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Zincate-Mediated Arylation Reactions of Acridine: Pre- and Postarylation Structural Insights

Abstract:

This study explores the synthetic utility of homo(aryl) lithum zincate reagents [LiZnPh<inf>3</inf>] (2) and [Li<inf>2</inf>ZnPh<inf>4</inf>] (3), made by cocomplexation of variable amounts of their monometallic components LiPh and ZnPh<inf>2</inf> (1), as chemoselective nucleophilic arylating reagents. Lithium zincates 2 and 3 were both characterized by multinuclear (1H, 13C, and 7Li) NMR spectroscopy, and in the case of 2, a classical reagent in heterobimetallic chemistry, the molecular structure of its OnBu<inf>2</inf> solvate [LiZnPh<inf>3</inf>(OnBu<inf>2</inf>)<inf>2</inf>] 2·2OBu<inf>2</inf> has been established by X-ray crystallography. Using the synthetically relevant N-heterocyclic molecule acridine (acr, NC<inf>13</inf>H<inf>9</inf>), a new zincate-mediated arylating approach is demonstrated which allows the chemoselective arylation of acr at its C9 position, affording 9,10-dihydro-9-phenylacridine (4) in 95% yield using microwave irradiation (125 °C, 20 min). These conditions are in contrast with previous transition-metal-catalyzed methodologies using ZnPh<inf>2</inf> as an arylating reagent, which require significantly longer reaction times (130 °C, 20 h). Oxidation of 4 with DDQ furnished 9-phenylacridine (5) in a 71% yield. New insights into the constitution of the intermediate organometallic species involved in these reactions prior to the hydrolysis step have been gained by trapping homometallic [(THF)<inf>3</inf>Li(NC<inf>13</inf>H<inf>9</inf>-Ph)] (6). Interestingly the reaction of acr with 3 equiv of PhLi/TMEDA led to the isolation of a different product, namely the novel paramagnetic [(THF)(TMEDA)Li{NC<inf>13</inf>H<inf>8</inf>-Ph}•-] (7), which contains a radical anion of 9-phenylacridine. The structure of the donor-acceptor complex [(acr)ZnPh<inf>2</inf>] (8) has also been included as a result of the reaction of 1 with acr. (Chemical Presented).