Studies in catalytic C-H amination involving nitrene C-H insertion

Article abstract of DOI:10.1039/c0dt00283f

Stereoselective catalytic intermolecular C-H amination of complex molecules is reported. Site-selective functionalizations occur with very good yields up to 91% and excellent d.e.s up to 99%. However, the precise nature of the nitrene C-H insertion remains a matter of debate despite several physical organic experiments.

Full text of DOI:10.1039/c0dt00283f

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www.rsc.org/dalton | Dalton Transactions
Studies in catalytic C–H amination involving nitrene C–H insertion†‡
Florence Collet, Camille Lescot, Chungen Liang and Philippe Dauban*
Received 9th April 2010, Accepted 21st June 2010
DOI: 10.1039/c0dt00283f
Stereoselective catalytic intermolecular C–H amination of complex molecules is reported. Site-selective
functionalizations occur with very good yields up to 91% and excellent d.e.s up to 99%. However, the
precise nature of the nitrene C–H insertion remains a matter of debate despite several physical organic
experiments.
Introduction
Catalytic C–H functionalization is revolutionizing today the way
of thinking in organic synthesis. The seminal book written by
Corey and Cheng fifteen years ago taught us how to disconnect
a complex molecule to simpler starting materials using retrosyn-
thetic analysis. This involves a series of transformations generally
based on functional group manipulations. Although remote C–H
functionalization has already been mentioned in the monograph,
the area was considered underdeveloped. Few transformations
were known, all of them relying either on intramolecular group
transfers or enzymatic oxidations.1 But as predicted by Seebach
in his overview of organic synthesis,2 the emergence of transition
metal organic chemistry has led to the discovery of new synthetic
methods, a statement particularly true for catalytic C–H func-
tionalization. Considerable attention has been paid to this field
as testified by the growing number of reviews highlighting the
multiple methods uncovered for the direct transformation of a C–
H bond.3 This has culminated in significant achievements which
have materialized through recent applications to total synthesis
of natural products4 as well as through examples of site-selective
functionalization of complex substrates.5
Mechanistic considerations have led Crabtree to classify cat-
alytic C–H functionalizations into two groups according to the
nature of the interaction between the metal and the C–H bond
(Scheme 1).6 C–H activation-based reactions proceed by initial C–
H bond cleavage which produces a carbon–metal bond, followed
by functionalization with an external reagent. Surprisingly, while
C–C bond formation has been extensively investigated by this
approach, this has only recently been applied to catalytic C–H
amination with copper, palladium or gold catalysts.7,8 Under these
conditions, primary positions as well as aromatic C–H bonds can
be efficiently aminated.9
By contrast, catalytic functionalization via C–H insertion
involves the formation of metal–carbene, –oxo or –nitrene species
which are able to directly react with a C–H bond. The metal
does not interact with the substrate hence the term “outer-sphere”
mechanism. Application of this strategy has led to notable achieve-
Scheme 1 Mechanistic scenarios in catalytic C–H amination.
ments in catalytic C–H amination as a consequence of the discov-
ery of mild conditions for the generation of nitrenes.7,10 Inter-
and intramolecular nitrene C–H insertions are thus catalyzed
by several transition metal complexes,11 particularly rhodium(II)
catalysts.12 Selective C–H functionalization of secondary benzylic
and allylic sites as well as of tertiary positions of simple alkanes
are generally observed via nitrene transfer. The latter occurs by
a concerted or a stepwise radical pathway depending on the
catalyst.
Of utmost importance has been the development of practical
procedures for the generation of nitrenes involving iodine(III)
oxidants. These have allowed the enhanced variety of nitrogenous
substrates, i.e. sulfonamides, sulfamates or carbamates, likely
to afford nitrenes under mild conditions thereby leading to a
better control of their reactivity.10 They have also been fruitful
in developing a stereoselective C–H amination based on the
generation of chiral nitrenes.
Use of a chiral sulfur reagent, i.e. sulfonimidamide 1, has thus
proved to be appropriate; its matched combination with the chiral
dirhodium(II) catalyst Rh2((S)-nta)4 2, the ligands of which are
derived from alanine, has led us to uncover an intermolecular
C–H amination which proceeds with excellent yield and high
levels of chemo- and diastereoselectivity (Scheme 2).13 Because
this transformation takes place with unprecedented efficiency and
stereocontrol, we then turned our attention to more complex
substrates in order to enhance its scope. We also investigated the
mechanism with the aim of elucidating the nature of the nitrene
transfer. Preliminary results of our studies are displayed below.
Institut de Chimie des Substances Naturelles, UPR 2301 CNRS, Centre
de Recherches de Gif, Avenue de la Terrasse, 91198, Gif-sur-Yvette Cedex,
France. E-mail: philippe.dauban@icsn.cnrs-gif.fr; Fax: +33 1 6907 7247;
Tel: +33 1 6982 4560
† Based on the presentation given at Dalton Discussion No. 12, 13–15th
September 2010, Durham University, UK.
‡ Electronic supplementary information (ESI) available: Experimental
details and Hammett plots. See DOI: 10.1039/c0dt00283f
This journal is
The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 10401–10413 | 10401
©

Table 1 Benzylic C–H amination of cyclic substratesa
Entry Substrate
1
Product
Yield (%)b d.e. (%)c
89d
98d
2
3
86
98
Scheme 2 Diastereoselective C–H amination with sulfonimidamides.
76
40
>90
Results and discussion
Scope of the intermolecular C–H amination
(a) Benzylic C–H amination and N-(acetyl)colchinol. We ini-
tially found that catalytic benzylic C–H amination occurs with very
good yield and nearly complete diastereoselectivity in the presence
of a stoichiometric amount of the C–H reacting substrate.13a Com-
pounds such as indan proved to be extremely reactive even using
only 0.5 mol% of rhodium(II) catalyst.13b This was the consequence
of a strong matched effect between the sulfonimidamide 1 and the
chiral complex 2, combination of (S)-1 and (S)-2 (or (R)-1 and
(R)-2) leading to the (R) (or (S))-C–H aminated product. Inspired
by these observations, we thus planned to apply the reaction to
tricyclic substrates. Such a transformation was expected to give a
straightforward access to analogs of N-(acetyl)colchinol (NAC), a
simplified colchicine derivative with potent antivascular activities
(Scheme 3).14
4
—
5
6
7
20
—
85
>90
—
99
a Reaction conditions: 3 (0.2 mmol) in a mixture of (Cl2CH)2/MeOH :
3/1 (1 mL) at -35 ◦C for 72 h. b Isolated yields based on 3. c d.e.s were
1
determined either by H NMR, HPLC (Hypercarb or Symmetry Shield
Column) or UPLC (BEH Shield RP18 Column). d With 0.5 mol% of
catalyst 2.
4), amination of 9,10-dihydrophenanthrene 3e turned out to occur
sluggishly though still with an excellent stereoselectivity (entry 5).
Reaction with substrate 3f proved to be even more sluggish since
only traces of the expected compound 4f, which can be considered
as a NAC derivative, were obtained regardless of the conditions
used (entry 6).15
We previously demonstrated that catalytic C–H amination with
sulfonimidamides is sensitive to steric hindrance, the reaction with
propylbenzene, for example, affording a lower yield than in the
case of ethylbenzene.13b Such factors can be invoked to explain
the moderate reactivity of fluorene. Although this could also
apply to the other tricyclic substrates 3e and 3f, we believe that
other parameters should be responsible for their lack of reactivity.
Scheme 3 N-(Acetyl)colchinol and synthetic strategies involving C–H
amination.
For the purpose of comparison, results previously obtained
in the cases of indan and tetrahydronaphthalene are indicated
in Table 1 (entries 1 and 2). As clearly shown, the reaction
efficiently takes place with nearly perfect diastereoselectivity. This
was corroborated by application of the catalytic C–H amination
to benzosuberane 3c that affords compound 4c in 76% yield and
with a diastereomeric excess greater than 90% (entry 3). However,
addition of an extra fused phenyl ring led to a complete change of
reactivity. Thus, whereas use of fluorene 3d allowed us to isolate
the corresponding C–H aminated product 4d in 40% yield (entry
10402 | Dalton Trans., 2010, 39, 10401–10413
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The Royal Society of Chemistry 2010
©

Table 2 Benzylic C–H amination of linear substratesa
Based on these observations, it was then decided to install the
nitrogen function prior to a coupling likely to afford dipheny-
lalkanes that could further be cyclized to NAC analogs. We were
pleased to observe that application of the reaction conditions
to bromo derivatives 5d and 5e led to the expected products 6d
and 6e with excellent d.e.s (entries 4 and 5). Not surprisingly,
the yields were found to decrease with the chain length as in the
case of 5b and 5c. More interestingly, inspired by the absence of
conversion in the case of the o-bromo substituted substrate 5f, we
managed to design a regioselective C–H amination of dissymetric
diphenylalkanes. Thus, we observed the exclusive formation of a
single regioisomer starting from substrates 5g and 5h, albeit in
modest yields and moderate d.e.s.17 Regioselective benzylic C–
H functionalization can therefore be achieved by introducing a
substitution at one of the ortho position. Finally, it should be
pointed out that application of Kumada or Negishi couplings to
the amino derivatives 6e or 6h did not afford the expected 1,3-
diphenylalkanes compounds.18
Entry Substrate
1
Product
Yield (%)b d.e. (%)c
<10
—
2
3
4
5
6
7
73
99
32
75
85
>90
99
(b) Allylic C–H amination of terpenes. Use of sulfonimi-
damides as nitrene precursors also allowed us to describe the
efficient catalytic C–H amination of allylic substrates starting
either from cyclic or acyclic alkenes. The reaction occurs selectively
at secondary positions with very good yields in the 66–90%
range and d.e.s up to 94%.13b Also worthy of note was the
complete chemoselectivity since no product arising from olefin
aziridination was isolated. These results convinced us to apply the
transformation to more complex substrates, i.e. to terpenes such
as limonene, pinene or geranyl derivatives (Table 3).
42
—
—
42
70
Both enantiomers of limonene 7a and 7b engaged in stoichio-
metric amounts were efficiently converted to the corresponding C–
H aminated products 8a and 8b with good yields of 73% and 68%,
respectively, and excellent d.e.s greater than 90% (entries 1 and 2).
These examples clearly illustrate the strong bias for nitrenes toward
insertion into secondary allylic sites.10b Moreover, the reaction
takes place again with high chemoselectivity (C–H amination
vs. alkene aziridination) and regioselectivity (secondary allylic
position “a” vs. “b”), the latter probably as a result of a steric effect.
Since the combination of (S)-1 and catalyst (S)-2 was previously
shown to give allylic amines with the (R)-configuration,13b we then
wondered whether the sense of the asymmetric induction was
here controlled by the reagents or the substrates. Deprotection of
aminolimonenes 8a and 8b was therefore performed by applying
our published conditions which involve introduction of a Boc
group prior to reductive cleavage of the sulfonimidoyl moiety
(Scheme 4).13b While the resulting derivatives 9a and 9b were
8
18
70
a Reaction conditions: 5 (0.2 mmol) in a mixture of (Cl2CH)2/MeOH : 3/1
(1 mL) at -35 ◦C for 72 h. b Isolated yields based on substrates 5. c The
d.e. were determined either by 1H NMR, HPLC (Hypercarb or Symmetry
Shield Column) or UPLC (BEH Shield RP18 Column).
The very good result obtained with dibenzosuberane 3g, i.e. the
amino derivative 4g has been isolated with a yield of 85% and an
excellent d.e. of 99% (entry 7), thus suggests the involvement of
conformational restrictions, particularly in the case of substrate
3f.
These somewhat disappointing yields then led us to consider
a second strategy for the preparation of NAC analogs based on
the application of C–H amination to linear substrates of type 5
(Table 2). 1,n-Diphenylalkanes were first reacted under classical
conditions and the reactivity was found to depend on the chain
length (entries 1–3). While 1,2-diphenylethane 5b proved to give
the expected C–H aminated product 6b with a good yield of 73%
and a high d.e., such was not the case with diphenylmethane 5a
and, to a lesser extent, 1,3-diphenylpropane 5c.16 Compound 6c
was isolated with a modest yield of 32% and a lower selectivity.
The bulky phenyl ring might be responsible for the low conversion
observed with 5a whereas the higher flexibility of 5c could generate
sterically demanding gauche conformations preventing the nitrene
from approaching.
1
isolated with a modest yield of 46% and 48%, respectively, H
NMR studies and optical rotations clearly indicate that 9a and 9b
are enantiomers. This led us to deduce that the stereochemistry
for the nitrene addition is directed by the chirality of the substrate,
NOESY experiments, moreover, demonstrating the formation of
a trans isomer in each case.
Reaction with both enantiomers of pinene 7c and 7d also
proved to afford the expected functionalized products 8c and
8d in very good yields and d.e.s (entries 3 and 4). The bicyclic
nature of this terpene allowed us to determine unambiguously
the relative stereochemistry of 8c and 8d by NOESY experiments
thereby confirming that C–H amination took place in a trans
manner with respect to the gem-dimethyl group. Finally, even
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Dalton Trans., 2010, 39, 10401–10413 | 10403
©

Table 3 Allylic C–H amination of terpenesa
the corresponding aminated compound 11 with a modest yield
of 30% (Scheme 5). More interesting, however, was the selectivity
observed in favor of the remote tertiary site. This matches that
previously reported by White in her seminal article devoted to
predictably selective aliphatic C–H oxidation.5a It can be explained
by the presence of the terminal electron withdrawing acetate
deactivating the proximal tertiary position towards amination.
Selective functionalization was also achieved in the case of decalin.
Importantly, the difference in reactivity between the cis and trans
isomers corroborates the previously reported preferred oxidation
of equatorial C–H bonds.4c,19 Thus, while trans-decalin 12 with two
tertiary axial C–H bonds led to product 13 in minute amounts, the
equatorial 3◦ C–H bond of cis-isomer 14 was selectively oxidized
to afford the amino derivative 15 in 89% yield as a mixture of
diastereoisomers.20
Entry
1
Substrate
Product
Yield (%)b
73
d.e. (%)c
96
2
68
94
3
4
5
91
71
90
95
96
90
a Reaction conditions: 7 (0.2 mmol) in a mixture of (Cl2CH)2/MeOH : 3/1
(1 mL) at -35 ◦C for 72 h. b Isolated yields based on 7. c The d.e. were
1
determined either by H NMR, HPLC (Hypercarb or Symmetry Shield
Column) or UPLC (BEH Shield RP18 Column).
Scheme 5 Catalytic C–H amination of alkanes (5 equiv.).
(d) Mechanistic investigations. Catalytic C–H amination via
nitrene transfer involves two distinct steps, i.e. formation of a
metallanitrene followed by nitrene C–H insertion as depicted in
Scheme 2. As far as the first step is concerned, it is generally
believed that, prior to the metallanitrene, an iminoiodane is
generated from the reaction between the nitrogenous reagent and
the iodine(III) oxidant. Recent experiments support the hypothesis
of an equilibrium for this transformation which, moreover, is
shifted towards the reactants because no trace of iminoiodane
could be detected by 1H NMR.12e,g In the case of sulfonimidamide-
derived nitrenes, the equilibrium was suggested by the kinetic
resolution of racemic nitrene precursors.13b The latter occurs
with yields in the 56–80% range and excellent diastereo- and
enantioselectivities (Scheme 6).21 This was confirmed by cross
experiments with quasi-enantiomeric sulfonimidamides 1 and
17. Thus, a combination of (S)-1 and its p-nitro analog (R)-17
(respectively, (R)-1 and (S)-17) led us to isolate the sole C–H
aminated product 4a in 80% yield (respectively, 18, 72% yield)
resulting from the matched pairing between the (S)-1 (respectively,
(S)-17) and the (S)-catalyst. Once again, the yield could not have
been greater than 55% in the absence of the equilibrium. This
result also allowed us to exclude an hypothetical isomerization of
the sulfur reagent under the oxidative conditions.
Scheme 4 Deprotection of C–H aminated products derived from
limonene.
more impressive was the result obtained in the case of geranyl
acetate 7e. Only one out of 15 available allylic C–H bonds was
aminated with a very good yield of 90% (entry 5) whereas a
single diastereoisomer, though still of unknown configuration, was
observed by 1H NMR. That the secondary allylic position “a” is
selectively functionalized is probably the consequence of a subtle
balance of steric and electronic effects. This example highlights the
exquisite chemo-, regio- and stereoselectivity that can be achieved
using sulfonimidamide-derived nitrenes.
(c) C–H amination of alkanes. Catalytic C–H amination of
simple alkanes can also be performed efficiently although an excess
of substrate was needed with linear alkanes to obtain noticeable
conversions.13b
When available, tertiary positions are in this case selectively
functionalized. This trend was confirmed by application of the
reaction conditions to tetrahydrogeranyl acetate 10 which affords
We then turned our attention to the nature of the nitrene
transfer. Several studies were previously aimed at elucidating the
mechanism of the rhodium-catalyzed C–H amination. Physical
organic experiments10f,12b,e,g such as reaction with a radical clock,
10404 | Dalton Trans., 2010, 39, 10401–10413
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The Royal Society of Chemistry 2010
©

Scheme 8 C–H amination in the presence of BHT
Comparison of the reactivity between ethylbenzene and its d2-
benzylic analog then allowed us to estimate the kinetic isotope
effect for this rhodium-catalyzed C–H amination. Separate reac-
tions carried out with each substrate clearly demonstrated the
lower reactivity of deuterated ethylbenzene 23-d (Scheme 9). An
intermolecular competition experiment confirmed this trend and
led us to measure by 13C NMR12g,24 a KIE of 4.5 0.5. The latter
is in the same range as those previously reported by Mu¨ller12b
and Lebel12j for analogous rhodium-catalyzed C–H aminations
although values between 1.2 and 2.1 are generally observed for
concerted nitrene or carbene transfer.12g,24 On the other hand,
C–H amination involving radical species displayed KIE typically
greater than 6.25 No clear-cut conclusion can therefore be drawn
from these experiments except that C–H bond cleavage might be
a rate-limiting step.
Scheme
cross-experiments.
6 Hypothesis for the formation of iminoiodanes and
Hammett analysis or Kinetic Isotope Effect measurement as
well as DFT studies22 all point to a concerted asynchronous
C–H insertion of a rhodium-bound singlet nitrene. This was
also suggested by the stereospecific insertion of nitrenes into
enantiopure tertiary positions.12b,e In our hands, application of
the reaction conditions to the classical radical clock 1912e,j and
optically pure (S)-2-phenylbutane 21 did not prove conclusive
since the expected products 20 and 22 were isolated in tiny amounts
(Scheme 7).
Scheme 7 Study of a radical clock and the stereospecificity of C–H
Scheme 9 Kinetic isotope effect.
amination.
Finally, a Hammett analysis was also performed and proved
to be as poorly conclusive. Competitive experiments between
ethylbenzene and its 4-substituted analogs, both used in excess,
all led to the same result, i.e. the C–H amination preferentially
occurred with the p-substituted substrate regardless of the elec-
tronic property of the substituent (Table 4). No correlation could
then be made (see ESI‡) even by considering the Total Effect
(TE) parameter26 previously taken into account by Che et al.
to rationalize the radical character of the ruthenium porphyrin-
catalyzed amidation of alkanes.25,27
Perez et al. demonstrated the implication of radicals in the silver-
catalyzed alkane C–H amination by carrying out experiments
in the presence of catalytic amounts of the radical inhibitor
2,6-di-tert-butylhydroxytoluene (BHT).11f Yields were thus shown
to decrease with increased quantity of BHT introduced, no
conversion being seen with one equivalent of the inhibitor. Based
on these experiments, we decided to run catalytic C–H amination
of various types of substrates in the presence of BHT (Scheme 8).
No significant alterations of the yields were observed starting from
indan, 1-phenylcyclohexene, adamantane and cycloheptane. Only
conversion of 2-methylbutane was found to be changed under
these conditions, 15% instead of 36% of the corresponding C–H
aminated product being isolated.23
All these physical organic experiments gave somewhat unex-
pected results and the precise nature of the nitrene transfer,
therefore, remains elusive. An asynchronous concerted pathway
can still be considered as a plausible scenario, particularly in the
This journal is
The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 10401–10413 | 10405
©

Table 4 Hammett analysis dataa
using standard procedures. Melting points (mp) were measured in
capillary tubes on a Bu¨chi B-540 apparatus and are uncorrected.
Optical rotations ([a]2D0) were determined with a JASCO P-1010
polarimeter. Mass spectra were obtained either with a LCT
(Micromass) instrument using electrospray ionization (ES), or
from a Time of Flight analyzer (ESI-MS) for the high reso-
lution mass spectra (HRMS). Elemental analyses (Anal.) were
performed on a Perkin Elmer CHN 2400 analyzer with detection
by catharometry, at the ICSN, CNRS, Gif-sur-Yvette, France.
Infrared spectra (IR) were recorded on a Perkin Elmer Spectrum
BX FT-IR spectrometer. Proton NMR (1H) spectra were recorded
with a Bruker 500 MHz or 300 MHz spectrometer. Carbon
NMR (13C) spectra were recorded at 125 or 75 MHz, using a
broadband decoupled mode with the multiplicities obtained using
a JMOD or DEPT sequence. Chemical shifts (d) are reported
in parts per million (ppm). NMR experiments were carried out in
deuterochloroform (CDCl3). The following abbreviations are used
+
b
Entry
X
s
TEc
p-XPh:Ph
1
2
3
4
5
6
7
OMe
Me
H
F
Cl
Br
NO2
-0.78
-0.31
0
1.08
0.42
0
0.16
0.23
—
10 : 1
3.1 : 1
1 : 1
2.1 : 1
3.1 : 1
3.1 : 1
1.8 : 1
—
0.15
0.15
0.79
1.04
a Reaction conditions: Ethylbenzene (2.0 mmol) and 4-substituted ethyl-
benzene (2.0 mmol) in a mixture of (Cl2CH)2/MeOH : 3/1 (1 mL) at
-35 ◦C for 72 h. b Hammett s-constant. c TE : total effect of substituent
on the benzylic C–H bond dissociation energy.
1
for the H spectra multiplicities: s: singlet, d: doublet, t: triplet,
q: quartet, quint: quintuplet, m: multiplet, br: broad. Coupling
constants (J) are reported in Hertz (Hz). Values in italics refer to
the minor diastereomer, where applicable.
case of highly reactive substrates. However, the involvement of
radicals which would recombine extremely fast, cannot be ruled
out.
Typical C–H amination procedure
Conclusions
˚
In an oven-dried tube were introduced activated 4 A molecular
Catalytic C–H amination of various hydrocarbons used in sto-
ichiometric amount can be achieved in good to excellent yields
and with exceptional levels of regio-, chemo- and stereoselectivity.
This results from the exquisite combination of a chiral sulfur(VI)
reagent with a chiral rhodium(II) complex that gives birth to a
highly discriminating oxidizing nitrene intermediate. Of utmost
importance is the ability to control the selective functionalization
of a particular C–H bond by fine-tuning its steric and electronic
environment. This has led to the selective amination of complex
substrates such as terpenes.
Physical organic experiments, i.e. use of a radical clock or
a stereochemical probe, reaction in the presence of a radical
inhibitor, kinetic isotope effect and Hammett analysis, were
designed in order to shed the light on the mechanism. They,
however, turned out to be poorly informative since they did not
allow us to discriminate between a concerted and a stepwise
pathway for the nitrene C–H insertion. Work is now in progress
to track a putative radical intermediate as well as to apply the
reaction to the total synthesis of nitrogen-containing products.
sieves (100 mg), Rh2{(S)-nta}4 (2) (7.7 mg, 0.006 mmol) and (-)-
N-(p-toluenesulfonyl)-p-toluenesulfonimidamide (-)-(1) (78 mg,
0.24 mmol). The tube was capped with a rubber septum and purged
with argon. 1,1,2,2-Tetrachloroethane (0.75 mL) and methanol
(0.25 mL) were added under argon, and the mixture was stirred
for 5 min before addition of the substrate (0.2 mmol). The tube
was cooled to -35 ◦C, and bis(tert-butylcarbonyloxy)iodobenzene
(115 mg, 0.2◦8 mmol) was added. The mixture was stored in the
freezer (-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 C–H insertion products.
(-)-N-(p-Toluenesulfonyl)-p-toluenesulfonimidamide ((S)-1)
To an ice cooled suspension of anhydrous sodium p-
toluenesulfinate (3.75 g, 21 mmol) in toluene (40 mL) under
argon was slowly added thionyl chloride (7.5 mL). The reaction
mixture was stirred at room temperature for 14 h before being
evaporated under vacuum. The resulting yellow oil was dissolved
in toluene (60 ml) and anhydrous chloramine-T (4.78 g, 21 mmol)
(Caution! The trihydrate was dried in a drying pistol at 80 ◦C
for 8 h. Explosion may occur at higher temperatures) was added
Experimental
General
All reagents were obtained from commercial suppliers unless
otherwise stated. When necessary, organic solvents were routinely
dried and/or distilled prior to use and stored over molecular
sieves under nitrogen. THF was distilled from sodium and
benzophenone. CH2Cl2 and CH3CN were distilled from calcium
hydride. Thin-layer chromatography was performed on silica gel
60 F254 on aluminium plates (Merck) and visualized under a
UVP Mineralight UVLS-28 lamp (254 nm) and with ninhydrin
and phosphomolybdic acid in ethanol. Flash chromatography
was conducted on Merck silica gel 60 (40–63 mm) at medium
pressure (300 mbar) or on CombiFlash (Serlabo Technologies)
◦
at room temperature. The reaction mixture was stirred at 80 C
for 1.5 h. The sodium chloride precipitate was filtered while the
reaction mixture was still hot and the filtrate was evaporated. The
crude N-(p-toluenesulfonyl)-p-toluene-sulfonimidoyl chloride was
dissolved in dichloromethane (80 ml) and a mixture of (R)-
(-)-a-methylbenzylamine (3.24 mL, 25.2 mmol) and sodium
hydrogencarbonate (2.1 g, 25.2 mmol) in water (50 ml) was added
at 0 ◦C. After 30 min, the ice bath was removed and the reaction
mixture was stirred overnight at room temperature. The organic
layer was separated and washed successively with 10% HCl and
10406 | Dalton Trans., 2010, 39, 10401–10413
This journal is
The Royal Society of Chemistry 2010
©

water, dried with MgSO4 and concentrated under vacuum to afford
a pasty yellow solid. The latter was dissolved in ethyl ether (40 ml)
and after cooling, filtration afforded 2.1 g of a white solid (d.e.>
95% as estimated by 1H NMR). A second crop was obtained from
the mother liquor (0.8 g) yielding a total of 2.9 g (6.77 mmol,
32%) of pure compound. mp 156–156.5 ◦C; [a]D20 + 118.8 (c 0.44,
CHCl3); IR (neat, cm-1) 3232, 1594, 1301, 1152, 1106, 1070, 1017,
(c 0.06, CHCl3–MeOH); IR (KBr, cm-1) 3492, 2939, 1698, 1658,
1585, 1409, 1376, 1357, 1338, 1294, 1237, 1191, 1127, 1096, 1035,
1
968, 888; H NMR (300 MHz, CDCl3/MeOD) d 1.71 (d, J =
6.8 Hz, 3H, CH3), 5.88 (q, J = 7.0 Hz, 1H, CH), 7.67 (t, J =
7.7 Hz, 2H, 2 ¥ CHAr), 8.05 (d, J = 8.0 Hz, 2H, 2 ¥ CHAr), 8.56 (d,
J = 7.1 Hz, 2H, 2 ¥ CHAr); 13C NMR (75 MHz, CDCl3/MeOD)
d 15.1, 50.6, 122.5, 126.8, 131.2, 131.3, 133.5, 163.3, 188.3;
HRMS m/z ((M+Na)+) calcd for C60H40N4Na016Rh21301.0447
found 1301.0491.
1
813, 755, 700, 657; H NMR (300 MHz, CDCl3) d 1.35 (d, J =
7.0 Hz, 3H, CH3), 2.41 (s, 3H, CH3), 2.43 (s, 3H, CH3), 4.52 (q,
J = 7.0 Hz, 1H, CH–N), 6.18 (d, J = 7.0 Hz, 1H, NH), 7.26 (m,
9H, 9 ¥ CHAr), 7.82 (m, 4H, 4 ¥ CHAr); 13C NMR (75 MHz,
CDCl3) d 21.5, 21.6, 23.0, 54.0, 126.4, 126.9, 127.8, 127.9, 128.7,
129.3, 129.7, 136.2, 140.5, 141.8, 142.9, 144.7; MS (ES) m/z 451
(M+Na)+; Anal. calcd (%) for C22H24N2O3S2: C, 61.66; H, 5.64;
N, 6.54; S, 14.96; found: C, 61.26; H, 5.53; N, 6.57; S, 14.93.
2.9 g (6.77 mmol) of the pure diastereoisomer was dissolved
in trifluoroacetic acid (6 mL). After stirring for 40 h at 35 ◦C,
the reaction mixture was evaporated under vacuum, leaving a
crude green solid. The latter was purified by flash chromatography
(heptane/ethyl acetate 1 : 1) and then crystallized from ethyl
(1R)-[N-(p-toluenesulfonyl)-p-toluenesulfonimidoyl]-1-
aminoindane (4a)13b
Prepared following the typical amination procedure from in-
dane, the corresponding C–H insertion product was obtained
(dichloromethane–ethyl acetate: 20/1) as a white solid in 89%
yield and >98% d.e. (HPLC, Hypercarb column, 100 ¥ 4.6 mm,
5 mm, MeCN + 0.1% HCOOH/H2O + 0.1% HCOOH: 80/20,
1 mL min-1, tmaj = 9.28 min).
◦
acetate to afford (S)-1 (1.6 g, 72%). mp 152.0–152.5 C; [a]D20
(1R)-[N-(p-toluenesulfonyl)-p-toluenesulfonimidoyl]-1-amino-
1,2,3,4-tetrahydronaphthalene (4b)13b
-110 (c 0.47, acetone); e.e.>99% (HPLC, Chiracel AD, 4.6 ¥ 250,
10 mm); IR (KBr, cm-1) 3212, 1284, 1149, 1107, 1087, 810, 748,
660; 1H NMR (300 MHz, CDCl3) d 2.40 (s, 3H, CH3), 2.42 (s, 3H,
CH3), 5.60 (s, 2H, NH2), 7.25 (d, J = 7.5 Hz, 2H, 2 ¥ CHAr), 7.29
(d, J = 7.9 Hz, 2H, 2 ¥ CHAr), 7.79 (d, J = 7.5 Hz, 2H, 2 ¥ CHAr),
7.84 (d, J = 7.6 Hz, 2H, 2 ¥ CHAr); 13C NMR (75 MHz, Acetone)
d 21.3, 21.4, 127.3, 127.8, 129.8, 130.3, 140.3, 142.6, 142.9, 144.8;
MS (ES) m/z 347 (M+Na)+; Anal. calcd (%) for C14H16N2O3S2: C,
51.83; H, 4.97; N, 8.63; S, 19.77; found: C, 51.58; H, 4.92; N, 8.55;
S, 20.04.
Prepared following the typical amination procedure from 1,2,3,4-
tetrahydronaphthalene, the corresponding C–H insertion product
was obtained (dichloromethane–ethyl acetate: 20/1) as a white
solid in 86% yield and 98% d.e. (HPLC, Symmetry shield column,
150 ¥ 4.6 mm, 5 mm, MeCN + 0.1% HCOOH/H2O + 0.1%
HCOOH: 46/54, 1 mL min-1, tmaj = 40.25 min).
(R)-[N-(p-toluenesulfonyl)-p-toluenesulfonimidoyl]-5-amino-
6,7,8,9-tetrahydrobenzo[7]annulene (4c)
Prepared following the typical amination procedure from
6,7,8,9-tetrahydro-5H-benzo[7]annulene (prepared from 1-
benzosuberone), the corresponding C–H insertion product
was obtained (dichloromethane–ethyl acetate: 20/1) as an oily
solid in 76% yield, >90% d.e (1H NMR evaluation). Rf 0.40
(heptane/ethyl acetate: 60/40); IR (neat, cm-1) 3219, 2925, 1726,
(S)-N-1,8-Naphthoylalanine
A mixture of L-alanine (0.687 g, 7.72 mmol) and 1,8-naphthalic
anhydride (1.71 g, 8.60 mmol) in DMSO (25 mL) was heated
under reflux in an atmosphere of argon for 1 h. The solvent was
evaporated under reduced pressure and the light-brown residue
was purified by flash chromatography (silica, dichloromethane–
MeOH: 90/10), to afford (S)-nta (1.84 g, 88%) as a brownish solid.
mp 266–267 ◦C; [a]D20 -39 (c 0.61, CHCl3–MeOH); IR (KBr, cm-1)
3204, 3013, 1715, 1694, 1652, 1585, 1376, 1335, 1231, 1190, 1092,
1
1596, 1453, 1286, 1254, 1149, 1104, 1089, 1015, 811; H NMR
(300 MHz, CDCl3) d (ppm) 1.63–1.89 (m, 4H, 2 ¥ CH2), 2.42
(s, 3H), 2.44 (s, 3H), 2.65–3.10 (m, 4H, 2 ¥ CH2), 3.50–3.58 (m,
1H, CH–N), 5.53–5.60 (m, 1H, NH), 7.05–7.37 (m, 8H, 8C–HAr),
7.74–7.86 (m, 4H, 4C–HAr); 13C NMR (75 MHz, CDCl3) d (ppm)
21.5 (CH3), 21.6 (CH3), 35.5 (CH2), 37.7 (CH2), 41.2 (CH2), 42.2
(CH2), 50.9 (CH–N), 126.6 (CH), 126.7 (2 ¥ CH), 127.5 (CH),
127.8 (2 ¥ CH), 129.0 (CH), 129.1 (2 ¥ CH), 129.2 (CH), 129.7
(CH), 129.8 (CH), 140.5 (C), 142.7 (C), 143.0 (C), 143.1 (C), 144.6
(C), 144.7 (C); MS (ES) m/z 469 ((M+H)+), 491 ((M+Na)+),
HRMS m/z ((M+Na)+) calcd for C25H28N2NaO3S2491.1439
found 491.1431.
1
1035, 964, 889, 843, 770, 655; H NMR(300 MHz, DMSO D6)
d1.55 (d, J = 7.0 Hz, 3H, CH3), 5.60 (q, J = 7.0 Hz, 1H, CH), 7.88
(m, 2H, 2 ¥ CHAr), 8.50 (m, 4H, 4 ¥ CHAr); 13C NMR (75 MHz,
DMSO D6) d 15.0, 49.0, 122.2, 127.8, 131.5, 131.8, 135.1, 163.3,
171.8; MS (ES) m/z 292 ((M+Na)+) HRMS m/z ((M+Na)+) calcd
for C15H11NNaO4292.0586 found 292.0563.
Rh2{(S)-nta}4 (2)
[Rh2(OAc)4] (110 mg, 0.25 mmol) and (S)-N-1,8-naphthoylalanine
(645 mg, 2.40 mmol) were heated to reflux under argon in
chlorobenzene in a flask fitted with a soxhlet extractor containing
a mixture of anhydrous Na2CO3 and sand. After 24 h, the
solvent was evaporated and the gummy residue was purified by
flash chromatography (Alox basic, dichloromethane–methanol:
90/10) to afford the desired catalyst which was precipitated from
acetonitrile to give the pure catalyst (288 mg, 90%). [a]2D0 -86
(R)-[N-(p-toluenesulfonyl)-p-toluenesulfonimidoyl]-1-amino
fluorene (4d)
Prepared following the typical amination procedure from flu-
orene, the corresponding C–H insertion product was obtained
(dichloromethane–ethyl acetate: 20/1) as an oily solid in 40% yield.
Rf 0.38 (heptane/ethyl acetate: 60/40); IR (neat, cm-1) 3214, 1595,
1
1451, 1302, 1259, 1151, 1107, 1088, 1041, 1016, 812; H NMR
This journal is
The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 10401–10413 | 10407
©

(500 MHz, CDCl3) d (ppm) 2.45 (s, 3H), 2.47 (s, 3H), 5.32 (d,
J = 9.0 Hz, 1H, CH–N), 6.38 (d, J = 9.0 Hz, 1H, NH), 7.25–7.48
(m, 6H, 6C–HAr), 7.56–7.68 (m, 4H, 4C–HAr), 7.77–7.90 (m, 2H,
2C–HAr), 7.92 (d, J = 8.0 Hz, 2H, 2C–HAr), 8.03 (d, J = 8.5 Hz,
2H, 2C–HAr); 13C NMR (75 MHz, CDCl3) d (ppm) 21.6 (CH3),
21.7 (CH3), 57.9 (CH–N), 119.9 (CH), 122.9 (CH), 123.4 (CH),
125.4 (CH), 126.1 (CH), 126.2 (CH), 126.8 (CH), 126.9 (CH),
127.9 (CH), 128.1 (CH), 128.2 (CH), 129.2 (CH), 129.3 (2 ¥ CH),
129.9 (CH), 130.1 (CH), 136.4 (2 ¥ C), 140.4 (2 ¥ C), 140.5 (2 ¥
C), 144.9 (2 ¥ C); MS (ES) m/z 489 ((M+H)+), 511 ((M+Na)+),
HRMS m/z ((M+Na)+) calcd for C27H24N2NaO3S2511.1126 found
511.1119.
(R)-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-
(1,2-diphenylethyl)amine (6b)
Prepared following the typical amination procedure from 1,2-
diphenylethane, the corresponding C–H insertion product was
obtained (dichloromethane–ethyl acetate: 20/1) as a white solid
in 73% yield, 99% d.e (UPLC, BEH shield RP18 column, 50 ¥
2.1 mm, 1.8 mm, MeCN + 0.1% HCOOH/H2O + 0.1% HCOOH:
55/45, 0.6 mL min-1, tmaj = 1.26 min). Rf 0.52 (heptane/ethyl
◦
acetate: 50/50); mp 139–141 C; [a]2D0 + 106.9 (c 1.00, CHCl3);
IR (neat, cm-1) 3229, 1695, 1597, 1454, 1287, 1148, 1067, 1041,
1014, 809, 696; 1H NMR (500 MHz, CDCl3) d (ppm) 2.38 (s, 3H),
2.39 (s, 3H), 2.91–3.00 (m, 2H, CH2), 4.42–4.46 (m, 1H, CH–N),
6.44 (d, J = 7.0 Hz, 1H, NH), 6.91 (d, J = 8.0 Hz, 2H), 7.08 (d,
J = 8.0 Hz, 2H), 7.14–7.30 (m, 10H), 7.46 (d, J = 8.0 Hz, 2H), 7.70
(d, J = 8.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) d (ppm) 21.5
(CH3), 21.6 (CH3), 43.9 (CH2), 59.9 (CH–N), 126.7 (CH), 126.8
(2 ¥ CH), 126.9 (2 ¥ CH), 127.6 (2 ¥ CH), 127.7 (CH), 128.4 (2 ¥
CH), 128.5 (2 ¥ CH), 129.1 (2 ¥ CH), 129.3 (2 ¥ CH), 129.5 (2 ¥
CH), 135.3 (C), 136.4 (C), 140.2 (C), 140.6 (C), 142.8 (C), 144.2
(C); MS (ES) m/z 527 ((M+Na)+), HRMS m/z ((M+Na)+) calcd
for C28H28N2NaO3S2 527.1439 found 527.1436.
(R)-[N-(p-toluenesulfonyl)-p-toluenesulfonimidoyl]-1-amino
dihydrophenanthrene (4e)
Prepared following the typical amination procedure from 9,10-
dihydrophenanthrene, the corresponding C–H insertion product
was obtained (dichloromethane–ethyl acetate: 20/1) as an oily
solid in 20% yield, >90% d.e (1H NMR evaluation). Rf 0.40
(heptane/ethyl acetate: 60/40); IR (neat, cm-1) 3214, 1596, 1434,
1300, 1255, 1149, 1105, 1088, 1044, 1016, 811; 1H NMR (500 MHz,
CDCl3) d (ppm) 2.44 (s, 3H), 2.47 (s, 3H), 2.76–2.80 (m, 2H, CH2),
4.57–4.60 (m, 1H, CH–N), 5.98 (d, J = 7.0 Hz, 1H, NH), 7.12–
7.28 (m, 10H, 10C–HAr), 7.64–7.70 (m, 2H, 2C–HAr), 7.74 (d, J =
8.5 Hz, 2H, 2C–HAr), 7.82 (d, J = 8.5 Hz, 2H, 2C–HAr); 13C NMR
(75 MHz, CDCl3) d (ppm) 21.5 (CH3), 21.6 (CH3), 29.0 (CH2),
51.9 (CH–N), 123.2 (CH), 123.7 (CH), 126.7 (CH), 126.8 (2 ¥
CH), 126.9 (2 ¥ CH), 127.0 (CH), 127.4 (CH), 127.8 (2 ¥ CH),
128.1 (2 ¥ CH), 129.2 (2 ¥ CH), 129.9 (CH), 136.6 (2 ¥ C), 140.5
(2 ¥ C), 140.6 (2 ¥ C), 145.6 (2 ¥ C); MS (ES) m/z 501 ((M-H)-),
HRMS m/z ((M-H)-) calcd for C28H25N2O3S2501.1307 found
501.1298.
(R)-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-
(1,3-diphenylpropyl)amine (6c)
Prepared following the typical amination procedure from 1,3-
diphenylpropane, the corresponding C–H insertion product was
obtained (dichloromethane–ethyl acetate: 20/1) as an oily solid in
32% yield, 75% d.e (1H NMR evaluation). Rf 0.33 (heptane/ethyl
acetate: 60/40); IR (neat, cm-1) 3242, 2922, 1724, 1597, 1455, 1264,
1151, 1109, 1016, 812, 738; 1H NMR (500 MHz, CDCl3) d (ppm)
1.98–2.05 (m, 2H, CH2m), 2.30–2.34 (m, 2H, CH2), 2.38 (s, 3H),
2.44 (s, 3H), 4.26 (q, J = 7.5 Hz, 1H, CH–N), 6.40 (d, J = 7.5 Hz,
1H, NH), 6.46 (d, J = 7.5 Hz, 1H, NH), 6.90 (d, J = 7.5 Hz,
2H), 7.16–7.34 (m, 12H), 7.68 (d, J = 7.5 Hz, 2H), 7.76 (d, J =
7.5 Hz, 2H); 13C NMR (75 MHz, CDCl3) d (ppm) 21.5 (CH3),
21.6 (CH3), 31.8 (CH2), 38.4 (CH2m), 58.0 (CH–N), 126.1 (CH),
126.7 (2 ¥ CH), 126.8 (2 ¥ CH), 127.6 (CH), 127.8 (2 ¥ CH), 128.2
(2 ¥ CH), 128.4 (2 ¥ CH), 128.7 (2 ¥ CH), 129.2 (2 ¥ CH), 129.7
(2 ¥ CH), 135.9 (C), 140.2 (C), 140.4 (2 ¥ C), 142.8 (C), 144.6 (C);
MS (ES) m/z 541 ((M+Na)+), HRMS m/z ((M+Na)+) calcd for
C29H30N2NaO3S2 541.1596 found 541.1589.
(R)-[N-(p-toluenesulfonyl)-p-toluenesulfonimidoyl] amino
dibenzosuberane (4g)
Prepared following the typical amination procedure from dibenzo-
suberane, the corresponding C–H insertion product was obtained
(dichloromethane–ethyl acetate: 20/1) as a white solid in 85%
yield, 99% d.e (UPLC, BEH shield RP18 column, 50 ¥ 2.1 mm,
1.8 mm, MeCN + 0.1% HCOOH/H2O + 0.1% HCOOH: 50/50,
0.6 mL min-1, tmaj = 2.51 min). Rf 0.40 (heptane/ethyl acetate:
60/40); mp 70–72 ◦C; [a]D20 + 38.1 (c 1.00, CHCl3); IR (neat, cm-1)
3233, 1596, 1492, 1400, 1315, 1249, 1150, 1112, 1091, 1014, 808,
(R)-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-(2-bromo-1-
phenylethyl)amine (6d)
1
750; H NMR (300 MHz, CDCl3) d (ppm) 2.40 (s, 3H), 2.50
(s, 3H), 2.70–2.77 (m, 1H, CH2b), 3.15–3.20 (m, 1H, CH2b), 3.87
(d, J = 15.0 Hz, 1H, CH2a), 4.17 (d, J = 15.0 Hz, 1H, CH2a),
4.99–5.04 (m, 1H, CH–N), 5.59 (d, J = 7.0 Hz, 1H, NH), 6.72
(d, J = 8.0 Hz, 1H, CHAr), 7.11–7.25 (m, 8H, 8C–HAr), 7.397.46
(m, 3H, 3C–HAr), 7.76 (d, J = 8.0 Hz, 2H, 2C–HAr), 7.93 (d, J =
8.5 Hz, 2H, 2C–HAr); 13C NMR (75 MHz, CDCl3) d (ppm) 21.6
(CH3), 21.7 (CH3), 37.5 (CH2b), 41.0 (CH2a), 54.2 (CH–N), 126.7
(2 ¥ CH), 126.9 (CH), 127.3 (CH), 127.4 (CH), 127.8 (2 ¥ CH),
128.0 (CH), 128.5 (CH), 129.2 (2 ¥ CH), 129.8 (CH), 129.9 (2 ¥
CH), 130.0 (CH), 132.2 (CH), 134.4 (C), 136.2 (C), 137.1 (C),
137.5 (C), 140.4 (C), 140.5 (C), 142.8 (C), 144.9 (C); MS (ES) m/z
517 ((M+H)+), 539 ((M+Na)+), HRMS m/z ((M+Na)+) calcd for
C29H28N2NaO3S2539.1439 found 539.1445.
Prepared following the typical amination procedure from 2-
bromoethylbenzene, the corresponding C–H insertion product
was obtained (dichloromethane–ethyl acetate: 20/1) as a white
solid in 85% yield, >90% d.e (1H NMR evaluation). Rf 0.32
◦
(heptane/ethyl acetate: 60/40); mp 130–131 C; [a]2D0 + 89.0 (c
0.55, CHCl3); IR (neat, cm-1) 3218, 1595, 1494, 1441, 1300, 1260,
1147, 1102, 1088, 1072, 1033, 810, 752, 658; 1H NMR (500 MHz,
CDCl3) d (ppm) 2.40 (s, 3H), 2.43 (s, 3H), 3.48–3.56 (m, 2H,
CH2–Br), 4.62 (q, J = 7.0 Hz, 1H, CH–N), 6.49 (d, J = 7.0 Hz,
1H, NH), 7.21 (d, J = 8.0 Hz, 2H), 7.26–7.35 (m, 7H), 7.76 (d,
J = 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H); 13C NMR (75 MHz,
CDCl3) d (ppm) 21.5 (CH3), 21.6 (CH3), 36.0 (CH2–Br), 58.2
(CH–N), 126.7 (2 ¥ CH), 126.9 (2 ¥ CH), 127.8 (2 ¥ CH), 128.5
10408 | Dalton Trans., 2010, 39, 10401–10413
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The Royal Society of Chemistry 2010
©

(CH), 128.7 (2 ¥ CH), 129.2 (2 ¥ CH), 129.7 (2 ¥ CH), 135.4 (C),
137.5 (C), 140.1 (C), 142.9 (C), 145.0 (C); MS (ES) m/z 79Br: 529
((M+Na)+),81Br: 531 ((M+Na)+), HRMS m/z ((M+Na)+) calcd
for C22H23N2O3S279Br 529.0231 found 529.0231, m/z ((M+Na)+)
calcd for C22H23N2O3S281Br 531.0211 found 531.0201.
product was obtained (dichloromethane–ethyl acetate: 20/1) as
a yellow oil in 18% yield, 70% d.e (1H NMR evaluation). Rf
0.49 (heptane–ethyl acetate: 50/50); IR (neat, cm-1) 3221, 1596,
1454, 1301, 1150, 1107, 1090, 1016, 906, 812; 1H NMR (500 MHz,
CDCl3) d (ppm) 1.96–2.01 (m, 2H, CH2), 2.38 (s, 3H), 2.42 (s,
3H), 2.69–2.81 (m, 2H, CH2), 4.30–4.34 (m, 1H, CH–N), 6.45
(d, J = 8.0 Hz, 1H, NH), 7.14–7.17 (m, 2H), 7.21–7.33 (m,
10H), 7.68 (d, J = 8.5 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.82–
7.85 (m, 1H); 13C NMR (75 MHz, CDCl3) d (ppm) 21.5 (CH3),
21.6 (CH3), 35.6 (CH2), 36.7 (CH2), 58.2 (CH–N), 125.8 (C–Br),
126.7 (4 ¥ CH), 126.9 (2 ¥ CH), 127.8 (2 ¥ CH), 128.3 (CH),
128.4 (CH), 128.7 (CH), 129.2 (2 ¥ CH), 129.3 (CH), 129.7 (2 ¥
CH), 132.8 (CH), 135.9 (C), 140.0 (C), 140.2 (C), 140.3 (C),
142.8 (C), 144.7 (C); MS (ES) m/z 79Br: 597 ((M+H)+),81Br:
599 ((M+H)+), 79Br: 619 ((M+Na)+),81Br: 621 ((M+Na)+),
HRMS m/z ((M+Na)+) calcd for C29H29N2NaO3S279Br 619.0701
found 619.0698, m/z ((M+Na)+) calcd for C29H29N2NaO3S281Br
621.0680 found 621.0695.
(R)-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-(3-bromo-1-
phenylpropyl)amine (6e)
Prepared following the typical amination procedure from 1-
bromo-3-phenylpropane, the corresponding C–H insertion prod-
uct was obtained (dichloromethane–ethyl acetate: 20/1) as a
white solid in 42% yield, 99% d.e (HPLC, Hypercarb column,
100 ¥ 4.6 mm, 5 mm, MeCN + 0.2% TFA/H2O + 0.2% TFA:
100/0, 1 mL min-1, tmaj = 10.18 min). Rf 0.36 (heptane/ethyl
◦
acetate: 60/40); mp 147–148 C; [a]2D0 + 103.6 (c 0.62, CHCl3);
IR (neat, cm-1) 3235, 1596, 1494, 1433, 1304, 1261, 1147, 1102,
1074, 1030, 1016, 811, 659; 1H NMR (500 MHz, CDCl3) d (ppm)
2.16–2.31 (m, 2H, CH2), 2.39 (s, 3H), 2.44 (s, 3H), 3.05–3.16 (m,
2H, CH2–Br), 4.56 (q, J = 7.5 Hz, 1H, CH–N), 6.55 (d, J =
7.5 Hz, 1H, NH), 7.18 (d, J = 8.0 Hz, 2H), 7.27–7.34 (m, 7H),
7.71 (d, J = 8.0 Hz, 2H), 7.82 (d, J = 8.0 Hz, 2H); 13C NMR
(75 MHz, CDCl3) d (ppm) 21.5 (CH3), 21.6 (CH3), 29.1 (CH2–
Br), 39.6 (CH2), 56.6 (CH–N), 126.7 (2 ¥ CH), 126.8 (2 ¥ CH),
127.8 (2 ¥ CH), 128.2 (CH), 128.9 (2 ¥ CH), 129.2 (2 ¥ CH), 129.8
(2 ¥ CH), 135.7 (C), 139.5 (C), 140.0 (C), 142.9 (C), 144.9 (C);
MS (ES) m/z 79Br: 519 ((M-H)-), 81Br: 521 ((M-H)-), 79Br: 543
((M+Na)+),81Br: 545 ((M+Na)+), HRMS m/z ((M-H)-) calcd for
C23H24N2O3S279Br 519.0412 found 519.0434, m/z ((M-H)-) calcd
for C23H24N2O3S281Br 521.0391 found 521.0417.
(1R,6S)-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-6-
isopropenyl-3-methylcyclohex-2-en-1-amine (8a)
Prepared following the typical amination procedure from (S)-
limonene, the corresponding C–H insertion product was obtained
(dichloromethane–ethyl acetate: 20/1) as a white solid in 73%
yield, 96% d.e (HPLC, Hypercarb column, 100 ¥ 4.6 mm,
5 mm, MeCN + 0.1% HCOOH/H2O + 0.1% HCOOH: 80/20,
1 mL min-1, tmaj = 46.38 min, or UPLC, BEH shield RP18
column, 50 ¥ 2.1 mm, 1.8 mm, MeCN + 0.1% HCOOH/H2O +
0.1% HCOOH: 55/45, 0.6 mL min-1, tmaj = 1.40 min). Rf 0.54
◦
(heptane/ethyl acetate: 50/50); mp 83–85 C; [a]2D0 + 105.5 (c
(R)-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-
(2-(o-bromophenyl)-1-phenylethyl)amine (6g)
1.00, CHCl3); IR (neat, cm-1) 3190, 1597, 1424, 1299, 1283, 1146,
1109, 1030, 1014, 806; 1H NMR (300 MHz, CDCl3) d 1.03 (s, 3H,
CH3), 1.39–1.56 (m, 2H, CH2), 1.60 (s, 3H, CH3), 1.79–1.81 (m,
1H, 1CH2), 1.81–1.98 (m, 2H, CH + 1CH2), 2.33 (s, 3H, CH3),
2.35 (s, 3H, CH3), 3.49–3.54 (m, 1H, CH–N), 4.49 (br s, 1H,
1CH2-isopren), 4.54 (br s, 1H, 1CH2-isopren), 5.41 (br s, 1H, CHvinyl),
5.67 (d, J = 8.0 Hz, 1H, NH), 7.16–7.19 (m, 4H, 4 ¥ CHAr), 7.69
(d, J = 8.5 Hz, 2H, 2 ¥ CHAr), 7.76 (d, J = 8.5 Hz, 2H, 2 ¥
CHAr); 13C NMR (75 MHz, CDCl3) d 18.4 (CH3), 21.5 (CH3),
21.6 (CH3), 23.2 (CH3), 26.9 (CH2), 29.4 (CH2), 48.2 (CH), 52.9
(CH–N), 113.5 (CH2-isopren), 122.7 (CHvinyl), 126.8 (2 ¥ CHAr), 128.4
(2 ¥ CHAr), 129.2 (2 ¥ CHAr), 129.4 (2 ¥ CHAr), 135.4 (C), 138.0
(C), 140.5 (C), 142.8 (C), 144.6 (C), 144.9 (C). MS (ES) m/z 481
((M+Na)+), HRMS m/z ((M+Na)+) calcd for C24H30N2NaO3S2
481.1596 found 481.1608.
Prepared following the typical amination procedure from 2-
(o-bromophenyl)ethylbenzene, the corresponding C–H insertion
product was obtained (dichloromethane–ethyl acetate: 20/1) as
a clear oil in 42% yield, 70% d.e (1H NMR evaluation). Rf 0.51
(heptane/ethyl acetate: 50/50); IR (neat, cm-1) 3222, 1596, 1454,
1287, 1148, 1089, 1041, 1014, 810, 697; 1H NMR (500 MHz,
CDCl3) d (ppm) 2.38 (s, 3H), 2.39 (s, 3H), 2.91–3.01 (m, 2H,
CH2), 4.42–4.47 (m, 1H, CH–N), 4.56–4.62 (m, 1H, CH–N), 6.41
(d, J = 7.0 Hz, 1H, NH), 6.50 (d, J = 7.0 Hz, 1H, NH), 6.87–
6.91 (m, 2H), 6.98–7.10 (m, 2H), 7.12–7.28 (m, 6H), 7.31–7.37
(m, 2H), 7.43–7.48 (m, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.82–
7.86 (m, 1H); 13C NMR (75 MHz, CDCl3) d (ppm) 21.5 (CH3),
21.6 (CH3), 44.0 (CH2), 59.8 (CH–N), 126.4 (CH), 126.7 (4 ¥
CH), 127.6 (2 ¥ CH), 127.7 (CH), 128.5 (2 ¥ CH), 128.6 (CH),
129.1 (2 ¥ CH), 129.3 (CH), 129.5 (2 ¥ CH), 129.8 (CH), 132.8
(C), 132.9 (C), 135.2 (C), 136.3 (C), 140.2 (C), 142.8 (C), 144.3
(C); MS (ES) m/z 79Br: 605 ((M+Na)+),81Br: 607 ((M+Na)+),
HRMS m/z ((M+Na)+) calcd for C28H27N2NaO3S279Br 605.0544
found 605.0532, m/z ((M+Na)+) calcd for C28H27N2NaO3S281Br
607.0524 found 607.0511.
(1S,6R)-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-6-
isopropenyl-3-methylcyclohex-2-en-1-amine (8b)
Prepared following the typical amination procedure from (R)-
limonene, the corresponding C–H insertion product was obtained
(dichloromethane–ethyl acetate: 20/1) as an oily solid in 68% yield,
94% d.e (HPLC, Hypercarb column, 100 ¥ 4.6 mm, 5 mm, MeCN +
0.1% HCOOH/H2O + 0.1% HCOOH: 80/20, 1 mL min-1, tmaj
=
(R)-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-1-
(3-(o-bromophenyl)-1-phenylpropyl)amine (6h)
26.34 min). Rf 0.54 (heptane/ethyl acetate: 50/50); [a]2D0 - 1.6 (c
1.00, CHCl3); IR (neat, cm-1) 3236, 2924, 1596, 1436, 1300, 1257,
1149, 1104, 1088, 1015, 812; 1H NMR (300 MHz, CDCl3) d 1.52
(s, 3H, CH3), 1.66 (s, 3H, CH3), 1.69–1.78 (m, 2H, CH2), 1.84–1.91
Prepared following the typical amination procedure from 3-(o-
bromophenyl)propylbenzene, the corresponding C–H insertion
This journal is
The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 10401–10413 | 10409
©

(m, 2H, CH2), 2.17–2.24 (m, 1H, CH), 2.40 (s, 3H, CH3), 2.44 (s,
3H, CH3), 3.80–3.85 (m, 1H, CH–N), 4.72 (br s, 1H, 1CH2-isopren),
4.82 (br s, 1H, 1CH2-isopren), 4.88 (br s, 1H, CHvinyl), 5.77 (d, J =
7.5 Hz, 1H, NH), 7.22–7.31 (m, 4H, 4 ¥ CHAr), 7.79–7.86 (m,
4H, 4 ¥ CHAr); 13C NMR (75 MHz, CDCl3) d 19.8 (CH3), 21.5
(CH3), 21.6 (CH3), 23.3 (CH3), 25.3 (CH2), 28.5 (CH2), 47.6 (CH),
52.5 (CH–N), 112.8 (CH2-isopren), 120.0 (CHvinyl), 126.8 (2 ¥ CHAr),
127.8 (2 ¥ CHAr), 129.1 (2 ¥ CHAr), 129.7 (2 ¥ CHAr), 136.8 (C),
139.1 (C), 140.5 (C), 142.7 (C), 144.6 (C), 144.7 (C). MS (ES) m/z
459 ((M+H)+), 481 ((M+Na)+), HRMS m/z ((M+H)+) calcd for
C24H31N2O3S2 459.1776 found 459.1796.
CHAr), 129.2 (2 ¥ CHAr), 129.7 (2 ¥ CHAr), 136.6 (C), 140.4 (C),
142.8 (C), 144.6 (C), 149.8 (C); MS (ES) m/z 459 ((M+H)+), 481
((M+Na)+), HRMS m/z ((M+Na)+) calcd for C24H30N2NaO3S2
481.1596 found 481.1575.
(R)-3,7-dimethyl-5-[N-(p-toluenesulfonyl)-p-toluene-
sulfonimidoyl]aminoocta-2,6-dien-1-yl acetate (8e)
Prepared following the typical amination procedure from (E)-3,7-
dimethylocta-2,6-dienyl acetate, the corresponding C–H insertion
product was obtained (dichloromethane–ethyl acetate: 20/1) as a
clear oil in 90% yield, 90% d.e (HPLC, Hypercarb column, 100 ¥
4.6 mm, 5 mm, MeCN + 0.1% HCOOH/H2O + 0.1% HCOOH:
80/20, 1 mL min-1, tmaj = 29.28 min, or UPLC, BEH shield RP18
column, 50 ¥ 2.1 mm, 1.8 mm, MeCN + 0.1% HCOOH/H2O +
0.1% HCOOH: 55/45, 0.6 mL min-1, tmaj = 1.04 min). Rf 0.36
(heptane/ethyl acetate: 60/40); [a]2D0 + 25.4 (c 1.00, CHCl3); IR
(neat, cm-1) 3229, 1732 (C O (Ac)), 1596, 1443, 1232, 1151, 1105,
(1R,2S,5R)-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-4,6,6-
trimethylbicyclo[3.1.1]hept-3-en-2-amine (8c)
Prepared following the typical amination procedure from (R)-
pinene, the corresponding C–H insertion product was obtained
(dichloromethane–ethyl acetate: 20/1) as a white solid in 91%
yield, 95% d.e (HPLC, Hypercarb column, 100 ¥ 4.6 mm,
5mm, MeCN + 0.1% HCOOH/H2O + 0.1% HCOOH: 80/20,
1 mL min-1, tmaj = 17.25 min, or UPLC, BEH shield RP18 column,
50 ¥ 2.1 mm, 1.8 mm, MeCN + 0.1% HCOOH/H2O + 0.1%
HCOOH: 55/45, 0.6 mL min-1, tmaj = 1.40 min). Rf 0.60 (heptane–
1
1089, 1016, 812; H NMR (500 MHz, CDCl3) d (ppm) 1.51 (s,
3H), 1.55 (s, 3H), 1.60 (s, 3H), 2.03–2.14 (m, 2H, CH2), 2.08 (s,
3H, Ac), 2.41 (s, 3H), 2.44 (s, 3H), 4.11–4.14 (m, 1H, CH–N), 4.51
(d, J = 7.0 Hz, 2H, CH2-OAc), 4.90 (d, J = 9.0 Hz, 1H, CHvinyl-CHN),
5.32–5.34 (m, 1H, CHvinyl), 5.59 (d, J = 5.0 Hz, 1H, NH), 7.25–
7.30 (m, 4H), 7.78 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 8.5 Hz, 2H);
13C NMR (75 MHz, CDCl3) d (ppm) 16.2 (CH3), 18.1 (CH3),
21.0 (CH3, Ac), 21.5 (CH3), 21.6 (CH3), 25.5 (CH3), 45.9 (CH2),
50.8 (CH–N), 60.9 (CH2-OAc), 123.1 (CHvinyl), 124.1 (CHvinyl-CHN),
126.7 (2 ¥ CHAr), 127.9 (2 ¥ CHAr), 129.2 (2 ¥ CHAr), 129.5 (2 ¥
CHAr), 135.8 (C), 136.4 (C), 136.9 (C), 140.5 (C), 142.7 (C), 144.6
(C), 171.0 (C O, Ac); MS (ES) m/z 541 ((M+Na)+), HRMS
m/z ((M+Na)+) calcd for C26H34N2NaO5S2 541.1807 found
541.1779.
◦
ethyl acetate: 50/50); mp 55–57 C; [a]2D0 -10.6 (c 1.00, CHCl3);
IR (neat, cm-1) 3218, 2925, 1596, 1403, 1301, 1258, 1150, 1105,
1089, 1074, 1016, 1002, 810; 1H NMR (300 MHz, CDCl3) d 0.69
(s, 3H, CH3), 1.17–1.20 (m, 1H, 1CH2), 1.21 (s, 3H, CH3), 1.55–
1.57 (m, 3H, CH3), 1.91–1.95 (m, 1H, CH), 2.12–2.17 (m, 1H,
CH), 2.24–2.31 (m, 1H, 1CH2), 2.33 (s, 3H, CH3), 2.37 (s, 3H,
CH3), 3.70–3.73 (m, 1H, CH–N), 4.74–4.76 (m, 1H, CHvinyl), 5.83
(d, J = 9.0 Hz, 1H, NH), 7.15–7.25 (m, 4H, 4 ¥ CHAr), 7.71–7.75
(m, 4H, 4 ¥ CHAr); 13C NMR (75 MHz, CDCl3) d 20.3 (CH3),
21.5 (CH3), 21.6 (CH3), 22.7 (CH3), 26.2 (CH3), 28.6 (CH2), 44.4
(C), 46.5 (CH), 47.0 (CH), 54.1 (CH–N), 114.8 (CHvinyl), 126.8
(2 ¥ CHAr), 127.7 (2 ¥ CHAr), 129.1 (2 ¥ CHAr), 129.8 (2 ¥ CHAr),
136.4 (C), 140.4 (C), 142.8 (C), 144.6 (C), 150.5 (C); MS (ES) m/z
459 ((M+H)+), 481 ((M+Na)+), HRMS m/z ((M+Na)+) calcd for
C24H30N2NaO3S2 481.1596 found 481.1588.
Typical procedure for cleaving the sulfonimidoyl moiety
To
a
solution of the (N-(p-toluenesulfonyl)-p-toluene-
sulfonimidoyl)amino product in dichloromethane were added
3 equiv. of (Boc)2O and 0.5 equiv. of DMAP. The mixture
was stirred at room temperature for 12 h under argon. The
solvent was evaporated and the residue was purified by flash
chromatography (dichloromethane–ethyl acetate: 90/10) to afford
the Boc-protected products.
(1S,2R,5S)-[N-(p-Toluenesulfonyl)-p-toluenesulfonimidoyl]-4,6,6-
trimethylbicyclo[3.1.1]hept-3-en-2-amine (8d)
To a solution of the N-(Boc)sulfonimidamide product in
methanol were added 10 equiv. of magnesium (powder, 50 Mesh).
The mixture was sonicated at room temperature for 25 min in
Prepared following the typical amination procedure from (S)-
pinene, the corresponding C–H insertion product was obtained
(dichloromethane–ethyl acetate: 20/1) as a white solid in 71%
yield, 96% d.e (HPLC, Hypercarb column, 100 ¥ 4.6 mm,
5 mm, MeCN + 0.1% HCOOH/H2O + 0.1% HCOOH: 90/10,
1 mL min-1, tmaj = 13.◦08 min). Rf 0.60 (heptane/ethyl acetate:
50/50); mp 123–125 C; [a]2D0 + 142.0 (c 1.00, CHCl3); IR
(neat, cm-1) 3236, 2920, 1596, 1420, 1300, 1245, 1150, 1104, 1088,
1016, 1000, 811; 1H NMR (300 MHz, CDCl3) d 0.69 (s, 3H, CH3),
1.11–1.14 (m, 1H, 1CH2), 1.12 (s, 3H, CH3), 1.62–1.64 (m, 3H,
CH3), 1.69–1.75 (m, 1H, CH), 1.89–1.93 (m, 1H, CH), 2.10–2.17
(m, 1H, 1CH2), 2.34 (s, 3H, CH3), 2.36 (s, 3H, CH3), 3.78–3.83 (m,
1H, CH–N), 5.12–5.15 (m, 1H, CHvinyl), 5.77 (d, J = 8.7 Hz, 1H,
NH), 7.17–7.22 (m, 4H, 4 ¥ CHAr), 7.69–7.77 (m, 4H, 4 ¥ CHAr);
13C NMR (75 MHz, CDCl3) d 20.3 (CH3), 21.5 (CH3), 21.6 (CH3),
22.7 (CH3), 26.2 (CH3), 28.6 (CH2), 44.3 (C), 46.3 (CH), 46.9
(CH), 54.1 (CH–N), 116.2 (CHvinyl), 126.8 (2 ¥ CHAr), 127.7 (2 ¥
R
a Bransonicꢀ DTH-2510 apparatus (Digital control, plus Heat
and Timer, 2.8 L, 130 W). The solvent was evaporated and the
residue was diluted with ether. The organic layer was washed with a
solution of saturated NH4Cl, dried over MgSO4 and concentrated
under vacuum to afford a clear oil which was purified by flash
chromatography (dichloromethane–ethyl acetate: 90/10) to afford
the deprotected amines.
(1R,6S)-N-(tert-butyloxycarbonyl)-6-isopropenyl-3-methyl
cyclohex-2-en-1-amine (9a) and (1S,6R)-N-(tert-butyloxy-
carbonyl)-6-isopropenyl-3-methylcyclohex-2-en-1-amine (9b)
Application of the typical deprotection procedure to compounds
8a and 8b allowed us to isolate the corresponding Boc-protected
products (heptane–ethyl acetate: 90/10) as oily solids in 46% and
10410 | Dalton Trans., 2010, 39, 10401–10413
This journal is
The Royal Society of Chemistry 2010
©

48% yield, respectively. Rf 0.42 (heptane–ethyl acetate: 90/10);
Typical procedure for cross experiments with quasi-enantiomeric
sulfonimidamides
IR (neat, cm-1) 3356, 2924, 1683, 1515, 1364, 1324, 1245, 1159,
1
1128, 1004, 864; H NMR (500 MHz, CDCl3) d 1.44 (s, 9H, 3 ¥
(Based on the typical procedure for kinetic resolution of sul-
fonimidamides described in ref. 13b). In an oven-dried tube
CH3), 1.67 (s, 3H, CH3), 1.68–1.72 (m, 2H, CH2), 1.73 (s, 3H,
CH3), 1.91–2.06 (m, 3H, CH2 + CH), 4.14–4.17 (m, 1H, CH–
N), 4.34 (br s, 1H, NH), 4.76 (br s, 1H, 1CH2-isopren), 4.79 (br s,
1H, 1CH2-isopren), 5.35 (br s, 1H, CHvinyl); 13C NMR (75 MHz,
CDCl3) d 19.2 (CH3), 23.2 (CH3), 27.1 (CH2), 28.5 (3 ¥ CH3),
29.8 (CH2), 49.2 (CH), 49.7 (CH–N), 112.0 (CH2-isopren), 120.6 (C),
121.1 (C), 123.8 (CHvinyl), 136.4 (C), 155.7 (C O). MS (ES) m/z
252 ((M+H)+), 274 ((M+Na)+), HRMS m/z ((M+Na)+) calcd for
C15H25NNaO2 274.1783 found 274.1781.
˚
were introduced 4 A molecular sieves (100 mg), chiral rhodium
catalyst Rh2{(S)-nta}4 (2) (3 mol%), 1.1 equiv. of (S or R)-N-(p-
toluenesulfonyl)-p-toluenesulfonimidamide (1) and 1.1 equiv. of
(S or R)-N-(p-toluenesulfonyl)-p-nitrobenzene-sulfonimidamide
(17), 1 mL of Cl2CHCHCl2/MeOH (v/v: 3/1) and substrate
(0.2 mmol). After stirring at room temperature for 5 min, the
mixture was cooled to -35 ◦C, and PhI(OCOt-Bu)2 (1.1 equiv.)
was added. The mixture was stored in a freezer (-35 ◦C) for 3 days.
After reaction, 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 C–H insertion products (CH2Cl2–EtOAc: 20/1) and
the sulfonimidamide (CH2Cl2–EtOAc: 5/2).
(1R,6S)-N-Boc-aminolimonene 9a: [a]2D0 + 66.8 (c 0.43, CHCl3),
(1S,6R)-N-Boc-aminolimonene 9b: [a]2D0 - 58.0 (c 0.43, CHCl3).
3,7-dimethyl-7-[N-(p-toluenesulfonyl)-p-toluene-
sulfonimidoyl]aminoocta-1-yl acetate (11)
Prepared following the typical amination procedure from 5
equivalents of 3,7-dimethyloctylacetate, the corresponding C–H
insertion product was obtained (dichloromethane–ethyl acetate:
20/1) as a clear oil in 30% yield. Rf 0.48 (heptane/ethyl acetate:
50/50); IR (neat, cm-1) 3239, 2926, 1732 (C O (Ac)), 1596, 1367,
(1R)-[N-(p-toluenesulfonyl)-p-nitrobenzenesulfonimidoyl]-1-amino
indan (18)
Prepared following the cross experiments procedure from
indane using 1.1 equiv. of (+)-(R)-N-(p-toluenesulfonyl)-p-
toluenesulfonimidamide (1) and 1.1 equiv. of (-)-(S)-N-(p-
toluenesulfonyl)-p-nitrobenzenesulfonimidamide (17), the corre-
sponding C–H insertion product was obtained (dichloromethane–
ethyl acetate: 20/1) as a white solid in 72% yield and >98% d.e.
(HPLC, Hypercarb column, 100 ¥ 4.6 mm, 5mm, MeCN + 0.2%
TFA/H2O + 0.2 %TFA: 100/0, 1 mL min-1, tmaj = 29.16 min). Rf
0.42 (heptane/ethyl acetate: 60/40); mp 159–161 ◦C; [a]D20 + 82.8 (c
1.00, CHCl3); IR (neat, cm-1) 3161, 1524, 1300, 1288, 1146, 1108,
1078, 1062, 986; 1H NMR (300 MHz, CDCl3) d 1.61–1.72 (m, 1H,
CH2–Ha), 2.00–2.11 (m, 1H, CH2–Ha), 2.35 (s, 3H), 2.58–2.69 (m,
1
1245, 1149, 1103, 1090, 1068, 1017, 812; H NMR (500 MHz,
CDCl3) d (ppm) 0.88–0.91 (m, 3H), 1.01–1.06 (m, 1H, CH(2)), 1.11
(s, 3H), 1.17–1.20 (m, 1H, CH(2)), 1.23 (s, 3H), 1.39–1.45 (m, 2H,
CH2), 1.50–1.54 (m, 2H, CH2), 1.61–1.66 (m, 2H, CH2), 2.06 (s,
3H, Ac), 2.42 (s, 3H), 2.43 (s, 3H), 4.06–4.14 (m, 2H, CH2-OAc),
6.21 (br s, 1H, NH), 7.26–7.29 (m, 4H), 7.30–7.32 (m, 1H, CH),
7.79–7.84 (m, 4H); 13C NMR (75 MHz, CDCl3) d (ppm) 19.4
(CH3), 21.0 (CH3, Ac), 21.1 (CH2), 21.5 (CH3), 21.6 (CH3), 27.0
(CH3), 28.0 (CH3), 35.5 (CH2), 37.0 (CH2), 43.5 (CH2), 59.5 (C–N),
62.9 (CH2-OAc), 77.2 (CH), 126.7 (2 ¥ CH), 127.7 (2 ¥ CH), 129.2
(2 ¥ CH), 129.6 (2 ¥ CH), 138.7 (C), 140.4 (C), 142.8 (C), 144.3
(C), 171.2 (C O, Ac); MS (ES) m/z 545 ((M+Na)+), HRMS
m/z ((M+Na)+) calcd for C26H38N2NaO5S2 545.2120 found
545.2114.
’
’
1H, CH2 -Hb), 2.78–2.88 (m, 1H, CH2 -Hb), 4.80 (q, J = 7.8 Hz, 1H,
CH–N), 6.49 (d, J = 8.5 Hz, 1H, NH), 7.11–7.29 (m, 6H), 7.68–
7.80 (m, 2H), 8.11 (d, J = 8.5 Hz, 2H), 8.24 (d, J = 8.5 Hz, 2H); 13
C
NMR (75 MHz, CDCl3) d 21.6 (CH3), 30.0 (CH2b), 33.3 (CH2a),
58.7 (CH–N), 124.4 (2 ¥ CHAr), 124.7 (CHAr), 124.9 (CHAr), 126.7
(2 ¥ CHAr), 127.1 (CHAr), 127.9 (CHAr), 129.0 (2 ¥ CHAr), 129.4
(2 ¥ CHAr), 139.8 (C), 140.4 (C), 142.7 (C), 143.5 (C), 145.8 (C),
150.4 (C); MS (ES) m/z 494 ((M+Na)+), HRMS m/z ((M+Na)+)
calcd for C22H21N3NaO5S2 494.0820 found 494.0819.
[N-(p-toluenesulfonyl)-p-toluenesulfonimidoyl]-
octahydronaphthalen-4a(2H)-amine (15)
Prepared following the typical amination procedure from cis-
decalin, the corresponding C–H insertion product was obtained
(dichloromethane–ethyl acetate: 20/1) as an oily solid in 89% yield.
Rf 0.51 (heptane–ethyl acetate: 50/50); IR (neat, cm-1) 3231, 2921,
2856, 1699, 1596, 1444, 1314, 1244, 1151, 1104, 1083, 1048, 1015,
(1R)-[N-(p-toluenesulfonyl)-p-toluenesulfonimidoyl]-1-amino
ethylbenzene (24)
Prepared following the typical amination procedure from ethyl-
benzene, the corresponding C–H insertion product was obtained
(dichloromethane–ethyl acetate: 20/1) as a white solid in 80%
yield, 98% d.e. (HPLC, Hypercarb column, 100 ¥ 4.6 mm,
5 mm, MeCN + 0.1% HCOOH/H2O + 0.1% HCOOH: 70/30,
1 mL min-1, tmaj = 12.◦03 min). Rf 0.40 (heptane–ethyl acetate:
50/50); mp 157–158 C; [a]2D0 + 103.0 (c 0.52, CHCl3); IR
(neat, cm-1) 3289, 1597, 1493, 1317, 1244, 1153, 1113, 1087, 1068,
1
971, 903, 809; H NMR (300 MHz, CDCl3) d (ppm) 1.18–1.63
(m, 16H, 8 ¥ CH2), 2.32 (s, 3H, CH3), 2.35 (s, 3H, CH3), 2.97–
3.04 (m, 1H, CH), 3.19–3.29 (m, 1H, CH), 5.66–5.88 (m, 2H,
NH +NH), 7.15–7.21 (m, 4H, 4 ¥ CHAr), 7.73 (td, J = 1.7 Hz
and 8.3 Hz, 4H, 4 ¥ CHAr); 13C NMR (75 MHz, CDCl3) d
20.7 (CH2), 21.6 (2 ¥ CH3), 25.0 (CH2), 25.4 (CH2), 26.6 (CH2),
28.0 (CH2), 30.7 (CH2), 31.5 (CH2), 33.9 (CH2), 49.4 and 54.0
(CH + CH), 126.7 (2 ¥ CHAr), 127.7 (2 ¥ CHAr), 129.2 (2 ¥
CHAr), 129.7 (2 ¥ CHAr), 136.4 (C), 140.5 (C), 142.7 (C), 144.5
(2 ¥ C); MS (ES) m/z 461 ((M+H)+), 483 ((M+Na)+), HRMS
m/z ((M+Na)+) calcd for C24H32N2NaO3S2 483.1752 found
483.1735.
1
1033; H NMR (500 MHz, CDCl3) d (ppm) 1.35 (d, J = 7.0 Hz,
3H, CH3), 2.40 (s, 3H), 2.42 (s, 3H), 4.51 (q, J = 7.0 Hz, 1H,
CH–N), 6.18 (d, J = 7.0 Hz, 1H, NH), 7.20–7.31 (m, 9H), 7.77–
7.80 (m, 4H); 13C NMR (75 MHz, CDCl3) d (ppm) 21.5 (CH3),
21.6 (CH3), 23.4 (CH3), 54.3 (CH–N), 126.8 (2 ¥ CHAr), 127.2
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The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 10401–10413 | 10411
©

(2 ¥ CHAr), 128.1 (CHAr), 128.2 (2 ¥ CHAr), 129.0 (2 ¥ CHAr),
129.6 (2 ¥ CHAr), 130.0 (2 ¥ CHAr), 136.4 (C), 140.8 (C), 142.1
(C), 143.2 (C), 145.0 (C); MS (ES) m/z 428 (M+), HRMS m/z
((M+Na)+) calcd for C22H24N2NaO3S2 451.1126 found 451.1103.
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1124.
(1R)-[N-(p-toluenesulfonyl)-p-toluenesulfonimidoyl]-1-amino-1-
deuterio-ethylbenzene (24-d)
Prepared following the typical amination procedure from ethyl-
a,a-d2-benzene, the corresponding C–H insertion product was
obtained (dichloromethane–ethyl acetate: 20/1) as a pale yellow
solid in 25% yield. Rf 0.48 (heptane–ethyl acetate: 50/50); mp
◦
150–152 C; IR (neat, cm-1) 3259, 2927, 1594, 1450, 1388, 1312,
6 R. H. Crabtree, J. Chem. Soc., Dalton Trans., 2001, 2437.
1260, 1148, 1100, 1060, 1015, 972; 1H NMR (500 MHz, CDCl3) d
(ppm) 1.35 (s, 3H, CH3), 2.40 (s, 3H), 2.42 (s, 3H), 6.14 (br s, 1H,
NH), 7.20–7.31 (m, 9H), 7.76–7.79 (m, 4H); 13C NMR (75 MHz,
CDCl3) d (ppm) 21.6 (2 ¥ CH3), 22.8 (CH3), 53.5 (t, J = 21.3 Hz,
C-D), 126.3 (2 ¥ CHAr), 126.8 (2 ¥ CHAr), 127.7 (CHAr), 127.8
(2 ¥ CHAr), 128.6 (2 ¥ CHAr), 129.2 (2 ¥ CHAr), 129.7 (2 ¥ CHAr),
136.0 (C), 140.3 (C), 141.5 (C), 142.8 (C), 144.6 (C); MS (ES) m/z
430 ((M+H)+), 452 ((M+Na)+), HRMS m/z ((M+Na)+) calcd for
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1
C22 H232HN2NaO3S2 452.1189 found 452.1199.
Typical procedure for Hammett experiments
˚
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 (-)-(1) (65 mg,
0.2 mmol). The tube was capped with a rubber septum and
purged with argon. 1,1,2,2-Tetrachloroethane (0.75 mL) and
methanol (0.25 mL) were added under argon, and the mixture
was stirred for 5 min before addition of the substrates (10 equiv.
of ethylbenzene, 2.0 mmol and 10 equiv. of para-substituted
ethylbenzene, 2.0 mmol). The tube was cooled to -35 ◦C, and
bis(tert-butylcarbonyloxy)iodobenzene (98 mg, 0.24 mmol) was
added. The mixture was stored in the freezer (-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. Product ratios were determined
by 1H NMR of either the unpurified reaction mixture or the pure
compounds isolated after flash chromatography on silica gel.
Acknowledgements
We would like to thank the Institut de Chimie des Substances
Naturelles and ANR-08-BLAN-0013-01 for financial support and
fellowships (F.C., C.L. and C.L.). Supports and sponsorships
concerted by COST Action D40 “Innovative Catalysis: New
Processes and Selectivities” are also kindly acknowledged.
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10412 | Dalton Trans., 2010, 39, 10401–10413
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The Royal Society of Chemistry 2010
©

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23 It should be pointed out that an unknown product resulting from a
reaction between the metallanitrene and BHT was also isolated in the
case of 2-methylbutane (yield in the 20–25% range). This could be
responsible for the lower yield observed.
15 C–H amination of 3f was unsuccessfully run at various temperatures
(rt or 40 ◦C) in the presence of 10 mol% of rhodium(II) catalyst.
Application of conditions previously described by Du Bois (see ref. 12e)
and involving use of Rh2(esp)2 and a sulfamate, led to the formation of
the corresponding C–H aminated product with a low yield of 18%.
16 A test experiment starting from the homolog 1,4-diphenylbutane did
not afford the corresponding C–H aminated product.
17 The observed ratio of 70% could have been attributed to the diastereos-
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out in the case of 6g by removing the o-bromo substituent under
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obtained with the p-nitro and the p-bromo derivatives. An acceptable
linearity was observed with a calculated rTEvalue of +0.82 (R2 = 0.91).
This journal is
The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 10401–10413 | 10413
©