Co(II) PCP Pincer Complexes as Catalysts for the Alkylation of Aromatic Amines with Primary Alcohols

Article abstract of DOI:10.1021/acs.orglett.6b01647

Efficient alkylations of amines by alcohols catalyzed by well-defined Co(II) complexes are described that are stabilized by a PCP ligand (N,N′-bis(diisopropylphosphino)-N,N′-dimethyl-1,3-diaminobenzene) based on the 1,3-diaminobenzene scaffold. This reaction is an environmentally benign process implementing inexpensive, earth-abundant nonprecious metal catalysts and is based on the acceptorless alcohol dehydrogenation concept. A range of primary alcohols and aromatic amines were efficiently converted into mono-N-alkylated amines in good to excellent isolated yields.

Full text of DOI:10.1021/acs.orglett.6b01647

Letter
pubs.acs.org/OrgLett
Co(II) PCP Pincer Complexes as Catalysts for the Alkylation of
Aromatic Amines with Primary Alcohols
Matthias Mastalir,† Gerald Tomsu,† Ernst Pittenauer,‡ Gunter Allmaier,‡ and Karl Kirchner*,†
̈
†Institute of Applied Synthetic Chemistry and ‡Institute of Chemical Technologies and Analytics, Vienna University of Technology,
Getreidemarkt 9/163-AC, A-1060 Wien, Austria
S
* Supporting Information
ABSTRACT: Efficient alkylations of amines by alcohols
catalyzed by well-defined Co(II) complexes are described
that are stabilized by a PCP ligand (N,N′-bis-
(diisopropylphosphino)-N,N′-dimethyl-1,3-diaminobenzene)
based on the 1,3-diaminobenzene scaffold. This reaction is an
environmentally benign process implementing inexpensive,
earth-abundant nonprecious metal catalysts and is based on
the acceptorless alcohol dehydrogenation concept. A range of
primary alcohols and aromatic amines were efficiently
converted into mono-N-alkylated amines in good to excellent isolated yields.
he catalytic alkylation of amines with alcohols represents
an environmentally benign and atom-economic pathway
T
for the synthesis of substituted imines or amines that have
important synthetic applications in the synthesis of dyes,
fragrances, fungicides, pharmaceuticals, and agricultural chem-
icals.1−3 In terms of sustainability, the choice of alcohols as
substrates is highly desirable as they are readily available by a
variety of industrial processes and can be obtained renewably
via fermentation or catalytic conversion of lignocellulosic
biomass.4 The catalytic cycle involves two or three successive
steps: (i) acceptorless dehydrogenation (AD) of alcohols,5 (ii)
imine formation, and (iii) in situ hydrogenation of imines
(borrowing hydrogen methodology). Key features are that the
process is hydrogen neutral and that the only stoichiometric
byproduct is water.
Figure 1. Efficient base metal catalysts for the alkylation of amines
with alcohols.
Despite the significance of such coupling reactions,
homogeneous catalysts mostly employ precious metals such
as Ru,6 Rh,7 Ir,8 and Os.9 In comparison, the same reaction with
catalysts that utilize nonprecious, earth-abundant metals10 is
much less developed, although base metals were found to
readily oxidize alcohols via AD.11,12 Kempe and co-workers
described for the first time new Co PNP pincer catalysts based
on a triazine backbone that was highly active for the alkylation
of aromatic amines (Figure 1).13 This compound was
particularly interesting since in the course of the catalytic
reaction species with deprotonated, i.e., anionic, triazines seem
to play a key role. Hanson14a and Zhang14b reported a Co
catalyst, stabilized by a bis(phosphino)amine (PNP) ligand
(Figure 1), which is able to afford imines and/or amines
depending on the reaction conditions. The groups of Feringa
and Barta,15a Wills,15b and Zhao15c reported the alkylation of
amines with alcohols to give amines by utilizing Fe catalysts
featuring functionalized cyclopentadienone or hydroxy cyclo-
Figure 2. Co(II) and Co(III) PCP pincer complexes tested as
catalysts.
Inspired by recent discoveries, we describe here the efficient
alkylation of amines with alcohols catalyzed by Co(II)
complexes which are stabilized by an anionic PCP ligand
based on the 1,3-diaminobenzene scaffold (Figure 2).17 It has
to be noted that Co PCP complexes have as yet not been
applied in catalysis.18
Co complexes 1 and 2 were screened for the alkylation of
aniline with benzyl alcohol (1.4 equiv) in toluene (4 mL) at 80
°C with t-BuOK (1.3 equiv) as the additive. Complexes 3 and 4
pentadienyl ligands based upon Knolker’s complex or
Received: June 7, 2016
̈
derivatives thereof.16
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b01647
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
bearing the strongly basic coligands Me and CH2SiMe3 were
studied under base-free conditions with the same substrates but
with added 3 Å (0.2 g) molecular sieves (MS) in toluene (4
mL). For this methodology, higher reaction temperatures (130
°C) were required. All reactions were performed in a closed
vial. The results are summarized in Table 1. The products were
Table 1. Catalyst Screening of the Alkylation of Aniline with
Benzyl Alcohol
1
analyzed by H and 13C{1H} NMR and ESI MS and identified
a
entry
cat.
temp (°C)
additive
yield (%)
by comparison with authentic samples. All new products were
additionally analyzed by HRMS. In general, isolated yields after
purification by column chromatography are reported. When 1
(2.0 mol % based on alcohol) was used as precatalyst, N-
benzylaniline was isolated selectively after 16 h in 93% yield
(Table 1, entry 1). Lower catalyst loading (1 mol %) or shorter
reaction times (8 and 4 h) resulted in slightly lower yields
(Table 1, entries 2−4). Co(III) precatalyst 2 exhibited poor
catalytic activity and an in addition to amine formation, large
amounts of the corresponding N-phenylmethylene benzenei-
mine were obtained (Table 1, entry 5). With 3 and 4, in both
cases N-benzylaniline was formed selectively, but the yield was
1
2
1
80
80
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
3 Å MS
none
93
84
79
65
b
1
c
3
1
1
2
3
3
4
80
d
4
80
e
5
6
7
8
9
80
30
130
130
130
130
74
15
94
22
3 Å MS
4
none
d
a
b
c
e
Isolated yields. 1 mol % of catalyst. 8 h. 4 h. 59% imine.
a
Table 2. Coupling of Primary Alcohols and Amines Catalyzed by 1
a
Isolated yields.
B
DOI: 10.1021/acs.orglett.6b01647
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Letter
BuOH) and aromatic amines were efficiently converted into
mono-N-alkylated amines in good to excellent isolated yields.
We believe that this work may contribute to the development
of waste-free sustainable base metal catalysis.
Table 3. Coupling of Primary Alcohols and Anilines
Catalyzed by 4
a
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b01647.
1
Synthetic procedures; H and 13C{1H} NMR spectra for
all organic products (PDF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: kkirch@mail.tuwien.ac.at.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
M.M. and K.K. gratefully acknowledge the Financial support by
the Austrian Science Fund (FWF) (Project No. P28866−N34).
■
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Having established 1 and 4 as efficient catalysts, the two
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