Hydrogen-Bond-Assisted Controlled C–H Functionalization via Adaptive Recognition of a Purine Directing Group

We
have developed the Rh-catalyzed selective C–H functionalization
of 6-aryl­purines, in which the purine moiety directs the C–H
bond activation of the aryl pendant. While the first C–H amination
proceeds via the N1-chelation assistance, the subsequent second C–H
bond activation takes advantage of an intramolecular hydrogen-bonding
interaction between the initially formed amino group and one nitrogen
atom, either N1 or N7, of the purinyl part. Isolation of a rhodacycle
intermediate and the substrate variation studies suggest that N1 is
the main active site for the C–H functionalization of both
the first and second amination in 6-arylpurines, while N7 plays an
essential role in controlling the degree of functionalization serving
as an intramolecular hydrogen-bonding site in the second amination
process. This pseudo-Curtin–Hammett situation was supported
by density functional calculations, which suggest that the intramolecular
hydrogen-bonding capability helps second amination by reducing the
steric repulsion between the first installed ArNH and the directing
group.