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

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.