Cobalt-catalyzed intramolecular C-H amination with arylsulfonyl azides

Article abstract of DOI:10.1021/ol702265h

(Chemical Equation Presented) Cobalt complexes of porphyrins are effective catalysts for intramolecular C-H amination with arylsulfonyl azides. The cobalt-catalyzed process can proceed efficiently under mild and neutral conditions in low catalyst loading

Full text of DOI:10.1021/ol702265h

ORGANIC
LETTERS
2007
Vol. 9, No. 23
4889-4892
Cobalt-Catalyzed Intramolecular C−H
Amination with Arylsulfonyl Azides
Joshua V. Ruppel, Rajesh M. Kamble, and X. Peter Zhang*
Department of Chemistry, UniVersity of South Florida, Tampa, Florida 33620-5250
pzhang@cas.usf.edu
Received September 16, 2007
ABSTRACT
Cobalt complexes of porphyrins are effective catalysts for intramolecular C
−H amination with arylsulfonyl azides. The cobalt-catalyzed process
can proceed efficiently under mild and neutral conditions in low catalyst loading without the need of other reagents or additives, generating
nitrogen gas as the only byproduct. The catalytic system can be applied to primary, secondary, and tertiary C
broad range of arylsulfonyl azides, leading to high-yielding syntheses of various benzosultams.
−H bonds and is suitable for a
Metal-mediated nitrene transfer reactions are important
chemical processes that allow the selective conversion of
hydrocarbons to valuable nitrogen-containing compounds via
direct C-N bond formation.1,2 Using PhIdNTs and related
iminoiodane derivatives as the primary nitrene sources,
significant progress has been made in both catalytic aziri-
dination of alkenes and amination of C-H bonds.2-4 Great
efforts have been made to overcome several limitations
associated with the use of the hypervalent iodine reagents,
which include their instability and the generation of ArI as
a byproduct. While the approach of in situ iminoiodane
generation in the presence of a terminal oxidant has met with
enormous successes recently,5,6 alternative nitrene sources
such as chloramine-T,4h,7 bromamine-T,8 and tosyloxycar-
bamates9 have been actively pursued to improve catalytic
nitrene transfer reactions.
(1) (a) Racci, A., Ed. Modern Amination Methods; Wiley-VCH: Wein-
heim, 2000. (b) Salvatore, R. N.; Yoon, C. H.; Jung, K. W. Tetrahedron
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Chem., Int. Ed. 2005, 44, 3518. (b) Espino, C. G.; Du Bois, J. In Modern
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Che, C.-M. Org. Lett. 2000, 2, 2233. (b) Dauban, P.; Saniere, L.; Tarrade,
A.; Dodd, R. H. J. Am. Chem. Soc. 2001, 123, 7707. (c) Espino, C. G.; Du
Bois, J. Angew. Chem., Int. Ed. 2001, 40, 598. (d) Cui, Y.; He, C. Angew.
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(a) Mahy, J.-P.; Bedi, G.; Battioni, P.; Mansuy, D. New J. Chem. 1989, 13,
651. (b) Nageli, I.; Baud, C.; Bernardinelli, G.; Jacquier, Y.; Moran, M.;
Muller, P. HelV. Chim. Acta 1997, 80, 1087. (c) Au, S.-M.; Huang, J.-S.;
Che, C.-M.; Yu, W.-Y. J. Org. Chem. 2000, 65, 7858. (d) Yang, J.;
Weinberg, R.; Breslow, R. Chem. Commun. 2000, 531. (e) Yamawaki, M.;
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10.1021/ol702265h CCC: $37.00
© 2007 American Chemical Society
Published on Web 10/13/2007

Azides represent a broad class of compounds that have
the potential to be considered as ideal nitrene sources for
metal-mediated nitrene transfer reactions.10,11 In addition to
their wide availability and ease of synthesis, azide-based
nitrene transfers generate chemically stable and environ-
mentally benign nitrogen gas as the only byproduct. Despite
these attributes, only a few catalytic systems have been
developed that can effectively catalyze the decomposition
of azides for aziridination and amination.11 Notable examples
include Co(Por)-based amination with aryl azides12 and
Ru(Salen)-based aziridination with arylsulfonyl azides.13,14
Scheme 1. Catalytic Intramolecular C-H Amination of
Arylsulfonyl Azides
sponding benzosultam derivatives (2) (Scheme 1), which
have been found in various important applications.19 The Co-
catalyzed process proceeded efficiently under mild and
neutral conditions in low catalyst loading without the need
of other reagents or additives, while generating dinitrogen
as the only byproduct.
Using the commercially available 2,4,6-triisopropylben-
zenesulfonyl azide (1a) as a model substrate, we first
surveyed potential catalytic activity of various metallopor-
phyrins (Figure 1) toward intramolecular C-H amination
(Table 1). The reactions were carried out with 2 mol % of
metalloporphyrin at 80 °C overnight in chlorobenzene, which
was identified previously as the solvent of choice for
aziridination with DPPA.17 It was evident that Co(II) was
by far the most active metal ion for the intramolecular C-H
amination with TPP as the supporting ligand, forming the
desired benzosultam 2a in 96% yield (Table 1, entry 5).
While the V(IV), Cr(III), Mn(III), Ni(II), Cu(II), and Zn(II)
complexes produced no or only trace amounts of 2a (Table
1, entries 1-3 and 6-8), Fe(TPP)Cl and Ru(TPP)(CO) could
In connection with our studies on the development of
Co(Por)-catalyzed carbene transfer reactions with diazo
reagents,15,16 we recently reported a Co-based catalytic system
that can catalyze olefin aziridination with the commercially
available diphenylphosphoryl azide (DPPA) as a convenient
new nitrene source, leading to the formation of N-phospho-
rylated aziridines with dinitrogen as the byproduct.17 As part
of our ongoing efforts to exploit the potential of azides for
nitrene transfer reactions, herein we describe our results on
Co-catalyzed intramolecular C-H amination with azides.
Commercially available Co(TPP) (Figure 1) was shown to
(13) (a) Omura, K.; Murakami, M.; Uchida, T.; Irie, R.; Katsuki, T. Chem.
Lett. 2003, 354. (b) Omura, K.; Uchida, T.; Irie, R.; Katsuki, T. Chem.
Commun. 2004, 2060.
(14) While this manuscript was in the process of submission, Driver and
co-workers reported a formal arene C-H insertion reaction of vinyl azides
catalyzed by dimeric rhodium perfluorobutyrate, see: Stokes, B. J.; Dong,
H.; Leslie, B. E.; Pumphrey, A. L.; Driver, T. G. J. Am. Chem. Soc. 2007,
129, 7500.
(15) (a) Huang, L.; Chen, Y.; Gao, G.-Y.; Zhang, X. P. J. Org. Chem.
2003, 68, 8179. (b) Lee, M.-Y.; Chen, Y.; Zhang, X. P. Organometallics
2003, 22, 4905. (c) Chen, Y.; Fields, K. B.; Zhang, X. P. J. Am. Chem.
Soc. 2004, 126, 14718. (d) Chen, Y.; Zhang, X. P. J. Org. Chem. 2007, 72,
5931. (e) Chen, Y.; Ruppel, J. V.; Zhang, X. P. J. Am. Chem. Soc. 2007,
129, 12074.
Figure 1. Structures of metalloporphyrin catalysts.
(16) For [Co(Por)]-catalyzed cyclopropanation, see: Penoni, A.; Wanke,
R.; Tollari, S.; Gallo, E.; Musella, D.; Ragaini, F.; Demartin, F.; Cenini, S.
Eur. J. Inorg. Chem. 2003, 1452.
(17) Gao, G.-Y.; Jones, J. E.; Vyas, R.; Harden, J. D.; Zhang, X. P. J.
Org. Chem. 2006, 71, 6655.
(18) Careful control experiments showed the arylsulfonyl azides reported
in this work were stable under the conditions used, but it should be noted
that some of the azide compounds may be explosive and should be handled
with great care.
(19) Among various important applications, benzosultams have been
demonstrated as versatile chiral auxiliaries, novel HIV-1 reverse transcriptase
inhibitors, and potential COX-2 inhibitors. For selected examples, see: (a)
Elgazwy, A.-S. S. H. Tetrahedron 2003, 59, 7445. (b) Lee, A. W. M.; Chan,
W. H.; Zhang, S.-J.; Zhang, H.-K. Curr. Org. Chem. 2007, 11, 213. (c)
Zaharevitz, D. W.; Gusio, R.; Wiegand, A.; Jailuri, R.; Pattabiraman, N.;
Kellogg, G. E.; Pallansch, L. A.; Yanf, S. S.; Buckheit, R. W., Jr. Med.
Chem. Res. 1999, 9, 551. (d) Headrick, S. A. Ph.D. Dissertation. University
of Tennessee, Knoxville, TN, U.S.A., 2003. (e) Baker, D. C.; Jiang, B.
U.S. Patent 6,353,112 B1, 2002. (f) Mao, J.; Baker, D. C. U.S. Patent
6,458,962 B1, 2002. (g) Baker, D. C.; Mayasundari, A.; Mao, J.; Johnson,
S. C.; Yan, S. U.S. Patent 6,562,850 B1, 2003. (h) Singh, S. K.; Reddy, P.
G.; Rao, K. S.; Lohray, B. B.; Misra, P.; Rajjak, S. A.; Rao, Y. K.;
Venkateswarlu, A. Bioorg. Med. Chem. Lett. 2004, 14, 499. (i) Pal, M.;
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Rajjak, S. A.; Lohray, V. B.; Casturi, S. R.; Yeleswarapu, K. R. Lett. Drug
Design DiscoVery 2005, 2, 329.
be an effective catalyst for intramolecular nitrene insertion
of C-H bonds with a broad range of arylsulfonyl azides
(1),18 leading to the high-yielding syntheses of the corre-
(8) (a) Chanda, B. M.; Vyas, R.; Bedekar, A. V. J. Org. Chem. 2001,
66, 30. (b) Vyas, R.; Gao, G.-Y.; Harden, J. D.; Zhang, X. P. Org. Lett.
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Table 1. Intramolecular Nitrene C-H Bond Insertion of
2,4,6-Triisopropylbenzenesulfonyl Azide Catalyzed by
Metalloporphyrinsa
Table 2. [Co(TPP)]-Catalyzed Intramolecular C-H Aminationa
a Performed for 18 h under N2 in the presence of 5 Å molecular sieves
with [1a] ) 0.20 M. b See Figure 1 for structures. c Catalyst loading.
d Isolated yields. e Estimated yield. f Carried out for 42 h.
also catalyze the reaction to produce 2a in 11% and 67%
yield, respectively (Table 1, entries 4 and 9). Control
experiments showed that no reaction was observed in the
absence of a catalyst (Table 1, entry 21). After the superiority
of Co ion was established, several common porphyrins with
different electronic and steric properties were applied to
probe the ligand effect (Figure 1). While both Co(OEP) and
Co(TMeOPP) could effectively catalyze the reaction (Table
1, entries 10 and 11), an increase in ligand steric hindrance
and/or electron deficiency resulted in poor catalytic activity
(Table 1, entries 12-14). The Co(TPP)-catalyzed reaction
could also proceed well at lower and even room temperatures
(Table 1, entries 15 and 16) and in different solvents (Table
1, entries 17 and 18). A decrease in catalyst loading to 0.5
mol % had no dramatic effect on the catalytic process (Table
1, entries 19 and 20).
The Co(TPP)-based catalytic system was found to be
suitable for a broad range of arylsulfonyl azides (Table 2),
which were readily prepared from the corresponding aryl
compounds (Supporting Information). For each arylsulfonyl
azide substrate, the catalytic reactions were evaluated at three
different temperatures: 80 °C, 40 °C, and room temperature.
In addition to intramolecular nitrene insertion into tertiary
a Performed in C6H5Cl for 18 h under N2 with 2 mol % [Co(TPP)] in
the presence of 5 Å MS; [azide] ) 0.20 M. b Isolated yields.
C-H bonds in 1a and 1b (Table 2, entries 1-2), secondary
(Table 2, entries 3-4), and even primary (Table 2, entries
5-7) C-H bonds having various aromatic substitution
patterns can be effectively aminated as well, resulting in
selective formation of the corresponding five-membered
heterocycles. Although they all could be intramolecularly
inserted in excellent yields at 80 °C, the reactivity seemed
to follow in the order of 3° > 2° > 1° C-H bonds. The
difference in their reactivities became more noticeable when
the reactions were conducted at lower temperatures (Table
2, entries 1-5). It is interesting to note that an increase in
substitution on the aromatic ring led to higher-yielding
formation of the amination products (Table 2, entries 5-7),
suggesting a positive buttressing effect of meta and para
groups on the nitrene insertion of ortho C-H bonds.
Org. Lett., Vol. 9, No. 23, 2007
4891

Arylsulfonyl azides containing functional groups such as
bromo and nitro at different positions could also be success-
fully catalyzed (Table 2, entries 8-9).
Table 3. Five- and Six-Membered Ring Formations via
Intramolecular C-H Amination Catalyzed by Cobalt
Porphyrinsa
The aforementioned reactivity order of 3° > 2° > 1° C-H
bonds, perhaps in combination with the higher reactivity of
benzylic C-H bonds, resulted in exclusive formation of five-
membered ring structures in all the above cases where 1°
and 3° or 1° and 2° C-H bonds coexist in the substrates
(Table 2, entries 1-4 and 8-9). Azide 1j represents a case
that contains both 2° and 3° C-H bonds (Table 2, entry 10).
As in the other cases (Table 2, entries 1-4 and 8-9), the
exclusive high-yielding formation of five-membered spiro-
heterocyclic product was observed as a result of the reactivity
order of 3° > 2° > 1° C-H bonds.
When an azide substrate containing different 2° C-H
bonds such as benzylic and non-benzylic types was em-
ployed, however, both five- and six-membered ring forma-
tions were observed. For example, Co(TPP)-catalyzed intra-
molecular C-H amination of azide 1k with an n-butyl group
led to the production of six-membered 3k as well as the five-
membered 2k (Table 3, entries 1-3). The ratio of 2k to 3k
was determined to be 72:28, 68:32, and 67:33 at 80 °C, 40
°C, and room temperature, respectively. The increase in the
ratio of 2k to 3k at elevated temperature suggests the higher
thermodynamic stability of the five-membered ring structure.
When 1l with an n-propyl group was used, both the five-
membered 2l and six-membered 3l were similarly formed
(Table 3, entries 4-6). The ratio of five- to six-membered
ring products, which was 56:44, 56:44, and 54:46 at 80 °C,
40 °C, and room temperature, respectively, however, was
significantly lower than the those of azide 1k reactions. Our
preliminary results indicated that the ratio of five- to six-
membered ring formations could be influenced with the use
of different porphyrin ligands. While a similar ratio of 2l to
3l was obtained for Co(TMP)- or Co(TMeOPP)-catalyzed
reactions (Table 3, entries 7 and 8), the ratio was significantly
increased to 73:27 when Co(OEP) was used as the catalyst
(Table 3, entry 9).
a Performed in C6H5Cl for 18 h under N2 with 2 mol % [Co(Por)] in the
presence of 5 Å MS; [azide] ) 0.20 M. b See Figure 1 for structures. c Ratio
of 5- to 6-membered ring products determined by NMR; see SI for details.
d Combined isolated yields of 5- and 6-membered ring products; see SI for
details.
five- or six-membered ring formation. Further studies are
required to render the Co-based catalytic system stereo-
selective by employing chiral porphyrin ligands with desired
electronic, steric, and chiral environments.15c
Acknowledgment. We are grateful for financial support
of this work from USF for Startup Funds, 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).
In summary, we have developed the first Co-based
catalytic system for intramolecular C-H amination with
azides. We demonstrated that the commercially available
Co(TPP) is an effective and general catalyst for catalyzing
intramolecular C-H amination with arylsulfonyl azides,
leading to the valuable benzosultam derivatives in excellent
yields.19 In addition to 1°, 2°, and 3° benzylic C-H bonds,
non-benzylic C-H bonds can also be intramolecularly
aminated. Continuous efforts are underway to identify
suitable catalysts with high regioselectivity toward either
Supporting Information Available: Analytical data and
NMR spectra for all products. This material is available free
of charge via the Internet at http://pubs.acs.org.
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