Amidation of unfunctionalized hydrocarbons catalyzed by ruthenium cyclic amine or bipyridine complexes

Article abstract of DOI:10.1021/jo000881s

Selective amidation of simple hydrocarbons with pre-isolated and in-situ formed iminoiodanes catalyzed by ruthenium complexes [Ru(III)(Me₃tacn)(CF₃CO₂)₃·H₂O] (2b, Me₃tacn = N,N',N_-trimethyl-1,4,7-triazacyclononane) and cis-[Ru(II)(6,6'-Cl₂bpy)₂Cl₂] (3, 6,6'-Cl₂bpy = 6,6'-dichloro-2,2'-bipyridine) was investigated. With PhI=NTs as nitrogen source, both catalysts efficiently promote the amidation of adamantane, cyclohexene, ethylbenzene, cumene, indan, tetralin, and diphenylmethane to afford N-substituted sulfonamides in 80-93% yields with high selectivity. Competitive amidations of para-substituted ethylbenzenes and kinetic isotope effect for the amidation of cyclohexene/cyclohexene-d₁₀ suggest that the amidation processes probably proceed via the hydrogen abstraction by a reactive Ru=NTs species to form a carboradical intermediate. The amidation with PhI(OAc)₂/TsNH₂ gave results comparable to those obtained with PhI=NTs. Extension of the 'PhI(OAc)₂/TsNH₂ + catalyst 2b or 3' protocol to MeSO₂NH₂ and PhCONH₂ with ethylbenzene as substrate produced the corresponding N-substituted amides in up to 89% yield.

Full text of DOI:10.1021/jo000881s

7
858
J . Org. Chem. 2000, 65, 7858-7864
Am id a tion of Un fu n ction a lized Hyd r oca r bon s Ca ta lyzed by
Ru th en iu m Cyclic Am in e or Bip yr id in e Com p lexes
Sze-Man Au, J ie-Sheng Huang, Chi-Ming Che,* and Wing-Yiu Yu
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong
cmche@hku.hk
Received J une 8, 2000
Selective amidation of simple hydrocarbons with pre-isolated and in-situ formed iminoiodanes
III
catalyzed by ruthenium complexes [Ru (Me
1
3
tacn)(CF
bpy) Cl
3
CO
] (3, 6,6′-Cl
2
)
3
‚H
2
O] (2b, Me
3
tacn ) N,N′,N′′-trimethyl-
II
,4,7-triazacyclononane) and cis-[Ru (6,6′-Cl
2
2
2
2
bpy ) 6,6′-dichloro-2,2′-bipyridine)
was investigated. With PhIdNTs as nitrogen source, both catalysts efficiently promote the amidation
of adamantane, cyclohexene, ethylbenzene, cumene, indan, tetralin, and diphenylmethane to afford
N-substituted sulfonamides in 80-93% yields with high selectivity. Competitive amidations of para-
substituted ethylbenzenes and kinetic isotope effect for the amidation of cyclohexene/cyclohexene-
d
10 suggest that the amidation processes probably proceed via the hydrogen abstraction by a reactive
RudNTs species to form a carboradical intermediate. The amidation with PhI(OAc) /TsNH gave
results comparable to those obtained with PhIdNTs. Extension of the “PhI(OAc) /TsNH + catalyst
b or 3” protocol to MeSO NH and PhCONH with ethylbenzene as substrate produced the
corresponding N-substituted amides in up to 89% yield.
2
2
2
2
2
2
2
2
6
7,8
In tr od u ction
The selective amination of unfunctionalized hydrocar-
ium catalysts” have been achieved. These putative
sulfonylimido group transfer processes provide a unique
approach to N-substituted sulfonamides that could be
bons in the presence of metal catalysts constitutes an
9
10
desulfonylated by hydrolytic or reductive methods to
amines or used directly as well-protected amines for
further functionalizations.
Our quest for ruthenium amination or amidation
catalysts was based on the well-documented oxidation
1
appealing route for the synthesis of amines. However,
so far only a few such aminations are known, including
the allylic amination of alkenes with “ArNHOH + iron
2
or molybdenum catalysts” and “ArNO
2
/CO + ruthenium
3
11
or iron catalysts”, which are proposed to proceed via an
ene-like reaction featuring alkene double bond trans-
chemistry of high-valent ruthenium-oxo complexes. We
envisaged that the ruthenium-imido analogues should
also exhibit rich oxidation chemistry that has potential
application in the C-H bond functionalization. Upon
2
,3b
position
or involve a metal-alkene complex as active
species.3 The metal-mediated direct amination of hydro-
carbons via alkyl- or arylimido insertion into saturated
C-H bonds, a nitrogen analogue of hydroxylation via oxo
group transfer process, would serve as another attractive
a
1
2
isolation of several imido ruthenium(VI) porphyrins, we
found that the bis(tosylimido) complexes 1a ,b can under-
go stoichiometric amidation with a variety of hydrocar-
4
12b,d
methodology but as yet remains unrealized. Notably,
bons.
In particular, the amidation of 2-ethylnaphtha-
direct amidations of hydrocarbons with “PhIdNTs +
lene by complex 1b with a chiral porphyrinato ligand
5
manganese porphyrin catalysts” or “PhIdNNs + dirhod-
(5) (a) Breslow, R.; Gellman, S. H. J . Chem. Soc., Chem. Commun.
1
982, 1400. (b) Breslow, R.; Gellman, S. H. J . Am. Chem. Soc. 1983,
(
1) (a) Roundhill, D. M. Chem. Rev. 1992, 92, 1. (b) M u¨ ller, T. E.;
105, 6728. (c) Mahy, J . P.; Bedi, G.; Battioni, P.; Mansuy, D.
Tetrahedron Lett. 1988, 29, 1927. (d) Mahy, J . P.; Bedi, G.; Battioni,
P.; Mansuy, D. New J . Chem. 1989, 13, 651. (e) Yang, J .; Weinberg,
R.; Breslow, R. Chem. Commun. 2000, 531.
Beller, M. Chem. Rev. 1998, 98, 675. (c) J ohannsen, M.; J φrgensen, K.
A. Chem. Rev. 1998, 98, 1689.
(
2) (a) Srivastava, A.; Ma, Y.-A.; Pankayatselvan, R.; Dinges, W.;
Nicholas, K. M. J . Chem. Soc., Chem. Commun. 1992, 853. (b)
J ohannsen, M.; J φrgensen, K. A. J . Org. Chem. 1994, 59, 214. (c)
Srivastava, R. S.; Nicholas, K. M. Tetrahedron Lett. 1994, 35, 8739.
(6) (a) M u¨ ller, P.; Baud, C.; J acquier, Y.; Moran, M.; N a¨ geli, I. J .
Phys. Org. Chem. 1996, 9, 341. (b) N a¨ geli, I.; Baud, C.; Bernardinelli,
G.; J acquier, Y.; Moran, M.; M u¨ ller, P. Hel. Chim. Acta 1997, 80, 1087.
(7) For related amidation with chloramine-T trihydrate (TsNClNa‚
(
d) Srivastava, R. S.; Nicholas, K. M. Chem. Commun. 1996, 2335.
(3) (a) Cenini, S.; Ragaini, F.; Tollari, S.; Paone, D. J . Am. Chem.
2
3H O) catalyzed by copper complex, see: Albone, D. P.; Aujla, P. S.;
Soc. 1996, 118, 11964. (b) Srivastava, R. S.; Nicholas, K. M. Chem.
Commun. 1998, 2705.
Taylor, P. C.; Challenger, S.; Derrick, A. M. J . Org. Chem. 1998, 63,
9569.
t
(4) Some zirconium bisamides, Cp
2
Zr(NHR)
2
, are known to catalyze
(8) For related amidation with alkyl peroxycarbamate (Bu OO-
the hydroamination of alkynes and allene to form enamines and imines
via zirconium alkyl- or arylimido intermediates, see for example: (a)
Walsh, P. J .; Baranger, A. M.; Bergman, R. G. J . Am. Chem. Soc. 1992,
CONHTs) catalyzed by copper complexes, see: Kohmura, Y.; Kawasaki,
K.-i.; Katsuki, T. Synlett 1997, 1456.
(9) Roemmele, R. C.; Rapoport, H. J . Org. Chem. 1988, 53, 2367.
(10) Fleming, I.; Frackenpohl, J .; Ila, H. J . Chem. Soc., Perkin Trans.
1 1998, 1229, and many references therein.
1
14, 1708. (b) Baranger, A. M.; Walsh, P. J .; Bergman, R. G. J . Am.
Chem. Soc. 1993, 115, 2753. These processes are characteristic of the
[
2 + 2] cycloaddition of ZrdNR multiple bonds with CtC or CdC
(11) For reviews, see: (a) Griffith, W. P. Chem. Soc. Rev. 1992, 21,
179. (b) Che, C.-M.; Yam, V. W. W. Adv. Inorg. Chem. 1992, 39, 233.
(12) (a) Huang, J . S.; Che, C.-M.; Poon, C.-K. J . Chem. Soc., Chem.
Commun. 1992, 161. (b) Au, S.-M.; Huang, J .-S.; Yu, W.-Y.; Fung, W.-
H.; Che, C.-M. J . Am. Chem. Soc. 1999, 121, 9120. (c) Huang, J .-S.;
Sun, X.-R.; Leung, S. K.-Y.; Cheung, K.-K.; Che, C.-M. Chem. Eur. J .
2000, 6, 334. (d) Zhou, X.-G.; Yu, X.-Q.; Huang, J .-S.; Che, C.-M. Chem.
Commun. 1999, 2377.
bonds, and result in a reduction of the alkynes or allene, unlike the
direct insertion of imido groups into saturated C-H bonds. Stoichio-
metric C-H bond activation of an alkane or arene can be effected by
t
transient TidNSiBu
3
species via the 1,2-addition of the C-H bond
across the TidN multiple bond (Cummins, C. C.; Baxter, S. M.;
Wolczanski, P. T. J . Am. Chem. Soc. 1988, 110, 8731) but such a
reaction does not result in imido group transfer to the hydrocarbon.
1
0.1021/jo000881s CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/21/2000

Amidation of Unfunctionalized Hydrocarbons
J . Org. Chem., Vol. 65, No. 23, 2000 7859
results in the highest enantiocontrol yet obtained for a
metal-mediated asymmetric amidation of saturated C-H
bonds.1 On the basis of these findings, catalytic ami-
constrained by the porphyrin ligands.18 In addition, by
3
employing the Ru-Me tacn complex 2b as a catalyst, the
2d
19
tert-butyl hydroperoxide epoxidation of alkenes and
oxidation of alcohols20 were found to be highly chemose-
lective.
dations with “PhIdNTs + ruthenium porphyrin 1c or 1d ”
were eventually developed.1
2d,13
However, isolated high-
valent ruthenium-imido complexes without porphyrin
auxiliaries are extremely rare,14 and none of them have
been reported to undergo amidation reactions with a
hydrocarbon.
The present work deals with the PhIdNTs amidation
of hydrocarbons catalyzed by ruthenium non-porphyrin
complexes 2 and 3,15 which proceeds probably via sulfo-
nylimido insertion into saturated C-H bonds. Moreover,
like electron-deficient manganese porphyrin [Mn(TPF-
PP)Cl],13 complexes 2b and 3 can catalyze the amidation
To uncover efficient non-porphyrin ruthenium amida-
tion catalysts, we screened a variety of ruthenium
complexes with tetra-, tri-, and bidentate ligands, of
3
which those containing Me tacn (complexes 2a ,b) and
21
6
,6′-Cl
2
bpy (complex 3) gave the best results. Catalysts
2
and 3 have several features in common. One is that
they are more easily accessible than the porphyrin
catalysts 1c,d . Further, they bear neutral chelating
17
ligands that are robust toward oxidation, with the
coordination atoms arranged in a facial or helical geom-
etry, in contrast to the planar coordination mode of the
porphyrinato dianions in 1c,d . Finally, they might be
converted preferentially to cis-bis(imido) species, as in
the case of the cis-dioxo analogues mentioned above,
directly with commercially available PhI(OAc)
without the necessity to pre-isolate PhIdNTs.16 The “PhI-
OAc) /TsNH + 2b or 3” protocol can be extended to
MeSO NH and PhCONH , in which cases the corres-
2 2
/TsNH
(
2
2
2
2
2
2
ponding iminoiodanes are either explosive (PhIdNSO -
which contrasts with the trans-bis(imido) active species
Me) or unknown (PhIdNCOPh).16 This significantly
increases the types of amides that can be prepared via
ruthenium-catalyzed amidations. Especially, the amida-
12d,13
in 1c- or 1d -catalyzed amidations.
These features
may cause the catalytic activity or selectivity of the non-
porphyrin complexes 2 and 3 to be different from that of
tion of ethylbenzene with “PhI(OAc)
2
/PhCONH
2
+ 2b or
15
the porphyrin complexes. With regard to catalysts 2a
3
” provides the first access to an N-substituted amide of
and 2b, the former was found to be rather moisture
sensitive. Consequently, catalyst 2b, which is stabler to
moisture yet effects the amidation more rapidly, was used
throughout this work.
carboxylic acid via metal-catalyzed amidation of satu-
rated C-H bonds.
Com p lex 2b- or 3-Ca ta lyzed Am id a tion w ith P h Id
NTs. (i) Su bstr a te Scop e. Both complexes 2b and 3 are
efficient catalysts for the PhIdNTs amidation of various
hydrocarbons from adamantane to allylic or benzylic
alkenes. The amidations were generally conducted at
room temperature for 3 h by employing 2 mol % catalysts
(
relative to the starting PhIdNTs) and a slight excess of
1
5
hydrocarbon substrates. This contrasts with catalyst 2a
and other non-porphyrin amidation catalysts,
6
-8
which
require much longer time (12 h for 2a and 15-72 h for
the others) to reach completion and often employ larger
excess of substrates. The results obtained for 2b or
3
-catalyzed amidations of adamantane, cyclohexene, eth-
ylbenzene, cumene, indan, tetralin, and diphenylmethane
in acetonitrile (2b) or dichloromethane (3) are sum-
marized in Table 1. In all cases the unsubstituted
sulfonamide (TsNH
uct, with the total moles of TsNH
2
) was observed to be a major byprod-
and the desired
2
N-substituted amide close to those of starting PhIdNTs.
Since excess substrates were used in the amidation
Resu lts a n d Discu ssion
Ca ta lyst Develop m en t. We previously demonstrated
that the ligands N,N′,N′′-trimethyl-1,4,7-triazacyclononane
(17) (a) Che, C.-M.; Leung, W.-H. J . Chem. Soc., Chem. Commun.
(
Me
3
tacn) and 6,6′-dichloro-2,2′-bipyridine (6,6′-Cl
2
bpy)
1987, 1376. (b) Wong, K.-Y.; Lee, W.-O.; Che, C.-M.; Anson, F. C. J .
Electroanal. Chem. 1991, 319, 207. (c) Cheng, W.-C.; Yu, W.-Y.;
Cheung, K.-K.; Che, C.-M. J . Chem. Soc., Dalton Trans. 1994, 57. (d)
Cheng, W.-C.; Yu, W.-Y.; Cheung, K.-K.; Che, C.-M. J . Chem. Soc.,
Chem. Commun. 1994, 1063.
are well suited for accessing highly oxidizing and steri-
cally bulky ruthenium-oxo complexes.17 Both ligands
exhibit a remarkable capability of stabilizing cis-dioxo
functional groups, contrary to the trans-dioxo groups
(
18) Selected examples: (a) Groves, J . T.; Quinn, R. Inorg. Chem.
1
984, 23, 3844. (b) Leung, W.-H.; Che, C.-M. J . Am. Chem. Soc. 1989,
11, 8812. (c) Ho, C.; Leung, W.-H.; Che, C.-M. J . Chem. Soc., Dalton
1
(
13) Yu, X.-Q.; Huang, J .-S.; Zhou, X.-G.; Che, C.-M. Org. Lett. 2000,
, 2233.
14) (a) Redshaw, C.; Clegg, W.; Wilkinson, G. J . Chem. Soc., Dalton
Trans. 1991, 2933.
(19) Cheng, W.-C.; Fung, W.-H.; Che, C.-M. J . Mol. Catal. A 1996,
113, 311.
2
(
Trans. 1992, 2059. (b) Danopoulos, A. A.; Wilkinson, G.; Hussain-Bates,
B.; Hursthouse, M. B. Polyhedron 1992, 11, 2961.
(20) Fung, W.-H.; Yu, W.-Y.; Che, C.-M. J . Org. Chem. 1998, 63,
2873.
II
(15) The stoichiometric amidation by complex 2a /AgClO
4
and the
(21) Other ruthenium complexes screened include [Ru (salen)-
PhIdNTs amidation catalyzed by complex 2a were preliminarily
reported elsewhere: Au, S.-M.; Zhang, S.-B.; Fung, W.-H.; Yu, W.-Y.;
Che, C.-M.; Cheung, K.-K. Chem. Commun. 1998, 2677.
(PPh
3 2
) ] (prepared as in: Bhowon, M. G.; Wah, H. L. K.; Narain, R.
Polyhedron 1999, 18, 341, salen ) 1,2-bis(3,5-dichlorosalicylideneami-
no)ethane dianion), [Ru (Tp)(PPh
Burns, I. D.; Claire, K. S.; Hill, A. F. Inorg. Chem. 1992, 31, 2906, Tp
II
3 2
) Cl] (prepared as in: Alcock, N. W.;
(16) The known iminoiodanes, such as PhIdNTs and PhIdNNs,
II
were all prepared from the reactions between PhI(OAc) and the
2
) hydrotris(pyrazol-1-yl)borate), [Ru (COD)Cl
2
]
n
(95%, Aldrich, COD
O (Aldrich). These complexes
were found to be poor catalysts for the amidation reactions.
4
corresponding amides under basic conditions, see: Stang, P. J .;
Zhdankin, V. V. Chem. Rev. 1996, 96, 1123 and the references therein.
3 2
) η -1,5-cyclooctadiene), and RuCl ‚xH

7
860 J . Org. Chem., Vol. 65, No. 23, 2000
Ta ble 1. Am id a tion of Sa tu r a ted C-H Bon d s w ith P h IdNTs Ca ta lyzed by Com p lex 2b or 3a
Au et al.
a
Reaction conditions: 25 °C, 3 h, catalyst:(PhIdNTs):substrate mole ratio ) 1:50:60, MeCN (2b) or CH2Cl2 (3). b GC yield based on
the amount of substrate consumed.
processes, the substrate conversions obtained are rather
good, the best (79%, entry 5) of which is close to the
quantitative value of ∼83%.
2
porphyrin amidation systems including “PhIdNNs + Rh -
6
7
(OAc)
4
” and “TsNClNa + copper catalyst” did afford a
mixture of the corresponding amide and aziridine. The
t
The amidation of adamantane (entries 1 and 2) selec-
tively occurred at the tertiary C-H bonds, with the
corresponding amide formed in ∼87% yields (based on
the amount of adamantane consumed). Such tertiary
C-H bond selectivity has been observed in the amida-
2
“Bu OOCONHTs + Cu(OTf) ” system was not reported
to produce the aziridine but the yield of the desired amide
was rather low (27%).8
Of the amidation results in Table 1, the best were
achieved for the benzylic substrate ethylbenzene (entries
5 and 6), whose amidation was directed toward the
saturated C-H bonds of the benzyl moiety to form the
corresponding amide in 93 (2b) and 90% (3) yields with
good to excellent substrate conversions. Extension of such
a benzylic amidation to other substrates, including
cumene (entries 7 and 8), indan (entries 9 and 10),
tetralin (entries 11 and 12), and diphenylmethane (en-
tries 13 and 14) gave comparable results but the sub-
strate conversions were considerably lower. It is aston-
ishing that diphenylmethane is a good substrate for
complex 2 or 3-catalyzed amidation,23 which is superior
to other benzylic hydrocarbons examined in this work
except ethylbenzene. Previously, only dirhodium acetate
was reported to effect the iminoiodane amidation of
diphenylmethane;6b however, in that case the yield of the
corresponding amide was much lower than those ob-
tained for other benzylic hydrocarbons such as indan and
tetralin.
1
2b
tions of the same substrate involving complexes 1a ,
1
1
3
15
d , and 2a . However, the PhIdNNs amidation of
adamantane catalyzed by previously reported dirhodium
catalyst took place at both tertiary and secondary C-H
bonds, affording a mixture of the corresponding amides
in a 71:5 ratio.6b
With cyclohexene as substrate, both catalysts 2b and
3
resulted in allylic amidations to form N-(cyclohex-2-
en-1-yl)tosylamide in excellent yields (entries 3 and 4).
Interestingly, no aziridine was detected in the reaction
although many metal-catalyzed aziridinations of unfunc-
tionalized alkenes with PhIdNTs have been known.22 In
contrast, the amidation of cyclohexene in other non-
(22) Representative examples: (a) Mansuy, D.; Mahy, J .-P.; Du-
reault, A.; Bedi, G.; Battioni, P. J . Chem. Soc., Chem. Commun. 1984,
1
1
161. (b) O’Connor, K. J .; Wey, S.-J .; Burrows, C. J . Tetrahedron Lett.
992, 33, 1001. (c) Li, Z.; Conser, K. R.; J acobsen, E. N. J . Am. Chem.
Soc. 1993, 115, 5326. (d) Noda, K.; Hosoya, N.; Irie, R.; Ito, Y.; Katsuki,
T. Synlett 1993, 469. (e) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J .
Am. Chem. Soc. 1994, 116, 2742.
(23) For related complex 2a -catalyzed amidations, see ref 15.

Amidation of Unfunctionalized Hydrocarbons
J . Org. Chem., Vol. 65, No. 23, 2000 7861
Ta ble 2. Effects of Solven t, Tem p er a tu r e, Nitr ogen Sou r ce, a n d Ca ta lyst Loa d in g in Am id a tion of Eth ylben zen e a n d
Cycloh exen e Ca ta lyzed by Com p lex 2b or 3
nitrogen
source
T
(°C)
conversion
(%)
yielda
(%)
entry
reaction
A (2b)
A (2b)
A (2b)
A (2b)
A (2b, 1 mol %)
A (2b)
A (3)
A (3)
B
B
B
solvent
1
2
3
4
5
6
7
8
9
PhIdNTs
PhIdNTs
PhIdNTs
PhIdNTs
PhIdNTs
PhI(OAc)2 + TsNH2
PhIdNTs
PhIdNTs
PhIdNTs
PhIdNTs
PhIdNTs
PhIdNTs
PhI(OAc)2 + TsNH2
toluene
CH2Cl2
MeCN
MeCN
MeCN
MeCN
CH2Cl2
CH2Cl2
acetone
MeCN
CH2Cl2
CH2Cl2
CH2Cl2
25
25
25
82
25
25
25
40
25
25
25
40
25
49
69
79
63
60
76
70
73
25
31
58
63
55
75
82
93
79
89
90
90
85
81
85
92
92
89
1
1
1
1
0
1
2
3
B
B
a
GC yield based on the amount of substrate consumed.
(
ii) Effect of Solven t, Tem p er a tu r e, a n d Ca ta lyst
Ta ble 3. Rela tive Ra tes (kr el) for th e P h IdNTs
Am id a tion of Eth ylben zen es (p-X-C6H4CH2CH3) Ca ta lyzed
by Com p lex 2b or 3
Loa d in g. While we preliminarily reported the complex
a -catalyzed amidations,15 the reactions were all con-
2
ducted in acetonitrile at room temperature with 2 mol %
catalyst. To ascertain how solvent, temperature and
catalyst loading affect the amidation efficiency of this
class of ruthenium catalyst, we carried out the amidation
reactions of ethylbenzene in various solvents, including
toluene, dichloromethane and acetonitrile at different
temperatures by employing the more reactive catalyst 2b.
The results are shown in entries 1-4 in Table 2.
Evidently, acetonitrile is the solvent of choice, which
results in a considerably higher yield of the amide than
either toluene or dichloromethane at room temperature.
With acetonitrile as solvent, increasing temperature to
krel
entry
X
catalyst 2b
catalyst 3
1
2
3
4
5
MeO
Me
Cl
4.65
2.09
1.39
1.09
1
5.66
1.88
1.29
1.12
1
F
H
alkene hydroxylations with PhIO, the PhIdNTs allylic
amidations catalyzed by manganese porphyrins are
postulated to proceed via hydrogen atom abstraction by
a high-valent MndNTs intermediate.5 Mechanistic stud-
ies on the dirhodium-catalyzed amidations6b reveal that
either a direct insertion or hydrogen abstraction/radical
recombination mechanism must be operative.
To help elucidate the mechanism of complex 2b or
3-catalyzed amidations, we performed competition ex-
periments for the catalytic PhIdNTs amidation of para-
substituted ethylbenzenes. The measured relative ami-
c
8
2 °C led to a significant decrease of both the substrate
conversion and amide selectivity (cf. entries 3 and 4 in
Table 2). This might be ascribed to the thermal decom-
position of PhIdNTs in this solvent. Not surprisingly,
reducing the loading of 2b from 2 to 1 mol % caused a
considerable decrease of the substrate conversion but
with a slight decerease in the amide selectivity (cf. entries
3
and 5).
6 4 2 3
dation rates, krel, of p-X-C H CH CH (X ) MeO, Me, Cl,
The effects of solvent and temperature were also
F) against that of ethylbenzene for both catalysts are
summarized in Table 3. It is evident from the table that
either electron-donating or -withdrawing para-substitu-
ents promote the amidation processes. This contrasts
with the dirhodium-catalyzed PhIdNNs amidations of
ethylbenzenes which are retarded by electron-withdraw-
ing, although promoted by electron-donating para-
substituents.6b However, the results in Table 3 are
parallel to those obtained for the stoichiometric amida-
tion of the same substituted ethylbenzenes by bis-
inspected in the case of complex 3-catalyzed amidation
of ethylbenzene and cyclohexene (entries 7-12 in Table
2
). Unlike the case of catalyst 2b, of the solvents
(dichloromethane, acetone, and acetonitrile) investigated
in the 3-catalyzed amidation at room temperature,
dichloromethane, rather than acetonitrile, is clearly the
superior one (cf. entries 9-11). Moreover, in contrast with
the deleterious effect of higher temperature on the 2b-
catalyzed amidation of ethylbenzene in acetonitrile,
elevation of temperature in the 3-catalyzed amidation of
either ethylbenzene or cyclohexene in dichloromethane
resulted in slightly higher substrate conversion with little
or no loss of amide selectivity (cf. entries 7 and 8; 11 and
1
2b
(tosylimido) ruthenium(VI) porphyrin 1a
porphyrin complex 2a /AgClO .
4
or the non-
1
5
In the case of either catalyst 2b or 3, plotting the log-
(krel) against the Hammett constant σ of the para-
substituent resulted in a concave instead of a straight
line, suggesting the intervention of a radical intermediate
in the amidation processes.24 Consequently, the log(krel)
1
2).
ii) Mech a n istic Asp ects. Metal-catalyzed amida-
(
tions of hydrocarbons with iminoiodanes such as PhId
2
5
NTs are generally proposed to involve metal-imido active
was plotted against a carboradical parameter, TE, as
species.5
,6,12d
However, only in the case of ruthenium
1
2d
porphyrin catalyst was an imido intermediate isolated.
(24) Groves, J . T.; Gross, Z.; Stern, M. K. Inorg. Chem. 1994, 33,
By analogy with iron- or manganese porphyrin-catalyzed
5065.

7
862 J . Org. Chem., Vol. 65, No. 23, 2000
Au et al.
(
6.1),12b and are not inconsistent with a hydrogen ab-
straction process.
Although the amidations catalyzed by complex 2b and
3
likely involve high-valent RudNTs intermediates,
attempts to isolate these species in the catalytic reactions
were unsuccessful. In fact, isolable high-valent ruthe-
nium imido complexes without porphyrin ligands are
extremely rare,14 as mentioned earlier. The possibility
3
of generating RudNTs species bearing a Me tacn ligand
has been discussed before.15 In this work, we examined
the behavior of complex 3 toward the attack by PhId
NTs and observed that treating a solution of 3 in
dichloromethane with PhIdNTs (∼2 equiv) resulted in
a color change to brown accompanied by the disappear-
ance of the MLCT band of 3 in the UV-visible spectrum.
Investigation of the reaction by electrospray mass spec-
F igu r e 1. Log(krel) vs TE plot for the 2b-catalyzed amidation
of para-substituted ethylbenzenes p-X-C H CH CH with PhId
6 4 2 3
NTs.
trometry gave an intense peak at m/z 756 which can be
+
ascribed to the [Ru(6,6′-Cl
2
bpy)
2
(NTs)Cl] species. Efforts
are underway to isolate and fully characterize the
intriguing new ruthenium complex.
Com p lex 2b- or 3-Ca ta lyzed Am id a tion w ith P h I-
(
OAc)
2
/RNH
2
2
(R ) Ts, MeSO , a n d P h CO). A major
drawback of the amidation with PhIdNR lies in the
rather limited types of the iminoiodanes currently at-
tainable.1
6,27
It would be interesting if the precursors to
and RNH , can be directly
PhIdNR, namely PhI(OAc)
2
2
used in the amidation reactions to allow the iminoiodanes
formed in-situ immediately amidate hydrocarbons in the
presence of a metal catalyst. In this manner, the prepa-
ration of N-substituted amides through amidation of
hydrocarbons for the R groups whose corresponding PhId
NR’s are unstable or unknown could be realized.
F igu r e 2. Log(krel) vs TE plot for the 3-catalyzed amidation
of para-substituted ethylbenzenes p-X-C H CH CH with PhId
6 4 2 3
NTs.
We initially explored the possibility of directly using
2 2
commercially available PhI(OAc) /TsNH instead of PhId
previously done for the stoichiometric amidation by
complex 1a .1 Interestingly, the log(krel) vs TE plots for
catalysts 2b and 3 both exhibit a good linearity, as shown
NTs as the nitrogen source. The results achieved for 2b-
catalyzed amidation of ethylbenzene and 3-catalyzed
amidation of cyclohexene are shown in Table 2 (entries
6 and 13), which are fairly similar to those obtained for
the corresponding amidations with PhIdNTs (cf. entries
6 and 3; entries 13 and 11). This encouraged us to
attempt extension of the “PhI(OAc) /TsNH + 2b or 3”
2b
•
in Figures 1 and 2. The slopes of the plots (FTE ) were
determined to be 0.63 (catalyst 2b) and 0.68 (catalyst 3),
•
which are similar to the FTE (0.62) obtained for the
1
2b
stoichiometric amidation by complex 1a . We previously
2
2
reported15 that plotting log(krel) against another radical
protocol to MeSO NH , the corresponding iminoiodane
2
2
•
26
parameter, σJ J
,
for the stoichiometric amidation by
gave rise to a good linearity. To
of which has never been used as the nitrogen source in
the amidations probably owing to its unstable and
explosive nature.16 Table 4 (entries 2 and 11) shows the
results obtained for the amidation of ethylbenzene with
“PhI(OAc) /MeSO NH + 2b or 3”. Notably, by employing
complex 2a /AgClO
4
compare this stoichiometric amidation with the closely
related catalytic amidation of 2b, we also plotted the log-
4
(krel) of 2a /AgClO against TE and obtained an excellent
2
2
2
•
linearity with FTE of 0.72, a value comparable to that
obtained for the 2b-catalyzed amidation. These observa-
tions indicate that the active species in these ruthenium-
mediated amidations should be similar. Therefore, the
PhIdNTs amidations of ethylbenzenes catalyzed by
complex 2b or 3 most probably involve a benzylic radical
intermediate generated via the hydrogen atom abstrac-
tion by a high-valent RudNTs species. To provide further
evidence for this mechanism, we inspected the kinetic
isotope effect for either 2b or 3-catalyzed amidation of
cyclohexene and cyclohexene-d10. These systems were
either of the catalysts, the N-substituted methane-
sulfonamide was obtained in 85% yield with ∼50%
substrate conversion.
Remarkably, the “PhI(OAc) /RNH + 2b or 3” protocol
2
2
is applicable to PhCONH . The results achieved for the
2
amidation of ethylbenzene to form N-(1-phenylethyl)-
benzamide are also shown in Table 4.28 When the 2b-
catalyzed amidation of ethylbenzene was carried out in
dichloromethane at room temperature for 12 h with 2b/
ethylbenzene/PhI(OAc) /PhCONH mole ratio of 1:60:50:
2
2
found to exhibit a primary kinetic isotope effect, with k
H
/
(
27) (a) S o¨ dergren, M. J .; Alonso, D. A.; Bedekar, A. V.; Andersson,
k
D
of 6.5 (catalyst 2b) and 6.1 (catalyst 3). The k /k
H
D
P. G. Tetrahedron Lett. 1997, 38, 6897. (b) Dauban, P.; Dodd, R. H. J .
Org. Chem. 1999, 64, 5304.
values are similar to that determined for the stoichio-
metric amidation of the same substrates by complex 1a
(28) We noted that N-(1-phenylethyl)benzamide could also be pre-
pared, in two steps, via mercury-mediated addition of benzamide to
styrene, see: (a) Barluenga, J .; J im e´ nez, C.; N a´ jera, C.; Yus, M. J .
Chem. Soc., Chem. Commun. 1981, 670. (b) Barluenga, J .; J im e´ nez,
C.; N a´ jera, C.; Yus, M. J . Chem. Soc., Perkin Trans. 1 1983, 591. These
processes result in a reduction of the hydrocarbon and require the use
of a stoichiometric amount of highly toxic mercury compounds.
(
25) Wu, Y.-D.; Wong, C.-L.; Chan, K. W. K.; J i, G.-Z.; J iang, X.-K.
J . Org. Chem. 1996, 61, 746.
26) J iang, X.-K. Acc. Chem. Res. 1997, 30, 283.
(

Amidation of Unfunctionalized Hydrocarbons
J . Org. Chem., Vol. 65, No. 23, 2000 7863
Ta ble 4. Am id a tion of Eth ylben zen e w ith P h I(OAc)2/RNH2 Ca ta lyzed by Com p lex 2b or 3a
conversion
(%)
yieldb
(%)
entry
catalyst
RNH2
solvent
additive
1
2
3
4
5
6
7
8
9
2b
2b
2b
2b
2b
2b
2b
3
PhCONH2
MeSO2NH2
PhCONH2
PhCONH2
PhCONH2
PhCONH2
PhCONH2
PhCONH2
PhCONH2
PhCONH2
MeSO2NH2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
63
51
36
31
34
47
19
59
49
29
46
89
85
83
82
82
85
80
87
85
82
85
Im or py
Lut
2,6-Cl2py
K2CO3
c
3
3
3
1
1
0
1
acetone
CH2Cl2
a
b
Reaction conditions: 25 °C, 12 h, catalyst/ethylbenzene/PhI(OAc)2/RNH2 mole ratio ) 1:60:50:50. GC yield based on the amount of
c
substrate consumed. NBS was used instead of PhI(OAc)2.
5
0, the corresponding N-substituted benzamide was
formed in 89% yield with 63% substrate conversion (entry
). Similar results were achieved under the same condi-
tions by employing catalyst 3 (entry 8). We found that
the amidation of ethylbenzene with “PhI(OAc) /PhCONH
2b” led to virtually indistinguishable results in dichlo-
romethane and acetonitrile; however, a considerable
solvent effect was observed for the “PhI(OAc) /PhCONH
3” system, with the substrate conversion and the amide
yield but with a low substrate conversion (19%, entry 7
in Table 4).
1
Con clu sion
2
2
+
Ruthenium complexes 2b and 3 are efficient catalysts
for the amidation of a series of unfunctionalized hydro-
carbons with PhIdNTs. These catalytic amidation reac-
tions exhibit high selectivity for adamantane (only the
tertiary C-H bonds are amidated), cyclohexene (no
aziridination was observed), ethylbenzene, cumene, in-
dan, tetralin, and diphenylmethane (all result in the
amidation of the benzylic C-H bond). Competition
experiments on para-substituted ethylbenzenes reveal
that both electron-donating and -withdrawing substitu-
ents promote the amidation processes, with log(krel) vs
TE (a carboradical parameter) plots exhibiting good
2
2
+
yield follow the order dichloromethane > acetonitrile >
acetone (cf. entries 8-10).
It can be expected that the amidations with PhI(OAc)
2
/
RNH would involve the formation of acetic acid. Accord-
2
ingly, addition of bases to the amidation reactions may
be beneficial to improving the catalyst efficiency. To our
surprise, when organic bases such as imidazole (Im),
pyridine (py), 2,6-dichloropyridine (2,6-Cl py), and 2,6-
2
lutidine (Lut) were introduced in either catalytic or
stoichiometric amounts to the amidation of ethylbenzene
•
linearity and having small FTE values of 0.63 (catalyst
2
b) and 0.68 (catalyst 3), which can accommodate a
2 2
with “PhI(OAc) /PhCONH + 2b”, the substrate conver-
hydrogen abstraction mechanism involving a carboradical
intermediate. Kinetic isotope effect measurements on the
amidation of cyclohexene/cyclohexene-d10 give k /k val-
H D
ues of 6.5 (catalyst 2b) and 6.1 (catalyst 3), consistent
with the hydrogen abstraction mechanism. Both com-
plexes 2b and 3 can also efficiently catalyze the amida-
tion of ethylbenzene or cyclohexene directly with com-
sions were approximately halved, accompanied by a
slight decrease in the amide selectivity (cf. entry 1 and
entries 3-5 in Table 4). Adding inorganic bases such as
2 3
K CO to the system also considerably reduced the
substrate conversion, with the amide selectivity de-
creased slightly (cf. entries 1 and 6). On the other hand,
although additives such as pyridine N-oxide or “pyridine
N-oxide + pyridine” are reported to promote sulfo-
nylimido group transfer to styrene in the “Ts
manganese-salen” system,29 introducing such additives
to the reaction of ethylbenzene with PhI(OAc) /PhCONH
mercially available PhI(OAc)
feasibility of an amidation protocol “PhI(OAc)
ruthenium catalyst”. The amidation of ethylbenzene with
PhI(OAc) /RNH + catalyst 2b or 3” affords the corre-
sponding N-substituted amides in 85% yield with R )
MeSO and up to 89% yield with R ) PhCO. The present
2
/TsNH
2
, demonstrating the
2
/RNH +
2
2
O + nitrido
“
2
2
2
2
in the presence of catalyst 2b or 3 made the catalyst
completely loss their activity toward the amidation.
2
work contributes the first metal-catalyzed amidation of
saturated C-H bonds that forms an N-substituted amide
of carboxylic acid.
2 2
Note that in the case of PhI(OAc) /TsNH amidations,
the in-situ formed PhIdNTs is most probably responsible
for the generation of active amidating species; however,
it is not clear whether the unknown PhIdNCOPh is
really involved in the PhI(OAc)
Recognizing the oxidative nature of PhI(OAc)
to replace PhI(OAc) with other oxidants such as N-
bromosuccinimide (NBS) and found that the “NBS/
PhCONH + catalyst 2b” system could also amidate
ethylbenzene to form N-(1-phenylethyl)benzamide in 80%
Exp er im en ta l Section
2
/PhCONH
2
counterparts.
2
, we tried
Gen er a l Meth od s. Acetonitrile (predistilled from potas-
sium permanganate), toluene, and cyclohexene were distilled
from calcium hydride under nitrogen. Dichloromethane was
2
12b
2
purified as described previously. Adamantane was recrystal-
lized from ethanol. Ethylbenzene and its para-substituted
derivatives, cumene, tetralin, indan, and diphenylmethane,
were purified by passing through a column of activated
(29) Minakata, S.; Ando, T.; Nishimura, M.; Ryu, I.; Komatsu, M.
III
20
Angew. Chem., Int. Ed. Engl. 1998, 37, 3392.
alumina. Complexes [Ru (Me
3
tacn)(CF
3
CO
2
)
3
2
‚H O] (2b) and

7
864 J . Org. Chem., Vol. 65, No. 23, 2000
Au et al.
II
] (3)17a,b were prepared by the litera-
cis-[Ru (6,6′-Cl
2
bpy)
2
Cl
2
Com p etitive P h IdNTs Am id a tion of P a r a -Su bstitu ted
Eth ylben zen es or Cycloh exen e/Cycloh exen e-d 10. Complex
ture methods.
2
b or 3 (0.02 mmol) was added to a mixture of PhIdNTs (0.5
Gen er a l P r oced u r e for Com p lex 2b- or 3-Ca ta lyzed
Am id a tion w ith P h IdNTs. To a mixture of substrate (0.72
mmol), catalyst (0.012 mmol), and solvent (10 mL) was added
PhIdNTs (0.6 mmol). The reaction mixture was stirred at room
temperature for 3 h and then evaporated to dryness. The
organic products were extracted with diethyl ether. Aliquots
of the extract were then analyzed by GC. The reaction products
were identified by comparing their retention times with those
mmol) and ethylbenzene/p-X-C CH CH or cyclohexene/
6
H
4
2
3
cyclohexene-d10 (1 mmol each) in acetonitrile or dichloro-
methane (10 mL) containing 1,4-dichlorobenzene (1 mmol) as
the internal standard. The mixture was stirred at room
temperature for 3 h. The remaining quantities of ethylbenzene
(
H
f
) and p-X-C
cyclohexene-d10 (D
amidation rates krel of the ethylbenzenes and the kinetic
isotope effects k /k of cyclohexene were calculated from the
following equations:
6
H
4
CH
2 3 f f
CH (X ) or cyclohexene (H ′) and
f
) were determined by GC. The relative
3
0
of authentic samples. The quantities of the products and the
consumed substrate were determined in the presence of an
internal standard.
H
D
2
0
Gen er a l P r oced u r e for Com p lex 2b- or 3-Ca ta lyzed
krel ) log(X /X )/log(H /H )
f
i
f
i
Am id a tion w ith P h I(OAc)
cal with that described above except that PhI(OAc)
0.6 mmol each) were used instead of PhIdNTs and that the
2
/RNH
2
. This procedure is identi-
2
and RNH
2
k /k ) log(H ′/H ′)/log(D /D )
H
D
f
i
f
i
(
3
1
reaction mixture was stirred for 12 h rather than 3 h.
where X
CH CH
respectively.
i
, H
i
, H
i
′, and D
i
are the initial quantities of p-X-C
6
H
4
-
,
2
3
, ethylbenzene, cyclohexene, and cyclohexene-d10
(30) For preparation of authentic samples of the hydrocarbon
amidation products, see: (a) Reference 12b (adamantane, cyclohexene,
ethylbenzene, and cumene). (b) Reference 7 (indan). (c) Reference 8
Ack n ow led gm en t. This work was supported by The
University of Hong Kong and the Hong Kong Research
Grants Council.
(
1
tetralin). (d) McFarland, J . W.; Schut, D.; Zwanenburg, B. Tetrahedron
981, 37, 389 (diphenylmethane).
31) For preparation of authentic samples of N-(1-phenylethyl)-
(
methanesulfonamide and N-(1-phenylethyl)benzamide, see, respec-
tively: (a) Kim, S. Y.; Sung, N.-D.; Choi, J .-K.; Kim, S. S. Tetrahedron
Lett. 1999, 40, 117. (b) Reference 28.
J O000881S