Pd-PEPPSI-IPentCl: An effective catalyst for the preparation of triarylamines

Article abstract of DOI:10.1002/chem.201203379

Third times a charm: A new Pd-NHC catalyst, Pd-PEPPSI-IPent^Cl, has been developed for applications in amination reactions for the preparation of triarylamines. The catalyst can be used under mild conditions (carbonate base/dioxane, 80 °C) to perform multiple aminations in sequence from simple aniline derivatives that contain highly base-sensitive functional groups. Copyright

Full text of DOI:10.1002/chem.201203379

COMMUNICATION
DOI: 10.1002/chem.201203379
Pd-PEPPSI-IPentCl: An Effective Catalyst for the Preparation of
Triarylamines**
Ka Hou Hoi,[a] Jennifer A. Coggan,[b] and Michael G. Organ*[a]
The ability to prepare secondary and tertiary amines in a
controlled fashion by metal-mediated catalysis constitutes a
major advancement for the preparation of alkaloids. In
1983, Migita and Kosugi reported on the Pd-catalyzed ami-
nation of aryl bromides with N,N-diethylaminotributyltin.[1]
In the following year, the intramolecular amination of a free
amine was achieved by Boger and Panek in the synthesis of
transformation. Taken together, this would point to aniline
coordination as the difficult step in the catalytic cycle. This
stands to reason as anilines are quite electron-poor, relative
to alkylamines, making them poorer bases. Once the aniline
is coordinated to Pd, the pKa of the metal–anilinium com-
plex would be around 4, thus readily deprotonatable, which
would suggest that deprotonation itself is actually quite fa-
vourable. In our experience with bulky Pd–NHC complexes,
OA and reductive elimination (RE) are typically not rate-
limiting.[16,17] With this understanding in place we set out to
develop a highly efficient amination protocol to produce ter-
tiary arylamines that will: 1) readily produce amines with
three different aryl rings, 2) allow multiple aminations in a
single step, 3) exhibit broad functional group tolerance and
4) perform the coupling under the most mild conditions pos-
sible.
We felt that the most reactive and therefore most general
catalyst would be one that combines bulk around the Pd
center, to assist with RE, with a Pd center that is (relatively)
electron poor to encourage aniline coordination and pro-
mote deprotonation. This analysis led us to Pd-PEPPSI-
IPentCl (1) that has bulky IPent (3-pentyl) groups and the
electron-withdrawing capacity of the chlorine atoms.[18,19] To
establish a baseline reactivity for 1, we developed the reac-
tion conditions shown in Scheme 1 to perform difficult cou-
plings of electron-rich and sterically hindered oxidative ad-
lavendamycin, albeit using stoichiometric [PdACTHNUTRGNEUNG
(PPh3)4].[2] The
use of catalytic Pd in intermolecular aryl amination was first
reported by Yagupolꢀskii and co-workers in 1985.[3] After
these seminal discoveries, the groups of Buchwald[4] and
Hartwig[5] recognized the value of these reactions in a
broader context and made a number of fundamental discov-
eries and practical advancements for Pd-catalyzed amina-
tion.
Pd-catalyzed amination has focused primarily on the
union of a primary or secondary alkyl amine with an aryl
halide, which has led to applications primarily in the phar-
maceutical sector.[6] While triarylamines have received less
attention, they are very important in materials science appli-
cations, including, for example, as components in organic
light-emitting diodes,[7] solar cells[8] and organic photocon-
ductors.[9] As a consequence, a number of groups have de-
voted efforts towards their synthesis.[10–15] We have devel-
oped a Pd–NHC platform for applications in a wide variety
of transformations,[16] including amination[17] and are inter-
ested in developing an efficient and general methodology to
prepare triarylamines.
Our investigations with aniline derivatives to make diary-
lamines[17b] have revealed that the rate of amination with
Pd–NHC complexes is accelerated by electron-withdrawing
groups on the oxidative addition (OA) partner, whereas
electron-donating groups on the aniline also promote the
[a] K. H. Hoi, Prof. M. G. Organ
Department of Chemistry, York University
4700 Keele Street, Toronto, ON, M3J 1P3 (Canada)
Fax : (+1) 416-736-5936
E-mail: organ@yorku.ca
Homepage: http://www.yorku.ca/organ/
[b] J. A. Coggan
Xerox Research Centre of Canada (XRCC)
2660 Speakman Drive, Mississauga, ON, L5K 2L1 (Canada)
[**] PEPPSI = Pyridine enhanced precatalyst preparation stabilization
and initiation.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203379.
Scheme 1. Preparation of anilines with three different aryl groups.
Chem. Eur. J. 2013, 19, 843 – 845
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843

line nucleophiles generally necessitates the use of harsh con-
ditions.[10–15] While very effective in promoting amination
and sulfination, tert-butoxide is a highly aggressive base that
attacks groups such as esters and nitriles, especially at the
high temperatures (ꢀ1008C) that are commonly used for
these reactions.[12–15] Of course, milder bases are less reac-
tive, which in the case of carbonate is exacerbated by the
baseꢀs insolubility. Under the mild conditions in Scheme 3,
compound 1 effectively navigated the aminations of base-
sensitive coupling partners to complete the bis-amination se-
quence in excellent yields. We recently reported a rationally
designed chromanoxide base (14)[20] that is mild, functional
group tolerant and homogeneous, with the hope of improv-
ing reactivity and the results are promising (18 and 19).
In summary, the new Pd–NHC complex Pd-PEPPSI-
IPentCl (1)[19] has been shown to be a highly effective cata-
lyst for the coupling of mono- and disubstituted anilines to
aryl chlorides. Aniline nucleophiles are intrinsically electron
poor, thus are reluctant partners in Pd-catalyzed amination.
This is especially true for diarylamines, which is why the
amination of simple anilines is so selective; that is, they do
not over add. The catalyst also shows excellent reactivity
even with carbonate base at relatively mild temperature
(808C) for the prepartion of compounds possessing highly
sensitive functional groups. Two consecutive aminations can
be carried out readily with two equivalents of the oxidative
addition partner to generate interesting triarylamines.
Scheme 2. Two consecutive aminations with two equivalents of oxidative
addition partner.
dition partners to produce products with three different aryl
groups. With these conditions in hand, we examined the pos-
sibility of coupling two equivalents of an oxidative addition
partner to a single aniline derivative (Scheme 2). With no
excess reagent, the couplings worked well in most cases with
yields of the two telescoped couplings in the 75–90% range.
Another important aspect of these couplings is dealing
with base-sensitive functionality. The poor reactivity of ani-
Acknowledgements
This work was supported by NSERC (Canada) and the Ontario Research
Fund (ORF, Ontario). M.G.O. acknowledges XRCC for a research fel-
lowship.
Keywords: amination · homogeneous catalysis · palladium ·
PEPPSI · triarylamines
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Scheme 3. Two consecutive aminations with two equivalents of oxidative
addition partner.
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Preparation of Triarylamines
COMMUNICATION
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Received: September 20, 2012
Published online: December 18, 2012
Chem. Eur. J. 2013, 19, 843 – 845
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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