Rhenium-catalyzed amination of alcohols by hydrogen transfer process

Article abstract of DOI:10.1016/j.tetlet.2014.05.068

The rhenium heptahydride complex [ReH₇(PCy₃) ₂] was found to be an effective homogeneous catalyst for amination of various alcohols through hydrogen transfer mechanism. Under carbon monoxide atmosphere, a variety of primary and secondary alcohols could directly undergo the CN coupling process.

Full text of DOI:10.1016/j.tetlet.2014.05.068

Tetrahedron Letters xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Rhenium-catalyzed amination of alcohols by hydrogen transfer
process
Ablimit Abdukader a,b, Hongming Jin a, Yixiang Cheng a, Chengjian Zhu a,
⇑
a School of Chemistry and Chemical Engineering, State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, China
b School of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The rhenium heptahydride complex [ReH7(PCy3)2] was found to be an effective homogeneous catalyst for
amination of various alcohols through hydrogen transfer mechanism. Under carbon monoxide atmo-
sphere, a variety of primary and secondary alcohols could directly undergo the CAN coupling process.
Ó 2014 Published by Elsevier Ltd.
Received 14 April 2014
Revised 7 May 2014
Accepted 15 May 2014
Available online xxxx
Keywords:
Alcohol
Hydrogen transfer
Rhenium
Homogeneous catalysis
Amination
Introduction
Amination
R1
NHR2
R1
OH
The nitrogen-containing compounds are of great importance
owing to their diverse biological activities, and thus the
development of efficient methods to construct CAN bonds has
emerged as a major task in organic synthesis.1 Copper-catalyzed
Ullmann and Goldberg couplings,2 as well as palladium-catalyzed
Buchwald–Hartwig aminations3 with haloarenes have been widely
accepted as the most efficient methods to construct CAN bonds.
The amination of alcohols through a hydrogen transfer process is
[Re]
iii
i
[ReH2]
ii
R1
R1
NR2
O
also
a
powerful tool for direct construction of CAN bond.4
Compared with alkyl halides, alcohols are much more favored in
terms of their simplicity of operation and storage. In those trans-
formations, most of them could be catalyzed by Ir5 or Ru.6 Catalysts
derived from other metals, such as Au, Ni, Pd, and Rh, have also
been explored.7 However, it is still desirable to develop a new
catalyst for this transformation.
R2NH2
H2O
Scheme 1. Rhenium-catalyzed dehydrogenative CAC coupling via dual activation
model.
In past decades, Re was widely applied to organic synthesis.8 As
our on-going interests in Re-complex-catalyzed hydrogen transfer
process,9 we are interested in the development of an amination
protocol of amines with alcohols by hydrogen transfer reaction fea-
turing the only waste to be the water generated in the reaction
(Scheme 1).
Results and discussion
In our initial study, the reaction of aniline 1a and 1-phenyleth-
anol 2a was chosen as the model reaction. The results are summa-
rized in Table 1. Treatment of the reaction under Ar, air or H2
atmosphere in the catalysis of ReH7(PCy3)2 (PCy3 = tricyclohexyl-
phosphine) did not give any desired product (Table 1, entries
1–3). To our delight, when the amination reaction was run under
CO atmosphere with the same catalyst, 3a was obtained in 80%
yield (Table 1, entry 4). Other rhenium heptahydride complexes
⇑
Corresponding author. Tel.: +86 25 83594886; fax: +86 25 83317761.
E-mail address: cjzhu@nju.edu.cn (C. Zhu).
http://dx.doi.org/10.1016/j.tetlet.2014.05.068
0040-4039/Ó 2014 Published by Elsevier Ltd.
Please cite this article in press as: Abdukader, A.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.05.068

2
A. Abdukader et al. / Tetrahedron Letters xxx (2014) xxx–xxx
Table 1
10 mol % ReH7(PCy3)2 at 150 °C under CO atmosphere (1.5 atm)
with anisole as the solvent (Table 1, entry 4).
The optimization of reaction conditions for amination
With the optimized reaction conditions established, we investi-
gated the reaction scope of this protocol. We investigated that if
the primary alcohols are employed, the corresponding aldehydes
are able to react with anilines readily followed by reduction
through hydrogen transfer process. In this way, we subsequently
tested the amination protocol with primary alcohols. The results
are summarized in Table 2. To our delight, it was found that a
wider range of anilines could run the N-benzyl reaction smoothly
to afford the expected products 3a–l in good to excellent yields.
The anilines bearing electron-deficient and electron-rich functional
groups in either meta or para positions were effective under the
optimal reaction conditions. When 2-chloroaniline was subjected
to the reaction conditions, moderate yield (3g, 67%) was obtained
owing to its steric hindrance of chlorine atom. Pleasingly, other
substituted primary alcohols were able to be alkylating reagent
in our protocol. The desired products 3m–q could be obtained in
78–95% yields. It is important to point out that the reaction has
good selectivity, and only the mono amination products are
observed.
NH2
H
N
OH
1a
2a
3a
Entry
Re complex
Atmosphere
Solvent
Additive
Yielda
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PPh3)2
ReH7(dppe)
ReH7(dppf)
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PCy3)2
ReH7(PCy3)2
Ar
Air
H2
Anisole
Anisole
Anisole
Anisole
Anisole
Anisole
Anisole
THF
DMF
Toluene
DCM
Chlorobenzene
CH3CN
Anisole
Anisole
Anisole
Anisole
0
0
0
80
30
0
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
0
42
48
50
40
40
0
51
67
46
50
LiCl
4 Å MS
MgBr2
MgSO4
Subsequently, different secondary alcohols were examined
(Table 3). It was found that benzyl alcohols bearing electron-
donating substituents on the aromatic rings could perform the
reaction smoothly to provide the amination products 5a–c in
85–97% yields. Satisfactory yields were obtained when the benzyl
a
Reaction conditions: 1a (1.2 mmol), 2a (0.4 mmol), Re complex (10 mol %),
solvent (0.5 mL), CO atmosphere (1.5 atm), 150 °C. Isolated yield.
alcohols involving
a
halide substitution (5d–f), and no
were also examined, but the results were not satisfactory (Table 1,
entries 5–7). From screening of various solvents and additives, it
was found that the Re-catalyzed amination reaction could not be
improved more efficiently (Table 1, entries 8–18). Consequently,
the optimal reaction conditions should include the catalysis by
dehalogenation products were detected. To our surprise, when
1,2,3,4-tetrahydronaphthalen-2-ol was subjected to the standard
reaction conditions, no desired product 5i could be formed mainly
owing to the relatively inert character of the generated cycloke-
tone. Besides the benzylic alcohols, the simple aliphatic alcohols
were also effective to generate the amination products (5h and
5k) in moderated yields.
To gain insight into the mechanistic pathway of Re-catalyzed
amination reaction, a H/D exchanging experiment was carried
out. When aniline 1a was reacted with a mixture of benzylic
Table 2
Scope of the reaction for the synthesis of indolequinonesa
R2
[ReH7(PCy3)2]
(10 mol%)
anisole, 150 oC
NH2
OH
N
H
R1
R1
R2
3
2
1
Cl
Table 3
CH3
Scope of the reaction for the synthesis of polysubstituted pyrrolesa
N
N
H
N
H
H
R3
H
N
[ReH7(PCy3)2]
(10 mol%)
3c
, 90 %
R2
3b
NH2
, 75 %
F
3a
, 80 %
O
OH
R1
R1
R2
150 o
C
Br
R3
OMe
N
N
1
N
4
5
H
H
H
Me
3e
, 77 %
3f
, 93 %
Me
3d
, 85 %
Me
H
N
H
N
H
N
Me
, 85 %
Me
, 95 %
Me Me
N
H
Br
N
H
N
H
Me
Cl
5c
, 97 %
5a
5b
Cl
F
3i
3g
, 77 %
, 67 %
3h
, 84 %
Cl
Br
H
N
H
Cl
H
N
N
Me
Cl
OMe
Me
Me
, 86 %
Me
N
H
N
5e
5f
, 84 %
5d
, 80 %
H
N
H
Br
3l
, 91 %
3k
, 80 %
3j
, 83 %
H
N
H
N
H
N
H3C
Me
, 78 %
N
H
Me
, 86 %
N
5i
, 0 %
N
H
5g
H
5h
Br
Cl
3o
, 95 %
Me
3n
, 78 %
3m
, 81 %
H
N
H
N
H
N
Me
Me
Me
N
H
N
H
Cl
Me
Me
Me
5l
, 82 %
3p
5k
, 86 %
, 90 %
3q
5j
, 86 %
, 89 %
Me
a
Reaction conditions: 1a (1.2 mmol), 4 (0.4 mmol), ReH7(PCy3)2 (10 mol %), anisole
(0.5 mL), CO atmosphere (1.5 atm), 150 °C. Isolated yield.
a
Reaction conditions: 1a (1.2 mmol), 2a (0.4 mmol), ReH7(PCy3)2 (10 mol %),
anisole (0.5 mL), CO atmosphere (1.5 atm), 150 °C. Isolated yield.
Please cite this article in press as: Abdukader, A.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.05.068

A. Abdukader et al. / Tetrahedron Letters xxx (2014) xxx–xxx
3
Me
OH
Me
Acknowledgments
Me
Me
F
Me
N
H
(D)H
(D)H
We gratefully acknowledge the National Natural Science
Foundation of China (21172106, 21372114), the National Basic
Research Program of China (2010CB923303) and the Research
Fund for the Doctoral Program of Higher Education of China
(20120091110010) for their financial support.
Ph
NH2
2c
Ph
N
H
[ReH7(PCy3)2] (10mol%)
Me
Me
F
CO (1.5 atm)
Me
D
OH
anisole,150 oC, 24 h
3f
42%-D
3c
38%-D
1a
2f'
2c 2f'
:
= 1:1
Supplementary data
Scheme 2. Deuteration experiments.
Supplementary data (experimental details and the characteriza-
tion data) associated with this article can be found, in the online
version, at http://dx.doi.org/10.1016/j.tetlet.2014.05.068.
Ar
H
R2
O
[Re]
CO
References and notes
H
6
Ar
Ar
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H2O
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[CO-Re]
CO [Re]
HCHO
Ar
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CO
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ReH7(PCy3)2
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Scheme 3. Proposed mechanism.
alcohols 2c and 2f0 under CO atmosphere at 150 °C for 24 h, it was
found that 42% D was observed in product 3f and 38%-D was
observed in product 3c (Scheme 2). This may suggest the alcohol
hydrogen transfer process. Based on our previous work,9 it was
found that the coordination of anilines to rhenium could lead to
catalyst deactivation. Thus, CO was introduced to stabilize the
active rhenium species.
At present, the proposed mechanism is shown in Scheme 3.
Firstly, ReH7(PCy3)2 decomposed into a rhenium carbonyl complex
via CO coordination. Then, coordination of the O atom of alcohol to
Re generates the intermediate 6. Subsequently, the corresponding
aldehyde or ketone is generated in situ from 6 through further loss
of hydrogen. Then, imine 8 could be formed under from carbonyl
compound and amine. Finally, reduction of imine 8 with [Re-H2]
species 7 produces the desired product and completes the catalytic
cycle.
Conclusions
In summary, we have developed a Re-catalyzed amination
protocol of primary and secondary alcohols. A variety of anilines
are able to convert to the corresponding secondary amines with
a range of benzyl alcohols in good to excellent yields, and no
over-alkylated products could be detected. Furthermore, the only
waste generated through the overall process is water. In addition,
it is a new development in the field of rhenium chemistry.
9. Jin, H.; Xie, J.; Pan, C.; Zhu, Z.; Cheng, Y.; Zhu, C. ACS Catal. 2013, 3, 2195.
Please cite this article in press as: Abdukader, A.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.05.068