Palladium-Catalyzed Amination of Unprotected Five-Membered Heterocyclic Bromides

Abstract

An efficient method for the palladium-catalyzed amination of unprotected bromoimidazoles and bromopyrazoles is presented. The transformation is facilitated by the use of our newly developed Pd precatalyst based on the bulky biarylphosphine ligand tBuBrettPhos (L4). The mild reaction conditions employed allow for the preparation of a broad scope of aminoimidazoles and aminopyrazoles in moderate to excellent yields.

C4-Alkylamination of C4-Halo-1H-1-tritylpyrazoles Using Pd(dba)2 or CuI

“…The reactions of 1 Br with adamantylamine or tert -butylamine afforded the corresponding products 2m and 2n in 90% and 53% yields, respectively (entries 13 and 14). Furthermore, reactions with aromatic amines (anilines and 1-naphtylamine) gave the corresponding 2o (94%) , 2p (91%), and 2q (85%) in high yields (entries 15–17) as being analogous to Buchwald’s findings [ 21 ]. As the reaction with diphenylamine afforded 2r in 45% yield, we surmised that bulkiness at the reaction center depresses the chemical yield (entry 18).…”

“…As the Buchwald–Hartwig coupling reaction for 4-halo-1 H -pyrazoles requires high temperatures (>80 °C) as well as prolonged time [ 19 , 20 , 21 ], we utilized microwave (MW) apparatus to expedite the experimental process. Ligand screening was performed with the fixed conditions of 4-iodo-1 H -1-tritylpyrazole ( 1 I, X = I), Pd(dba) 2 , xylene, 160 °C, and 10 min under MW irradiation (entries 1–4).…”

“…In the following year, the same group described the amidation of five-membered heterocycles with aromatic amides, wherein three examples using 1-benzyl-4-bromopyrazoles and one example using 4-bromo-1-methylpyrazole were reported (Equation (2)) [ 20 ]. In their subsequent study on the amination of unprotected five-membered bromoheterocycles, Pd-catalyzed coupling reactions of 4-bromopyrazole with eleven aromatic amines, as well as one benzylic amine, were disclosed (Equation (3)) [ 21 ]. Recently, Buchwald et al described visible-light-mediated amination of aryl halides in the presence of nickel and photoredox catalysts, for which one example of the reaction between 1-benzyl-4-bromopyrazole and pyrrolidine was included (Equation (4)) [ 22 ].…”

Palladium Immobilized onto Functionalized Magnetic Nanoparticles as Robust Catalysts for Amination and Room‐Temperature Ullmann Homocoupling of Aryl Halides: A Walk Around the C−F Bond Activation

“…The development of novel ligands for palladium and optimization of catalytic conditions are important aspects of Pd‐catalyzed reactions. To date, several efficient Pd–ligand systems have been developed to promote C−C and C−N bond formation in Ullmann and Buchwald–Hartwig reactions, respectively . Direct homocoupling of aryl halides (Ullmann reaction) is the best method for the construction of aryl–aryl bonds.…”

The palladium‐catalyzed C‐N cross‐coupling reaction of diheteroaryl disulfides with heterocyclic amines

“…[11][12][13] Driven by the need for an efficient synthetic route to these privileged motifs, [14][15][16] several research groups have aimed at preparation of these privileged structures via metal-catalyzed coupling reactions. In the area of Pd-catalyzed amination of aryl halides, [17][18][19][20][21] the Buchwald-Hartwig amination remains outstanding owing to its mild reaction conditions, wide substrate scope, high functional group compatibility, and further applications. [22][23][24][25] Our group has successfully accomplished conventional approaches for the synthesis of tetra-substituted pyrimidines via the Buchwald reactions [26][27][28][29] by using aryl halides or aryl sulfonates as electrophiles.…”