Catalytic C-H amination of alkanes with sulfonimidamides: Silver(I)-scorpionates vs. dirhodium(II) carboxylates

Article abstract of DOI:10.1016/j.tet.2013.02.005

The silver complex [Tp*^,BrAg]₂ (Tp*^,Br: hydrotris(4-bromo-3,5-dimethyl)pyrazolyl borate) and the rhodium complex Rh₂(S-nta)₄ (nta: N-(1,8-naphthoyl)- alanine) are competent catalysts for C-H bond func

Full text of DOI:10.1016/j.tet.2013.02.005

Tetrahedron 69 (2013) 4488e4492
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Tetrahedron
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Catalytic CeH amination of alkanes with sulfonimidamides:
silver(I)-scorpionates vs. dirhodium(II) carboxylates
a
b
a
,
a,
*
ꢀ
*
ꢀ
ꢀ
Alvaro Beltran , Camille Lescot , M. Mar Díaz-Requejo , Pedro J. Perez
,
Philippe Dauban b
,
*
a
ꢀ
ꢀ
ꢀ
Laboratorio de Catalisis Homogenea, CIQSO-Centro de Investigacion en Química Sostenible, Departamento de Química y Ciencia de los Materiales,
Unidad Asociada al CSIC, Universidad de Huelva, Campus de El Carmen s/n, Huelva 21007, Spain
b Centre de Recherche de Gif-sur-Yvette, Institut de Chimie des Substances Naturelles, UPR 2301 CNRS, Avenue de la Terrasse, Gif-sur-Yvette F-91198,
France
a r t i c l e i n f o
a b s t r a c t
The silver complex [Tp*,BrAg]2 (Tp*,Br
: hydrotris(4-bromo-3,5-dimethyl)pyrazolyl borate) and the
Article history:
Received 28 November 2012
Received in revised form 24 January 2013
Accepted 1 February 2013
rhodium complex Rh2(S-nta)4 (nta: N-(1,8-naphthoyl)-alanine) are competent catalysts for CeH bond
functionalization by nitrene insertion. Both complexes display similar catalytic activity for the func-
tionalization of benzylic CeH bonds, although the silver derivative does not provide the very high
diastereoselection induced by the rhodium complex. On the other hand, when starting from 5 equiv of
alkanes, such as pentane and other C6eC8 branched non-activated hydrocarbons, it is the silver catalyst
that promotes the amination of the CeH bonds with yields of up to 70%, higher than those provided by
the rhodium counterpart. When available, the tertiary CeH bonds of the substrate are preferentially
derivatized, as a consequence of a stepwise mechanism in which carbon-centered radicals are involved.
Ó 2013 Elsevier Ltd. All rights reserved.
Available online 8 February 2013
Keywords:
Nitrene
Silver
Rhodium
Iodine oxidant
Amination
1. Introduction
of hydrocarbons has been reported using PhI]NTs as the nitrene
precursor. Whereas copper complexes have proved effective for the
The ubiquity of nitrogen in natural products, pharmaceuticals,
or agrochemicals makes the search for efficient syntheses of opti-
cally pure amines still a topic of paramount importance in organic
chemistry.1 New opportunities for CeN bond forming reactions, in
this context, have arisen from recent investigations aimed at de-
veloping the direct amination of Csp3eH bonds through the in-
sertion of a metallanitrene. Various reagents and catalysts are
described to this end, which are overviewed in several reviews
published in the last five years.2 Among these conditions, the most
significant achievements in catalytic CeH amination have un-
doubtedly been made with the use of trivalent iodine oxidants3 that
have led to elegant applications in synthesis.4 However, despite the
discovery of processes, which occur in good yields and with high
levels of selectivity, some issues remain to be addressed, one of the
most challenging being the efficient selective catalytic CeH ami-
nation of simple alkanes.5
selective functionalization of alkyl aromatics and cyclohexane,6a,c the
higher reactivity of silver-scorpionate complex [Tp*,BrAg]2 1 (Tp*,Br
:
hydrotris(4-bromo-3,5-dimethyl)pyrazolyl borate, Fig. 1)7 has
allowed the CeH amination of linear and branched alkanes to be
performedingoodyieldsofupto80%inthecaseof2-methylbutane.6d
Nevertheless, it should be mentioned that these very good results are
observed for reactions carried out in neat alkanes at 80 ꢀC.
Highly active catalysts derived from group 11 elements and
scorpionate ligands have been described in the context of catalytic
nitrene transfers.6 In particular, efficient selective Csp3eH amination
Fig. 1. The monomeric form of the silver catalyst [Tp*,BrAg]2 1, the rhodium catalyst
Rh2(S-nta)4 2, and (S)-sulfonimidamide 3a.
The discovery of practical procedures for the generation in situ
of nitrenes with iodine(III) oxidants,3c,g,8 on the other hand, has led
to greatly expand the scope of catalytic nitrene transfers in terms of
ꢀ
* Corresponding authors. E-mail addresses: perez@dqcm.uhu.es (P.J. Perez),
philippe.dauban@icsn.cnrs-gif.fr (P. Dauban).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.005

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A. Beltran et al. / Tetrahedron 69 (2013) 4488e4492
4489
nitrogen sources. Chiral nitrenes of high reactivity have therefore
been generated from sulfonimidamides.9 The combination of the
chiral rhodium carboxylate Rh2(S-nta)4 2 (nta: N-(1,8-naphthoyl)-
alanine) with the (S)-N-(p-toluenesulfonyl)-p-toluenesulfonimida-
mide (S)-3a, especially, was optimal to develop the stereoselective
Csp3eH amination of benzylic and allylic substrates used as the
limiting agent.10 However, this pair of reagent has proved to be of
low efficiency for the functionalization of alkanes, such as the
branched derivative 2-methylbutane, though complete selectivity
in favor of the tertiary site is observed.10b
Based on the respective performance of both aforementioned
systems, it was decided to combine the highly efficient nitrene
precursor 3 with the very active silver catalyst 1 with the aim to
observe a synergetic effect likely to help addressing the issue of
alkane CeH amination. The results of our investigations are re-
ported in this article, that also provides a direct comparison with
the sulfonimidamide 3/rhodium catalyst 2 system.
sulfonimidamides led to the conclusion that the derivative 3a
(entry 1 vs. entries 2e5) affords the best compromise between
reactivity, selectivity, and ease of preparation. However, the yields
remain generally low in the 20e35% range whereas a modest di-
astereomeric ratio of 2:1 is observed in the case of 3a.11 Application
of conditions inspired by the previous optimal protocol using
rhodium,10 i.e., carrying out the reaction at ꢁ30 ꢀC for 3 days,12
together by using 5 equiv of ethylbenzene, then allowed to im-
prove the results. The expected CeH aminated product 4a was thus
obtained with a higher yield of 82% albeit with essentially no dia-
stereoselectivity (entry 6).
These conditions were applied to the functionalization of
various benzylic substrates in the presence of the enantiomeri-
cally pure (S)-3a with both the silver 1 or rhodium 2 catalysts
(Scheme 1). Pleasingly, high conversions greater than 90% were
observed with the silver-based catalyst. A test experiment run
with p-chloroethylbenzene at room temperature, in addition,
demonstrates the influence of the temperature since the corre-
sponding product is formed with a lower conversion of 40%. By
contrast, indan, which is efficiently aminated by this methodol-
ogy, underwent CeH amination at room temperature with com-
parable levels of conversion. However, the diastereoselectivity
remains low in all cases, a diastereomeric ratio of 2:1 being ob-
tained in the case of p-chloroethylbenzene.13
2. Results and discussion
2.1. Catalytic benzylic CeH amination
It was initially decided to focus on the catalytic amination
of benzylic Csp3eH bonds in order to test the relevance of our
hypothetical combination. To this end, ethylbenzene used in
stoichiometric amounts was chosen as a test substrate in the
first experiments conducted at room temperature in dichloro-
methane (Table 1). The screening of various racemic substituted
(S)-3a (1.0 equiv)
1 (4 mol%) or 2 (3 mol%)
NHS*
*
PhI(OAc)2 (1.2 equiv)
X
X
O
S
NTs
Table 1
x equiv
CH2Cl2, −30 °C, 72 h
Solvent
Screening of the sulfonimidamide reagent for the silver-catalyzed CeH amination of
ethylbenzene
1 as catalyst: CH2Cl2
2 as catalyst: Cl2CHCHCl2/MeOH : 3/1
S*:
H
R
H
N
Sulfonimidamide (1.0 equiv)
NHS*
NHS*
NHS*
Tp*,BrAg (4 mol%)
NHS*
4
5
6
7
PhI(OAc)2 (1.2 equiv)
CH2Cl2, rt, 12 h
MeO
Cl
Substrate
(5 equiv)
Tp*,BrAg 1
Substrate
(1 equiv)
4
1 equiv
82%
>99%
90% (40% at rt)
d.r. = 66/34 (53/47 at rt)
>99% at rt
d.r. = 56/44
d.r. = 52/48
d.r. = 55/45
Entry
1
Sulfonimidamide
Yield %
20
d.r.a
65%
92%
d.r. = 99/1
93%
89%
d.r. = 98/2
d.r. = 98/2
d.r. = 99/1
Rh2(S-nta)4
2
68/32
Scheme 1. Catalytic benzylic CeH amination with 1 or 2.
The comparison of these results with those already reported
using a combination of the rhodium catalyst 2 and the same ni-
trogen reagent (S)-3a10b clearly assesses the higher efficiency of this
system since very good yields and high diastereoselectivities are
obtained with only 1 equiv of benzylic substrates. Nonetheless, on
the basis of the previous work6d in which complex 1 induced high
yields of the alkane amidation reaction with PhI]NTs as the
nitrene precursor, we decided to examine its potential with the (S)-
3a reagent and a series of non-activated saturated hydrocarbons.5,14
2
3
4
<5
35
27
d
50/50
50/50
2.2. Silver- and rhodium-catalyzed CeH amination of alkanes
Several reaction conditions were screened for the amination of
n-pentane. As expected from the previous studies,6d a mixture of
three products derived from the formal insertion of the nitrene
moiety into the three different CeH bonds of pentane was obtained
(Scheme 2). The first experiment carried out at 40 ꢀC in dichloro-
methane gave an overall 70% conversion determined by 1H NMR.
The products 8, 9, and 10 were formed with a distribution of 24, 47,
and 29%, respectively. Importantly, this result was obtained using
5 equiv of pentane with respect to the sulfonimidamide. This is
a remarkable feature since the yield compares favorably with those
described in our previous work that employed the alkane as the
5
<5
d
6b
82
52/48
a
Determined by 1H NMR.
b
Reaction run 3 days at ꢁ30 ꢀC using 5 equiv of ethylbenzene.

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A. Beltran et al. / Tetrahedron 69 (2013) 4488e4492
Table 2
CeH amination of alkanes with (S)-3a and complexes 1 or 2 as the catalysts
Entry
1
Substrate
Product
Yield %a with 1 Yield %b with 2
25
35
70c
2
3
30
nrd,e
75c
25
60
nrd,e
Scheme 2. CeH amination of n-pentane using sulfonimidamide (S)-3a and the silver
complex 1 as catalyst.
4
23d
solvent (5 mL). We have also used the hydrocarbon in such that
large excess, with 2 and 5 mL (17 or 43 mmol, respectively), in the
presence of (S)-3a. The overall conversion, however, was identical
to that observed with only 5 equiv, and the regioselectivity,
intended as 8:9:10, varied with a ca. 10% decrease into the product
derived from the primary CeH bond functionalization.
Determined by 1H NMR.
Isolated yields.
Reaction performed in the presence of 0.5 mL (ca. 30 equiv) of alkane.
Reaction performed in the presence of 10 equiv of alkane.
nr: no reaction observed.
a
b
c
d
e
The insertion of the nitrene group in the secondary site at C2
originates a stereocenter that in combination with the chirality of
the sulfur center, provides the formation of diastereomers. Un-
fortunately, and in line with the aforementioned observations with
the benzylic substrates, the diastereoselection induced by complex
1 was low in each case, the diastereomeric ratios ranging from 51/
49 to 56/44. Carrying out the reaction at lower temperatures using
the 5:1 ratio of pentane and (S)-3a, however, did not improve the
results. The conversion dropped to 25% at room temperature,
whereas the d.r. remains essentially in the same order of magni-
tude. These results, nevertheless, compare favorably with those
recorded with rhodium(II) complexes since catalytic CeH amina-
tion of pentane in the presence of Rh2(S-nta)4 2 only gives a low
conversion of 14% at ꢁ30 ꢀC for 3 days. Therefore, and at variance
with the results discussed above on the functionalization of the
benzylic sites, the silver complex 1 displays a pronounced catalytic
activity toward the Csp3eH bonds of pentane when compared with
that of the rhodium complex 2.
Once demonstrated the catalytic performance of 1 for the ami-
nation of pentane with (S)-3a, we targeted a series of C5eC8 alkanes,
such as 2-methylbutane, 2,3-dimethylbutane, 3-methylpentane,
and 2,5-dimethylhexane. The reactions were performed at 40 ꢀC for
7 h, generally using a 5:1 ratio of the alkane and (S)-3a. The results
are shown in Table 2. In all cases, the only product observed was that
derived from the formal insertion of the nitrene group into the
tertiary sites. This is in contrast with our previous report,6d in which,
for example, 2-methylbutane gave a ca. 9:1 mixture of products
corresponding to the functionalization of the tertiary and secondary
sites. The yields range from 25 to 60% but these can be improved by
increasing the relative amount of alkanes. This resulted beneficial
for the reaction outcome in most cases, as inferred from the values in
Table 1, entries 1 and 2.
2,5-dimethylhexane led to the opposite behavior. In addition, 2,3-
dimethylbutane and 3-methylpentane did not react in the pres-
ence of 2. Despite the different conditions,15 these data are in ac-
cordance with a higher capacity of the silver complex 1 to mediate
the CeH amination of non-activated alkanes.
The absence of products arising from the functionalization of
primary and secondary CeH bonds is at variance with the metal-
catalyzed carbene insertion reaction from diazocompounds. For
example, the silver complexes TpBr3Ag(acetone)7a and F21
-
Tp4Bo,3CF3Ag(acetone)16 induce the functionalization of 2-
methylbutane giving rise to a mixture of products upon insertion
of the carbene group into the tertiary, secondary, and primary sites.
These data support the different nature of both reactions, in spite of
the use of the same catalysts. The carbene transfer reaction has
been proposed to occur in a concerted manner5,17 whereas the CeH
amination seems to proceed with the intermediacy of carbon-
centered radicals in the presence of silver,6d ruthenium18, and co-
balt complexes.5 Scheme 3 shows a plausible mechanistic picture
for the silver-based catalyst based on previous experiments,6d the
formation of a metallanitrene species being the first step of the
reaction pathway. Hydrogen abstraction would lead to an Ag-amido
species along with an organic radical that, upon a step similar to the
so-called rebound mechanism,5 extensively proposed in CeH hy-
droxylation reactions, would liberate the amidated CeH bond and
the metal center to re-start the catalytic cycle. This would be in
PhI + 2AcOH
TpxAg=NS*
S*NH2 + PhI(OAc)2
TpxAg
S*
In addition, a series of experiments with the rhodium catalyst 2
was performed using 5 or 10 equiv of alkanes, though at ꢁ30 ꢀC and
in a 3/1 mixture of 1,1,2,2-tetrachloroethane/MeOH. The products
observed, when the reaction proceeded to a certain extend, were
the same as with the silver catalyst, i.e., those from the function-
alization of the tertiary CeH bonds. 2-Methylbutane gave 35%
yield, a value higher than that induced by complex 1, whereas
C-N-H
C-H
TpxAg NHS*
C
Scheme 3. Plausible mechanistic pathway for the Ag-catalyzed CeH amination of
alkane using (S)-3a as the nitrene source.

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4491
agreement with the preferential functionalization of the tertiary
sites since they would originate the most stable radical along the
reaction pathway. In the case of pentane, both primary and sec-
ondary sites were functionalized since there is not a very large
difference in energy between their corresponding radicals.
the mixture was stirred for 5 min before addition of the substrate
(0.2 mmol). The tube was cooled to ꢁ78 ꢀC, and bis(tert-butylcar-
bonyloxy)iodobenzene (115 mg, 0.28 mmol) was added. The mix-
ture was stirred at ꢁ35 ꢀC for 3 days. After dilution with
dichloromethane (3 mL), the molecular sieves were removed by
filtration and the filtrate was evaporated to dryness under reduced
pressure. The oily residue was purified by flash chromatography on
silica gel, affording the following CeH insertion products.
Compounds 4e7 have been previously reported.10b In addition,
the compounds 8e14 have been described for the NTs deri-
vatives.6d
3. Conclusion
The silver complex [Tp*,BrAg]2 catalyzes the functionalization of
CeH bonds using a chiral sulfonimidamide as the nitrene source
with moderate to high yields. When compared to the rhodium
[Rh2(S-nta)4] catalyst, the relative catalytic capabilities depend on
the nature of the hydrocarbon. For benzylic sites, both catalysts
induce similar conversions, although the rhodium catalyst secures
excellent levels of diastereocontrol. For non-activated CeH bonds,
such as those found in pentane and other alkanes, the silver
complex seems to be more active and the yields obtained are higher
than those previously reported starting from PhI]NTs, taking in
consideration the lower amounts of alkanes. The combination
of silver complex 1 and nitrene precursor 3a thus proves to improve
the efficiency of catalytic nitrene transfer in this case. However,
none of both catalytic systems provide noticeable diastereosel-
ectivity. As a result of this work, it seems feasible that more elab-
orated silver-based complexes could exert better diastereoselection
following an appropriate design, which is currently under invest-
igation.
4.3.1. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-(1-
aminoethyl)benzene (4). (1R-4) 1H NMR (400 MHz, CDCl3)
d (ppm)
1.26 (d, J¼6.9 Hz, 3H), 2.31 (s, 3H), 2.33 (s, 3H), 4.39 (q, J¼7.0 Hz,
1H), 6.14 (d, J¼6.8 Hz, 1H), 6.84e7.32 (m, 8H), 7.40e7.80 (m, 4H).
(1S-4) 1H NMR (400 MHz, CDCl3)
d
(ppm) 1.48 (d, J¼6.9 Hz, 3H),
2.25 (s, 3H), 2.34 (s, 3H), 4.39 (q, J¼7.0 Hz, 1H), 6.29 (d, J¼6.8 Hz,
1H), 6.84e7.32 (m, 8H), 7.40e7.80 (m, 4H).
4.3.2. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-4-(1-
aminoethyl)anisole (5). (1R-5) 1H NMR (400 MHz, CDCl3)
d (ppm)
1.32 (d, J¼6.9 Hz, 3H), 2.39 (s, 3H), 2.41 (s, 3H), 3.79 (s, 3H), 4.46 (m,
1H), 6.30 (br s, 1H), 6.79e6.90 (m, 2H), 7.07e7.25 (m, 6H), 7.71e7.86
(m, 4H).
(1S-5) 1H NMR (400 MHz, CDCl3)
2.41 (s, 3H), 3.72 (s, 3H), 4.46 (m, 1H), 6.44 (br s, 1H), 6.79e6.90 (m,
2H), 7.07e7.25 (m, 6H), 7.71e7.86 (m, 4H).
d
(ppm) 1.54 (d, J¼6.9 Hz, 3H),
4. Experimental section
4.1. General methods
4.3.3. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-(1-
aminoethyl)-4-chlorobenzene (6). (Major diastereoisomer-6) 1H
All manipulations were carried out under a nitrogen atmo-
sphere using standard Schlenk techniques or inside a glovebox.
Solvents were dried and degassed before use. All the substrates
were purchased from Aldrich. The sulfonimidamides9 and the
NMR (400 MHz, CDCl3)
d
(ppm) 1.41 (d, J¼6.9 Hz, 3H), 2.49 (br s,
6H), 4.52 (m, 1H), 6.64 (d, J¼6.9 Hz, 1H), 6.99e7.34 (m, 4H),
7.79e7.91 (m, 8H).
(Minor diastereoisomer-6) 1H NMR (400 MHz, CDCl3)
d (ppm)
10
complexes [Tp*,BrAg]2,19 and Rh2(S-nta)4 were prepared accord-
1.59 (d, J¼6.9 Hz, 3H), 2.43 (s, 3H), 2.47 (s, 3H), 4.52 (m, 1H), 6.80 (d,
ing to the literature. NMR experiments were recorded on a Varian
Mercury 400 MHz spectrometer in CDCl3 as solvent.
J¼6.9 Hz, 1H), 6.99e7.34 (m, 4H), 7.79e7.91 (m, 8H).
4.3.4. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-
4.2. General catalytic CeH amination using [Tp*,BrAg]2 1
aminoindane (7). (1R-7) 1H NMR (400 MHz, CDCl3)
d (ppm)
1.67e1.76 (m, 1H), 2e2.16 (m, 1H), 2.41 (s, 3H), 2.44 (s, 3H),
2.65e2.72 (m,1H), 2.84e2.89 (m,1H), 4.79 (q, J¼7.8 Hz,1H), 6.28 (d,
J¼8.3 Hz, 1H), 7.09e7.26 (m, 6H), 7.30e7.38 (m, 2H), 7.79e7.91
(m, 4H).
(1S-7) 2.03e2.11 (m, 1H), 2.35e2.52 (m, 1H), 2.40 (s, 3H), 2.44 (s,
3H), 2.72e2.80 (m, 1H), 2.95e3.02 (m, 1H), 4.70 (q, J¼7.8 Hz, 1H),
6.20 (d, J¼8.9 Hz, 1H), 7.09e7.26 (m, 6H), 7.30e7.38 (m, 2H),
7.79e7.91 (m, 4H).
A Teflon-capped ampoule containing a magnetic stirring bar
was charged with sulfonimidamide 3a (0.486 g, 0.15 mmol),
Tp*,BrAg 1 (0.038 g, 0.006 mmol calculated as monomeric unit
Tp*,BrAg), and PhI(OAc)2 (0.058 g, 0.18 mmol). After deoxygenation,
5 mL of anhydrous dichloromethane were added. The mixture was
stirred for 5 min before addition of the substrate (0.75 mmol or the
corresponding amount), being then covered with aluminum foil to
maintain the reaction mixture in the dark. The vessel was either
stored in the freezer (ꢁ30 ꢀC) for 3 days or stirred at room tem-
perature or at 40 ꢀC in an oil bath. After the reaction time, volatiles
were removed under vacuum. The residue was dissolved in CDCl3
and, then, investigated by 1H NMR. The new products as well as
unreacted sulfonimidamide were identified. Accordingly, conver-
sions and yields were estimated upon integration of representative
resonances.6d
4.3.5. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-amino-pen-
tane (8). 1H NMR (400 MHz, CDCl3)
0.96e1.57 (m, 6H), 2.39 (s, 3H), 2.40 (s, 3H), 3.22 (q, J¼8.5 Hz, 1H),
5.48 (m, 1H), 7.09e7.35 (m, 4H), 7.64e7.85 (m, 4H).
d
(ppm) 0.91 (t, J¼7.5 Hz, 3H),
4.3.6. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-2-amino-pen-
tane (9). (Major diastereoisomer-9) 1H NMR (400 MHz, CDCl3)
d
(ppm) 0.64 (t, J¼7.3 Hz, 3H), 0.85 (d, J¼6.5 Hz, 3H), 1.00e2.06 (m,
4.3. General procedure for catalytic CeH amination using
4H), 2.42 (br s, 6H), 3.25e3.34 (m, 1H), 5.92 (m, 1H), 7.09e7.35 (m,
4H), 7.64e7.85 (m, 4H).
Rh2(S-nta)4
2
(Minor diastereoisomer-9) 1H NMR (400 MHz, CDCl3)
d (ppm)
ꢁ
In an oven-dried tube were introduced activated 4 A molecular
sieves (100 mg), Rh2[(S)-nta]4 2 (7.7 mg, 0.006 mmol), and (ꢁ)-N-
(p-toluenesulfonyl)-p-toluenesulfonimidamide (ꢁ)-(S)-3a (78 mg,
0.24 mmol). The tube was capped with a rubber septum and purged
with argon. Anhydrous and degassed 1,1,2,2-tetrachloroethane
(0.75 mL) and methanol (0.25 mL) were added under argon, and
0.64 (t, J¼7.3 Hz, 3H), 1.22 (d, J¼6.5 Hz, 3H), 1.00e2.06 (m, 8H), 2.42
(br s, 12H), 3.25e3.34 (m, 2H), 5.92 (m, 2H), 7.09e7.35 (m, 8H),
7.64e7.85 (m, 8H).
4.3.7. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-3-amino-pen-
tane (10). 1H NMR (400 MHz, CDCl3)
d
(ppm) 0.57 (t, J¼7.4 Hz, 6H),

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Du Bois, J. J. Am. Chem. Soc. 2011, 133, 17207; (k) Li, Z.; Capretto, D. A.; Rahaman,
R.; He, C. Angew. Chem., Int. Ed. 2007, 46, 5184; (l) Paradine, S. M.; White, M. C. J.
Am. Chem. Soc. 2012, 134, 2036; (m) Ton, T. M. Y.; Tejo, C.; Tiong, D. L. Y.; Chan, P.
W. H. J. Am. Chem. Soc. 2012, 134, 7344.
1.05e1.43 (m, 4H), 2.39 (s, 3H), 2.40 (s, 3H), 3.00e3.09 (m, 1H), 5.97
(d, J¼8.6 Hz, 1H), 7.09e7.35 (m, 4H), 7.64e7.85 (m, 4H).
4.3.8. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-2-amino-2-
methylbutane (11). 1H NMR (400 MHz, CDCl3)
d (ppm) 0.86 (t,
J¼7.5 Hz, 3H), 1.05 (s, 3H), 1.19 (s, 3H), 1.46 (m, 1H), 1.60 (m,1H), 2.39
(s, 3H), 2.40 (s, 3H), 6.19 (br s, 1H), 7.22e7.26 (m, 4H), 7.78e7.84 (m,
4H).13C NMR (75 MHz, CDCl3)
d (ppm) 21.5, 21.6, 26.2, 27.5, 36.0, 38.6,
4. For some relevant examples, see: (a) Wehn, P. M.; Du Bois, J. J. Am. Chem. Soc.
2002, 124, 12950; (b) Hinman, A.; Du Bois, J. J. Am. Chem. Soc. 2003, 125, 11510;
(c) Parker, K. A.; Chang, W. A. Org. Lett. 2003, 5, 3891; (d) Tanino, T.; Ichikawa,
S.; Matsuda, A. Org. Lett. 2011, 13, 4028; (e) Huters, A. D.; Quasdorf, K. W.;
Styduhar, E. D.; Garg, N. K. J. Am. Chem. Soc. 2012, 133, 15797; (f) Takahashi, K.;
Yamaguchi, D.; Ishihara, J.; Hatakeyama, S. Org. Lett. 2012, 14, 1644.
59.7, 126.8 (2C), 127.7 (2C), 129.2 (2C), 129.6 (2C), 136.5, 140.6, 142.7,
144.6. IR (neat) nmax 3240, 2973, 1596, 1300, 1148, 1103, 1089, 1065,
1017 cmꢁ1. HRMS (ESI): MNaþ, found 417.1243. C19H26N2NaO3S2
requires 417.1283.
ꢀ
5. Díaz-Requejo, M. M.; Caballero, A.; Fructos, M. R.; Perez, P. J. In Alkane CeH
ꢀ
Activation by Single-site Catalysis; Perez, P. J., Ed.; Springer: 2012, Chapter 6.
6. (a) Díaz-Requejo, M. M.; Belderrain, T. R.; Nicasio, M. C.; Trofimenko, S.; Perez,
P. J. J. Am. Chem. Soc. 2003, 125, 12078; (b) Mairena, M. A.; Díaz-Requejo, M. M.;
Belderrain, T. R.; Nicasio, M. C.; Trofimenko, S.; Perez, P. J. Organometallics 2004,
23, 253; (c) Fructos, M. R.; Trofimenko, S.; Díaz-Requejo, M. M.; Perez, P. J. J. Am.
Chem. Soc. 2006, 128, 11784; (d) Gomez-Emeterio, B. P.; Urbano, J.;
Díaz-Requejo, M. M.; Perez, P. J. Organometallics 2008, 27, 4126; (e) Llaveria, J.;
4.3.9. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-2-amino-2,3-
dimethylbutane (12). 1H NMR (400 MHz, CDCl3)
d (ppm) 0.85 (d,
J¼6.8 Hz, 3H), 0.93 (d, J¼6.8 Hz, 3H), 0.95 (s, 3H), 1.23 (s, 3H), 1.72
(m, 1H), 2.39 (s, 3H), 2.40 (s, 3H), 6.27 (br s, 1H), 7.17e7.35 (m, 4H),
7.53e7.88 (m, 4H).
ꢀ
ꢀ
ꢀ
ꢀ
Beltran, A.; Díaz-Requejo, M. M.; Matheu, M. I.; Castillon, S.; Perez, P. J. Angew.
ꢀ
Chem., Int. Ed. 2010, 49, 7092; (f) Fructos, M. R.; Alvarez, E.; Díaz-Requejo, M. M.;
Perez, P. J. J. Am. Chem. Soc. 2010, 132, 4600; (g) Maestre, L.; Fructos, M. R.;
Díaz-Requejo, M. M.; Perez, P. J. Organometallics 2012, 31, 7839; (h) Baidei, Y. M.;
Dinescu, A.; Dai, X.; Palomino, R. M.; Heinemann, F. W.; Cundari, T. R.; Warren,
T. H. Angew. Chem., Int. Ed. 2008, 47, 9961.
4.3.10. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-3-amino-3-
methylpentane (13). 1H NMR (400 MHz, CDCl3)
d (ppm) 0.75 (t,
J¼7.4 Hz, 3H), 0.85 (t, J¼7.2 Hz, 3H), 1.25 (s, 3H), 1.35 (m, 2H), 1.51
(m, 2H), 2.39 (s, 3H), 2.40 (s, 3H), 6.14 (br s, 1H), 7.16e7.34 (m, 4H),
7.64e7.86 (m, 4H).
7. Silver-scorpionate complexes have also proved superior to copper analogs in
catalytic alkane functionalization through carbene insertion. (a) Urbano, J.;
Belderrain, T. R.; Nicasio, M. C.; Trofimenko, S.; Díaz-Requejo, M. M.; Perez, P. J.
Organometallics 2005, 24, 1528; (b) Dias, H. V. R.; Browning, R. G.; Richey, S. A.;
Lovely, C. J. Organometallics 2005, 24, 5784.
4.3.11. [N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-2-amino-2,5-
dimethylhexane (14). 1H NMR (400 MHz, CDCl3)
d (ppm) 0.80 (d,
ꢂ
8. Dauban, P.; Saniere, L.; Tarrade, A.; Dodd, R. H. J. Am. Chem. Soc. 2001, 123, 7707.
9. (a) Di Chenna, P. H.; Robert-Peillard, F.; Dodd, R. H.; Dauban, P. Org. Lett. 2004, 6,
J¼6.6 Hz, 3H), 0.83 (d, J¼6.6 Hz, 3H), 1.07 (s, 3H), 1.19 (s, 3H), 1.33
(m, 2H), 1.37 (m, 1H), 1.50 (m, 2H), 2.39 (s, 3H), 2.40 (s, 3H), 6.20 (br
s, 1H), 7.20e7.34 (m, 4H), 7.64e7.84 (m, 4H). 13C NMR (75 MHz,
€
4503; (b) Fruit, C.; Robert-Peillard, F.; Bernardinelli, G.; Muller, P.; Dodd, R. H.;
Dauban, P. Tetrahedron: Asymmetry 2005, 16, 3484; (c) Robert-Peillard, F.; Di
Chenna, P. H.; Liang, C.; Lescot, C.; Collet, F.; Dodd, R. H.; Dauban, P. Tetrahedron:
Asymmetry 2010, 21, 1447.
CDCl3)
d (ppm) 21.6, 22.4, 22.5, 26.9, 28.0, 28.3, 32.6, 41.2, 59.6,
€
10. (a) Liang, C.; Robert-Peillard, F.; Fruit, C.; Muller, P.; Dodd, R. H.; Dauban, P.
126.8 (2C), 127.7 (2C), 129.2 (2C), 129.6 (2C), 138.8, 140.4, 142.8,
144.3. IR (neat) nmax 3234, 2954, 1597, 1467, 1387, 1312, 1301, 1260,
1149, 1104, 1090, 1068, 1017 cmꢁ1. HRMS (ESI): MHþ, found
437.1932. C22H32N2O3S2 requires 437.1933.
Angew. Chem., Int. Ed. 2006, 45, 4641; (b) Liang, C.; Collet, F.; Robert-Peillard, F.;
Muller, P.; Dodd, R. H.; Dauban, P. J. Am. Chem. Soc. 2008, 130, 343; (c) Collet, F.;
€
Lescot, C.; Liang, C.; Dauban, P. Dalton Trans. 2010, 39, 10401; (d) Lescot, C.;
Darses, B.; Collet, F.; Retailleau, P.; Dauban, P. J. Org. Chem. 2012, 77, 7232.
11. It should be pointed out that the previous study with this catalyst (see Ref. 6d)
was carried out with PhI]NTs as the nitrene source, in contrast to the
present strategy based on the in situ generation of the imidoiodinane from
a sulfonimidamide and PhI(OAc)2.
Acknowledgements
12. The optimal protocol requires the use of methanol as a cosolvent. However,
such a protic source is not compatible with a nitrene transfer catalyzed by
We wish to thank MINECO (CTQ2011-28942-CO2-01) and Junta
de Andalucía (Proyecto P10-FQM-06292), as well as the EDRF Funds
and ANR-08-BLAN-0013-01 for funding and fellowships (C.L.).
Support and sponsorship concerted by COST Action D40 “In-
novative Catalysis: New Processes and Selectivities” are kindly
acknowledged.
a
metal-scorpionate complex due to
a side reaction currently under
investigation.
13. These poor diastereoselectivities are comparable to those observed with
sulfonimidamides either in the aziridination of styrene catalyzed by non-chiral
copper complexes (see Ref. 9) or in the benzylic CeH amination using
Rh2(OAc)4. Accordingly, the sole chirality of the sulfur reagent is not sufficient
to provide the stereoselective addition of the nitrene. Good stereocontrol
is thus obtained only when the sulfonimidamide is combined with an
appropriate chiral catalyst as the result of matched effects (see Ref. 10b).
14. For a recent key study on the catalytic CeH amination of alkanes with a
bromine(III) oxidant, see: Ochiai, M.; Miyamoto, K.; Kaneaki, T.; Hayashi, S.;
Nakanishi, W. Science 2011, 332, 448.
References and notes
1. (a) Nugent, T. C. Chiral Amine Synthesis; Wiley-VCH: Weinheim, Germany,
2010; (b) Ricci, A. Amino Group Chemistry. From Synthesis to the Life Sciences;
Wiley-VCH: Weinheim, Germany, 2008.
15. It is worth mentioning that the catalytic CeH amination of alkanes with 2 did
not proceed at room temperature. In addition, increasing the amounts of
alkanes did not improve the results, as it has been the case with the silver
complex 1.
2. For recent reviews: (a) Davies, H. M. L.; Manning, J. R. Nature 2008, 451, 417; (b)
ꢀ
Díaz-Requejo, M. M.; Perez, P. J. Chem. Rev. 2008, 108, 3379; (c) Fantauzzi, S.;
ꢀ
16. Despagnet-Ayoub, E.; Jacob, K.; Vendier, L.; Etienne, M.; Alvarez, E.; Caballero,
Caselli, A.; Gallo, E. Dalton Trans. 2009, 5434; (d) Collet, F.; Dodd, R.; Dauban, P.
Chem. Commun. 2009, 5061; (e) Zalatan, D. N.; Du Bois, J. Top. Curr. Chem. 2010,
292, 347; (f) Driver, T. G. Org. Biomol. Chem. 2010, 8, 3831; (g) Collet, F.; Lescot,
C.; Dauban, P. Chem. Soc. Rev. 2011, 40, 1926; (h) Chang, J. W. W.; Ton, T. M. U.;
Chan, P. W. H. Chem. Rec. 2011, 11, 331; (i) Roizen, J. L.; Harvey, M. E.; Du Bois, J.
Acc. Chem. Res. 2012, 45, 911; (j) Ramires, T. A.; Zhao, B.; Shi, Y. Chem. Soc. Rev.
2012, 41, 931; (k) Gephart, R. T., III; Warren, T. H. Organometallics 2012, 31, 7728.
3. For some representative examples, see: (a) Breslow, R.; Gellman, S. H. J. Am.
ꢀ
A.; Díaz-Requejo, M. M.; Perez, P. J. Organometallics 2008, 27, 4779.
17. (a) Braga, A. A. C.; Maseras, F.; Urbano, J.; Caballero, A.; Díaz-Requejo, M. M.;
ꢀ
Perez, P. J. Organometallics 2006, 25, 5292; (b) Braga, A. A. C.; Caballero, A.;
ꢀ
Urbano, J.; Díaz-Requejo, M. M.; Perez, P. J.; Maseras, F. ChemCatChem 2011, 3,
1646.
18. (a) Au, S.-M.; Huang, J.-S.; Yu, W.-Y.; Fung, W.-H.; Che, C.-M. J. Am. Chem.
Soc. 1999, 121, 9120; (b) Leun, S. K.-Y.; Tsui, W.-M.; Huang, J.-S.; Che, C.-M.;
Liang, J.-L.; Zhu, N. J. Am. Chem. Soc. 2005, 127, 16629.
19. For the synthesis of complex 1, X-ray structure and behavior in solution
€
Chem. Soc. 1983, 105, 6728; (b) Nageli, I.; Baud, C.; Bernardinelli, G.; Jacquier, Y.;
€
Moran, M.; Muller, P. Helv. Chim. Acta 1997, 80, 1087; (c) Espino, C. G.; Du Bois, J.
delivering mononuclear Tp
*
,BrAg units see: Urbano, J.; Braga, A. A. C.; Maseras,
Angew. Chem., Int. Ed. 2001, 40, 598; (d) Espino, C. G.; Wehn, P. M.; Chow, J.; Du
Bois, J. J. Am. Chem. Soc. 2001, 123, 6935; (e) Fiori, K. W.; Du Bois, J. J. Am. Chem.
ꢀ
ꢀ
F.; Alvarez, E.; Díaz-Requejo, M. M.; Perez, P. J. Organometallics 2009, 28, 5968.