A highly effective cobalt catalyst for olefin aziridination with azides: Hydrogen bonding guided catalyst design

Article abstract of DOI:10.1021/ol800588p

[Co(P1)], which was designed on the basis of potential hydrogen-bonding interactions in the metal-nitrene Intermediate, Is a highly active aziridination catalyst with azides. [Co(P1)] can effectively azlridlnate various aromatic olefins with arylsulfonyl azides under mild conditions, forming sulfonylated aziridines in excellent yields. The Co-based system enjoys several attributes associated with the relatively low cost of cobalt and the wide accessibility of arylsulfonyl azides. Furthermore, it generates stable dinitrogen as the only byproduct.

Full text of DOI:10.1021/ol800588p

ORGANIC
LETTERS
2008
Vol. 10, No. 10
1995-1998
A Highly Effective Cobalt Catalyst for
Olefin Aziridination with Azides:
Hydrogen Bonding Guided Catalyst
Design
Joshua V. Ruppel, Jess E. Jones, Chelsea A. Huff, Rajesh M. Kamble,
Ying Chen, and X. Peter Zhang*
Department of Chemistry, UniVersity of South Florida, Tampa, Florida 33620-5250
pzhang@cas.usf.edu
Received March 13, 2008
ABSTRACT
[Co(P1)], which was designed on the basis of potential hydrogen-bonding interactions in the metal-nitrene intermediate, is a highly active
aziridination catalyst with azides. [Co(P1)] can effectively aziridinate various aromatic olefins with arylsulfonyl azides under mild conditions,
forming sulfonylated aziridines in excellent yields. The Co-based system enjoys several attributes associated with the relatively low cost of
cobalt and the wide accessibility of arylsulfonyl azides. Furthermore, it generates stable dinitrogen as the only byproduct.
Metal-catalyzed olefin aziridination is a fundamentally and
practically important chemical process that has received
increasing research attention.1 The resulting aziridines, the
smallest nitrogen-containing heterocyclic compounds, are key
elements in many biologically and pharmaceutically interest-
ing compounds and serve as a class of versatile synthons
for preparation of functionalized amines.1 Since the introduc-
tion of PhIdNTs as a nitrene source more than three decades
ago,2 considerable progress has been made in metal-catalyzed
olefin aziridination with PhIdNTs and related iminoiodane
derivatives,1,3 including the notable recent developments with
the use of their in situ variants.4,5 Despite these advances,
the search for alternative nitrene sources is warranted as the
use of PhIdNTs has met with several difficulties. Besides
its short shelf life and poor solubility in common solvents,
aziridination with PhIdNTs generates a stoichiometric
amount of PhI as a byproduct. In view of the similarity to
diazo reagents for carbene transfer processes, azides should
have the potential to serve as a general class of nitrenesources
for metal-mediated nitrene transfer reactions, including aziri-
dination (Scheme 1). In addition to their wide availability and
(4) For recent in situ variants, see: (a) Esteoule, A.; Duran, F.; Retailleau,
P.; Dodd, R. H.; Dauban, P. Synthesis 2007, 1251. (b) Guthikonda, K.;
Wehn, P. M.; Caliando, B. J.; Du Bois, J. Tetrahedron 2006, 62, 11331.
(c) Li, Z.; Ding, X.; He, C. J. Org. Chem. 2006, 71, 5876. (d) Xu, Q.;
Appella, D. H. Org. Lett. 2008, 10, 1497.
(1) (a) Muller, P.; Fruit, C. Chem. ReV. 2003, 103, 2905. (b) Hu, X. E.
Tetrahedron 2004, 60, 2701.
(2) Yamada, Y.; Yamamoto, T.; Okawara, M. Chem. Lett. 1975, 361.
(3) For recent examples with PhIdNTs: (a) Klotz, K. L.; Slominski,
L. M.; Hull, A. V.; Gottsacker, V. M.; Que, L., Jr.; Halfen, J. A. Chem.
Commun. 2007, 2063. (b) Zdilla, M. J.; Abu-Omar, M. M. J. Am. Chem.
Soc. 2006, 128, 16971. (c) Cui, Y.; He, C. J. Am. Chem. Soc. 2003, 125,
(5) For other approaches, see: (a) Antilla, J. C.; Wulff, W. D J. Am.
Chem. Soc. 1999, 121, 5099. (b) Williams, A. L.; Johnston, J. N. J. Am.
Chem. Soc. 2004, 126, 1612. (c) Vyas, R.; Gao, G.-Y.; Harden, J. D.; Zhang,
X. P Org. Lett. 2004, 6, 1907. (d) Catino, A. J.; Nichols, J. M.; Forslund,
R. E.; Doyle, M. P. Org. Lett. 2005, 7, 2787.
16202
.
10.1021/ol800588p CCC: $40.75
Published on Web 04/19/2008
2008 American Chemical Society

Scheme 1
.
Cobalt-Catalyzed Olefin Aziridination with Azides
Scheme 2. Synthesis of Chiral Diporphyrin
ease of synthesis,6 azide-based nitrene transfers would generate
chemically stable and environmentally 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.7–11
We recently reported a Co-based system for catalytic
aziridination with azide.12a It was shown that [Co(TPP)]
(Figure 1) can catalyze olefin aziridination with commercially
aziridination with bromamine-T,12b produced the desired
product in less than 5% yield for each of the cases (Scheme
2).14 As part of our efforts to develop new porphyrin ligands
to enhance Co-based catalytic processes, herein we describe
the design and synthesis of a new porphyrin P1 based on
potential hydrogen bonding interaction in the assumed
metal-nitrene intermediate (Figure 1). The Co(II) complex
of P1 [Co(P1)] was shown to be a highly active catalyst for
aziridination of different aromatic olefins with various
arylsulfonyl azides, forming the corresponding aziridines in
excellent yields under mild conditions (Scheme 2).
Similar to that proposed for other metal-based systems,1
the Co-catalyzed aziridination can be assumed to proceed
via a mechanism involving a key electrophilic Co-nitrene
intermediate.12 Accordingly, elements that can stabilize the
formation of and enhance the electrophilicity of the nitrene
intermediate should facilitate the catalytic cycle. Due to the
existence of the SO2 group in sulfonyl azides, the D2h-
symmetric porphyrin P1-containing amide functional groups
at the ortho positions of meso-phenyl groups was designed
to invoke a potential hydrogen bonding interaction between
the SdO and N-H unit in the supposed nitrene intermediate
of [Co(P1)] (A, Scheme 1).15 As a result of stabilization and
activation of A from the hydrogen-bonding interaction,16
[Co(P1)] was expected to be a superior catalyst, in com-
parison with [Co(TPP)] and [Co(TDClPP)], for aziridination
with sulfonyl azides.
Figure 1. Structures of porphyrin cobalt(II) complexes.
available diphenylphosphoryl azide (DPPA) as a convenient
new nitrene source, leading to the formation of N-phospho-
rylated aziridines. In an attempt to expand the catalytic
process for other azides, it was found that [Co(TPP)] was
ineffective for olefin aziridination with sulfonyl azides.13 For
example, the desired aziridines 2a-c were obtained only in
11-24% yields from styrene when the common azides 1a-c
were used (Scheme 2).14 Changing the catalyst to Co(TD-
ClPP) (Figure 1), which was shown to be effective for
P1 was synthesized from its tetrabrominated precursor via
a Pd-mediated quadruple amidation reaction with isobuty-
lamide by following the previously established method (see
(12) (a) Gao, G.-Y.; Jones, J. E.; Vyas, R.; Harden, J. D.; Zhang, X. P.
J. Org. Chem. 2006, 71, 6655. (b) Gao, G.-Y.; Harden, J. D.; Zhang, X. P.
Org. Lett. 2005, 7, 3191. (c) Ruppel, J. V.; Kamble, R. M.; Zhang,
X. P. Org. Lett. 2007, 9, 4889.
(6) (a) Scriven, E. F. V.; Turnbull, K. Chem. ReV. 1988, 88, 297. (b)
Brase, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem., Int. Ed.
(13) Careful control experiments showed that 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.
2005, 44, 5188
(7) (a) Kwart, H.; Khan, A. A. J. Am. Chem. Soc. 1967, 89, 1951. (b)
Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5889
.
.
(14) Except unreacted azides and styrene, no other products were
observed.
(8) (a) Cenini, S.; Gallo, E.; Caselli, A.; Ragaini, F.; Fantauzzi, S.;
Piangiolino, C. Coord. Chem. ReV. 2006, 250, 1234. (b) Piangiolino, C.;
Gallo, E.; Caselli, A.; Fantauzzi, S.; Ragaini, F.; Cenini, S. Eur. J. Org.
(15) Simple computer modeling by molecular mechanics with Spartan
04 resulted in a minimized geometry with an O--N-H distance of 2.9 Å,
suggesting a possibility of significant hydrogen bonding interaction. It should
be noted that there is no experimental evidence for such interactions other
than the modeling.
Chem. 2007, 743
(9) (a) Katsuki, T. Chem. Lett. 2005, 1304. (b) Kawabata, H.; Omura,
K.; Uchida, T.; Katsuki, T. Chem. Asian J. 2007, 2, 248
(10) For a Co-catalyzed hydroazidation of olefins, see: Waser, J.; Nambu,
H.; Carreira, E. M. J. Am. Chem. Soc. 2005, 127, 8294
(11) For a Brønsted acid-promoted process, see: Mahoney, J. M.; Smith,
.
.
(16) For an example of stabilization and activation of reactive intermedi-
ate by hydrogen bonding interactions, see: Lucas, R. L.; Zart, M. K.;
Mukerjee, J.; Sorrell, T. N.; Powell, D. R.; Borovik, A. S. J. Am. Chem.
Soc. 2006, 128, 15476.
.
C. R.; Johnston, J. N. J. Am. Chem. Soc. 2005, 127, 1354
.
1996
Org. Lett., Vol. 10, No. 10, 2008

Table 1. [Co(P1)]-Catalyzed Aziridination of Styrene with
Table 2. Aziridination of Aromatic Olefins with Arylsulfonyl
Azides by [Co(P1)]a
Different Arylsulfonyl Azidesa
a Reactions were carried out for 18 h in chlorobenzene at 40 °C under
N2 in the presence of 4 Å molecular sieves using 2 mol % of [Co(P1)].
Concentration: 0.20 mmol of azide/1 mL of chlorobenzene; Styrene:Azide
) 5:1. b Isolated yields.
the Supporting Information).17 [Co(P1)] was readily prepared
from reaction of P1 with CoCl2 in THF in the presence of
2,6-lutidine (see the Supporting Information). Under the same
conditions used for the aforementioned reactions by [Co(T-
PP)] and [Co(TDClPP)], we were delighted to find that
employment of [Co(P1)] resulted in a dramatic improvement
of the catalytic aziridination (Scheme 2). The desired
aziridines 2a, 2b, and 2c were obtained in 94%, 88%, and
98% isolated yields, respectively, supporting the hydrogen
bonding guided catalyst design.18
In addition to azides 1a, 1b, and 1c that contain -methyl,
-methoxy, and -acetamide groups (entries 1-3), [Co(P1)]
could effectively activate a wide range of arylsulfonyl azides
for aziridination (Table 1). For example, the use of arylsul-
fonyl azides having p-cyano (1d), p-nitro (1e), and o-nitro
(1f) substituents afforded the corresponding aziridination
products of styrene 2d-b in excellent yields (entries 4-6).
Naphthalene-1-sulfonyl azide 1g was found to be an equally
active nitrene source (entry 7). The [Co(P1)]-based catalytic
a Reactions were carried out for 18 h in chlorobenzene at 40 °C under
N2 in the presence of 4 Å molecular sieves using 2 mol % [Co(P1)]; Olefin:
Azide ) 5:1; Concentration: 0.20 mmmol azide/1 mL chlorobenzene.
b Isolated yields. c Olefin:Azide ) 1:1.2. Concentration: 0.20 mmol of
azide/1 mL of chlorobenzene. d Performed at 60 °C.
(17) (a) Chen, Y.; Fields, K. B.; Zhang, X. P. J. Am. Chem. Soc. 2004,
126, 14718. (b) Chen, Y.; Ruppel, J. V.; Zhang, X. P. J. Am. Chem. Soc.
2007, 129, 12074. (c) Zhu, S.; Ruppel, J. V.; Lu, H.; Wojtas, L.; Zhang,
X. P. J. Am. Chem. Soc. 2008, 130, 5042.
aziridination system could be successfully applied to various
combinations of arylsulfonyl azides and aromatic olefins
(Table 2).19 For example, using azide 1e as a nitrene source,
Org. Lett., Vol. 10, No. 10, 2008
1997

various styrene derivatives as well as 2-vinylnaphthalene
could be aziridinated in high to excellent yields (entries
1-10). Similar results were obtained for azide 1c (entries
11-14). While most of the reactions were carried out with
5 equiv of olefin, the catalytic process could be operated
with olefins as the limiting reagent as demonstrated with
some selected examples, albeit in relatively lower yields
(entries 1, 2, 5, 6, and 8).
In summary, guided by potential hydrogen-bonding in-
teraction in the proposed intermediate (A), we designed and
synthesized the new porphyrin P1 whose Co complex
[Co(P1)] was shown to be a highly effective catalyst for
aziridination of aromatic olefins with arylsulfonyl azides
under mild conditions. Efforts are underway to expand the
substrate scope to include nonaromatic olefins and to develop
its asymmetric variants.
Acknowledgment. We are grateful for financial support
of this work from the University of South Florida 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 the NSF
(CRIF: MU-0443611).
Supporting Information Available: Analytical data and
spectra for all products. This material is available free of
charge via the Internet at http://pubs.acs.org.
(18) [Co(P1)] could effectively catalyze aziridination of styrene with
PhIdNTs, forming the desired aziridine in 84% isolated yield.
(19) The current [Co(P1)]-based catalytic system was ineffective for
multiple substituted and aliphatic olefins.
OL800588P
1998
Org. Lett., Vol. 10, No. 10, 2008