Gessner, Viktoria H.,Goo?en, Lukas J.
supporting information, p. 6778 - 6783 (2021/02/01)
The coupling of aryl chlorides with Reformatsky reagents is a desirable strategy for the construction of α-aryl esters but has so far been substantially limited in the substrate scope due to many challenges posed by various possible side reactions. This limitation has now been overcome by the tailoring of ylide-functionalized phosphines to fit the requirements of Negishi couplings. Record-setting activities were achieved in palladium-catalyzed arylations of organozinc reagents with aryl electrophiles using a cyclohexyl-YPhos ligand bearing an ortho-tolyl-substituent in the backbone. This highly electron-rich, bulky ligand enables the use of aryl chlorides in room temperature couplings of Reformatsky reagents. The reaction scope covers diversely functionalized arylacetic and arylpropionic acid derivatives. Aryl bromides and chlorides can be converted selectively over triflate electrophiles, which permits consecutive coupling strategies.
Iron-Catalyzed Isopropylation of Electron-Deficient Aryl and Heteroaryl Chlorides
Sanderson, James N.,Dominey, Andrew P.,Percy, Jonathan M.
, p. 1007 - 1017 (2017/03/27)
Traditional methods for the preparation of secondary alkyl-substituted aryl and heteroaryl chlorides challenge both selectivity and functional group tolerance. This contribution describes the use of statistical design of experiments to develop an effective procedure for the preparation of isopropyl-substituted (hetero)arenes with minimal isopropyl to n-propyl isomerization. The reaction tolerates electronically diverse aryl chloride coupling partners, with excellent conversion observed for strongly electron-deficient aromatic rings, such as esters and amides. Electron-rich systems, including methyl- and methoxy-substituted aryl chlorides, were found to be less reactive. Furthermore, the reaction was found to be most successful when heteroaryl chlorides were submitted to the cross-coupling protocol. By mapping substituent effects on reaction selectivity, we were able to show that electron-deficient aryl chlorides are essential for efficient coupling, and use electronic structure calculations to predict the likelihood of successful coupling through the estimation of the electron affinity of each aryl chloride. Moderate isolated yields were achieved with selected aryl chlorides, and moderate to good isolated yields were obtained for all the heteroaryl chlorides coupled. Excellent selectivity was observed when a 2,6-dichloroquinoline was used, allowing mono-substitution on a challenging substrate. (Figure presented.).
Palladium-catalysed direct cross-coupling of secondary alkyllithium reagents
Vila, Carlos,Giannerini, Massimo,Hornillos, Valentin,Fananas-Mastral, Martin,Feringa, Ben L.
, p. 1361 - 1367 (2014/03/21)
Palladium-catalysed cross-coupling of secondary C(sp3) organometallic reagents has been a long-standing challenge in organic synthesis, due to the problems associated with undesired isomerisation or the formation of reduction products. Based on our recently developed catalytic C-C bond formation with organolithium reagents, herein we present a Pd-catalysed cross-coupling of secondary alkyllithium reagents with aryl and alkenyl bromides. The reaction proceeds at room temperature and on short timescales with high selectivity and yields. This methodology is also applicable to hindered aryl bromides, which are a major challenge in the field of metal catalysed cross-coupling reactions.
