Synthesis of imidazo[1,2a]pyridines via three-component reaction of 2-aminopyridines, aldehydes and alkynes

Gold‐Catalyzed Redox Synthesis of Imidazo[1,2‐a]pyridines using Pyridine N‐Oxide and Alkynes

“…[9] The imidazo[1,2- a ]pyridine ring system can be formed in many ways: typically they are formed via condensation of aminopyridines and α-haloketones [10] and can be formed by a one-pot condensation of an aldehydes, isonitrile and a 2-aminopyridine though this approach can require harsh conditions so limiting the scope of functionalities tolerated in this reaction. [11] More recently a number of copper catalysed methodologies have been developed, namely a three-component reaction of a 2-aminopyridine with an aldehyde and an alkyne, [12] a dehydrogenative coupling of a ketone with a 2-aminopyridine conducted at 40°C, [13] an oxidative cyclization of a halo-alkyne with an amino-pyridine at 60°C, [14] and an oxidative reaction between a ketone and a 2-aminopyridine carried out at 120°C. [15] Two further methods reported recently are worthy of note, the iron(III)-catalysed reaction between a nitro-olefin and an amino-pyridine achieved at 80°C, [16] and the silver-mediated oxidative coupling between terminal alkynes and a 2-aminopyridine conducted at 110°C.…”

Copper‐Catalysed Multicomponent Syntheses of Heterocycles

“…Liu and co‐workers developed a CuSO 4 /TsOH catalysed three‐component reaction for the synthesis of imidazo[1,2‐ a ]pyridines based on 2‐aminopyridines, aldehydes and alkynes (Scheme ) . The reaction was performed using aminopyridine, benzaldehyde and ethynyl benzene (3CR) in presence of CuSO 4 combined with Bronsted acids such as TsOH in the ratio 10 : 10 mol% as catalyst in toluene (5 ml).…”

Recent advances in the chemistry of imine-based multicomponent reactions (MCRs)

“…The electrophilic character of imines was also explored by Liu et al 26 for the synthesis of imidazo[1,2-a]pyridines 25 via a threecomponent reaction of 2-aminopyridines, aldehydes and alkynes in the presence of CuSO 4 /TsOH as catalyst (Scheme 8). A variety of functional groups on the aromatic moieties are tolerable, but this methodology remains unsuitable for substrates containing hydroxy, dialkylamino, and bromo substituents.…”