Cobalt-catalyzed intermolecular C-H amination with bromamine-T as nitrene source

Article abstract of DOI:10.1039/b710677g

Cobalt, supported by porphyrin ligands, is capable of catalyzing intermolecular nitrene insertion of sp³ C-H bonds with bromamine-T as the nitrene source, forming the desired tosyl-protected amines with NaBr as the by-product. The Royal Society

Full text of DOI:10.1039/b710677g

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Cobalt-catalyzed intermolecular C–H amination with bromamine-T as
nitrene source{
Jeremiah D. Harden, Joshua V. Ruppel, Guang-Yao Gao and X. Peter Zhang*
Received (in Austin, TX, USA) 12th July 2007, Accepted 22nd August 2007
First published as an Advance Article on the web 3rd September 2007
DOI: 10.1039/b710677g
alkenes with diphenylphosphoryl azide (DPPA)14 and bromamine-
Cobalt, supported by porphyrin ligands, is capable of catalyz-
T.15 The Co(Por)/bromamine-T system, which proved to be
superior to the Fe(Por)Cl/bromamine-T system,16 can be effec-
tively operated under mild conditions with alkenes as the limiting
reagent, generating NaBr as the by-product, and is generally
suitable for a wide range of alkene substrates. While the desired
aziridines were formed in high yields for most of the substrates,
low aziridination yields were obtained from certain substrates
containing activated C–H bonds, such as 1,2-dihydronaphtha-
lene.15 At that time, without being able to obtain concrete
experimental data, we presumed a competitive amination reaction
to be the cause of low yields. Since then, we have carried out a
thorough study on the possibility of catalytic C–H amination by
Co(Por) with bromamine-T as the nitrene source (Scheme 1).
Herein, we wish to report our findings.
ing intermolecular nitrene insertion of sp3 C–H bonds with
bromamine-T as the nitrene source, forming the desired tosyl-
protected amines with NaBr as the by-product.
Nitrogen-containing molecules are abundant in nature and their
importance in biology and medicine has been widely documented.
Among modern amination methods,1 metal-catalyzed nitrene
insertion provides an attractive strategy for direct transformation
of ubiquitous C–H bonds to value-added amine functionalities
through the use of appropriate nitrene sources.2 The reagent
PhILNTs and related iminoiodane derivatives have been widely
used as primary nitrene sources,2,3 resulting in significant advances
in amination of C–H bonds.4 In view of some limitations
associated with the use of the hypervalent iodine reagents,
including their instability and the generation of ArI as a by-
product, considerable efforts have been made to develop
alternative nitrene sources for catalytic C–H amination. One such
remarkably successful effort has been the approach of in situ
iminoiodane generation from amides using terminal oxidants such
as the combination of sulfamates with PhI(OAc)2 or sulfonamides
with PhILO.3,5 In addition, efforts have been devoted to employ
other potential nitrene sources that obviate the need of terminal
oxidants for the catalytic amination process, including chloramine-
T,4g,6 bromamine-T,7 tosyloxycarbamates,8 and azides.9 Using
these nitrene sources, complexes of manganese, iron, ruthenium,
rhodium, and copper supported by various ligands have been
identified to catalyze C–H amination reactions, with dirhodium
tetracarboxylates being the most widely used catalysts.2–5 In the
light of various remaining challenges in intermolecular C–H
amination,2–5 it is desirable to search for new catalytic systems
based on other metal ions in combination with alternative nitrene
sources. To this end, silver10- and cobalt11-based systems were
recently reported to aminate C–H bonds with PhILNNs and aryl
azides, respectively.
Using indan as a model substrate, we systematically evaluated
its catalytic C–H nitrene insertion with bromamine-T under
different conditions by cobalt complexes of porphyrin ligands
possessing varied electronic and steric environments (Fig. 1).
Selected results are summarized in Table 1. While most of
the tested cobalt complexes exhibited poor catalytic activity toward
C–H amination, the cobalt complex of electron-deficient porphyrin
Co(TPFPP) was found to aminate one of the benzylic C–H bonds
of indan effectively to form the desired product 2a in 66% yield at
room temperature (Table 1, entries 9–13). Further experiments
indicated the use of electron-deficient as well as more sterically
demanding porphyrin TDClPP could further improve the Co-
catalyzed amination reaction, producing 2a in 75% yield (Table 1,
entry 3). This reaction was performed with a 1a : bromamine-T
ratio of 10 : 1 since the use of other reactant ratios appeared to give
lower yields of 2a (Table 1, entries 1–3). Among the solvents
examined, CH3CN proved to be the best for the catalytic process
(Table 1, entries 3–7). Although the employment of lower catalyst
loading could result in the formation of the desired amination
product (Table 1, entry 8), 5 mol% of Co(TDClPP) was needed for
an effective transformation (Table 1, entry 3).
Attracted by their practical attributes as alternative nitrene
sources, we recently initiated a research project on the development
of catalytic nitrene transfer processes using bromamine-T and
azides. In connection with our studies on catalytic carbene transfer
reactions by cobalt porphyrins [Co(Por)],12,13 we documented new
Co-based catalytic systems that can catalyze aziridination of
Under the optimized catalytic conditions derived from the
above experiments for the amination of indan, the Co(TDClPP)/
bromamine-T catalytic systems could also be applied to aminate
other substrates at room temperature (Table 2). While the isolated
Department of Chemistry, University of South FloridaDepartment of
Chemistry, University of Tennessee, Tampa, Florida 33620-5250,
USA.Knoxville, Tennessee 37996-1600, USA.
E-mail: pzhang@cas.usf.edu; Fax: +1 813 974 7249; Tel: +1 813 974 1733
{ Electronic supplementary information (ESI) available: Full experimental
procedures for the synthesis of compounds 2a–f, their characterization
1
Scheme 1 Cobalt-catalyzed C–H amination with bromamine-T.
This journal is ß The Royal Society of Chemistry 2007
data and H NMR spectra. See DOI: 10.1039/b710677g
4644 | Chem. Commun., 2007, 4644–4646

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Table 2 Co(TDClPP)-catalyzed intermolecular C–H amination reac-
tions with bromamine-Ta
Entry
1
Substrate
Product
Yield (%)b
73
2
66
3
4
50
14
Fig. 1 Structures of cobalt(II) complexes of porphyrins.
Table 1 Intermolecular C–H amination of indan with bromamine-T
by cobalt(II) porphyrinsa
5
6
34
33
mol
(%) Solvent
Yield
Time/h (%)d
Entry S : BTb [Co(Por)]c
a
Reactions were carried out at room temperature in CH3CN under
N2 with bromamine-T as the limiting reagent (substrate/bromamine-
T = 10 : 1) using 5 mol% Co(TDClPP) in the presence of 5 s
molecular sieves at a concentration of 2.0 mmol substrate/3–5 mL
CH3CN. Yields represent isolated yields in .95% purity as
determined by 1H NMR.
1
2
3
4
5
6
7
8
9
10
11
12
13
a
1 : 1
1 : 5
Co(TDClPP)
Co(TDClPP)
Co(TDClPP)
Co(TDClPP)
Co(TDClPP)
Co(TDClPP)
Co(TDClPP)
Co(TDClPP)
Co(TPP)
5
5
5
5
5
5
5
2
5
5
5
5
5
CH3CN
CH3CN
CH3CN
THF
19
17
18
20
43
30
75
15
14
12
,2
15
,2
,2
66
7
10 : 1
10 : 1
10 : 1
10 : 1
10 : 1
10 : 1
10 : 1
10 : 1
10 : 1
10 : 1
10 : 1
b
CH3C6H5 18
ClC6H5
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
20
18
20
19
18
18
18
20
and 1f) were used, the corresponding amination products of the
benzylic C–H bonds 2e and 2f were produced as the major
products, albeit in lower yields (Table 2, entries 5–6), affirming the
high chemoselectivity towards benzylic C–H bonds.
Co(TMP)
Co(TPFPP)
Co(OEP)
Co(TMeOPP)
23
Reactions were carried out at room temperature under N2 with
bromamine-T in the presence of molecular sieves at
concentration of 2.0 mmol substrate/3–5 mL solvent. The mole
ratio of indan substrate to bromamine-T. See Fig. 1 for structures.
Yields represent GC yields using tridecane as an internal standard.
In summary, we have demonstrated the capability of cobalt
porphyrins in catalyzing intermolecular nitrene insertion of sp3
C–H bonds with bromamine-T at room temperature. In addition
to mild conditions, the cobalt-based catalytic system enjoys the use
of bromamine-T as the nitrene source since it produces innocent
NaBr as the by-product. Furthermore, the current Co(TDClPP)/
bromamine-T catalytic intermolecular amination system has high
chemoselectivity towards benzylic C–H bonds. Efforts are under-
way to design and synthesize new porphyrin ligands to further
improve the scope and efficacy of the Co-catalyzed intermolecular
C–H amination system.
5
s
a
b
c
d
yield of 2a was 73% (Table 2, entry 1), the corresponding
amination product 2b from 1,2,3,4-tetrahydronaphthalene (1b)
was isolated in 66% yield (Table 2, entry 2). In both of the cases,
high chemoselectivity toward benzylic C–H bonds was observed.
The benzylic C–H bond of the cyclic ether 1c seemed to be
similarly aminated with bromamine-T. The reaction, however,
didn’t afford the corresponding amine product. Instead, the
corresponding imine product 2c was isolated in 50% yield (Table 2,
entry 3), presumably formed from the initial amine via a secondary
reaction.17 Although fluorene 1d contains more activated benzylic
C–H bonds, its catalytic amination reaction by Co(TDClPP) gave
the C–H insertion product 2d in a much lower yield (Table 2,
entry 4). Steric hindrance is likely responsible for the adverse
outcome. When substrates that contain both secondary benzylic
and primary C–H bonds such as 1- and 2-ethylnaphthalene (1e
We are grateful for financial support of this work from the
University of Tennessee and the University of South Florida for
Startup Funds, the American Chemical Society for a PRF-AC
grant, and the National Science Foundation for a CAREER
Award. Funding for the USF Department of Chemistry Mass
Spectrometry Facility has been furnished in part by NSF
(CRIF:MU-0443611). We would like to thank an anonymous
reviewer for the insightful comment that led to the correct
assignment of product 2c.
This journal is ß The Royal Society of Chemistry 2007
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6 D. P. Albone, S. Challenger, A. M. Derrick, S. M. Fillery, J. L. Irwin,
C. M. Parsons, H. Takada, P. C. Taylor and D. J. Wilson, Org. Biomol.
Chem., 2005, 3, 107.
7 B. M. Chanda, R. Vyas and A. V. Bedekar, J. Org. Chem., 2001, 66, 30.
8 (a) H. Lebel, K. Huard and S. Lectard, J. Am. Chem. Soc., 2005, 127,
14198; (b) H. Lebel, O. Leogane, K. Huard and S. Lectard, Pure Appl.
Chem., 2006, 78, 363; (c) H. Lebel and K. Huard, Org. Lett., 2007, 9,
639.
9 (a) H. Kwart and A. A. Kahn, J. Am. Chem. Soc., 1967, 89, 1951; (b)
K. Omura, M. Murakami, T. Uchida, R. Irie and T. Katsuki, Chem.
Lett., 2003, 32, 354.
10 Z. Li, D. A. Capretto, R. Rahaman and C. He, Angew. Chem., Int. Ed.,
2007, 46, 5184.
11 (a) S. Cenini, E. Gallo, A. Penoni, F. Ragaini and S. Tollari, Chem.
Commun., 2000, 2265; (b) F. Ragaini, A. Penoni, E. Gallo, S. Tollari,
C. L. Gotti, M. Lapadula, E. Mangioni and S. Cenini, Chem.–Eur. J.,
2003, 9, 249.
12 (a) L. Huang, Y. Chen, G.-Y. Gao and X. P. Zhang, J. Org. Chem.,
2003, 68, 8179; (b) M.-Y. Lee, Y. Chen and X. P. Zhang,
Organometallics, 2003, 22, 4905; (c) Y. Chen, K. B. Fields and
X. P. Zhang, J. Am. Chem. Soc., 2004, 126, 14718; (d) Y. Chen and
X. P. Zhang, J. Org. Chem., 2007, 72, 5931.
13 For a contribution by others on [Co(Por)] catalyzed cyclopropanation,
see: A. Penoni, R. Wanke, S. Tollari, E. Gallo, D. Musella, F. Ragaini,
F. Demartin and S. Cenini, Eur. J. Inorg. Chem., 2003, 1452.
14 G.-Y. Gao, J. E. Jones, R. Vyas, J. D. Harden and X. P. Zhang, J. Org.
Chem., 2006, 71, 6655.
15 G.-Y. Gao, J. D. Harden and X. P. Zhang, Org. Lett., 2005, 7, 3191.
16 R. Vyas, G.-Y. Gao, J. D. Harden and X. P. Zhang, Org. Lett., 2004, 6,
1907.
Notes and references
1 (a) Modern Amination Methods, ed. A. Racci, Wiley-VCH, Weinheim,
2000; (b) R. N. Salvatore, C. H. Yoon and K. W. Jung, Tetrahedron,
2001, 57, 7785; (c) M. Johannsen and K. A. Jorgensen, Chem. Rev.,
1998, 98, 1689; (d) T. E. Muller and M. Beller, Chem. Rev., 1998, 98,
675.
2 (a) P. Muller and V. Fruit, Chem. Rev., 2003, 103, 2905; (b) P. Dauban
and R. H. Dodd, Synlett, 2003, 1571; (c) G. F. Koser, Top. Curr. Chem.,
2003, 224, 137; (d) J. A. Halfen, Curr. Org. Chem., 2005, 9, 657.
3 For recent reviews, see: (a) H. M. L. Davies and M. S. Long, Angew.
Chem., Int. Ed., 2005, 44, 3518; (b) C. G. Espino and J. Du Bois, in
Modern Rhodium-Catalyzed Organic Reactions, ed. P. A. Evans, Wiley-
VCH, Weinheim, 2005, pp. 379–416; (c) H. M. L. Davies, Angew.
Chem., Int. Ed., 2006, 45, 6422.
4 For representative examples of intermolecular C–H amination
with ArILNTs, see: (a) J.-P. Mahy, G. Bedi, P. Battioni and
D. Mansuy, New J. Chem., 1989, 13, 651; (b) I. Nageli, C. Baud,
G. Bernardinelli, Y. Jacquier, M. Moran and P. Muller, Helv. Chim.
Acta, 1997, 80, 1087; (c) S.-M. Au, J.-S. Huang, C.-M. Che and
W.-Y. Yu, J. Org. Chem., 2000, 65, 7858; (d) J. Yang, R. Weinberg and
R. Breslow, Chem. Commun., 2000, 531; (e) M. Yamawaki, H. Tsutsui,
S. Kitagaki, M. Anada and S. Hashimoto, Tetrahedron Lett., 2002, 43,
9561; (f) J.-L. Liang, J.-S. Huang, X.-Q. Yu, N. Zhu and C.-M. Che,
Chem.–Eur. J., 2002, 8, 1563; (g) M. R. Fructos, S. Trofimenko,
M. M. Diaz-Requejo and P. J. Perez, J. Am. Chem. Soc., 2006, 128,
11784.
5 For representative examples of intermolecular C–H amination with in
situ generated ArILNTs, see: (a) X.-Q. Yu, J.-S. Huang, X.-G. Zhou
and C.-M. Che, Org. Lett., 2000, 2, 2233; (b) R. P. Reddy and
H. M. L. Davies, Org. Lett., 2006, 8, 5013; (c) C. Liang, F. Robert-
Peillard, C. Fruit, P. Muller, R. H. Dodd and P. Dauban, Angew.
Chem., Int. Ed., 2006, 45, 4641; (d) K. W. Fiori and J. Du Bois, J. Am.
Chem. Soc., 2007, 129, 562.
17 A similar secondary reaction was reported previously in ref. 11. The
presence of the electron-rich oxygen heteroatom presumably activated
the initial amine product toward the formation of the corresponding
imine 2c. Attempts at arresting the reaction for the amine formation
were unsuccessful, indicating a fast secondary reaction.
4646 | Chem. Commun., 2007, 4644–4646
This journal is ß The Royal Society of Chemistry 2007