Microwave‐promoted piperidination of halopyridines: a comparison between Ullmann, Buchwald–Hartwig and uncatalysed S_NAr reactions

Abstract

A comparative study between the most used methodologies for the preparation of piperidinyl pyridines (Buchwald-Hartwig reaction, Ullmann reaction and nucleophilic aromatic substitution (S N Ar)) by microwave-assisted piperidination of halopyridines is reported. Our results suggest that the Ullmann reaction is most effective for less reactive halopyridines, while uncatalysed S N Ar is sufficient for more reactive ones.

Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense

“…First, treating 2-chloro-6-iodopyridin-3-ol with benzyl bromide and K 2 CO 3 in tetrahydrofuran (THF) at 65 °C for 4 h gave the expected product 2 in 85% yield . Subsequently, (±)-anabasine and 2 underwent a coupling reaction to produce 3-(benzyloxy)-2-chloro-6-(2-(pyridin-3-yl)­piperidin-1-yl) pyridine 3 with 54% yield under catalysis of a combination of Pd­(pph 3 ) 4 and butyldi-1-adamantylphosphine . Then, treating 3-pyridylboronic acid and 3 with PdCl 2 (pph 3 ) 2 , Cs 2 CO 3 , and K 3 PO 4 for 66 h, we obtained the benzyl-protected alanginenmine A ( 4 ) in 71% yield .…”

“…10 Subsequently, (±)-anabasine and 2 underwent a coupling reaction to produce 3-(benzyloxy)-2chloro-6-(2-(pyridin-3-yl)piperidin-1-yl) pyridine 3 with 54% yield under catalysis of a combination of Pd(pph 3 ) 4 and butyldi-1-adamantylphosphine. 11 Then, treating 3-pyridylboronic acid and 3 with PdCl 2 (pph 3 ) 2 , Cs 2 CO 3 , and K 3 PO 4 for 66 h, we obtained the benzyl-protected alanginenmine A (4) in 71% yield. 12 Finally, we removed the benzyl group of 4 to obtain the target 1 in a stepwise 99% yield by using NaH and Pd(OAc) 2 .…”

Immobilization of nickel ions onto the magnetic nanocomposite based on cross‐linked melamine groups: Effective heterogeneous catalyst for N‐Arylation of Arylboronic acids

“…A wide range of applications of these compounds leads to the development of several protocols for C‐N bond formation over the years . An essential methodology for the preparation of aromatic amines is based on the C–N cross‐coupling reactions such as Ullmann coupling reaction, Buchwald‐Hartwig amination and Chan‐Lam coupling . Ullmann and Buchwald‐Hartwig protocols have been reported C‐N bond formation through the coupling of amines with aryl halides catalyzed by copper and palladium complexes, respectively .…”

“…[4][5][6][7][8][9] An essential methodology for the preparation of aromatic amines is based on the C-N cross-coupling reactions such as Ullmann coupling reaction, Buchwald-Hartwig amination and Chan-Lam coupling. [10][11][12][13][14] Ullmann and Buchwald-Hartwig protocols have been reported C-N bond formation through the coupling of amines with aryl halides catalyzed by copper and palladium complexes, respectively. [10,15,16] Both of these protocols suffer from several drawbacks like harsh conditions and low yields in most cases.…”