Expedient synthesis of tricyclic benzopyran-2-ones via N-Heterocyclic carbene catalyzed annulation of enals to α-methylene cycloalkanones

Article abstract of DOI:10.1016/j.tet.2015.08.062

Tricyclic benzopyrans are medicinally important biologically active compounds. Synthesis of a series of tricyclic benzopyrans derivatives via N-Heterocyclic carbene (NHC) catalyzed annulation of enals to α-methylidenetetralones/chromanones is described. T

Full text of DOI:10.1016/j.tet.2015.08.062

Accepted Manuscript
Expedient Synthesis of Tricyclic Benzopyran-2-ones via N-Heterocyclic Carbene
Catalyzed Annulation of Enals to α-Methylene Cycloalkanones
D. Venkata Mani Padmaja, C.R. Sinu, Jagadeesh Krishnan, Rony Rajan Paul, Sunil
Varughese, K.C. Seetha Lakshmi, Vijay Nair
PII:
S0040-4020(15)30016-8
10.1016/j.tet.2015.08.062
TET 27084
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 21 July 2015
Revised Date: 24 August 2015
Accepted Date: 25 August 2015
Please cite this article as: Venkata Mani Padmaja D, Sinu CR, Krishnan J, Paul RR, Varughese S,
Seetha Lakshmi KC, Nair V, Expedient Synthesis of Tricyclic Benzopyran-2-ones via N-Heterocyclic
Carbene Catalyzed Annulation of Enals to α-Methylene Cycloalkanones, Tetrahedron (2015), doi:
10.1016/j.tet.2015.08.062.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Expedient Synthesis of Tricyclic
Leave this area blank for abstract info.
Benzopyran-2-ones via N-Heterocyclic
Carbene Catalyzed Annulation of Enals to α-
Methylene Cycloalkanones
a
a
a
b
a
Venkata Mani Padmaja D., Sinu C. R., Jagadeesh Krishnan, Rony Rajan Paul, Sunil Varughese, Seetha
a,c
*a
Lakshmi K. C., and Vijay Nair
a
Chemical Science and Technology Division, National Institute for Interdisciplinary Science and Technology
(
CSIR-NIIST),Trivandrum-695019, India. E-mail: vijaynair_2001@yahoo.com
b
Department of Chemistry CMS College Kottayam, Kerala- 686001
c
School of Chemical Sciences, Mahatma Gandhi University, Kottayam -686560, India

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Expedient Synthesis of Tricyclic Benzopyran-2-ones via N-Heterocyclic Carbene
#
Catalyzed Annulation of Enals to α-Methylene Cycloalkanones
a
a
a
b
a
Venkata Mani Padmaja D., Sinu C. R., Jagadeesh Krishnan, Rony Rajan Paul, Sunil Varughese, Seetha
a,c
*a
Lakshmi K. C., and Vijay Nair
a
Chemical Science and Technology Division, National Institute for Interdisciplinary Science and Technology (CSIR-NIIST),Trivandrum-695019, India.
Department of Chemistry CMS College Kottayam, Kerala- 686001. India
b
c
School of Chemical Sciences, Mahatma Gandhi University, Kottayam-686560, India
#
This paper is dedicated with best regards to Dr. Stanley Lang in honor of his contributions to Heterocyclic Chemistry and his service to ISHC.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Tricyclic benzopyrans are medicinally important biologically active compounds. Synthesis of a
series of tricyclic benzopyrans derivatives via N-Heterocyclic carbene (NHC) catalyzed
annulation of enals to α-methylidenetetralones/chromanones is described. This reaction afforded
the benzopyrans in high yield with aromatic as well as aliphatic enals.
Available online
2
009 Elsevier Ltd. All rights reserved.
Keywords:
N-Heterocyclic carbene
Homoenolate
α-methylidenetetralones/chromanones
Tricyclic benzopyrans
1
. Introduction
This reactivity has been utilized in the synthesis of
8b,9 10
dihydropyranones,
and dihydropyridones. The observation
Ever since the demonstration by Glorius and Bode that N-
that in contrast to the well-established synthesis of cyclopentenes
by the homoenolate annulation of chalcones, vinyl ketones
Heterocyclic Carbenes (NHC) can catalyze the annulation of
1,2
enals to aldehydes to deliver γ-lactones, via the intermediacy of
homoenolates, the chemistry of the latter has received
extraordinary attention from organic chemists. There have been
intense efforts in exploiting homoenolate reactivity in several
9c
afforded dihydropyranones (scheme 2) is noteworthy.
3
laboratories including our own. These explorations have
succeeded in directing homoenolate reactivity towards a variety
of electrophiles leading to the synthesis of a wide range of
4
products. Contemporaneous to the development of homoenolate
5
6
chemistry, as early as 2004, Bode and Rovis independently
observed that NHC can transform α-functionalized aldehydes to
ester enolate equivalents that can participate in a variety of7
interesting reactions. More recently it was reported by Scheidt
Scheme 2. Homoenolate annulation of vinyl ketones
In this context, it was of interest to explore the possibility of
developing a synthesis of benzopyranones, mainly because of the
impressive medicinal properties displayed by several natural and
8
11
and others that, under controlled experimental conditions and
with the use of appropriate base, homoenolate can endure β-
protonation thus transforming it to enol (enolate) (Scheme 1).
synthetic benzopyranones. Some selected benzopyranones
endowed with medicinal properties are shown in figure 1.
Scheme 1. NHC mediated homoenolate and enolate formation
.
Figure 1. Biologically active tricyclic benzopyranones

2
Tetrahedron
ACCEPTED MANUSCRIPT
o
2
. Results and Discussion
12
K
2
CO
3
THF
24
66 C
10
a Overall yield, b Reaction condition: enone 5a (0.5 mmol), enal 1a (2.5 mmol), catalyst 3a (15
Our studies commenced by refluxing a mixture of 4-
methoxycinnamaldehyde and 2-methylene-3,4-
mol %), DBU (30 mol %) and toluene 7 mL, refluxed under argon atmosphere for 2 h.
dihydronaphthalen-1(2H)-one with catalytic amount (15 mol %)
of imidazolium salt (IMesꢀHCl) and DBU (30 mol %) in dry THF
under argon atmosphere for about 2 h. Then the reaction mixture
was purified by silica gel chromatography (ethyl acetate-hexane
After establishing the most favorable conditions, the
generality of the reaction was investigated with various α, β-
unsaturated aldehydes and α-methylene tetralones and oxa
analogs of the latter. The results are summarized in Scheme 4.
(5:95)) to give product as white solid in 43% yield (Scheme 3).
Scheme 3. Synthesis of tricyclic benzopyran-2-one
The structure of the product was established by spectroscopic
-
1
analysis. The IR spectrum of 6a showed absorption at 1759 cm
corresponding to the lactone carbonyl, which was supported by
13
the C NMR signal at δ 170.6. Conclusive evidence for the
structure of 6a was obtained from single crystal X-ray analysis of
12
6
b (Figure 2).
Scheme 4. Scope of the reaction with various aromatic enals
In the view of the interesting results obtained by the reaction
of tethered α- methylene ketones with aromatic enals, it was
obligatory to extend our studies to aliphatic enals (Scheme 5).
Figure 2. ORTEP of 6b.
13
Satisfactorily,
the
reaction
of
2-methylene-3,4-
After the catalyst screening, a brief screening of various
dihydronaphthalen-1(2H)-one 5a with crotonaldehyde in
presence of IMes.HCl and DBU in an inert atmosphere of argon
under reflux condition for 2h, afforded the product 6k in 90%
yield as white solid.
bases and solvents were undertaken (Table 1). These studies
revealed that DBU and toluene under refluxing offered optimum
condition for this reaction.
Table 1. Optimization of Reaction
Mes
O
O
N
Cl
O
H
O
N
3a
Mes
OMe
+
MeO
Base, Solvent
5a
1a
6a
a
Entry
Base
Solvent
Time
Temperature
Yield
(h)
(%)
1
2
3
4
5
6
7
8
9
DBU
DCM
24
24
8
RT
RT
-
DBU
THF
-
o
DBU
THF
66 C
43
o
DBU
Toluene
Toluene
24
2
66 C
Trace
o
b
DBU
110 C
84
o
DBU
CH
3
CN
24
24
24
24
24
24
82 C
38
49
-
o
DBU
DMF
110 C
Scheme 5. Scope of the reaction with various aliphatic enals
Encouraged by these results, we extended this strategy to yet
another interesting α-methylene cycloalkanones like 2-methylene
cycloheptanone and 2-methylene cyclooctanone under similar
reaction condition. In these studies also the expected products
were obtained in high yields (Scheme 6).
DMAP
DMAP
DMAP
DMAP
DCM
RT
o
THF
66 C
15
-
1
1
0
1
Toluene
Toluene
RT
o
110 C
22

3
4
.2. Preparation of α-methylidene ketones (α-
ACCEPTED MANUSCRIPT
methylidenetetralones)
α-methylidene ketones were prepared according to the known
14
literature procedure. In a 100 mL round bottom flask, added α-
tetralone (1.0 mmol) and paraformaldehyde (2.0 mmol) and THF
(
1.0 mL) into this catalyst-i-Pr NH:TFA (1.0 mmol),
2
trifluoroacetic acid (0.1 mmol) was added. The reaction mixture
was stirred, open to the atmosphere and reflux for 2 h. Reaction
mixture was cooled down to room temperature and
paraformaldehyde (2.0 mmol) was added again and it was
refluxed for 6 h open to the atmosphere. After completion of the
reaction, the reaction mixture was cooled down to room
Scheme 6. Extension of the reaction to α-methylene
cycloalkanones
temperature, solvent was removed and dissolved in Et O and
2
A mechanistic rationalization for this unexpected reaction may
be postulated as follows (Scheme 7). The homoenolate
equivalent I formed initially from the enal and NHC undergoes
β- protonation to afford the enol II. The latter on Michael
addition to the exo-methylene cyclanones affords the species III
which on intramolecular O-acylation reaction delivers the
product (IV). It is noteworthy that isomerization of enolate III to
a more stable enolate V and subsequent intramolecular aldol-type
reaction, analogous to the events observed in the case of
cyclopentene formation from chalcone, is precluded here since
that would involve a four-membered transition state.
washed with 1N HCl, 1N NaOH, and brine, then dried using
Na SO and concentrated under vacuum. The crude product was
2
4
purified by (100-200 mesh) silica-gel column chromatography
using 1% EtOAc–Hexane as eluent.
4.3. Synthesis of substituted dihydropyranones
To a solution of 2-methylene-3,4-dihydronaphthalen-1(2H)-
one 5a (79 mg, 0.5 mmol) and 4-methoxy cinnamaldehyde (203
mg, 2.5 mmol) 1a in toluene (7 mL) was added IMes.HCl (15
mol %) and DBU (30 mol %) in an inert atmosphere of argon
under reflux condition for about 2 h. Then the reaction mixture
was purified by column chromatography using 100-200 mesh
silica using ethyl acetate-hexane (5:95) as eluent to afford the
corresponding product 6a in 84% yield.
3
-(4-Methoxybenzyl)-3,4,5,6-tetrahydro-2H-benzo[h]chromen-2-
one (6a) :
Chemical Formula: C H O ; Yield:135 mg (84%); mp: 122-
2
1
20
3
o
1
1
7
2
2
24 C; H NMR (500 MHz, CDCl ) δ: 7.49 (d, J = 7.5 Hz, 1H),
3
.22 - 7.15 (m, 2H), 7.11 (d, J = 8.5 Hz, 3H), 6.83 (d, J = 8.5 Hz,
H), 3.79 (s, 3H), 3.31 (dd, J = 14 Hz, J = 4.5 Hz, 1H), 2.91 –
1
2
.82 (m, 3H), 2.75-2.70 (m,1H), 2.33 (t, J = 8.0 Hz, 2H), 2.27 (d,
13
J = 8.5 Hz, 2H). C NMR (126 MHz, CDCl ) δ: 170.6, 158.4,
3
1
1
2
43.7, 135.0, 130.2, 130.1, 128.8, 127.8, 127.3, 126.6, 120.9,
14.0, 110.7, 55.2, 40.8, 35.1, 29.1, 27.5, 26.5. IR (film) νmax:
-
1
955, 2918, 2850, 1759, 1612, 1512, 1247,1129 cm . HRMS:
+
m/z (ESI) (M+H) calcd. for C H O is 321.1492; found
21
20
3
3
21.1499.
3
-(2-Methoxybenzyl)-3,4,5,6-tetrahydro-2H-benzo[h]chromen-2-
one (6b):
Chemical Formula: C H O ; Yield:144 mg (90%); mp: 104-
2
1
20
3
o
1
1
7
1
–
06 C; H NMR (500 MHz, CDCl ) δ: 7.50 (d, J = 7.5 Hz, 1H),
3
Scheme 7. Postulated reaction mechanism
.23 – 7.10 (m, 5H), 6.90 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 8.0 Hz,
H), 3.81 (s, 3H), 3.43 (dd, J = 13.5 Hz, J = 4.5 Hz, 1H), 3.10
3
. Conclusion
1
2
3.04 (m, 1H), 2.83 (t, J = 8.5 Hz, 2H), 2.75 – 2.71 (m, 1H),
13
In conclusion, we have successfully employed the NHC
2.31 (t, J = 8.0 Hz, 2H), 2.27 – 2.20 (m, 2H). C NMR (126
catalyzed annulation for the synthesis of polycyclic di-
hydropyran-2-ones. Parenthetically it may be added that the
pyrone motif is present in a number of natural products with
important biological activity.
MHz, CDCl ) δ: 171.3, 157.7, 143.5, 131.2, 128.1, 127.7, 127.3,
126.7, 126.6, 120.8, 120.5, 111.2, 110.3, 55.2, 38.8, 31.2, 29.3,
3
27.5, 26.5. IR (film) ν : 2933, 2887, 2834, 1759, 1587, 1493,
max
-
1
+
1243, 1132 cm . HRMS: m/z (ESI) (M+H) calcd. for C H O
2
1
20
3
is 321.1492; found 321.1497.
4
. Experimental Section
3
-Benzyl-3,4,5,6-tetrahydro-2H-benzo[h]chromen-2-one(6c):
4
.1. General Remarks
Chemical Formula: C H O ; Yield:139 mg (95%); mp: 110-
2
0
18
2
1
13
o
1
NMR spectra were recorded at 500 ( H) and 126 ( C) MHz
respectively on a Bruker DPX-500 MHz NMR spectrometer.
1
7
12 C; H NMR (500 MHz, CDCl ) δ: 7.40 (d, J = 7.5 Hz, 1H),
3
.21 - 7.18 (m, 2H), 7.15 - 7.05 (m, 5H), 7.00 (d, J = 7.0 Hz, 1H),
1
Chemical shifts (d) are reported relative to TMS ( H) and CDCl
3
3.30 (dd, J = 14.0 Hz, J = 4.5 Hz, 1H), 2.87 - 2.79 (m, 1H),
1 2
1
3
(
C) as the internal standards. Coupling constant (J) is reported
2
2
1
.73 (t, J = 8.0 Hz, 2H), 2.69 – 2.64 (m, 1H), 2.22 (t, J = 8.0 Hz,
H), 2.18 – 2.16 (m, 2H). C NMR (126 MHz, CDCl ) δ: 170.4,
43.7, 138.3, 135.0, 129.1, 128.8, 128.6, 127.8, 127.3, 126.7,
13
in Hertz (Hz). Mass spectra were recorded on Thermo
Scientific™ Exactive mass Spectrometer for ESI. IR spectra were
recorded on a Bruker Alpha-T FT-IR spectrophotometer.
3

4
Tetrahedron
ACCEPTED MANUSCRIPT
1
3
26.6, 120.9, 110.7, 40.6, 36.0, 29.6, 27.5, 26.5. IR (film) ν
028, 2926, 2855, 1777, 1682, 1454, 1225, 1158 cm . HRMS:
:
max
3-Benzyl-8-methoxy-3,4,5,6-tetrahydro-2H-benzo[h]chromen-2-
-
1
one (6h)
+
m/z (ESI) (M+H) calcd. for C H O is 291.1385; found
20
18
2
Chemical Formula: C H O ; Yield:147 mg (92%); mp: 113-
21
20
3
2
91.1391.
o
1
1
15 C; H NMR (500 MHz, CDCl ) δ: 7.40 (d, J = 8.5 Hz, 1H),
3
3
-(4-Fluorobenzyl)-3,4,5,6-tetrahydro-2H-benzo[h]chromen-2-
7.29 (t, J = 7.0 Hz, 2H), 7.24 – 7.12 (m, 3H), 6.70 (dd, J = 8.5
Hz, J = 2.6 Hz, 1H), 6.65 (d, J = 2.5 Hz, 1H), 3.78 (s, 3H), 3.38
1
one (6d):
2
(
dd, J = 13.8 Hz, J = 4.5 Hz, 1H), 2.96 – 2.87 (m, 1H), 2.84 –
1 2
13
Chemical Formula: C H FO ; Yield:131 mg (85%); mp:
20
17
2
o
1
2.71 (m, 3H), 2.30 – 2.21 (m, 4H). C NMR (126 MHz, CDCl
δ: 170.7, 159.4, 143.6, 138.4, 137.0, 129.1, 128.6, 126.7, 122.2,
21.8, 114.0, 110.8, 107.9, 55.1, 40.7, 36.0, 29.0, 27.9, 26.5. IR
film) νmax: 3028, 2927, 2843, 1777, 1731, 1673, 1596, 1495,
3
)
1
1
42-144 C; H NMR (500 MHz, CDCl ) δ: 7.47 (d, J = 7.5 Hz,
3
H), 7.21 – 7.15 (m, 4H), 7.09 (d, J = 7.5Hz, 1H), 6.98 (t, J = 8.5
1
(
Hz, 2H), 3.32 (dd, J = 14.0 Hz, J = 4.5 Hz, 1H), 2.91 – 2.87
1
2
(
8
m, 1H), 2.83 (t, J = 8.0 Hz, 2H), 2.79 – 2.74 (m, 1H), 2.32 (t, J =
-1
+
13
1247, 1158 cm . HRMS: m/z (ESI) (M+H) calcd. for C21
is 321.1490; found 321.1494.
H O
20 3
.0 Hz, 2H), 2.29 – 2.24 (m, 2H). C NMR (126 MHz, CDCl3)
δ: 170.1, 162.7, 160.8, 143.8, 134.9, 133.9, 130.6, 130.5, 128.7,
1
27.9, 127.3, 126.6, 120.9, 115.6, 115.4, 110.5, 40.6, 35.2, 29.2,
3-(2-Methoxybenzyl)-3,4-dihydropyrano[3,2-c]chromen-2(5H)-
2
1
7.5, 26.5. IR (film) ν : 2955, 2918, 2851, 1730, 1681, 1510,
one (6i):
max
-
1
+
223, 1158 cm . HRMS: m/z (ESI) (M+H) calcd. for C H FO
20 17 2
Chemical Formula: C H O ; Yield:140 mg (87%); mp: 132-
20
18
4
is 309.1290; found 309.1291.
o
1
1
34 C; H NMR (500 MHz, CDCl ) δ: 7.83 (d, J = 7.5 Hz, 1H),
3
3
2
-(Furan-2-ylmethyl)-3,4,5,6-tetrahydro-2H-benzo[h]chromen-
-one (6e):
7.43 (t, J = 8.0 Hz, 1H), 7.20 - 7.14 (m, 2H), 6.97 (t, J = 7.5 Hz,
H), 6.92 (d, J = 8.5 Hz, 1H), 6.87 (t, J = 7.5 Hz, 1H), 6.80 (d, J
8.0 Hz, 1H), 4.56 (d, J = 11.5 Hz, 1H), 4.32 (d, J = 11.5 Hz,
1H), 3.78 (s, 3H), 3.70 – 3.62 (m, 1H), 2.77 – 2.72 (m, 1H), 2.68
1
=
Chemical Formula: C H O ; Yield: 112 mg (80%), Viscous
18
16
3
1
liquid; H NMR (500 MHz, CDCl ) δ: 7.47 (d, J = 7.5 Hz, 1H),
7
Hz, 1H), 6.28 (s, 1H), 6.11 (d, J = 2.0 Hz, 1H), 3.33 (dd, J =
1
3
1
1
2
13
3
–
2.55 (m, 2H), 2.43 – 2.39 (m, 1H); C NMR (126 MHz,
.31 (d, J = 7.0 Hz, 1H), 7.20 – 7.14 (m, 2H), 7.09 (d, J = 7.5
CDCl ) δ: 160.3, 156.3, 135.1, 127.0, 126.7, 125.6, 120.7, 119.7,
3
1
1
16.8, 109.3, 69.0, 59.9, 54.1, 44.8, 34.1, 31.7. IR (film) νmax:
5.0 Hz, J = 4.5 Hz, 1H), 3.04 – 2.96 (m, 1H), 2.91 – 2.81 (m,
-1
2
13
3068, 2928, 2838, 1737, 1684, 1604, 1493, 1242, 1179 cm .
HRMS: m/z (ESI) (M+H) calcd. for C H O is 323.1283;
H), 2.36 – 2.32 (m, 4H). C NMR (126 MHz, CDCl ) δ: 169.9,
+
3
20
18
4
52.2, 143.7, 141.6, 135.0, 128.7, 127.8, 127.3, 126.6, 120.8,
found 323.1286.
10.9, 110.4, 107.3, 38.5, 29.6, 28.5, 27.5, 26.5. IR (film) ν
:
max
-
1
956, 2918, 2851, 1732, 1681, 1600, 1435, 1224, 1156 cm .
9-Fluoro-3-(2-methoxybenzyl)-3,4-dihydropyrano[3,2-
c]chromen-2(5H)-one (6j):
+
HRMS: m/z (ESI) (M+H) calcd. for C H O is 281.1177;
18
16
3
found 281.1183.
Chemical Formula: C H FO ; Yield:140 mg (82%); mp:
20
17
4
o
1
8
-Methoxy-3-(2-methoxybenzyl)-3,4,5,6-tetrahydro-2H-
164-166 C; H NMR (500 MHz, CDCl ) δ: 7.21 (t, J = 7.5 Hz,
3
benzo[h]chromen-2-one (6f):
1
1
H), 7.11 (d, J = 7.5 Hz, 1H), 7.07 (dd, J = 8.5 Hz, J = 2.5 Hz,
1 2
H), 6.88 (t, J = 7.5 Hz, 1H), 6.85 – 6.79 (m, 2H), 6.71- 6.68 (m,
= 13.5 Hz, J = 4.5
Hz, 1H), 3.14 – 3.07 (m, 1H), 2.76 – 2.71 (m, 1H), 2.18 – 2.08
Chemical Formula: C H O ; Yield:170 mg (97%); mp: 109-
2
2
22
4
o
1
1H), 4.73 (s, 2H), 3.83 (s, 3H), 3.42 (dd, J
1
2
1
7
-
11 C; H NMR (500 MHz, CDCl ) δ: 7.41 (d, J = 8.5 Hz, 1H),
3
.22 – 7.19 (m, 1H), 7.12 (dd, J = 7.5 Hz, J = 1.5 Hz, 1H), 6.89
6.83 (m, 2H), 6.70 (dd, J = 8.5 Hz, J =2.5 Hz, 1H), 6.65 (d, J
13
1
2
(
m, 2H). C NMR (126 MHz, CDCl ) δ: 169.1, 158.5, 157.6,
3
1
2
1
1
3
56.6, 149.8, 140.2, 131.1, 128.3, 126.0, 120.6, 118.3, 116.5,
16.4, 116.0, 115.8, 110.3, 108.2, 108.0, 105.5, 67.6, 55.2, 38.5,
=
2.5 Hz, 1H), 3.81 (s, 3H), 3.79 (s, 3H), 3.42 (dd, J = 13.5 Hz,
1
J2 = 4.5 Hz, 1H), 3.07- 3.01 (m, 1H), 2.79 (t, J = 8.0 Hz, 2H),
1.2, 25.5. IR (film) ν : 2956, 2920, 2851, 1770, 1743, 1650,
max
2
2
1
1
2
.73 – 2.68 (m, 1H), 2.28 (t, J = 8.0 Hz, 2H), 2.25 – 2.16 (m,
H); C NMR (126 MHz, CDCl ) δ: 171.1, 159.3, 157.6, 143.5,
37.0, 131.2, 128.0, 126.7, 122.1, 122.0, 120.5, 113.9, 110.8,
10.3, 108.1, 55.1, 38.9, 31.2, 29.3, 28.0, 26.5. IR (film) ν
-1
+
13
1439, 1245, 1179cm . HRMS: m/z (ESI) (M+H) calcd. For
C H FO is 341.1189; found 341.1190.
3
2
0
17
4
:
3-Ethyl-3,4,5,6-tetrahydro-2H-benzo[h]chromen-2-one (6k):
max
-
1
937, 2838, 1703, 1776, 1672, 1598, 1494, 1244, 1159 cm .
+
Chemical Formula: C H O ; Yield:103 mg (90%); mp: 75-
1
5
16
2
HRMS: m/z (ESI) (M+H) calcd. for C H O is 351.1596;
found 351.1598.
22
22
4
o
1
7
7
2
2
1
7 C; H NMR (500 MHz, CDCl ) δ: 7.48 (d, J = 7.0 Hz, 1H),
3
.25 - 7.15 (m, 2H), 7.12 - 7.06 (m, 1H), 2.87 (t, J = 8.0 Hz, 2H),
.63 – 2.57 (m, 1H), 2.48 (dd, J = 17.0 Hz, J = 7.0 Hz, 1H),
8
-Methoxy-3-(4-methoxybenzyl)-3,4,5,6-tetrahydro-2H-
1
2
benzo[h]chromen-2-one (6g)
.40 – 2.32 (m, 3H), 2.02 – 1.94 (m, 1H), 1.66 – 1.54 (m, 1H),
13
.05 (t, J = 7.5 Hz, 3H); C NMR (126 MHz, CDCl ) δ: 170.8,
3
Chemical Formula: C H O ; Yield:147 mg (84%); mp: 105-
22
22
4
o
1
143.5, 134.9, 128.9, 127.7, 127.3, 126.6, 120.9, 110.7, 40.3, 29.8,
1
7
07 C; H NMR (500 MHz, CDCl ) δ: 7.40 (d, J = 8.5 Hz, 1H),
3
2
1
7.6, 26.7, 23.3, 11.4. IR (film) νmax: 2961, 2925, 2857, 1731,
.11 – 7.09 (m, 2H), 6.83 – 6.82 (m, 2H), 6.71 (dd, J = 8.5 Hz,
-
1
+
1
682, 1600, 1455, 1223, 1157 cm . HRMS: m/z (ESI) (M+H)
J2 = 2.5 Hz, 1H), 6.66 (d, J = 2.5 Hz, 1H), 3.79 (s, 3H), 3.78 (s,
calcd. for C H O is 229.1228; found 229.1230.
15
16
2
3
1
H), 3.29 (dd, , J = 14.0 Hz, J = 5.0 Hz, 1H), 2.90 – 2.83 (m,
H), 2.79 (t, J = 8.0 Hz, 2H), 2.73 – 2.68 (m, 1H), 2.31 - 2.28
1 2
3-Ethyl-3,4-dihydropyrano[3,2-c]chromen-2(5H)-one (6l):
1
3
(m, 2H), 2.23 (d, J = 9.0 Hz, 2H). C NMR (126 MHz, CDCl3)
Chemical Formula: C H O ; Yield:109 mg (95%); mp: 205-
δ: 170.8, 159.3, 158.4, 143.5, 136.9, 130.2, 130.1, 122.1, 121.8,
14 14
3
o
1
2
7
07 C; H NMR (500 MHz, CDCl δ: 7.34 (d, J = 7.5 Hz, 1H),
1
2
1
14.4, 114.0, 113.9, 110.8, 107.9, 55.2, 55.1, 40.9, 35.1, 28.9,
7.9, 26.5. IR (film) ν : 2922, 2839, 1774, 1731, 1672, 1598,
494, 1244, 1159 cm . HRMS: m/z (ESI) (M+H) calcd. for
3
.14 (t, J = 7.5 Hz, 1H), 6.91 (t, J = 7.5 Hz, 1H), 6.78 (d, J = 8.0
Hz, 1H), 4.88 - 4.82 (m, 2H), 2.67 – 2.62 (m, 1H), 2.40 – 2.35
max
-
1
+
(
(
m, 1H), 2.24 – 2.19 (m, 1H), 2.04 – 1.95 (m, 1H), 1.66 – 1.59
C H O is 351.1596; found 351.1599.
22
22
4
13
m, 1H), 1.04 (t, J = 7.5 Hz, 3H). C NMR (126 MHz, CDCl ) δ:
3

5
1
6
1
69.7, 154.0, 140.7, 129.9, 121.3, 121.1, 117
A
.1
C
, 1
C
1
E
5.6
P
,
T
10
E
3
D
.9, MAN
C
U
he
S
m
C
ica
R
l Formula: C H O ; Yield:132 mg (88%), Viscous
19 24 3
I
P
T
1
7.5, 40.1, 25.9, 23.4, 11.3. IR (film) ν : 2966, 2932, 2877,
liquid; H NMR (500 MHz, CDCl ) δ: 7.18 (t, J = 8.0 Hz, 1H),
7.09 (d, J = 7.0 Hz, 1H), 6.87 – 6.81 (m, 2H), 3.81 (s, 3H), 3.37
(dd, J = 13.5 Hz, J = 5.0 Hz, 1H), 2.92 – 2.84 (m, 1H), 2.65 –
max
3
-
1
787, 1697, 1579, 1478, 1296, 1185 cm . HRMS: m/z (ESI)
+
(M+H) calcd. for C H O is 231.1021; found 231.1025.
14 14 3
1
2
2
2
6
1
2
.6 (m, 1H), 2.15-2.03 (dd, J = 11.0 Hz, J = 5.1 Hz, 2H), 2.15 –
1 2
3
-Ethyl-9-fluoro-3,4-dihydropyrano[3,2-c]chromen-2(5H)-one
.02 (m, 3H), 1.97 (m, 1H), 1.65 – 1.67 (m, 2H), 1.58 – 1.48 (m,
(6m):
13
H). C NMR (126 MHz, CDCl ) δ: 171.7, 157.6, 147.3, 131.0,
3
27.9, 127.0, 120.5, 110.9, 110.3, 55.1, 38.7, 31.1, 30.0, 29.2,
Chemical Formula: C H FO ; Yield:106 mg (85%); mp:
1
4
13
3
o
1
8.9, 28.7, 28.5, 26.5, 26.2. IR (film) ν : 2925,2855, 1698
1
16-118 C; H NMR (500 MHz, CDCl ) δ: 7.07 (dd, J = 8.5 Hz,
max
3
1
-
1
+
(broad), 1602, 1464 cm . HRMS: m/z (ESI) (M+H) calcd. for
J = 2.7 Hz, 1H), 6.84 (td, J = 8.5 Hz, J = 2.7 Hz, 1H), 6.73 (dd,
2
1
2
C H O is 301.1803 found 301.1806.
J = 8.8 Hz, J = 4.4 Hz, 1H), 4.88 – 4.76 (m, 2H), 2.66 (dq, J =
1
19 24
3
2
1
1
1
1
3.7 Hz, J = 6.9 Hz, 1H), 2.41 (dd, J1 = 17.2 Hz, J = 7.2 Hz,
2
2
Acknowledgements
H), 2.25 (dd, J = 17.2 Hz, J = 10.5 Hz, 1H), 2.07 – 1.93 (m,
1
2
13
H), 1.69 – 1.59 (m, 1H), 1.05 (t, J = 7.5 Hz, 3H). C NMR (126
We thank the Science & Engineering Research Board (SERB),
New Delhi, for the project SB/S1/OC-22/2014. We also thank the
Council of Scientific and Industrial Research (CSIR) and the
University Grants Commission (UGC) New Delhi, for financial
assistance.
MHz, CDCl ) δ: 169.2, 158.5, 156.9, 149.8, 140.2, 118.2, 116.6,
1
1
1
3
16.5, 116.1, 115.9, 108.2, 108.0, 105.3, 67.6, 40.1, 26.0, 23.4,
1.3. IR (film) ν : 2966, 2931, 2879, 1788, 1622, 1581, 1486,
max
-
1
+
274, 1184 cm . HRMS: m/z (ESI) (M+H) calcd. for C H FO
14 13 3
is 249.1629; found 249.1631.
3
-(But-2-enyl)-8-methoxy-3,4,5,6-tetrahydro-2H-
References
benzo[h]chromen-2-one (6n):
1
.
Burstein, C.; Glorius, F. Angew. Chem., Int. Ed. 2004, 43, 6205.
Chemical Formula: C H O ; Yield:115 mg (81%); mp: 95-
18
20
3
o
1
2. Sohn, S.; Rosen, E.; Bode, J. J. Am. Chem. Soc. 2004, 126, 14370.
3
9
6
(
2
5
7 C; H NMR (500 MHz, CDCl ) δ: 7.40 (d, J = 8.5 Hz, 1H),
3
.
For reviews of NHC organocatalysis, see: (a) Christmann, M.
Angew. Chem., Int. Ed. 2005, 44, 2632. (b) Zeitler, K. Angew.
Chem., Int. Ed. 2005, 44, 7506. (c) Enders, D. Niemeier, O.;
Henseler, A. Chem. Rev. 2007, 107, 5606. (d) Marion, N.; Díez-
González, S.; Nolan, S. Angew. Chem., Int. Ed. 2007, 46, 2988.
.70 (dd, J = 8.5 Hz, J = 2.5 Hz, 1H), 6.67 (s, 1H), 5.56 - 5.49
1
2
m, 1H), 5.46 – 5.39 (m, 1H), 3.79 (s, 3H), 2.82 (t, J = 8.0 Hz,
H), 2.73 – 2.63 (m, 1H), 2.60 - 2.55 (m, 1H), 2.40 – 2.30 (m,
13
H), 1.68 (dd, J = 6.2 Hz, J = 1.0 Hz, 3H). C NMR (126
1
2
(e) Nair, V.; Vellalath, S.; Babu, B. P.; Chem. Soc. Rev. 2008, 37,
MHz, CDCl ) δ: 170.7, 159.3, 143.4, 136.9, 128.5, 127.1, 122.1,
3
2
2
691. (f) Phillips, E.; Chan, A.; Scheidt, K. A. Aldrichimica Acta
009, 42, 55. (g) Moore, J.; Rovis, T. Top. Curr. Chem. 2010, 291,
1
(
21.9, 113.9, 110.8, 108.1, 55.1, 39.0, 33.2, 28.0, 26.5, 18.0. IR
-1
film) νmax: 2918, 2851, 1775, 1674, 1597, 1495, 1250,1160 cm .
77. (h) Biju, A. T.; Kuhl, N.; Glorius, F. Acc. Chem. Res. 2011,
44, 1182. (i) Hirano, K.; Piel, I.; Glorius, F. Chem. Lett. 2011, 40,
+
HRMS: m/z (ESI) (M+H) calcd. for C H O is 285.1490;
18
20
3
7
86. (j) Chiang, P. –C.; Bode, J. W. TCI MAIL 2011, 149, 2. (k)
found 285.1494.
Nair, V.; Menon, R. S.; Biju, A. T.; Sinu, C. R.; Paul, R. R.; Jose,
A.; Sreekumar, V. Chem. Soc. Rev. 2011, 40, 5336. (l) Vora, H.
U.; Rovis, T. Aldrichimica Acta 2011, 44, 3. (m) Cohen, D. T.;
Scheidt, K. A.; Chem. Sci. 2012, 3, 53. (n) Bugaut, X.; Glorius, F.
Chem. Soc. Rev. 2012, 41, 3511. (o) Grossmann, A.; Enders, D.
Angew. Chem. Int. Ed. 2012, 51, 314. (p) Douglas, J.; Churchill,
G.; Smith, A. Synthesis 2012, 44, 2295. (q) Izquierdo, J.; Hutson,
G. E.; Cohen, D. T.; Scheidt, K. A. Angew. Chem., Int. Ed. 2012,
51, 11686. (r) Ryan, S. J.; Candish, L.; Lupton, D. W. Chem. Soc.
Rev. 2013, 42, 4906. (s) De Sarkar, S.; Biswas, A.; Samanta, R.
C.; Studer, A. Chem. – Eur. J. 2013, 19, 4664. (t) Connon, S. J.
Angew. Chem. Int. Ed. 2014, 53, 1203. (u) Mahatthananchai, J.;
Bode, J. W. Acc. Chem. Res. 2014, 47, 696. (v) Hopkinson, M. N.;
Richter, C.; Schedler, M.; Glorius, F. Nature 2014, 510, 485.
3
-Butyl-8-methoxy-3,4,5,6-tetrahydro-2H-benzo[h]chromen-2-
one (6o):
Chemical Formula: C H O ; Yield:120.3 mg (77%); mp:
1
8
22
3
o
1
1
1
1
2
1
0
1
3
2
28-130 C; H NMR (500 MHz, CDCl ) δ: 7.40 (d, J = 8.5 Hz,
3
H), 6.71 (dd, J = 8.5 Hz, J = 2.5 Hz, 1H), 6.68 (d, J = 2.0 Hz,
1
2
H), 3.80 (s, 3H), 2.83 (t, J = 8.0 Hz, 2H), 2.68 – 2.61 (m, 1H),
.45 – 2.44 (m, 1H), 2.39 -2.35 (m, 2H), 2.32 – 2.27 (m, 1H),
.99 – 1.92 (m, 1H), 1.56 - 1.49 (m, 1H), 1.45 – 1.33 (m, 4H),
13
.93 (t, J = 7.0 Hz, 3H). C NMR (126 MHz, CDCl ) δ: 171.2,
3
59.3, 143.4, 136.9, 122.1, 121.9, 113.9, 110.8, 107.9, 55.2, 39.0,
0.1, 29.9, 29.1, 28.0, 26.6, 22.6, 14.0; IR (film) ν : 2955,
4. Some selected examples of NHC catalyzed homoenolate reaction;
max
-
1
926, 2857, 1778, 1675, 1598, 1495, 1251, 1160 cm . HRMS:
see (a) Burstein, C.; Tschan, S.; Xie, X.; Glorius, F. Synthesis
+
2
006, 2418. (b) Nair, V.; Vellalath, S.; Poonoth, M.; Suresh, E. J.
m/z (ESI) (M+H) calcd. for C H O is 287.1647; found
2
18
22
3
Am. Chem. Soc. 2006, 128, 8736. (c) Wadamoto, M.; Phillips, E.;
Reynolds, T.; Scheidt, K. A. J. Am. Chem. Soc. 2007, 129,
87.1643.
1
0098.(d) Chiang, P. –C.; Kaeobamrung, J.; Bode, J. W. J. Am.
3
2
-(2-Methoxybenzyl)-3,4,6,7,8,9-hexahydrocyclohepta[b]pyran-
(5H)-one (6p):
Chem. Soc. 2007, 129, 3520. (e) He, M.; Bode, J. W. Org. Lett.
2
2
005, 7, 3131. (f) Chan, A.; Scheidt, K. A. J. Am. Chem. Soc.
008, 130, 2740. (g) Ryan, S. J.; Candish, L.; Lupton, D. W. J.
Chemical Formula: C H O ; Yield:116 mg (81%), Viscous
18
22
3
Am. Chem. Soc. 2009, 131, 14176. (h) Nair, V.; Sinu, C. R.; Babu,
B. P.; Varghese, V.; Jose, A.; Suresh, E. Org. Lett. 2009, 11, 5570.
(i) Nair, V.; Varghese, V.; Babu, B. P.; Sinu, C. R.; Suresh, E.
Org. Biomol. Chem. 2010, 8, 761. (j) White, N.; DiRocco, D.;
Rovis, T. J. Am. Chem. Soc. 2013, 135, 8504. (k) Sinu, C. R.;
Padmaja, D. V. M.; Ranjini, U. P.; Seetha Lakshmi, k. C.; Suresh,
E.; Nair, V. Org. Lett. 2013, 15, 68. (l) Guo, C.; Schedler, M.;
Daniliuc, C. G.; Glorius, F. Angew. Chem. Int. Ed. 2014, 53,
10232. (m) Wang, M.; Rong, Z. –Q.; Zhao, Y. Chem. Commun.
2014, 50, 15309.
Chow, K.; Bode, J. W. J. Am. Chem. Soc. 2004, 126, 8126.
Reynolds, N. T.; Alaniz, J. R.; Rovis, T. J. Am. Chem. Soc. 2004,
126, 9518.
(a) Maki, B. E.; Chan, A.; Scheidt, K. A. Synthesis 2008, 1306. (b)
Maki, B. E.; Patterson, E. V.; Cramer, C. J.; Scheidt, K. A. Org.
Lett. 2009, 11, 3942.
1
liquid; H NMR (500 MHz, CDCl ) δ: 7.20 (t, J = 8.0 Hz, 1H),
7
3
.09 (d, J = 7.5 Hz, 1H), 6.89 - 6.83 (m, 2H), 3.81 (s, 3H), 3.35
(dd, J = 13.5 Hz, J = 5.0 Hz, 1H), 2.87 - 2.80 (m, 1H), 2.68 –
1
2
2
1
1
3
1
.60 (m, 1H), 2.33 (t, J = 5.5 Hz, 2H), 2.13 - 1.98 (m, 4H), 1.73 –
13
.53 (m, 6H). C NMR (126 MHz, CDCl ) δ: 171.6, 157.6,
3
49.6, 131.1, 127.9, 127.0, 120.4, 113.5, 110.2, 55.1, 38.4, 31.7,
1.6, 31.5, 30.8, 30.5, 26.5, 25.1. IR (film) ν : 2928, 2855,
max
-
1
+
774, 1703, 1601, 1494 cm . HRMS: m/z (ESI) (M+H) calcd.
5
6
.
.
for C H O is 287.1647; found 287.1650.
18
22
3
3
-(2-Methoxybenzyl)-3,4,5,6,7,8,9,10-octahydro-2H-
7
.
cycloocta[b]pyran-2-one (6q):

6
Tetrahedron
ACCEPTED MANUSCRIPT
8
9
.
.
(a) Fu, Z.; Sun, H.; Chen, S.; Tiwari, B.; Li, G.; Chi, Y. R. Chem.
Commun. 2012, 49, 261. (b) Kaeobamrung, J.; Kozlowski, M. C.;
Bode, J. W. Proc. Natl. Acad. Sci. 2010, 107, 20661.
(a) Albanese, D. C. M.; Gaggero, N. Eur. J. Org. Chem. 2014,
5
631. (b) Phillips, E.; Wadamoto, M.; Chan, A.; Scheidt, K. A.;
Angew. Chem. Int. Ed. 2007, 46, 3107. (c) Nair, V. Paul,R. R.;
Seetha Lakshmi, K. C.; Menon, R. S.; Jose, A.; Sinu, C. R.;
Tetrahedron Letters 2011, 52, 5992. (d) Fu, Z.; Sun, H.; Chen, S.;
Tiwari, B.; Li, G.; Chi, Y. R.; Chem. Commun. 2013, 49, 261.
1
1
0. He, M.; Struble, J. R.; Bode, J. W. J. Am. Chem. Soc. 2006, 128,
418.
1. (a) Dong, Nakagawa-Goto, K.; Lai, C.-Y.; Morris-Natschke, S. L.;
8
Bastow, K. F.; Kim, Y.; Lee, E. Y.-H. P.; Lee, K.-H. J. Nat. Prod.
2
012, 75, 370. (b) Wang, X.; Nakagawa-Goto, K.; Bastow, K. F.;
Don, M.-J.;,Lin, Y.-L.; Wu, T.-S.; Lee, K.-H. J. Med. Chem. 2006,
4
1
9, 5631. (c) Hua, D. H.; Saha, S.; Recl. Trav. Chim. Pays-Bas.
995, 114, 341. (d) Posakony, J.; Hirao, M.; Stevens, S.; Simon, J.
A.; Bedalov, A.; J. Med. Chem. 2004, 47, 2635. (e) Neugebauer,
R. C.; Uchiechowska, U.; Meier, R.; Hruby, H.; Valkov, V.;
Verdin, E.; Sippl, W.; Jung, M. J. Med. Chem. 2008, 51, 1203.
2. Crystal structure of compound 6b has been deposited at
Cambridge Crystallographic Data Centre and allocated the
reference No. CCDC 1054134.
1
1
1
3. For details of catalyst screening see supporting information.
4. Bugarin, A.; Jones, K. D.; Connell, B. T. Chem. Commun. 2010,
4
6, 1715.

ACCEPTED MANUSCRIPT
Expedient Synthesis of Tricyclic Benzopyran-2-ones via N-Heterocyclic
Carbene Catalyzed Annulation of Enals to α-Methylene Cycloalkanones
a
a
a
b
Venkata Mani Padmaja D., Sinu C. R., Jagadeesh Krishnan, Rony Rajan Paul, Sunil
a
a,c
a
Varughese, Seetha Lakshmi K. C., and Vijay Nair *
a
Chemical Science and Technology Division, National Institute for Interdisciplinary Science and Technology
(
CSIR-NIIST),Trivandrum-695 019, India.
Department of Chemistry CMS College Kottayam, Kerala- 686001,
School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686560, India
b
c
Optimization Reactions
a
Entry
Catalyst
Condition
Time (h)
Yield
(
%)
-
1
2
3
4
5
6
7
8
9
3a
3a
3a
3b
3c
3d
3e
3a
3a
3a
3a
3a
3a
3a
3a
3a
DBU, DCM, rt
DBU, THF, rt
24
24
8
-
O
DBU, THF, 66 C
43
O
DBU, THF, 66 C
24
24
24
24
24
2
Trace
O
DBU, THF, 66 C
-
-
O
DBU, THF, 66 C
O
DBU, THF, 66 C
-
O
DBU, Toluene, 66 C
Trace
84
38
49
-
O
DBU, Toluene, 110 C
O
1
1
1
1
1
1
1
0
1
2
3
4
5
6
DBU, CH CN, 82 C
24
24
24
24
24
24
24
3
O
DBU, DMF, 110 C
DMAP, DCM, rt
O
DMAP, DCM, 66 C
15
-
DMAP, Toluene, rt
O
DMAP, Toluene, 110 C
22
10
O
K CO , THF, 66 C
2
3
a
Isolated yield
S1

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6a
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6a
3
S2

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6b
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6b
3
S3

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6c
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6c
3
S4

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6d
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6d
3
S5

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6e
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6e
3
S6

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6f
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6f
3
S7

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6g
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6g
3
S8

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6h
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6h
3
S9

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6i
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6i
3
S10

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6j
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6j
3
S11

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6k
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6k
3
S12

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6l
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6l
3
S13

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6m
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6m
3
S14

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6n
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6n
3
S15

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6o
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6o
3
S16

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6p
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6p
3
S17

ACCEPTED MANUSCRIPT
1
H NMR (500 MHz, CDCl ) of Compound 6q
3
1
3
C NMR (126 MHz, CDCl ) of Compound 6q
3
S18

ACCEPTED MANUSCRIPT
ORTEP of 6b, CCDC number: 1054134
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