Oxidative NHC Catalysis for the Generation of Imidoyl Azoliums: Synthesis of Benzoxazoles

Article abstract of DOI:10.1021/acs.joc.8b02598

N-Heterocyclic carbene (NHC)-catalyzed intramolecular cyclization of aldimines generated from 2-amino phenols and aromatic aldehydes leading to the synthesis of 2-arylbenzoxazoles under mild conditions is presented. The reaction proceeds via the generation of the aza-Breslow intermediates from imines and NHC, which under oxidative conditions form the key imidoyl azoliums and a subsequent intramolecular cyclization furnishes the product. The reaction tolerates a broad range of functional groups, and the products are formed in generally good yields.

Full text of DOI:10.1021/acs.joc.8b02598

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Note
Oxidative NHC-Catalysis for the Generation of
Imidoyl Azoliums: Synthesis of Benzoxazoles
Atanu Patra, Anjima James, Tamal Kanti Das, and Akkattu T. Biju
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02598 • Publication Date (Web): 29 Oct 2018
Downloaded from http://pubs.acs.org on October 29, 2018
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Oxidative NHC-Catalysis for the Generation of Imidoyl Azoliums:
Synthesis of Benzoxazoles
†
†
†
,‡
Atanu Patra, Anjima James, Tamal Kanti Das, and Akkattu T. Biju*
1
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†Organic Chemistry Division, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi
Bhabha Road, Pune 411008, India
‡Department of Organic Chemistry, Indian Institute of Science, Bangalore-560012, India
E-mail: atbiju@iisc.ac.in
N
BF4
N
N
Ph
XH
Ar
XH
N
Ph
X
N
(20 mol %)
R
Ar
R
Ar
N
N
KOt-Bu (20 mol %)
oxidant (1.0 equiv)
DMSO, 30 °C, 12 h
N
N
via.
X = O, S
(+) mild conditions (+) 26 examples (+) up to 99% yield
ABSTRACT: N-Heterocyclic carbene (NHC)-catalyzed intramolecular cyclization of aldimines
generated from 2-amino phenols and aromatic aldehydes leading to the synthesis of 2-
arylbenzoxazoles under mild conditions is presented. The reaction proceeds via the generation of
the aza-Breslow intermediates from imines and NHC, which under oxidative conditions forms
the key imidoyl azoliums and a subsequent intramolecular cyclization furnishes the product. The
reaction tolerates a broad range of functional groups and the products are formed in generally
good yields.
One of the unconventional ways of forging carbon-carbon and carbon-heteroatom bonds
and thereby construction of new or existing molecules is by using N-heterocyclic carbene (NHC)
1
organocatalysis. The underlying principle behind many of these reactions is the remarkable
ability of NHCs to reverse the normal mode of reactivity of electrophiles (the umpolung
2
,3
concept). In majority cases, the electrophiles used are aldehydes, and the reactions proceed via
4
the generation of nucleophilic Breslow intermediates (acyl anion equivalents). Two important
transformations proceeding via the umpolung of aldehydes are benzoin reaction and the Stetter
reaction. Intriguingly, catalysis using this concept employing NHCs has been extended to the
5
6,7
umpolung of Michael acceptors and aldimines. NHCs are also useful for catalyzing
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transformations, which proceed in the normal way without polarity reversal. One such
intermediate is the activated carboxylate generated from suitably substituted aldehydes and
NHCs, which can undergo redox esterification to furnish functionalized esters.9
0
1
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0
In 2010, Studer and co-workers demonstrated the NHC-catalyzed oxidation of aldehydes
to esters using the bisquinone oxidant developed by Kharasch and Joshi.10a,11 These reactions
proceed via the initial generation of the Breslow intermediate from aldehyde and NHC followed
by the two electron oxidation using bisquinone to form the key acyl azolium intermediate, and a
subsequent acylation to form the ester product (Scheme 1, eq 1). In the context of our interest in
1
2
the NHC-catalyzed transformations in general and umpolung of aldimines triggered by NHCs
in particular,6a,6b we envisioned that aldimines could be converted into analogous imidoyl
azoliums by the addition of NHC to imines followed by the two electron oxidation of the initially
formed aza-Breslow intermediate (eq 2). Herein, we report the synthesis of 2-arylbenzoxazoles
by the NHC-catalyzed intramolecular cyclization of aldimines generated from 2-amino phenols
and aromatic aldehydes proceeding under oxidative conditions. Notably, benzoxazole moiety is
found is various biologically active natural products and marketed drugs.13
Scheme 1. NHC-Catalyzed Generation of Acyl Azoliums and Imidoyl Azoliums
NHC-catalyzed oxidative esterification of aldehydes (Studer)
Y
OH
O
N
O
O
Ar
Y
[O]
Y
HOR2
R
R
OR2
(1)
R
H
Y = S, NR1
R
N
N
Ar
Ar
Breslow intermediate
Acyl azolium
NHC-catalyzed oxidative generation of imidoyl azoliums (this work)
Ar
N
XH
XH
Ar
N
X
Ar
XH
Ar
Ar
N
[
O]
Y
Ar
Ar (2)
N
N
N
H
Y
N
X = O, S
Y
aza-Breslow intermediate
Imidoyl azolium
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Encouraged by our recent findings on NHC-catalyzed umpolung of imines,6a,6b the
present studies were initiated by treating the aldimine 1a with the carbene generated from the
1
1
triazolium salt 3 using KOt-Bu under oxidative conditions using bisquinone 4 in DMF at 30
C. Interestingly, under these conditions, the expected 2-aryl benzoxa-zole 2a was formed in
2% yield (Table 1, entry 1). The reactions performed using NHC generated from other
1
1
1
1
1
1
1
1
1
1
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9
0
°
7
1
4
commonly used triazolium salts 5-7 returned reduced yields of 2a (entries 2-4). KOt-Bu was
found to be the optimal base for this annulation as the reactions carried out using other organic
and inorganic bases furnished low yields of 2a (entries 5-8). The screening of different solvents
for this transformation revealed that 1,4-dioxane, toluene and CH Cl are inefficient for this
2
2
oxidative annulation (entries 9-11), whereas DMSO provided an improvement in yield to 86%
entry 12). With the high yield of 2a obtained in DMSO, we then performed a series of control
(
experiments to confirm the role of both carbene and oxidant in this transformation at 30 °C.15
The reaction afforded only 7% of 2a when performed in the absence of the triazolium salt 3
(
entry 13). Moreover, in the absence of 3 and KOt-Bu, the reaction did not proceed at all at 30 °C
and 60 °C (entries 14, 15). In addition, the presence of triazolium salt and the oxidant were
essential for this reaction (entry 16). These experiments (entries 13-16; repeated four times)
confirms the involvement of both NHC and oxidant. The use of excess oxidant reduced the yield
of 2a to 51% (entry 17). Furthermore, employing air as the oxidant afforded only 8% yield of 2a
and the use of DDQ furnished 51% of 2a (entries 18, 19).
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Table 1. Optimization of the Reaction Conditionsa
O
N
BF4
Ph
t-Bu
t-Bu
N
N
OH
N
3 (20 mol %)
O
N
Ph
Ph
KOt-Bu (20 mol %)
4
(1.5 equiv)
1a
DMF, 12 h, 30 °C
2a
t-Bu
t-Bu
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
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8
9
0
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0
1
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9
0
1
2
3
4
5
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7
8
9
0
4
O
"
Standard conditions"
variation of standard conditionsa
yield of 2a (%)b
entry
1
2
3
4
5
6
7
8
9
none
5 instead of 3
6 instead of 3
7 instead of 3
DBU instead of KOt-Bu
DIPEA instead of KOt-Bu
72
51
64
<5
11
<5
45
61
<5
<5
K
2
CO instead of KOt-Bu
3
Cs CO instead of KOt-Bu
2
3
1,4-dioxane instead of DMF
toluene instead of DMF
10
11
CH
2
Cl
2
instead of DMF
19
86
7
12
DMSO instead of DMF
no 3
1
3c,d
4c,d
5c,d
6c,d
1
1
1
no 3 and KOt-Bu
no 3 and KOt-Bu, run at 60 °C
no 3 and 4
<5
<5
<5
51
8
1
7c
8c
9c
a
2.0 equiv 4 instead of 1.5 equiv
air as an oxidant
1
1
8 instead of 4
51
Standard conditions: 1a (0.25 mmol), 3 (0.05 mmol), KOt-Bu (0.05 mmol), 4 (0.375 mmol), DMF (2.0 mL), 30
b
c
d
°C, 12 h. Isolated yields are given. Reactions performed in DMSO. These experiments were repeated four times.
O
Ph
Cl
N
I
N
N
N
ClO4 Cl
CN
CN
N
N
N
N
N
Ph
Ph
Cl
5
6
7
8
O
1
6
With the optimized reaction conditions (Table 1, entry 12), we examined the substrate
scope of this annulation reaction (Scheme 2). A variety of aldimines synthesized by the
condensation of 2-aminophenol and aromatic aldehydes bearing electron-releasing, -neutral and -
withdrawing groups at the 4-position of the ring underwent smooth annulation reaction under
mild reaction conditions under NHC-catalysis leading to the synthesis of functionalized 2-aryl
benzoxazoles in high yields in most cases (2a-2i). Moreover, aldimines derived from 3-
substituted, 2-substituted and disubstituted aromatic aldehydes are well tolerated under present
reaction conditions to afford the desired products in good yields (2j-2q). In addition, the
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heteroaromatic aldehydes-derived aldimines also worked under the present conditions to furnish
the benzoxazoles in moderate to good yields (2r-2t), thus expanding the usefulness of this
method. It is noteworthy that the reaction of aldimine synthesized from ferrocene
carboxaldehyde resulted in the formation of the corresponding product 2u in 43% yield. Besides,
electronically different aldimines formed from substituted 2-aminophenols and benzaldehyde
worked well under the present NHC-catalyzed conditions to furnish substituted 2-phenyl
benzoxazoles in good yields (2v-2y). Furthermore, this annulation is not limited to the synthesis
of benzoxazoles, but instead treatment of 2-aminothiophenol-derived aldimine under the present
reaction conditions afforded 2-phenyl benzothiazole 2z in 91% yield, thus validating the
versatility of the present protocol. Disappointingly, aldimines derived from aliphatic aldehydes
did not afford the desired products under the present reaction conditions.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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3
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3
3
3
3
3
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5
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0
1
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0
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0
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0
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3
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9
0
Scheme 2. Substrate Scope of the Annulation Reactiona
XH
X
N
3
(20 mol %)
R
Ar
R
Ar
KOt-Bu (20 mol %)
4 (1.5 equiv)
DMSO, 30 °C, 12 h
N
X = O, S
1
2
R1 = H, 2a, 86%
O
N
R1 = NMe2, 2b, 67%b
R1 = OMe, 2c, 80%b
R1 = Me, 2d, 99%
R1 = Br, 2e, 91%
R1 = Cl, 2f, 92%
R1 = F, 2g, 71%
R1 = CN, 2h, 97%
R1 = CF3, 2i, 90%
R2 = OMe, 2j, 85%
R2 = Br, 2k, 77%
R2
O
N
R1
O
N
R3 = Br, 2l, 89% R3
R3 = Cl, 2m, 96%
Br
O
Cl
Br
O
O
Cl
Me
N
N
N
F
2n, 93%
2o, 80%
2p, 63%
O
O
O
S
N
N
S
N
2
q, 32%b
2r, 50%
2s, 55%
O
O
O
N
N
N
R4
N
Fe
2
t, 82%
2u, 43%
R4 = Cl, 2v, 83%
R4 = CN, 2w, 90%
OBn
F
F
O
N
O
S
Cl
N
N
2x, 73%
2y, 94%
2z, 91%
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1
1
1
1
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2
2
2
2
2
2
2
3
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5
6
a
General reaction conditions: 1 (0.50 mmol), 3 (20 mol %), KOt-Bu (20 mol %), 4 (1.5 equiv) in DMSO
b
(4.0 mL) at 30 °C for 12 h. Yields of the isolated products are given. The reaction run for 24 h.
A few additional experiments have been performed to get insight into the mechanism as
well as the usefulness of this reaction. Intermolecular competition experiments performed using
electronically dissimilar aldimines 1c and 1h conveyed that the electron-deficient aldimine 1h
reacted ~41 times faster than the electron-rich one 1c (Scheme 3, eq 3). It is reasonable to
assume that the imidoyl azolium generated from 1h will be more electrophilic for the
intramolecular cyclization leading to 2h.16 It may be noted in this context that aldimines
synthesized from electron-deficient aldehydes react poorly in the NHC-catalyzed imine
umpolung for indole synthesis owing to the less nucleophilicity of the generated aza-Breslow
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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8
9
0
1
2
3
4
5
6
7
8
9
0
6
b
intermediates. Performing a one-pot reaction starting from 2-amino phenol and benzaldehyde
under the present reaction conditions afforded the benzoxazoles 2a in 48% yield (eq 4).
Scheme 3. Competition Experiment and One-pot Reaction
Competition experiment
OH
O
OMe
OMe
N
N
3
(20 mol%)
1
c
2c
+
+
(3)
KOt-Bu (20 mol %)
4 (1.5 equiv)
OH
O
CN
DMSO, 30 °C
CN
N
N
1h
after 1 h, 2c (<1%)
2h (41%)
2h
One-pot reaction
OH
H
(i) DMSO, 30 °C, 12 h
O
N
+
Ph (4)
O
Ph
(ii) 3 (20 mol%)
KOt-Bu (20 mol%)
NH2
2
a
4
(1.5 equiv)
DMSO, 30 °C, 12 h
one-pot, 48%
A tentative mechanism of this NHC-catalyzed annulation is shown in Scheme 4. The
reaction is likely initiated by the nucleophilic addition of the NHC generated from 3 to aldimine
1
to form the tetrahedral intermediate A, followed by proton transfer to generate the nucleophilic
aza-Breslow intermediate B.4a,17,18 In the presence of oxidant 4, the aza-Breslow intermediate B
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gets converted into the key imidoyl azolium intermediate C. Intramolecular nucleophilic addition
of phenolic-OH to imine carbon generates the NHC-bound zwitterion D, which on subsequent
elimination of NHC results in the formation of the product 2. The direct cyclization of 1 to 2 is
not occurring in the absence of 3 under the present reaction conditions as evident from the
control experiments.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 4. Proposed Mechanism of the Reaction
Ar
N
nucleophilic
attack
O
N
2
N
N
Ph
N
Ar
N
OH
1
N
N
Ph
base
Ar
N
N
N
O
H
Cl
N
N
N
BH
N
N
Ph
Ph
D
H
3
Ar
OH
A
N
N
N
Ph
proton
transfer
N
N
Ar
OH
N
N
Ph
N
H
Ar
aza-Breslow
intermediate B
imidoyl
azolium C
OH
4
We also performed additional experiments to confirm the role of NHCs to catalyze this
reaction at 30 °C. Given the precedence of the intramolecular cyclization of 1a under oxidative
1
5
conditions, a reaction was performed by treating 1a with the quinone oxidant 4 in the absence
of base and NHC precursor. Interestingly, this reaction did not work at all indicating that 4 alone
cannot mediate this reaction (Table 2, entry 1). When the reaction was carried out using 20 mol
%
KOt-Bu in presence of 4, only 7% of 2a was formed (entry 2). The formation of 2a in 86%
yield under analogous conditions in the presence of triazolium salt 3 is a clear indication of the
involvement of NHCs in this annulation reaction (see Table 1, entry 12). Notably, a further
increase in the base loading (in the absence of triazolium salt 3) resulted in the increase in the
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2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
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amount of 2a formed, indicating that oxidant 4 along with the base can mediate this reaction in
moderate yields (entries 3, 4).
Table 2. Reactions in the absence of NHCsa
OH
KOt-Bu (x mol %)
O
N
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Ph
Ph
N
4 (1.5 equiv)
DMSO, 12 h, 30 °C
1a
2a
entry
x (mol %)
Yield of 2a (%)a
1
2
3
4
0
<1
7
20
50
16
37
100
a
Isolated yields are given.
In conclusion, we have demonstrated the NHC-organocatalyzed synthesis of 2-aryl
benzoxazoles under mild conditions. The catalytically generated aza-Breslow intermediate from
-amino phenols is oxidized to the imidoyl azolium intermediate, which is the key for this
2
transformation. The intramolecular cyclization of imidoyl azolium resulted in the desired product
in moderate to good yield and broad scope. Control experiments indicated the involvement of
both NHC and oxidant for efficient conversion to the products.
Experimental Section
General Information:
Unless otherwise specified, all reactions were carried out under an atmosphere of argon in
flame-dried reaction vessels with Teflon screw cap. 30 °C Corresponds to the room temperature
of the lab when the experiments were carried out. Dry DMSO was purchased from commercial
sources and stored under argon over 4 Å molecular sieves. The 2-aminophenol and aldehydes
were purchased from commercial sources and were used without any further purification. The
phenolic imines 1 were synthesized from the corresponding aldehydes and 2-aminophenols
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following the literature procedure. KOt-Bu was purchased from Sigma Aldrich and was used as
2
0
received. The triazolium salt 3 was synthesized following the literature procedure. Melting
1
13
points were determined with a melting apparatus. H and C NMR spectra were recorded in
1
1
1
1
1
1
1
1
1
1
2
2
2
2
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2
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9
0
CDCl as solvent. Chemical shifts (δ) are given in ppm. The residual solvent signals were used
3
as references and the chemical shifts converted to the TMS scale (CDCl : δH = 7.26 ppm, δC =
3
7
7.16 ppm). HRMS measurements were carried out using ESI method and ion-trap mass
analyzer. Infrared (IR) spectra were recorded on an FT-IR spectrometer as thin films using NaCl
plates.
General Procedure for the Optimization of Reaction Conditions
To a flame-dried screw-capped test tube equipped with a magnetic stir bar was added the
azolium salt (0.05 mmol) and base (0.05 mmol). Then the screw-capped tube was evacuated and
backfilled with argon. To this mixture was added solvent (2.0 mL) under argon atmosphere. The
resultant reaction mixture was kept stirring at ambient temperature (30 °C) for 15 min. To this
mixture was added the aldimine 1a (0.25 mmol) and oxidant (0.375 mmol). Then the reaction
mixture was stirred at 30 °C for 12 h. After 12 h stirring, work-up of the reaction mixture was
done using EtOAc (3x10 mL) and organic fractions were dried using Na SO , and solvent was
2
4
evaporated. The crude residue was purified by flash column chromatography (Pet. ether/DCM =
0/20) on silica gel to afford the corresponding benzoxazole derivative 2a.
8
General Procedure for the Synthesis of 2-Aryl Benzoxazole Derivatives
To a flame-dried screw-capped test tube equipped with a magnetic stir bar was added the
triazolium salt 3 (0.027 g, 0.10 mmol) and KOt-Bu (0.011 g, 0.10 mmol) was added. Then the
screw-capped tube was evacuated and backfilled with argon. To this mixture was added DMSO
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(
4.00 mL) under argon atmosphere. The resultant reaction mixture was kept stirring at ambient
temperature (30 °C) for 15 min. To this mixture was added the phenolic imine 1 (0.5 mmol)
(solid aldimines were transferred to the screw-capped tube by closing the argon flow and liquid
aldimines were transferred via syringe under argon flow) and oxidant 4 (0.306 mg, 0.75 mmol.).
Then the reaction mixture was stirred at 30 °C for 12 h. When the reaction is complete, work-up
of the reaction mixture was done using EtOAc (10 mL) and organic fractions were dried with
Na SO , solvent was evaporated. The crude residue was purified by flash column
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chromatography (Pet. ether/DCM = 70/30) on silica gel to afford the corresponding 2-aryl
benzoxazole derivative 2.
Procedure for the 1.0 mmol scale Synthesis of 2a
To a flame-dried screw-capped test tube equipped with a magnetic stir bar the triazolium salt 3
(0.0546 g, 0.20 mmol) and KOt-Bu (0.022 g, 0.20 mmol) was added. Then the screw-capped
tube was evacuated and backfilled with argon. To this mixture was added DMSO (8.00 mL)
under argon atmosphere. The resultant reaction mixture was kept stirring at ambient temperature
(30 °C) for 15 min. To this mixture was added the (E)-2-(benzylideneamino)phenol 1a (0.197 g,
1
.0 mmol) and oxidant 4 (0.613 g, 1.50 mmol). Then the reaction mixture was stirred at 30 °C
for 12 h. After 12h, when the reaction was complete, work-up of the reaction mixture was done
using EtOAc (30 mL) and organic fractions were dried with Na SO , solvent was evaporated.
2
4
The crude residue was purified by flash column chromatography (Pet. ether/DCM = 70/30) on
silica gel to afford the corresponding 2-phenylbenzo[d]oxazole 2a as white solid (0.164 g, 84%
yield).
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One-Pot Reaction for the Synthesis of 2-phenylbenzo[d]oxazole 2a
To a flame-dried screw-capped test tube equipped with a magnetic stir bar was added 2-
aminophenol (0.054 g, 0.50 mmol.) under argon atmosphere. To this mixture were added DMSO
1
1
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0
(2.00 mL) and benzaldehyde (0.053 g, 51 µL, and 0.50 mmol.) under argon atmosphere. The
reaction mixture was stirred for 12 h at 30 °C. After the complete consumption of the starting
materials, in situ generated free carbene (from triazolium salt 3 (0.027 g, 0.10 mmol) and KOt-
Bu base (0.011 g, 0.10 mmol) in DMSO (2.00 mL) stirred for 15 min.) and oxidant 4 were added
under argon atmosphere. Then the reaction mixture was stirred at 30 °C (rt) for 12 h. After 12 h
stirring, workup of the reaction mixture was done using EtOAc (10 mL) twice and organic
fractions were dried with Na SO , solvent was evaporated. The crude residue was purified by
2
4
flash column chromatography (pet ether:DCM = 80:20) on silica gel to afford 2-
phenylbenzo[d]oxazole 2a as white solid (0.047 g, 48% yield).
2-Phenylbenzo[d]oxazole (2a):19b White solid, 0.084 g in 0.5 mmol scale, 86% yield. R (Pet.
f
1
ether /DCM = 70/30): 0.20; mp 102-104 °C; H NMR (CDCl , 400 MHz) δ 8.27-8.26 (m, 2H),
3
1
3
1
7
1
.80-7.78 (m, 2H), 7.60-7.52 (m, 4H), 7.37-7.34 (m, 2H). C{ H} NMR (CDCl , 100 MHz) δ
3
63.2, 150.9, 142.2, 131.6, 129.0, 127.8, 127.3, 125.2, 124.7, 120.1, 110.7. HRMS: calculated
+
-1
[
M+H] for C H ON: 196.0757, found: 196.0756. FTIR (cm ): 3025, 2100, 1642, 1216, 1044,
13 10
9
4
26, 768, 671.
-(Benzo[d]oxazol-2-yl)-N,N-dimethylaniline (2b): White sticky solid, 0.080 g in 0.5 mmol
1
scale, 67% yield. R (Pet. ether /DCM = 70/30): 0.12; H NMR (CDCl , 400 MHz) δ 8.13 (d, J
f
3
=
8.6 Hz, 2H), 7.72 (d, J = 7.5 Hz, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.34-7.26 (m, 2H), 6.77 (d, J =
1
3
1
8
.6 Hz, 2H), 3.05 (s, 6H). C{ H} NMR (CDCl , 100 MHz) δ 164.3, 152.5, 150.6, 142.6,
3
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2
2
2
2
2
2
2
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5
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5
5
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6
+
1
29.2, 124.2, 124.0, 119.2, 114.2, 111.7, 110.2, 40.2. HRMS: calculated [M+H] for C H ON :
15 15 2
-1
2
39.1179, found: 239.1180. FTIR (cm ): 3027, 2105, 1645, 1316, 1210, 1117, 1045, 921, 765,
672.
-(4-Methoxyphenyl)benzo[d]oxazole (2c):19b Yellow solid, 0.090 g in 0.5 mmol scale, 80%
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
1
yield. R (Pet. ether /DCM = 70/30): 0.15; mp 98-100 °C; H NMR (CDCl , 400 MHz) δ 8.19
f
3
(
d, J = 8.9 Hz, 2H), 7.75-7.73 (m, 1H), 7.55-7.53 (m, 1H), 7.34-7.29 (m, 2H), 7.01 (d, J = 8.7
1
3
1
Hz, 2H), 3.86 (s, 3H). C{ H} NMR (CDCl , 100 MHz) δ 163.3, 162.5, 150.7, 142.3, 129.5,
3
+
1
24.7, 124.5, 119.7, 114.5, 110.5, 55.5. HRMS: calculated [M+H] for C H O N: 226.0863,
1
4
12
2
-1
found: 226.0862. FTIR (cm ): 3026, 2099, 1632, 1504, 1458, 1216, 1175, 1032, 926, 847, 769,
670.
2
-(p-Tolyl)benzo[d]oxazole (2d):19b White solid, 0.103 g in 0.5 mmol scale, 99% yield. R (Pet.
f
1
ether /DCM = 70/30): 0.26; mp 112-114 °C; H NMR (CDCl , 400 MHz) δ 8.15 (d, J = 8.1 Hz,
3
1
3
1
2H), 7.78-7.75 (m, 1H), 7.58-7.56 (m, 1H), 7.36-7.32 (m, 4H), 2.43 (s, 3H). C{ H} NMR
(
CDCl , 100 MHz) δ 163.4, 150.8, 142.2, 129.8, 127.7, 125.0, 124.6, 124.5, 120.0, 110.6, 21.8.
3
+
-1
HRMS: calculated [M+H] for C H ON: 210.0913, found: 210.0911. FTIR (cm ): 3024,
1
4
12
2
102, 1641, 1216, 1045, 927, 768, 671.
2
-(4-Bromophenyl)benzo[d]oxazole (2e): Yellow solid, 0.125 g in 0.5 mmol scale, 91% yield.
1
R (Pet. ether /DCM = 70/30): 0.29; mp 152-154 °C; H NMR (CDCl , 400 MHz) δ 8.10 (d, J =
f
3
8
.2 Hz, 2H), 7.78-7.75 (m, 1H), 7.65 (d, J = 8.2 Hz, 2H), 7.58-7.55 (m, 1H), 7.37-7.35 (m, 2H).
1
3
1
C{ H} NMR (CDCl , 100 MHz) δ 162.3, 150.9, 142.1, 132.4, 129.1, 126.4, 126.2, 125.5,
3
+
1
24.9, 120.2, 110.8. HRMS: calculated [M+H] for C H ONBr: 273.9862, found: 273.9862.
1
3
9
-1
FTIR (cm ): 3026, 2100, 1645, 1483, 1411, 1216, 1065, 1014, 927, 767, 671.
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-(4-Chlorophenyl)benzo[d]oxazole (2f):19b Yellow solid, 0.106 g in 0.5 mmol scale, 92%
1
yield. R (Pet. ether /DCM = 70/30): 0.28; mp 148-150 °C; H NMR (CDCl , 400 MHz) δ 8.17
f
3
(d, J = 8.3 Hz, 2H), 7.77-7.75 (m, 1H), 7.57-7.55 (m, 1H), 7.58 (d, J = 8.3 Hz, 2H), 7.37-7.34
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
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1
2
3
4
5
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7
8
9
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1
2
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6
7
8
9
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
1
(m, 2H). C{ H} NMR (CDCl , 100 MHz) δ 162.2, 150.9, 142.1, 137.9, 129.4, 129.0, 125.8,
3
+
1
2
2
25.5, 124.9, 120.2, 110.8. HRMS: calculated [M+H] for C H ONCl: 230.0367, found:
1
3
9
-1
30.0367. FTIR (cm ): 3024, 2101, 1645, 1484, 1216, 1047, 927, 768, 671.
-(4-Fluorophenyl)benzo[d]oxazole (2g): Yellow solid, 0.075 g in 0.5 mmol scale, 71% yield.
1
R (Pet. ether /DCM = 70/30): 0.26; mp 102-104 °C; H NMR (CDCl , 400 MHz) δ 8.27-8.24
f
3
(m, 2H), 7.77-7.75 (m, 1H), 7.58-7.56 (m, 1H), 7.37-7.34 (m, 2H), 7.21 (t, J = 8.6 Hz, 2H).
1
3
1
C{ H} NMR (CDCl , 100 MHz) δ 165.0, (d, J = 252.9 Hz), 162.3, 150.9, 142.2, 130.0 (d,
3
C-F
JC-F = 8.8 Hz), 125.3, 124.8, 123.6 (d, JC-F = 2.9 Hz), 120.1, 116.3 (d, JC-F = 22.4 Hz), 116.2,
+
-1
1
10.7. HRMS: calculated [M+H] for C H ONF: 214.0663, found: 214.0660. FTIR (cm ):
13 9
3026, 2101, 1641, 1217, 1045, 927, 768, 671.
4
-(Benzo[d]oxazol-2-yl)benzonitrile (2h): Yellow solid (0.107 g in 0.5 mmol scale, 97% yield.
1
R (Pet. ether /DCM = 70/30): 0.12; mp 130-132 °C; H NMR (CDCl , 400 MHz) δ 8.36 (d, J =
f
3
1
3
1
7
.9 Hz, 2H), 7.82 (d, J = 7.9 Hz, 3H), 7.62-7.61 (m, 1H), 7.44-7.38 (m, 2H). C{ H} NMR
(CDCl , 100 MHz) δ 161.1, 151.1, 142.0, 132.8, 131.3, 128.1, 126.3, 125.3, 120.7, 118.3, 114.9,
3
+
-1
1
3
11.0. HRMS: calculated [M+H] for C H ON : 221.0709, found: 221.0706. FTIR (cm ):
14 9 2
025, 2102, 1643, 1216, 1049, 927, 850, 768, 671.
2-(4-(Trifluoromethyl)phenyl)benzo[d]oxazole (2i): Yellow solid, 0.119 g in 0.5 mmol scale,
1
9
8
0% yield. R (Pet. ether /DCM = 70/30): 0.36; mp 148-150 °C; H NMR (CDCl , 400 MHz) δ
f
3
1
3
1
.37 (d, J = 7.9 Hz, 2H), 7.82-7.78 (m, 3H), 7.62-7.60 (m, 1H), 7.42-7.39 (m, 2H). C{ H}
NMR (CDCl , 100 MHz) δ 161.6, 151.0, 142.0, 133.1 (q, J = 33.0 Hz), 130.6, 128.0, 126.1,
3
C-F
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26.1, 126.0, 125.1, 123.9 (q, JC-F = 271.9 Hz), 120.6, 110.9. HRMS: calculated [M+H] for
-1
C H ONF : 264.0631, found: 264.0627. FTIR (cm ): 3028, 2099, 1642, 1323, 1216, 1174,
1
4
9
3
1131, 1065, 927, 767, 672.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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6
7
8
9
0
1
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0
2
-(3-Methoxyphenyl)benzo[d]oxazole (2j): Yellow solid, 0.095 g in 0.5 mmol scale, 85% yield.
1
R (Pet. ether /DCM = 70/30): 0.21; mp 70-72 °C; H NMR (CDCl , 400 MHz) δ 7.84 (d, J =
f
3
7
.6 Hz, 1H), 7.78 (bs, 2H), 7.58-7.56 (m, 1H), 7.41 (t, J = 7.9 Hz, 1H), 7.36-7.34 (m, 2H), 7.07
1
3
1
(
d, J = 8.1 Hz, 1H), 3.90 (s, 3H). C{ H} NMR (CDCl , 100 MHz) δ 163.1, 160.0, 150.8,
3
1
42.1, 130.1, 128.4, 125.3, 124.7, 120.2, 120.1, 118.4, 112.0, 110.7, 55.6. HRMS: calculated
+
-1
[
M+H] for C H O N: 226.0863, found: 226.0861. FTIR (cm ): 3021, 2402, 1597, 1425,
14 12 2
1216, 1042, 929, 865, 762, 670.
2
-(3-Bromophenyl)benzo[d]oxazole (2k): Yellow solid, 0.106g in 0.5 mmol scale, 77% yield.
1
R (Pet. ether /DCM = 70/30): 0.22; mp 100-102 °C; H NMR (CDCl , 400 MHz) δ 8.42 (s,
f
3
1H), 8.18 (d, J = 7.7 Hz, 1H), 7.79-7.77 (m, 1H), 7.66 (d, J = 7.7 Hz, 1H), 7.60-7.58 (m, 1H)
.41-7.36 (m, 3H). 13C{ H} NMR (CDCl , 100 MHz) δ 161.6, 150.9, 142.0, 134.6, 130.7,
1
7
1
3
+
30.6, 129.2, 126.2, 125.7, 125.0, 123.1, 120.4, 110.9. HRMS: calculated [M+H] for
-1
C H ONBr: 273.9862, found: 273.9865. FTIR (cm ): 3026, 2100, 1643, 1217, 1044, 927, 769,
13
9
6
70.
2
-(2-Bromophenyl)benzo[d]oxazole (2l): Yellow solid, 0.123g in 0.5 mmol scale, 89% yield. Rf
1
(
Pet. ether /DCM = 70/30): 0.17; mp 54-56 °C; H NMR (CDCl , 400 MHz) δ 8.07 (d, J = 7.7
3
Hz, 1H), 7.87-7.84 (m, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.62-7.60 (m, 1H), 7.44 (t, J = 7.6 Hz, 1H),
.41-7.32 (m, 3H). 13C{ H} NMR (CDCl , 100 MHz) δ 161.6, 150.7, 141.7, 134.8, 132.2,
1
7
1
3
+
32.1, 128.4, 127.5, 125.7, 124.7, 122.0, 120.6, 110.9. HRMS: calculated [M+H] for
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C H ONBr: 273.9862, found: 273.9864. FTIR (cm ): 3024, 2101, 1642, 1442, 1217, 1037,
1
3
9
9
27, 765, 671.
2-(2-Chlorophenyl)benzo[d]oxazole (2m): Yellow solid, 0.110 g in 0.5 mmol scale, 96% yield.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
R (Pet. ether /DCM = 70/30): 0.17; mp 65-67 °C; H NMR (CDCl , 400 MHz) δ 8.16-8.14 (m,
f
3
1
3
1
1
H), 7.87-7.85 (m, 1H), 7.63-7.61 (m, 1H), 7.56 (d, J = 7.7 Hz, 1H), 7.46-7.38 (m, 4H). C{ H}
NMR (CDCl , 100 MHz) δ 161.1, 150.7, 141.8, 133.6, 132.0, 131.9, 131.5, 127.1, 126.3, 125.7,
3
+
1
24.88, 120.6, 110.9. HRMS: calculated [M+H] for C H ONCl: 230.0367, found: 230.0367.
1
3
9
-1
FTIR (cm ): 3022, 2099, 1640, 1440, 1217, 1038, 769, 670.
2
-(2-Bromo-5-fluorophenyl)benzo[d]oxazole (2n): Yellow solid, 0.136 g in 0.5 mmol scale,
1
93% yield. R (Pet. ether /DCM = 70/30): 0.33; mp 72-74 °C; H NMR (CDCl , 400 MHz) δ
f
3
7
.85-7.83 (m, 2H), 7.74-7.70 (m, 1H), 7.62-7.61 (m, 1H), 7.43-7.37 (m, 2H), 7.11-7.07 (m, 1H).
1
3
1
C{ H} NMR (CDCl , 100 MHz) δ 161.6 (d, J = 248.8 Hz), 160.4 (d, JC-F = 2.1 Hz), 150.7,
3
C-F
141.6, 136.4 (d, JC-F = 7.9 Hz), 129.8 (d, JC-F = 8.5 Hz), 129.8, 126.1, 125.0, 120.8, 119.5 (d, JC-F
22.2 Hz), 119.1 (d, JC-F = 25.1 Hz), 116.3 (d, JC-F = 3.5 Hz), 111.0. HRMS: calculated [M+H]+
=
-1
for C H ONBrF: 291.9768, found: 291.9770. FTIR (cm ): 3025, 2101, 1643, 1464, 1216,
1
3
8
1
035, 934, 882, 768, 671.
2
-(3,4-Dichlorophenyl)benzo[d]oxazole (2o): Yellow solid, 0.105 g in 0.5 mmol scale, 80%
1
yield. R (Pet. ether /DCM = 70/30): 0.27; mp 144-146 °C; H NMR (CDCl , 400 MHz) δ 8.35
f
3
(
s, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.79-7.77 (m, 1H), 7.61-7.58 (m, 2H) 7.40-7.38 (m, 2H).
1
3
1
C{ H} NMR (CDCl , 100 MHz) δ 161.0, 151.0, 142.0, 136.1, 133.7, 131.2, 129.5, 127.2,
3
+
1
2
26.7, 125.9, 125.1, 120.4, 110.9. HRMS: calculated [M+H] for C H ONCl : 263.9977, found:
1
3
8
2
-1
63.9977. FTIR (cm ): 3025, 2101, 1644, 1460, 1216, 1041, 927, 768, 671.
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-(2-Bromo-4-methylphenyl)benzo[d]oxazole (2p): Yellow solid, 0.091 g in 0.5 mmol scale,
1
6
3% yield. R (Pet. ether /DCM = 70/30): 0.26; mp 75-77 °C; H NMR (CDCl , 400 MHz) δ
f
3
7.98 (d, J = 8.0 Hz, 1H), 7.85-7.83 (m, 1H), 7.61-7.59 (m, 2H), 7.38-7.36 (m, 2H), 7.25 (d, J =
0
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2
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4
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6
7
8
9
0
13
1
7
1
.5 Hz, 1H), 2.40 (s, 3H). C{ H} NMR (CDCl , 100 MHz) δ 161.8, 150.7, 143.0, 141.8,
3
+
35.3, 132.0, 128.5, 125.5, 124.7, 121.7, 120.5, 110.8, 21.2. HRMS: calculated [M+H] for
-1
C H ONBr: 288.0019, found: 288.0022. FTIR (cm ): 3025, 2100, 1642, 1216, 1038, 926,
14 11
7
67, 671.
2
-(Naphthalen-2-yl)benzo[d]oxazole (2q):19b Yellowish solid, 0.039g in 0.5 mmol scale, 32%
1
yield. R (Pet. ether /DCM = 70/30): 0.19; mp 112-114 °C; H NMR (CDCl , 400 MHz) δ 8.77
f
3
(s, 1H), 8.32 (d, J = 8.5 Hz, 1H), 7.99-7.95 (m, 2H), 7.89-7.81 (m, 2H) 7.62-7.55 (m, 3H), 7.38-
13
1
7
.37 (m, 2H). C{ H} NMR (CDCl , 100 MHz) δ 163.3, 151.0, 142.3, 134.9, 133.1, 129.1,
3
1
28.9, 128.3, 128.0, 127.9, 127.0, 125.3, 124.8, 124.5, 124.1, 120.1, 110.7. HRMS: calculated
+
-1
[M+H] for C H ON: 246.0913, found: 246.0911. FTIR (cm ): 3023, 2401, 2101, 1632, 1452,
1
7
12
1
364, 1216, 1123, 1052, 940, 861, 768, 670.
2
-(Thiophen-2-yl)benzo[d]oxazole (2r):19b White solid, 0.050 g in 0.5 mmol scale, 50% yield.
1
R (Pet. ether /DCM = 70/30): 0.18; mp 107-109 °C; H NMR (CDCl , 400 MHz) δ 7.93-7.92
f
3
(m, 1H), 7.75-7.73 (m, 1H), 7.57-7.54 (m, 2H), 7.35-7.33 (m, 2H), 7.19 (t, J = 4.2 Hz, 1H).
1
3
1
C{ H} NMR (CDCl , 100 MHz) δ 159.2, 150.5, 142.0, 130.5, 130.2, 129.7, 128.4, 125.2,
3
+
1
24.9, 119.9, 110.6. HRMS: calculated [M+H] for C H ONS: 202.0321, found: 202.0323.
11
8
-1
FTIR (cm ): 3024, 2102, 1642, 1216, 1047, 926, 767, 671, 659.
2-(Thiophen-3-yl)benzo[d]oxazole (2s): White solid, 0.055 g in 0.5 mmol scale, 55% yield. Rf
1
(Pet. ether /DCM = 70/30): 0.25; mp 147-149 °C; H NMR (CDCl , 400 MHz) δ 8.19 (bs, 1H),
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.79 (d, J = 5.0 Hz, 1H), 7.76-7.74 (m, 1H), 7.55-7.53 (m, 1H), 7.45-7.43 (m, 1H), 7.35-7.32 (m,
1
3
1
H). C{ H} NMR (CDCl , 100 MHz) δ 159.8, 150.5, 142.0, 129.4, 128.2, 127.1, 126.7, 125.1,
3
+
124.7, 120.0, 110.6. HRMS: calculated [M+H] for C H ONS: 202.0321, found: 202.0323.
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1
8
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0
-1
FTIR (cm ): 3025, 2101, 1642, 1314, 1216, 1044, 925, 768, 670, 659.
2
-(pyridin-4-yl)benzo[d]oxazole (2t):19b Yellow solid, 0.081 g in 0.5 mmol scale, 82% yield. Rf
1
(Pet. ether /EtOAc = 90/10): 0.15; mp 127-129 °C; H NMR (CDCl , 400 MHz) δ 8.79 (d, J =
3
4
7
1
.7 Hz, 2H), 8.05 (d, J = 4.5 Hz, 2H), 7.79 (d, J = 7.4 Hz, 1H), 7.59 (d, J = 7.5 Hz, 1H), 7.42 –
1
3
1
.36 (m, 2H). C{ H} NMR (CDCl , 100 MHz) δ 160.6, 150.9, 150.8, 141.8, 134.4, 126.4,
3
+
25.2, 121.1, 120.7, 111.0. HRMS: calculated [M+H] for C H ON : 197.0715, found:
12
9
2
-1
197.0720. FTIR (cm ): 3044, 2277, 2211, 2173, 2027, 1333, 1862, 1732, 1699, 1533, 1537,
1
447, 1407, 1290, 1223, 1141, 1110, 1060, 992, 926, 833, 805.
2
-(2-Ferrocenyl)benzo[d]oxazole (2u): Pale brown solid, 0.065 g in 0.5 mmol scale, 43% yield.
1
R (Pet. ether /DCM = 70/30): 0.14; mp >200 °C; H NMR (CDCl , 400 MHz) δ 7.69 (s, 1H),
f
3
13
1
7
.51 (s, 1H), 7.31 (s, 2H), 5.09 (s, 2H), 4.52 (s, 2H), 4.19 (s, 5H). C{ H} NMR (CDCl , 100
3
MHz) δ 166.5, 150.6, 142.4, 124.4, 124.3, 119.2, 110.3, 77.5, 70.1, 69.8, 68.7. HRMS:
+
-1
calculated [M+H] for C H ONFe: 304.0419, found: 304.0417. FTIR (cm ): 3025, 2400,
17 14
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100, 1642, 1455, 1381, 1216, 1150, 1044, 1029, 926, 768, 671.
5
-Chloro-2-phenylbenzo[d]oxazole (2v):19b White solid, 0.095 g in 0.5 mmol scale, 83% yield.
1
R (Pet. ether /DCM = 70/30): 0.24; mp 107-109 °C; H NMR (CDCl , 400 MHz) δ 8.22 (d, J =
f
3
1
3
1
7.2 Hz, 2H), 7.74 (s, 1H), 7.57-7.48 (m, 4H), 7.31 (d, J = 8.6 Hz, 1H). C{ H} NMR (CDCl ,
3
1
00 MHz) δ 164.5, 149.5, 143.3, 132.1, 130.2, 129.1, 127.9, 126.8, 125.5, 120.1, 111.4. HRMS:
+
-1
calculated [M+H] for C H ONCl: 230.0367, found: 230.0368. FTIR (cm ): 3027, 2100, 1641,
1
3
9
1178, 1285, 1215, 1042, 926, 765, 670.
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-Phenylbenzo[d]oxazole-5-carbonitrile (2w): White solid, 0.099 g in 0.5 mmol scale, 90%
1
yield. R (Pet. ether /DCM = 70/30): 0.12; mp 110-112 °C; H NMR (CDCl , 400 MHz) δ 8.24
f
3
1
3
1
(d, J = 7.4 Hz, 2H), 8.06 (s, 1H), 7.68-7.62 (m, 2H), 7.59-7.53 (m, 3H). C{ H} NMR (CDCl ,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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7
8
9
0
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2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
00 MHz) δ 165.3, 153.2, 142.7, 132.6, 129.2, 128.1, 126.1, 124.7, 118.9, 112.0, 108.7. HRMS:
+
-1
calculated [M+H] for C H ON : 221.0709, found: 221.0711. FTIR (cm ): 3025, 2101, 1642,
1
4
9
2
1
251, 1216, 1044, 927, 768, 670.
7
-(Benzyloxy)-2-phenylbenzo[d]oxazole (2x): White solid, 0.055 g in 0.25 mmol scale, 73%
1
yield. R (Pet. ether /DCM = 70/30): 0.13; mp 116-118 °C; H NMR (CDCl , 400 MHz) δ 8.32-
f
3
8
.30 (m, 2H), 7.55-7.54 (m, 5H), 7.46-7.36 (m, 4H), 7.26 (t, J = 8.1 Hz, 1H), 6.95 (d, J = 8.1 Hz,
1
3
1
1H), 5.38 (s, 2H). C{ H} NMR (CDCl , 100 MHz) δ 163.1, 144.1, 140.4, 136.7, 131.7, 129.0,
3
+
1
28.8, 128.4, 127.9, 127.7, 127.1, 125.2, 112.9, 110.2, 71.5. HRMS: calculated [M+H] for
-1
C H O N: 302.1176, found: 302.1178. FTIR (cm ): 3025, 2105, 1642, 1471, 1317, 1216,
2
0
16
2
1045, 924, 767, 671.
5
,6-Difluoro-2-phenylbenzo[d]oxazole (2y): White solid, 0.109 g, in 0.5 mmol scale, 94%
1
yield. R (Pet. ether /DCM = 70/30): 0.26; mp >200 °C; H NMR (CDCl , 400 MHz) δ 8.19 (d,
f
3
1
3
1
J = 6.8 Hz, 2H), 7.57-7.52 (m, 4H), 7.44-7.40 (m, 1H). C{ H} NMR (CDCl , 100 MHz) δ
3
1
65.0, 150.1, 147.7, 146.0, 137.7, 132.0, 129.2, 127.7, 126.7, 107.8, 107.5, 100.1, 99.8. HRMS:
+
-1
calculated [M+H] for C H ONF : 232.0568, found: 232.0570. FTIR (cm ): 3025, 2102, 1640,
1
3
8
2
1
215, 1043, 1022, 921, 764, 671.
2-(4-Chlorophenyl)benzo[d]thiazole (2z): White solid, 0.112 g, in 0.25 mmol scale, 91% yield.
1
R (Pet. ether /DCM = 70/30): 0.25; mp 116-118 °C; H NMR (CDCl , 400 MHz) δ 8.07 (d, J =
f
3
8
.2 Hz, 1H), 8.02 (d, J = 8.2 Hz, 2H), 7.89 (d, J = 7.9 Hz, 1H), 7.52-7.45 (m, 3H), 7.39 (d, J =
1
3
1
7.5 Hz, 1H). C{ H} NMR (CDCl , 100 MHz) δ 166.8, 154.1, 137.2, 135.1, 132.1, 129.4,
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2
28.8, 126.6, 125.6, 123.4, 121.8. HRMS: calculated [M+H] for C H NClS: 246.0139, found:
1
3
9
-1
46.0141. FTIR (cm ): 3025, 2110, 1645, 1213, 1123, 1079, 1045, 924, 765, 671.
Supporting Information
Details on mechanistic experiments and the copies of H and C NMR spectra of all products
PDF). The Supporting Information is available free of charge on the ACS Publications website.
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(
Acknowledgement
Generous financial support from the Indian Institute of Science (start-up grant for ATB) is
gratefully acknowledged. AP thanks CSIR for the senior research fellowship. We thank Mr
Santigopal Mondal and Mr Tony Roy for repeating all the control experiments.
References

 For recent reviews on NHC organocatalysis, see: (a) Murauski, K. J. R.; Jaworski, A. A.; Scheidt,
K. A. A Continuing Challenge: N-Heterocyclic Carbene-Catalyzed Syntheses of γ-
Butyrolactones, Chem. Soc. Rev. 2018, 47, 1773-1782. (b) Flanigan, D. M.; Romanov-
Michailidis, F.; White, N. A.; Rovis, T. Organocatalytic Reactions Enabled by N-Heterocyclic
Carbenes. Chem. Rev. 2015, 115, 9307-9387. (c) Menon, R. S.; Biju, A. T.; Nair, V. Recent
Advances in Employing Homoenolates Generated by N-Heterocyclic Carbene (NHC) Catalysis in
Carbon–Carbon Bond-Forming Reactions. Chem. Soc. Rev. 2015, 44, 5040-5052. (d) Yetra, S. R.;
Patra, A.; Biju, A. T. Recent Advances in the N-Heterocyclic Carbene (NHC)-Organocatalyzed
Stetter Reaction and Related Chemistry. Synthesis 2015, 47, 1357-1378. (e) Hopkinson, M. N.;
Richter, C.; Schedler, M.; Glorius, F. An Overview of N-Heterocyclic Carbenes. Nature 2014,
5
10, 485-496. (f) Biju, A. T., Kuhl, N.; Glorius, F. Extending NHC-Catalysis: Coupling
Aldehydes with Unconventional Reaction Partners. Acc. Chem. Res. 2011, 44, 1182-1195. (g)
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Enders, D.; Niemeier, O.; Henseler, A. Organocatalysis by N-Heterocyclic Carbenes. Chem. Rev.
2007, 107, 5606-5655.
 For the evolution of cyanide catalyzed umpolung, see: Wöhler, F.; Liebig, J. Untersuchungen über
das Radikal der Benzoesäure. Ann. Der. Pharm. 1832, 3, 249-282.
0
1
2
3
4
5
6
7
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0

 Seebach, D. Methods of Reactivity Umpolung. Angew. Chem., Int. Ed. Engl. 1979, 18, 239-336.
 (a) Breslow, R. On the Mechanism of Thiamine Action. 1V. Evidence from Studies on Model
Systems J. Am. Chem. Soc. 1958, 80, 3719-3726. (b) Ukai, T.; Tanaka, R.; Dokawa, T. A New
Catalyst for Acyloin Condensation. J. Pharm. Soc. Jpn. 1943, 63, 296-300.
 For selected reports, see: (a) Nakano, Y.; Lupton D. W. Enantioselective N-Heterocyclic Carbene
Catalysis by the Umpolung of -Unsaturated Ketones. Angew. Chem. Int. Ed. 2016, 55, 3135-
3139. (b) Matsuoka, S.; Ota, Y.; Washio, A.; Katada, A.; Ichioka, K.; Takagi, K.; Suzuki, M.
Organocatalytic Tail-to-Tail Dimerization of Olefin: Umpolung of Methyl Methacrylate Mediated
by N-Heterocyclic Carbene. Org. Lett. 2011, 13, 3722-3725. (c) Biju, A. T.; Padmanaban, M.;
Wurz, N. E.; Glorius, F. N-Heterocyclic Carbene Catalyzed Umpolung of Michael Acceptors for
Intermolecular Reactions. Angew. Chem. Int. Ed. 2011, 50, 8412-8415. (d) Fischer, C.; Smith, S.
W.; Powell, D. A.; Fu, G. C. Umpolung of Michael Acceptors Catalyzed by N-Heterocyclic
Carbenes. J. Am. Chem. Soc. 2006, 128, 1472-1473.
 (a) Patra, A.; Gelat, F.; Pannecoucke, X.; Poisson, T.; Besset. T.; Biju, A. T. Synthesis of 4-
Difluoromethylquinolines by NHC-Catalyzed Umpolung of Imines. Org. Lett. 2018, 20, 1086-
1
089. (b) Patra, A.; Mukherjee, S.; Das, T. K.; Jain, S.; Gonnade, R. G.; Biju, A. T. N-
Heterocyclic Carbene-Catalyzed Umpolung of Imines. Angew. Chem. Int. Ed. 2017, 56, 2730-
734. (c) Harish, B.; Subbireddy, M.; Suresh, S. N-Heterocyclic Carbene (NHC)-Catalysed Atom
2
Economical Construction of 2,3-Disubstituted Indoles. Chem. Commun. 2017, 53, 3338-3341. For
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a related cyanide catalyzed imine umpolung, see: (d) For the related cyanide-catalyzed umpolung,
see: Lee, S. J.; Seo, H.-A.; Cheon, C.-H. Synthesis of 2‐Aryl‐Substituted Indole‐3‐acetic Acid
Derivatives via Intramolecular Imino‐Stetter Reaction of Aldimines with Cyanide. Adv. Synth.
Catal. 2016, 358, 1566-1570. For a surprising vinylogous carbonate to carbamate rearrangement
detected in an envisioned imine umpolung, see: Das, T. K.; Mondal, S.; Gonnade, R. G.; Biju, A.
T. Base-Free and Catalyst-Free Synthesis of Functionalized Dihydrobenzoxazoles via Vinylogous
Carbonate to Carbamate Rearrangement. Org. Lett. 2017, 19, 5597-5600.
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 For the umpolung of alkyl halides, see: (a) Maji, B.; Horn, M.; Mayr, H. Nucleophilic Reactivities
of Deoxy Breslow Intermediates: How Does Aromaticity Affect the Catalytic Activities of
N‐Heterocyclic Carbenes? Angew. Chem. Int. Ed. 2012, 51, 6231-6235. (b) Knappke, C. E. I.;
Neudörfl, J. M.; Jacobi von Wangelin, A. On New N-Heterocyclic Carbene Derived Alkylidene
Imidazolines. Org, Biomol. Chem. 2010, 8, 1695-1705. (c) Knappke, C. E. I.; Arduengo III, A. J.;
Jiao, H.; Neudörfl, J. M.; Jacobi von Wangelin, A. On the Dual Role of N-Heterocyclic Carbenes
as Bases and Nucleophiles in Reactions with Organic Halides. Synthesis 2011, 23, 3784-3795.
 For reviews, see: (a) Ryan, S. J.; Candish, L.; Lupton, D. W. Acyl Anion Free N-Heterocyclic
Carbene Organocatalysis. Chem. Soc. Rev. 2013, 42, 4906-4917. (b) Sarkar, S. De.; Biswas, A.;
Samanta, R. C.; Studer, A. Catalysis with N-Heterocyclic Carbenes under Oxidative Conditions.
Chem. Eur. J. 2013, 19, 4664-4678. (c) Vora, H. U.; Wheeler, P.; Rovis, T. Exploiting Acyl and
Enol Azolium Intermediates via N-Heterocyclic Carbene-Catalyzed Reactions of -Reducible
Aldehydes. Adv. Synth. Catal. 2012, 354, 1617-1639. (d) Mahatthananchai, J.; Bode, J. W. On the
Mechanism of N-Heterocyclic Carbene-Catalyzed Reactions Involving Acyl Azoliums. Acc.
Chem. Res. 2014, 47, 696-707.
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 (a) Chan, A.; Scheidt, K. A. Conversion of α,β-Unsaturated Aldehydes into Saturated Esters: An
Umpolung Reaction Catalyzed by Nucleophilic Carbenes. Org. Lett. 2005, 7, 905-908. (b)
Reynolds, N. T.; Read de Alaniz, J.; Rovis, T. Conversion of α-Haloaldehydes into Acylating
Agents by an Internal Redox Reaction Catalyzed by Nucleophilic Carbenes. J. Am. Chem. Soc.
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2004, 126, 9518-9519. (c) Chow, K. Y.-K.; Bode, J. W. Catalytic Generation of Activated
Carboxylates:ꢀ Direct, Stereoselective Synthesis of β-Hydroxyesters from Epoxyaldehydes. J. Am.
Chem. Soc. 2004, 126, 8126-8127.
 (a) De Sarkar, S.; Grimme, S.; Studer, A. NHC Catalyzed Oxidations of Aldehydes to Esters:
Chemoselective Acylation of Alcohols in Presence of Amines. J. Am. Chem. Soc. 2010, 132,
1190-1191. For the NHC-catalyzed oxidative conversion of aldehydes to TEMPO esters, see: (b)
Guin, J.; De Sarkar, S.; Grimme, S.; Studer, A. Biomimetic carbene-catalyzed oxidations of
aldehydes using TEMPO. Angew. Chem., Int. Ed. 2008, 47, 8727-8730. For the NHC-catalyzed
amidation of aldehydes, see: (c) De Sarkar, S.; Studer, A. Oxidative Amidation and Azidation of
Aldehydes by NHC Catalysis, Org. Lett. 2010, 12, 1992-1995. See also: (d) Maki, B. E.; Chan,
A.; Phillips, E. M.; Scheidt, K. A. N-Heterocyclic Carbene-Catalyzed Oxidations, Tetrahedron,
2009, 65, 3102-3109. (e) Castells, J.; Llitjos, H.; Moreno-Mañas, Nitrobenzene Aldehyde
Oxidations Catalyzed by the Conjugate Bases of Thiazolium Ions, Tetrahedron Lett. 1977, 18,
205-206.
 Kharasch, M. S.; Joshi, B. S. Reactions of Hindered Phenols. 11. Base-Catalyzed Oxidations of
Hindered Phenols. J. Org. Chem. 1957, 22, 1439-1443.
 For selected references, see: (a) Patra, A.; Bhunia, A.; Yetra, S. R.; Gonnade. R. G.; Biju, A. T.
Diastereoselective Synthesis of Cyclopentanone-fused Spirooxindoles by N-Heterocyclic
Carbene-Catalyzed Homoenolate Annulation with Isatilidenes. Org. Chem. Front. 2015, 2, 1584-
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588. (b) Bhunia, A.; Yetra, S. R.; Bhojgude, S. S.; Biju, A. T. Efficient Synthesis of γ-Keto
Sulfones by NHC-Catalyzed Intermolecular Stetter Reaction. Org. Lett. 2012, 14, 2830-2833.
 For reviews, see: (a) Rajasekhar, S.; Maiti, B.; Chanda, K. A Decade Update on Benzoxazoles, a
Privileged Scaffold in Synthetic Organic Chemistry. Synlett 2017, 28, 521-541. (b) Demmer, C.
S.; Bunch, L. Benzoxazoles and Oxazolopyridines in Medicinal Chemistry Studies. Eur. J. Med.
Chem. 2015, 97, 778-785. (c) Noёl, S.; Cadet, S.; Gras, E.; Hureau, C. The Benzazole Scaffold: A
SWAT to Combat Alzheimer's Disease. Chem. Soc. Rev. 2013, 42, 7747-7762.
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 Moreover, the NHCs generated from common imidazolium and thiazolium salts using KOt-Bu
were found to be inefficient in this transformation.

 For selected recent reports on related benzoxazoles synthesis, see: (a) Koleda, O.; Broese, T.;
Noetzel, J.; Roemelt, M.; Suna, E.; Francke, R. Synthesis of Benzoxazoles Using
Electrochemically Generated Hypervalent Iodine. J. Org. Chem. 2017, 82, 11669-11682. (b) Yu,
C.; Guo, X.; Xi, Z.; Muzzio, M.; Yin, Z.; Shen, B.; Li, J.; Seto, C. T.; Sun, S. AgPd Nanoparticles
Deposited on WO2.72 Nanorods as an Efficient Catalyst for One-Pot Conversion of
Nitrophenol/Nitroacetophenone into Benzoxazole/Quinazoline. J. Am. Chem. Soc. 2017, 139,
5712-5715. (c) Gao, S.; Gao, L.; Meng, H.; Luo, M.; Zeng, X. Iron-Catalyzed Synthesis of
Benzoxazoles by Oxidative Coupling/Cyclization of Phenol Derivatives with Benzoyl Aldehyde
Oximes. Chem. Commun. 2017, 53, 9886-9889. (d) Meng, X.; Wang, Y.; Chen, B.; Chen, G.;
Jing, Z.; Zhao, P. OMS-2/H O /Dimethyl Carbonate: An Environmentally-Friendly
2
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Heterogeneous Catalytic System for the Oxidative Synthesis of Benzoxazoles at Room
Temperature, Org. Process Res. Dev. 2017, 21, 2018-2024. (e) Chen, W.; An, W.; Wang, Y.; Yu,
A. Mechanisms of Metal-Free Aerobic Oxidation to Prepare Benzoxazole Catalyzed by Cyanide:
A Direct Cyclization or Stepwise Oxidative Dehydrogenation and Cyclization? J. Org. Chem.
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016, 81, 10857-10862. (f) Wang, L.; Ma, Z.-G.; Wei, X.-J.; Meng, Q.-Y.; Yang, D.-T.; Du, S.-F.;
Chen, Z.-F.; Wu, L.-Z.; Liu, Q. Synthesis of 2-Substituted Pyrimidines and Benzoxazoles via a
Visible-Light-Driven Organocatalytic Aerobic Oxidation: Enhancement of the Reaction Rate and
Selectivity by a Base. Green. Chem. 2014, 16, 3752-3757.
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 For details, See the Supporting Information.
 For a related amide synthesis envisioned to proceed via the aza-Breslow intermediate, see: (a)
Wang, G.; Fu, Z.; Huang, W. Access to Amide from Aldimine via Aerobic Oxidative Carbene
Catalysis and LiCl as Cooperative Lewis Acid. Org. Lett. 2017, 19, 3362-3365. See also: (b)
Premaletha, S.; Ghosh, A.; Joseph, S.; Yetra, S. R.; Biju, A. T. Facile Synthesis of N-Acyl 2-
Aminobenzothiazoles by NHC-Catalyzed Direct Oxidative Amidation of Aldehydes. Chem.
Commun. 2017, 53, 1478-1481.
 For the isolation of aza-Breslow intermediates, see: (a) DiRocco, D. A.; Oberg, K. M.; Rovis, T.
Isolable Analogues of the Breslow Intermediate Derived from Chiral Triazolylidene Carbenes J.
Am. Chem. Soc. 2012, 134, 6143-6145. (b) Simonovic, S.; Frison, J.-C.; Koyuncu, H.; Whitwood,
A. C.; Douthwaite, R. E. Addition of N-Heterocyclic Carbenes to Imines: Phenoxide Assisted
Deprotonation of an Imidazolium Moiety and Generation of Breslow Intermediates Derived from
IminesOrg. Lett. 2009, 11, 245-247.

 (a) He, J.; Lin, F.; Yang, X.; Wang, D.; Tan, X.; Zhang, S. Sustainable Synthesis of 2-
Arylbenzoxazoles over a Cobalt-Based Nanocomposite Catalyst. Org. Process Res. Dev. 2016,
20, 1093-1096. (b) Cho, Y. H.; Lee, C. Y.; Ha, D. C.; Cheon, C. H. Cyanide as a Powerful
Catalyst for Facile Preparation of 2-Substituted Benzoxazoles via Aerobic Oxidation. Adv. Synth.
Catal. 2012, 354, 2992-2996.
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 F. R. Michailidis, C. Besnard, A. Alexakis, N-Heterocyclic Carbene-Catalyzed Annulation of α-
Cyano-1,4-diketones with Ynals. Org. Lett. 2012, 14, 4906-4909.
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