N-Heterocyclic carbene triazolium salts containing brominated aromatic motifs: Features and synthetic protocol

Article abstract of DOI:10.2533/CHIMIA.2020.878

In this work, we provide a brief overview of the role of N-aryl substituents on triazolium N-heterocyclic carbene (NHC) catalysis. This synopsis provides context for the disclosed synthetic protocol for new chiral N-heterocyclic carbene (NHC) triazolium salts with brominated aromatic motifs. Incorporating brominated aryl rings into NHC structures is challenging, probably due to the substantial steric and electronic influence these substituents exert throughout the synthetic protocol. However, these exact characteristics make it an interesting N-aryl substituent, because the electronic and steric diversity it offers could find broad use in organometallic- A nd organo-catalysis. Following the synthetic reaction by NMR guided the extensive modification of a known protocol to enable the preparation of these challenging NHC pre-catalysts.

Full text of DOI:10.2533/CHIMIA.2020.878

878 CHIMIA 2020, 74, No. 11
doi:10.2533/chimia.2020.878
InnovatIve tools In organIc / organometallIc chemIstry
Chimia 74 (2020) 878–882 © A. Abo Raed, V. Dhayalan, S. Barkai, A. Milo
N-Heterocyclic Carbene Triazolium Salts
Containing Brominated Aromatic Motifs:
Features and Synthetic Protocol
Anas Abo Raed‡, Vasudevan Dhayalan‡, Shahar Barkai, and Anat Milo*
We dedicate this work to the late Supreme Court Justice Ruth Bader Ginsburg.
Abstract: In this work, we provide a brief overview of the role of N-aryl substituents on triazolium N-heterocyclic
carbene (NHC) catalysis. This synopsis provides context for the disclosed synthetic protocol for new chiral
N-heterocyclic carbene (NHC) triazolium salts with brominated aromatic motifs. Incorporating brominated aryl
rings into NHC structures is challenging, probably due to the substantial steric and electronic influence these
substituents exert throughout the synthetic protocol. However, these exact characteristics make it an interesting
N-aryl substituent, because the electronic and steric diversity it offers could find broad use in organometallic- and
organo-catalysis. Following the synthetic reaction by NMR guided the extensive modification of a known protocol
to enable the preparation of these challenging NHC pre-catalysts.
Keywords: Arylhydrazine · De-silylation · NHC · Organocatalysis · Triazolium salts
Shahar Barkai received his BSc degree in chemistry from
Ben-Gurion University of the Negev in 2019. He is currently pur-
suing his MSc in Anat Milo’s group. His research focuses on the
employment of statistical and computational tools to study the
influence of structural features on reaction mechanisms.
Anat Milo received her BSc/BA in Chemistry and Humanities
from the Hebrew University of Jerusalem in 2001, MSc from
UPMC Paris in 2004 with Berhold Hasenknopf, and PhD from
the Weizmann Institute of Science in 2011 with Ronny Neumann.
Her postdoctoral studies at the University of Utah with Matthew
Sigman focused on developing physical organic descriptors and
data analysis approaches for chemical reactions. In October 2015,
she returned to Israel to join the Department of Chemistry at Ben-
Gurion University of the Negev, where her research group de-
velops experimental, statistical, and computational strategies for
identifying molecular design principles in catalysis with a particu-
lar focus on stabilizing and intercepting reactive intermediates by
second sphere interactions.
Anas Abo Raed received his BSc in chemistry from Ben-
Gurion University of the Negev in 2017. He is currently pursuing
his combined MSc and PhD in Anat Milo’s group. His research
focuses on NHC-catalyzed cross-coupling reactions.
Low-energy barriers between competing reaction pathways
are the double-edged sword at the core of organocatalysis. On the
one hand, these small energy differences make it challenging to
control organocatalytic selectivity and reproducibility, on the oth-
er, it is possible to control selectivity and reactivity by slight modi-
fications to the catalyst structures. N-heterocyclic carbenes (NHC)
have been widely applied in numerous classes of organocatalytic
reactions due to their highly tunable structures and triazolium-
based NHCs have been particularly instrumental in enantio- and
chemo-selective reactions. Notably, the substitution pattern on
their aromatic motif shows a striking difference in catalytic and
Vasudevan Dhayalan obtained his MSc in Organic Chemistry
(2005) and his PhD in Organic Chemistry (2011) at the Universityof
Madras, India. He then joined the group of Prof. Masahiko Hayashi
at Kobe University, Japan, as a postdoctoral researcher (2011–
2012). Later, he worked with Prof. Paul Knochel at the Ludwig-
Maximilians-University Munich, Germany (2013–2015). In 2016,
he joined the group of Prof.Anat Milo at the Ben-Gurion University
of the Negev with a PBC outstanding postdoctoral research fellow-
ship. Recently, he was awarded the prestigious Ramanujan fellow-
ship from Science and Engineering Research Board (SERB) India.
*Correspondence: Dr. A. Milo, E-mail: anatmilo@bgu.ac.il
Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
‡These authors contributed equally

InnovatIve tools In organIc / organometallIc chemIstry
CHIMIA 2020, 74, No. 11 879
chemical activities under different reaction setups. This catalytic
Following up on these intriguing observations, Smith,
versatility is well demonstrated by two well-studied examples of O’Donoghue and coworkers[2] examined the role of different
N-aryl NHC substituents, pentafluoro-phenyl and mesityl, which N-aryl substituents by monitoring protonated NHC–aldehyde
are often compared due to their diverse electronic and steric char- acyl anion adducts in situ by NMR (Fig. 2). They studied reaction
acteristics (Fig. 1).
rates as well as the protonated acyl anions’ equilibrium constants,
A study by Bode and coworkers[1] meticulously assessed their acidities, and deuterium exchange rates. They asserted based on
diverging effects on catalytic reactions of α-functionalized al- the equilibrium observed for the protonated acyl anion adducts
dehydes and provided mechanistic insight on the nature of this that, at least in the system they studied, the addition of the alde-
difference. They suggest that this difference stems from the re-
hyde to the NHC was reversible, even using N-mesityl triazolyli-
versible formation of the N-pentafluoro-phenyl acyl anion adduct dene. Interestingly, they introduced an N-2,4,6-trichloro-phenyl
compared to the irreversible formation of this adduct using the substituent, which presumably has electronic properties similar
N-mesityl-substituted catalyst (Fig. 1E).
to those of N-pentafluoro-phenyl and steric hindrance similar to
N-mesityl. The reaction rates revealed that the 2,4,6-trichloro-
Their conclusions are based on experimental differences in
deprotonation, namely, mesityl undergoes partial deprotonation in phenyl-substituted NHC performed very similarly to the penta-
the presence of DBU while pentafluoro-phenyl is fully deproton- fluoro-phenyl-substituted one, while the deuterium exchange
ated. This result is supported by a series of esterification experi-
rate of the trichloro-phenyl was in mid-range between the pen-
ments in which the catalytic activity was evaluated for different tafluoro- and mesityl-substituted one. However, the equilibrium
NHC catalysts (select examples are presented in Fig. 1).
constants revealed the trichloro-phenyl substituted NHC as be-
Fig. 1. Examples presented by
Bode and coworkers[1] of different
reactions with N-pentafluoro and
N-mesityl NHCs: (A) redox esteri-
fication of cinnamaldehydes and
(B) α-chloroaldehyde, (C) intramo-
lecular Stetter reaction, (D) hetero
Diels-Alder reaction. (E) Proposed
mechanistic rationalization for the
differences in reactivity and selec-
tivity between N-pentafluoro and
N-mesityl NHCs.
A
C
O
H
O
O
NHC (10 mol%)
NHC (10 mol%)
O
iPr2NEt (10 mol%)
iPr2NEt (10 mol%)
H
Ph
Cl
MeO
OMe
MeO
Ph
0.1 M Tol-d8
40 °C, 90 mins
Tol-d8 (0.1 M)
40 °C, 170 mins
OMe
MeOH
MeOH
BF4
BF4
Cl
BF4
Cl
N
N
N
N
N
N
N
F
N
N
N
N
N
N
F
N
N
F
2X faster than
F
F
Cl
F
F
Cl
F
F
F
100%
90%
50%
O
D
B
O
O
Ph
O
O
NHC (10 mol%)
iPr2NEt( 1 eq.)
NHC (10 mol%)
NMM (1 eq.)
O
O
H
Ph
Cl
MeOH
H
Ph
MeO
Ph
0.1 M CD2Cl2
23 °C, 6 h
CDCl3 (0.1 M)
23 °C, 15 mins
OR
R= H
O
or
F
Ph
BF4
BF4
BF4
N
N
Cl
Cl
N
N
N
N
N
N
N
N
N
N
N
N
Cl
N
F
8X faster than
F
F
Cl
F
F
Cl
F
F
F
E
F
0%
F
50%
100%
O
F
F
F
F
F
F
F
F
H
F
F
F
F
F
F
R
F
F
F
O
F
BF4
O
F
DBU
N
OH
N
N
N
E
N
N
reversible
N
H
N
H
N
N
DBU–H+
N
N
R
R
R
Acyl-anion adduct
Breslow
intermediate
Benzoin
Stetter
O
H
O
H
R
Cl
DBU
O
N
N
OH
N
N
N
N
irreversible
N
N
H
N
N
H
E
R
DBU–H+
N
N
R
Oxidation
Annulation
R

880 CHIMIA 2020, 74, No. 11
InnovatIve tools In organIc / organometallIc chemIstry
ing more stable than the pentafluoro but at the same magnitude, N-2,4,6-trichloro-phenyl substituent diverges in selectivity. This
while the mesityl was less stable (with K values of 601, 521 result points to non-trivial underlying electronic and steric effects
and 143 (M–1) respectively). The authors speculate that increased
that cannot always be foreseen by a single parameter such as the
stability is due to a better accommodation of the acyl anion ad- NHC pre-catalyst pKa. If that were the case, 2,4,6-trichloro and
duct, which stems from the propensity of large 2,6-substituents the 2,4,6-tribromo would be expected to have similar activities in
to enforce the N-aryl ring to adopt an orientation orthogonal to the mid-range between N-pentafluoro-phenyl and N-mesityl sub-
the triazole ring.
stituted NHCs.
O
O
CO2Et
Br
O
O
O
O
CO2Et
NHC (40 mol%)
NEt3 (40 mol%)
OH Br
1
OH
2
NHC (4 mol%)
O
Br
O
CD2Cl2, r.t
K2CO3 (4 mol%)
H
H
THF (1.1 M)
r.t, 48h
Br
O
O
BF4
BF4
N
N
BF4
OH
3
OH Br
4
N
N
N
N
N
Cl
N
F
N
F
BF4
BF4
Br
Cl
BF4
BF4
Cl
F
N
N
Cl
N
N
N
N
N
F
N
N
N
N
N
F
F
F
Br
Cl
F
Br
<5
11
4720
t50%(min)
Cl
F
F
Product
1
Yield %
0
Yield %
Yield %
1
Yield %
1
Fig. 2. Smith, O’Donoghue and coworkers[2] examination of different aryl
substituents. t50% represents the time it took to reach 50% conversion.
4
2
3
1
0
21
11
18
7
1
0
Lee, Rovis and coworkers[3] studied the influence of N-aryl
substituents on both computationally and experimentally derived
acidities of protonated NHC precursors. The computed acidities
4
1
66
75
15
are well correlated with the experimental results, however, since
the experiments were based on mass spectrometry gas-phase pro-
ton transfer reactions between the NHC precursors and various
bases, the resolution in values was limited to the pK values of the
Fig. 4. Comparison of NHC pre-catalysts in the cross-benzoin reaction
by Connon and coworkers.[4]
bases (Fig. 3). Thus, the authors selected to correlateathe computed
pKa values with the diastereoselectivity of a model reaction (see We employed DFT optimizations of the structures of the
Fig 4 below), which demonstrated that the triazolium salt acidi- N-mesityl, N-pentafluoro-phenyl and N-2,4,6-tribromo-phenyl
ties are key in predicting the selectivity of the resulting catalyst.
triazolium salts in order to compare their steric and electronic
In a study by Connon and coworkers[4] the influence of the properties (Fig. 5). This optimization gave rise to a few unsurpris-
N-aryl substituent was examined on the cross-coupling benzoin ing characteristics that provide clear reasoning for the mid-range
condensation of benzaldehyde and o-bromobenzaldehyde (Fig. acidity of the 2,4,6-tribromo N-aryl substituent. Sterimol param-
4). This report presents a similar selectivity for N-pentafluoro-
eters[5] serve as a steric description of the N-aryl substituent with
phenyl- and N-2,4,6-trichloro-phenyl-substituted NHCs, while the L being the length of the substituted ring, B is the minimal width
perpendicular to the principal axis L and B 1is the maximal width
perpendicular to the principal axis L (Tab5le 1). NPA charges of
the acidic carbon (C2) and the substituted nitrogen (N ) serve as
a description of electron distribution, such that the mo1r1e negative
value corresponds to a higher electron occupancy and vice versa.
Dipole moments and their Cartesian components are computed
upon NPA charges and taken with respect to a shared coordinate
system. The torsion angle is taken between the triazolium ring and
the N-aryl substituent. The results support the hypothesis that the
2,4,6-tribromo-phenyl holds a similar steric nature to that of the
mesityl substituent, based on the Sterimol values and the torsion
angle. The charges indicate that N-2,4,6-tribromo-phenyl more
closely resembles N-pentafluoro-phenyl in terms of its elec-
tronic properties. However, the dipole moments, combine steric
and electronic characteristics, thus are less conclusive, putting
2,4,6-tribromo-phenyl somewhere between the two extremes.
With these considerations in mind we set out to synthesize several
chiral N-tribromo-phenyl substituted NHC pre-catalysts.
Many NHC triazolium salts with a variety of aromatic motifs
have previously been prepared,[6] however, the introduction of
brominated aryl rings remains challenging, probably due to the
substantial steric and electronic influence these substituents ex-
erted throughout the synthetic protocol.[7,8] The common synthetic
route for the preparation of NHC triazolium catalysts includes
the following steps. The reaction begins with a nucleophilic at-
Fig. 3. Acidity-selectivity relationship for NHC-catalyzed homoenolate
addition of enals to nitroalkenes by Lee, Rovis and coworkers.[3]

InnovatIve tools In organIc / organometallIc chemIstry
CHIMIA 2020, 74, No. 11 881
primary alcohol 3, whereas the reaction of 2 with the Grignard
reactant, phenyl magnesium bromide, leads to tertiary alcohol 5.
Selectively protecting the hydroxyl on 3 and 5 with silyl chloride
and silyl triflate lead to the formation of the corresponding silyl
ethers 4 and 6 (Scheme 2).
O
O
SOCl2 (1.5 eq.)
MeOH, 0 °C to r.t, 3 h
NaBH4 (2 eq.)
EtOH, 0-20 °C, 24 h
NH
OMe
O
NH
O
Fig. 5. Computed physical parameters exemplified upon N-2,4,6-
tribromo NHC. (A) Sterimol steric parameters. (B) Shared coordinate
system with origin at N11. (C) Highlighted atoms for which the torsion
angle was calculated.
OH
90%
84%
1
2
Imidazole (2.5 eq.)
RCl (1.2 eq.)
O
O
NH
NH
4a) R= TIPS, 97%
4b) R= TBS, 99%
DMF, 20 °C, 24 h
OR
OH
3
4a-b
Table 1. Computed physical parameters
2,6-Lutidine (3 eq.)
O
O
O
Ph MgBr (3.2 eq.)
ROTf (2.5 eq.)
NH
NH
NH
Ph
Ph
O
Ph
Ph
THF, 0 °C to r.t, 24 h
DCM, 0 °C to r.t, 20 h
OR
OMe
OH
76%
2
5
6a-b
Mesityl
2.81
2,4,6-tribromo pentafluoro
6a) R=TMS, 95%
6b) R=TBS, 96%
B1 [Å]
B5 [Å]
L [Å]
2.88
4.79
6.98
2.32
3.70
Scheme 2. Synthesis of functionalized pyrrolidinones 4a,b and 6a,b.
4.37
To prepare a brominated NHC triazolium salt we were required
to first synthesize 2,4,6-tribromophenyl hydrazine from 2,4,6-tri-
bromoaniline. We optimized a known procedure and achieved a
6.15
5.83
Torsion
72.48o
91.77o
53.42o
50% boost in reaction yield (Scheme 3).[4]
y axis dipole
[eÅ]
Using compounds 4a,b, and 6a,b and 2-pyrrolidinone (4c)
as starting materials and hydrazine 8 as the brominated phenyl
source, we applied our previously optimized procedure for the
–0.921
–1.06
–1.78
Total dipole
preparation of the NHC pre-catalyst.[4] Unfortunately, this effort
resulted in only one of the corresponding products in low yield
(Scheme 4A).
1.14
1.27
1.90
[eÅ]
C2 NPA [e]a
N11 NPA [e]a
0.267
0.287
0.284
With the goal of identifying the key to improving these results,
we closely examined the reaction that provided catalyst 9a by
following its progress in H NMR. By analyzing the conversion
over time, we realized that the timing of each step was crucial and
longer reaction times led to the formation of byproducts that in-
terfered with the following steps while shorter reaction times did
not lead to full conversion and hampered the isolation of products.
Once we identified the optimal timing for each reaction step, the
–0.119
–0.131
–0.128
1
ae represents the elementary charge unit
tack of 2-pyrrolidinone by trimethyloxonium tetrafluoroborate
(Me3OBF ) to form an iminium salt, which then reacts with a
hydrazine4to form a hydrazone. The latter step introduces the aro-
reaction yields for 9a substantially improved. We then applied
matic motif into the resultant NHC catalyst and the hydrazine then
undergoes cyclization to afford an NHC pre-catalyst (Scheme 1).
the new found timing to the rest of the tested starting materials,
but once again did not manage to identify general conditions for
To obtain the chiral version of these catalysts where the 2-pyrro-
the full set of catalysts. The only additional product we were able
to prepare was 9b in 24% yield. Nonetheless, we were able to
de-protect the TIPS group on 9b, affording another hydroxyl pre-
catalyst (9f, Scheme 4B).
Following the reaction progress by NMR provided important
insights regarding the phenyl hydrazine addition. We managed to
isolate intermediate 1 and thus could follow its disappearance and
the formation of an additional intermediate, which we were unable
lidinone contains a silyl protected hydroxyl group, the cyclization
is followed by a de-protection step (step 4).
In our search for an appropriate procedure that will enable the
incorporation of brominated aromatic motifs, we first applied our
previously optimized protocol for the preparation of NHC triazo-
lium catalysts.[9] Our aim was to provide a synthetic protocol for
two types of chiral catalysts with different steric profiles, thus,
we prepared a precursor with a benzylic pendant hydroxyl group
(3) and another with two phenyl rings at the benzylic position (5).
In the presence of thionyl chloride, the commercially available
starting material (S)-pyroglutamic acid (1) is converted into an
to isolate. Based on the crude NMR and the proposed mechanism,
we assume this intermediate has the structure of putative interme-
diate 2 (Scheme 4B). We speculated that the reaction was impeded
by the stability of putative intermediate 2. To face this issue, we
ester (2). The reduction of ester 2 with sodium borohydride forms
decided to focus again on optimizing the reaction conditions of
1. Me3OBF4, DCM, 20 °C
2. ArNHNH2, DCM, 20 °C
1- t-butyl nitrite
Boron trifluoride etherate
DCM, -20 °C
2- SnCl2, HCl 37%, 8-10 °C
3- NaOH 1N, DCM, 0 °C
NHNH2
Br
NH2
O
Br
Br
Br
N
N
R
N
NH
3. (EtO)3CH, PhCl, 130 °C
4. TMSBr, CH3OH
Or
R
BF4
Ar
Br
Br
R= CH2OTIPS, CH2OTBS
R= CPh2OTMS, CPh2OTBS
R= CH2OH
R= CPh2OH
HBF4 OEt2, PhCl
7
8
Scheme 1. General procedure for the synthesis of NHC triazolium cata-
lysts.
Scheme 3. Optimized conditions for the synthesis of 2,4,6-tribromophe-
nyl hydrazine.

882 CHIMIA 2020, 74, No. 11
InnovatIve tools In organIc / organometallIc chemIstry
A
Scheme 4. (A) One pot synthesis
of NHC triazolium salts 9a–e. (B)
Optimized timing of reaction steps
achieved by following reaction
progress in 1H NMR.
BF4
1. Me3OBF4, DCM, 20 °C, 15h
2. ArNHNH2, DCM, 2-8h
N
N
9a) R= H, 16%
R
N
Br
O
9b) R= CH2OTIPS, 0%
9c) R= CH2OTBS, 0%
9d) R= CPh2OTMS, 0%
9e) R= CPh2OTBS, 0%
Ar= (2,4,6)-Br3-Ph
NH
3. (EtO)3CH, PhCl, 130 °C, 24h
4. TMSBr, CH3OH
Or
R
Br
Br
HBF4 OEt2, PhCl
4a-c
6a-b
9a-e
B
Br
Me3OBF4, DCM
20 °C, 15h
OMe
N
ArNHNH2, DCM
20 °C, 5h
O
Br
HN
N
NH
NH
R
R
R
Br
4c, R=H
Intermediate 1
Putative
Intermediate 2
BF4
Br
BF4
Br
9a) R= H, 50%
9b) R= CH2OTIPS, 24%
9c) R= CH2OTBS, 0%
9d) R= CPh2OTMS, 0%
9e) R= CPh2OTBS, 0%
9f) R= CH2OH, 24%
9g) R= CPh2OH, 0%
Ar= (2,4,6)-Br3-Ph
N
N
N
N
R
N
R
N
(EtO)3CH, PhCl
130 °C, 1h
TMSBr, CH3OH
Or
HBF4 OEt2, PhCl
Br
Br
Br
Br
9a-e
9f-g
9a (Table 1 in the Supplementary Information). We found that
and 9g) and the improvement of the yield of a known pre-catalyst
both Lewis and Brønsted acids stabilized the reaction intermedi- (9a). These new catalysts could find broad use in organometal-
ates, but Lewis acids stabilized intermediate 1 to the extent that lic- and organo-catalysis due to the diversity they offer in their
it was unreactive. Based on the proposed mechanism of the first electronic and steric attributes compared to known NHC catalysts.
step, the release of the tetra-fluoroboric acid (HBF4) is essential to
Supplementary Information
Supplementary information is available on https://www.ingentacon-
nect.com/content/scs/chimia
the process, as it can protonate intermediate 1 making it a better
electrophile in the reaction with the phenyl hydrazine. However,
the addition of HBF4 to the reaction mixture also stabilized inter-
mediate 1, which brought the reaction to a halt.
Acknowledgments
To further investigate the role of HBF4 in reaction, we isolated
This research was supported by the Israel Science Foundation (Grant
intermediate 1, which allowed the application of different amounts
No. 1193/17). V.D. gratefully acknowledges the PBC for a postdoctoral
of HBF4. The desired isolated intermediate was stable enough to
fellowship and A.A.R. gratefully acknowledges the Kreitman school of
be purified by column chromatography, the isolated intermediate
Advanced Graduate Studies for the Chemo-tech PhD fellowship.
for material 4c evaporated with the solvent, but starting materi-
als 6a,b resulted in isolated intermediates (10a,b) in high yields.
Reacting the resulting imine ethers 10a,b with the brominated
phenyl hydrazine 8 in the presence of precisely one equivalent
HBF4 led to the conversion to putative intermediates 2, which in
turn was successfully cyclized and afforded a substantial amount
Received: September 25, 2020
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ates 1, preventing the reaction from moving forward and using
less yielded a new, unknown intermediate that failed to cyclize
properly. Eventually, by a de-protection we were able to produce
pre-catalysts 9f in a good yield (Scheme 5).
[3] Y. Niu, N. Wang, A. Muꢀoz, J. Xu, H. Zeng, T. Rovis, J. K. Lee, J. Am.
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In conclusion, we have presented a rational analysis and opti-
mization of triazolium NHC synthesis steps in an effort to incor-
porate a tri-brominated phenyl substituent. We report the synthesis
of five new NHC pre-catalysts in practical yields (9b, 9d, 9e, 9f,
[6] D. M. Flanigan, F. Romanov-Michailidis, N. A. White, T. Rovis, Chem. Rev.
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BF4
N
N
Br
OMe
1. (2,4,6)-Br3PhNHNH2, HBF4
DCM, 20 °C, 24 h
2. (EtO)3CH, PhCl, 130 °C
O
N
Ph
Ph
Me3OBF4, DCM
20 °C, 15 h
N
Ph
Ph
NH
Ph
Ph
OR
OR
License and Terms
OR
Br
Br
This is an Open Access article under the
terms of the Creative Commons Attribution
6a-b
10a) R= TMS, 88%
10b) R= TBS, 91%
9d) R= TMS, 30%
9e) R= TBS, 67%
License CC BY_NC 4.0. The material may
not be used for commercial purposes.
The license is subject to the CHIMIA terms and conditions: (http://
chimia.ch/component/sppagebuilder/?view=page&id=12).
The definitive version of this article is the electronic one that can be
found at https://doi.org/10.2533/chimia.2020.878
N
N
Br
N
Ph
Ph
TMSBr, MeOH
20 °C, 3 h
OH
Br Br
Br
9g
70% (TMS)
0% (TBS)
Scheme 5. Chiral NHC triazolium salt two-pot synthesis reaction under
optimized conditions.