Rapid and Efficient Microwave-Assisted Synthesis of 4-, 5-, 6- and 7-Azaindoles

Abstract

Under microwave irradiation conditions, the imines/ enamines formed between aminopyridines and ketones are converted in moderate to good yields to the corresponding 4-, 5-, 6-or 7azaindoles via the Hegedus-Mori-Heck reaction (intramolecular Heck reaction). A systematic examination of all isomeric azaindoles synthesis revealed this one-pot procedure to be general in scope.

Transition metals in organic synthesis: Highlights for the year 2005

“…(31)) [436] and of alkenes with O-pentafluorobenzoylamidoximes [437] were reported. Intramolecular Heck reactions [394,[438][439][440][441][442] were used as the key step toward an array of synthetic targets for example, stephacidin A [443], 1-epi aglycon of cripowellins A and B [444], hamigeran B [202], mensacarcin [445], (−)-galanthamine and (−)-morphine [446], gelsemine [447], 5-substituted azepino [3,4-b]indoles [448], komaroviquinone and faveline methyl ether [449], pseudopteroxazole [450], diazonamide A [75], 4,7-azaindoles [451], substituted tryptophans (Eq. (32)) [452], 3,5,7-substituted indoles [453], morphine fragments [454], (+)-wortmannin [255], umbrosone [85] and the tricyclic core of cyathin diterpenoids [455].…”

Evolution of microwave irradiation and its application in green chemistry and biosciences

“…Imines/enamines 26 can be converted via a microwave-assisted intermolecular Heck reaction to the corresponding azaindoles 27 in good yields [59]. Several synthesis routes have been investigated, including the one-step reaction (route A) of amino pyridines 23 with ketals or ketones 25, respectively, as well as the one-pot, two-step reaction (route B), leading to azaindoles as a class of anti-infective agent, anti-inflammatory agent, and antibacterial agent 24, 27 as shown in Scheme 8.…”

Synthesis of Substituted 4-, 5-, 6-, and 7-Azaindoles from Aminopyridines via a Cascade C–N Cross-Coupling/Heck Reaction

“…16,17 However, azaindoles are only attained in good yields when either cyclic ketones under microwave conditions, pyruvate derivatives, or activated aromatic ketones are used. Strategies to obtain imine/enamine from deactivated ketones and amino-ortho-halogenated pyridines are scarce; they generally require harsh reaction conditions; they possess low functional group tolerance; and chemo-and stereoselectivity are compromised.…”