Cyclohexane and benzene amination by catalytic nitrene insertion into C-H bonds with the copper-homoscorpionate catalyst TpBr3Cu(NCMe)

Article abstract of DOI:10.1021/ja037072l

The complex Tp^Br3Cu(NCMe) catalyzes, at room temperature, the insertion of a nitrene group from PhINTs into the carbon-hydrogen bond of cyclohexane and benzene, as well as into the primary C-H bonds of the methyl groups of toluene and mesitylene, in moderate to high yield. Copyright

Full text of DOI:10.1021/ja037072l

Published on Web 09/12/2003
Cyclohexane and Benzene Amination by Catalytic Nitrene Insertion into C-H
Bonds with the Copper-Homoscorpionate Catalyst TpBr3Cu(NCMe)
M. Mar D´ıaz-Requejo,† Toma´s R. Belderra´ın,† M. Carmen Nicasio,† Swiatoslaw Trofimenko,‡ and
Pedro J. Pe´rez*,†
Departamento de Qu´ımica y Ciencia de Materiales, UniVersidad de HuelVa, Campus de El Carmen,
21071-HuelVa, Spain, and Department of Chemistry and Biochemistry, UniVersity of Delaware,
Newark, Delaware 19716
Received July 4, 2003; E-mail: perez@dqcm.uhu.es
One of the most interesting reactions to functionalize a carbon-
hydrogen bond consists of the catalytic formation of an amine by
means of the formal insertion of a nitrene group into such unit, in
the so-called amination reaction (eq 1). This methodology has been
conversion of benzene into other derivatives such as nitro- or
chlorobenzene, or into phenol as an intermediate step. Despite that
interest, very few examples for the amination of benzene have been
reported to date.8
In recent years we have studied the use of copper(I)-homoscor-
pionate9 complexes as catalysts for the carbene,10 nitrene,11 and
oxo12 transfer reactions to a variety of substrates. Now we have
turned our attention toward the amination of C-H bonds, and we
have tested the catalytic capabilities of this type of complex toward
such transformation. We have chosen TpBr3Cu(NCMe) (1), a
known for years since the seminal work by Breslow and co-
workers,1 that demonstrated the capabilities of the Cytochrome P450
for the tosylamidation of cyclohexane, that is, the insertion of a
NTs fragment (Ts ) p-tolylsulfonyl) into a C-H bond. Motherwell
et al.2 later reported the use of ferrous chloride as the catalyst for
this transformation. The yields in both cases were low, but these
reactions heralded the opening of a new field in the area of C-N
bond formation. In recent years, impressive results have been
obtained by Che and co-workers,3 showing the capabilities of
ruthenium porphyrins for the tosylamination reaction. Other
manganese-,4 cobalt-,5 rhodium-6 or copper-based7 systems have
also been reported to induce this insertion reaction. However, most
of these results supposed the transfer of a nitrene group from
iminoiodanes of formula PhIdNR to substrates that contain a
somewhat activated carbon-hydrogen bond (Scheme 1): allylic
or benzylic C-H bonds have been the preferred reaction sites for
the above catalytic systems, whereas very few examples of the
tosylamidation of unactivated C-H bonds have been reported to
date. Thus, the conversion of cyclohexane into N-(p-tolylsulfonyl)-
aminocyclohexane has been reported only in a few cases, and has
never been achieved in yields higher than 20%, based in the nitrene
compound that is readily prepared by direct reaction of TlTpBr3
and CuI to carry out this preliminary study.10h When PhINTs13 (0.5
mmol) was added to a solution of 1 (0.025 mmol) in neat toluene
(10 mL), the initial suspension gradually converted into a solution.
After 1 h of stirring, a clear, greenish solution was obtained. GC
and NMR studies revealed the quantitative conversion of toluene
into N-(p-tolylsulfonyl)aminotoluene (eq 2). As mentioned above,
Scheme 1. Usual Substrates Employed in the Metal-Catalyzed
Tosylamidation Reaction by Nitrene Insertion; Arrow Indicates the
Reaction Site
other authors have reported related transformations in low yields.
Thus, Che et al.3h reported a 11% yield for the stoichiometric
transfer from a ruthenium complex, whereas Cenini and co-workers5
obtained even lower conversions of such amines when using
cobalt-porphyrin catalysts and azides as the nitrene source. The
related reaction with mesitylene has also been investigated, with
very similar results: quantitative conversion of the nitrene source
into the corresponding amine (eq 3) has been observed. To our
source.1-3h Another representative example is toluene: in contrast
with the common use of ethylbenzene as a probe molecule for this
transformation, and the ease with which its secondary sites have
been activated, the primary C-H bonds of toluene have remained
unreactive by this method for the majority of catalysts reported,
with just a few exceptions.3h,5 The extreme case of a molecule of
considerable interest to be converted into an amine is benzene:
aniline is currently obtained by indirect methods that require the
† Universidad de Huelva.
‡ University of Delaware.
knowledge, the activation of such primary C-H bonds of toluene
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10.1021/ja037072l CCC: $25.00 © 2003 American Chemical Society

C O MMU N I C A T I O N S
and mesitylene by this methodology and with these degrees of
conversion finds no precedent in the literature.
that these findings will allow the design of new catalysts that
will lead to the achievement of higher conversions as well as to
the control of the selectivity with the use of the appropriate ligands
around copper.
Having demonstrated the exceptional catalytic activity of the
complex TpBr3Cu(NCMe) toward the tosylamidation of those
primary C-H bonds, we wondered about its behavior when facing
secondary carbon-hydrogen sites. However, instead of using
ethylbenzene, we have employed the less reactive cyclohexane.
Acknowledgment. We thank the MCYT (Proyecto BQU2002-
01114) for financial support and the Universidad de Huelva for
the Servicio de Resonancia Magne´tica Nuclear.
References
(1) (a) Breslow, R.; Gellman, S. M. J. Chem. Soc., Chem. Commun. 1982,
1400. (b) Breslow, R.; Gellman, S. M. J. Am. Chem. Soc. 1983, 105,
6728. (c) Svastist, E. W.; Dawson, J. H.; Breslow, R.; Gellman, S. M. J.
Am. Chem. Soc. 1985, 107, 6427.
(2) Barton, D. H. R.; Hay-Motherwell, R. S.; Motherwell, W. B. J. Chem.
Soc., Perkin Trans. 1 1983, 445.
(3) (a) Leung, S. K.-Y.; Huang, J.-S.; Liang, J.-L.; Che, C.-M.; Zhou, Z.-Y.
Angew. Chem., Int. Ed. 2003, 42, 340. (b) Liang, J.-L.; Yuan, S.-X.; Chan,
P. W. H.; Che, C.-M. Org. Lett. 2002, 4, 4507. (c) Liang, J.-L.; Huang,
J.-S.; Yu, X.-Q.; Zhu, N.; Che, C.-M. Chem. Eur. J. 2002, 8, 1563. (d)
Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.; Yu, W.-Y.; Che, C.-M. Angew.
Chem., Int. Ed. 2002, 41, 3465. (e) Li, Y.; Huang, J.-S.; Zhou, Z.-Y.;
Che, C.-M. J. Am. Chem. Soc. 2001, 123, 4843. (f) Au, S.-M.; Huang,
J.-S.; Che, C.-M.; Yu, W.-Y. J. Org. Chem. 2000, 65, 7858. (g) Yu, X.-
Q.; Huang, J.-S.; Zhou, X.-G.; Che, C.-M. Org. Lett. 2000, 2, 2233. (h)
Au, S.-M.; Huang, J.-S.; Yu, W.-Y.; Fung, W.-H.; Che, C.-M. J. Am.
Chem. Soc. 1999, 121, 9120. (i) Zhou, X.-G.; Yu, X.-Q.; Huang, J.-S.;
Che, C.-M. Chem. Commun. 1999, 2377.
Under conditions similar14 to those employed for toluene and
mesitylene, cyclohexane has been converted into N-(p-tolylsulfo-
nyl)aminocyclohexane in 65% yield, based in PhINTs. p-Toluene-
sulfonamide, TsNH2, was also obtained, accounting for 100% of
the initial PhINTs, resulting from the presence of adventitious water.
Therefore, experimental work must be carried out with special
precaution to avoid the presence of water in the reaction mixture.
As pointed out above, very few examples for this reaction have
appeared in the literature. The initial report by Breslow gave a 3%
yield,1 whereas Che3h has reported a 10% yield for a stoichiometric
nitrene transfer with Ru-porphyrins. Regarding the use of copper
for these transformations, only reports by Katsuki4b and Taylor4a
refer to the use of this metal, and only with the aforementioned
activated substrates: the use of copper for the tosylamidation of
cyclohexane seems to be restricted to the system we present herein.
We have also carried out the reaction of PhINTs and benzene in
the presence of catalytic amounts of 1 following an identical
procedure. After the complete dissolution of the nitrene precursor,
the resulting solution was analyzed by GC as well as by NMR. A
mixture of TsNH2 and N-(p-tolylsulfonyl)aminobenzene in a 60:
40 ratio was observed (eq 5), the latter compound being formed as
(4) (a) Kohmura, Y.; Katsuki, T. Tetrahedron Lett. 2001, 42, 3339. (b) Mahy,
J.-P.; Bedi, G.; Battioni, P.; Mansuy, D. Tetrahedron Lett. 1988, 29, 1927.
(5) Ragaini, F.; Penoni, A.; Gallo, E.; Tollari, S.; Li Gotti, C.; Lapadula, M.;
Magioni, E.; Cenini, S. Chem. Eur. J. 2003, 9, 249.
(6) (a) Yamawaki, M.; Tsutsui, H.; Kitagaki, S.; Anada, M.; Hashimito, S.
Tetrahedron Lett. 2002, 43, 9561. (b) Mueller, P.; Baud, C.; Naegeli, I.
J. Phys. Org. Chem. 1998, 11, 597. (c) Chanda, B. M.; Vyas, R.; Bedekar,
A. V. J. Org. Chem. 2001, 66, 30.
(7) (a) Albone, D. P.; Aujla, P. S.; Taylor, P. C. J. Org. Chem. 2001, 63,
9569. (b) Kohmura, Y.; Kawasaki, K.-I.; Katsuki, T. Synlett 1997, 1456.
(8) (a) Hagemeyer, A.; Borade, R.; Desrosiers, P.; Guan, S.; Lowe, D. M.;
Poojary, D. M.; Turner, H.; Weinberg, H.; Zhou, X.; Armbrust, R.; Fengler,
G.; Notheis, U. Appl. Catal., A 2002, 227, 43. (b) Kutnetsova, N. I.;
Kutnetsova, L. I.; Detusheva, L. G.; Likholobov, V. A.; Pez, G. P.; Cheng,
H. J. Mol. Catal. A: Chem. 2000, 161, 1. (c) Becker, J.; Ho¨lderich, W.
F. Catal. Lett. 1998, 54, 125. (d) Diversi, P.; Ermini, L.; Ingrosso, G.;
Lucherini, A.; Pinzino, C.; Sagramora, L. J. Organomet. Chem. 1995,
494, C1. (e) Ayyangar, N.; Bambal, R. B.; Lugade, A. G. J. Chem. Soc.,
Chem. Commun. 1981, 790.
(9) Trofimenko, S. Scorpionates, The Coordination Chemistry of Poly-
pyrazolborate Ligands; Imperial College Press: London, 1999.
(10) (a) D´ıaz-Requejo, M. M.; Nicasio, M. C.; Pe´rez, P. J. Organometallics
1998, 15, 3051. (b) D´ıaz-Requejo, M. M.; Belderrain T. R.; Nicasio, M.
C.; Prieto, F.; Pe´rez, P. J. Organometallics 1999, 18, 2601. (c) D´ıaz-
Requejo, M. M.; Belderrain, T. R.; Trofimenko, S.; Pe´rez, P. J. J. Am.
Chem. Soc. 2001, 123, 3167. (d) D´ıaz-Requejo, M. M.; Mairena, M. A.;
Belderrain, T. R.; Nicasio, M. C.; Trofimenko, S.; Pe´rez, P. J. Chem.
Commun. 2001, 1804. (e) D´ıaz-Requejo, M. M.; Belderrain, T. R.; Nicasio,
M. C.; Trofimenko, S.; Pe´rez, P. J. J. Am. Chem. Soc. 2002, 124, 896. (f)
D´ıaz-Requejo, M. M.; Caballero, A.; Belderrain, T. R.; Nicasio, M. C.;
Trofimenko, S.; Pe´rez, P. J. J. Am. Chem. Soc. 2002, 124, 978. (g) Morilla,
M. E.; D´ıaz-Requejo, M. M.; Belderrain, T. R.; Nicasio, M. C.;
Trofimenko, S.; Pe´rez, P. J. Chem. Commun. 2002, 2998. (h) Caballero,
A.; D´ıaz-Requejo, M. M.; Belderrain, T. R.; Nicasio, M. C.; Trofimenko,
S.; Pe´rez, P. J. J. Am. Chem. Soc. 2003, 125, 1446.
the result of the formal insertion of the nitrene group into the
carbon-hydrogen bond of the benzene ring. A noncatalytic method
for the synthesis of such amine was reported by Ayyangar et al.8e
in low yield and as part of a mixture of compounds. Ingrosso later
reported8d the reaction of benzene and diethylamine in the presence
of a complex Ir/Hg system, that gave diethylaniline in ca. 20%
yield at 130 °C. Heterogeneous catalysts under drastic conditions
have been employed for the direct reaction of benzene and
ammonia,8a,c but with low conversions. Similar results have been
obtained when using several transition metals as catalysts for the
reaction of benzene and hydroxylamine. On the basis of these data,
the procedure reported in this contribution for the amidation of
benzene constitutes, to our knowledge, the first example of such
transformation that provides the aniline derivative in acceptable
yields, under very mild conditions and with a simple catalyst.
In conclusion, we have discovered that the complex TpBr3Cu-
(NCMe) catalyzes the insertion of a nitrene group into the
carbon-hydrogen bond of cyclohexane and benzene, as well as
into the primary C-H bonds of the methyl groups of toluene and
mesitylene, in moderate to high yield, respectively. We believe
(11) (a) Pe´rez, P. J.; Brookhart, M.; Templeton, J. L. Organometallics 1993,
12, 261. (b) D´ıaz-Requejo, M. M.; Pe´rez, P. J.; Brookhart, M.; Templeton,
J. L. Organometallics 1997, 16, 4399.
(12) D´ıaz-Requejo, M. M.; Belderrain, T. R.; Pe´rez, P. J. Chem. Commun.
2000, 1853.
(13) Yamada, Y.; Yamamoto, T.; Okawara, M. Chem Lett. 1975, 361.
(14) General catalytic procedure: inside a drybox, 0.025 mmol of 1 was
dissolved in neat toluene or mesitylene (10 mL). Molecular sieves were
added to diminish the presence of water. PhINTs (0.5 mmol) were added
in one portion to the solution. After 1 h stirring, no solid PhINTs was
observed. The greenish solution was filtered to retire the sieves and was
investigated by GC. Volatiles were removed under vacuum, and the residue
was investigated by NMR. Spectroscopic data were similar to those
reported by Che for related compounds (ref 3h). In the case of the less
reactive cyclohexane and benzene, a 1:20 ratio of 1 and PhINTs was
employed, and the reaction times were up to 12-18 h. The cyclohexane
derivative was identified by NMR, the spectra being identical to those
reported by Che (ref 3h). The benzene derivative was characterized by
comparison with an authentic sample prepared by reaction of aniline and
tosyl chloride in the presence of base.
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