B(C6F5)3-catalyzed metal-free hydrogenation of naphthylamines

Article abstract of DOI:10.1039/c5ob00009b

A catalytic metal-free hydrogenation of naphthylamines using B(C₆F₅)₃ as a catalyst was successfully achieved under mild conditions for the first time to furnish a variety of tetrahydronaphthylamines in 88-99% yields.

Full text of DOI:10.1039/c5ob00009b

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DOI: 10.1039/C5OB00009B
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ARTICLE TYPE
B(C6F5)3-catalyzed metal-free hydrogenation of naphthylamines†
Gen Lia, Yongbing Liua and Haifeng Du*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
mixture of regio-isomers was obtained in some cases (Scheme
2).11 However, to the best of our knowledge, the metal-free
45 homogeneous hydrogenation has rarely been reported. As part of
our general interest in the FLP chemistry, recently, we reported
the asymmetric hydrogenation of imines, silyl enol ethers, and
2,3-disustituted quinoxalines, and the highly cis-selective
hydrogenation of pyridines, in which borane catalysts were
50 generated in situ by the hydroboration of alkenes with Piers’
borane HB(C6F5)2.12-14 In searching for challenging unsaturated
compounds for the FLP catalysis, the hydrogenation of hazardous
naphthylamines 1 to tetrahydronaphthylamines 2 attracts our
interest. Herein, we wish to report our preliminary results on this
55 subject.
5
A catalytic metal-free hydrogenation of naphthylamines using
B(C6F5)3 as a catalyst was successfully achieved under mild
conditions for the first time to furnish
tetrahydronaphthylamines in 88-99% yields.
a variety of
Catalytic hydrogenation of unsaturated compounds represents one
10 of the most useful transformations in both academia and
industry.1 Particularly, the hydrogenation of hazardous
compounds such as polycyclic aromatic hydrocarbons (PAHs) to
the less toxic and high-valued partial saturated materials is a very
meaningful transformation for the environment and the chemical
15 production. Usually, transition metals were the most often used
catalysts for the heterogeneous or homogeneous hydrogenation of
PAHs.2,3 In contrast, the metal-free approach has been less
developed. From 1989 to 1990, Köster, Yalpani, and co-workers
employed boranes as catalysts to realize the hydrogenation of
20 naphthalene, anthracene, phenanthrene and other aromatic
compounds, but harsh reaction conditions were required (170-
200 °C and 25-100 atm H2).4 The recent advent chemistry of
frustrated Lewis pairs (FLPs) opens a new era for the metal-free
hydrogenation.5 A wide range of unsaturated compounds have
25 been successfully reduced using stoichiometric or catalytic
amount of FLPs.6,7 In 2012, Stephan and Segawa reported the
hydrogenation of the PAHs including anthracene derivatives,
tetracene and tetraphene at 80 °C and 100 atm H2 pressure used
B(C6F5)3 and Ph2PC6F5 as a FLP catalyst.8 Significantly, Stephan,
30 Grimme, and co-workers achieved a highly challenging aromatic
hydrogenation of anilines using one equivalent of B(C6F5)3 at
110 °C and 4 atm H2 pressure (Scheme 1).9 Despite these
advances, the development of metal-free hydrogenation of PAHs
using catalytic amount of FLP catalyst under mild condition is
35 still highly desirable.
Raney Ni, NiMo/Al2O3,
NHR'
quenched skeletal Ni
NHR'
previous work
R
NHR'
1
this work
R
metal-free hydrogenation
2
Scheme 2 Catalytic hydrogenation of naphthylamines.
Initially, we examined the in situ catalyst generation strategy
for the hydrogenation of naphthylamine 1a. Unfortunately, in the
60 presence of 10 mol
% of Piers’ borane HB(C6F5)2 and
pentafluorostyrene, the hydrogenation of naphthylamine 1a at
110 °C with H2 (50 bar) did not occur at all (Scheme 3), which is
likely due to the relatively weaker Lewis acidity of the borane
catalyst. To our pleasure, a stronger Lewis acidic borane
15
65 B(C6F5)3 can give a quantitative conversion under the same
conditions, and the reduction of the phenyl ring in naphthylamine
1a was not observed(Scheme 3).
NHR
NH2R
B(C6F5)3
NHPh
NHPh
borane (10 mol %)
(1.0 equiv)
[HB(C6F5)3]
R'
H2 (50 bar), toluene
110 °C, 20 h
R'
H2 (4 atm)
1a
2a
S. Grimme and D. W. Stephan
Scheme 1 Metal-free hydrogenation of anilines.
+
HB(C6F5)2
C6F5
B(C6F5)3
no reaction
>99% conv.
Tetrahydronaphthyl amines are important functional moieties
present in various biologically active compounds.10 The
40 hydrogenation of naphthylamines provides a straightforward
access to them. Several heterogeneous nickel catalysts have been
well developed for the hydrogenation of naphthylamines 1, and a
Scheme 3 Metal-free hydrogenation of naphthylamine 1a.
70
The reaction conditions were further optimized, and some
results are summarized in Table 1. The B(C6F5)3-catalyzed
hydrogenation of naphthylamine 1a went smoothly at 60 °C with
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NHR'
NHR'
H2 (20 bar) for 6 h to give tetrahydronaphthylamine 2a in a
B(C6F5)3 (10 mol %)
R
quantitative conversion (Table 1, entry 5). Further reducing the
catalyst loading from 10 mol % to 5 mol % only led a slight
lower conversion (Table 1, entry 6). Solvents were found to have
an obvious influence on the reactivities, and toluene proved to be
the optimal solvent (Table 1, entries 5, 7-10).
R
H2 (20 bar)
toluene, 60 °C, 6 h
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DOI: 10.1039/C5OB00009B
2a-p
1a-p
5
Table 2. Metal-free hydrogenation of naphthylamines 1a
Entry
Product (2)
Yield (%)b
Table
1 Optimization of reaction conditions for hydrogenation of
naphthylamine 1aa
NHR'
Entry
Catalyst
( mol %)
H2
(bar)
50
50
50
50
20
20
20
Solvent
Temp.
(°C)
110
110
60
rt
60
60
60
Time
(h)
20
6
6
20
6
6
6
6
6
Conv.
(%)b
>99
>99
>99
92
>99
95
97
1
2
3
4
5
6
7
8
9
10
10
10
10
10
5
10
10
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Hexane
CH2Cl2
C6H5Br
Et2O
1
2
3
4
5
6
2a: R’ = Ph
94
95
90
98
99
93
2b: R’ = 4-MeC6H4
2c: R’ = 4-MeOC6H4
2d: R’ = 4-ClC6H4
2e: R’ = 4-FC6H4
2f: R’ = 2,4,6-Me3C6H2
NHPh
20
20
20
60
60
60
98
78
58
10
10
R
10
6
7
2g: R = OMe
2h: R = CO2Me
2i: R = F
91
90
95
8c
9c
a All reactions were carried out with naphthylamine 1a (0.25 mmol) in
10 solvent (2.0 mL). b Determined by crude 1H NMR.
MeO
NHPh
10
89
2j
The substrate scope for the metal-free hydrogenation was next
studied under the optimal conditions. As shown in Table 2,
15 several aryl-protecting groups for 2-naphthylamines were well
tolerated for this transformation to give the desired products 2a-f
in 90-99% yields (entries 1-6). But free 2-naphthylamine and 2-
nathphtylamines bearing alkyl-protecting groups (Bn or tert-butyl)
were not suitable substrates for this reaction. Various substituents
20 at the 6 or 7-position of 2-naphthylamines gave high yields,
except that a longer reaction time was required for the electron-
NHPh
11
12d
13
88
93
95
PhHN
2k
PhHN
NHPh
2l
NHPh
withdrawing
substituents
(Table
2,
entries
7-10).
2m
Naphthyldiamines were also effective substrates for the
hydrogenation to give products 2k and 2l in high yields (Table 2,
25 entries 11 and 12). The hydrogenation of N-phenyl-2-anthracene
proceeded well to afford the desired product 2m in 95% yield
(Table 2, entry 13). Moreover, 1-naphthylamines were also
suitable substrates for the metal-free hydrogenation to furnish
tetrahedronaphthyl amines 2n-p in 92-95% yields (Table 2,
30 entries 14-16). However, the introduction of additional
substituents to the aromatic ring containing the amine groups will
inhibit the hydrogenation (Figure 1). Further efforts on searching
for more efficient catalysts are still necessary to solve this
restriction.
NHR'
14
15
2n: R’ = Ph
2o: R’ = 4-MeC6H4
94
95
Br NHPh
16
92
2p
a All reactions were carried out with naphthylamines 1 (0.25 mmol) and
B(C6F5)3 (0.025 mmol) in toluene (2.0 mL) under H2 (20 bar) at 60 °C for
45 6 h unless otherwise noted. b Isolated yield. c Reaction time was 20 h. d
The reaction was run at 45 °C for 20 h.
NHPh
NHPh
NHPh
Me
NHPh
OMe
tetrahydronaphthylamines were furnished in 88-99% yields. This
mild condition provides a possibility for the development of
asymmetric reactions by searching for effective chiral borane
50 catalysts. Further efforts on expanding the substrate scope and
developing the asymmetric transformation are underway in our
laboratory.
Me
F
no reaction
Figure 1 Unreactive substrates for the hydrogenation.
35
Conclusions
Acknowledgements
In summary, the first metal-free hydrogenation of naphthylamines
was successfully achieved using 10 mol % of B(C6F5)3 as a
40 catalyst under a mild condition, and a variety of
This work was supported by the National Science Foundation of
55 China (21222207), the National Basic Research Program of
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Beijing National Laboratory of Molecular Sciences, CAS Key
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haifengdu@iccas.ac.cn
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