Redox-Neutral Cobalt(III)-Catalyzed C-H Activation/Annulation of α,β-Unsaturated Oxime Ether with Alkyne: One-Step Access to Multisubstituted Pyridine

Article abstract of DOI:10.1021/acs.joc.0c02558

A redox neutral Co(III)-catalyzed annulation of α,β-unsaturated oxime ether with alkyne has been reported. Multisubstituted pyridines were synthesized in good yields without the use of any heavy metal oxidants. The developed methodology tolerates a variety of functional groups. Notably, this transformation has been applied to the late-stage modification of the bioactive molecule dehydropregnenolone.

Full text of DOI:10.1021/acs.joc.0c02558

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Article
Redox-Neutral Cobalt(III)-Catalyzed C−H Activation/Annulation of
α,β-Unsaturated Oxime Ether with Alkyne: One-Step Access to
Multisubstituted Pyridine
Smruti Ranjan Mohanty, Bedadyuti Vedvyas Pati, Shyam Kumar Banjare, Gopal Krushna Das Adhikari,
and Ponneri Chandrababu Ravikumar*
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ABSTRACT: A redox neutral Co(III)-catalyzed annulation of α,β-unsatu-
rated oxime ether with alkyne has been reported. Multisubstituted pyridines
were synthesized in good yields without the use of any heavy metal oxidants.
The developed methodology tolerates a variety of functional groups. Notably,
this transformation has been applied to the late-stage modification of the
bioactive molecule dehydropregnenolone.
INTRODUCTION
■
The transition-metal-catalyzed functionalization of C−H
bonds is considered an atom economic process in organic
synthesis.1 Among all of the heterocycles, nitrogen-containing
heterocycles hold significance in organic synthesis because of
their presence in a wide range of natural products,
pharmaceuticals, and agrochemicals.2 Hence, the development
of efficient synthetic methodology to obtain those molecules
has received extensive importance over the years.
Multisubstituted pyridine (tetrahydroquinoline) is an
important structural skeleton among all of the nitrogen-
containing heterocycles and biologically active natural
products, such as haplophyllidine3 and megistosarcimine.4
Moreover, molecules that contain the tetrahydroquinoline
moiety have been found to show biological activities such as
anti-HIV,5 anticancer,6 and antifungal7 properties (Figure 1).
Figure 1. Representative examples of natural products and a bioactive
Therefore, significant efforts have been dedicated to the
development of methodologies for the synthesis of tetrahy-
droquinoline using mainly second and third row transition
metal catalysts (Rh, Ir, and Pd).8,9 However, these catalytic
systems are associated with several undesirable factors: (i) the
use of an expensive metal catalyst, (ii) harsh reaction
conditions, and (iii) low functional group tolerance. Hence,
in order to tackle the above-mentioned challenges, efficient
and benign reaction conditions are of paramount importance.
So far, there is no report for the synthesis of
tetrahydroquinoline by using a cobalt catalyst. Previously,
Matsunaga,10 Ackermann,11 Sundararaju,12 and Cheng13 have
reported the synthesis of isoquinoline from oxime and alkyne
by using the Cp*Co(III) catalyst (Scheme 1a). However, all of
the reports are based on arene C−H bond activation. The
activation of nonaromatic vinylic C−H bonds is challenging,
and it is less explored.14 Yoshikai and Petit groups have
accomplished vinylic C−H activation of α,β-unsaturated
molecule-containing tetrahydroquinoline moiety.
imines using a low valent cobalt catalyst and subsequent
annulation with alkynes for the synthesis of dihydropyridines
(Scheme 1b,c).15,16 However, these method suffers from some
drawbacks: (a) the metal complex that is highly sensitive to air,
(b) the requirement of high temperatures in one case, which
goes against the introduction of sensitive groups, and (c) the
necessity of an extra step to access aromatic pyridine
derivatives.17 Therefore, direct synthesis of multisubstituted
Received: October 28, 2020
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© XXXX American Chemical Society
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A

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a
Scheme 1. Comparison with Previous Work
Table 1. Optimization of Reaction Conditions
silver salt (20
mol %)
additive (20
mol %)
solvent (0.1
M)
yield
b
entry
(%)
1
2
3
4
5
6
7
8
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgBF4
AgOTf
AgNTf2
AgNTf2
AgNTf2
AgNTf2
AgNTf2
AgNTf2
1-AdCOOH
1-AdCOOH
1-AdCOOH
1-AdCOOH
TFA
NaOAc
LiOAc
AgOAc
CsOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
THF
nd
nd
nd
9
1,4-dioxane
EtOH
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
7
31
34
35
37
61
47
58
75
9
10
11
12
13
14
15
16
17
18
19
c
88
d
53
e
69
f
nd
g
trace
h
KOAc
79
a
Reaction conditions: 1a (0.112 mmol), 2a (0.056 mmol), [Cp*Co-
(CO)I2] (10 mol %), silver salt (20 mol %), additive (100 mol %),
b
c
pyridine via olefinic C−H activation followed by annulations is
still an unresolved problem.
solvent (0.1 M), 120 °C for 12 h. Isolated yield. 1 equiv of additive.
d
e
f
Reaction at 60 °C. 5 mol % of [Cp*Co(CO)I2]. Absence of cobalt
g
h
catalyst. Absence of additive. Absence of AgNTf2; nd = not
detected.
Although there are a handful of reports on Co(III)-catalyzed
olefinic C−H activation,15,16,18−22,25 to the best of our
knowledge, there is no report of Co(III)-catalyzed annulations
of α,β-unsaturated oxime ether with alkyne to synthesize
multisubstituted pyridine under redox neutral conditions
(Scheme 1d). Hence, it is highly desirable to develop an
efficient methodology for annulations of α,β-unsaturated oxime
ether with alkyne using a cobalt catalyst.
screened different silver additives such as AgBF4, AgOTf, and
AgNTf2 (Table 1, entries 11−13). Delightfully, AgNTf2
produced the best yield of 3aa, 75% (Table 1, entry 13).
Further,when we increased the base (KOAc) equivalence from
20 mol % to 1 equiv, we obtained 88% of the desired product
3aa (Table 1, entry 14). It was found that lower temperature
and reduced catalyst loading were found to be ineffective to
afford the annulation product in better yields (entries 15 and
16).
We performed a few control experiments to understand the
influence of catalyst, silver additive, and base. In the absence of
catalyst, no reaction could occur (Table 1, entry 17); in the
absence of additive only, a trace amount of product was
formed (Table 1, entry 18). Whereas without a silver additive,
a 79% yield of 3aa was obtained (Table 1, entry 19).
With the optimized reaction conditions in hand, the
generality of the reaction was examined (Scheme 2). As seen
before, unsubstituted oxime ether gave the desired product in
excellent yield (88%). The structure of 3aa was confirmed by
single-crystal X-ray analysis. para-Halogen-substituted α,β-
unsaturated oxime ethers (−F, −Br, −I) were found to be
compatible and produced the desired product in good to
excellent yields (Scheme 2, 3ba, 3ca, 3da). The oxime ether
with the electron-donating group at the para-position (−Me)
furnished a good yield of the corresponding product (Scheme
2, 3ea), whereas the electron-withdrawing group (−NO2) at
the para-position gave only 23% yield of the products (Scheme
2, 3fa). Heterocycle-substituted oxime ether underwent
RESULTS AND DISCUSSION
■
To achieve this goal, we initiated our optimization by taking
(1E,2E)-2-benzylidenecyclohexanone o-methyl oxime ether 1a
as a model substrate and diphenylacetylene 2a as a coupling
partner, [CoCp*(CO)I2] (10 mol %) as a catalyst, and AgSbF6
(20 mol %) as an activator along with 1-adamantanecarboxylic
acid (20 mol %) as an additive in tetrahydrofuran (THF).
Unfortunately, we did not get any product (Table 1, entry 1).
Keeping all other reaction conditions constant, we varied the
solvent to dioxane and ethanol (Table 1, entries 2 and 3);
unfortunately, we were again met with failure. Gratifyingly,
when we performed the reaction with HFIP as a solvent, we
obtained the desired product 3aa in 9% yield (Table 1, entry
4). In order to improve the yield further, we decided to change
the additive to trifluoroacetic acid (TFA), but we obtained
only 7% yield of 3aa (entry 5). Since acetates are known to
promote the C−H activation reaction, we decided to explore
various acetate-assisted bases such as NaOAc, LiOAc, AgOAc,
CsOAc, and KOAc (Table 1, entries 6−10). Among the
examined additives, KOAc was found to be the most effective
in producing the desired annulated product 3aa in 61% (Table
1, entry 10). For further improvement of the product yield, we
B
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Scheme 2. Scope of α,β-Unsaturated Oxime Ethers
Scheme 3. Scope of Alkynes
a
Reaction conditions: 1a (0.112 mmol), 2a (0.056 mmol), [Cp*Co-
(CO)I2] (10 mol %), AgNTf2 (20 mol %), KOAc (100 mol %), HFIP
(0.1 M), 120 °C for 12 h.
underwent cyclization in a good yield (Scheme 3, 3ae). The
meta-methyl substituted alkyne also gave an expected product
in a good yield (Scheme 3, 3af). Dialkyl-substituted alkynes
such as 3-hexyne and 4-octyne gave the products in good yields
(Scheme 3, 3ag, 3ah). Then, we turned our attention toward
unsymmetrical aryl-alkyl alkynes. In the case of 1-phenel-1-
propyne, we obtained a single isomer, where the aryl ring is
oriented toward the nitrogen atom of tetrahydroquinoline
(Scheme 3, 3ai).8,23 Other unsymmetrical alkynes such as 1-
phenyl-1-butyne, 1-phenyl-1-hexyne, 1-phenyl-1-heptyne, and
1-phenyl-1-octyne smoothly gave the annulated product with
good regioselectivity and good yields (Scheme 3, 3aj−3am),
wherein the aryl ring orienting toward the nitrogen atom of
tetrahydroquinoline is the major product.23 Formation of the
major regio-isomeric product can be rationalized with the
stabilization of intermediate III (Scheme 6) by the phenyl ring
through π-interaction with the metal orbitals.
a
Reaction conditions: 1a (0.112 mmol), 2a (0.056 mmol), [Cp*Co-
(CO)I2] (10 mol %), AgNTf2 (20 mol %), KOAc (100 mol %), HFIP
(0.1 M), 120 °C for 12 h.
cyclization, producing a moderate yield of the products
(Scheme 2, 3ga, 3ha). A trace amount of product was
observed with ortho-Br-substituted oxime ether; it might be
due to steric hindrance of the bulky −Br group near the
reaction site (Scheme 2, 3ia). Notably, the −OMe group
substituted at the ortho-position gave the desired product
(Scheme 2, 3ja) in 71% yield. With meta-substituted oxime
ether (meta-OMe), the desired product was obtained in 61%
yield (Scheme 2, 3ka), whereas, with meta-NO2-substituted
oxime ether, only a trace amount of product was formed
(Scheme 2, 3la). Dimethoxy-substituted oxime ether also gave
a trace amount of the product (Scheme 2, 3ma). Whereas
acyclic unsaturated oxime ether failed to give the desired
product, it might be due to the flexibility of the C−C bond in
acyclic unsaturated imine, which might be restricting the
formation of the five-membered planar cobaltacycle in the C−
H activation step (Scheme 2, 3oa, 3pa).
Next, to extend the generality of this methodology, we
examined the reaction using different alkynes (Scheme 3). The
alkynes with electron-donating groups such as −OMe and
−Me at the para position furnished the corresponding
annulations product in good yields (Scheme 3, 3ab, 3ac).
Surprisingly diphenylacetylene with an electron-withdrawing
group (p-NO2) failed to produce the annulation product 3ad.
Notably, heteroaryl alkyne such as di(2-thiophenyl)ethyne
The scope of the developed annulation method has been
extended to complex bioactive molecule dehydropregneno-
lone. To our delight, the desired annulated adduct was
obtained in a moderate yield (Scheme 4, 3na). These results
Scheme 4. Late-Stage Functionalization of
Dehydropregnenolone
C
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indicated that the annulations protocol developed may be
useful for rapid generation of the derivatives of bioactive
compounds. The synthetic applicability of this reaction in a
larger scale was confirmed from a 1 mmol scale reaction, which
gave 3aa in a 66% yield.
Scheme 6. Plausible Mechanism
In order to have better insight of the reaction mechanism, a
few mechanistic experiments were performed. The deuterium
labeling experiment of oxime ether 1a with D2O under the
standard reaction condition showed 18% deuterium incorpo-
ration of the vinylic C-H of oxime ether 1a, which indicates an
acetate-assisted reversible cyclometalation pathway of the
Co(III) catalyst (Scheme 5a).
Scheme 5. Competitive and Mechanistic Studies
catalyzed annulations of α,β-unsaturated oxime ether with
alkyne. The importance of this reaction is the exclusive
formation of multisubstituted pyridine. This methodology is
applicable to a wide range of substrates and as well as
compatible with a variety of functional group. This trans-
formation has been applied to the late-stage functionalization
of the bioactive molecule dehydropregnenolone.
EXPERIMENTAL SECTION
■
General Information.26 Reactions were performed using a
borosil-sealed tube vial under a N2 atmosphere. Column chromatog-
raphy was done by using 230−400 mesh silica gel of Acme synthetic
chemicals company. A gradient elution was performed by using
distilled petroleum ether and ethyl acetate. TLC plates were detected
Further, an intermolecular competitive reaction between two
different internal alkynes 2a and 2h with oxime ether 1a
resulted in 3aa/3ah in a 1:2.38 ratio. The results of the above
experiment indicate that the developed annulation protocol is
favorable for the electron-rich alkyne (Scheme 5b). A control
experiment was performed without a cobalt catalyst, but no
product was observed, which confirms the vital role of the
cobalt catalyst (Scheme 5c).
On the basis of the above mechanistic studies and previous
literature reports,24,25,12 we propose a plausible reaction
mechanism (Scheme 6). Initially [CoCp*(CO)I2] undergoes
decarbonylation in the presence of AgNTf2 and KOAc to give
the cationic complex I. Co-ordination of olefinic oxime ether
1a followed by reversible concerted cyclometalation deproto-
nation leads to cobaltacycle II. Coordination of alkyne 2a to
cobaltacycle II gives intermediate III; then, subsequent
insertion of the alkyne into the Co−C bond of intermediate
III affords a seven-membered cobaltacycle IV. The inter-
mediate IV undergoes reductive elimination (C−N Coupling)
followed by oxidative insertion of cobalt on to the weak N−O
bond to give [Cp*Co(Pyridine)(OMe)]+. Finally, intermedi-
ate V undergoes protodemetalation to give the desired product
3aa and the catalytically active species I and byproduct MeOH.
under UV light at 254 nm and vanillin. H NMR and 13C NMR
1
spectra were recorded on Bruker AV 400 MHz and Jeol ECZ-400 R
spectrometers using CDCl3 as the deuterated solvent.27 Multiplicity (s
= singlet, d = doublet, t = triplet, q = quartet, quint = quintet, sept =
septet, m = multiplet, dd = double of doublet, br = broad signal),
integration, and coupling constants (J) in hertz (Hz). HRMS signal
analysis was performed using a micro TOF Q-II mass spectrometer.
Reagents and starting materials were purchased from Sigma-Aldrich,
TCI, Avra, Spectrochem, and other commercially available sources,
used without further purification unless otherwise noted. All aldol
condensation derivatives,28 imine derivative,29 and alkyne deriva-
tives30 were prepared according to the reported literature procedure.
General Procedure A: The Synthesis of the Condensation
Product.28 The condensation reactions were performed according
to a literature procedure.28 Cycloalkanone (326 mmol, 2.91 equiv)
was added to a solution of NaOH (6.52 g, 163 mmol, 1.45 equiv) in
water (750 mL, 0.149 M) and stirred under ice bath for 5 min,
followed by the addition of benzaldehyde (11.88 g, 112 mmol, 1.0
equiv). After 3 days of stirring, the reaction mixture was neutralized
with glacial acetic acid. The product was extracted with toluene (3 ×
200 mL) and purified by vacuum distillation, affording both the
ketones as bright yellow solids. The analytical data of these
synthesized compounds were well matched with known literature
data.
General Procedure B: The Synthesis of (1E,2E)-2-Benzylidenecy-
clohexanone o-Methyl Oxime Ether.29 (1E,2E)-2-Benzylidenecyclo-
hexanone o-methyl oxime ether was prepared according to a
previously reported procedure. α,β-Unsaturated ketone or aldehyde
derivatives (5 mmol, 1.0 equiv) were taken in a 50 mL round-bottom
CONCLUSIONS
In conclusion, we have successfully developed an efficient
strategy to access multisubstituted pyridines by Co(III)-
■
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flask. Then a mixture of water (10 mL, 0.5 M) and ethanol (5 mL, 1
M) was added to it. Further, alkoxylamine hydrochloride (15 mmol,
3.0 equiv) and sodium acetate (25 mmol, 5.0 equiv) were added to
the suspension, respectively. The resulting suspension was refluxed at
80 °C for 1−4 h. The progress of the reaction was regularly checked
by TLC. After complete consumption of the starting materials,
additional water was added to the reaction mixture and extracted with
ethyl acetate. The organic phase was dried over anhydrous sodium
sulfate and concentrated under reduced pressure. Oxime ether 1a was
purified using silica gel flash column chromatography in 60−95%
yield [eluent: hexane−ethyl acetate mixture (98:2 to 95:5)].
General Procedure C: The Synthesis of 2,3,4-Triphenyl-5,6,7,8-
tetrahydroquinoline. An oven-dried Schlenk tube was equipped with
a magnetic stir bar was charged with [Cp*Co(CO)I2] (0.02 mmol,
0.1 equiv) and potassium acetate (0.2 mmol, 100 mol %).
Subsequently, o-methyl oxime ether 1a (0.4 mmol, 2.0 equiv), alkyne
2 (0.2 mmol, 1.0 equiv), and AgNTf2 (0.04 mmol, 0.2 equiv) followed
by HFIP (2 mL, 0.1 M) were added under a N2 atmosphere. The
reaction mixture was vigorously stirred (750 rpm) in a preheated
aluminum block at 120 °C for 12 h. After 12 h (completion of the
reaction as monitored by TLC analysis), the reaction mixture was
cooled to room temperature and diluted with dichloromethane and
passed through a short pad of Celite; the solvent was evaporated
under reduced pressure, and the residue was purified by column
chromatography using a 1:9 mixture of EtOAc/hexane on silica gel to
give pure product 3.
General Procedure D: Cobalt-Catalyzed Annulation Reaction
between Olefinic Imine with Alkyne in a 1 mmol Scale. An oven-
dried Schlenk tube equipped with a magnetic stir bar was charged
with [Cp*Co(CO)I2] (0.02 mmol, 0.1 equiv) and potassium acetate
(1.0 mmol, 100 mol %). Subsequently, o-methyl oxime ether 1a (2.0
mmol, 2.0 equiv), alkyne 2a (1.0 mmol, 1.0 equiv), and AgNTf2 (0.2
mmol, 0.2 equiv) followed by HFIP (10 mL, 0.1 M) were added
under a N2 atmosphere. The reaction mixture was vigorously stirred
(750 rpm) in a preheated aluminum block at 120 °C for 12 h. After
12 h (completion of reaction as monitored by TLC analysis), the
reaction mixture was cooled to room temperature and diluted with
dichloromethane and passed through a short pad of Celite; the
solvent was evaporated under reduced pressure, and the residue was
purified by column chromatography using a 1:9 mixture of EtOAc/
hexane on silica gel to give pure product 3aa (238 mg) with 66%
yield.
3ah with a combined yield of 75%. The ratio of 3aa/3ah (1:2.38) was
calculated using NMR.
Experimental Characterization Data for Olefinic Imines.
(1E,2E)-2-Benzylidenecyclohexanone o-Methyl Oxime (1a). The
compound was prepared according to general procedure B. The crude
reaction mixture was purified by column chromatography using silica
gel (230−400 mesh) giving 1a (93 mg) in 80% yield. Physical state:
1
yellow liquid. Rf: 0.55 (5% EtOAc/hexane). H NMR (400 MHz,
CDCl3): δ 7.26−7.21 (m, 4H), 7.16−7.12 (m, 1H), 6.85 (s, 1H), 3.86
(s, 3H), 2.58 (t, J = 6.0 Hz, 2H), 2.51 (t, J = 6.4 Hz, 2H), 1.64−1.50
(m, 4H). 13C{1H} NMR (100 MHz, CDCl3): δ 160.1, 137.3, 135.2,
130.1, 128.4, 127.8, 127.3, 62.0, 29.3, 26.0, 25.3, 23.7. IR (KBr,
cm−1): 2933, 1457, 1337, 1048. HRMS (ESI) m/z: [M + H]+ calcd
for C14H18NO, 216.1383; found, 216.1363.
(1E,2E)-2-(4-Fluorobenzylidene)cyclohexanone o-Methyl Oxime
(1b). The compound was prepared according to general procedure B.
The crude reaction mixture was purified by column chromatography
using silica gel (230−400 mesh) giving 1b (78 mg) in 68% yield.
1
Physical state: yellow liquid. Rf: 0.5 (5% EtOAc/hexane). H NMR
(400 MHz, CDCl3): δ 7.29−7.25 (m, 2H), 7.03−6.99 (m, 2H), 6.88
(s, 1H), 3.94 (s, 3H), 2.64−2.57 (m, 4H), 1.73−1.59 (m, 4H).
13C{1H} NMR (100 MHz, CDCl3): δ 162.0 (d, JC−F= 245 Hz), 159.9,
135.0 (d, JC−F = 2 Hz), 133.3 (d, JC−F = 4 Hz), 131.6 (d, JC−F= 9 Hz),
126.6, 115.3 (d, JC−F = 22 Hz), 62.0, 29.2, 25.9, 25.2, 23.7. IR (KBr,
cm−1): 2935, 1600, 1505, 1223, 1156, 1048. HRMS (ESI) m/z: [M +
H]+ calcd for C14H17FNO, 234.1289; found, 234.1301.
(1E,2E)-2-(4-Bromobenzylidene)cyclohexanone o-Methyl Oxime
(1c). The compound was prepared according to general procedure B.
The crude reaction mixture was purified by column chromatography
using silica gel (230−400 mesh) giving 1c (92 mg) in 83% yield.
Physical state: white solid. Mp: 61−63 °C. Rf: 0.5 (5% EtOAc/
1
hexane). H NMR (400 MHz, CDCl3): δ 7.44 (d, J = 8.4 Hz, 2H),
7.17 (d, J = 8.4 Hz, 2H), 6.85 (s, 1H), 3.94 (s, 3H), 2.63−2.57 (m,
4H), 1.72−1.59 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3): δ
159.8, 136.2, 135.9, 131.6, 131.5, 126.5, 121.3, 62.0, 29.3, 25.9, 25.2,
23.7. IR (KBr, cm−1): 2933, 1485, 1048, 870. HRMS (ESI) m/z: [M
+ H]+ calcd for C14H17BrNO, 294.0488; found, 294.0507.
(1E,2E)-2-(4-Iodobenzylidene)cyclohexanone o-Methyl Oxime
(1d). The compound was prepared according to general procedure
B. The crude reaction mixture was purified by column chromatog-
raphy using silica gel (230−400 mesh) giving 1d (80 mg) in 74%
1
yield. Physical state: colorless oil. Rf: 0.8 (5% EtOAc/hexane). H
NMR (400 MHz, CDCl3): δ 7.66−7.63 (m, 2H), 7.03 (d, J = 7.6 Hz,
2H), 6.83 (s, 1H), 3.94 (s, 3H), 2.63−2.56 (m, 4H), 1.68−1.56 (m,
4H). 13C{1H} NMR (100 MHz, CDCl3): δ 159.7, 137.5, 136.7, 136.0,
131.8, 126.6, 93.0, 62.1, 29.4, 26.0, 25.2, 23.7. IR (KBr, cm−1): 2932,
1482, 1048, 508. HRMS (ESI) m/z: [M + H]+ calcd for C14H17INO,
342.0349; found, 342.0334.
General Procedure E: Deuterium Labeling Experiments. An oven-
dried Schlenk tube equipped with a magnetic stir bar was charged
with [Cp*Co(CO)I2] (0.02 mmol, 0.1 equiv) and potassium acetate
(0.2 mmol, 100 mol %). Subsequently, o-methyl oxime ether 1a (0.4
mmol, 2.0 equiv) and D2O (2 mmol, 10.0 equiv), and AgNTf2 (0.04
mmol, 0.2 equiv) followed by HFIP (2 mL, 0.1 M) were added under
a N2 atmosphere. The reaction mixture was vigorously stirred (750
rpm) in a preheated aluminum block at 120 °C for 30 min. After 30
min, the reaction mixture was cooled to room temperature, diluted
with dichloromethane, and passed through a short pad of Celite; the
solvent was evaporated under reduced pressure. The 18% H/D
(1E,2E)-2-(4-Methylbenzylidene)cyclohexanone o-Methyl Oxime
(1e). The compound was prepared according to general procedure B.
The crude reaction mixture was purified by column chromatography
using silica gel (230−400 mesh) giving 1e (88 mg) in 77% yield.
Physical state: white solid. Mp: 58−60 °C. Rf: 0.55 (5% EtOAc/
1
hexane). H NMR (400 MHz, CDCl3): δ 7.21 (d, J = 8.0 Hz, 2H),
1
exchange was calculated by H NMR analysis of the crude mixture.
7.13 (d, J = 8.0 Hz, 2H), 6.90 (s, 1H), 3.94 (s, 3H), 2.66 (td, J = 6.8,
1.6 Hz, 2H), 2.58 (t, J = 6.4 Hz, 2H), 2.34 (s, 3H), 1.72−1.58 (m,
4H). 13C{1H} NMR (100 MHz, CDCl3): δ 160.2, 137.2, 134.4, 134.4,
130.0, 129.1, 127.8, 62.0, 29.4, 26.0, 25.2, 23.7, 21.6. IR (KBr, cm−1):
2934, 1510, 1449, 1049. HRMS (ESI) m/z: [M + H]+ calcd for
C15H20NO, 230.1539; found, 230.1561.
(1E,2E)-2-(4-Nitrobenzylidene)cyclohexanone o-Methyl Oxime
(1f). The compound was prepared according to general procedure
B. The crude reaction mixture was purified by column chromatog-
raphy using silica gel (230−400 mesh) giving 1f (69 mg) in 61%
yield. Physical state: yellow solid. Mp: 92−94 °C. Rf: 0.25 (5%
EtOAc/hexane). 1H NMR (400 MHz, CDCl3): δ 8.21−8.17 (m, 2H),
7.47−7.43 (m, 2H), 6.96 (s, 1H), 3.96 (s, 3H), 2.66 (td, J = 6.4, 2.0
Hz, 2H), 2.61 (t, J = 6.8 Hz, 2H), 1.74−1.63 (m, 4H). 13C{1H} NMR
(100 MHz, CDCl3): δ 159.2, 146.7, 144.0, 139.0, 130.6, 125.4, 123.8,
62.2, 29.6, 25.9, 25.1, 23.5. IR (KBr, cm−1): 2936, 1594, 1515, 1343,
General Procedure F: Competitive Experiment with Alkynes. An
oven-dried Schlenk tube equipped with a magnetic stir bar was
charged with [Cp*Co(CO)I2] (0.02 mmol, 0.1 equiv) and potassium
acetate (0.2 mmol, 100 mol %). Subsequently, o-methyl oxime ether
1a (0.4 mmol, 2.0 equiv), diphenylacetylene 2a (0.2 mmol, 1.0 equiv)
and 4-octyne 2h (0.2 mmol, 1.0 equiv), and AgNTf2 (0.04 mmol, 0.2
equiv) followed by HFIP (2 mL, 0.1 M) were added under a N2
atmosphere. The reaction mixture was vigorously stirred (750 rpm) in
a preheated aluminum block at 120 °C for 12 h. After 12 h
(completion of reaction as monitored by TLC analysis), the reaction
mixture was cooled to room temperature, diluted with dichloro-
methane, and passed through a short pad of Celite; the solvent was
evaporated under reduced pressure, and the residue purified by
column chromatography using a 1:9 mixture of EtOAc/hexane on
silica gel afforded tetrahydroquinoline 3aa and tetrahydroquinoline
E
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1047. HRMS (ESI) m/z: [M + H]+ calcd for C14H17N2O3, 261.1234;
found, 261.1241.
J = 7.6 Hz, 1H), 7.41 (t, J = 8 Hz, 1H), 6.86 (s, 1H), 3.86 (s, 3H),
2.57 (t, J = 5.6 Hz, 2H), 2.52 (t, J = 6.4 Hz, 2H), 1.66−1.53 (m, 4H).
13C{1H} NMR (100 MHz, CDCl3): δ 159.0, 148.3, 138.8, 137.9,
135.8, 129.2, 124.9, 124.4, 121.9, 62.0, 29.2, 25.8, 25.0,, 23.4. IR (KBr,
cm−1): 2935, 1528, 1348, 1047. HRMS (ESI) m/z: [M + H]+ calcd
for, C14H17N2O3; 261.1234; found, 261.1238.
(1E,2E)-2-(3,4-Dimethoxybenzylidene)cyclohexanone o-Methyl
Oxime (1m). The compound was prepared according to general
procedure B. The crude reaction mixture was purified by column
chromatography using silica gel (230−400 mesh) giving 1m (74 mg)
in 66% yield. Physical state: yellow viscous liquid. Rf: 0.15 (5%
EtOAc/hexane). 1H NMR (400 MHz, CDCl3): δ 6.92−6.82 (m, 4H),
3.94 (s, 3H), 3.88 (s, 3H), 3.86 (s, 3H), 2.68 (t, J = 5.6 Hz, 2H), 2.58
(t, J = 6.4 Hz, 2H), 1.72−1.60 (m, 4H). 13C{1H} NMR (100 MHz,
CDCl3): δ 160.2, 148.7, 148.5, 133.7, 130.3, 127.7, 122.9, 113.4,
111.1, 62.0, 56.2, 56.2, 29.4, 26.0, 25.2, 23.7. IR (KBr, cm−1): 2934,
1513, 1463, 1255, 1140, 1048. HRMS (ESI) m/z: [M + H]+ calcd for
C16H22NO3, 276.1594; found, 276.1595.
(1E,2E)-2-(Furan-2-yl-methylene)cyclohexanone o-Methyl
Oxime (1g). The compound was prepared according to general
procedure B. The crude reaction mixture was purified by column
chromatography using silica gel (230−400 mesh) giving 1g (94 mg)
in 81% yield. Physical state: yellow liquid. Rf: 0.5 (5% EtOAc/
1
hexane). H NMR (400 MHz, CDCl3): δ 7.41 (d, J = 1.6 Hz, 1H),
6.84 (t, J = 2.0 Hz, 1H), 6.42−6.41 (m, 1H), 6.37 (d, J = 3.2 Hz, 1H),
3.93 (s, 3H), 2.78−2.74 (m, 2H), 2.58−2.54 (m, 2H), 1.68−1.65 (m,
4H). 13C{1H} NMR (100 MHz, CDCl3): δ 158.9, 153.5, 142.5, 132.2,
115.5, 111.8, 111.7, 62.1, 29.3, 25.9, 24.1, 23.0. IR (KBr, cm−1): 2935,
1463, 1435,1049. HRMS (ESI) m/z: [M + H]+ calcd for C12H16NO2,
206.1176; found, 206.1190.
(1E,2E)-2-(Thiophen-2-yl-methylene)cyclohexanone o-Methyl
Oxime (1h). The compound was prepared according to general
procedure B. The crude reaction mixture was purified by column
chromatography using silica gel (230−400 mesh) giving 1h (86 mg)
in 75% yield. Physical state: yellow liquid. Rf: 0.5 (5% EtOAc/
(2Z,3E)-4-Cyclohexylbut-3-en-2-One o-Methyl Oxime (1o). The
compound was prepared according to general procedure B. The crude
reaction mixture was purified by column chromatography using silica
gel (230−400 mesh) giving 1o (77 mg) in 60% yield. Physical state:
1
hexane). H NMR (400 MHz, CDCl3): δ 7.31 (d, J = 5.2 Hz, 1H),
7.21 (t, J = 2.0 Hz, 1H), 7.12 (d, J = 3.6 Hz, 1H), 7.04 (dd, J = 5.2,
3.6 Hz, 1H), 3.94 (s, 3H), 2.72 (m, 2H), 2.57 (t, J = 6.0 Hz, 2H),
1.70−1.66 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3): δ 159.2,
140.8, 131.9, 129.5, 127.3, 126.6, 120.7, 62.1, 29.4, 25.9, 24.0, 22.8. IR
(KBr, cm−1): 2933, 1615, 1461, 1421, 1048. HRMS (ESI) m/z: [M +
H]+ calcd for C12H16NOS, 222.0947; found, 222.0964.
(1E,2E)-2-(2-Bromobenzylidene)cyclohexanone o-Methyl Oxime
(1i). The compound was prepared according to general procedure B.
The crude reaction mixture was purified by column chromatography
using silica gel (230−400 mesh) giving 1i (80 mg) in 72% yield.
Physical state: white solid. Mp: 53−55 °C. Rf: 0.45 (5% EtOAc/
hexane). 1H NMR (400 MHz, CDCl3): δ 7.59−7.57 (m, 1H), 7.26−
7.25 (m, 2H), 7.13−7.08 (m, 1H), 6.87 (s, 1H), 3.96 (s, 3H), 2.62 (t,
J = 6.8 Hz, 2H), 2.49 (td, J = 6.8, 1.6 Hz, 2H), 1.74−1.68 (m, 2H),
1.64−1.58 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 159.5,
137.3, 136.5, 132.9, 131.5, 128.9, 127.0, 126.9, 125.3, 62.0, 29.5, 26.0,
25.5, 24.0. IR (KBr, cm−1): 2933, 1463, 1048, 1024, 746. HRMS
(ESI) m/z: [M + H]+ calcd for C14H17BrNO, 294.0488; found,
294.0496.
1
colorless liquid. Rf:0.6 (5% EtOAc/hexane). H NMR (400 MHz,
CDCl3): δ 6.09−5.95 (m, 2H), 3.88 (s, 3H), 2.11−2.04 (m, 1H), 1.93
(s, 3H), 1.76−1.65 (m, 5H), 1.31−1.11 (m, 5H). 13C{1H} NMR
(100 MHz, CDCl3): δ 156.2, 142.0, 125.3, 61.9, 41.2, 32.9, 26.4, 26.3,
10.4. IR (KBr, cm−1): 1062, 1257, 1452, 2900. HRMS (ESI) m/z: [M
+ H]+ calcd for C11H20NO, 182.1539; found, 182.1552.
(E)-1-(Cyclohex-1-en-1-yl)ethan-1-One o-Methyl Oxime (1p).
The compound was prepared according to general procedure B.
The crude reaction mixture was purified by column chromatography
using silica gel (230−400 mesh) giving 1p (63 mg) in 51% yield.
1
Physical state: colorless liquid. Rf:0.8 (5% EtOAc/hexane). H NMR
(400 MHz, CDCl3): δ 6.13−6.10 (m, 1H), 3.88 (s, 3H), 2.30−2.27
(m, 2H), 2.18−2.15 (m, 2H), 1.93 (s, 3H), 1.66−1.59 (m, 4H).
13C{1H} NMR (100 MHz, CDCl3): δ 156.4, 135.2, 129.3, 61.8, 26.3,
24.8, 22.8, 22.5, 10.6. IR (KBr, cm−1): 1052, 1264, 1299, 1442, 2930.
HRMS (ESI) m/z: [M + H]+ calcd for C9H16NO, 154.1226; found,
154.1231.
(1E,2E)-2-(2-Methoxybenzylidene)cyclohexanone o-Methyl
Oxime (1j). The compound was prepared according to general
procedure B. The crude reaction mixture was purified by column
chromatography using silica gel (230- 400 mesh) giving 1j (76 mg) in
66% yield. Physical state: yellow liquid. Rf: 0.3 (5% EtOAc/hexane).
1H NMR (400 MHz, CDCl3): δ 7.28−7.24 (m, 2H), 6.88−6.85 (m,
3H), 3.94 (s, 3H), 3.81 (s, 3H), 2.66 (td, J = 6.4, 1.6 Hz, 2H), 2.58 (t,
J = 6.8 Hz, 2H), 1.70−1.60 (m, 4H). 13C{1H} NMR (100 MHz,
CDCl3): δ 160.3, 158.9, 133.4, 131.5, 130.0, 128.7, 127.5, 113.8,
113.8, 61.9, 55.5, 29.3, 26.0, 25.2, 23.7. IR (KBr, cm−1): 2934, 1604,
1463, 1177, 1048. HRMS (ESI) m/z: [M + H]+ calcd for C15H20NO2,
246.1489; found, 246.1501.
(1E,2E)-2-(3-Methoxybenzylidene)cyclohexanone o-Methyl
Oxime (1k). The compound was prepared according to general
procedure B. The crude reaction mixture was purified by column
chromatography using silica gel (230−400 mesh) giving 1k (58 mg)
in 51% yield. Physical state: colorless oil. Rf: 0.4 (5% EtOAc/hexane).
1H NMR (400 MHz, CDCl3): δ 7.16 (t, J = 7.6 Hz, 1H), 6.83 (d, J =
5.6 Hz, 2H), 6.77 (s, 1H), 6.71 (dd, J = 8.0, 2.4 Hz, 1H), 3.86 (s,
3H), 3.71 (s, 3H), 2.60−2.57 (m, 2H), 2.51 (t, J = 6.4 Hz, 2H),
1.64−1.51 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3): δ 159.9,
159.6, 138.6, 135.4, 129.3, 127.6, 122.6, 115.5, 112.9, 61.9, 55.5, 29.4,
25.9, 25.2, 23.7. IR (KBr, cm−1): 2934, 1596, 1487, 1157, 1048.
HRMS (ESI) m/z: [M + H]+ calcd for C15H20NO2, 246.1489; found,
246.1508.
Experimental Characterization Data for Annulated Prod-
ucts. 2,3,4-Triphenyl-5,6,7,8-tetrahydroquinoline (3aa).8 The com-
pound was prepared according to general procedure C. The crude
reaction mixture was purified by column chromatography using silica
gel (230−400 mesh) giving 3aa (18 mg) in 88% yield. Physical state:
white solid. Mp: 163−165 °C. Rf: 0.5 (10% EtOAc/hexane). 1H
NMR (400 MHz, CDCl3): δ 7.27−7.25 (m, 2H), 7.20−7.12 (m, 6H),
6.97−6.91 (m, 5H), 6.82−6.79 (m, 2H), 3.11 (t, J = 6.8 Hz, 2H),
2.46 (t, J = 6.4 Hz, 2H), 1.95−1.89 (m, 2H), 1.77−1.74 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ 156.5, 155.2, 150.1, 141.4,
138.8, 138.6, 132.9, 131.5, 130.2, 129.5, 129.2, 128.1, 127.9, 127.5,
127.3, 127.0, 126.3, 33.6, 28.2, 23.4, 23.3. IR (KBr, cm−1): 3056,
2934, 1634, 1443. HRMS (ESI) m/z: [M + H]+ calcd for C27H24N,
362.1903; found, 362.1921. The spectral data were in accordance with
those reported in the literature.8
4-(4-Fluorophenyl)-2,3-diphenyl-5,6,7,8-tetrahydroquinoline
(3ba). The compound was prepared according to general procedure
C. The crude reaction mixture was purified by column chromatog-
raphy using silica gel (230−400 mesh) giving 3ba (14 mg) in 68%
yield. Physical state: white solid. Mp: 181−182 °C. Rf: 0.4 (10%
EtOAc/hexane). 1H NMR (400 MHz, CDCl3): δ 7.26−7.24 (m, 2H),
7.15−7.13 (m, 3H), 6.97−6.86 (m, 7H), 6.79−6.77 (m, 2H), 3.11 (t,
J = 6.4 Hz, 2H), 2.45 (t, J = 6.4 Hz, 2H), 1.96−1.90 (m, 2H), 1.81−
1.75 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 161.9 (d, JC−F
=
244 Hz), 156.7, 155.3, 149.2, 141.3, 138.7, 134.5 (d, JC−F = 3 Hz),
133.1, 131.5, 131.2 (d, JC−F = 8 Hz), 130.1, 129.4, 127.9, 127.7, 127.4,
126.4, 115.2 (d, JC−F = 22 Hz), 33.6, 28.3, 23.4, 23.3. IR (KBr, cm−1):
3056, 2936, 1603, 1510, 1221. HRMS (ESI) m/z: [M + H]+ calcd for
C27H23FN, 380.1809; found, 380.1822.
(1E,2E)-2-(3-Nitrobenzylidene)cyclohexanone o-Methyl Oxime
(1l). The compound was prepared according to general procedure
B. The crude reaction mixture was purified by column chromatog-
raphy using silica gel (230−400 mesh) giving 1l (71 mg) in 63% yield.
1
Physical state: yellow liquid. Rf: 0.25 (5% EtOAc/hexane). H NMR
4-(4-Bromophenyl)-2,3-diphenyl-5,6,7,8tetrahydroquinoline
(3ca). The compound was prepared according to general procedure
(400 MHz, CDCl3): δ 8.07 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.53 (d,
F
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C. The crude reaction mixture was purified by column chromatog-
raphy using silica gel (230−400 mesh) giving 3ca (16 mg) in 66%
yield. Physical state: white solid. Mp: 161−163 °C. Rf: 0.45 (10%
EtOAc/hexane). 1H NMR (400 MHz, CDCl3): δ 7.33 (d, J = 8.0 Hz,
2H), 7.24 (d, J = 4.0 Hz, 2H), 7.14 (d, J = 3.6 Hz, 3H), 6.98 (d, J =
4.8 Hz, 3H), 6.84 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 5.2 Hz, 2H), 3.11
(t, J = 6.4 Hz, 2H), 2.44 (t, J = 6.4 Hz, 2H), 1.96−1.91 (m, 2H),
1.80−1.74 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 156.8,
155.4, 148.9, 141.2, 138.5, 137.6, 132.8, 131.5, 131.4, 131.2, 130.1,
129.1, 127.9, 127.8, 127.4, 126.5, 121.3, 33.6, 28.3, 23.3, 23.2. IR
(KBr, cm−1): 3056, 2934, 1548, 1488, 1012. HRMS (ESI) m/z: [M +
H]+ calcd for C27H23BrN, 440.1008; found, 440.1026.
C. The crude reaction mixture was purified by column chromatog-
raphy using silica gel (230−400 mesh) giving 3ha (10 mg) in 47%
yield. Physical state: yellow solid. Mp: 135−137 °C. Rf: 0.5 (10%
EtOAc/hexane). 1H NMR (400 MHz, CDCl3): δ 7.26−7.24 (m, 2H),
7.20 (d, J = 4.8 Hz, 1H), 7.14 (d, J = 3.6 Hz, 3H), 7.02−7.01 (m,
3H), 6.90−6.86 (m, 3H), 6.68 (d, J = 3.2 Hz, 1H), 3.11 (t, J = 6.4 Hz,
2H), 2.64 (t, J = 6.4 Hz, 2H), 1.97−1.91 (m, 2H), 1.83−1.77 (m,
2H). 13C{1H} NMR (100 MHz, CDCl3): δ 156.8, 155.3, 143.2, 141.3,
138.8, 138.6, 134.4, 131.2, 130.9, 130.1, 128.2, 127.9, 127.6, 127.4,
126.8, 126.6, 126.4, 33.6, 28.2, 23.3, 23.2. IR (KBr, cm−1): 3060,
2924, 1744, 1398, 1086. HRMS (ESI) m/z: [M + H]+ calcd for
C25H22NS, 368.1467; found, 368.1458.
4-(4-Iodophenyl)-2,3-diphenyl-5,6,7,8-tetrahydroquinoline
(3da). The compound was prepared according to general procedure
C. The crude reaction mixture was purified by column chromatog-
raphy using silica gel (230−400 mesh) giving 3da (23 mg) in 83%
yield. Physical state: light yellow solid. Mp: 174−176 °C. Rf: 0.42
4-(2-Bromophenyl)-2,3-diphenyl-5,6,7,8-tetrahydroquinoline
(3ia). The compound was prepared according to general procedure C.
The crude reaction mixture was submitted for HRMS giving 3ia in a
trace amount. HRMS (ESI) m/z: [M + H]+ calcd for C27H23BrN,
440.1008; found, 440.1011.
1
(10% EtOAc/hexane). H NMR (400 MHz, CDCl3): δ 7.53 (d, J =
4-(2-Methoxyphenyl)-2,3-diphenyl-5,6,7,8-tetrahydroquinoline
(3ja). The compound was prepared according to general procedure C.
The crude reaction mixture was purified by column chromatography
using silica gel (230−400 mesh) giving 3ja (16 mg) in 71% yield.
Physical state: yellow solid. Mp: 152−154 °C. Rf: 0.4 (10% EtOAc/
8.0 Hz, 2H), 7.26−7.23 (m, 2H), 7.14−7.13 (m, 3H), 6.98−6.95 (m,
3H), 6.79−6.77 (m, 2H), 6.71 (d, J = 8.4 Hz, 2H), 3.10 (t, J = 6.4 Hz,
2H), 2.43 (t, J = 6.4 Hz, 2H), 1.96−1.89 (m, 2H), 1.80−1.75 (m,
2H). 13C{1H} NMR (100 MHz, CDCl3): δ 156.8, 155.4, 148.9, 141.3,
138.5, 138.3, 137.3, 132.7, 131.5, 131.5, 130.2, 129.0, 127.9, 127.8,
127.4, 126.6, 92.8, 33.6, 28.3, 23.4, 23.3. IR (KBr, cm−1): 3060, 2933,
1545, 1484, 699. HRMS (ESI) m/z: [M + H]+ calcd for C27H23IN,
488.0870; found, 488.0838.
1
hexane). H NMR (400 MHz, CDCl3): δ 7.26−7.23 (m, 2H), 7.13
(dd, J = 4.8, 1.6 Hz, 3H), 6.96−6.94 (m, 3H), 6.87 (d, J = 8.8 Hz,
2H), 6.81−6.78 (m, 2H), 6.73 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.11
(t, J = 6.4 Hz, 2H), 2.48 (t, J = 6.4 Hz, 2H), 1.96−1.90 (m, 2H),
1.79−1.75 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 158.5,
156.5, 155.2, 149.9, 141.5, 139.0, 133.3, 132.6, 131.9, 131.6, 130.8,
130.6, 130.2, 129.7, 127.9, 127.6, 127.3, 126.2, 113.6, 55.4, 33.6, 28.3,
23.4, 23.3. IR (KBr, cm−1): 3059, 2931, 1609, 1513, 1245. HRMS
(ESI) m/z: [M + H]+ calcd for C28H26NO, 392.2009; found,
392.2021.
2,3-Diphenyl-4-(p-tolyl)-5,6,7,8-tetrahydroquinoline (3ea). The
compound was prepared according to general procedure C. The crude
reaction mixture was purified by column chromatography using silica
gel (230−400 mesh) giving 3ea (15 mg) in 73% yield. Physical state:
1
white solid. Mp: 125−127 °C. Rf: 0.45 (10% EtOAc/hexane). H
NMR (400 MHz, CDCl3): δ 7.26−7.23 (m, 2H), 7.15−7.12 (m, 3H),
6.99 (d, J = 8.0 Hz, 2H), 6.96−6.93 (m, 3H), 6.84−6.79 (m, 4H),
3.11 (t, J = 6.8 Hz, 2H), 2.46 (t, J = 6.4 Hz, 2H), 2.26 (s, 3H), 1.95−
1.89 (m, 2H), 1.79−1.73 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 156.4, 155.2, 150.3, 141.4, 138.9, 136.6, 135.5, 133.1,
131.6, 130.2, 129.5, 129.4, 128.8, 127.9, 127.5, 127.3, 126.2, 33.6,
28.3, 23.4, 23.3, 21.5. IR (KBr, cm−1): 3055, 2931, 1546, 1444.
HRMS (ESI) m/z: [M + H]+ calcd for C28H26N, 376.2060; found,
376.2072.
4-(3-Methoxyphenyl)-2,3-diphenyl-5,6,7,8 tetrahydroquinoline
(3ka). The compound was prepared according to general procedure
C. The crude reaction mixture was purified by column chromatog-
raphy using silica gel (230−400 mesh) giving 3ka (13 mg) in 61%
yield. Physical state: yellow solid. Mp: 65−67 °C. Rf: 0.4 (10%
EtOAc/hexane). 1H NMR (400 MHz, CDCl3): δ 7.27−7.26 (m, 2H),
7.15−7.09 (m, 4H), 6.96−6.95 (m, 3H), 6.82 (d, J = 2.4 Hz, 2H),
6.69 (dd, J = 7.6, 1.8 Hz, 1H), 6.58 (d, J = 7.6 Hz, 1H), 6.48 (s, 1H),
3.64 (s, 3H), 3.11 (t, J = 6.4 Hz, 2H), 2.50 (t, J = 6.0 Hz, 2H), 1.96−
1.90 (m, 2H), 1.80−1.73 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 159.4, 156.6, 155.2, 149.9, 141.4, 139.9, 138.8, 132.8,
131.5, 130.2, 129.2, 129.2, 127.9, 127.6, 127.3, 126.3, 122.1, 115.2,
112.8, 55.5, 33.6, 28.1, 23.4, 23.3. IR (KBr, cm−1): 3056, 2934, 1600,
1491, 1229. HRMS (ESI) m/z: [M + H]+ calcd for C28H26NO,
392.2009; found, 392.2020.
4-(3-Nitrophenyl)-2,3-diphenyl-5,6,7,8-tetrahydroquinoline
(3la). The compound was prepared according to general procedure C.
The crude reaction mixture was submitted for HRMS giving 3la in a
trace amount. HRMS (ESI) m/z: [M + H]+ calcd for C27H23N2O2,
407.1754; found, 407.1771.
4-(3,4-Dimethoxyphenyl)-2,3-diphenyl-5,6,7,8-tetrahydroquino-
line (3ma). The compound was prepared according to general
procedure C. The crude reaction mixture was submitted for HRMS
giving 3ma in a trace amount. HRMS (ESI) m/z: [M + H]+ calcd for
C29H28NO2, 422.2115; found, 422.2112.
2,3-Bis(4-methoxyphenyl)-4-phenyl-5,6,7,8-tetrahydroquinoline
(3ab). The compound was prepared according to general procedure
C. The crude reaction mixture was purified by column chromatog-
raphy using silica gel (230−400 mesh) giving 3ab (18 mg) in 76%
yield. Physical state: yellow solid. Mp: 171−173 °C. Rf: 0.2 (10%
EtOAc/hexane). 1H NMR (400 MHz, CDCl3): δ 7.22−7.14 (m, 5H),
6.95−6.93 (m, 2H), 6.71−6.68 (m, 4H), 6.52−6.49 (m, 2H), 3.74 (s,
3H), 3.65 (s, 3H), 3.09 (t, J = 6.4 Hz, 2H), 2.43 (t, J = 6.4 Hz, 2H),
1.93−1.88 (m, 2H), 1.76−1.73 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 158.9, 157.9, 156.2, 155.0, 150.4, 138.9, 134.2, 132.6,
132.3, 131.4, 131.3, 129.5, 128.9, 128.1, 126.9, 113.4, 113.1, 55.5,
55.3, 33.6, 28.2, 23.4, 23.3. IR (KBr, cm−1): 3000, 2931, 1608, 1513,
4-(4-Nitrophenyl)-2,3-diphenyl-5,6,7,8-tetrahydroquinoline
(3fa). The compound was prepared according to general procedure C.
The crude reaction mixture was purified by column chromatography
using silica gel (230−400 mesh) giving 3fa (5 mg) in 23% yield.
Physical state: yellow solid. Mp: 218−220 °C. Rf: 0.3 (10% EtOAc/
1
hexane). H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.0 Hz, 2H),
7.26 (br, 4H), 7.16 (d, J = 6.4 Hz, 4H), 6.97 (d, J = 4.8 Hz, 2H), 6.79
(d, J = 6.4 Hz, 2H), 3.13 (t, J = 6.0 Hz, 2H), 2.41 (t, J = 6.0 Hz, 2H),
1.98−1.92 (m, 2H), 1.82−1.76 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 157.1, 155.5, 147.9, 147.0, 146.0, 140.8, 138.0, 132.4,
131.3, 130.6, 130.1, 128.4, 128.0, 128.0, 127.7, 126.9, 123.5, 33.6,
28.2, 23.2, 23.1. IR (KBr, cm−1): 3059, 2925, 1547, 1518, 1346.
HRMS (ESI) m/z: [M + H]+ calcd for C27H23N2O2, 407.1754; found,
407.1752.
4-(Furan-2-yl)-2,3-diphenyl-5,6,7,8-tetrahydroquinoline (3ga).
The compound was prepared according to general procedure C.
The crude reaction mixture was purified by column chromatography
using silica gel (230−400 mesh) giving 3ga (11 mg) in 54% yield.
Physical state: brown solid. Mp: 134−136 °C. Rf: 0.5 (10% EtOAc/
1
hexane). H NMR (400 MHz, CDCl3): δ 7.34 (s, 1H), 7.23 (d, J =
3.6 Hz, 2H), 7.15 (d, J = 2.8 Hz, 3H), 7.07 (d, J = 4.8 Hz, 3H), 6.89
(d, J = 4.4 Hz, 2H), 6.23 (d, J = 1.2 Hz, 1H), 5.83 (d, J = 2.8 Hz, 1H),
3.10 (t, J = 6.4 Hz, 2H), 2.69 (t, J = 6.4 Hz, 2H), 1.98−1.92 (m, 2H),
1.84−1.80 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ 157.0,
155.5, 150.0, 142.2, 141.2, 139.5, 139.0, 133.9, 131.0, 130.8, 130.1,
127.9, 127.8, 127.4, 126.7, 111.3, 110.9, 33.5, 27.6, 23.2. IR (KBr,
cm−1): 3056, 2935, 1545, 1397, 1076. HRMS (ESI) m/z: [M + H]+
calcd for C25H22NO, 352.1696; found, 352.1693.
2,3-Diphenyl-4-(thiophen-2-yl)-5,6,7,8-tetrahydroquinoline
(3ha). The compound was prepared according to general procedure
G
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1288, 1245. HRMS (ESI) m/z: [M + H]+ calcd for C29H28NO2,
422.2115; found, 422.2108.
1434, 1406. HRMS (ESI) m/z: [M + H]+ calcd for C21H28N,
294.2216; found, 294.2215.
3-Methyl-2,4-diphenyl-5,6,7,8-tetrahydroquinoline (3ai).8 The
compound was prepared according to general procedure C. The
crude reaction mixture was purified by column chromatography using
silica gel (230−400 mesh) giving 3ai (13 mg) in 81% yield. Physical
state: white solid. Mp: 106−109 °C. Rf: 0.48 (10% EtOAc/hexane).
4-Phenyl-2,3-di-p-tolyl-5,6,7,8-tetrahydroquinoline (3ac). The
compound was prepared according to general procedure C. The
crude reaction mixture was purified by column chromatography using
silica gel (230−400 mesh) giving 3ac (14 mg) in 63% yield. Physical
state: yellow solid. Mp: 168−170 °C. Rf: 0.35 (10% EtOAc/hexane).
1H NMR (400 MHz, CDCl3): δ 7.24−7.17 (m, 3H), 7.08−6.96 (m,
1
Mp: 103−105 °C. H NMR (400 MHz, CDCl3): δ 7.51−7.33 (m,
8H), 7.15−7.13 (m, 2H), 3.01 (t, J = 6.4 Hz, 2H), 2.36 (t, J = 6.4 Hz,
2H), 1.91−1.84 (m, 5H), 1.74−1.68 (m, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ 156.6, 154.5, 150.9, 141.9, 139.5, 129.4, 129.1,
128.5, 128.4, 127.8, 127.6, 126.2, 33.4, 28.1, 23.3, 18.0. IR (KBr,
cm−1): 3031, 1562, 1402, 1263. HRMS (ESI) m/z: [M + H]+ calcd
for C22H22N, 300.1747; found, 300.1763. The spectral data were in
accordance with those reported in the literature.8
10H), 3.07 (t, J = 6.4 Hz, 2H), 2.44 (t, J = 6.0 Hz, 2H), 2.29 (s, 3H),
2.27 (s, 3H), 1.93−1.87 (m, 2H), 1.76−1.71 (m, 2H). 13C{1H} NMR
(100 MHz, CDCl3): δ 157.0, 149.3, 140.1, 138.9, 138.0, 137.4, 136.5,
135.0, 132.0, 130.9, 130.4, 129.4, 129.2, 128.2, 127.3, 120.1, 92.0,
33.5, 28.4, 23.2, 23.1, 21.8, 21.5. IR (KBr, cm−1): 3055, 2936, 1521,
1394. HRMS (ESI) m/z: [M + H]+ calcd for C29H28N, 390.2216;
found, 390.2215.
3-Ethyl-2,4-diphenyl-5,6,7,8-tetrahydroquinoline (3aj). The com-
pound was prepared according to general procedure C. The crude
reaction mixture was purified by column chromatography using silica
gel (230−400 mesh) giving 3aj (9 mg) in 51% yield. Physical state:
white solid. Mp: 125−127 °C. Rf: 0.75 (10% EtOAc/DCM). 1H
NMR (400 MHz, CDCl3): δ 7.47−7.33 (m, 8H), 7.18−7.16 (m, 2H),
2.99 (t, J = 6.4 Hz, 2H), 2.36−2.29 (m, 4H), 1.89−1.83 (m, 2H),
1.73−1.67 (m, 2H), 0.70 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 156.9, 154.3, 150.5, 142.0, 139.0, 132.6, 129.6,
129.1, 128.8, 128.5, 127.7, 127.6, 33.3, 28.1, 23.3, 23.1, 15.4. IR (KBr,
cm−1): 3059, 2872, 1557, 1441, 1401. HRMS (ESI) m/z: [M + H]+
calcd for C23H24N, 314.1903; found, 314.1928.
4-Phenyl-2,3-di(thiophen-2-yl)-5,6,7,8-tetrahydroquinoline
(3ae). The compound was prepared according to general procedure
C. The crude reaction mixture was purified by column chromatog-
raphy using silica gel (230−400 mesh) giving 3ae (12 mg) in 59%
yield. Physical state: yellow solid. Mp: 182−184 °C. Rf: 0.75 (10%
EtOAc/hexane). 1H NMR (400 MHz, CDCl3): δ 7.26−7.17 (m, 5H),
7.02−7.00 (m, 2H), 6.82 (dd, J = 4.8, 4.0 Hz, 2H), 6.66 (dd, J = 3.2,
1.8 Hz, 1H), 6.56 (dd, J = 3.6, 1.8 Hz, 1H), 3.06 (t, J = 6.4 Hz, 2H),
2.37 (t, J = 6.4 Hz, 2H), 1.93−1.87 (m, 2H), 1.76−1.70 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ 157.6, 152.2, 149.3, 139.4,
138.2, 130.0, 129.3, 129.1, 129.0, 128.1, 127.7, 127.5, 127.5, 127.3,
127.1, 126.9, 123.9, 33.5, 28.1, 23.3, 23.1. IR (KBr, cm−1): 3100,
2934, 1491, 1436, 1389. HRMS (ESI) m/z: [M + H]+ calcd for
C23H20NS2, 374.1032; found, 374.1048.
2-Ethyl-3,4-diphenyl-5,6,7,8-tetrahydroquinoline (3aj′) The com-
pound was prepared according to general procedure C. The crude
reaction mixture was purified by column chromatography using silica
gel (230−400 mesh) giving 3aj′ (4 mg) in 23% yield. Physical state:
4-Phenyl-2,3-di-m-tolyl-5,6,7,8-tetrahydroquinoline (3af). The
compound was prepared according to general procedure C. The
crude reaction mixture was purified by column chromatography using
silica gel (230−400 mesh) giving 3af (15 mg) in 69% yield. Physical
state: yellow solid. Mp: 115−117 °C. Rf: 0.5 (10% EtOAc/hexane).
1H NMR (400 MHz, CDCl3): δ 7.20−7.12 (m, 4H), 7.00−6.93 (m,
5H), 6.82 (t, J = 7.6 Hz, 1H), 6.74 (d, J = 7.6 Hz, 1H), 6.61−6.57 (m,
2H), 3.11 (t, J = 6.8 Hz, 2H), 2.45 (d, J = 5.6 Hz, 2H), 2.23 (s, 3H),
2.03 (s, 3H), 1.94−1.90 (m, 2H), 1.79−1.73 (m, 2H). 13C{1H} NMR
(100 MHz, CDCl3): δ 156.3, 155.3, 150.1, 141.3, 138.8, 138.6, 137.3,
136.8, 133.1, 132.4, 130.9, 129.5, 129.1, 128.7, 128.6, 128.0, 127.5,
127.3, 127.3, 127.0, 126.9, 33.6, 28.2, 23.4, 23.3, 21.7, 21.5. IR (KBr,
cm−1): 3059, 2933, 1545, 1394. HRMS (ESI) m/z: [M + H]+ calcd
for C29H28N, 390.2216; found, 390.2243.
1
colorless liquid. Rf: 0.5 (10% EtOAc/DCM). H NMR (400 MHz,
CDCl3): δ 7.17−7.07 (m, 6H), 6.98−6.96 (m, 2H), 6.91−6.89 (m,
2H), 3.03 (t, J = 6.4 Hz, 2H), 2.59 (q, J = 7.2 Hz, 2H), 2.37 (t, J = 6.4
Hz, 2H), 1.93−1.87 (m, 2H), 1.73−1.71 (m, 2H), 1.12 (t, J = 7.6 Hz,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ 158.3, 156.1, 149.7, 139.0,
138.7, 133.3, 130.5, 129.3, 128.0, 127.8, 127.7, 126.9, 126.7, 33.4,
29.6, 28.0, 23.4, 23.4, 15.0. IR (KBr, cm−1): 3059, 2932, 1492, 1432,
1401. HRMS (ESI) m/z: [M + H]+ calcd for C23H24N, 314.1903;
found, 314.1896.
3-Butyl-2,4-diphenyl-5,6,7,8-tetrahydroquinoline and 2-Butyl-
3,4-diphenyl-5,6,7,8-tetrahydroquinoline (3ak and 3ak′). The
compound was prepared according to general procedure C. The
crude reaction mixture was purified by column chromatography using
silica gel (230−400 mesh) giving 3ak and 3ak′ as an inseparable
regio-isomer (13 mg) in 70% yield. Physical state: colorless liquid. Rf:
2,3-Diethyl-4-phenyl-5,6,7,8-tetrahydroquinoline (3ag).8 The
compound was prepared according to general procedure C. The
crude reaction mixture was purified by column chromatography using
silica gel (230−400 mesh) giving 3ag (8 mg) in 56% yield. Physical
1
0.45 (10% EtOAc/hexane). H NMR (400 MHz, CDCl3): δ 7.46−
7.33 (m, 8H), 7.17−7.15 (m, 2H), 2.99 (t, J = 6.8 Hz, 2H), 2.33−
2.26 (m, 4H), 1.89−1.83 (m, 2H), 1.73−1.67 (m, 2H), 1.11−1.04
(m, 2H), 0.88−0.81 (m, 2H), 0.46 (t, J = 7.2 Hz, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ 157.0, 154.2, 150.6, 142.0, 139.0, 131.5, 129.5,
129.2, 128.8, 128.7, 128.4, 127.7, 127.5, 33.3, 32.9, 29.4, 28.1, 23.3,
23.3, 22.8, 13.5. IR (KBr, cm−1): 3055, 2931, 1556, 1492, 1431, 1400.
HRMS (ESI) m/z: [M + H]+ calcd for C25H28N, 342.2216; found,
342.2235.
1
state: yellow solid. Mp: 61−63 °C. Rf: 0.4 (10% EtOAc/hexane). H
NMR (400 MHz, CDCl3): δ 7.43 (t, J = 7.2 Hz, 2H), 7.36 (t, J = 7.2
Hz, 1H), 7.09 (d, J = 8.0 Hz, 2H), 2.93 (t, J = 6.4 Hz, 2H), 2.83 (q, J
= 7.6 Hz, 2H), 2.35 (q, J = 7.6 Hz, 2H), 2.21 (t, J = 6.4 Hz, 2H),
1.85−1.79 (m, 2H), 1.68−1.62 (m, 2H), 1.32 (t, J = 7.6 Hz, 3H),
0.93 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 158.7,
154.1, 150.1, 139.4, 132.0, 128.7, 128.6, 128.0, 127.4, 33.2, 28.6, 27.9,
23.4, 23.3, 22.6, 15.7, 15.1. IR (KBr, cm−1): 3055, 2931, 1565, 1406.
HRMS (ESI) m/z: [M + H]+ calcd for C19H24N, 266.1903; found,
266.1894. The spectral data were in accordance with those reported in
the literature.8
3-Pentyl-2,4-diphenyl-5,6,7,8-tetrahydroquinoline (3al). The
compound was prepared according to general procedure C. The
crude reaction mixture was purified by column chromatography using
silica gel (230−400 mesh) giving 3al (9 mg) in 46% yield. Physical
1
4-Phenyl-2,3-dipropyl-5,6,7,8-tetrahydroquinoline (3ah). The
compound was prepared according to general procedure C. The
crude reaction mixture was purified by column chromatography using
silica gel (230−400 mesh) giving 3ah (10 mg) in 60% yield. Physical
state: colorless liquid. Rf: 0.4 (10% EtOAc/hexane). H NMR (400
MHz, CDCl3): δ 7.46−7.32 (m, 8H), 7.17−7.15 (m, 2H), 2.99 (t, J =
6.4 Hz, 2H), 2.34−2.26 (m, 4H), 1.89−1.83 (m, 2H), 1.74−1.68 (m,
2H), 1.14−1.07 (m, 2H), 0.89−0.80 (m, 4H), 0.60 (t, J = 6.8 Hz,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ 157.1, 154.3, 150.6, 142.2,
139.1, 131.5, 129.4, 129.2, 128.8, 128.8, 128.4, 127.7, 127.5, 33.4,
32.0, 30.4, 29.8, 28.1, 23.4, 23.3, 22.0, 13.9. IR (KBr, cm−1): 3057,
2928, 1556, 1431, 1401. HRMS (ESI) m/z: [M + H]+ calcd for
C26H30N, 356.2373; found, 356.2387.
1
state: white solid. Mp: 68−70 °C. Rf: 0.5 (10% EtOAc/hexane). H
NMR (400 MHz, CDCl3): δ 7.44−7.33 (m, 3H), 7.08 (d, J = 8.0 Hz,
2H), 2.92 (t, J = 6.4 Hz, 2H), 2.76−2.72 (m, 2H), 2.28−2.19 (m,
4H), 1.83−1.63 (m, 6H), 1.35−1.29 (m, 2H), 1.04 (t, J = 7.2 Hz,
3H), 0.73 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
157.7, 154.0, 150.2, 139.4, 130.9, 128.7, 127.9, 127.4, 37.8, 33.2, 31.9,
28.0, 24.7, 24.3, 23.4, 23.3, 14.9, 14.8. IR (KBr, cm−1): 3056, 2930,
2-Pentyl-3,4-diphenyl-5,6,7,8-tetrahydroquinoline (3al′). The
compound was prepared according to general procedure C. The
H
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Article
crude reaction mixture was purified by column chromatography using
silica gel (230−400 mesh) giving 3al′ (6 mg) in 31% yield. Physical
3ka, 3ab, 3ac, 3ae, 3af, 3ag, 3ah, 3ai, 3aj, 3aj′, 3ak, 3ak′,
3al, 3al′, 3am, 3am′, and 3na (ZIP)
1
state: yellow liquid. Rf: 0.5 (10% EtOAc/hexane). H NMR (400
MHz, CDCl3): δ 7.16−7.06 (m, 6H), 6.97−6.94 (m, 2H), 6.91−6.89
(m, 2H), 3.02 (t, J = 6.4 Hz, 2H), 2.57−2.53 (m, 2H), 2.36 (t, J = 6.4
Hz, 2H), 1.92−1.86 (m, 2H), 1.73−1.68 (m, 2H), 1.60−1.52 (m,
2H), 1.17−1.14 (m, 4H), 0.79−0.75 (m, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 157.4, 156.0, 149.6, 139.0, 138.8, 133.5, 130.6,
129.3, 128.0, 127.8, 127.6, 126.9, 126.6, 36.5, 33.5, 32.2, 30.4, 28.0,
23.4, 22.6, 14.2. IR (KBr, cm−1): 3059, 2929, 1555, 1442, 1400.
HRMS (ESI) m/z: [M + H]+ calcd for C26H30N, 356.2373; found,
356.2370.
Accession Codes
CCDC 2011120 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
3-Hexyl-2,4-diphenyl-5,6,7,8-tetrahydroquinoline (3am). The
compound was prepared according to general procedure C. The
crude reaction mixture was purified by column chromatography using
silica gel (230−400 mesh) giving 3am (11 mg) in 55% yield. Physical
AUTHOR INFORMATION
Corresponding Author
■
Ponneri Chandrababu Ravikumar − School of Chemical
Sciences, National Institute of Science Education and
Research (NISER) Bhubaneswar, HBNI, Khurda, Odisha
752050, India; orcid.org/0000-0002-5264-820X;
Email: pcr@niser.ac.in
1
state: yellow liquid. Rf: 0.4 (10% EtOAc/hexane). H NMR (400
MHz, CDCl3): δ 7.47−7.34 (m, 8H), 7.17−7.15 (m, 2H), 3.03 (t, J =
6.4 Hz, 2H), 2.34−2.26 (m, 4H), 1.87−1.83 (m, 2H), 1.73−1.69 (m,
2H), 1.11−1.07 (m, 2H), 0.98−0.95 (m, 2H), 0.83−0.79 (m, 4H),
0.69 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 157.0,
154.2, 150.6, 142.0, 139.0, 131.5, 129.5, 129.2, 128.8, 128.7, 128.4,
127.7, 127.5, 33.3, 31.1, 30.6, 29.7, 29.3, 28.1, 23.3, 23.3, 22.5, 14.2.
IR (KBr, cm−1): 3062, 2928, 1545, 1441, 1431, 1400. HRMS (ESI)
m/z: [M + H]+ calcd for C27H32N, 370.2529; found, 370.2548.
2-Hexyl-3,4-diphenyl-5,6,7,8-tetrahydroquinoline (3am′). The
compound was prepared according to general procedure C. The
crude reaction mixture was purified by column chromatography using
silica gel (230−400 mesh) giving 3am′ (4 mg) in 20% yield. Physical
Authors
Smruti Ranjan Mohanty − School of Chemical Sciences,
National Institute of Science Education and Research
(NISER) Bhubaneswar, HBNI, Khurda, Odisha 752050,
India
Bedadyuti Vedvyas Pati − School of Chemical Sciences,
National Institute of Science Education and Research
(NISER) Bhubaneswar, HBNI, Khurda, Odisha 752050,
India
Shyam Kumar Banjare − School of Chemical Sciences,
National Institute of Science Education and Research
(NISER) Bhubaneswar, HBNI, Khurda, Odisha 752050,
India
Gopal Krushna Das Adhikari − School of Chemical Sciences,
National Institute of Science Education and Research
(NISER) Bhubaneswar, HBNI, Khurda, Odisha 752050,
India
1
state: yellow liquid. Rf: 0.5 (10% EtOAc/hexane). H NMR (400
MHz, CDCl3): δ 7.17−7.06 (m, 6H), 6.97−6.95 (m, 2H), 6.91−6.89
(m, 2H), 3.03 (t, J = 6.8 Hz, 2H), 2.57−2.53 (m, 2H), 2.36 (t, J = 6.4
Hz, 2H), 1.93−1.86 (m, 2H), 1.74−1.73 (m, 2H), 1.58−1.50 (m,
2H), 1.19−1.09 (m, 6H), 0.79 (t, J = 6.8 Hz, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ 157.4, 155.9, 149.7, 138.9, 138.8, 133.5, 130.6,
129.3, 128.0, 127.8, 127.6, 126.9, 126.6, 36.4, 33.4, 31.8, 30.7, 29.6,
28.0, 23.3, 23.4, 22.8, 14.4. IR (KBr, cm−1): 3062, 2929, 1555, 1442,
1431, 1400. HRMS (ESI) m/z: [M + H]+ calcd for C27H32N,
370.2529; found, 370.2521.
(4S,6aR,6bS,8aS,13aS,13bR)-6a,8a,9-Trimethyl-11,12-diphenyl-
3,4,5,6,6a,6b,7,8,8a,13,13a,13b-dodecahydro-1H-naphtho-
[2′,1′:4,5]indeno[1,2-c]pyridin-4-yl Acetate (3na). The compound
was prepared according to general procedure C. The crude reaction
mixture was purified by column chromatography using silica gel
(230−400 mesh) giving 3na (14 mg) in 46% yield. Physical state:
white solid. Mp: 208−210 °C. Rf: 0.2 (10% EtOAc/hexane). 1H
NMR (400 MHz, CDCl3): δ 7.28−7.21 (m, 5H), 7.16−7.14 (m, 3H),
7.06 (d, J = 7.6 Hz, 2H), 5.36 (d, J = 4.8 Hz, 1H), 4.64−4.57 (m,
1H), 2.64 (s, 3H), 2.53−2.40 (m, 3H), 2.34 (d, J = 6.8 Hz, 2H), 2.03
(s, 3H), 1.99−1.88 (m, 3H), 1.82−1.70 (m, 4H), 1.67−1.57 (m, 3H),
1.28−1.16 (m, 2H), 1.13 (s, 3H), 1.10 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 170.9, 154.8, 152.5, 151.3, 145.2, 141.1, 140.3,
139.0, 131.4, 130.4, 130.3, 128.3, 127.9, 127.4, 127.0, 122.4, 74.1,
57.3, 50.5, 46.2, 38.4, 37.2, 37.1, 36.3, 32.5, 31.9, 31.0, 28.1, 22.7,
21.8, 21.2, 19.6, 17.0. IR (KBr, cm−1): 3056, 2956, 1730, 1562, 1378,
1244, 1034. HRMS (ESI) m/z: [M + H]+ calcd for C37H42NO2,
532.3210; found, 532.3192.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02558
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are thankful to NISER, Department of Atomic Energy
(DAE), for access to facilities. We acknowledge the Council for
Scientific and Industrial Research (CSIR), New Delhi (grant
02(0256)/16/EMR II), and Science and Engineering Research
Board (SERB) New Delhi (grant EMRII/2017/001475) for
the financial support. S.R.M. and B.V.P. thank DST-INSPIRE
for a research fellowship, and S.K.B. thanks the DAE for a
research fellowship. G.K.D.A. thanks the Council for Scientific
and Industrial Research for a research fellowship (CSIR). We
are thankful to Mr. Bibhuti Bhusana Palai, NISER
Bhubaneswar, for solving single-crystal X-ray data.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02558.
■
sı
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