One-Pot Tandem ortho-Naphthoquinone-Catalyzed Aerobic Nitrosation of N-Alkylanilines and Rh(III)-Catalyzed C-H Functionalization Sequence to Indole and Aniline Derivatives

Article abstract of DOI:10.1021/acs.joc.0c02776

The nitroso group served as a traceless directing group for the C-H functionalization of N-alkylanilines, ultimately removed after functioning either as an internal oxidant or under subsequent reducing conditions. The unique ability of o-NQ catalysts to aerobically oxidize the N-alkylanilines without using solvents and stoichiometric amounts of oxidants has rendered the new opportunity to develop the telescoped catalyst systems without a need for directly handling the hazardous N-nitroso compounds.

Full text of DOI:10.1021/acs.joc.0c02776

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Article
One-Pot Tandem ortho-Naphthoquinone-Catalyzed Aerobic
Nitrosation of N‑Alkylanilines and Rh(III)-Catalyzed C−H
Functionalization Sequence to Indole and Aniline Derivatives
Tengda Si, Hun Young Kim,* and Kyungsoo Oh*
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ABSTRACT: The nitroso group served as a traceless directing group for
the C−H functionalization of N-alkylanilines, ultimately removed after
functioning either as an internal oxidant or under subsequent reducing
conditions. The unique ability of o-NQ catalysts to aerobically oxidize the
N-alkylanilines without using solvents and stoichiometric amounts of
oxidants has rendered the new opportunity to develop the telescoped
catalyst systems without a need for directly handling the hazardous N-
nitroso compounds.
Nevertheless, the preparation of N-nitroso compounds with
the use of stoichiometric amounts of oxidants10 combined with
the inherent toxicity associated with N-nitroso compounds11
calls for new catalytic approaches to the N-nitrosation as well
as one-pot/tandem C−H functionalization of N-nitroso
compounds. Recently, our group developed the ortho-
naphthoquinone (o-NQ)-catalyzed aerobic N-nitrosation of
amines, where 2-nitropropane served as the source of “NO”
and molecular oxygen as the sole oxidant.12 Encouraged by the
mild reaction conditions of the o-NQ-catalyzed aerobic N-
nitrosation of amines without needs for solvent combined with
the synthetic versatility of N-nitrosoaniline derivatives as a
directing group,9 we envisioned the one-pot N-nitrosation
followed by the C−H functionalization of in situ generated N-
nitrosoanilines (Scheme 1c). Herein, we report the aerobic C−
H functionalization of anilines with alkynes and alkenes via N-
nitrosoaniline intermediates to give the highly substituted
indole and aniline derivatives. The successful implementation
of one-pot N-nitrosation, C−H functionalization, and removal
of the nitroso group owes to the fact that the involved catalyst
systems are tolerant to moisture and air, the key features for
the development of practical catalytic transformations.
INTRODUCTION
■
Aniline derivatives serve as synthetic precursors to various
commodity chemicals, and the strategic functionalization of
anilines has been the focus of academic as well as industrial
research efforts.1 While the ortho-C−H activation strategies of
anilines without directing groups have been explored in the
Ru-catalyzed cyclization to 1,2-dihydroquinolines,2 the Pd-
catalyzed synthesis of indoles,3 and the Rh-catalyzed synthesis
of quinolines,4 the alkyne partners in the indole synthesis are
limited to highly electrophilic alkynes such as methyl
acetylenedicarboxylates and methyl propiolate (Scheme 1a).
Currently there are three distinctive ortho-C−H directing
group approaches for anilines:5 (1) the introduction of
carbonyl directing groups, (2) the transformation to other
functional groups, and (3) the conversion to heterocyclic
directing groups. Among the directing group-assisted ortho-C−
H functionalization strategies of anilines, the in situ acetylation
of anilines allows the concomitant directing group introduction
and removal in a one-pot fashion. Thus, the Huang group in
2014 demonstrated the in situ formation of acetanilides of
anilines followed by the Rh-catalyzed oxidative annulation to
indole derivatives after hydrolysis using NaOH (Scheme 1b).6
In 2017, the Kapur group also disclosed the in situ acetylation
of anilines followed by the Ru-catalyzed annulation to
quinolines, in which the aromatization of acetanilide products
concomitantly removed the directing group.7 While the one-
pot introduction of directing group and removal has opened
new opportunities for the traceless C−H functionalizations,8
the majority of directing group strategies requires the
prefunctionalization of anilines. In particular, the recent
emergence of N-nitroso directing groups has spurred the
rapid advancement of C−H functionalization of anilines.9
Received: November 19, 2020
https://dx.doi.org/10.1021/acs.joc.0c02776
© XXXX American Chemical Society
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Scheme 1. C−H Functionalization Strategies for Anilines
Table 1. Optimization of One-Pot Tandem
Functionalization of N-Methylaniline
a
b
entry
catalyst
additive
solvent
yield (%)
1
2
3
4
5
6
7
8
9
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[IrCp*Cl2]2
Co(Cp*)2PF6
[RuCp*Cl2]2
[RhCp*Cl2]2
AgOAc
AgSbF6
Cu(OAc)2
NaOAc
Cu(OAc)2
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
MeOH
MeOH
MeOH
MeOH
EtOH
EtOH
i-PrOH
t-BuOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
78
42
86
<5
85
90
67
30
9
10
11
12
13
0
0
<5
0
80
38
66
AgOAc
AgOAc
AgOAc
AgOAc
c
14
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
d
15
e
16
a
Reaction conditions: 1a (0.4 mmol), i-PrNO2 (4 mmol), and o-NQ
(0.04 mmol; 10 mol %) under O2 balloon at 120 °C for 12 h, then 2a
(0.2 mmol), catalyst (0.006 mmol; 3 mol %), and additive (0.12
mmol; 60 mol %) in solvent (0.15 mL) under O2 balloon at 80 °C for
b
c
7 h. Isolated yields of 3a after column chromatography. Use of 30
d
e
mol % of AgOAc. Use of 1 mol % of [RhCp*Cl2]2. Reaction under
argon.
manner (1.3 M), which led to the 90% yield of 3a (entries 5−
8). The use of other commercially available metal catalysts was
not effective (entries 9−11). The control experiments
confirmed the critical roles of both Rh catalyst and silver
additive, where the reaction did not proceed in the absence of
either one (entries 12 and 13). The reduced amount of AgOAc
additive to 30 mol % slightly lowered the yield of 3a to 80%, as
opposed to 90% upon using 60 mol % (entries 6 and 14). The
reduced amount of [RhCp*Cl2]2 catalyst from 3 to 1 mol %
significantly lowered the yield of 3a to 38% (entry 15). Finally,
the reaction was conducted under argon instead of O2, and the
reduced yield of 3a was still observed in 66% yield, possibly
due to the residual O2 content in EtOH that still promotes the
generation of active Rh(III) species from [RhCp*Cl2]2 (entry
16).
The substrate scope for the optimized one-pot tandem
reaction was investigated with aniline derivatives (Scheme 2).
The examination of N-alkyl groups revealed that the presence
of sterically demanding i-Pr group, oxidizable Bn group, and
conjugated Ph group lowered the isolated yields of indole
derivatives 3c−3e to 35−47%. The electronic effect of the
para-position of N-methylaniline derivatives was not apparent,
where the electron-donating methoxy-substituted and the
electron-withdrawing fluorine or nitrile-substituted N-methyl-
anilines provided the low yields of indole products 3g, 3h, and
3k in 45−53%. Nevertheless, the optimized one-pot tandem
functionalization of anilines tolerated various halogen atoms
and carbonyl groups, where the desired indole derivatives 3f,
3i−3j, and 3l−3o were obtained in 60−95% yields. In
addition, meta-substituted N-methylaniline provided the
RESULTS AND DISCUSSION
■
The development of one-pot N-nitrosation of anilines and the
C−H activation sequence heavily relies on the efficiency as
well as the effectiveness of the o-NQ-catalyzed aerobic N-
nitrosation of anilines. Thus, the previous aerobic N-nitro-
sation conditions for secondary/tertiary amines were further
optimized for N-methylaniline 1a: 10 mol % of o-NQ catalyst
and 10 equiv of i-PrNO2 as the “NO” source at 120 °C for 12
h.13 Thus, after the N-methylaniline 1a was subjected under
the aerobic N-nitrosation conditions, the direct addition of
alkyne 2a, metal catalyst, and additive was tested in alcoholic
solvents (Table 1). The use of commercially available
[RhCp*Cl2]2 catalyst in combination with AgOAc additive
in MeOH provided the desired indole derivative 3a in 78%
yield (entry 1). The use of other silver salts such as AgSbF6
lowered the isolated yield of 3a to 42% (entry 2), possibly due
to the short lifetime of AgSbF6 in alcoholic solvents. Switching
silver to copper additive improved the isolated yield of 3a to
86% (entry 3). The redox function of the additives was
confirmed using NaOAc, where the desired product 3a was
merely observed (entry 4). The solvent screening indicated
that the use of unpurified EtOH, a class III solvent,14 was
tolerated and the reaction proceeded in a highly concentrated
B
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isolating the N-nitroso intermediates merits in terms of
operational simplicity as well as enhanced environmental/
safety features (no direct handling of N-nitroso compounds
and the use of a class III solvent, unpurified EtOH, in a highly
concentrated manner).
Scheme 2. Aniline Substrate Scope for One-Pot Tandem
Functionalization
a
Encouraged by the facile C−H functionalization of anilines
using alkynes, we further investigated the use of alkenes,
instead of alkynes, under the optimized tandem reaction
sequence (Scheme 4). Gratifyingly, the desired alkenylation of
Scheme 4. Alkene Substrate Scope for One-Pot Tandem
a
Functionalization
a
(a) Reaction on the 1 mmol scale in 76% yield.
regioselective formation of indole 3p in 77% yield. However,
the desired indole product 3q from tetrahydroquinoline was
obtained in 31% yield, and the use of N-methylnaphthalen-2-
amine provided the indole product 3r as a 1.2:1 mixture of
regioisomers in 32% yield.
Next, the one-pot tandem functionalization of N-methylani-
line 1a was examined with a variety of alkynes (Scheme 3).
Scheme 3. Alkyne Substrate Scope for One-Pot Tandem
a
Functionalization
a
(a) Reaction on the1 mmol scale in 72% yield. (b) 10 mol % AgSbF6
was used instead of AgOAc. (c) Reaction at 90 °C.
N-alkylanilines using methyl acrylate 4a proceeded smoothly in
unpurified EtOH, providing the alkenylated N-nitrosoanilines
5a−5c in 69−95% yields. The electronic effect of N-
methylaniline derivatives somewhat mirrored the reactions
with alkynes, where the 4-methoxy-, 4-bromo-, and 4-phenyl-
substituted N-methylanilines resulted in the products 5e, 5h,
and 5l in 35−44% yields. However, other functionalized N-
methylanilines provided the corresponding alkenylated N-
alkylanilines 5d, 5f−5g, and 5i−5m in higher yields of 68−
93%. The use of t-butyl acrylate 4b and styrene 4c as alkene
coupling partners was also applicable, where the products 5n−
5o were obtained in 70−80% yields. In addition, the use of p-
quinones also provided the desired products 5p−5t at a higher
reaction temperature of 90 °C in 37−88% yields. The N-nitro
products 5 were obtained as a mixture of anti/syn-isomers due
to the different orientations of R−N−NO;15 thus the
a
(a) 2.0 equiv of Cu(OAc)2 was used instead of AgOAc.
The use of disubstituted alkynes with different electronic
characters provided the desired indole products 3s−3v in 60−
83% yields. Also, the sterically demanding 1- and 2-naphthyl-
substituted alkynes underwent the desired one-pot tandem
reaction to give the indole product 3w−3x in 41−55% yields.
While the isolated yields of the indole products with
thiophenyl 3y, unsymmetric 3z, electron-deficient 3za, and
dialkyl 3zb−3zc moieties were modest, given the multiple
reaction sequence of the current one-pot tandem functional-
ization, the rapid access to a variety of indole products without
C
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denitrosation of the alkenylated N-nitrosoanilines 5 was
performed using the Kandasamy method,16 where the I2-
catalyzed reduction of the nitroso group was performed with
Et3SiH. The application of Kandasamy’s reduction protocol
resulted in the formation of the alkenylated N-methylanilines 6
within 10 min, where the three-step reaction sequence
provided the final products 6a−6o in 30−86% yields from
N-methylanilines 1. In practice, Kandasamy’s denitrosation
conditions resulted in low yields of 6 upon using the crude
mixture of alkenylated N-nitrosoanilines 5; thus the quick
removal of impurities was needed for the high yielding
denitrosation conditions to give the alkenylated N-methylani-
lines 6. Unfortunately, the p-quinone moiety in 5p−5t was not
compatible and led to the decomposition with Kandasamy’s
denitrosation conditions.17
The development of the tandem C−H functionalization of
anilines benefits from the compatibility of o-NQ catalyst and 2-
nitropropane in the subsequent Rh(III)-catalyzed C−H
functionalization of N-nitrosoanilines. However, the control
experiments using the N-nitrosoaniline 1a-NO confirmed the
deleterious effects of o-NQ catalyst and 2-nitropropane on the
formation of the indole 3a (Scheme 5). The investigation into
subsequent C−H functionalization of N-nitrosoaniline 1a-NO.
The removal of the N-nitroso directing group significantly
hindered the direct C−H functionalization of anilines, and this
leads to the formation of 3a in 22% yield, but not 5a. While
more studies are needed for the underlying mechanism for the
direct C−H functionalization of aniline, it is possible to
speculate the Rh-catalyzed hydroamination pathway4 between
N-methyl aniline 1a and diphenylacetylene 2a to give the
enamine intermediate for a subsequent cyclization to give the
indole product 3a.3 One of the key features of the current
tandem C−H functionalization of anilines is the use of a class
III solvent, unpurified EtOH, as opposed to other class I
solvents, DCM,9e HFIP,9c and DCE,9b−f and class II solvents,
MeOH9a−e and CH3CN.9d Thus, the investigation into the
amount of EtOH usage revealed that the reaction concen-
tration was not critical for the efficiency of the reaction, and
the optimal concentration of EtOH turned out to be 1.3 M.20
Finally, the tandem C−H functionalization reaction in EtOD-
d6 resulted in the formation of 1a-NO without the deuterium
incorporation due to the water byproduct from the o-NQ-
catalyzed aerobic N-nitrosation conditions. Thus, the deute-
rium incorporation experiment with an isolated 1a-NO
confirmed the ready C−H activation of N-nitrosoaniline 1a-
NO under the optimized reaction conditions, and this suggests
the critical role of the N-nitroso group for the projected C−H
activation pathway. Accordingly, the N-nitro directing group of
1a-NO in EtOD-d6 promoted the formation of 3a without the
deuterium incorporation, and this supports the direct
cyclization pathway of alkenylrhodium C from the migratory
insertion of arylrhodium B to the indole product 3a without
the proto-demetalation step.9d
Scheme 5. Control Experiments for the Effect of Reagents,
Nitroso Directing Group, and C−H Activation Pathway
CONCLUSION
■
In summary, we have developed the one-pot aerobic C−H
functionalization of anilines via a sequence of o-NQ-catalyzed
N-nitrosation followed by the Rh(III)-catalyzed alkenylations
of in situ generated N-nitrosoaniline derivatives to indole and
alkenylated aniline derivatives. The use of a class III solvent,
unpurified EtOH, in a highly concentrated condition combined
with the high tolerance of moisture and air is one of the key
features of the current tandem reaction sequence. In addition,
the telescoping of the N-nitroso compounds for the
subsequent reaction avoids the hazard risk associated with
the handling of the harmful N-nitroso compounds in the
laboratory and industrial settings. Given the wide synthetic
versatility of the N-nitroso compounds in organic synthesis, the
development of tandem reaction sequences involving the o-
NQ-catalyzed aerobic N-nitrosation of amines provides ample
possibility for the preparation of value-added chemicals. Our
current efforts are directed to the further exploration of one-
pot tandem aerobic reactions of amines via the o-NQ-catalyzed
aerobic N-nitrosation method, and our results will be reported
in due course.
EXPERIMENTAL SECTION
■
General Procedures for the Synthesis of Methylanilines
using Different Aryl Bromides. Aryl bromides (5 mmol, 1 equiv),
40% aqueous methylamine solution (4.1 mL, 25 mmol, 5 equiv), and
copper powder (0.016 g, 5 mol %) were combined in a 30 mL
screwed sealed vial and placed in an oil bath. The reaction mixture
was magnetically stirred and heated to 100 °C. When the reaction was
completed, the reaction mixture was cooled to room temperature, and
ethyl acetate was added to extract the N-methylanilines. The organic
the fate of o-NQ catalyst and 2-nitropropane after the aerobic
oxidation of N-methylaniline 1a suggested that the crude
mixture did not contain the o-NQ catalyst,18 and less than 3−4
equiv of 2-nitropropane was left in the crude reaction
mixture.19 Thus, it is conceivable that the residual amounts
of o-NQ catalyst and 2-nitropropane are low enough in the
D
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layer was separated, and the aqueous layer was extracted by the ethyl
acetate (3 × 10 mL). The combined extracts were dried by anhydrous
sodium sulfate and then concentrated under reduced pressure and
purified by silica-gel column chromatography (eluent: 90:10 hexanes/
ethyl acetate) to afford the title compounds.
and the residue was purified by silica gel flash chromatography using
hexane/EtOAc (80:1 to 30:1) to afford the indole derivatives.
1-Methyl-2,3-diphenyl-1H-indole (3a). Eluent: 80:1 hexanes/ethyl
acetate; 51 mg, 90% yield, yellow amorphous solid. The product was
prepared via the general procedure A. 1H NMR and 13C NMR spectra
for this compound are consistent with previously reported literature
data.9e 1H NMR (CDCl3, 600 MHz): δ 7.84 (d, J = 7.8 Hz, 1H), 7.45
(d, J = 8.4 Hz, 1H), 7.42−7.39 (m, 3H), 7.37−7.32 (m, 5H), 7.31 (t,
J = 8.4 Hz, 2H), 7.24−7.19 (m, 2H), 3.71 (s, 3H). 13C{1H} NMR
(CDCl3, 150 MHz): δ 137.6, 137.5, 135.4, 132.0, 131.3, 130.0, 128.5,
128.3, 128.2, 127.1, 125.6, 122.3, 120.3, 119.7, 115.2, 109.7, 31.1.
For the scale-up reaction, a flame-dried 25 mL flask was charged
with N-alkyl aniline derivatives (2.0 mmol), catalyst o-NQ (0.20
mmol, 10 mol %), and 2-nitropropane (20 mmol). The solution was
stirred under O2 at 120 °C. After the reaction was complete by TLC
(24 h), the reaction mixture was then cooled to room temperature.
[RhCp*Cl2]2 (0.030 mmol, 3 mol %), AgOAc (0.60 mmol, 60 mol
%), and diphenylacetylene (1.0 mmol) in ethanol (0.75 mL) were
added to the vial. The mixture was stirred at 80 °C under O2 for 18 h.
Upon the complete consumption of alkyne, the reaction was cooled to
room temperature. Volatile solvent and reagents were removed by
rotary evaporation, and the residue was purified by silica gel flash
chromatography using hexane/EtOAc (80:1) to afford the indole
derivative 3a in 76% yield (215 mg).
1-Ethyl-2,3-diphenyl-1H-indole (3b). Eluent: 80:1 hexanes/ethyl
acetate; 56 mg, 95% yield, yellow crystalline solid. The product was
prepared via the general procedure A. 1H NMR and 13C NMR spectra
for this compound are consistent with previously reported literature
data.9e 1H NMR (CDCl3, 600 MHz): δ 7.82 (d, J = 7.2 Hz, 1H), 7.45
(d, J = 7.8 Hz, 1H), 7.41−7.37 (m, 3H), 7.36−7.34 (m, 2H), 7.32−
7.28 (m, 3H), 7.28−7.24 (m, 2H), 7.21−7.15 (m, 2H), 4.15 (q, J =
7.2 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (CDCl3, 150
MHz): δ 137.4, 136.2, 135.4, 132.4, 131.2, 129.9, 128.6, 128.2, 127.4,
125.5, 122.2, 120.2, 119.9, 115.5, 109.9, 38.8, 15.5.
N-Methyl-[1,1′-biphenyl]-4-amine. Eluent: 90:10 hexanes/ethyl
acetate; 170 mg, 47% yield, white amorphous solid. 1H NMR and 13
C
NMR spectra for this compound are consistent with previously
reported literature data.21 1H NMR (CDCl3, 600 MHz): δ 7.56 (d, J
= 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.41 (t, J = 7.2 Hz, 2H),
7.28−7.25 (m, 1H), 6.70 (d, J = 9.0 Hz, 2H), 3.80 (bro, 1H), 2.89 (s,
3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 148.9, 141.5, 130.3, 128.8,
128.0, 126.4, 126.2, 112.8, 30.9.
N-Methylnaphthalen-2-amine. Eluent: 90:10 hexanes/ethyl ac-
1
etate; 123 mg, 39% yield, brown amorphous solid. H NMR and 13C
NMR spectra for this compound are consistent with previously
reported literature data.22 1H NMR (CDCl3, 600 MHz): δ 7.69 (d, J
= 7.8 Hz, 1H), 7.67−7.63 (m, 2H), 7.40−7.37 (m, 1H), 7.24−7.21
(m, 1H), 6.92 (dd, J = 8.4, 2.4 Hz, 1H), 6.86 (d, J = 1.8 Hz, 1H), 2.92
(s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 146.7, 135.3, 129.0,
127.8, 126.5, 126.1, 122.2, 118.1, 104.5, 31.1.
General Procedures for the Synthesis of Symmetrical
Diarylalkynes. A solution of aryl halides (1.0 equiv) and
trimethylsilylacetylene (0.6 equiv), Pd(OAc)2 (10 mol %), Cu-
(Xantphos)I (10 mol %), and Cs2CO3 (2 equiv) in anhydrous DMF
(10 mL) was heated at 60 °C for 12−24 h under argon. After the
reaction was completed, DMF was removed under reduced pressure.
The remaining mixture was extracted with ethyl acetate (3 × 10 mL),
and the combined organic layers were dried over anhydrous Na2SO4
and filtered. After removal of the solvent, the residue was purified by
flash column chromatography on the silica gel (eluent: 95:5 hexanes/
ethyl acetate) to afford the desired products.
4,4′-(Ethyne-1,2-diyl)dibenzonitrile. Eluent: 95:5 hexanes/ethyl
1
acetate; 220 mg, 19% yield, brown amorphous solid. H NMR and
13C NMR spectra for this compound are consistent with previously
reported literature data.23 1H NMR (CDCl3, 600 MHz): δ 7.68−7.66
(m, 4H), 7.64−7.62 (m, 4H). 13C{1H} NMR (CDCl3, 150 MHz):
132.4, 132.3, 127.2, 118.4, 112.6, 91.7.
1-Isopropyl-2,3-diphenyl-1H-indole (3c). Eluent: 80:1 hexanes/
ethyl acetate; 29 mg, 47% yield, yellow crystalline solid. The product
1
was prepared via the general procedure A. H NMR and 13C NMR
spectra for this compound are consistent with previously reported
literature data.9e 1H NMR (CDCl3, 600 MHz): δ 7.82 (d, J = 7.8 Hz,
1H), 7.68 (d, J = 8.4 Hz, 1H), 7.42−7.39 (m, 3H), 7.35−7.32 (m,
2H), 7.30−7.24 (m, 5H), 7.20−7.15 (m, 2H), 4.59 (septet, J = 6.6
Hz, 2H), 1.65 (t, J = 6.6 Hz, 6H). 13C{1H} NMR (CDCl3, 150
MHz): δ 137.7, 135.4, 134.7, 132.9, 131.3, 130.1, 128.5, 128.3,
128.2(1), 128.1(5), 125.5, 121.6, 120.0, 119.8, 115. 3, 112.4, 48.0,
21.7.
1,2-Di(naphthalen-2-yl)ethyne. Eluent: 95:5 hexanes/ethyl ac-
1
etate; 250 mg, 36% yield, yellow crystalline solid. H NMR and 13C
NMR spectra for this compound are consistent with previously
reported literature data.24 1H NMR (CDCl3, 600 MHz): δ 8.11 (s,
2H), 7.86−7.83 (m, 6H), 7.64 (d, J = 8.4 Hz, 2H), 7.54−7.49 (m,
4H). 13C{1H} NMR (CDCl3, 150 MHz): δ 133.2, 133.0, 131.7, 128.6,
128.2, 128.0, 127.9, 126.9, 126.7, 120.7, 90.3.
1,2-Di(naphthalen-1-yl)ethyne. Eluent: 95:5 hexanes/ethyl ac-
1-Benzyl-2,3-diphenyl-1H-indole (3d). Eluent: 70:1 hexanes/ethyl
acetate; 25 mg, 35% yield, yellow amorphous solid. The product was
prepared via the general procedure A. 1H NMR and 13C NMR spectra
for this compound are consistent with previously reported literature
data.9e 1H NMR (CDCl3, 600 MHz): δ 7.86−7.84 (m, 1H), 7.36 (dd,
J = 7.8, 1.2 Hz, 1H), 7.34−7.26 (m, 10H), 7.26−7.18 (m, 4H), 7.04
(d, J = 6.6 Hz, 2H), 5.32 (s, 2H). 13C{1H} NMR (CDCl3, 150 MHz):
δ 138.2, 138.0, 137.1, 135.2, 131.9, 131.2, 130.0, 128.8, 128.5, 128.3,
127.5, 127.3, 126.3, 125.7, 122.5, 120.6, 119.9, 115.8, 110.7, 47.7.
1,2,3-Triphenyl-1H-indole (3e). Eluent: 70:1 hexanes/ethyl ac-
etate; 28 mg, 41% yield, yellow crystalline solid. The product was
prepared via the general procedure A. 1H NMR and 13C NMR spectra
for this compound are consistent with previously reported literature
data.9e 1H NMR (CDCl3, 600 MHz): δ 7.82−7.80 (m, 1H), 7.38 (t, J
= 7.2 Hz, 4H), 7.36−7.31 (m, 4H), 7.26−7.22 (m, 5H), 7.18−7.12
(m, 3H), 7.11−7.08 (m, 2H). 13C{1H} NMR (CDCl3, 150 MHz): δ
138.3, 138.0, 137.2, 135.1, 131.7, 131.3, 130.4, 129.2, 128.4(3),
128.4(0), 127.7, 127.5, 127.3, 126.1, 122.9, 121.0, 119.7, 117.9, 116.8,
110.8.
1
etate; 83 mg, 30% yield, yellow crystalline solid. H NMR and 13C
NMR spectra for this compound are consistent with previously
reported literature data.24 1H NMR (CDCl3, 600 MHz): δ 8.58 (d, J
= 7.8 Hz, 2H), 7.92−7.88 (m, 6H), 7.65 (t, J = 7.8 Hz, 2H), 7.59−
7.56 (m, 2H), 7.52 (t, J = 7.8 Hz, 2H). 13C{1H} NMR (CDCl3, 150
MHz): δ 133.4, 130.7, 129.0, 128.5, 127.1, 126.6, 126.5, 125.5, 121.2,
92.6.
1,2-Di(thiophen-3-yl)ethyne. Eluent: 95:5 hexanes/ethyl acetate;
1
210 mg, 44% yield, brown amorphous solid. H NMR and 13C NMR
spectra for this compound are consistent with previously reported
literature data.25 1H NMR (CDCl3, 600 MHz): δ 7.50 (d, J = 2.4 Hz,
2H), 7.31−7.29 (m, 2H), 7.19−7.18 (m, 2H). 13C{1H} NMR
(CDCl3, 150 MHz): δ 130.0, 128.6, 125.5, 122.3, 84.1.
General Procedure A: Synthesis of Indole Derivatives. A
flame-dried 10 mL vial was charged with N-alkyl aniline derivatives
(0.4 mmol, 2 equiv), catalyst o-NQ (0.04 mmol, 20 mol %), and 2-
nitropropane (4 mmol, 20 equiv). The solution was stirred under O2
at 120 °C. After the reaction was complete by TLC (12 h), the
reaction mixture was then cooled to room temperature. [RhCp*Cl2]2
(0.006 mmol, 3 mol %), AgOAc (0.12 mmol, 60 mol %), and alkyne
(0.2 mmol, 1 equiv) in ethanol (0.15 mL) were added to the vial. The
mixture was stirred at 80 °C under O2 for 7 h. Upon the complete
consumption of alkyne, the reaction was cooled to room temperature.
Volatile solvent and reagents were removed by rotary evaporation,
1,5-Dimethyl-2,3-diphenyl-1H-indole (3f). Eluent: 80:1 hexanes/
ethyl acetate; 55 mg, 92% yield, yellow amorphous solid. The product
1
was prepared via the general procedure A. H NMR and 13C NMR
spectra for this compound are consistent with previously reported
literature data.9e 1H NMR (CDCl3, 600 MHz): δ 7.63 (s, 1H), 7.42−
7.39 (m, 3H), 7.38−7.30 (m, 7H), 7.23−7.20 (m, 1H), 7.18 (dd, J =
E
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8.4, 1.2 Hz, 1H), 3.69 (s, 3H), 2.52 (s, 3H). 13C{1H} NMR (CDCl3,
150 MHz): δ 137.9, 135.9, 135.4, 132.2, 131.3, 130.0, 129.6, 128.5,
128.3, 128.1, 127.3, 125.5, 123.9, 119.3, 114.8, 109.4, 31.1, 21.7.
5-Methoxy-1-methyl-2,3-diphenyl-1H-indole (3g). Eluent: 60:1
hexanes/ethyl acetate; 28 mg, 45% yield, yellow amorphous solid. The
A. H NMR and 13C NMR spectra for this compound are consistent
with previously reported literature data.9e 1H NMR (CDCl3, 600
MHz): δ 8.53 (d, J = 1.2 Hz, 1H), 8.02 (dd, J = 9.0, 1.8 Hz, 1H), 7.42
(d, J = 8.4 Hz, 1H), 7.40 (dd, J = 8.4, 1.8 Hz, 3H), 7.35−7.32 (m,
2H), 7.31 (J = 4.2 Hz, 4H), 7.34−7.20 (m, 1H), 3.93 (s, 3H), 3.70 (s,
3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 168.3, 139.8, 139.1, 134.5,
131.4, 131.2, 130.1, 128.6, 128.5, 126.8, 126.1, 123.7, 122.8, 122.3,
116.6, 109.4, 52.0, 31.3.
1
product was prepared via the general procedure A. 1H NMR and 13
C
NMR spectra for this compound are consistent with previously
reported literature data.9e 1H NMR (CDCl3, 600 MHz): δ 7.40−7.35
(m, 3H), 7.33−7.30 (m, 3H), 7.29 (dd, J = 7.2, 1.8 Hz, 3H), 7.25 (d,
J = 1.8 Hz, 1H), 7.20−7.17 (m, 1H), 3.86 (s, 3H), 3.66 (s, 3H).
13C{1H} NMR (CDCl3, 150 MHz): δ 154.9, 138.5, 135.5, 132.1,
132.0, 131.2, 129.9, 128.5, 128.4, 128.1, 127.4, 125.6, 115.0, 112.6,
110.5, 101.4, 56.2, 31.2.
1-(1-Methyl-2,3-diphenyl-1H-indol-5-yl)ethan-1-one (3n). Elu-
ent: 50:1 hexanes/ethyl acetate; 62 mg, 95% yield, yellow amorphous
1
solid. The product was prepared via the general procedure A. H
NMR and 13C NMR spectra for this compound are consistent with
previously reported literature data.9e 1H NMR (CDCl3, 600 MHz): δ
8.43 (d, J = 1.8 Hz, 1H), 7.99 (dd, J = 9.0, 1.2 Hz, 1H), 7.44 (d, J =
9.0 Hz, 1H), 7.42−7.40 (m, 3H), 7.35−7.30 (m, 6H), 7.25−7.22 (m,
1H), 3.71 (s, 3H), 2.67 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz):
δ 198.4, 139.7, 139.3, 134.4, 131.3, 131.2, 130.4, 130.0, 128.6, 128.5,
126.7, 126.2, 122.6, 122.0, 116.9, 109.6, 31.3, 26.8.
5-Fluoro-1-methyl-2,3-diphenyl-1H-indole (3h). Eluent: 70:1
hexanes/ethyl acetate; 32 mg, 53% yield, yellow amorphous solid.
The product was prepared via the general procedure A. 1H NMR and
13C NMR spectra for this compound are consistent with previously
reported literature data.9e 1H NMR (CDCl3, 600 MHz): δ 7.46 (dd, J
= 9.0, 2.4 Hz, 1H), 7.41−7.39 (m, 3H), 7.35−7.31 (m, 3H), 7.30−
1-Methyl-2,3,5-triphenyl-1H-indole (3o). Eluent: 50:1 hexanes/
ethyl acetate; 58 mg, 81% yield, orange amorphous solid. The product
7.26 (m, 4H), 7.21−7.17 (m, 1H), 7.06 (dt, J = 9.0, 2.4 Hz, 1H), 3.68
1
was prepared via the general procedure A. H NMR and 13C NMR
1
(s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 158.7 (C−F, JC−F
=
spectra for this compound are consistent with previously reported
literature data.9f 1H NMR (CDCl3, 600 MHz): δ 8.07 (d, J = 1.8 Hz,
1H), 7.72 (d, J = 7.8 Hz, 2H), 7.62 (dd, J = 9.0, 1.8 Hz, 1H), 7.52 (d,
J = 8.4 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.46−7.42 (m, 3H), 7.41−
7.38 (m, 4H), 7.38−7.33 (m, 3H), 7.26−7.23 (m, 1H), 3.75 (s, 3H).
13C{1H} NMR (CDCl3, 150 MHz): δ 142.8, 138.5, 137.0, 135.2,
134.0, 131.9, 131.2, 130.1, 128.6, 128.5, 128.4, 128.2, 127.6, 126.5,
125.8, 122.2, 118.3, 115.7, 110.0, 31.2.
232.7 Hz), 139.4, 134.9, 134.1, 131.7, 131.2, 129.8, 128.6, 128.4(3),
128.3(8), 127.4 (C−F, 3JC−F = 10.1 Hz), 125.8, 115.3 (C−F, 3JC−F
=
2
3
4.4 Hz), 110.6 (C−F, JC−F = 25.8 Hz), 110.4 (C−F, JC−F = 10.1
Hz), 104.6 (C−F, JC−F = 23.0 Hz), 31.3. 19F NMR (CDCl3, 564
2
MHz): δ −124.0.
5-Chloro-1-methyl-2,3-diphenyl-1H-indole (3i). Eluent: 70:1
hexanes/ethyl acetate; 48 mg, 76% yield, yellow amorphous solid.
The product was prepared via the general procedure A. 1H NMR and
13C NMR spectra for this compound are consistent with previously
reported literature data.9f 1H NMR (CDCl3, 600 MHz): δ 7.78 (d, J =
1.8 Hz, 1H), 7.42−7.39 (m, 3H), 7.35−7.31 (m, 3H), 7.31−7.25 (m,
5H), 7.23−7.20 (m, 1H), 3.68 (s, 3H). 13C{1H} NMR (CDCl3, 150
MHz): δ 139.1, 135.9, 134.7, 131.5, 131.2, 129.9, 128.6, 128.4(4),
128.4(2), 128.1, 126.1, 126.0, 122.5, 119.1, 115.0, 110.8, 31.2.
5-Bromo-1-methyl-2,3-diphenyl-1H-indole (3j). Eluent: 70:1
hexanes/ethyl acetate; 67 mg, 93% yield, yellow amorphous solid.
The product was prepared via the general procedure A. 1H NMR and
13C NMR spectra for this compound are consistent with previously
reported literature data.9f 1H NMR (CDCl3, 600 MHz): δ 7.92 (d, J =
1.2 Hz, 1H), 7.42−7.38 (m, 4H), 7.35−7.32 (m, 2H), 7.32−7.27 (m,
5H), 7.23−7.19 (m, 1H), 3.67 (s, 3H). 13C{1H} NMR (CDCl3, 150
MHz): δ 138.9, 136.1, 134.6, 131.2, 129.9, 128.8, 128.6, 128.5, 126.0,
125.0, 122.2, 114.9, 113.6, 111.2, 31.2.
1,6-Dimethyl-2,3-diphenyl-1H-indole (3p). Eluent: 80:1 hexanes/
ethyl acetate; 46 mg, 77% yield, yellow amorphous solid. The product
1
was prepared via the general procedure A. H NMR and 13C NMR
spectra for this compound are consistent with previously reported
literature data.9f 1H NMR (CDCl3, 600 MHz): δ 7.68 (d, J = 8.4 Hz,
1H), 7.40−7.35 (m, 3H), 7.33−7.29 (m, 4H), 7.28−7.24 (m, 2H),
7.21 (s, 1H), 7.18−7.15 (m, 1H), 7.03 (d, J = 7.8 Hz, 1H), 3.64 (s,
3H), 2.55 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 137.9,
137.2, 135.6, 132.2(2), 132.2(0), 131.3, 129.9, 128.5, 128.3, 128.0,
125.5, 125.0, 122.0, 119.4, 115.1, 109.7, 31.0, 22.1.
1,2-Diphenyl-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline (3q). Elu-
ent: 50:1 hexanes/ethyl acetate; 19 mg, 31% yield, yellow crystalline
1
solid. The product was prepared via the general procedure A. H
NMR and 13C NMR spectra for this compound are consistent with
previously reported literature data.9e 1H NMR (CDCl3, 600 MHz): δ
7.64 (d, J = 7.8 Hz, 1H), 7.41−7.35 (m, 7H), 7.29 (t, J = 7.8 Hz, 2H),
7.20−7.17 (m, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.01 (d, J = 1.2 Hz, 1H),
4.10 (t, J = 6.0 Hz, 2H), 3.07 (t, J = 6.0 Hz, 2H), 2.25 (qui, J = 6.0
Hz, 2H). 13C{1H} NMR (CDCl3, 150 MHz): δ 136.2, 135.8, 134.5,
132.0, 130.9, 129.8, 128.5, 128.3, 128.0, 125.5, 125.1, 122.2, 120.4,
119.3, 117.2, 114.6, 43.3, 25.3, 23.1.
1-Methyl-2,3-diphenyl-1H-indole-5-carbonitrile (3k). Eluent:
30:1 hexanes/ethyl acetate; 28 mg, 45% yield, yellow amorphous
1
solid. The product was prepared via the general procedure A. H
NMR and 13C NMR spectra for this compound are consistent with
previously reported literature data.9f 1H NMR (CDCl3, 600 MHz): δ
8.11 (d, J = 1.2 Hz, 1H), 7.52 (dd, J = 8.4, 1.2 Hz, 1H), 7.45 (d, J =
7.8 Hz, 1H), 7.43−7.40 (m, 3H), 7.34−7.29 (m, 4H), 7.26−7.22 (m,
3H), 3.71 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 139.9,
138.9, 133.8, 131.1, 130.9, 129.9, 128.8(8), 128.7(8), 128.6, 127.1,
126.5, 125.5, 125.1, 121.0, 116.1, 110.5, 103.3, 31.4.
1-Methyl-2,3-diphenyl-1H-benzo[f]indole (3r). Eluent: 50:1 hex-
anes/ethyl acetate; 21 mg, 32% yield (1.2:1), yellow amorphous solid,
mp 139−142 °C. The product was prepared via the general procedure
1
A. H NMR (CDCl3, 600 MHz): δ 8.29 (s, 1.00H), 7.99 (d, J = 7.8
Hz, 1.20H), 7.96 (d, J = 8.4 Hz, 1.11H), 7.91 (d, J = 7.8 Hz, 0.92H),
7.85 (d, J = 8.4 Hz, 0.96H), 7.80 (s, 1.00H), 7.70 (d, J = 9.0 Hz,
0.82H), 7.61 (d, J = 8.4 Hz, 0.91H), 7.43−7.39 (m, 10.66H), 7.37−
7.29 (m, 9.80H), 7.28−7.26 (m, 2.34H), 7.25−7.22 (m, 1.37H), 3.82
(s, 2.74H), 3.77 (s, 3.26H). 13C{1H} NMR (CDCl3, 150 MHz): δ
141.6, 138.5, 137.2, 137.0, 135.2, 133.6, 131.9, 131.8, 131.7, 131.3,
131.2, 130.6, 130.1, 130.0, 129.3, 129.0, 128.8(4), 128.7(6), 128.6,
128.5, 128.3, 128.2(7), 128.1(5), 127.7, 127.6, 126.7, 125.8, 125.4,
124.0, 123.5, 123.4, 123.1, 122.7, 120.5, 118.2, 117.2, 111.3, 104.9,
31.5, 31.4. IR (neat): 1600, 1459, 1442, 1402, 1362, 1273, 1068,
1027, 844, 799, 781, 714, 697 cm−1. HRMS (ESI): m/z calcd for
C25H19N [M + H]+, 334.1590; found, 334.1599.
1-Methyl-2,3-diphenyl-5-(trifluoromethyl)-1H-indole (3l). Eluent:
70:1 hexanes/ethyl acetate; 59 mg, 84% yield, yellow amorphous
1
solid. The product was prepared via the general procedure A. H
NMR and 13C NMR spectra for this compound are consistent with
previously reported literature data.9f 1H NMR (CDCl3, 600 MHz): δ
8.07 (s, 1H), 7.54 (dd, J = 6.4, 1.8 Hz, 1H), 7.48 (d, J = 9.0 Hz, 1H),
7.43−7.40 (m, 3H), 7.36−7.28 (m, 6H), 7.25−7.22 (s, 1H), 3.73 (s,
3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 139.5, 138.7, 134.4, 131.3,
131.2, 130.0, 128.7, 128.6(1), 128.5(8), 126.6, 126.2, 125.6 (C−F,
1JC−F = 225 Hz), 122.7 (C−F, 2JC−F = 26.4 Hz), 119.0 (C−F, 3JC−F
=
3
3.6 Hz), 117.5 (C−F, JC−F = 1.9 Hz), 116.2, 110.0, 31.3. 19F NMR
(CDCl3, 564 MHz): δ −60.0.
1-Methyl-2,3-di-p-tolyl-1H-indole (3s). Eluent: 80:1 hexanes/ethyl
acetate; 51 mg, 83% yield, yellow crystalline solid. The product was
prepared via the general procedure A. 1H NMR and 13C NMR spectra
for this compound are consistent with previously reported literature
Methyl 1-Methyl-2,3-diphenyl-1H-indole-5-carboxylate (3m).
Eluent: 40:1 hexanes/ethyl acetate; 41 mg, 60% yield, yellow
amorphous solid. The product was prepared via the general procedure
F
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data.9e 1H NMR (CDCl3, 600 MHz): δ 7.83 (d, J = 8.4 Hz, 1H), 7.44
(d, J = 8.4 Hz, 1H), 7.34 (t, J = 7.2 Hz, 1H), 7.28−7.21 (m, 7H), 7.14
(d, J = 7.2 Hz, 2H), 3.71 (s, 3H), 2.44 (s, 3H), 2.38 (s, 3H). 13C{1H}
NMR (CDCl3, 150 MHz): δ 137.9, 137.8, 137.4, 135.0, 132.5, 131.1,
129.8, 129.2, 129.1(3), 129.0(5), 127.2, 122.1, 120.1, 119.7, 114.9,
109.6, 31.0, 21.5, 21.3.
1-Methyl-2,3-di(thiophen-3-yl)-1H-indole (3y). Eluent: 40:1 hex-
anes/ethyl acetate; 24 mg, 41% yield, yellow amorphous solid, mp
99−101 °C. The product was prepared via the general procedure A.
1H NMR (CDCl3, 600 MHz): δ 7.82 (d, J = 7.8 Hz, 1H), 7.41−7.39
(m, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.32−7.28 (m, 2H), 7.25 (t, J = 8.4
Hz, 1H), 7.20 (t, J = 7.8 Hz, 1H), 7.16 (dd, J = 8.4, 1.8 Hz, 2H),
7.07−7.06 (m, 1H), 6.96 (dd, J = 8.4, 1.8 Hz, 1H), 3.69 (s, 3H).
13C{1H} NMR (CDCl3, 150 MHz): δ 137.3, 135.4, 132.9, 132.2,
129.6, 1287, 126.9, 126.2, 125.9, 124.7, 122.4, 120.3, 119.8, 110.9,
109.6, 31.0. IR (neat): 1468, 1342, 1316, 1254, 791, 743, 671 cm−1.
HRMS (ESI): m/z calcd for C17H13NS2 [M + H]+, 296.0562; found,
296.0562.
1,2-Dimethyl-3-phenyl-1H-indole (3z). Eluent: 80:1 hexanes/ethyl
acetate; 15 mg, 33% yield, yellow amorphous solid. The product was
prepared via the general procedure A. 1H NMR and 13C NMR spectra
for this compound are consistent with previously reported literature
data.26 1H NMR (CDCl3, 600 MHz): δ 7.62 (d, J = 7.8 Hz, 1H), 7.50
(t, J = 8.4 Hz, 2H), 7.44−7.40 (m, 3H), 7.35 (d, J = 7.8 Hz, 1H), 7.27
(t, J = 7.8 Hz, 1H), 7.17 (t, J = 7.8 Hz, 1H), 3.63 (s, 3H), 2.30 (s,
3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 137.8, 137.3, 132.3, 130.8,
128.6, 128.5, 127.9, 121.9, 119.2, 118.9, 109.4, 108.7, 31.1, 9.5.
Methyl-1-methyl-3-phenyl-1H-indole-2-carboxylate (3za). Elu-
2,3-Bis(4-methoxyphenyl)-1-methyl-1H-indole (3t). Eluent: 70:1
hexanes/ethyl acetate; 53 mg, 78% yield, yellow amorphous solid. The
product was prepared via the general procedure A. 1H NMR and 13
C
NMR spectra for this compound are consistent with previously
reported literature data.9e 1H NMR (CDCl3, 600 MHz): δ 7.78 (d, J =
7.8 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.31 (t, J = 7.2 Hz, 1H), 7.30
(td, J = 7.8, 1.2 Hz, 1H), 7.28−7.24 (m, 3H), 7.19 (t, J = 8.4 Hz, 1H),
6.94−6.92 (m, 2H), 6.87−6.85 (m, 2H), 3.85 (s, 3H), 3.81 (s, 3H),
3.67 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 159.4, 157.6,
137.3, 137.3, 132.4, 130.9, 127.9, 127.2, 124.3, 122.0, 120.1, 119.6,
114.5, 114.0, 113.8, 109.6, 55.4, 55.3, 31.0.
2,3-Bis(4-bromophenyl)-1-methyl-1H-indole (3u). Eluent: 80:1
hexanes/ethyl acetate; 70 mg, 80% yield, yellow crystalline solid. The
product was prepared via the general procedure A. 1H NMR and 13
C
NMR spectra for this compound are consistent with previously
reported literature data.9e 1H NMR (CDCl3, 600 MHz): δ 7.74 (d, J =
8.4 Hz, 1H), 7.55 (dd, J = 6.0, 1.8 Hz, 2H), 7.44−7.41 (m, 3H), 7.34
(td, J = 8.4, 1.8 Hz, 1H), 7.30−7.20 (m, 1H), 7.19 (dd, J = 6.0, 1.8
Hz, 2H), 7.16 (dd, J = 8.4, 1.8 Hz, 2H), 3.68 (s, 3H). 13C{1H} NMR
(CDCl3, 150 MHz): δ 137.6, 136.6, 134.0, 132.7, 132.0, 131.6, 131.5,
130.6, 126.7, 122.8, 120.7, 119.8, 119.5, 114.5, 109.9, 31.1.
ent: 40:1 hexanes/ethyl acetate; 19 mg, 35% yield, yellow gum. The
1
product was prepared via the general procedure A. H NMR and 13
C
NMR spectra for this compound are consistent with previously
reported literature data.9f 1H NMR (CDCl3, 600 MHz): δ 8.24 (dd, J
= 7.2, 1.8 Hz, 1H), 7.53−7.49 (m, 3H), 7.43−7.39 (m, 3H), 7.36−
7.32 (m, 2H), 3.76 (s, 3H), 3.58 (s, 3H). 13C{1H} NMR (CDCl3, 150
MHz): δ 165.7, 147.1, 136.9, 131.6, 130.4, 129.1, 128.2, 126.7, 123.0,
122.3, 122.1, 109.9, 105.1, 50.9, 31.0.
4,4′-(1-Methyl-1H-indole-2,3-diyl)dibenzonitrile (3v). Eluent:
30:1 hexanes/ethyl acetate; 40 mg, 60% yield, yellow amorphous
solid, mp 265−267 °C. The product was prepared via the general
1
procedure A. H NMR (CDCl3, 600 MHz): δ 7.74 (d, J = 8.4 Hz,
2,3-Diethyl-1-methyl-1H-indole (3zb). Eluent: 80:1 hexanes/ethyl
acetate; 17 mg, 45% yield, yellow liquid. The product was prepared
1H), 7.72 (dd, J = 6.6, 1.8 Hz, 2H), 7.57 (dd, J = 6.6, 1.2 Hz, 2H),
7.47 (d, J = 8.4 Hz, 1H), 7.44 (dd, J = 6.6, 1.8 Hz, 2H), 7.39 (t, J =
7.2 Hz, 1H), 7.34 (dd, J = 6.6, 2.4 Hz, 2H), 7.26 (t, J = 8.4 Hz, 1H),
3.72 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 139.8, 138.0,
136.4, 136.1, 132.6, 132.4, 131.8, 130.3, 126.4, 123.7, 121.5, 119.5,
119.2, 118.4, 115.0, 112.5, 110.3, 109.5, 31.4. IR (neat): 2229, 1605,
1469, 1370, 1264, 1090, 1017, 869, 833, 751 cm−1. HRMS (ESI): m/z
calcd for C23H15N3 [M + H]+, 334.1338; found, 334.1347.
1
via the general procedure A. H NMR and 13C NMR spectra for this
compound are consistent with previously reported literature data.26
1H NMR (CDCl3, 600 MHz): δ 7.55 (d, J = 7.2 Hz, 1H), 7.25 (d, J =
7.8 Hz, 1H), 7.16 (t, J = 7.8 Hz, 1H), 7.07 (t, J = 7.2 Hz, 1H), 3.68 (s,
3H), 2.78 (q, J = 7.8 Hz, 2H), 2.75 (q, J = 7.8 Hz, 2H), 1.24 (t, J = 7.8
Hz, 3H), 1.22 (t, J = 7.8 Hz, 3H). 13C{1H} NMR (CDCl3, 150
MHz): δ 138.1, 136.8, 127.6, 120.6, 118.7, 118.3, 112.8, 108.7, 29.5,
17.8(1), 17.7(5), 16.4, 15.1.
1-Methyl-2,3-di(naphthalen-1-yl)-1H-indole (3w). Eluent: 50:1
hexanes/ethyl acetate; 31 mg, 41% yield, yellow amorphous solid, mp
195−198 °C. The product was prepared via the general procedure A.
1H NMR (CDCl3, 600 MHz): δ 8.04 (d, J = 8.4 Hz, 1.0H), 7.91−7.89
(m, 0.91H), 7.86 (t, J = 8.4 Hz, 1.57H), 7.81−7.75 (m, 3.34H), 7.73
(d, J = 8.4 Hz, 1H), 7.69−7.64 (m, 2.53H), 7.55−7.51 (m, 4.96H),
7.49−7.46 (m, 2H), 7.43−7.39 (m, 1.53H), 7.38−7.29 (m, 4.94H),
7.25−7.19 (m, 2.84H), 7.17−7.09 (m, 3.49H), 7.00 (d, J = 6.0 Hz,
1.0H), 3.57 (s, 2.07H), 3.53 (s, 2.85H). 13C{1H} NMR (CDCl3, 150
MHz): δ 137.9, 137.3, 137.2, 137.1, 133.8, 133.7, 133.5, 133.4, 133.1,
132.9(3), 132.9(0), 132.8, 130.0, 129.8, 129.0, 128.6, 128.5, 128.3,
128.2, 128.0, 127.3, 127.0(3), 127.0(0), 126.9(5), 126.9(1), 126.1,
126.0(4), 125.9(6), 125.7, 125.5, 125.3, 125.2, 125.0, 122.2, 122.1,
120.8, 120.5, 120.0(3), 119.9(5), 115.4, 115.2, 109.6, 31.1. IR (neat):
1595, 1469, 1359, 1265, 1247, 1014, 803, 777, 751, 702 cm−1. HRMS
(ESI): m/z calcd for C29H21N [M + H]+, 384.1746; found, 384.1756.
1-Methyl-2,3-di(naphthalen-2-yl)-1H-indole (3x). Eluent: 50:1
hexanes/ethyl acetate; 42 mg, 55% yield, yellow amorphous solid,
mp 181−183 °C. The product was prepared via the general procedure
A. 1H NMR (CDCl3, 600 MHz): δ 7.98 (s, 1H), 7.96 (d, J = 7.2 Hz,
1H), 7.90 (s, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.82 (t, J = 7.2 Hz, 2H),
7.70 (t, J = 9.0 Hz, 2H), 7.65 (d, J = 7.8 Hz, 1H), 7.55−7.49 (m, 3H),
7.46 (dd, J = 8.4, 1.2 Hz, 1H), 7.45−7.41 (m, 2H), 7.39 (t, J = 7.8 Hz,
1H), 7.35 (dd, J = 8.4, 1.2 Hz, 1H), 7.29 (t, J = 7.8 Hz, 1H), 3.78 (s,
3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 138.1, 137.8, 133.8, 133.3,
133.0, 132.9, 131.9, 130.5, 129.5, 128.9, 128.8, 128.3,
128.2(0),128.1(7), 127.9(1), 127.8(8), 127.7(3), 127.7(0), 127.3,
126.7, 126.5, 125.9, 125.3, 122.5, 120.6, 119.8, 115.5, 109.9, 31.3. IR
(neat): 1629, 1601, 1547, 1470, 1402, 1373, 1336, 1313, 1265, 1241,
1087, 1019, 863, 826, 740 cm−1. HRMS (ESI): m/z calcd for
C29H21N [M + H]+, 384.1746; found, 384.1755.
1-Methyl-2,3-dipropyl-1H-indole (3zc). Eluent: 80:1 hexanes/
ethyl acetate; 22 mg, 51% yield, yellow liquid. The product was
prepared via the general procedure A. 1H NMR and 13C NMR spectra
for this compound are consistent with previously reported literature
data.26 1H NMR (CDCl3, 600 MHz): δ 7.56 (d, J = 8.4 Hz, 1H), 7.27
(d, J = 7.8 Hz, 1H), 7.16 (td, J = 7.8, 1.2 Hz, 1H), 7.10−7.07 (m,
1H), 3.68 (s, 3H), 2.74 (t, J = 7.8 Hz, 2H), 2.71 (t, J = 7.8 Hz, 2H),
1.68 (sext, J = 7.8 Hz, 2H), 1.63 (sext, J = 7.8 Hz, 2H), 1.03 (t, J = 7.8
Hz, 3H), 1.00 (t, J = 7.8 Hz, 3H). 13C{1H} NMR (CDCl3, 150
MHz): δ 137.0, 136.8, 128.0, 120.5, 118.6, 118.5, 111.8, 108.7, 29.7,
26.9, 26.7, 24.6, 23.7, 14.5, 14.2.
General Procedure B: Synthesis of Alkenylated Products. A
flame-dried 10 mL vial was charged with N-alkyl aniline derivatives
(0.4 mmol, 2 equiv), catalyst o-NQ (0.04 mmol, 10 mol %), and 2-
nitropropane (4 mmol, 20 equiv). The solution was stirred under O2
at 120 °C. After the reaction was complete by TLC (12 h), the
reaction mixture was cooled to room temperature. [RhCp*Cl2]2
(0.006 mmol, 3 mol %), AgOAc (0.12 mmol, 60 mol %), and alkene
(0.2 mmol, 1 equiv) in ethanol (0.15 mL) were added to the vial. The
mixture was stirred at 60 °C under O2 for 7−12 h. Upon the complete
consumption of alkyne, the reaction was cooled to room temperature.
Volatile solvent and reagents were removed by rotary evaporation,
and the residue was purified by silica gel flash chromatography using
hexane/EtOAc (50:1 to 30:1) to afford the alkenylated product.
(E)-Methyl 3-(2-(Methyl(nitroso)amino)phenyl)acrylate (5a). Elu-
ent: 50:1 hexanes/ethyl acetate; 42 mg, 95% yield, yellow crystalline
solid. The product was prepared via the general procedure B. The title
compound was obtained as an inseparable mixture of syn- and anti-
isomers due to the different conformations of the NO bond
(>20:1). 1H NMR and 13C NMR spectra for this compound are
G
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consistent with previously reported literature data.9a 1H NMR
(CDCl3, 600 MHz): δ 7.74 (dd, J = 7.8, 1.8 Hz, 1H), 7.55−7.48
(m, 3H), 7.33 (dd, J = 7.8, 1.2 Hz, 1H), 6.43 (d, J = 15.6 Hz, 1H),
3.77 (s, 3H), 3.41 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ
166.7, 141.6, 139.4, 131.0, 130.6, 129.4, 128.1, 126.0, 121.3, 52.0,
36.0. IR (neat): 1716, 1638, 1437, 1321, 1291, 1195, 1172, 1073, 978,
960, 764 cm−1. HRMS (ESI): m/z calcd for C11H12N2O3 [M + Na]+,
243.0740; found, 243.0749.
For the scale-up reaction, a flame-dried 25 mL flask was charged
with N-alkyl aniline derivatives (2.0 mmol), catalyst o-NQ (0.20
mmol, 10 mol %), and 2-nitropropane (20 mmol). The solution was
stirred under O2 at 120 °C. After the reaction was complete by TLC
(24 h), the reaction mixture was then cooled to room temperature.
[RhCp*Cl2]2 (0.030 mmol, 3 mol %), AgOAc (0.60 mmol, 60 mol
%), and methylacrylate (1.0 mmol) in ethanol (0.75 mL) were added
to the vial. The mixture was stirred at 60 °C under O2 for 18 h. Upon
the complete consumption of alkene, the reaction was cooled to room
temperature. Volatile solvent and reagents were removed by rotary
evaporation, and the residue was purified by silica gel flash
chromatography using hexane/EtOAc (50:1) to afford the N-nitroso
alkenylated 5a in 72% yield (158 mg).
inseparable mixture of syn- and anti-isomers due to the different
1
conformations of the NO bond (1:0.12). H NMR and 13C NMR
spectra for this compound are consistent with previously reported
literature data.9a 1H NMR (CDCl3, 600 MHz): δ 7.46 (d, J = 15.6 Hz,
1H), 7.23 (d, J = 9.0 Hz, 1H), 7.19 (d, J = 2.4 Hz, 1H), 7.16 (d, J =
2.4 Hz, 0.12H), 7.12 (d, J = 15.6 Hz, 0.12H), 7.03 (dd, J = 9.0, 2.4
Hz, 1H), 7.03 (dd, J = 9.0, 2.4 Hz, 0.12H), 6.91 (d, J = 9.0 Hz,
0.12H), 6.40 (d, J = 15.6 Hz, 1H), 6.36 (d, J = 16.8 Hz, 0.12H), 4.07
(s, 0.36H), 3.87 (s, 3H), 3.83 (s, 0.36), 3.76 (s, 3H), 3.75 (s, 0.36H),
3.36 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 166.6(3),
166.5(9), 160.4, 160.1, 139.2, 138.7, 134.9, 132.8, 132.2, 131.9, 127.7,
127.6, 121.5, 121.3, 117.2, 116.7, 112.4, 112.0, 55.8, 55.7, 52.0, 41.5,
36.3, 35.5.
Methyl (E)-3-(5-Fluoro-2-(methyl(nitroso)amino)phenyl)acrylate
(5f). Eluent: 50:1 hexanes/ethyl acetate; 43 mg, 90% yield, yellow
amorphous solid. The product was prepared via the general procedure
B. The title compound was obtained as an inseparable mixture of syn-
and anti-isomers due to the different conformations of the NO
bond (1:0.12). 1H NMR and 13C NMR spectra for this compound are
consistent with previously reported literature data.9a 1H NMR
(CDCl3, 600 MHz): δ 7.45 (dd, J = 15.6, 1.2 Hz, 1H), 7.42 (dd, J
= 9.0, 3.0 Hz, 1H), 7.38 (dd, J = 9.0, 3.0 Hz, 0.12H), 7.32 (dd, J = 9.0,
4.8 Hz, 1H), 7.22 (dt, J = 9.0, 3.0 Hz, 1H), 7.19−7.15 (m, 0.19H),
7.09 (dd, J = 9.6, 1.2 Hz, 0.12H), 7.00 (dd, J = 9.0, 4.8 Hz, 0.12H),
6.42 (d, J = 16.2 Hz, 1H), 6.38 (d, J = 16.2 Hz, 0.12H), 4.10 (s,
0.36H), 3.78 (s, 3H), 3.77 (s, 0.36H), 3.38 (s, 3H). 13C{1H} NMR
(E)-Methyl 3-(2-(Ethyl(nitroso)amino)phenyl)acrylate (5b). Elu-
ent: 50:1 hexanes/ethyl acetate; 45 mg, 95% yield, yellow crystalline
solid. The product was prepared via the general procedure B. The title
compound was obtained as an inseparable mixture of syn- and anti-
isomers due to the different conformations of the NO bond
1
1
(1:0.39). H NMR and 13C NMR spectra for this compound are
(CDCl31, 150 MHz): δ 166.3, 163.0 (C−F, JC−F = 207.0 Hz), 162.9
consistent with previously reported literature data.9a 1H NMR
(CDCl3, 600 MHz): δ 7.76 (dd, J = 7.8, 1.2 Hz, 1H), 7.73 (dd, J =
7.8, 1.2 Hz, 0.39H), 7.55−7.50 (m, 2.63H), 7.49−7.45 (m, 0.85H),
7.31 (dd, J = 7.8, 1.2 Hz, 1H), 7.21 (d, J = 16.8 Hz, 0.35H), 6.99 (dd,
J = 7.8, 1.8 Hz, 0.39H), 6.44 (d, J = 15.6 Hz, 1.12H), 6.40 (d, J = 16.2
Hz, 0.20H), 4.55 (bro, 0.71H), 3.98 (q, J = 7.2 Hz, 1.91H), 3.78 (s,
3.08H), 3.77 (s, 1.02H), 1.39 (t, J = 7.2 Hz, 1.17H), 1.09 (t, J = 7.2
Hz, 2.93H). 13C{1H} NMR (CDCl3, 150 MHz): δ 166.7, 140.3,
139.4, 138.9, 137.8, 132.4, 131.6, 131.2, 131.0, 130.0, 129.7, 128.1,
127.6, 127.4, 127.4, 121.4, 121.2, 52.0(3), 51.9(9), 49.4, 42.7, 14.3,
11.3.
(C−F, JC−F = 207.0 Hz), 138.2, 137.9, 137.8, 137.5, 135.0, 134.1
2
3
(C−F, JC−F = 15.6 Hz), 132.9 (C−F, JC−F = 7.1 Hz), 128.6 (C−F,
2JC−F = 20.4 Hz), 128.1 (C−F, JC−F = 7.3 Hz), 122.5, 122.4, 118.5
3
(C−F, 2JC−F = 19.1 Hz), 118.0 (C−F, 2JC−F = 19.1 Hz), 114.5 (C−F,
2JC−F = 19.1 Hz), 114.1 (C−F, JC−F = 19.1 Hz), 52.1, 41.3, 36.1.
2
Methyl (E)-3-(5-Chloro-2-(methyl(nitroso)amino)phenyl)acrylate
(5g). Eluent: 50:1 hexanes/ethyl acetate; 42 mg, 83% yield, yellow
amorphous solid, mp 130−132 °C. The product was prepared via the
general procedure B. The title compound was obtained as an
inseparable mixture of syn- and anti-isomers due to the different
1
conformations of the NO bond (1:0.11). H NMR (CDCl3, 600
(E)-Methyl 3-(2-(Isopropyl(nitroso)amino)phenyl)acrylate (5c).
Eluent: 50:1 hexanes/ethyl acetate; 34 mg, 69% yield, yellow
crystalline solid. The product was prepared via the general procedure
B. The title compound was obtained as an inseparable mixture of syn-
and anti-isomers due to the different conformations of the NO
bond (1:0.5). 1H NMR and 13C NMR spectra for this compound are
consistent with previously reported literature data.9a 1H NMR
(CDCl3, 600 MHz): δ 7.81−7.79 (m, 0.5H), 7.74−7.72 (m, 1H),
7.57−7.51 (m, 1H), 7.49−7.44 (m, 2H), 7.30−7.28 (m, 0.5H), 7.21
(d, J = 15.6 Hz, 1H), 6.98−6.95 (m, 1H), 6.44 (d, J = 15.6 Hz, 0.5H),
6.39 (d, J = 15.6 Hz, 1H), 5.15 (septet, J = 7.2 Hz, 0.5H), 4.93
(septet, J = 7.2 Hz, 1H), 3.76 (s, 4.5H), 1.59 (d, J = 7.2 Hz, 3H), 1.44
(d, J = 7.2 Hz, 3H), 1.12 (d, J = 6.6 Hz, 3H). 13C{1H} NMR (CDCl3,
150 MHz): δ 166.6(9), 166.6(6), 139.7, 139.4, 138.5, 137.5, 133.6,
132.8, 131.0, 130.7, 130.0, 129.1, 128.2, 127.7, 127.2, 121.2, 120.9,
57.1, 52.0, 47.9, 22.8, 21.7, 19.6.
(E)-Methyl 3-(5-Methyl-2-(methyl(nitroso)amino)phenyl)acrylate
(5d). Eluent: 50:1 hexanes/ethyl acetate; 44 mg, 93% yield, yellow
crystalline solid. The product was prepared via the general procedure
B. The title compound was obtained as an inseparable mixture of syn-
and anti-isomers due to the different conformations of the NO
bond (1:0.1). 1H NMR and 13C NMR spectra for this compound are
consistent with previously reported literature data.9a 1H NMR
(CDCl3, 600 MHz): δ 7.53 (bro, 1H), 7.50 (d, J = 15.6 Hz, 1H),
7.32 (dd, J = 7.2, 1.2 Hz, 1H), 7.21 (d, J = 9.8 Hz, 1H), 6.41 (m, d, J
= 15.6 Hz, 1H), 3.76 (s, 3H), 3.38 (s, 3H), 2.43 (s, 3H). 13C{1H}
NMR (CDCl3, 150 MHz): δ 166.7, 139.6, 139.5, 139.3, 131.8, 130.3,
128.5, 126.0, 121.0, 52.0, 36.1, 21.3.
MHz): δ 7.70 (d, J = 1.8 Hz, 1H), 7.67 (d, J = 2.4 Hz, 0.11H), 7.48
(dd, J = 8.4, 2.4 Hz, 1H), 7.46 (d, J = 16.2 Hz, 1H), 7.28 (d, J = 8.4
Hz, 1H), 7.08 (d, J = 15.6 Hz, 0.11H), 6.96 (d, J = 8.4 Hz, 0.11H),
6.43 (d, J = 15.6 Hz, 1H), 6.39 (d, J = 16.2 Hz, 0.11H), 4.10 (s, 0.33),
3.78 (s, 3H), 3.77 (s, 0.33H), 3.38 (s, 3H). 13C{1H} NMR (CDCl3,
150 MHz): δ 160.3, 140.0, 138.2, 137.4, 137.3, 136.1, 135.3, 133.6,
132.1, 131.3, 130.9, 128.0, 127.4, 127.2, 122.5, 52.2, 41.1, 35.9. IR
(neat): 1703, 1491, 1450, 1433, 1413, 1288, 1249, 1197, 1105, 1071,
1031, 967, 909, 859, 834, 820 cm−1. HRMS (ESI): m/z calcd for
C11H11ClN2O3 [M + H]+, 255.0531; found, 255.0539.
Methyl (E)-3-(5-Bromo-2-(methyl(nitroso)amino)phenyl)acrylate
(5h). Eluent: 50:1 hexanes/ethyl acetate; 25 mg, 42% yield, yellow
crystalline solid, mp 120−121 °C. The product was prepared via the
general procedure B. The title compound was obtained as an
inseparable mixture of syn- and anti-isomers due to the different
1
conformations of the NO bond (1:0.14). H NMR (CDCl3, 600
MHz): δ 7.87 (d, J = 2.4 Hz, 1H), 7.83 (d, J = 1.8 Hz, 0.14H), 7.64
(dd, J = 8.4, 2.4 Hz, 1H), 7.59 (dd, J = 8.4, 2.4 Hz, 0.14H), 7.46 (d, J
= 15.6 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.08 (d, J = 16.2 Hz,
0.14H), 6.90 (d, J = 3.0 Hz, 0.14H), 6.43 (d, J = 15.6 Hz, 1H), 6.40
(d, J = 16.2 Hz, 0.14H), 4.10 (s, 0.42H), 3.79 (s, 3H), 3.78 (s,
0.42H), 3.38 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 166.3,
140.6, 138.1, 137.3, 134.3, 133.9, 132.4, 131.0, 128.1, 127.3, 123.2,
122.9, 122.5, 51.2, 41.1, 35.8. IR (neat): 1716, 1638, 1485, 1437,
1340, 1314, 1286, 1262, 1195, 1168, 1092, 1068, 984, 870, 818, 755
cm−1. HRMS (ESI): m/z calcd for C11H11BrN2O3 [M + H]+,
299.0025; found, 299.0018.
Methyl (E)-3-(2-(Methyl(nitroso)amino)-5-(trifluoromethyl)-
phenyl)acrylate (5i). Eluent: 40:1 hexanes/ethyl acetate; 47 mg,
81% yield, yellow crystalline solid, mp 110−112 °C. The product was
prepared via the general procedure B. The title compound was
obtained as an inseparable mixture of syn- and anti-isomers due to the
Methyl (E)-3-(5-Methoxy-2-(methyl(nitroso)amino)phenyl)-
acrylate (5e). Eluent: 40:1 hexanes/ethyl acetate; 18 mg, 35%
yield, yellow crystalline solid. The product was prepared via the
general procedure B. The title compound was obtained as an
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different conformations of the NO bond (1:0.08). 1H NMR
(CDCl3, 600 MHz): δ 7.98 (d, J = 1.8 Hz, 1H), 7.78 (dd, J = 8.4, 1.2
Hz, 1H), 7.56 (d, J = 15.6 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 6.51 (d,
J = 15.6 Hz, 1H), 3.80 (s, 3H), 3.43 (s, 3H). 13C{1H} NMR (CDCl3,
isomers due to the different conformations of the NO bond
1
(1:0.4). H NMR (CDCl3, 600 MHz): δ 7.74 (dd, J = 8.4, 1.8 Hz,
1H), 7.51−7.42 (m, 3H+1.2H), 7.32 (dd, J = 7.8, 1.8 Hz, 1H+0.4H),
6.84 (d, J = 12.6 Hz, 0.4H), 6.37 (d, J = 16.2 Hz, 1H), 5.96 (d, J =
12.0 Hz, 0.4H), 3.40 (s, 3H), 3.35 (s, 1.2 H), 1.50 (s, 9H), 1.32 (s,
3.6H). 13C{1H} NMR (CDCl3, 150 MHz): δ 165.5, 164.9, 141.6,
140.5, 138.4, 138.0, 137.3, 132.2, 131.1, 130.8(1), 130.7(5), 130.5,
130.0, 129.4, 129.2, 128.4, 128.0, 127.4, 126.2, 125.0, 124.7, 123.6,
123.5, 81.1, 36.1, 35.4, 28.2, 28.0. IR (neat): 1705, 1638, 1442, 1370,
1323, 1295, 1148, 1074, 1045, 978, 958, 762 cm−1. HRMS (ESI): m/z
calcd for C14H18N2O3 [M + Na]+, 285.1209; found, 285.1214.
(E)-N-Methyl-N-(2-styrylphenyl)nitrous Amide (5o). Eluent: 50:1
hexanes/ethyl acetate; 38 mg, 80% yield, yellow liquid. The product
was prepared via the general procedure B. The title compound was
obtained as an inseparable mixture of syn- and anti-isomers due to the
different conformations of the NO bond (1:0.1). 1H NMR (CDCl3,
600 MHz): δ 7.81 (d, J = 6.6 Hz, 1H), 7.49 (t, J = 7.8 Hz, 1H), 7.46
(d, J = 7.2 Hz, 2H), 7.43−7.40 (m, 1H), 7.38−7.34 (m, 2H), 7.33−
7.28 (m, 2H), 7.13 (d, J = 16.2 Hz, 1H), 6.92 (d, J = 15.6 Hz, 1H),
3.42 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 140.5, 136.7,
133.6, 132.5, 129.6, 128.9, 128.8, 128.5(4), 128.4(9), 128.4, 127.1,
127.0, 126.9, 126.5, 123.0, 36.1. IR (neat): 1498, 1437, 1396, 1202,
1120, 1074, 962, 759, 691 cm−1. HRMS (ESI): m/z calcd for
C15H14N2O [M + H]+, 239.1178; found, 239.1183.
N-(2′,5′-Dioxo-2′,5′-dihydro-[1,1′-biphenyl]-2-yl)-N-methylni-
trous Amide (5p). Eluent: 30:1 hexanes/ethyl acetate; 29 mg, 60%
yield, brown amorphous solid. The product was prepared via the
general procedure B. 1H NMR and 13C NMR spectra for this
compound are consistent with previously reported literature data.27
1H NMR (CDCl3, 600 MHz): δ 7.64−7.61 (m, 1H), 7.51 (t, J = 7.8
Hz, 1H), 7.43−7.41 (m, 1H), 7.37 (d, J = 7.2 Hz, 1H), 6.86 (d, J =
2.4 Hz, 1H), 6.77 (dd, J = 10.2, 2.4 Hz, 1H), 6.70 (d, J = 9.6 Hz, 1H),
3.40 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 187.2, 185.4,
147.0, 141.2, 136.8, 136.4, 134.6, 131.3, 131.1, 128.8, 128.6, 123.1,
34.8.
2
150 MHz): δ 166.3, 144.1, 138.4, 131.5 (C−F, JC−F = 27.5 Hz),
3
3
131.1, 127.6 (C−F, JC−F = 3.6 Hz), 126.0, 125.5 (C−F, JC−F = 3.6
1
Hz), 123.4 (C−F, JC−F = 229.9 Hz), 122.9, 52.2, 35.6. 19F NMR
(CDCl3, 564 MHz): δ −62.7. IR (neat): 1716, 1642, 1620, 1441,
1314, 1295, 1271, 1161, 1122, 1088, 988, 895, 872, 837 cm−1. HRMS
(ESI): m/z calcd for C12H11F3N2O3 [M + K]+, 327.0353; found,
327.0360.
Methyl (E)-3-(3-Methoxy-3-oxoprop-1-en-1-yl)-4-(methyl-
(nitroso)amino)benzoate (5j). Eluent: 30:1 hexanes/ethyl acetate;
49 mg, 88% yield, yellow crystalline solid, mp 121−123 °C. The
product was prepared via the general procedure B. The title
compound was obtained as an inseparable mixture of syn- and anti-
isomers due to the different conformations of the NO bond
1
(1:0.07). H NMR (CDCl3, 600 MHz): δ 8.41 (d, J = 1.8 Hz, 1H),
8.16 (dd, J = 8.4, 1.8 Hz, 1H), 7.55 (d, J = 16.2 Hz, 1H), 7.42 (d, J =
7.8 Hz, 1H), 6.40 (d, J = 15.6 Hz, 1H), 3.97 (s, 3H), 3.79 (s, 3H),
3.42 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 166.5, 165.7,
144.8, 138.9, 131.8, 130.8, 130.4, 129.8, 125.3, 122.2, 52.8, 52.1, 35.6.
IR (neat): 1716, 1640, 1610, 1437, 1282, 1256, 1198, 1167, 1113,
1068, 982, 962, 874, 807, 770, 753 cm−1. HRMS (ESI): m/z calcd for
C13H14N2O5 [M + Na]+, 301.0794; found, 301.0801.
Methyl (E)-3-(5-Acetyl-2-(methyl(nitroso)amino)phenyl)acrylate
(5k). Eluent: 40:1 hexanes/ethyl acetate; 36 mg, 68% yield, yellow
crystalline solid, mp 104−107 °C. The product was prepared via the
general procedure B. The title compound was obtained as an
inseparable mixture of syn- and anti-isomers due to the different
1
conformations of the NO bond (1:0.08). H NMR (CDCl3, 600
MHz): δ 8.30 (d, J = 1.8 Hz, 1H), 8.08 (dd, J = 8.4, 1.8 Hz, 1H), 7.57
(d, J = 16.2 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 6.53 (d, J = 15.6 Hz,
1H), 3.79 (s, 3H), 3.42 (s, 3H), 2.67 (s, 3H). 13C{1H} NMR (CDCl3,
150 MHz): δ 196.4, 166.5, 144.8, 139.1, 137.2, 130.5, 128.5, 125.5,
122.3, 52.1, 35.6, 26.8. IR (neat): 1709, 1687, 1638, 1603, 1439,
1329, 1282, 1245, 1195, 1176, 1094, 1059, 982, 876, 840, 816, 755
cm−1. HRMS (ESI): m/z calcd for C13H14N2O4 [M + H]+, 263.1026;
found, 263.1017.
N-Methyl-N-(4′-methyl-2′,5′-dioxo-2′,5′-dihydro-[1,1′-biphenyl]-
2-yl)nitrous Amide (5q). Eluent: 30:1 hexanes/ethyl acetate; 44 mg,
88% yield, brown gum. The product was prepared via the general
procedure B. The title compound was obtained as an inseparable
1
Methyl (E)-3-(4-(Methyl(nitroso)amino)-[1,1′-biphenyl]-3-yl)-
acrylate (5l). Eluent: 40:1 hexanes/ethyl acetate; 26 mg, 44% yield,
yellow crystalline solid, mp 110−112 °C. The product was prepared
via the general procedure B. The title compound was obtained as an
inseparable mixture of syn- and anti-isomers due to the different
mixture of regioisomers (1:0.51). H NMR (CDCl3, 600 MHz): δ
7.62−7.58 (m, 1.5H), 7.48 (dt, J = 7.8, 1.8 Hz, 1.43H), 7.41−7.38
(m, 1.61H), 7.37−7.34 (m, 1.44H), 6.83 (s, 0.91H), 6.77 (d, J = 3.0
Hz, 1.00H), 6.60−6.59 (m, 1.13H), 6.52 (d, J = 1.2 Hz, 1.83H), 3.39
(s, 5.42H), 3.38 (s, 3.17H), 2.04 (d, J = 1.2 Hz, 5.84H), 1.98 (d, J =
1.2 Hz, 3.00H). 13C{1H} NMR (CDCl3, 150 MHz): δ 187.7, 187.1,
186.1, 185.6, 147.0, 146.8, 146.3, 145.8, 141.2, 141.1, 134.6, 134.5,
133.6, 133.3, 133.1, 131.3, 131.2, 131.0, 129.7, 129.2, 128.8, 128.6,
123.1, 35.0, 34.9, 16.3, 15.7. IR (neat): 1709, 1687, 1599, 1437, 1361,
1327, 1245, 1193, 1172, 1094, 1060, 984, 844, 818, 755 cm−1. HRMS
(ESI): m/z calcd for C14H12N2O3 [M + Na]+, 279.0740; found,
279.0740.
N-(2-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)phenyl)-N-methyl-
nitrous Amide (5r). Eluent: 30:1 hexanes/ethyl acetate; 41 mg, 70%
yield, brown amorphous solid, mp 122−124 °C. The product was
prepared via the general procedure B. 1H NMR (CDCl3, 600 MHz): δ
8.07 (dd, J = 7.2, 1.2 Hz, 1H), 7.99 (dd, J = 7.2, 1.2 Hz, 1H), 7.76−
7.71 (m, 2H), 7.63 (dt, J = 7.8, 1.8 Hz, 1H), 7.53 (dt, J = 7.8, 1.8 Hz,
1H), 7.48 (dd, J = 7.8, 1.8 Hz, 1H), 7.40 (d, J = 9.0 Hz, 1H), 7.07 (s,
1H), 3.43 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 184.8,
183.5, 148.9, 141.3, 137.1, 134.2, 134.0, 132.2, 131.8, 131.4, 131.0,
129.5, 128.6, 127.1, 126.3, 123.3, 34.9. IR (neat): 1668, 1655, 1614,
1593, 1497, 1456, 1353, 1332, 1280, 1254, 1195, 1085, 1053, 964,
926, 781, 760, 710 cm−1. HRMS (ESI): m/z calcd for C17H12N2O3
[M + H]+, 293.0920; found, 293.0926.
1
conformations of the NO bond (1:0.08). H NMR (CDCl3, 600
MHz): δ 7.93 (d, J = 2.4 Hz, 1H), 7.73 (dd, J = 8.4, 2.4 Hz, 1H),
7.64−7.59 (m, 3H), 7.50 (t, J = 7.2 Hz, 2H), 7.45−7.42 (m, 1H),
7.42 (d, J = 8.4 Hz, 2H), 6.52 (d, J = 9.6 Hz, 1H), 3.80 (s, 3H), 3.45
(s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ 166.7, 142.6, 140.7,
139.6, 139.4, 130.8, 129.7, 129.5, 129.2(4), 129.1(8), 128.4, 127.3,
127.0, 126.8, 126.3, 121.6, 121.5, 52.1, 36.0. IR (neat): 1703, 1438,
1403, 1273, 1247, 1183, 1079, 1040, 993, 964, 835, 759, 699 cm−1.
HRMS (ESI): m/z calcd for C17H16N2O3 [M + Na]+, 319.1053;
found, 319.1051.
Methyl (E)-3-(4-Methyl-2-(methyl(nitroso)amino)phenyl)acrylate
(5m). Eluent: 50:1 hexanes/ethyl acetate; 45 mg, 95% yield, yellow
crystalline solid. The product was prepared via the general procedure
B. The title compound was obtained as an inseparable mixture of syn-
and anti-isomers due to the different conformations of the NO
bond (1:0.1). 1H NMR and 13C NMR spectra for this compound are
consistent with previously reported literature data.9a 1H NMR
(CDCl3, 600 MHz): δ 7.64 (d, J = 9.0 Hz, 1H), 7.50 (d, J = 16.2
Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H), 7.14 (s, 1H), 6.39 (d, J = 15.6 Hz,
1H), 3.77 (s, 3H), 3.39 (s, 3H), 2.43 (s, 3H). 13C{1H} NMR (CDCl3,
150 MHz): δ 166.9, 141.9, 141.5, 139.3, 130.3, 127.9, 127.7, 127.3,
126.7, 120.3, 51.9, 36.1, 21.4.
N-(2-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-5-methylphenyl)-
N-methylnitrous Amide (5s). Eluent: 30:1 hexanes/ethyl acetate; 31
mg, 51% yield, brown amorphous solid, mp 180−182 °C. The
product was prepared via the general procedure B. 1H NMR (CDCl3,
600 MHz): δ 8.08−8.06 (m, 1H), 7.98 (dd, J = 7.2, 1.2 Hz, 1H),
7.75−7.68 (m, 2H), 7.37 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 8.4 Hz,
tert-Butyl (E)-3-(2-(Methyl(nitroso)amino)phenyl)acrylate (5n).
Eluent: 50:1 hexanes/ethyl acetate; 37 mg, 70% yield, yellow liquid.
The product was prepared via the general procedure B. The title
compound was obtained as an inseparable mixture of syn- and anti-
I
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Article
1H), 7.21 (bro, 1H), 7.05 (s, 1H), 3.42 (s, 3H), 2.50 (s, 3H).
150 MHz): δ 167.9, 145.5, 140.5, 132.5, 128.6, 126.7, 120.0, 117.7,
111.6, 51.7, 31.1, 20.4.
13C{1H} NMR (CDCl3, 150 MHz): δ 184.8, 183.6, 148.9, 141.6,
Methyl (E)-3-(5-Methoxy-2-(methylamino)phenyl)acrylate (6e).
Eluent: 20:1 hexanes/ethyl acetate; 13 mg, 30% yield, yellow
crystalline solid. The product was prepared via the general procedure
141.2, 136.8, 134.1, 134.0, 132.2, 131.9, 1312, 129.4, 127.0, 126.3,
123.9, 35.0, 21.5. IR (neat): 1657, 1593, 1441, 1413, 1398, 1292,
1275, 1248, 1232, 1206, 1087, 1046, 1021, 893, 837, 783, 751, 714
cm−1. HRMS (ESI): m/z calcd for C18H14N2O3 [M + H]+, 307.1077;
found, 307.1083.
1
C. H NMR and 13C NMR spectra for this compound are consistent
with previously reported literature data.9a 1H NMR (CDCl3, 600
MHz): δ 7.81 (d, J = 16.2 Hz, 1H), 6.95 (d, J = 3.0 Hz, 1H), 6.92 (dd,
J = 8.4, 3.0 Hz, 1H), 6.40 (d, J = 8.4 Hz, 1H), 6.33 (d, J = 16.2 Hz,
1H), 3.80 (s, 3H), 3.77 (s, 3H), 2.87 (s, 3H). 13C{1H} NMR (CDCl3,
150 MHz): δ 167.8, 151.9, 142.6, 140.3, 120.8, 118.4, 118.2, 112.7(5),
112.6(9), 56.0, 51.8, 31.4.
N-(4-Chloro-2-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)phenyl)-
N-methylnitrous Amide (5t). Eluent: 30:1 hexanes/ethyl acetate; 24
mg, 37% yield, brown gum. The product was prepared via the general
1
procedure B. H NMR (CDCl3, 600 MHz): δ 8.08 (dd, J = 7.2, 1.2
Hz, 1H), 7.99 (dd, J = 7.2, 1.2 Hz, 1H), 7.77−7.72 (m, 2H), 7.60 (dd,
J = 8.4, 3.0 Hz, 1H), 7.48 (d, J = 3.0 Hz, 1H), 7.34 (d, J = 8.4 Hz,
1H), 7.07 (s, 1H), 3.40 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz):
δ 184.4, 183.1, 147.6, 139.9, 137.4, 134.4, 134.3, 134.2, 132.1, 131.7,
131.3, 131.0, 130.9, 127.1, 126.5, 124.5, 34.8. IR (neat): 1657, 1593,
1493, 1452, 1398, 1344, 1306, 1273, 1251, 1191, 1105, 1079, 1049,
1025, 958, 891, 818, 781, 744, 716, 669 cm−1. HRMS (ESI): m/z
calcd for C17H11ClN2O3 [M + H]+, 327.0531; found, 327.0538.
General Procedure C: Denitrosation of N-Nitrosamines. N-
Nitrosamine (1.0 equiv) was stirred in dichloromethane for
approximately 2 min at room temperature after the addition of
iodine (0.3 equiv) and triethylsilane (1.5 equiv). The reaction was
further allowed to stir for 10 min, and the progress of the reaction was
monitored by TLC. After the complete consumption of N-
nitrosoamine, the reaction mixture was quenched with a saturated
solution of sodium thiosulfate (20 mL) extracted with ethyl acetate (2
× 25 mL). The organic layer was dried over anhydrous sodium
sulfate, concentrated, and subjected to column chromatography using
hexanes/ethyl acetate (20:1) to obtain the corresponding substituted
secondary amines.
Methyl (E)-3-(5-Fluoro-2-(methylamino)phenyl)acrylate (6f).
Eluent: 20:1 hexanes/ethyl acetate; 29 mg, 69% yield, yellow
crystalline solid. The product was prepared via the general procedure
1
C. H NMR and 13C NMR spectra for this compound are consistent
with previously reported literature data.9a 1H NMR (CDCl3, 600
MHz): δ 7.76 (d, J = 16.8 Hz, 1H), 7.08 (dd, J = 9.6, 2.4 Hz, 1H),
7.00 (dt, J = 9.0, 2.4 Hz, 1H), 6.61 (dd, J = 9.0, 3.6 Hz, 1H), 6.31 (d, J
= 15.6 Hz, 1H), 3.80 (s, 3H), 2.86 (s, 3H). 13C{1H} NMR (CDCl3,
1
150 MHz): δ 167.5, 156.4 (C−F, JC−F = 195.0 Hz), 144.1, 139.2,
3
2
121.0 (C−F, JC−F = 6.0 Hz), 119.2, 118.4 (C−F, JC−F = 18.0 Hz),
2
3
114.0 (C−F, JC−F = 19.1 Hz), 112.4 (C−F, JC−F = 4.8 Hz), 51.9,
31.3. 19F NMR (CDCl3, 564 MHz): δ −127.6.
Methyl (E)-3-(5-Chloro-2-(methylamino)phenyl)acrylate (6g).
Eluent: 20:1 hexanes/ethyl acetate; 33 mg, 72% yield, yellow
crystalline solid. The product was prepared via the general procedure
C. H NMR and 13C NMR spectra for this compound are consistent
1
with previously reported literature data.28 1H NMR (CDCl3, 600
MHz): δ 7.72 (d, J = 15.6 Hz, 1H), 7.31 (d, J = 1.8 Hz, 1H), 7.21 (dd,
J = 9.0, 2.4 Hz, 1H), 6.60 (d, J = 9.0 Hz, 1H), 6.32 (d, J = 16.2 Hz,
1H), 3.80 (s, 3H), 2.87 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz):
δ 167.4, 145.9, 138.9, 131.3, 127.5, 122.5, 121.3, 119.3, 112.6, 51.9,
31.0.
Methyl (E)-3-(2-(Methylamino)phenyl)acrylate (6a). Eluent: 20:1
hexanes/ethyl acetate; 31 mg, 81% yield, yellow crystalline solid. The
product was prepared via the general procedure C. 1H NMR and 13
C
NMR spectra for this compound are consistent with previously
reported literature data.9a 1H NMR (CDCl3, 600 MHz): δ 7.83 (d, J =
15.6 Hz, 1H), 7.37 (dd, J = 7.8, 1.2 Hz, 1H), 7.31−7.27 (m, 1H), 6.73
(t, J = 7.8 Hz, 1H), 6.67 (d, J = 7.8 Hz, 1H), 6.34 (d, J = 15.6 Hz,
1H), 4.24 (bro, 1H), 3.80 (s, 3H), 2.89 (s, 3H). 13C{1H} NMR
(CDCl3, 150 MHz): δ 167.8, 147.7, 140.5, 131.7, 128.2, 119.9, 117.8,
117.4, 111.0, 51.7, 30.7.
Methyl (E)-3-(5-Bromo-2-(methylamino)phenyl)acrylate (6h).
Eluent: 20:1 hexanes/ethyl acetate; 20 mg, 37% yield, yellow
crystalline solid. The product was prepared via the general procedure
1
C. H NMR and 13C NMR spectra for this compound are consistent
with previously reported literature data.28 1H NMR (CDCl3, 600
MHz): δ 7.68 (d, J = 15.6 Hz, 1H), 7.42 (d, J = 1.8 Hz, 1H), 7.32 (dd,
J = 8.4, 2.4 Hz, 1H), 6.50 (d, J = 9.0 Hz, 1H), 6.30 (d, J = 15.0 Hz,
1H), 4.15 (bro, 1H), 3.78 (s, 3H), 2.84 (s, 3H). 13C{1H} NMR
(CDCl3, 150 MHz): δ 167.4, 146.6, 138.9, 134.0, 130.2, 121.5, 119.0,
112.5, 109.0, 51.8, 30.7.
Methyl (E)-3-(2-(Ethylamino)phenyl)acrylate (6b). Eluent: 20:1
hexanes/ethyl acetate; 35 mg 86% yield, yellow crystalline solid. The
product was prepared via the general procedure C. 1H NMR and 13
C
NMR spectra for this compound are consistent with previously
reported literature data.9a 1H NMR (CDCl3, 600 MHz): δ 7.83 (d, J =
15.6 Hz, 1H), 7.36 (dd, J = 7.8, 1.8 Hz, 1H), 7.27−7.23 (m, 1H), 6.70
(t, J = 7.8 Hz, 1H), 6.67 (d, J = 8.4 Hz, 1H), 6.33 (d, J = 16.2 Hz,
1H), 3.79 (s, 3H), 3.19 (q, J = 7.2 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H).
13C{1H} NMR (CDCl3, 150 MHz): δ 167.9, 146.8, 140.5, 131.7,
128.3, 119.7, 117.8, 117.3, 111.6, 51.7, 38.6, 14.8.
Methyl (E)-3-(2-(Methylamino)-5-(trifluoromethyl)phenyl)-
acrylate (6i). Eluent: 20:1 hexanes/ethyl acetate; 34 mg, 65% yield,
yellow crystalline solid, mp 66−68 °C. The product was prepared via
the general procedure C. 1H NMR (CDCl3, 600 MHz): δ 7.74 (d, J =
15.6 Hz, 1H), 7.56 (d, J = 1.8 Hz, 1H), 7.49 (dd, J = 8.4, 1.8 Hz, 1H),
6.67 (d, J = 8.4 Hz, 1H), 6.38 (d, J = 15.6 Hz, 1H), 4.39 (bro, 1H),
3.82 (s, 3H), 2.93 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ
1
167.4, 149.7, 139.1, 128.4 (C−F, 3JC−F = 2.5 Hz), 125.5 (C−F, JC−F
Methyl (E)-3-(2-(Isopropylamino)phenyl)acrylate (6c). Eluent:
= 225.0 Hz), 125.3 (C−F, 3JC−F = 3.6 Hz), 119.8, 119.3, 119.0 C−F,
20:1 hexanes/ethyl acetate; 23 mg, 52% yield, yellow crystalline
2JC−F = 27.5 Hz), 110.3, 52.0, 30.5. 19F NMR (CDCl3, 564 MHz): δ
1
solid. The product was prepared via the general procedure C. H
NMR and 13C NMR spectra for this compound are consistent with
previously reported literature data.9a 1H NMR (CDCl3, 600 MHz): δ
7.81 (d, J = 16.2 Hz, 1H), 7.36 (dd, J = 7.8, 1.8 Hz, 1H), 7.27−7.23
(m, 1H), 6.70−6.67 (m, 1H), 6.33 (d, J = 15.6 Hz, 1H), 3.81 (s, 3H),
3.70 (septet, J = 6.0 Hz, 1H), 1.26 (d, J = 6.0 Hz, 6H). 13C{1H} NMR
(CDCl3, 150 MHz): δ 167.9, 146.0, 140.6, 131.6, 128.5, 119.8, 117.8,
117.0, 112.2, 51.7, 44.4, 23.1.
−61.2. IR (neat): 3414, 1703, 1617, 1580, 1536, 1323, 1263, 1156,
1107, 977, 902, 861, 820 cm−1. HRMS (ESI): m/z calcd for
C12H12F3NO2 [M + H]+, 260.0892; found, 260.0888.
Methyl (E)-3-(3-Methoxy-3-oxoprop-1-en-1-yl)-4-
(methylamino)benzoate (6j). Eluent: 20:1 hexanes/ethyl acetate;
39 mg, 79% yield, yellow crystalline solid, mp 75−77 °C. The product
1
was prepared via the general procedure C. Yellow solid. H NMR
(CDCl3, 600 MHz): δ 8.01 (d, J = 2.4 Hz, 1H), 7.90 (dd, J = 8.4, 1.8
Hz, 1H), 7.72 (d, J = 16.2 Hz, 1H), 6.58 (d, J = 8.4 Hz, 1H), 6.38 (d,
J = 15.6 Hz, 1H), 3.84 (s, 3H), 3.76 (s, 3H), 2.90 (s, 3H). 13C{1H}
NMR (CDCl3, 150 MHz): δ 167.5, 167.0, 150.8, 139.3, 133.1, 130.0,
119.1, 118.8, 118.3, 109.8, 51.8 51.7, 30.4. IR (neat): 3047, 1692,
1607, 1528, 1435, 1349, 1293, 1245, 1197, 1152, 999, 973, 854, 746
cm−1. HRMS (ESI): m/z calcd for C13H15NO4 [M + H]+, 250.1073;
found, 250.1071.
Methyl (E)-3-(5-Methyl-2-(methylamino)phenyl)acrylate (6d).
Eluent: 20:1 hexanes/ethyl acetate; 31 mg, 75% yield, yellow
crystalline solid. The product was prepared via the general procedure
1
C. H NMR and 13C NMR spectra for this compound are consistent
with previously reported literature data.9a 1H NMR (CDCl3, 600
MHz): δ 7.82 (d, J = 15.0 Hz, 1H), 7.19 (d, J = 1.8 Hz, 1H), 7.11 (dd,
J = 8.4, 2.4 Hz, 1H), 6.62 (d, J = 8.4 Hz, 1H), 6.33 (d, J = 15.0 Hz,
1H), 3.80 (s, 3H), 2.87 (s, 3H), 2.25 (s, 3H). 13C{1H} NMR (CDCl3,
J
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Methyl (E)-3-(5-Acetyl-2-(methylamino)phenyl)acrylate (6k).
Eluent: 20:1 hexanes/ethyl acetate; 19 mg, 40% yield, yellow
crystalline solid, mp 74−76 °C. The product was prepared via the
AUTHOR INFORMATION
Corresponding Authors
■
1
Hun Young Kim − Department of Global Innovative Drugs,
Chung-Ang University, Seoul 06974, Republic of Korea;
orcid.org/0000-0002-8461-8910; Email: hunnykim@
cau.ac.kr
Kyungsoo Oh − Center for Metareceptome Research,
Graduate School of Pharmaceutical Sciences, Chung-Ang
University, Seoul 06974, Republic of Korea; orcid.org/
0000-0002-4566-6573; Email: kyungsoooh@cau.ac.kr
general procedure C. Yellow solid. H NMR (CDCl3, 600 MHz): δ
7.99 (d, J = 2.4 Hz, 1H), 7.91 (dd, J = 7.8, 1.8 Hz, 1H), 7.75 (d, J =
15.6 Hz, 1H), 6.64 (d, J = 7.8 Hz, 1H), 6.42 (d, J = 15.0 Hz, 1H),
4.66 (bro, 1H), 3.81 (s, 3H), 2.97 (d, J = 4.8 Hz, 3H), 2.52 (s, 3H).
13C{1H} NMR (CDCl3, 150 MHz): δ 196.3, 167.5, 151.0, 139.4,
132.5, 129.4, 126.6, 119.6, 118.9, 109.8, 52.0, 30.5, 26.2. IR (neat):
3336, 1715, 1603, 1551, 1431, 1349, 1293, 1256, 1163, 962, 857, 726
cm−1. HRMS (ESI): m/z calcd for C13H15NO3 [M + H]+, 234.1124;
found, 234.1121.
Methyl (E)-3-(4-(Methylamino)-[1,1′-biphenyl]-3-yl)acrylate (6l).
Eluent: 20:1 hexanes/ethyl acetate; 21 mg, 40% yield, yellow
crystalline solid, mp 110−112 °C. The product was prepared via
the general procedure C. 1H NMR (CDCl3, 600 MHz): δ 7.86 (d, J =
9.6 Hz, 1H), 7.62 (d, J = 1.8 Hz, 1H), 7.57−7.54 (m, 3H), 7.42 (t, J =
7.8 Hz, 2H), 7.31−7.28 (m, 1H), 6.75 (d, J = 7.8 Hz, 1H), 6.43 (d, J
= 16.2 Hz, 1H), 4.20 (bro, 1H), 3.82 (s, 3H), 2.95 (s, 3H). 13C{1H}
NMR (CDCl3, 150 MHz): δ 167.8, 147.2, 140.8, 140.5, 130.5, 130.3,
128.9, 126.8, 126.6, 126.5, 120.1, 118.3, 111.4, 51.8, 30.8. IR (neat):
3422, 1700, 1614, 1528, 1498, 1323, 1290, 1163, 988, 857, 816, 753,
690 cm−1. HRMS (ESI): m/z calcd for C17H17NO2 [M + H]+,
268.1332; found, 268.1328.
Author
Tengda Si − Center for Metareceptome Research, Graduate
School of Pharmaceutical Sciences, Chung-Ang University,
Seoul 06974, Republic of Korea
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02776
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Methyl (E)-3-(4-Methyl-2-(methylamino)phenyl)acrylate (6m).
Eluent: 20:1 hexanes/ethyl acetate; 22 mg, 54% yield, yellow
crystalline solid. The product was prepared via the general procedure
■
This research was supported by the National Research
Foundation of Korea (NRF) grant funded by the Korean
government (MSICT) (NRF-2015R1A5A1008958 and NRF-
2019R1A2C2089953).
1
C. H NMR and 13C NMR spectra for this compound are consistent
with previously reported literature data.9a 1H NMR (CDCl3, 600
MHz): δ 7.80 (d, J = 16.2 Hz, 1H), 7.28 (d, J = 8.4 Hz, 1H), 6.55 (d,
J = 8.4 Hz, 1H), 6.49 (s, 1H), 6.30 (d, J = 8.4 Hz, 1H), 3.79 (s, 3H),
2.88 (s, 3H), 2.33 (s, 3H). 13C{1H} NMR (CDCl3, 150 MHz): δ
168.1, 147.7, 142.4, 140.4, 128.3, 118.5, 117.2, 116.5, 111.7, 51.7,
30.8, 22.0.
REFERENCES
■
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NMR spectra for this compound are consistent with previously
reported literature data.28 1H NMR (CDCl3, 600 MHz): δ 7.71 (d, J
= 15.0 Hz, 1H), 7.36−7.33 (m, 1H), 7.29−7.26 (m, 1H), 6.70 (t, J =
7.2 Hz, 1H), 6.66 (d, J = 8.4 Hz, 1H), 6.26 (d, J = 16.2 Hz, 1H), 4.89
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(E)-N-Methyl-2-styrylaniline (6o). Eluent: 20:1 hexanes/ethyl
acetate; 23 mg, 56% yield, yellow liquid. The product was prepared
1
via the general procedure C. H NMR and 13C NMR spectra for this
compound are consistent with previously reported literature data.28
1H NMR (CDCl3, 600 MHz): δ 7.53 (d, J = 7.8 Hz, 2H), 7.41 (dd, J
= 7.8, 1.8 Hz, 1H), 7.38 (t, J = 7.8 Hz, 2H), 7.30−7.24 (m, 2H), 7.20
(d, J = 15.6 Hz, 1H), 6.99 (d, J = 16.2 Hz, 1H), 6.83 (t, J = 7.8 Hz,
1H), 6.76 (d, J = 8.4 Hz, 1H), 2.92 (s, 3H). 13C{1H} NMR (CDCl3,
150 MHz): δ 146.0, 137.7, 131.2, 129.1, 128.8, 127.7, 127.4, 127.0,
126.6, 124.6, 124.3, 118.4, 111.3, 31.4.
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ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02776.
̈
Schonbauer, D.; Blieck, R.; Dao-Huy, T.; Pototschnig, G.; Schaaf, P.;
Wiesinger, T.; Zia, M. F.; Wencel-Delord, J.; Besset, T.; Maes, B. U.
Experimental procedure and characterization data for all
new compounds, and NMR spectra (PDF)
W.; Schnurch, M. A Comprehensive Overview of Directing Groups
̈
Applied in Metal-Catalyzed C−H Functionalization Chemistry. Chem.
Soc. Rev. 2018, 47, 6603−6743. (f) Dey, A.; Sinha, S. K.; Achar, T. K.;
Maiti, D. Accessing Remote meta- and para-C(sp2)−H Bonds with
Covalently Attached Directing Groups. Angew. Chem., Int. Ed. 2019,
58, 10820−10843. (g) Rej, S.; Ano, Y.; Chatani, N. Bidentate
Directing Groups: An Efficient Tool in C−H Bond Functionalization
Chemistry for the Expedient Construction of C−C Bonds. Chem. Rev.
2020, 120, 1788−1887.
FAIR data, including the primary NMR FID files, for
1,2-di(naphthalen-1-yl)ethyne, 1,2-di(naphthalen-2-yl)-
ethyne, 1,2-di(thiophen-3-yl)ethyne, 4,4′-(ethyne-1,2-
diyl)dibenzonitrile, N-methyl-[1,1′-biphenyl]-4-amine,
N-methylnaphthalen-2-amine, 3a−3zc, 5a−5t, and 6a−
6o (ZIP)
K
https://dx.doi.org/10.1021/acs.joc.0c02776
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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