Uncatalyzed Oxidative C?H Amination of 9,10-Dihydro-9-Heteroanthracenes: A Mechanistic Study

Article abstract of DOI:10.1002/chem.201900377

A new method for the one-step C?H amination of xanthene and thioxanthene with sulfonamides is reported, without the need for any metal catalyst. A benzoquinone was employed as a hydride (or two-electron and one-proton) acceptor. Moreover, a previously unknown and uncatalyzed reaction between iminoiodanes and xanthene, thioxanthene and dihydroacridines (9,10-dihydro-9-heteroanthracenes or dihydroheteroanthracenes) is disclosed. The reactions proceed through hydride transfer from the heteroarene substrate to the iminoiodane or benzoquinone, followed by conjugate addition of the sulfonamide to the oxidized heteroaromatic compounds. These findings may have important mechanistic implications for metal-catalyzed C?H amination processes involving nitrene transfer from iminoiodanes to dihydroheteroanthracenes. Due to the weak C?H bond, xanthene is an often-employed substrate in mechanistic studies of C?H amination reactions, which are generally proposed to proceed via metal-catalyzed nitrene insertion, especially for reactions involving nitrene or imido complexes that are less reactive (i.e., less strongly oxidizing). However, these substrates clearly undergo non-catalyzed (proton-coupled) redox coupling with amines, thus providing alternative pathways to the widely assumed metal-catalyzed pathways.

Full text of DOI:10.1002/chem.201900377

A Journal of
Accepted Article
Title: Uncatalyzed Oxidative C‒H Amination of 9,10-Dihydro-9-
Heteroanthracenes: A Mechanistic Study
Authors: Nicolaas P. van Leest, Lars Grooten, Jarl Ivar van der Vlugt,
and Bas de Bruin
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To be cited as: Chem. Eur. J. 10.1002/chem.201900377
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10.1002/chem.201900377
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Uncatalyzed Oxidative C‒H Amination of 9,10-Dihydro-9-
Heteroanthracenes: A Mechanistic Study
Nicolaas P. van Leest, Lars Grooten, Jarl Ivar van der Vlugt and Bas de Bruin*[a]
Abstract: A new method for the one-step C‒H amination of xanthene
and thioxanthene with sulfonamides is reported, without the need for
any metal catalyst. A benzoquinone is employed as a hydride (or two-
electron and one-proton) acceptor. Moreover, a previously unknown
and uncatalyzed reaction between iminoiodanes and xanthene,
thioxanthene
and
dihydroacridines
(9,10-dihydro-9-
heteroanthracenes or dihydroheteroanthracenes) is disclosed. The
reactions proceed via hydride transfer from the heteroarene substrate
to the iminoiodane or benzoquinone, followed by conjugate addition
of the sulfonamide to the oxidized heteroaromatic compounds. These
findings may have important mechanistic implications for metal-
catalyzed C‒H amination processes involving nitrene transfer from
iminoiodanes to dihydroheteroanthracenes. Due to the weak C‒H
bond, xanthene is an often-employed substrate in mechanistic studies
of C‒H amination reactions, which are generally proposed to proceed
via metal-catalyzed nitrene insertion, especially for reactions involving
nitrene or imido complexes that are less reactive (i.e. less strongly
oxidizing). However, these substrates clearly undergo non-catalyzed
(proton-coupled) redox coupling with amines, thus providing
alternative pathways to the widely assumed metal-catalyzed
pathways.
Figure 1. Comparison between previously reported (transition metal) catalyzed
amination of C‒H bonds and the catalyst-free protocols presented in this work.
Introduction
Our group is interested in the formation and characterization
of new metal-nitrene complexes from known nitrene precursors
and ideally directly from primary amines. As others, we adopted
the reasoning that successful nitrene transfer could be dictated by
the relative bond dissociation free energy (BDFE) of the CH
bond, with a lower BDFE expectedly resulting in faster nitrene
The development of new synthetic methods for the synthesis
of (secondary) amines is a constantly evolving field, due to the
ever increasing demand for nitrogen containing compounds in e.g.
pharmaceuticals and agrochemicals.[1] Direct (sp3) CH amination
via metal-nitrene intermediates has received increasing attention
in the last two decades, as no pre-functionalization of the
hydrocarbon substrates is required.[2-5] Key developments are the
use of activated[6-8] and non-activated organic azides,[9-15]
Haloamine-T[16,17] and (in situ generated) iminoiodanes (PhI=NR)
as nitrene precursors (Figure 1).[18-23] Transition metal complexes
have proven to be excellent catalysts for these amination
reactions, and the commonly accepted mechanism comprises the
formation of a reactive metal-nitrene intermediate, followed by
stepwise hydrogen atom abstraction and radical recombination or
concerted insertion of the nitrene into the CH bond.[3,5,24] In
addition, organocatalysts are reported that are also capable of
nitrene transfer.[25,26]
insertion.[25,27-33]
Dihydroheteroanthracenes
(xanthene,
thioxanthene and dihydroacridine derivatives) have low CH bond
dissociation energies (BDE) in the range of 74-81 kcal mol-1.[34]
Therefore, dihydroheteroanthracenes are often assumed to be
suitable model substrates to test for basic CH amination activity,
even for relatively non-reactive nitrene intermediates.[35]
Especially xanthene is a commonly used substrate to investigate
reaction kinetics of such reactions.[28-31,33]
In the course of our investigations, we initially reasoned in a
similar manner. However, much to our surprise, we observed that
sulfonamides are able to react with xanthene and thioxanthene in
the presence of a benzoquinone derivative as a sacrificial oxidant
and base, without the need for a (transition metal) catalyst. Even
more
interestingly,
we
react
also
with
observed
commonly
that
used
dihydroheteroanthracenes
iminoiodanes to afford the corresponding amination product in the
absence of any catalyst (Figure 1). To the best of our knowledge,
this background reaction has not been reported in literature. In
this contribution, we disclose the details of catalyst-free amination
reactions of dihydroheteroanthracenes. The obtained insights are
of considerable interest for researchers interested in (transition
metal) catalyzed nitrene transfer, as we describe hitherto
[a]
N. P. van Leest, L. Grooten, Dr. Ir. J. I. van der Vlugt, Prof. Dr. B. de
Bruin
Van ’t Hoff Insitute for Molecular Sciences (HIMS)
University of Amsterdam (UvA)
Science Park 904, 1098 XH Amsterdam (The Netherlands)
E-mail: b.debruin@uva.nl
Supporting information for this article is given via a link at the end of
the document.
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unknown, uncatalyzed background reactions and report a new
mechanism for amination of dihydroheteroanthracenes that is
very different from the generally accepted (metal) catalyzed
nitrene transfer processes.
Table 1. Optimization of the reaction conditions for the amination of
xanthene with TsNH2 and chloranil.
Results and Discussion
During our efforts to develop new (transition) metal catalyzed
sp3 CH amination strategies directly from amines, we stumbled
across the uncatalyzed amination of xanthene with
p-toluenesulfonamide (TsNH2) in the presence of tetrachloro-p-
benzoquinone (chloranil) as an oxidant. We decided to optimize
the reaction conditions of this reaction (Table 1) in order to shine
more light on this unexpected reaction. The C‒H aminated
product 1 was obtained in 22-48% yield after 20 hours at 30 oC in
solvents most commonly used in nitrene transfer reactions
(entries 1-4). Decreasing the reaction time to 5 hours resulted in
a lower yield, whereas increasing the reaction temperature to
60 oC afforded 1 in 43% yield in benzene (entries 5 and 6).
Entry
Solvent
C6H6
Temp (oC)
Time (h)
Yield[a]
26%
22%
23%
48%
18%
43%
72%
83%
1
30
30
30
30
30
60
60
60
20
20
20
20
5
2
PhCH3
MeCN
CH2Cl2
C6H6
3
4
5
6
C6H6
5
7
C6H6
20
20
o
Performing the reaction at 60 C for a longer time (20 hours) in
benzene led to the formation of 1 in 72% or 83% in the presence
and absence of light, respectively (entries 7 and 8). The
conditions in entry 8 proved to be the optimal reaction conditions.
For practical purposes we employed the conditions in entry 7 for
further screening (vide infra).[36] Dilution of the total concentration
from 50 mM to 25 mM, increasing the amount of chloranil or
performing the reaction under an argon atmosphere did not
improve the yield (see Table S1 in the Supporting Information). It
is worth mentioning that the reaction can be performed without
drying the solvent and that the only by-product is xanthone
(3-7%).[37]
8[b]
C6H6
[a] Based on 1H-NMR integration using 1,3,5-tris-(tert-butyl)benzene as an
internal standard. [b] Performed in absence of light.
With the optimized conditions in hand, we screened various
p-benzoquinone derivatives for their reactivity in the amination of
xanthene by TsNH2 (Scheme 1). The mildly oxidizing parent
p-benzoquinone did not lead to conversion of xanthene. However,
the
use
of
2-chloro-p-benzoquinone,
2,6-dichloro-p-
benzoquinone,
chloranil or 2,3-dichloro-5,6-dicyano-p-
benzoquinone (DDQ) afforded 1 in 17, 34, 72 and 81%,
respectively. The trends in the yield of 1 nicely correlate with the
reported 1e- and 2e-
/
1H+ reduction potentials of the
corresponding benzoquinones.[38] The more oxidizing quinones
lead to higher yields, therefore indicating that oxidation of one of
the substrates is involved in the reaction mechanism. DDQ, the
strongest oxidant employed, is capable of oxidizing 1 to the
corresponding imine, which was detected as a side product (10%
yield). Moreover, when using this oxidant 9% of xanthone was
formed. Other quinones showed the same correlation between
yield and redox potential, but afforded larger amounts of
(unidentified) side products (Table S2 in the SI).
A small, but representative substrate scope of different
sulfonamides and dihydroheteroanthracenes was explored, as
shown in Scheme 2. TsNH2 and 2,2,2-trichloroethoxysulfonamide
(TcesNH2) form 1 (72%) and 2 (67%) in comparable yields.
However, the use of p-nitrobenzenesulfonamide (NsNH2) yields
only 15% of 3 with a considerable amount of xanthone. This is
Scheme 1. Screening of various p-benzoquinones for the synthesis of 1 from
xanthene and TsNH2. Yields based on 1H NMR integration using 1,3,5-tris-(tert-
butyl)benzene as internal standard. [a] 10% oxidation of 1 to the imine and 9%
xanthone observed. Potentials for the 1e- (Q/Q-) and 2e-/1H+ (Q,H+/HQ-) couples
versus NHE in water.[38] Potentials versus Fc+/0 are estimated by a correction of
-0.40 V versus NHE.[39]
most likely caused by the reduced nucleophilicity of NsNH2
compared to TsNH2 and TcesNH2, thus leading to higher yields of
reaction products stemming from reaction with H2O (which is
present in the solvent, vide infra). Performing the reaction in
thoroughly dried benzene led to reduced xanthone formation (2%),
but does not increase the yield of 3. 9,10-Dihydroanthracene did
not afford the desired product 4, but generated anthracene in 22%
yield. Similarly, various 9,10-dihydroacridine derivatives did not
afford the desired products 5-H, 5-Me or 5-Boc; 9,10-
dihydroacridine was quantitatively converted to acridine,
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N-methyldihydroacridine was oxidised to unidentified products
and N-Boc-9,10-dihydroacridine was not converted. However,
thioxanthene reacted in a similar manner as xanthene producing
product 6 in 37% yield. Other hydrocarbon substrates with weak
CH bonds, e.g. ethylbenzene and cyclohexadiene, did not afford
the desired aminated products (Table S3 in the SI).
nucleophilic attack of the amine. We therefore investigated the
redox potentials of the dihydroheteroanthracenes with cyclic
voltammetry and differential pulse voltammetry (Figure S26 and
S27). All observed electrochemical oxidations were found to be
irreversible, with the potentials varying from +0.32
V
(dihydroacridine) to +1.28 V (dihydroanthracene) versus Fc+/0
,
see Figure 2. These potentials seem to be too high for outer-
sphere single-electron transfer from the dihydroheteroanthracene
to chloranil in absence of a proton donor (Eo = 0.43 V versus
½
Fc+/0 in DCM, see Figure S29 in the SI).
Figure 2. Eo versus Fc+/0 in DCM for various dihydroheteroanthracenes,
½
obtained from DPV measurements in a three-electrode cell with a glassy carbon
working electrode, Pt auxiliary electrode and leak-free Ag/AgCl 3.0 M KCl
reference electrode.
However, as alternative, the reaction could proceed via a
hydride transfer step from the dihydroheteroanthracenes to
chloranil, followed by conjugate addition of the sulfonamide to the
cationic heteroanthracenium derivative. The two-electron
oxidation and deprotonation of xanthene, thioxanthene and
N-methyldihydroacridine has previously been studied by
electrochemical or combined radiolytic and photochemical
oxidation and hydride transfer to triphenylmethyl perchlorate
(Scheme 3a and 3b).[40-42]
Scheme
2.
Substrate
scope
with
different
amines
and
dihydroheteroanthracenes. R = Ts, Tces or Ns. Yields based on 1H NMR
integration using 1,3,5-tris-(tert-butyl)benzene or 1,3,5-trimethoxybenzene as
an internal standard. [a] 28% xanthone formation and 2% xanthone formation in
anhydrous solvent. [b] 22% anthracene formation. [c] Quantitative conversion
to acridine. [d] Quantitative conversion of substrate, no conversion of TsNH2.
Tetrachloro-p-hydroquinone formation was observed by 1H
NMR
spectroscopy
for
all
reactions
where
the
dihydroheteroanthracene was converted. We also obtained
crystals of tetrachloro-p-hydroquinone from the reaction mixture,
and single crystal X-ray diffraction analysis of these crystals
confirmed the formation of the aromatic hydroquinone (Figure
S25 in the SI). This, in combination with the observed oxidation of
the dihydroheteroanthracenes and absence of reaction between
chloranil and TsNH2, proves that chloranil is acting as a proton
and electron acceptor in the oxidative amination process.
Moreover, in absence of a sulfonamide, the only formed product
is xanthone.[37] To rule out the possible involvement of xanthone
in the formation of 1 through nucleophilic reaction of the
sulfonamide with the carbonyl moiety, we also tested xanthone as
the substrate under the same reaction conditions. However,
neither in presence or absence of chloranil we observed formation
of any product. We therefore rule out that xanthone is involved in
the formation of the C‒H aminated product 1. Moreover, we
exclude the involvement of oxygen-sensitive free-radical species
that result from single-electron transfer, as the conversion and
yield do not change in presence or absence of oxygen (vide
supra).
Scheme 3. [a] Electrochemical or combined radiolytic and photochemical
stepwise
two-electron
and
one-proton
transfer
from
dihydroheteroanthracenes.[40,41] [b] Chemical hydride transfer of xanthene to
(Ph3C)ClO4.[42] [c] Stepwise two-electron and one-proton transfer from
9-substituted 10-methyl-9,10-dihydroacridines to DDQ.[43]
Surprised by these results, we wondered if these reactions
could perhaps proceed via two-electron oxidation and
deprotonation of the dihydroheteroanthracenes followed by
The hydride transfer reactions were shown to proceed
through sequential electron-proton-electron transfer to form the
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heteroanthracenium ions. Moreover, hydride transfer from
different 9-substituted 10-methyl-9,10-dihydroacridines (0.41 <
and sulfonamides as the nitrogen source in the amination of
xanthene and thioxanthene, we wondered whether the oxidant
and nitrogen group donor could also be combined in a single
reagent. We therefore decided to investigate the use of
hypervalent iodine reagents such as PhINTs could be used as
amide delivering oxidant in absence of a transition metal catalyst.
PhINTs is a common nitrene precursor for CH amination and
alkene aziridination reactions in combination with various
transition metal catalysts, but the free iminoiodane is considered
to be non-reactive towards hydrocarbons.[45] The hypervalent
iodine oxidant can be synthesized separately or formed in situ
from TsNH2 and di-(pivaloyloxy)iodobenzene (PhI(OPiv)2). To the
best of our knowledge, there is no report on the direct (non-
catalyzed) use of PhINTs for net CH amination. Recently though,
the use of an in situ generated hypervalent iodine reagent from
PhI and mCPBA was reported for a dehydrogenative C‒H
imination reaction with benzylic anilines.[46]
Eoox < 0.52 V versus Fc+/0) to DDQ (Eo = +0.70 V versus Fc+/0
)
½
has been studied in detail and was shown to proceed through
formation of a charge-transfer complex, followed by stepwise
electron-proton-electron transfer within the charge-transfer
complex (Scheme 3c).[43] Interestingly, it was shown that the initial
electron transfer step is in equilibrium and the proton transfer is
rate determining. Moreover, the separately prepared xanthylium
ion (obtained by hydride transfer of xanthene to triphenylmethyl
perchlorate) was recently indeed shown to react with
4-cyclohepta-2,4,5-trien-1-yl)aniline and pyrimidin-2-amine to
produce aminated products.[42,44] These data and observations
suggest that the reactions in Scheme 2 might indeed proceed via
initial hydride transfer as well.
To test our hypothesis that chloranil might act as a hydride
acceptor, we performed an intermolecular kinetic isotope
competition study with xanthene, xanthene-d2, TsNH2 and
chloranil. This led to a kinetic isotope effect (KIE) of 2.6, clearly
indicating that a proton or hydride transfer step is involved in the
rate determining step or in a pre-equilibrium leading to the rate
determining step. To obtain more insight in this step, we
monitored the reaction under standard conditions in absence of
sulfonamide. We were unable to detect the formation of the
xanthylium cation by 1H NMR spectroscopy. However, under
aerobic conditions larger amounts of oxidized products (xanthone
and xanthydrol) were observed than when the reaction was
performed under argon. This indicates that hydride transfer from
xanthene to chloranil is in a thermodynamically unfavorable
equilibrium with the xanthylium ion and the 2,3,5,6-tetrachloro-4-
hydroxyphenoxyl anion. However, in presence of a nucleophile
(H2O or sulfonamide) the xanthylium cation can react to form the
aminated or hydrated products (vide supra).
However, much to our surprise the reaction between
xanthene and PhINTs cleanly afforded 1 in 62% yield after 60
minutes and 68% yield (49% yield with in situ generated PhINTs)
after 20 hours, see Figure 4 and Scheme 4. Performing the
reaction at lower temperatures afforded 1 in 23% yield after 3.5
o
o
o
hours at 27 C, or 21% after 1.5 hours at 40 C. At 60 C, the
reaction almost reached full conversion after 1 hour. Using
PhINTces and PhINNs afforded 2 and 3 after 20 hours in
comparable yields as observed for the amination reaction
described in Scheme 2. Dihydroanthracene did not afford 4 and
reactions with ethylbenzene and 1,4-cyclohexadiene also did not
lead to the desired products. However, 5-Me (46%), 5-Boc (40%)
and
6
(47%) were obtained from the corresponding
dihydroacridines and thioxanthene after 1 hour. Interestingly, the
yield of 5-Me is higher after 1 hour than after 20 hours, suggesting
that the product is over-oxidized under these reaction
conditions.[47] Consistent with these observations, hydride
abstraction reactions from substrates similar to 5-Me have been
described (vide supra and Scheme 3c). In general (except for 5-
Me) the highest yields were obtained with pre-formed iminoiodane.
We therefore propose that chloranil acts as a hydride (or one-
proton and two-electron) acceptor for dihydroheteroanthracene
oxidation to form the heteroanthracenium ion and the 2,3,5,6-
tetrachloro-4-hydroxy-phenoxyl anion (Figure 3). Subsequent
conjugate addition of the sulfonamide to the heteroanthracenium
ion leads to product formation. The products 4 and 5 are not
formed, probably because the oxidized substrates from
anthracene and acridine are not electrophilic enough to react with
the weakly nucleophilic TsNH2. A control reaction with acridine as
the substrate indeed confirmed this (Scheme S4 in the SI).
Figure 3. Proposed reaction mechanism for the amination reaction with
chloranil and sulfonamides. X = O or S, R = Ts, Tces or Ns. Intermolecular KIE
(2.6) for the formation of 1.
Figure 4. Formation of 1 from xanthene and PhINTs at different temperatures
and reaction times. Yields based on 1H NMR integration using 1,3,5-tris-(tert-
butyl)benzene as an internal standard.
Intrigued by the results obtained using the combination of
chloranil as the hydride (or two-electron and one-proton) acceptor
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Scheme 5. Proposed mechanism for the C‒H amination of xanthene with
PhINTs. Energies in ΔGo at 298 K calculated with DFT at the B3LYP/def2-
TZVP/disp3/m4-grid/COSMO(benzene)
level
of
theory.
Graphical
representation of TS generated with IboView. Grey = C, white = H, purple = I,
yellow = S, red = O, blue = N.
Scheme 4. C‒H Amination of dihydroheteroanthracenes by PhINR (R = Ts,
Tces, Ns). Yields in parentheses concern reactions using in situ generated
PhINR, generated from RNH2 and PhI(OPiv)2 in the presence of MgO. Yields
based on 1H NMR integration using 1,3,5-tris-(tert-butyl)benzene or 1,3,5-
trimethoxybenzene as an internal standard. [a] Unidentified by-products formed.
Conclusions
To conclude, we have shown that xanthene and thioxanthene
can be aminated at the bridgehead sp3 CH position using
chloranil (or a related benzoquinone) as the oxidant and with
sulfonamides as the nitrogen donor. The benzoquinone acts as a
hydride (or two-electron and one-proton) acceptor and the
amination step proceeds through conjugate addition of a
sulfonamide to the formed heteroanthracenium ion. We have also
demonstrated that often-employed iminoiodanes can react in an
uncatalyzed manner with xanthene, thioxanthene and
dihydroacridines to afford the sp3 CH aminated products. The
Mechanistic insight was obtained from an intermolecular
competition experiment between xanthene and xanthene-d2 in the
reaction with PhINTs, which gave a KIE of 2.1. Analogous to the
2e- / 1H+ transfer described above, this suggests that proton or
hydride transfer is involved in, or before, the rate determining step.
Moreover, the reaction of dihydroacridine with PhINTs, which did
not afford the desired product 5-H, gave quantitative conversion
to acridine, iodobenzene and TsNH2. Hydride (or two-electron and
one-proton) transfer from the substrate to the iminoiodane is thus
a feasible process. For acridine the reaction stops at this point,
whereas for the substrates that afford the respective desired
product this step is followed by conjugate addition of the
sulfonamide to the oxidized substrate.
key mechanistic step is
a
hydride transfer from the
dihydroheteroanthracene to the iminoiodane, followed by
conjugate addition of an anionic sulfonamido intermediate to the
thus formed heteroanthracenium cation. This finding is relevant
for the chemical community interested in (the mechanisms of)
nitrene transfer catalysis, as it describes a previously unknown
background reaction that may compete with the postulated
catalytic cycles. We would therefore like to emphasize that this
uncatalyzed process should be carefully considered when using
xanthene-like substrates in mechanistic studies of catalytic
nitrene transfer reactions.
Based on the above combined data, we propose the reaction
mechanism shown in Scheme 5. The mechanism is supported by
DFT calculations at the B3LYP/def2-TZVP/disp3 level of theory
with implicit solvation in benzene (COSMO), a method that
typically affords reliable energies for charged intermediates.[38]
Endergonic hydride transfer from xanthene to the nitrogen atom
in PhINTs (ΔGo = +12.6 kcal mol-1 at 298 K) affords intermediate
B through transition state TS (ΔG‡ = +17.7 kcal mol-1).
Simultaneously with the hydride transfer, heterolytic cleavage of
the IN bond is observed, as the bond elongates from 1.999 Å (A)
to 2.447 Å (TS). The IN bond is completely cleaved in B, wherein
iodobenzene and the anionic tosylamide remain as a close-
contact pair. Slightly exergonic breaking of this close contact pair
affords the negatively charged tosylamido and positively charged
xanthylium ion (C, ΔGo = +10.1 kcal mol-1). Product D is formed
by a virtually barrierless conjugate addition in an overall highly
Experimental Section
General procedure for the oxidative amination with chloranil: A 4.0
mL vial was charged with TsNH2, NsNH2 or TcesNH2 (0.11 mmol, 1.1 eq),
the dihydroheteroanthracene (0.10 mmol, 1.0 eq), chloranil (0.11 mmol,
1.1 eq) and benzene (2.0 mL). The resulting suspension was stirred, with
a closed cap, under aerobic conditions at 60 C for 20 h. After cooling to
room temperature and concentration under reduced pressure, the yield
o
1
was determined by H NMR, using 1,3,5-tris-(tertbutyl)benzene or 1,3,5-
trimethoxybenzene as an internal standard.
exergonic reaction (ΔGo
=
62.1 kcal mol-1). The use of
dihydroacridine as the substrate is believed to follow the same
mechanism until intermediate C, after which the tosylamide
deprotonates the cationic N-protonated-acridinium cation to afford
acridine and TsNH2, as was experimentally observed.
General procedure for the oxidative amination with PhINR: A 4.0 mL
vial was charged with the PhINTs, PhINNs or PhINTces (0.11 mmol, 1.1
eq), the dihydroheteroanthracene (0.10 mmol, 1.0 eq) and benzene (2.0
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mL). The resulting suspension was stirred, with a closed cap, under
aerobic conditions at 60 oC for 20 h (or 1 hour if specified). After cooling to
room temperature and concentration under reduced pressure, the yield
was determined by H NMR, using 1,3,5-tris-(tertbutyl)benzene or 1,3,5-
trimethoxybenzene as an internal standard.
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Keywords: C‒H amination • Iminoiodane • Benzoquinone •
Dihydroheteroanthracene • Hydride Transfer
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10.1002/chem.201900377
Chemistry - A European Journal
FULL PAPER
Entry for the Table of Contents
FULL PAPER
Nicolaas P. van Leest, Lars Grooten, Jarl
Ivar van der Vlugt and Bas de Bruin*
Page No. – Page No.
Uncatalyzed Oxidative C‒H Amination
of 9,10-Dihydro-9-Heteroanthracenes:
A Mechanistic Study
The previously unknown direct and uncatalyzed C‒H amination of
dihydroheteroanthracenes is demonstrated by usage of i) sulfonamides and chloranil
or ii) iminoiodanes. The reactions proceed through hydride (or two-electron, one-
proton) transfer from the dihydroanthracene to the benzoquinone or the iminoiodane,
followed by conjugate addition of RSO2NH2 or RSO2NH, respectively.
This article is protected by copyright. All rights reserved.