Highly efficient oxidative carbon-carbon coupling with SBA-15-support iron terpyridine catalyst

Article abstract of DOI:10.1039/c001209b

SBA-15-Fe(terpy)²⁺ complex efficiently catalyzed oxidative C-C cross-coupling reactions of tertiary amines with carbon nucleophiles in high product yields. The supported terpyridine ligand can be recycled by filtration.

Full text of DOI:10.1039/c001209b

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Highly efficient oxidative carbon–carbon coupling with SBA-15-support
iron terpyridine catalystw
Peng Liu, Cong-Ying Zhou, Song Xiang and Chi-Ming Che*
Received (in College Park, MD, USA) 19th January 2010, Accepted 10th February 2010
First published as an Advance Article on the web 4th March 2010
DOI: 10.1039/c001209b
SBA-15-Fe(terpy)2+ complex efficiently catalyzed oxidative
C–C cross-coupling reactions of tertiary amines with carbon
nucleophiles in high product yields. The supported terpyridine
ligand can be recycled by filtration.
Transition metal-catalyzed oxidative C–C cross-coupling of
tertiary amines with carbon nucleophiles is an efficient strategy
for the synthesis of amino compounds which are prevalent in
bioactive natural products and therapeutic drug molecules.1
4
Transition metal catalysts such as CuBr,2,3 RuCl3 and
5
Rh2(OAc)4 have been used for this transformation. For the
Ru-catalyzed oxidative coupling reactions, RuQO species has
been proposed to be responsible for the oxidation of amine to
Scheme 1 Synthesis of silica supported iron terpyridine complex.
iminium ion which is trapped by nucleophile to give coupling
product.1b,4 As iron and ruthenium are in same subgroup and
Treatment of terpyridine tethered triethoxysilane 2 with
SBA-15 in toluene under reflux for 24 h led to organic–inorganic
hybrid ligand 3; the terpyridine ligand 2 was grafted on the
surface of mesoporous SBA-15 material via covalent bonds
(Scheme 1). Ligand 3 reacts with Fe(ClO4)2ꢀ6H2O in MeCN at
room temperature to give solid supported iron terpyridine
complex 4. The FT-IR and solid diffuse-reflectance UV-vis
spectra of 4 are similar to that of [Fe(terpy)2](ClO4)2 (terpy =
2,20:60,20 0-terpyridine), revealing the coordination of surface
anchored terpyridine units to Fe2+ in the SBA-15 material.
The powder XRD pattern of 4 displayed the characteristic
peaks of SBA-15, thus the mesoporous structure of SBA-15
was retained and the supported Fe(terpy)2+ moieties were
dispersed on the surface of the support. The loading of iron
determined by atom absorption spectroscopy was 1.9 wt%.
At the outset, we examined the catalytic activity of complex
4 for the oxidative coupling reaction of 1,2,3,4-tetrahydro-
isoquinoline with indole using TBHP as oxidant. As depicted
in Table 1, treatment of N-phenyl-1,2,3,4-tetrahydroisoquinoline
6a with indole 5a and TBHP in the presence of complex 4
under reflux for 12 h afforded coupling product 7a in 80%
isolated yield along with trace amounts of tert-butyldioxygenated
amine 8 and amide 9. Under the same conditions, the use
the oxidation chemistry of non-heme iron-oxo complexes can
be as rich as its ruthenium analogues,6 we envision that iron
complexes are useful catalysts for oxidative coupling of
tertiary amines with nucleophiles. Indeed, iron-catalyzed
oxidative coupling reactions of tertiary amines with various
nucleophiles such as NaCN,4c terminal alkynes7 and hetero-
arenes8 have been documented in the literature, whereas there
is still room for improvement of substrate conversion and
catalyst loading. The search for efficient and practical
iron-catalyzed oxidative C–C cross-coupling of tertiary amines
with various carbon nucleophiles remains a challenge.
Immobilization of transition metal complexes onto solid
supports is a way to make catalysis practical. In recent years,
the use of organic–inorganic hybrid materials for catalysis has
attracted a surge of interest due to their superior mechanical
and thermal stability, excellent recyclability and convenient
separation.9 SBA-15 is a class of mesoporous molecular sieves
with large surface area, big pore size and high porosity.10
These features facilitate high accessibility of reactants to active
sites, revealing SBA-15 to be a good solid support material for
heterogeneous catalysis.10c,d In previous work, we found that
iron terpyridine complexes are highly effective for alkene
epoxidation and aziridination.11 Herein we describe a highly
efficient oxidative C–C cross-coupling of tertiary amines with
carbon nucleophiles catalyzed by SBA-15 supported iron
terpyridine complex.
of [Fe(Cl3terpy)2](ClO4)2 (Cl3terpy
=
4,40,40 0-trichloro-
2,20:60,20 0-terpyridine) as catalyst led to a lower product yield
(entry 2). When [Fe(F20TPP)Cl] [H2F20TPP = 5,10,15,20-
tetrakis(pentafluorophenyl)porphyrin] was used as catalyst,
amide 9 was obtained as the major product (entry 3). Low
substrate conversion was found with FeCl2ꢀ4H2O as catalyst
or in the absence of iron complex (entries 4, 5). With complex
4 as catalyst, the effect of varying the oxidant was examined.
Both H2O2 and oxone/NH4HCO3 were found to lead to low
substrate conversions (entries 6, 7).
Department of Chemistry and Open Laboratory of Chemical Biology
of the Institute of Molecular Technology for Drug Discovery and
Synthesis, The University of Hong Kong, Pokfulam Road, Hong
Kong, China. E-mail: cmche@hku.hk; Fax: (852)-2857-1586;
Tel: (852)-2859-2154
w Electronic supplementary information (ESI) available: Experimental
procedures, compound characterization data and supports for
mechanistic studies. See DOI: 10.1039/c001209b
The substrate scope of complex 4-catalyzed oxidative
coupling of tertiary amines with indoles was examined and
ꢁc
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Table 1 Optimization of conditions (solvent = toluene)a
Table 2 Complex 4-catalyzed oxidative coupling reaction of tertiary
amines with indoles
Conv.b 7ac 8c
9c
(%) (%) (%)
Entry Catalyst
Oxidant
TBHP
[Fe(Cl3terpy)2](ClO4)2 TBHP
(%)
1
2
3
4
5
6
7
4
100
100
100
26
23
9
28
80
63
32
8
10
—
73
8
—
—
6
38
—
5
6
21
56
60
14
5
Fe(F20TTP)Cl
FeCl2
—
4
TBHP
TBHP
TBHP
H2O2
Oxone/
NH4HCO3
4
—
d
a
Indole 5a (0.24 mmol), tetrahydroisoquinolines 6a (0.2 mmol),
oxidant (0.6 mmol), catalyst (3 mol%), reflux, 12 h, toluene.
b
c
Determined by 1H NMR based on tetrahydroisoquinolines. Yield
d
based on the conversion. Reaction in MeCN–H2O.
the results are depicted in Table 2. Various indoles react with
tetrahydroisoquinolines and N,N-dimethylanilines to give
coupling products in good yields. For example, the reactions
of tetrahydroisoquinoline 6a with free indoles (NH) or
N-methylindoles containing electron-donating or electron-
withdrawing groups gave corresponding products with yields
up to 87% (entries 1–7). N,N-dimethylanilines are also reactive
substrates, affording a-indolylated anilines in good yields
(entries 8–11). Various functional groups including nitro,
chloro, bromo and methoxy groups could be tolerated under
the employed conditions.
We also examined complex 4-catalyzed oxidative coupling
of tetrahydroisoquinoline with pyrroles. The results are
depicted in Table 3. When pyrrole 10a and tetrahydroiso-
quinoline 6a were employed in a ratio of 1 : 1, 2,5-dialkylated
pyrrole 11a was obtained in 76% yield based on 58% conversion
(entry 1). Increasing the ratio to 4 : 1 led to mono-alkylated
pyrrole 11b in 71% yield with 100% substrate conversion
(entry 2). The reaction is regioselective with alkylation at C-2
position and without alkylation at C-3 position being
observed. N-Methylpyrrole also reacted with 6a to give the
corresponding product in 73% yield. When 3-methylpyrrole
was employed as substrate, two regioisomers, 2-alkylated-
3-methylpyrrole and 5-alkylated-3-methylpyrrole, were obtained
in 56 and 14% yields, respectively.
Reaction conditions: a Indoles (0.24 mmol), tetrahydroisoquinoline
t
(0.2 mmol), BuOOH (0.6 mmol), 4 (3 mol%), 1 mL toluene, reflux,
t
12 h. b Indoles (0.2 mmol), anilines (0.4 mmol), BuOOH (0.6 mmol),
4 (3 mol%), 1 mL toluene, reflux, 12 h. c Determined by 1H NMR
based on tetrahydroisoquinolines. d Determined by 1H NMR based on
indoles. e Yield based on the conversion.
Oxidative cross-coupling of tertiary amines with terminal
alkynes can be used to prepare propargylamines which are
versatile intermediates used in organic synthesis. Complex 4 is
effective for this transformation; the results are depicted in
Table 4. Under similar conditions, both 1,2,3,4-tetrahydro-
isoquinolines and N,N-dimethylanilines could react with
phenylacetylenes to give coupling products in 56–72% yields
(entries 1–5).
iron-oxo species by TBHP. When tetrahydroisoquinoline 6a
was treated with TBHP and a catalytic amount of complex 4 in
the absence of nucleophile, the major product was 3,4-dihydro-
2-phenylisoquinolinium ion (see ESIw). These results are
indicative that complex 4-catalyzed oxidative coupling of
tertiary amines with nucleophiles involves iminium ion inter-
mediate generated through oxidation of amine by iron-oxo
species, and this intermediate is subsequently trapped by
nucleophile to give C–C bond coupling product.
We previously reported an iron terpyridine complex-
catalyzed alkene epoxidation involving reactive iron-oxo
intermediates. In this work, complex 4 was also found to
catalyze epoxidation of styrene (1 equiv.) with TBHP
(1.5 equiv.) to give styrene oxide in 73% yield. This may be
taken as an indirect evidence for the oxidation of complex 4 to
We examined the recyclability of solid supported terpyridine
ligand 3. A purple solid was prepared in situ by mixing
of SBA-15 supported terpyridine ligand 3 (3 mol%) and
ꢁc
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Table 3 Complex 4-catalyzed oxidative coupling of tertiary amines
with pyrroles
Table 5 Recycling the silica supported terpyridine ligand 3 for the
oxidative coupling of tetrahydroisoquinoline 6a with indole 5a in the
presence of Fe(II) salta
Cycle
Conv.b (%)
Yieldc (%)
1
2
3
4
5
100
100
100
100
100
79
78
78
74
72
a
Indole 5a (0.24 mmol), tetrahydroisoquinoline 6a (0.2 mmol),
tBuOOH (0.6 mmol), 3 (3 mol%), Fe(ClO4)2ꢀ6H2O (3 mol%), 1 mL
toluene, reflux, 12 h. Determined by 1H NMR based on tetra-
c
hydroisoquinoline 6a. Isolated yield.
b
good product yields (72–79%) were obtained in five consecutive
runs without apparent loss of catalytic activity.
In summary, an active silica supported iron terpyridine
complex for oxidative C–C cross-coupling reactions of tertiary
amines with various carbon nucleophiles has been developed.
The ligand could be recycled by filtration and reused for five
times without apparent loss of catalytic activity.
Reaction conditions: a Pyrroles (0.2 mmol), tetrahydroisoquinoline 6a
t
(0.2 mmol), BuOOH (0.5 mmol), 4 (3 mol%), 1 mL toluene, reflux,
We are thankful for the financial support of The University
of Hong Kong (University Development Fund), Hong Kong
Research Grant Council (HKU 7052/07P), Research Grants
Council (CityU 2/06C and HKU1/CRF/08) and the Areas of
Excellence Scheme established under the University Grants
Committee of the Hong Kong SAR, China (AoE/P-10/01).
12 h. b Pyrroles (0.8 mmol), tetrahydroisoquinoline 6a (0.2 mmol),
tBuOOH (0.6 mmol), 4 (3 mol%), 1 mL toluene, reflux, 12 h.
c Determined by 1H NMR based on tetrahydroisoquinoline. d Yield
based on the conversion.
Notes and references
Table 4 Complex 4-catalyzed oxidative coupling of tertiary amines
with alkynes
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ꢁc
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 2739–2741 | 2741