Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• proceeds through a domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction sequence. Keywords: 2-aminochromene; domino reaction; imidazo[1,2-a]pyridine; 2-iminochromene; Michael addition; multicomponent reaction; oxidation; pyridine amination; Introduction Domino reactions are well

• interesting approaches towards the imidazo[1,2-a]pyridine core are being published nowadays [25][26][27][28][29][30], this molecular entity is still a pursued synthetic target and novel routes to diverse imidazopyridines are of value. Another privileged scaffold for drug discovery is 2-aminochromene, which

• . Subsequent treatment of the reaction mixture with nucleophile, oxidant and a base leads to the Michael addition on C(4) of the chromene ring to produce 2-aminochromene B with incorporated nucleophilic moiety. Further cyclization and deprotonation furnishes anion C, which is easily oxidized to final product 5

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• 2 equivalents of malonitrile (20) in the presence of NaHCO3 afforded 2-aminochromene 22 in 91% yield (Scheme 8) [22]. This product is thought to be the result of a Michael addition of the extra malononitrile to product 21. In addition to inorganic bases such as Na2CO3 and NaHCO3, the use of amines

• in catalytic and quantitative amounts in the synthesis of chromane derivatives by the reaction of salicylaldehyde (5) and malononitrile (20) has been reported. Costa and co-workers used Et3N in the reaction of salicylaldehyde and 2 equivalents of malononitrile (20) in CH3OH to afford 2-aminochromene

• 24 in 94% yield (Scheme 9) [22]. In 2009, Shanthi and co-workers reported the use of the amino acid L-proline as a catalyst in a three component reaction of salicylaldehyde, malononitrile and indole for the synthesis of 2-aminochromene 27 in 90% yield (Scheme 10) [23] The synthesis proceeds through a