Amidation of saturated C-H bonds catalyzed by electron-deficient ruthenium and manganese porphyrins. A highly catalytic nitrogen atom transfer process

Article abstract of DOI:10.1021/ol000107r

(equation presented) Amidation of a variety of hydrocarbons with PhI=NTs catalyzed by ruthenium and manganese meso-tetrakis(pentafluorophenyl)porphyrins 1 and 2 afforded N-substituted amides in up to 92% yields with good to excellent substrate conversions. By employing catalyst 2, exceptionally high turnovers (up to 2600) were achieved, and the amidations can be effected by directly using PhI(OAc)₂/NH₂R as amidating reagents; in the case of R = COCF₃ a direct amination was realized in up to 90% yield.

Full text of DOI:10.1021/ol000107r

ORGANIC
LETTERS
2000
Vol. 2, No. 15
2233-2236
Amidation of Saturated C−H Bonds
Catalyzed by Electron-Deficient
Ruthenium and Manganese Porphyrins.
A Highly Catalytic Nitrogen Atom
Transfer Process
Xiao-Qi Yu, Jie-Sheng Huang, Xiang-Ge Zhou, and Chi-Ming Che*
Department of Chemistry, The UniVersity of Hong Kong, Pokfulam Road, Hong Kong
cmche@hku.hk
Received April 24, 2000
ABSTRACT
Amidation of a variety of hydrocarbons with PhIdNTs catalyzed by ruthenium and manganese meso-tetrakis(pentafluorophenyl)porphyrins 1
and 2 afforded N-substituted amides in up to 92% yields with good to excellent substrate conversions. By employing catalyst 2, exceptionally
high turnovers (up to 2600) were achieved, and the amidations can be effected by directly using PhI(OAc)2/NH R as amidating reagents; in the
2
case of R ) COCF3 a direct amination was realized in up to 90% yield.
Metal complex-catalyzed nitrogen atom transfer reactions are
among the most attractive methodologies for the syntheses
of aziridines,1 amides,2-5 or amines.6 Despite encouraging
advances, a conspicuous problem currently facing these
systems lies in their rather low catalyst turnovers (rarely
>50). This contrasts with closely related epoxidation or
hydroxylation processes via metal-mediated oxygen atom
transfer reactions, for which thousands of catalyst turnovers
are not uncommon.7 We report here the amidation of
(1) Selected examples: (a) Groves, J. T.; Takahashi, T. J. Am. Chem.
Soc. 1983, 105, 2073. (b) Mansuy, D.; Mahy, J.-P.; Dureault, A.; Bedi, G.;
Battioni, P. J. Chem. Soc., Chem. Commun. 1984, 1161. (c) Evans, D. A.;
Faul, M. M.; Bilodeau, M. T. J. Org. Chem. 1991, 56, 6744. (d) O’Connor,
K. J.; Wey, S.-J.; Burrows, C. J. Tetrahedron Lett. 1992, 33, 1001. (e) Pe´rez,
P. J.; Brookhart, M.; Templeton, J. L. Organometallics 1993, 12, 261. (f)
Li, Z.; Conser, K. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1993, 115, 5326.
(g) Noda, K.; Hosoya, N.; Irie, R.; Ito, Y.; Katsuki, T. Synlett 1993, 469.
(h) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Am. Chem. Soc. 1994,
116, 2742. (i) Tanner, D.; Andersson, P. G.; Harden, A.; Somfai, P.
Tetrahedron Lett. 1994, 35, 4631. (j) Knight, J. G.; Muldowney, M. P.
Synlett 1995, 949. (k) Mu¨ller, P.; Baud, C.; Jacquier, Y. Tetrahedron 1996,
52, 1543. (l) So¨dergren, M. J.; Alonso, D. A.; Bedekar, A. V.; Andersson,
P. G. Tetrahedron Lett. 1997, 38, 6897. (m) Ando, T.; Minakata, S.; Ryu,
I.; Komatsu, M. Tetrahedron Lett. 1998, 39, 309. (n) Vyas, R.; Chanda, B.
M.; Bedekar, A. V. Tetrahedron Lett. 1998, 39, 4715. (o) Simonato, J.-P.;
Pe´caut, J.; Scheidt, W. R.; Marchon, J.-C. Chem. Commun. 1999, 989. (p)
Dauban, P.; Dodd, R. H. J. Org. Chem. 1999, 64, 5304.
(4) (a) Mu¨ller, P.; Baud, C.; Jacquier, Y.; Moran, M.; Na¨geli, I. J. Phys.
Org. Chem. 1996, 9, 341. (b) Na¨geli, I.; Baud, C.; Bernardinelli, G.; Jacquier,
Y.; Moran, M.; Mu¨ller, P. Hel. Chim. Acta 1997, 80, 1087.
(5) (a) Au, S.-M.; Zhang, S.-B.; Fung, W.-H.; Yu, W.-Y.; Che, C.-M.;
Cheung, K.-K. Chem. Commun. 1998, 2677. (b) Au, S.-M.; Huang, J.-S.;
Yu, W.-Y.; Fung, W.-H.; Che, C.-M. J. Am. Chem. Soc. 1999, 121, 9120.
(c) Zhou, X.-G.; Yu, X.-Q.; Huang, J.-S.; Che, C.-M. Chem. Commun. 1999,
2377.
(6) Selected examples: (a) Srivastava, A.; Ma, Y.-A.; Pankayatselvan,
R.; Dinges, W.; Nicholas, K. M. J. Chem. Soc., Chem. Commun. 1992,
853. (b) Johannsen, M.; Jφrgensen, K. A. J. Org. Chem. 1994, 59, 214. (c)
Srivastava, R. S.; Nicholas, K. M. Tetrahedron Lett. 1994, 35, 8739. (d)
Srivastava, R. S.; Nicholas, K. M. Chem. Commun. 1996, 2335. (e) Cenini,
S.; Ragaini, F.; Tollari, S.; Paone, D. J. Am. Chem. Soc. 1996, 118, 11964.
(f) Srivastava, R. S.; Nicholas, K. M. Chem. Commun. 1998, 2705.
(7) Selected examples: (a) Traylor, P. S.; Dolphin, D.; Traylor, T. G. J.
Chem. Soc., Chem. Commun. 1984, 279. (b) Ellis, P. E., Jr.; Lyons, J. E.
Coord. Chem. ReV. 1990, 105, 181. (c) Ohtake, H.; Higuchi, T.; Hirobe,
M. J. Am. Chem. Soc. 1992, 114, 10660. (d) Groves, J. T.; Bonchio, M.;
Carofiglio, T.; Shalyaev, K. J. Am. Chem. Soc. 1996, 118, 8961. (e) Collman,
J. P.; Wang, Z.; Straumanis, A.; Quelquejeu, M. J. Am. Chem. Soc. 1999,
121, 460.
(2) (a) Breslow, R.; Gellman, S. H. J. Chem. Soc., Chem. Commun. 1982,
1400. (b) Breslow, R.; Gellman, S. H. J. Am. Chem. Soc. 1983, 105, 6728.
(3) (a) Mahy, J. P.; Bedi, G.; Battioni, P.; Mansuy, D. Tetrahedron Lett.
1988, 29, 1927. (b) Mahy, J. P.; Bedi, G.; Battioni, P.; Mansuy, D. New J.
Chem. 1989, 13, 651.
10.1021/ol000107r CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/24/2000

Table 1. Amidation of Saturated C-H Bonds with PhIdNTs Catalyzed by [Ru(TPFPP)(CO)] (1) or [Mn(TPFPP)Cl] (2)a
a All reactions were performed in CH2Cl2 at 40 °C for 2 h with a catalyst:substrate:(PhIdNTs) molar ratio of 1:75:150. b On the basis of the amount of
substrate consumed.
saturated C-H bonds with PhIdNTs catalyzed by electron-
deficient ruthenium and manganese porphyrins (complexes
1 and 2, respectively),8 which features exceptionally high
turnoVers (up to 2600 with 2 as catalyst) for a catalytic
nitrogen atom transfer process.
SO2Me) as amidating reagents. Especially interesting is that
in the case of R ) COCF3 a direct amination of indan was
realized.
Complexes 1 and 2 each bear an electron-deficient
porphyrin macrocyclesmeso-tetrakis(pentafluorophenyl)por-
phyrinato dianion (TPFPP). Like their counterparts with other
porphyrinato ligands,2,3,5c both complexes are efficient cata-
lysts toward PhIdNTs amidation of a variety of hydrocar-
bons including ethylbenzene, indan, adamantane, cyclohex-
ene, tetrahydrofuran, 1,2-dihydronaphthalene, 2-ethylnaph-
thalene, and 3-hexene. In contrast to previous amidation
studies, which were usually carried out with up to a 100
fold-excess of substrates3-5 or in an equivolume mixture of
substrate and solvent2a to minimize catalyst decomposition,4b
complex 1 or 2-catalyzed amidations can be performed
efficiently by employing excess PhIdNTs with substrates
as limiting reagents. The results obtained for the reactions
in dichloromethane at 40 °C with a catalyst:substrate:(PhId
NTs) molar ratio of 1:75:150 are shown in Table 1. It can
be seen from Table 1 that indan (entries 3 and 4), adamantane
(entries 5 and 6), and 1,2-dihydronaphthalene (entries 11 and
The metal-mediated amidation of saturated C-H bonds
with a nitrene source was pioneered in 1982 by Breslow and
co-workers,2a who successfully amidated cyclohexane with
PhIdNTs in the presence of iron or manganese porphyrins.
Thereafter, Mansuy and co-workers demonstrated that iron
and particularly manganese porphyrins can catalyze PhId
NTs amidation of adamantane or allylic amidation of alkenes
in up to 70% yields.3 Recent investigations by Mu¨ller4 and
us5 revealed the efficacy of dirhodium and ruthenium
catalysts, respectively, for the amidation of a series of
hydrocarbons with PhIdNR (R ) Ns (SO2-p-C6H4NO2)4 and
Ts5). However, all these amidation systems require the
presynthesis of a nitrene source from PhI(OAc)2 and NH2R.
In the present work, complex 2 also serves as a good catalyst
for amidation of several hydrocarbons directly with com-
mercially available PhI(OAc)2 and NH2R (R ) Ts, Ns, and
2234
Org. Lett., Vol. 2, No. 15, 2000

catalyst 1 or 2 generated aziridines instead of amides as the
predominant products, as shown in entries 16-21 in Table
1. Again, complex 2 is a more efficient catalyst in these
cases, catalyzing the aziridination of cyclooctene in 81%
yield with 95% substrate conversion (entry 19). For the
reactions using allyl benzene (entries 16 and 17) and 1-octene
(entries 20 and 21) as substrates, although catalyst 2 resulted
in higher conversions of the substrates and higher overall
yields of aziridines, the aziridine selectivities were lower than
those of catalyst 1.
The solvent and temperature effects were examined by
using indan as the substrate. It was found that dichlo-
romethane was superior to acetonitrile or benzene, and with
dichloromethane as solvent the amidations were best per-
formed at 40 °C. For example, decreasing the temperature
from 40 to 20 °C led to a decrease in the yield of N-tosyl-
1-aminoindan (3) from 73 to 60% (catalyst 1). In contrast
to oxygen atom transfer reactions such as alkene epoxida-
tions, which usually benefit from donating additives such
as methylimidazole (MeIm) and pyridine N-oxide (pyO),9
introducing additives 1-MeIm, pyO, and 4-Ph-pyO to
complex 2-catalyzed amidation of indan led to a considerable
decrease in the yield of amide 3. For instance, when
equimolar quantities of 1-MeIm and PhIdNTs were used,
only traces of 3 were obtained.
12) are superior substrates for the amidation reaction
catalyzed by either complex 1 or 2, with excellent conver-
sions obtained for both catalysts. Note that for almost all
the amidations shown in Table 1 complex 2 is a more
efficient catalyst than complex 1. With ethylbenzene (entries
1 and 2), tetrahydrofuran (entries 9 and 10), and 2-ethyl-
naphthalene (entries 13 and 14) as substrates, much higher
conversions were obtained by using catalyst 2. However, in
these cases, the yields of N-substituted amides (relative to
the amounts of substrates consumed) are slightly lower than
those obtained for catalyst 1. Of all the substrates examined,
cyclohexene was amidated to the corresponding amide in
the highest yield (92%) with a 93% conversion of the alkene
(entry 8, catalyst 2).
The effect of catalyst loading was inspected in the case
of complex 2-catalyzed amidation of indan. Remarkably,
reducing the loading of 2 to 0.04 mol % (relative to starting
PhIdNTs) caused almost no decrease in the yield of 3, with
turnovers increasing to 1600. When 0.013 mol % of 2 was
used, turnovers as high as 2600 were achieved. Complex 2
Note that the reactions of hydrocarbons allyl benzene,
cyclooctene, and 1-octene with PhIdNTs in the presence of
Table 2. Amidation of Saturated C-H Bonds with PhI(OAc)2 and NH2R (R ) Ts, Ns, SO2Me) Catalyzed by Complex 2a
a All reactions were performed in CH2Cl2 at 40 °C for 2 h with a catalyst:substrate:PhI(OAc)2:NH2R molar ratio of 1:100:125:150. b On the basis of the
amount of substrate consumed.
Org. Lett., Vol. 2, No. 15, 2000
2235

is also a robust catalyst for alkene aziridination. For example,
the PhIdNTs aziridination of 1-octene catalyzed by 2 (0.019
mol %) gave rise to 1944 turnovers.
Table 3. Amination of Indan with PhI(OAc)2 and NH2COCF3
Catalyzed by Complex 2a
The amidations of ethylbenzene, indan, adamantane,
cyclohexene, and tetrahydrofuran directly with PhI(OAc)2
and NH2Ts as amidating reagents were explored by employ-
ing catalyst 2. In dichloromethane at 40 °C, with a
2:substrate:PhI(OAc)2:NH2Ts molar ratio of 1:100:125:150,
the corresponding N-substituted amides were obtained in 72-
90% yields within 2 h with good to excellent substrate
conversions (Table 2). A comparison of the data in Tables
1 and 2 reveals that the PhI(OAc)2/NH2Ts amidations result
in comparable or even higher yields than their PhIdNTs
counterparts. However, the substrate conversions in the
former cases are lower except that for ethylbenzene.
Attempts were made to extend the 2/PhI(OAc)2/NH2Ts
system to other commercially available amides, such as
NH2R (R ) Ns, SO2Me) and NH2COCF3. As shown in
entries 3 and 4 in Table 2, the amidation of indan with PhI-
(OAc)2/NH2R (R ) Ns or SO2Me) afforded excellent
conversions of the substrate, with the corresponding N-
substituted amides isolated in up to 92% yields. Remarkably,
by employing PhI(OAc)2/NH2COCF3 as the amidating
reagent, a direct amination of indan was achieved (entry 1
in Table 3). Addition of inorganic bases such as Na2CO3
and NaOH led to a significant increase in both the conversion
of indan and the yield of 1-aminoindan (entries 2 and 3 in
Table 3). For example, in the presence of NaOH, the complex
2-catalyzed amination of indan with PhI(OAc)2/NH2COCF3
afforded 1-aminoindan in 90% isolated yield with good
substrate conversion. However, addition of 1-MeIm instead
of NaOH to the reaction rendered the catalyst almost
completely inactive toward the amination (entry 4 in Table
3).
entry
additive
conversion (%)
isolated yield (%)b
1
2
3
4
55
69
73
trace
61
88
90
trace
Na2CO3
NaOH
1-MeIm
a Reaction conditions: identical with those in Table 2. b On the basis of
the amount of substrate consumed.
(OAc)2/NH2R” could offer a new entry for amidation of
organic nature products such as aromatic steroid equilenin
acetate, which may be important for developing novel types
of biologically useful nitrogen-containing products.
Acknowledgment. This work was supported by The
University of Hong Kong, Hong Kong University Founda-
tion, and the Hong Kong Research Grants Council.
Supporting Information Available: Detailed experi-
mental procedures and spectral data of the amidation
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL000107R
(8) During the preparation of the manuscript, Breslow and co-workers
reported the amidation of equilenin acetate with PhIdNTs catalyzed by
complex 2, see: Yang, J.; Weinberg, R.; Breslow, R. Chem. Commun. 2000,
531.
(9) (a) Samsel, E. G.; Srinivasan, K.; Kochi, J. K. J. Am. Chem. Soc.
1985, 107, 7606. (b) Irie, R.; Ito, Y.; Katsuki, T. Synlett 1991, 265.
According to the recent discovery by Breslow and co-
workers,8 the above-described protocol “complex 1 or 2/PhI-
2236
Org. Lett., Vol. 2, No. 15, 2000