Iron-catalyzed efficient intermolecular amination of C(sp3)-H bonds with bromamine-T as nitrene source

Article abstract of DOI:10.1039/c4ra02240h

[Fe(N4Py)(CH₃CN)](ClO₄)₂ can efficiently catalyze intermolecular nitrene insertion of sp³ C-H bonds with bromamine-T as the nitrene source, forming the desired tosylprotected amines with NaBr as the by-product.

Full text of DOI:10.1039/c4ra02240h

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Iron-catalyzed efficient intermolecular amination
of C(sp3)–H bonds with bromamine-T as nitrene
source†
Cite this: RSC Adv., 2014, 4, 25287
Haiyu Wang,a Yuxi Li,a Zhiming Wang,a Jun Lou,a Yuling Xiao,a Guofu Qiu,a
Received 19th March 2014
Accepted 29th May 2014
a
b
a
*
Xianming Hu, Hans-Josef Altenbach and Peng Liu
DOI: 10.1039/c4ra02240h
www.rsc.org/advances
[Fe(N4Py)(CH3CN)](ClO4)2 can efficiently catalyze intermolecular bond formation.11 However, development of nonheme iron
nitrene insertion of sp3 C–H bonds with bromamine-T as the nitrene catalysts for intermolecular amination of C(sp3)–H bonds
source, forming the desired tosylprotected amines with NaBr as the remain a challenge. Complex [Fe(N4Py)(CH3CN)](ClO4)2 (1)
by-product.
(N4Py
¼
N,N-bis(2-pyridyl-methyl)bis(2-pyridyl)methylamine,
Fig. 1) was designed and synthesized by Que and co-workers,
and has signicant oxygen activation.12 Imidoiron units are
nitrogen analogues of oxoiron species. It should be capable of
catalyze the amination of C–H bonds. In this paper, we reported
that 1 is an efficient nonheme iron catalyst for intermolecular
amination of the C(sp3)–H bond using bromamine-T as nitrene
source.
Initially, we investigated the catalysis conditions, including
optimization of nitrene sources, solvent and temperature. The
results are summarized in Table 1. Using ethyl benzene 2a as a
model substrate, we systematically evaluated its catalytic C–H
bond nitrene insertion with different nitrene sources catalyzed
by complex 1. The reagent PhINTs and related iminoiodane
derivatives have been widely used as primary nitrene sources in
amination of C–H bonds by iron catalysts.11 Treatment of ethyl
benzene with PhINTs (1.5 equiv.) in the presence of catalytic
amount oꢀf [Fe(N4Py)(CH3CN)](ClO4)2 (5 mol%) in acetonitrile
under 80 C for 8 h form the desired product 3a in 12% yield
(Table 1, entry 1). In contrast, using chloramine-T as nitrene
sources, no reaction detected under similar reaction conditions
(entry 2). We then examined the TsNBrNa (bromamine-T) as
nitrene sources. Under similar reaction conditions, 1 catalyzed
the amination to give 3a in 62% yield (entry 3). The effects of
temperature and solvent were also examined. The reaction in
Nitrogen-containing compounds are abundant in nature and
their important applications in biology and medicine have been
widely documented. Metal-mediated C–N bond formation via a
C–H activation strategy is a highly attractive chemical process
for synthesis of valuable nitrogen-containing compounds.1 This
C–H bond amination method can ideally install an amino group
in an organic skeleton in a single step, avoiding tedious
multiple-step functional group transformations. In recent years,
complex of rhodium-,2 ruthenium-,3 copper-,4 cobalt-catalyzed5
this transformation with iminoiodane, azides, bromamine-T,
and tosyloxycarbamates as the nitrene precursors have been
reported. Ochiai and co-workers reported a method for the
direct and chemoselective amination of aliphatic C–H bonds
under metal-free conditions, in which N-triylimino-l3-bro-
mane functions as an active organonitrenoid species.6 Very
recently, there has been a surge of interest in developing iron
catalysts for atom- and group-transfer reactions for the C–N
bond formation because of the natural abundance and
biocompatibility of iron.7 In literature, oxoiron(IV) centers in
nonheme ligand have been characterized in both enzymes8 and
model systems9 and have been shown to efficiently catalyze the
hydroxylation of C–H bonds.10 Now, studies on nonheme iron-
catalyzed amination of C(sp3)–H bonds via nitrogen group
insertion have emerged as a powerful methodology for C–N
aState Key Laboratory of Virology, Ministry of Education Key Laboratory of
Combinatorial Biosynthesis and Drug Discovery, Wuhan University, School of
Pharmaceutical Sciences, Wuhan University, Wuhan, China. E-mail: liupengwhu@
whu.edu.cn; Fax: +86-027-6875-9850; Tel: +86-027-6875-9100
b
¨
Bergische Universitat Wuppertal, FB 9, Organische Chemie, Gauss-Str. 20, 42097
Wuppertal, Germany
† Electronic supplementary information (ESI) available: Experimental procedures
and compound characterization. See DOI: 10.1039/c4ra02240h
Fig. 1 Structure of N4Py and [Fe(N4Py)(CH3CN)].
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Table 1 Optimization of conditionsa
Table 2 1 catalyzed C–H amination with bromamine-Ta
Entry
Substrate
Product
Yieldb (%)
78
1
Entry
Catalyst
N source
Solvent
T (ꢀC)
Yield (%)
2
3
76
69
1
2
3
4
1
1
1
1
1
1
1
1
PhINTs
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2Cl2
DCE
80
80
80
40
r.t.
80
40
80
60
80
80
80
12
TsNClNa
TsNBrNa
TsNBrNa
TsNBrNa
TsNBrNa
TsNBrNa
TsNBrNa
TsNBrNa
TsNBrNa
TsNBrNa
TsNBrNa
NRb
62
76
71
81
38
46
21
55
NR
NR
5
6c
7c
8c
9c
10c
11c
12c
4
5
82
86
1
1
CHCl3
CH3NO2
CH3CN
CH3CN
Fe(ClO4)2
—
a
Ethylbenzene (0.3 mmol), nitrene source (0.45 mmol), catalyst (5
6
73
76
mol%), solvent (2 mL), 8 h. b NR ¼ no reaction. c Reaction time: 4 h.
7
8
ꢀ
acetonitrile at 80 C for 4 h gave the best result (entries 4–10,
81% yield). The yield of 3a increased by decreasing the
temperature (entry 3 with entry 4) and the reaction time (entry 3
with entry 6), because the product 3a decomposed slowly at high
temperature with iron salt under air. No decomposition of 3a
detected at 80 ꢀC for 8 h, while 5% of 3a decomposed with iron
complex 1 at the same condition. When the amination reaction
stopped, we found the iron complex 1 was decomposed and the
free ligand N4Py can be isolated. So we added Fe(ClO4)2$6H2O
(5 mol%) into the acetonitrile solution of 3a, 13% of 3a
decomposition was detected aer 8 h at 80 ꢀC under air. No
reaction was observed in the absence of catalyst or with
80
44
37
9
10
83
ꢀ
11
12
72
76
Fe(ClO4)2 as catalyst at 80 C (entries 11 and 12).
With the optimized conditions, we examined the substrate
scope of [Fe(N4Py)(CH3CN)](ClO4)2 catalyzed amination of
C(sp3)–H bonds with bromamine-T. As depicted in Table 2, a
variety of sp3 C–H bonds of benzylic and heterocycles reacted
with bromamine-T in the presence of 1 to give corresponding
products in good to excellent yields.
13
52
1 readily catalyzed amination with various substituted
benzylic C–H bonds, including electron-donating or electron-
withdrawing substituents on the aryl ring, to give the corre-
sponding products in moderate to good yield (Table 2, entries
1–5). While 1,2,3,4-tetrahydronaphthalene 2g and indan 2h
were employed, the corresponding isolated yield were 73% and
76% (entries 6 and 7). In both of the cases, high chemo-
selectivity toward benzylic C–H bonds was observed. Notably, 1
can active the C–H bond of toluene. The reaction, however,
didn't afford the corresponding amine product. Instead, the
corresponding imine product 3i was isolated in 80% yield
(entry 8), presumably formed from the initial amine via a
secondary reaction.5 When o-xylene was used as the substrate,
corresponding amine 3ja and imine product 3jb were obtained
14
15
a
3i
70
NRc
Substrate (0.3 mmol), TsNBrNa (0.45 mmol), 1 (5 mol%), CH3CN (2
mL), 4 h. b Isolated yield. c NR ¼ no reaction.
in 44% and 37% yields (entry 9). While only 3jb was detected in
70% yield, when 2 equiv. TsNBrNa added into the reaction
mixture. In cases of cycloethers, the amination reaction
occurred at the position adjacent to O atoms (entries 10–12).
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The corresponding amination products were obtained in
good yields. While 2n was employed, the imine compound was
detected as the only product in 52% yield (entry 13). We nd
that our standard condition was also effective for the amination
of acyclic ether 2o (entry 14). In the case, the hemiaminal
products could not be isolated, since elimination of alcohol
leading to imine 3i was observed. The fact that hemiaminals are
imine equivalents has been reported.13 We also used the ethyl-
ether 2p as substrate, but no reaction was detected (entry 15).
The catalyst loading for the amination reaction can be
reduced to 3 mol% without signicantly affecting the product
yield. As an example, using ethyl benzene 2a as substrate, 3a
was obtained in 79% yield under the same reaction conditions
over 4 h. Moreover, the N4Py ligand is robust and can be reused
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complex [Fe(N4Py)(CH3CN)](ClO4)2 (1) is an active catalyst for
the intermolecular amination of various C(sp3)–H bonds with
bromamine-T at mild conditions. The benet of using brom-
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Acknowledgements
We thank the nancial support of National Natural Science
Foundation of China (21102107), National Mega Project on
Major Drug Development (2011ZX09401-302), Special Financial
Grant from the China Postdoctoral Science Foundation
(2012T50664) and the Scientic and Technological Innovative
Research Team of Wuhan (2013070204020048).
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