Diversely Substituted Imidazo[1,2‐a]pyrazine‐8‐oxo‐3‐carbaldehydes: An Iodine‐Mediated Cyclization/Oxidation Approach

Abstract

A mild and efficient iodine‐mediated intramolecular heteroannulation approach for the construction of the imidazo[1,2‐a]pyrazinone core has been developed. Under ambient conditions, this metal‐free protocol allows easy access to densely functionalized imidazo[1,2‐a]pyrazinone‐3‐carbaldehydes or (aminomethyl)imidazo[1,2‐a]pyrazinones from substrates containing terminal alkynes by cyclization and subsequent oxidation or amination. Further diversification may be introduced by using substrates containing an internal alkyne and/or Suzuki coupling after cyclization to generate polysubstituted (dihydro)imidazo[1,2‐a]pyrazinones.

Preparation of 1,2,5‐Trisubstituted 1H‐Imidazoles from Ketenimines and Prop­arg­ylic Amines by Silver‐Catalyzed or Iodine‐Promoted Electrophilic Cyclization Reaction of Alkynes

“…Propargylic amidine A is generated by nucleophilic addition of propargylic amine 2a to ketenimine 4a . Subsequently, A undergoes iodine‐mediated electrophilic cyclization reaction to form vinyl iodide B ,11b which can aromatize to form C . Finally, C is immediately oxidized to aldehyde 6a via a cascade hydrolysis/oxidation11b or through a free radical process 11c,11e…”

Synthesis of quinoxalines or quinolin-8-amines from N-propargyl aniline derivatives employing tin and indium chlorides

“…Metallic Lewis acids can bind weakly in a side-on manner to the triple bond or attach directly to an sp-carbon. 24 Besides the more frequent reports on transition 25 or main group 26 metals and iodine 27 to promote exo-and endo-digcyclizations, 28 indium(III) species 29 are able to promote such bond formations. The given reaction mixtures seem to be favouring intramolecular hydroaminations 30 or hydroarylations.…”

Recent advances in development of imidazo[1,2-a]pyrazines: synthesis, reactivity and their biological applications

“…47 Later, an efficient iodine-mediated intramolecular heteroannulation approach for easy access to imidazo[1,2-a] pyrazinones was developed. 48 However, 42 underwent iodinemediated heteroannulation at room temperature to obtain three products 45-47, with 45 as the major product. The yield of 45 (99%) also increased with 2 equiv.…”

“…in THF-water (7 : 3) at 110 °C for 30 min under microwave irradiation to afford 313 (Scheme 70). 48 The dihydroimdazo[1,2-a]pyrazine 314 was reduced to tetrahydroimidazo [1,2- inomethylpolystyrene resin to afford N-substituted 2,6,7,8tetrahydroimidazo[1,2-a]pyrazine 315 (Scheme 71). 71…”