First Copper‐Catalyzed Intramolecular Amidation in Substituted 4‐Iodopyrazoles Leading to the Synthesis of Pyrazolo[4,3‐b]‐ pyridin‐5‐ones

Abstract

An unprecedented copper-catalyzed intramolecular amidation of substituted 4-iodopyrazoles generated either via Baylis-Hillman or Horner-Wadsworth-Emmons chemistry for the synthesis of pyrazoloA C H T U N G T R E N N U N G [4,3-b]pyridine-5-ones is described. In addition, the effect of the stereochemistry of the acrylamide on the cross-coupling reaction has been investigated and it is demonstrated that only the Z-isomer is favoured to undergo the intramolecular cyclization.

Exploration of pyrazole based aldo‐x bifunctional building blocks for the synthesis of pyrazole annulated molecular architectures

“…An intramolecular C‐N bond formation of various substituted 4‐iodopyrazoles 17 toward construction of pyrazolo[4,3‐ b ]pyridine‐5‐ones 22 has been reported under the catalysis of CuI. [ 36 ] Firstly, the reaction of 4‐iodopyrazole‐3‐carbaldehydes 17 with acrylonitrile in presence of DABCO yielded the MBH adducts 18 , which upon acetylation followed by S N 2‐displacement with NaBH 4 and controlled hydrolysis with TFA/H 2 SO 4 produced the pyrazole linked amides 21 . Thereafter, the cyclized products, pyrazolo[4,3‐ b ]pyridine‐5‐ones 22 were obtained in 32%‐39% yields via Cu assisted intramolecular C‐N coupling reaction.…”

Copper‐Catalyzed Cascade Reaction of 4‐Iodopyrazole Derivatives with Amidines for the Synthesis of Pyrazolo[4,3‐d]pyrimidine Derivatives

“…[3][4][5] 4-Iodo-1,5-diphenyl-1H-pyrazole-3-carbaldehyde and acetamidine hydrochloride were selected as model substrates to optimize the reaction conditions, including optimization of the copper source, ligands, base, and solvents under a nitrogen atmosphere. As delineated in Table 1, four ligands were investigated at 90°C using 10 mol-% CuI as catalyst and 300 mol-% Cs 2 CO 3 as base in dimethyl sulfoxide (DMSO) ( Table 1, entries 2-5); it was found that l-proline (20 mol-%) displayed the best activity.…”

“…For example, we have demonstrated that amides derived from the Morita-Baylis-Hillman (MBH) adducts of 4-iodopyrazolecarbaldehyde undergo copper-catalyzed intramolecular Goldberg-type C-N coupling to afford substituted pyrazolo [4,3-b]pyridin-5-ones, whereas the allylamines obtained from the MBH adducts undergo Ullman-type C-N coupling to afford substituted pyrazolo [4,3-b]pyridines. [3,4] In addition, we success-fully synthesized pyrazolo-fused benzodiazepines and benzoxazoazepines through copper-mediated C-N and C-O cross-coupling cascade reactions of 4-iodopyrazolecarbaldehydes with 1,2-phenylenediamines and 2-aminophenols, respectively. [5] However, interestingly, during the study we discovered that only intramolecular C-N and C-O couplings could be performed; the intermolecular version resulted in failure.…”

Copper‐Catalyzed Cascade Reactions of Substituted 4‐Iodopyrazolecarbaldehydes with 1,2‐Phenylenediamines and 2‐Aminophenols

“…[4] Recently, we reported the synthesis of pyrazoloA C H T U N G T R E N N U N G [4,3-b]pyridine-5-ones via the first copper-promoted intramolecular amidation in 4-iodopyrazole derivatives generated either from Morita-Baylis-Hillman (MBH) or HornerWadsworth-Emmon chemistry. [5] Although during this study the C À N coupling with allylamides was successful, we failed to achieve similar cross-coupling reactions with allylamines accessed via MBH chemistry. Nevertheless, we were keen to explore the copperpromoted cross-coupling of substituted 4-iodopyrazoles as it would allow access to intermediates suitable for generating novel annulated pyrazoles.…”