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

This study explores the synthetic utility of homo(aryl) lithum zincate reagents [LiZriPh(3)] (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 (H-1, C-13, and Li-7) NMR spectroscopy,. and in the case of 2, a classical reagent in heterobimetallic chemistry, the molecular structure of its OnBu(2) solvate [LiZnPh3(OnBu(2))(2)] has been established by X-ray crystallography. Using the synthetically relevant N-heterocyclic molecule acridine (acr, NC13H9), a new znicate-mediated arylating approach is demonstrated which allows the ehemoselective arylation of acr at its C9 position, affording 9,10-dihydro-9-phenylacridine (4) in 95% yield using microwave irradiation (125 degrees 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 degrees 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)(3)Li(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}(center dot-)] (7), which contains, a radical anion of 9-phenylacridine. The structure of the donor acceptor complex [(act)ZnPh2] (8) has also been included as a result of the reaction of 1 with acr.