One-Pot Synthesis of 3-Substituted 2-Arylpyrrole in Aqueous Media via Addition–Annulation of Arylboronic Acid and Substituted Aliphatic Nitriles

Abstract

Pd(II)-catalyzed C-C coupling reactions between substituted aliphatic nitriles and arylboronic acids followed by in situ cyclodehydration have been employed for the first time to synthesize a wide variety of 3-substituted 2-aryl-1H-pyrroles in aqueous acetic acid. This one-pot synthesis is green, and it conforms to atom economy. The structures of two representative pyrroles, 3k and 5f, were confirmed by X-ray crystallographic analysis.

Palladium-Catalyzed Cascade Reactions of δ-Ketonitriles with Arylboronic Acids: Synthesis of Pyridines

“…For example, the Shao group reported the carbopalladation of arylboronic acids to nitriles, followed by intramolecular cyclization to construct imidazoles . The Adhikari group reported Pd­(II)-catalyzed coupling substituted aliphatic nitriles with arylboronic acids to synthesize 3-substituted 2-aryl-1 H -pyrroles . The Liao group described Pd-catalyzed addition of arylboronic acids to carbonic ester substituted nitriles to synthesize spirooxindolyl oxazol-2­(5 H )-ones .…”

Two‐Step One‐Pot Synthesis of Unsymmetrical (Hetero)Aryl 1,2‐Diketones by Addition‐Oxygenation of Potassium Aryltrifluoroborates to (Hetero)Arylacetonitriles

“…Taking the above results and previous reports into consideration, we then proposed a possible reaction mechanism (Scheme ). First, arylpalladium species A is generated by transmetalation with the potassium aryltrifluoroborate.…”

“…The one‐pot procedure is an important and prevalent technique in synthetic organic chemistry, as it satisfies the demands of green and sustainable chemistry by reducing reaction time, cost, and undesired chemical waste. [15d], [16a], [18a] Because of its widespread use and low toxicity, copper‐catalyzed aerobic benzylic C–H oxygenation reactions are an efficient method for the synthesis of complex functionalized organic molecules . Taking these facts into consideration, we began our investigation by selecting 2‐phenylacetonitrile ( 1a ) and potassium phenyltrifluoroborate ( 2a ) as model substrates to optimize the reaction conditions (Table ).…”

“…By pursuing these challenges, we envisioned that cost‐effective and commercially available phenylacetonitrile, in which a phenyl ring is attached at the α‐position to the cyano group, may serve as an ideal starting material for the synthesis of 1,2‐diketones. In recent years, nitriles and their derivatives have been extensively used for the synthesis of diverse heterocyclic compounds, as they are inexpensive, stable, nontoxic, and abundant in nature (Scheme a–c) . Nitriles may also serve as useful building blocks in organic synthesis.…”

Recent Advances for the Synthesis of N‐Unsubstituted Pyrroles

“…3-Substituted 2-aryl-1H-pyrroles 178 were prepared from substituted aliphatic nitriles 175 and arylboronic acids 176 as a result of CÀ C coupling reactions in presence of Pd(II) catalyst followed by cyclodehydration. [57] Nucleophilic addition of arylboronic acid to nitrile in mild acidic conditions (aqueous acetic acid) leads to Paal-Knorr intermediate -1,4-iminoaldehyde 177 (Scheme 58). The latter spontaneously undergoes in situ intramolecular annulation and dehydration.…”