.
Angewandte
Communications
dichlorocarbazole (3d,h,i,k isolated in 77, 77, 96, and 82%
yield, respectively) as well as 4,4’-diphenyldiarylamine (3j,k).
It is interesting to note that “perycarbazole” 1p, a compound
of industrial interest in high-performance semiconducting
devices,[17] undergoes our reaction, affording 3p in 50% yield
(Scheme 1). Intriguingly, diphenylamine is not effective as an
N-nucleophile (no homocoupling product 4). Neither are 2,3-
diphenylindole (electronically similar to carbazole, 5), 3,5-
trifluoromethylaniline (6), nor tosylamine (7).
Furthermore, sterics do not seem to alter reactivity. For
instance 2,7-dimethoxycarbazole still leads to 3m in 51%
yield. Even more illustrative, 1,3,5-dixylylamine still affords
3l,n,o in 67, 72, and 63% yield, respectively, in spite of
À
a methyl group ortho to the C H functionalization position.
Steric pressure could be utilized in order to induce regiose-
À
lective C N bond formation (product 3q, 5:1 in favor of the
À
less sterically hindered C H position, Scheme 2). Electronic
Scheme 2. Steering the regioselectivity by means of sterics and/or
electronics, reaction conditions: see Scheme 1. The ratio of regio-
isomers is given in parentheses.
effects are somewhat less efficient in inducing a regioselective
reaction, however, whether with electron-donating or with-
drawing substituents (3r and 3s, 2:1 and 1.5:1, respectively, in
favor of functionalization at the most electron-rich position).
Our method is also remarkably efficient for the prepara-
tion of unsymmetrical selectively isotopically labeled ortho
diamine compounds. For example, 3t (tertiary 15N, 98 +%),
and 3u (secondary 15N, 98 +%), were both readily prepared in
64% yield (Scheme 3).[15]
A biologically active carbazole could also be engaged:
Carprofen, a nonsteroidal antiinflammatory drug, notably
commercialized by Pfizer as a racemate under the trade name
Rimadyl.[18] The corresponding coupling product 3w could be
obtained with a promising 40% yield.[15,19] We expect that our
late-stage CDC-amination method could be used to generate
rapidly libraries of new drug candidates [Eq. (5)].
Scheme 1. Substrate scope, yields of isolated products. [a] All reactions
are carried out in a sealed reactor of circa 170 mL, on a 1 mmol scale
of N-coupling partner (carbazole), and 3 mmol of C-coupling partner
(diarylamine). [b] Those entries were carried out on 0.5 mmol scale, in
a circa 70 mL sealed reactor. [c] Entry 3p gives 50% NMR yield of the
expected product, but only 32% were isolated due to a difficult
separation.
we refer to this novel class of diamine compounds as
lauternamines. It should be noted that: 1) cumene is a signifi-
cantly better cosolvent than chlorobenzene, toluene, tert-
butylbenzene, or even para-cymene (the ligand on the Ru
precursor); 2) TCE is a necessary component of the reaction,
its omission typically leads to low conversion and/or decom-
position;[16] 3) O2 is the preferred oxidant, its replacement by
N2 (Cu(OAc)2 as sole oxidant) decreases the yield of 3a from
64 to 39%; 4) neither primary aniline nor acetanilide react
with carbazole, making diarylamines a privileged substrate
class in this reaction.
With these conditions in hand, we found this novel cross-
dehydrogenative amination reaction to tolerate a number of
functional groups, including halides such as Cl and Br (3c,d,g–
i,k). Selected substrates react with high efficiency, notably 3,6-
Surprisingly, engaging nonsymmetrical carbazoles system-
À
atically leads to chiral C N cross-coupling products, due to
À
constrained rotation about the C Ntert axis. We suspect that
À
the intramolecular N H···N hydrogen bond is partly respon-
3506
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 3505 –3509