Carbocation Catalyzed Bromination of Alkyl Arenes, a Chemoselective sp3 vs. sp2 C?H functionalization.

Article abstract of DOI:10.1002/adsc.201800788

The versatility of the trityl cation (TrBF₄) as a highly efficient Lewis acid organocatalyst is demonstrated in a light induced benzylic brominaion of alkyl-arenes under mild conditions. The reaction was conducted at ambient temperature under common hood light (55 W fluorescent light) with catalyst loadings down to 2.0 mol% using N-bromosuccinimide (NBS) as the brominating agent. The protocol is applicable to an extensive number of substrates to give benzyl bromides in good to excellent yields. In contrast to most previously reported strategies, this protocol does not require any radical initiator or extensive heating. For electron-rich alkyl-arenes, the trityl ion catalyzed bromination could be easily switched between benzylic sp³ C?H functionalization and arene sp² C?H functionalization by simply alternating the solvent. This chemoselective switch allows for high substrate control and easy preparation of benzyl bromides and bromoarenes, respectively. The chemoselective switch was also applied in a one-pot reaction of 1-methylnaphthalene for direct introduction of both sp³ C?Br and sp² C?Br functionality. (Figure presented.).

Full text of DOI:10.1002/adsc.201800788

Title: Carbocation Catalyzed Bromination of Alkyl Arenes, a
Chemoselective sp3 vs. sp2 C-H functionalization.
Authors: Johan Franzén, Shengjun Ni, and omar elhady
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800788
Link to VoR: http://dx.doi.org/10.1002/adsc.201800788

10.1002/adsc.201800788
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Carbocation Catalyzed Bromination of Alkyl Arenes, a Chemoselective
sp3 vs. sp2 C-H functionalization.
Shengjun Ni a, Mahmoud Abd El Aleem Ali Ali El Remaily a and Johan Franzén a *
a
KTH, Royal Institute of Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health,
Department of Chemistry / Division of Organic Chemistry, Teknikringen 30, SE-100 44 Stockholm, Sweden, phone:
+46-735424911; e-mail: jfranze@kth.se.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201####
Abstract. The versatility of the trityl cation (TrBF4) as a bromination could be easily switched between benzylic sp3
highly efficient Lewis acid organocatalyst is demonstrated in C-H functionalization and arene sp2 C-H functionalization
a light induced benzylic brominaion of alkyl-arenes under by simply alternating the solvent. This chemoselective
mild conditions The reaction was conducted at ambient switch allows for high substrate control and easy preparation
temperature under common hood light (55 W fluorescent of benzyl bromides and bromoarenes, respectively. The
light) with catalyst loadings down to 2.0 mol% using N-bromo chemoselective switch was also applied in a one-pot reaction
succinimide (NBS) as the brominating agent. The protocol is of 1-methylnaphthalene for direct introduction of both sp3 C-
applicable to an extensive number of substrates to give benzyl Br and sp2 C-Br functionality.
bromides in good to excellent yields. In contrast to most
previously reported strategies, this protocol does not require
any radical initiator or extensive heating. For electron-rich
alkyl-arenes, the trityl ion catalysed
Keywords: Carbocation; Trityl; Bromination; Benzylic;
EAS
This leads to a thorny problem concerning the
chemoselectivity between arene sp2 C-H and benzylic
sp3 C-H bond functionaliztion, in particularly for
activated and moderately activated arenes and mixture
of -bromoalkyl arenes and bromoarenes are always
formed in these cases. Interestingly, Shibatomi et al.
showed that chemoselectivity between arene sp2 C-H
and benzylic sp3 C-H bond functionaliztion could be
controlled by switching between a metal based Lewis
acid and a Brønsted acid for a limited number of
selected substrates.[10]
Introduction
Brominated aromatic compounds, e.g. -bromoalkyl
arenes and bromoarenes, are highly valuable and
versatile bulk chemicals in organic synthesis[1] and
material science,[2] in particular as benzylation
agents,[3] precursors for organometallic reagent[4] not
to mention their vast applications in transition metal
cross-coupling reactions.[5] -Bromoalkyl arenes can
be directly prepared from its corresponding alkyl arene
(benzylic sp3 C-H bond functionalization) using N–
bromosuccinimide (NBS) in the presences of a radical
initiator such as benzoyl peroxide or AIBN in
refluxing CCl4, a classic reaction known as the
Wohl−Ziegler reaction.[6] Since its establishment in
around 1940 numerous strategies has been reported as
improved versions of the original protocol.[7] Despite
this, the Wohl–Ziegler bromination generally requires
high reaction temperatures and radical initiators and
surprisingly small efforts have been made to develop
Lewis acid catalyzed protocols, thus allowing for
milder reaction conditions.[8] On the other hand, NBS
in the presences of Lewis acid is the general choice of
reagents for preparation of bromoarenes through
electrophilic aromatic substitution (arene sp2 C-H
bond functionalization).[9]
Herein we describe
a
mild and highly
chemoselective Lewis acid organocatalyzed protocol
for benzylic sp3 C-H bromination at room temperature
without any observable competing arene sp2 C-H
bromation even for highly activated aromatic
compounds. This reaction is photo-induced by simply
using standard hood fluorescent light (55 W F.L.), thus
completely avoiding the use of any toxic radical
initiator.
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800788
Advanced Synthesis & Catalysis
Arene sp2 C-H
functionalization
Benzylic sp3 C-H
functionalization
7
DCM
DCM
DCM
DCM
DCM
HBF4·Et2O
BF3·Et2O
p-TsOH
AlCl3
14
15
17
2
91
8
86
R
Br
R
9
90
R
Ph
Ph
Ph
Ph
BF4
O
BF4
Ph
Ph
(2 mol%)
10
11
84
(2 mol%)
N
Br
Br
Benzene or DCM, RT
CH3CN, RT
(p-MeOPh)- 21
(Ph)2CBF4
trace
R’
70-92%
55 W F.L.
R’
R’
O
55-96%
(NBS)
[a] The catalyst (2.0 mol%) was added to a solution of
toluene 1a (1.0 equiv.) and NBS 2 (1.0 equiv.) in DCM (0.3
M) and irradiated by 55 W F.L. for the indicated time. [b]
Determined by 1H NMR spectroscopy using CH3NO2 as the
internal standard. [c] 1.0 mol% catalyst was used. [d] The
reaction was performed in dark.
Scheme 1. Chemoselective trityl ion catalyzed sp3-C vs.
sp2-C bromination of alkyl-arenes.
For activated and weakly activated arenes, the
chemoselectivity of the bromination could be
completely switched from benzylic sp3 C-H
functionalization to arene sp2 C-H functionalization
simply by changing the solvent of the reaction. In
addition, this protocol completely suppresses over-
oxidation to give mono-brominated compounds as the
sole products.
In order to evaluate the ability of the trityl ion to
catalyze the benzylic bromination, a series of Lewis
and Brønsted acids were screened. Interestingly,
HBF4·Et2O, BF3·Et2O and p-toluenesulfonic acid all
turned out to be competent catalysts for this reaction
providing compatible yields to TrBF4 (Table 1, entries
1, 7-9), However, the latter acids all gave a
substantially increased reaction times compared to
TrBF4. In contrast, AlCl3 gave full conversion of the
starting materials in only 2 h, although with the lowest
yield of the screened Lewis acids (Table 1, entry 10).
The substantially less Lewis acidic mono-p-methoxy-
Results and Discussion
Carbocation catalyzed Benzylic sp3 C-H
functionalization. Recently the trityl cation (TrBF4)
has been reported as a novel and highly efficient Lewis
susbstituted
trityl
ion
((4-methoxyphenyl)-
acid
organocatalyst
for
various
organic
diphenylmethylium tetraflouroborate) did not catalyze
the bromination under these reaction conditions (Table
1, entry 11).
transformations.[11] In the course of our previous
studies we found that when toluene 1a and NBS 2 was
irradiated by standard hood fluorescent light (55 W
F.L.) in the presences of only 2.0 mol% TrBF4 as the
catalyst, full conversion was observed within 7 h
giving benzyl bromide 3a in 90% yield. It should be
noted that no observable traces of aromatic sp2 C-H
bromination was observed (Table 1, entry 1). The
catalyst loading could be even further reduced down to
1.0 mol% without any notable decrease in yield,
although the reaction time increased up to 24 h (Table
1, entry 2). Control experiment showed that no
reaction occurred in the absence of light or in the
absence of catalyst (Table 1, entries 3 and 4).
Changing the solvent from DCM to benzene had no
effect on the yield, however reaction time increased to
17 h for full conversion (Table 1, entry 5). On the other
hand, using the more polar solvent acetonitrile resulted
in a drastic decrease of yield (Table 1, entry 6).
After establishing the optimal conditions for the
trityl ion catalyzed benzylic bromination, we started to
investigate the reaction of various aromatic
compounds 1a-n (Table 2). Thus, using the standard
reaction conditions benzyl bromide 3a was isolated in
82% yield from toluene 1a after work up and flash
column. The isolated yield of 3a is lower compared to
the observed 1H NMR-yield for the same reaction most
likely due to the inherent instability generally observed
for benzyl bromide derivatives (cf. Table 2 and Table
1 entry 1). In addition, o- and p-bromotoluene 1b-c and
1-bromo-4-methylnaphthalene 1d all gave the
corresponding benzylbromides 3b-d in excellent
isolated yields (Table 2). Ethylbenzene 1e gave 3e in
92% yield. For 4-methyl-ethylbenzene 1f and
diphenylmethane 1g a clean benzylic bromination
occurred and the corresponding benzyl bromide could
1
be observed as the sole product by H NMR on the
Table 1. Optimization of reaction condition for the benzylic
crude reaction mixtures. Unfortunately, these
bromides turned out to be rather unstable and
spontaneously hydrolyzed during isolation and
purification and was isolated as the corresponding
alcohols 3f-3g in 66% and 71% yield respectively
(Table 2). It is worth mentioning that 4-methyl-
ethylbenzene was brominated exclusively on the ethyl-
group in preference of the methyl-group, which is
expected due to the higher stability of the intermediate
secondary radical species.
bromination.[a]
Entry Solvent Catalyst
T (h)
7
Yield (%)[b]
1
DCM
DCM
DCM
DCM
TrBF4
TrBF4
TrBF4
-
90
2[c]
3[d]
4
24
24
24
17
17
90
trace
trace
90
Electron-withdrawing
groups,
e.g.
nitro-,
5
Benzene TrBF4
CH3CN TrBF4
ethoxycarbonyl- and cyano-groups were all well
6
43
tolerated and provided 3h-3j with excellent yields.
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800788
Advanced Synthesis & Catalysis
Interestingly, as high as 55% isolated yield was
obtained
from
benzylic
bromination
of
toluenesulfonyl chloride despite the relatively unstable
chlorosulfonyl group (Table 2, 3k). 2-Methylfuran 1l
was selectively brominated at the methyl group to give
3l in 96% isolated yield (Table 2), in spite of the highly
acid sensitive furan moiety and the tendency of
electrophilic aromatic bromination often observed for
activated furans. The nitrogen containing heterocyclic
aromatics, quinoxaline and quinoline 1m-n turned out
to be less reactive and required 20 mol% catalyst
loading to achieve acceptable conversions. However,
under these conditions they were smoothly brominated
at the benzylic position to give 3m-n in good yields
(Table 2).
Scheme 2. Direct one-pot oxidative benzylic C-H amination.
Carbocation catalyzed bromination: Benzylic
sp3 vs. aromatic sp2 C-H functionalization: The
substrates screened so far (see Table 2) are moderately
activated or deactivated and this protocol showed high
selectivity for mono-bromination only at the benzylic
position. For more activated aromatic compounds,
such as anisol, aniline, etc. chemoselectivity became
an issue and electrophilic aromatic substitution started
to out-compete benzylic bromination to give mainly
bromoarenes. For example, bromination of 1-
methylnaphthalene 1o under the standard reaction
conditions (2.0 mol% TrBF4, NBS, 55 W F.L., DCM)
gave a 2:98 mixture of 1-(bromomethyl)naphthalene
3o and 1-bromo-4-methylnaphthalene 5o, almost
complete selectivity for arene sp2-C bromination
(Table 3, entry 1). The benzylic bromination pathway
could be completely suppressed by performing the
reaction in absence of light, which will prevent radical
formation giving 5o as the single observable product.
(Table 3, entry 2). In addition, using the more polar
solvent acetonitrile favored the intermediate ionic
species involved in the electrophilic aromatic
substitution leading to selective formation of 5o with
drastically reduced reaction time (Table 3, entry 3). In
fact, absence of light did not affect the selectivity of
the reaction in acetonitrile and no percussions to avoid
day/hood light were necessary (Table 3, entry 4).
Table 2. TrBF4 catalyzed benzylic bromination.[a]
Table 3. Optimization of reaction condition for the
chemoselective switch: Benzylic sp3 vs. aromatic sp2 C-H
functionalization.[a]
[a] TrBF4 (2.0 mol%, 0.25 M in DCM) was added to 1 (1.5
equiv.) and 2 (1.0 equiv.) in DCM (0.3 M) and irradiated by
55 W F.L. [b] 20 mol% of the catalyst was used.
[b]
Ratio
Entry
Solvent
t (h)
3o:5o
2:98
1
2[c]
DCM
20
20
2
DCM
0:100
0:100
0:100
100:0
This protocol was also extended into an easy
manageable, transition metal free, one-pot benzylic C-
H amination where NBS acts both as the oxidating
agent and the sources of nitrogen (Scheme 2). Simply,
after full conversion of toluene 1a using the standard
reaction conditions (NBS, TrBF4, 55 W F.L., DCM)
the solvent was changed to CH3CN followed by
addition of K2CO3. Subsequent heating of the resulting
reaction mixture at 80 °C for 24 h gave N-benzyl-
succinimide 4 in 90% isolated overall yield.[12]
3
CH3CN
CH3CN
benzene
4[c]
5
2
15
[a] The TrBF4 (2.0 mol%, 0.25 M in DCM) was added to a
solution of 1-methylnaphthalene 1o (1.2 equiv.) and NBS
(1.0 equiv.) in the indicated solvent (0.3 M) and irradiated
by 55 W F.L. [b] Determined by 1H NMR using CH3NO2 as
internal standard after completed reaction. [c] The reaction
was performed in dark.
On the other hand, we reasoned that selective
benzylic sp3-C bromination should be possible through
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800788
Advanced Synthesis & Catalysis
trityl ion catalysis also for activated arenes. Thus, we
thought to take advantage of this in order to develop
an easily available chemoselective switch between the
two reaction modes. Gratifyingly, by simply changing
the solvent of the reaction from DCM to the more
nonpolar benzene, electrophilic aromatic substitution
was completely suppressed and 1-(bromomethyl)-
naphthalene 3o was obtained as the sole product
(Table 3, entry 5). With these optimized conditions in
hand, 1- and 2-methyInaphthalenes 1o and 1p was
brominated in benzene to give the benzylic
bromination product 1- and 2-(bromomethyl)-
naphthalene 3o and 3p in high yields (Table 4). The
analogous reactions in acetonitrile resulted in
and acetonitrile to give benzyl bromides 3q-r and
bromobenzenes 5q-r, respectively, in moderate to
excellent yields (Table 4). Furthermore, the TrBF4
catalyzed benzylic bromination of m-iodotoluene 1s,
m-xylene 1t and mesitylene 1u in benzene gave 3s-u
as single products in moderate to excellent yield
(Table 4). For the analogous reactions of 1s-u in
acetonitrile (Table 4) a complete switch in selectivity
to aromatic substitution was observed to give the
corresponding bromobenzene derivatives 5s-u in high
yields (Table 4). As for the reaction of compound 1f-g
(c.f. Table 2), the benzylic bromination product of
1,3,5-triethylbenzene 1v was isolated as the
corresponding alcohol 3v after flash column in 61%
yield due to the instability of the secondary bromide
(Table 4). Bromination of 1,3,5-triethylbenzene 1v in
acetonitrile smoothly gave bromobenzene 5v in high
yield (Table 4). Finally, fluorene was brominated in
benzene (Conditon A) and acetonitrile (Conditon B) to
give the benzylic bromination product 3w and
bromoarene 5w, respectively, in high yields (Table 4).
As expected, less electron rich aromatics such as
toluene 1a and 4-nitro-toluene 1h, which could be
efficiently brominated in the benzylic position (cf.
Table 3), was completely unreacted under the aromatic
sp2 C-H functionalization reaction conditions and non
of product 5a and 5h could be isolated (Table 4).
As a proof of concept, this chemoselective switch
was developed into a selective one-pot dibromination
of the aromatic and benzylic positions in 1-
methylnaphthalene 1o using 2 equivalents of NBS and
2 mol% TrBF4 (Scheme 3). The one-pot sequence was
initiated with arene brominiation using acetonitrile as
the solvent. After full conversion of 1-
methylnaphthalene 1o, the solvent was simply
changed to benzene and the reaction was allowed to
continue for an additional 16 h (Scheme 3). Under
these conditions the dibrominated product 3d was
isolated in 84% yield, which can be compared to the
notable lower yield obtained for the more tedious two-
step procedure (Scheme 3).
complete
switch
in
chemoselectivity
and
bromonaphthalenes 5o and 5p was isolated in 92% and
90% isolated yields, respectively (Table 4).
Table 4. Selected substrates for the chemoselective switch:
Benzylic sp3 vs. aromatic sp2 C-H functionalization.[a]
Method A
Method B
TrBF4 (2.0 mol%)
CH3CN, RT
R
R
R
TrBF4 (2.0 mol%)
Br
R’
R’
R’
NBS
Benzene
55 W F.L., RT
Br
3
1
2
5
Br
One-Pot
One-Pot = 84% yield
NBS
Two Steps = 75% overall yield
Two Steps
Br
2
3d
1o
Scheme 3. One-pot vs. two-step dibromination of 1-
methylnaphthalene. One-pot: 1) TrBF4 (2.0 mol%, 0.25 M
in DCM), NBS (2.0 equiv.), 55 W F.L., CH3CN. 2) Benzene,
55 W F.L. Two-step: 1) TrBF4 (2.0 mol%, 0.25 M in DCM),
NBS (1.0 equiv.), 55 W F.L., CH3CN. 2) TrBF4 (2.0 mol%,
0.25 M in DCM), NBS (1.0 equiv.), benzene, 55 W F.L.
[a] Method A: TrBF4 (2.0 mol%, 0.25 M in DCM) was
added to 1a (1.5 equiv.) and 2 (1.0 equiv.) in benzene (0.3
M). Method B: TrBF4 (2.0 mol%, 0.25 M in DCM) was
added to 1a (1.2 equiv.) and 2 (1.0 equiv.) in CH3CN (0.3
M). [b] 1.5 eq. of 1s was used. [c] No reaction, starting
material was recovered.
Mechanistic considerations: Lewis acid activation
of NBS by AlCl3, FeCl3, ZrCl4 among others have been
previously reported to catalyze electrophilic aromatic
bromination.[8c,13] The activation mode in these cases
involves metal coordination to the carbonyl oxygen in
NBS thereby making the bromine atom more
In the same manner, the highly activated arenes p-
methylanisol 1q and N-methyl-N-(p-tolyl)acetamide
1r could be chemoselectively brominated in benzene
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800788
Advanced Synthesis & Catalysis
electrophilic.
In an attempt to verify such a
no reaction occurs in the absence of daylight (Table 1,
entry 4) or in the present of a radical inhibitor, which
supports a radical chain reaction (Scheme 4).
coordination of the trityl ion, TrBF4 and NBS was
1
mixed in 1:1 ratio in CD2Cl2. A smal changes in H-
NMR shifts from 2.959 to 2.962 MHz could be
observed for the CH2-groups on succinimide. The
signals corresponding to the trityl ion did not change
shift upon addition of succinimide witch is suggesting
a weak coordination. Furthermore, investigation of the
IR-absorption band of NBS with mixtures of TrBF4
and NBS reveled a shift in the absorption band from
1695 cm-1 to 1700 cm-1 even at such low catalyst
loadings as 2.0 mol% (Figure 1). Such an increase in
absorption frequency is consistent with a more
electron deficient carbonyl carbon supporting
activation of NBS through trityl ion coordination.
Scheme 4. Radical quenching control experiment.
The time course of the trityl ion catalyzed benzylic
bromination of toluene shows a relatively slow initial
conversion of NBS to succinimide. After 4 h and
approximately 40 % conversion of NBS, an increase
in reaction rate was observed to give full conversion
after 6 h (Figure 3). Such a pronounced induction
period is characteristic for a free radical reaction.
conv. of toluen(%)
100
80
60
40
20
0
Figure 1. IR absorption of a) blue line: NBS (100%), b) red
line: NBS/ TRBF4 (50:1), c) purple line: NBS/ TRBF4 (2:1),
d) yellow line: NBS/ TRBF4 (1:2).
0
2
4
6
t (h)
Thus, the role of the trityl ion in the electrophilic
aromatic substitution is rather straightforward and is
believed to involve Lewis acid activation of NBS
making it a more potent electrophile (Figure 2). It
should also be mentioned that no adduct formation
between the NBS derived byproduct succinimide and
the trity ion was observed under the benzylic sp3 or
aromatic sp2 C-H functionalization reaction conditions,
despite the nucleophilic potential of succinimid.
Figure 3. Reaction profile for the trityl ion catalyzed
benzylic bromination of toluene with NBS. Reaction
conditions: TrBF4 (2.0 mol%, 0.25 M in DCM) was added
to a solution of toluene 1a (1.0 equiv.) and NBS (1.0 equiv.)
in DCM (0.3 M) and irradiated by 55 W F.L.
Based on the fact that both the trityl ion and light is
needed for the radical benzylic bromination to proceed,
it could be suggested that the role of the trityl ion is to
assist in the generation of bromine from HBr and NBS
by further activation of NBS towards nucleophilic
attack of bromide (Figure 4).[14]
Figure 2. Trityl ion catalyzed EAS process.
On the other hand, the benzylic bromination (Wohl–
Ziegler reaction) involves a radical chain reaction that
usually requires a radical initiator (AIBN) or UV-light
to generate atomic bromine. In this case the exact role
of the trityl ion catalyst is not obvious. As previously
shown, essentially no background reaction occurs in
the absence of catalyst (Table 1, entry 1). Furthermore,
Figure 4. Proposed trityl ion catalyzed bromine formation.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800788
Advanced Synthesis & Catalysis
1o (99.5 mg, 0.45 mmol) and N-bromosuccinimide 2 (53.4
mg, 0.90 mmol) in CH3CN (1 ml). The reaction was stirred
for 2 h before the solvent was removed under vacuum. The
crude mixture was redissolved in benzene (1 ml) stirred at
RT for an additional 16 h. One drop of water was added to
quench the reaction. The residue was purified by flash
chromatography to afford 3d as a white solid (75.6 mg,
84%). Spectral data were in accordance with those
previously reported.[18]
Conclusion
In conclusion, we have developed a photo-induced
trityl ion catalyzed benzylic bromination that operates
under mild reaction conditions with low catalyst
loading avoiding the use of toxic radical initiators.
This protocol is applicable both on electron-deficient
and electron-rich alkyl-arenes to give -bromoalkyl
arenes in good to excellent yields without any traces of
over-oxidation to dibrominated compounds. In
addition, for activated and weakly activated arenes we
show that the trityl ion is an efficient Lewis acid
catalyst for activation of NBS towards electrophilic
aromatic substitution. This allowed for the
development of a chemoselective switch between
benzylic sp3 C-H functionalization and arene sp2 C-H
functionalization by simply changing the solvent of the
reaction
Acknowledgements
This work was made possible by grants from the Swedish Research
Council (VR). S. N. thanks the Chinese Scholarship Council (CSC)
for a grant. M. A. A. E.-R. thanks the Erasmus Mundus Action 2.
Welcome project for a grant.
References
[1] a) R. C. Larock, Comprehensive Organic
Transformations: A Guide to Functional Group
Preparations, 2nd ed.; Wiley-VCH: New York, 1999. b)
F. A. Carey and R. J. Sundberg, Advanced Organic
Chemistry, Plenum, New York, 3rd ed., 1990. c) J.
March, Advanced Organic Chemistry: Reactions,
Mechanism and Structure, John Wiley & Sons, New
York, 4th ed., 1992.
Experimental Section
General: All reactions are preformed in pre-dried solvents
under nitrogen atmosphere. TrBF4 was dissolved in DCM
(0.25 M) and used as a stock solution (for further details see
supporting information).
General procedure for the preparation of benzyl
bromides 3: Synthesis of 1-(Bromomethyl)naphthalene
3o. TrBF4 (24 μl, [TrBF4]DCM = 0.25 M) was added to a
solution of 1-methyl naphthalene 1o (64.0 mg, 0.45 mmol)
and N-bromosuccinimide 2 (53.4 mg, 0.30 mmol) in
benzene (1.0 ml). The resulting mixture was exposed to
standard hood fluorescent light (55 W F.L.) and stirred until
full conversion of 2 was observed (determined by 1H NMR
on the crude reaction mixture). The reaction was quenched
by adding a drop of water. The solvent was removed under
vacuum and the residue was purified by flash
chromatography to give 1-(bromomethyl)naphthalene 3o as
a colorless oil (53.7 mg, 81%). Spectral data were in
accordance with those previously reported.[15]
[2] For selected examples, see: a) Q. Xue, Z. Hu, J. Liu, J.
Lin, C. Sun, Z. Chen, C. Duan, J. Wang, C. Liao, W. M.
Lau, F. Huang, H.-L. Yip, Y Cao, J. Mater. Chem. A
2014, 2, 19598. b) B. Pan, B. Wang, Y. Wang, P. Xu, L.
Wang, J. Chen, D. Ma, J. Mater. Chem. C 2014, 2, 2466.
c) Y. Li, X. Liu, F.-P. Wu, Y. Zhou, Z.-Q. Jiang, B. Song,
Y. Xia, Z.-G. Zhang, F. Gao, O. Inganäs, Y. Li, L.-S.
Liao, J. Mater. Chem. A 2016, 4, 5890. d) X. Wang, L.
Zhang, J. Yang, F. Liu, F. Dai, R. Wang, D. Sun, J.
Mater. Chem. A 2015, 3, 12777. e) M.-L. Ma, J.-H. Qin,
C. Ji, H. Xu, R. Wang, B.-J. Li, S.-Q. Zang, H.g-W. Hou,
S. R. Batten, J. Mater. Chem. C 2014, 2, 1085. f) P. Xue,
B. Yao, X. Liu, J. Sun, P. Gong, Z. Zhang, C. Qian, Y.
Zhang, R. Lu, J. Mater. Chem. C 2015, 3, 1018.
General procedure for the preparation of aryl bromides
5: Synthesis of 1-Bromo-4-methylnaphthalene 5o. TrBF4
(24 μl, [TrBF4]DCM = 0.25 M) was added to a solution of 1-
methyl naphthalene 1o (51.2 mg, 0.36 mmol) and N-
bromosuccinimide 2 (53.4 mg, 0.30 mmol) in CH3CN (1.0
ml). The resulting mixture was stirred until full conversion
[3] For selected examples, see: a) Z. Yao, M. Zhang, H. Wu,
L. Yang, R. Li, P. Wang, J. Am. Chem. Soc. 2015, 137,
3799. b) Y. Yuan, R. T. K. Kwok, B. Z. Tang, B Liu, J.
Am. Chem. Soc. 2014, 136, 2546. c) H. Huo, X. Shen, C.
Wang, L. Zhang, P. Röse, L.-A. Chen, K. Harms, M.
Marsch, G. Hilt, E. Meggers, Nature, 2014, 515, 100. d)
J. Jeong, P. Patel, H. Hwang, S. Chang, Org. Lett. 2014,
16, 4598. e) A. S. Deeming, C. J. Russell, A. J. Hennessy,
M. C. Willis, Org. Lett. 2014, 16, 150.
1
of 2 was observed (determined by H NMR on the crude
reaction mixture). The reaction was quenched by adding a
drop of water. The solvent was removed under vacuum and
the residue was purified by flash chromatography to give 1-
Bromo-4-methylnaphthalene 5o as a colorless oil (61.0 mg,
92%). Spectral data were in accordance with those
previously reported.[16]
One-pot synthesis of N-(benzyl)succinimide 4: TrBF4 (2
mol%, 24 µl, [TrBF4]DCM = 0.25 M) was added to a solution
of toluene 1a (48 µL, 0.45 mmol) and N-bromosuccinimide
2 (53.4 mg, 0.30 mmol) in DCM (1 ml). The reaction was
stirred at RT for 6 h before the solvent was removed under
vacuum. The crude mixture was redissolved in CH3CN (1
ml) and K2CO3 (82.9 mg, 0.6 mmol) was added. The
[4] For selected examples, see: a) B. Zheng, F. Tang, J. Luo,
J. W. Schultz, N. P. Rath, L. M. Mirica, J. Am. Chem.
Soc. 2014, 136, 6499. b) J. Guenther, S. Mallet-Ladeira,
L. Estevez, K. Miqueu, A. Amgoune, D. Bourissou, J.
Am. Chem. Soc. 2014, 136, 1778. c) L. Huang, F.
Rominger, M. Rudolph, A. S. K. Hashmi, Chem.
Commun. 2016, 52, 6435. d) B. T. Ingoglia, S. L.
Buchwald, Org. Lett. 2017, 19, 2853. e) K. Nagata, T.
Agou, N. Tokitoh, Angew. Chem. Int. Ed. 2014, 53, 3881.
°
resulting mixture was heated at 80 C for 24 h. The residue
was purified by flash chromatography (PE/EA = 1/1) to give
N-(benzyl)succinimide 4 as a white solid (51 mg, 90%).
Spectral data were in accordance with those previously
reported.[17]
One-pot
synthesis
of
1-bromo-4-
[5] F. Diederich, P. J. Stang, Metal-Catalyzed Cross-
Coupling Reactions; Wiley-VCH: Weinheim, 1998.
(bromomethyl)naphthalene 3d: TrBF4 (2 mol%, 24 μl,
[TrBF4]DCM = 0.25 M) was added to 1-methylnaphthalene
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800788
Advanced Synthesis & Catalysis
[6] a) A. Wohl, Ber. Dtsch. Chem. Ges. 1919, 52, 51. b) K.
Ziegler, A. Spath, E. Schaaf, W. Schumann, E.
Winkelmann, Justus Liebigs Ann. Chem. 1942, 551, 80.
Chem. 2015, 1834. c) J. Bah, V. R. Naidu, J. Teske, J.
Franzén. Adv Synth Catal 2015, 357, 148. d) J. Bah, J.
Franzén, Chem. Eur. J. 2014, 20, 1066. e) M. A. A. El
Remaily, V. R. Naidu, S. Ni, J. Franzén, Eur. J. Org.
Chem. 2015, 6610. f) S. Ni, V. R. Naidu, J. Franzén, Eur.
J. Org. Chem. 2016, 1708. g) Y. Huang, C. Qiu, Z. Li,
W. Feng, H. Gan, J. Liu, K. Guo, ACS Sustainable Chem.
Eng. 2016, 4, 47. h) J. Liu, J. Xu, Z. Li, Y. Huang, H.
Wang, Y. Gao, T. Guo, P. Ouyang, K. Guo, Eur. J. Org.
Chem. 2017, 3996. i) S. R. Roy, A. Nijamudheen, A.
Pariyar, A. Ghosh, P. K. Vardhanapu, P. K. Mandal, A.
Datta, S. K. Mandal, ACS Catal. 2014, 4, 4307. j) J. Lv,
Q. Zhang, X. Zhong, S. Luo, J. Am. Chem. Soc. 2015,
137, 15576. k) Q. Zhang, J. Lv, S. Luo, Acta Chim.
Sinica. 2016, 74, 61. l) C. Nicolas, C. Herse, J. Lacour,
Tetrahedron Lett. 2005, 46, 4605; m) C. Nicolas, J.
Lacour, Org. Lett. 2006, 8, 4343. n) E. Follet, P. Mayer,
B. Berionni. Chem. Eur. J. 2017, 23, 623. o) M. Horn,
M. Mayr, J. Phys. Org. Chem. 2012, 25, 979 and
references therein. p) P. Pommerening, J. Mohr, J.
Friebel, M. Oestreich, Eur. J. Org. Chem., 2017, 2312.
q) Y. A. Rulev, Z. T. Gugkaeva, A. V. Lokutova, V. I.
Maleev, A. S. Peregudov, X. Wu, M. North, Y. N.
Belokon, ChemSusChem, 2017, 10, 1152. r) L. Wan, W.
Zhu, K. Qiao, X. Sun, Z. Fang, K. Guo, Asian J. Org.
Chem., 2016, 5, 920. s) Q. Zhang, J. Lv, S. Li, S. Luo,
Org. Lett. 2018, 20, 2269.
[7] For a recent review see: V. P. Boyarskiy, D. S.
Ryabukhin, N. A. Bokach, A. V. Vasilyev, Chem. Rev.
2016, 116, 5894. For selected recent examples, see: a) D.
Cantillo, O. de Frutos, J. A. Rincon, C. Mateos, C. O.
Kappe, J. Org. Chem. 2014, 79, 223. b) Y. Manabe, Y.
Kitawaki, M. Nagasaki, K. Fukase, H. Matsubara, Y.
Hino, T. Fukuyama, I. Ryu, Chem. Eur. J. 2014, 20,
12750. c) D. Cantilloab, C. O. Kappe, React. Chem. Eng.
2017, 2, 7. d) A. Podgorꢀek, S. Stavber, M. Zupan, J.
Iskra, Tetrahedron Lett. 2006, 47, 7245. e) S. Adimurthy,
G. Ramachandraiah, A. V. Bedekar, S. Ghosh, A. S.
Mehta, B. C. Ranu, P. K. Ghosh, Green Chem. 2006, 8,
916. f) S. Adimurthy, S. Ghosh, P. U. Patoliya, G.
Ramachandraiah, M. Agrawal, M. R. Gandhi, S. C.
Upadhyay, P. K. Ghosh, B. C. Ranu, Green Chem. 2008,
10, 232. g) Y. Nishina, B. Ohtani, K. Kikushima,
Beilstein J. Org. Chem. 2013, 9, 1663. h) A. Podgorꢀek,
S. Stavber, M. Zupan, J. Iskra, Tetrahedron Lett. 2006,
47, 1097. i) M. Jereb, M. Zupan, S. Stavber, Helv. Chim.
Acta 2009, 92, 555. j) S. Ghosh, J. Das, Tetrahedron Lett.
2011, 52, 1112. k) D. Suarez, G. Laval, S.-M. Tu, D.
Jiang, C. L. Robinson, R. Scott, B. T. Golding, Synthesis
2009, 1807.
[8] a) T. A. Salama, Z. Novꢁk, Tetrahedron Lett. 2011, 52,
4026. b) K. Shibatomi, Y. Zhang, H. Yamamoto, Chem.
Asian J. 2008, 3, 1581. c) Y. Zhang, K. Shibatomi, H.
Yamamoto, Synlett 2005, 2837. d) S. Deshpande, B.
Gadilohar, Y. Shinde, D. Pinjari, A. Pandit, G.
Shankarling Solar Energy 2015, 113, 332.
[12] H. Shimojo, K. Moriyama, H. Togo, Synthesis 2015, 47,
1280.
[13] K. Tanemura, T. Suzuki, Y. Nishida, K.
Satsumabayashi, T. Horaguchi, Chem. Lett. 2003, 32,
932.
[9] a) S. K. Santra, A. Banerjee, N. Khatun, A. Samanta, B.
K. Patel, RSC Adv. 2015, 5, 11960. b) S.-C. So, W.-M.
Cheung, G.-C. Wang, E. Kwan Huang, M.-K. Lau, Q.-
F. Zhang, H. H.-Y. Sung, I. D. Williams, W.-H. Leung,
Organometallics 2014, 33, 4497. c) M. S. Bennington,
H. L. C. Feltham, Z. J. Buxton, N. G. White, S. Brooker,
Dalton Trans. 2017, 46, 4696.
[14] G. K. S. Prakash, T. Mathew, D. Hoole, P. M. Esteves,
Q. Wang, G. Rasul, G. A. Olah, J. Am. Chem. Soc. 2004,
126, 15770.
[15] L. S. De Almeida, P. M. Esteves, M. C. S. De Mattos,
Tetrahedron Lett. 2015, 56, 6843.
[16] P. R. Wells, D. P. Arnold, D. Doddrell, J. Chem. Soc.
1974, 1745.
[10] a) K. Shibatomi, Y. Zhang, H. Yamamoto, Chem. Asian
J. 2008, 3, 1581. b) D. Kikuchi, S. Sakaguchi, Y. Ishii,
J. Org. Chem. 1998, 63, 6023. c) L. Fang, H. Zhang, X.
Fang, S. Gou, L. Cheng Indian J of Chem. 2014, 53B,
635.
[17] H. Shimojo, D. Moriyama, H. Togo, Synthesis 2015, 47,
1280.
[18] M. Carmen Carreño, R. Hernández-Sánchez, J.
Mahugo, A. Urbano, J. Org. Chem., 1999, 64, 1387.
[11] a) V. R. Naidu, S. Ni, J. Franzén, ChemCatChem 2015,
7, 13. b) V. R. Naidu, J. Bah, J. Franzén, Eur. J. Org.
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800788
Advanced Synthesis & Catalysis
FULL PAPER
Br
Carbocation Catalyzed Bromination of Alkyl
Arenes, a Chemoselective sp3 vs. sp2 C-H
functionalization
Benzene or DCM,
RT
R’
R
Benzylic sp3 C-H
functionalization
O
55 W F.L.
R’
R
55-96% yield
N
Br
Ph
Ph
Ph
Adv. Synth. Catal. Year, Volume, Page – Page
O
(2 mol%)
(NBS)
R’
Arene sp2 C-H
functionalization
R
Shengjun Ni, Mahmoud Abd El Aleem Ali Ali El
Remaily Johan Franzén*
CH3CN, RT
Br
70-92% yield
8
This article is protected by copyright. All rights reserved.