Zincate-mediated arylation reactions of acridine : pre- and postarylation structural insights

Hernán-Gómez, Alberto and Herd, Emma and Uzelac, Marina and Cadenbach, Thomas and Kennedy, Alan R. and Borilovic, Ivana and Aromí, Guillem and Hevia, Eva (2015) Zincate-mediated arylation reactions of acridine : pre- and postarylation structural insights. Organometallics, 34 (11). pp. 2614-2623. ISSN 0276-7333 (https://doi.org/10.1021/om501251q)

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This study explores the synthetic utility of homo(aryl) lithum zincate reagents [LiZnPh3] (2) and [Li2ZnPh4] (3), made by cocomplexation of variable amounts of their monometallic components LiPh and ZnPh2 (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 OnBu2 solvate [LiZnPh3(OnBu2)2] 2·2OBu2 has been established by X-ray crystallography. Using the synthetically relevant N-heterocyclic molecule acridine (acr, NC13H9), 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 ZnPh2 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)3Li(NC13H9-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{NC13H8-Ph}•−] (7), which contains a radical anion of 9-phenylacridine. The structure of the donor−acceptor complex [(acr)ZnPh2] (8) has also been included as a result of the reaction of 1 with acr.