Formal cycloaddition of ethyl 2-aroyl-1-chlorocyclopropanecarboxylates:facile synthesis of diversified tetrahydrocyclopropa[b]chromenes

Article abstract of DOI:10.1016/j.tet.2018.02.010

Tandem reaction of ortho-hydroxy chalcone with ethyl 2-aroyl-1-chlorocyclopropanecarboxylates has been disclosed, affording facile synthesis of diversified tetrahydrocyclopropa[b]chromenes via electron-deficient cyclopropene intermediate.

Full text of DOI:10.1016/j.tet.2018.02.010

Accepted Manuscript
Formal cycloaddition of ethyl 2-aroyl-1-chlorocyclopropanecarboxylates:facile
synthesis of diversified tetrahydrocyclopropa[b]chromenes
Guoxi Xiong, Yong Liao, Xue-Hui Liu, Xiangying Tang, Yuefa Gong
PII:
S0040-4020(18)30135-2
10.1016/j.tet.2018.02.010
TET 29281
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 December 2017
Revised Date: 31 January 2018
Accepted Date: 2 February 2018
Please cite this article as: Xiong G, Liao Y, Liu X-H, Tang X, Gong Y, Formal cycloaddition
of ethyl 2-aroyl-1-chlorocyclopropanecarboxylates:facile synthesis of diversified
tetrahydrocyclopropa[b]chromenes, Tetrahedron (2018), doi: 10.1016/j.tet.2018.02.010.
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Formal cycloaddition of ethyl 2-Aroyl-1-
chlorocyclopropanecarboxylates:facile
synthesis of diversified
Leave this area blank for abstract info.
tetrahydrocyclopropa[b]chromenes
a,b
b
b
b
b
Guoxi Xiong, Yong Liao, Xue-Hui Liu, Xiangying Tang* , Yuefa Gong*
a
Technology Center of China Tabacco, Hubei Industrial Co. ltd, Wuhan 430040, People’s Republic of China.
School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan
b
4
30074,People’s Republic of China.

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Formal cycloaddition of ethyl 2-Aroyl-1-chlorocyclopropanecarboxylates: facile synthesis of diversified
tetrahydrocyclopropa[b]chromenes
a, b
a
b
a,
b,
Guoxi Xiong , Yong Liao , Xue-Hui Liu, Xiangying Tang ∗ and Yuefa Gong ∗
a
Technology Center of China Tabacco, Hubei Industrial Co. ltd, Wuhan 430040, People’s Republic of China
School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074,People’s Republic of
b
China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Tandem
reaction
of
ortho-hydroxy
chalcone
with
ethyl
2-aroyl-1-
chlorocyclopropanecarboxylates has been disclosed, affording facile synthesis of diversified
tetrahydrocyclopropa[b]chromenes via electron-deficient cyclopropene intermediate.
2
009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Cycloaddition
Chromenes
Cyclopropenes
Cyclopropanation
Heterocycles
—
——
∗
Corresponding author.
E-mail: xytang@hust.edu.cn; gongyf@hust.edu.cn.

2
Tetrahedron
ACCEPTED MANUSCRIPT
1
. Introduction
Cyclopropenes are highly strained but useful building blocks
[
1]
in organic synthesis. During the last decades, the investigation
of cyclopropenes has attracted much attention due to their wide
range of reactivities beyond those of olefins, allenes and
[
2]
alkynes. In general, electron-rich cyclopropenes are used as
excellent π–donators which can coordinate with many transition
metal catalysts as well as Brønsted acids or Lewis acids. For
example, In 2010, Wang and coworkers reported a novel gold
catalyzed rearrangement of 1,5-cyclopropene-ynes to afford
[
2f]
benzene derivatives.
Shi and coworkers also found that
nitrogen or carbon-tethered indolylcyclopropenes could undergo
novel intramolecular cycloisomerizations of to furnish
biologically and pharmaceutically valuable heterocycles
[
3]
catalyzed by gold- and silver-catalysts or HOTf. However, to
our great surprise, the chemistry of electron-deficient
cyclopropenes remain largely unexplored, mainly because such
molecules are difficult to be activated by metal or acid catalysts
and very limited types of such cyclopropenes were reported
probably due to their instability.
Polyfunctionalized chromenes are found in many natural
scaffolds and drug candidates displaying a broad range of
biological and pharmacological activities. In particular,
cyclopropane fused chromenes are of great importance, because
they are not only served as potential drug candidates in drug
discovery, but also are important intermediates in the synthesis of
Scheme 1. Reported method to construct cyclopropane-fused
chromenes and our method.
2. Result and discussion
diversified
(
(
heterocycles.
hydroxyimino)cyclopropa[b]chromen-1a-carboxamide
PHCCC), which acts as a glutamate receptor ligand, has been
For
example,
N-phenyl-7-
Our initial investigation started with the optimization of the
reaction conditions using 1a and 2a as the model substrates. To our
delight, treatment of 1a and 2a with Cs CO in DMSO (dimethyl
[
4, 5]
suggested as novel treatments for Parkinson’s disease.
Another related drug molecule, namely CPCCPEt, is used mainly
in basic research as a non-competitive antagonist at the
2
3
o
sulfoxide) at 25 C (room temperature) for 6 h, the reaction went on
smoothly to give the desired product 3aa in 56% yield, along with
1
[
6]
good diastereoselectivity (3.4:1) as determined by crude H NMR
metabotropic glutamate receptor subtype mGluR1 (Figure 1).
(Table 1, entry 1). After careful separation of the diastereoisomers by
silica gel chromatography and subjected to the 2D NOESY, the
major product was determined as cis configuration (for details, see
Supporting Information). When another highly polar solvent, DMF
(N,N-dimethylformamide) was used in replace of DMSO, the yield
of 3aa increased to 88% with a 3.5:1 dr value (Table 1, entry 2).
Further solvent effect study revealed that DMF was the best solvent
for this transformation (Table 1, entries 3-8). It is worth nothing that
the polarity of the solvents plays an important role to control the
diastereoselectivity: high polar solvents favor cis products, while
non-polar solvents have opposite selectivity. Next, using DMF as the
solvent, the effect of different bases was evaluated. When K CO
Figure 1. Bioactive cyclopropane fused chromenes.
Meanwhile, it is reported that transformation of such
cyclopropane containing substance into other useful heterocyclic
2
3
[
7]
have also been achieved. Traditionally, cyclopropane fused
chromenes can be constructed by Michael-initiated ring-closure
and K PO were used, the reactions were less effective than Cs CO ,
3 4 2 3
giving the corresponding products in 49% and 78% yields,
respectively (Table 1, entries 9-10). For strong base KOH, the yield
of 3aa dropped to 30%, probably due to that the cyclopropene
intermediate is formed too fast and undergoes self-polymerization
during the reaction process (Table 1, entry 11). Similar results were
[
8]
of methyl ketones with 3-bromochromones (Scheme 1a), or
treatment of electron-deficient chromenes with sulfur ylides
[
9]
under basic conditions (Scheme 1b),
and also by
[10]
cyclopropanation of chromenes with carbenoids (Scheme 1c).
However, in a sharp contrast, beyond cyclopropanation of
chromenes, other methods to access cyclopropane fused
chromenes are extremely limited. In view of the current
circumstances, and also to continue our research interest in
obtained in the cases of LiOH and Mg(OEt) (Table 1, entries 12-
13). In addition, because of the nuclephilicity of the nitrogen atom,
2
organic bases such as Et N and DBU were found not suitable for this
3
reaction (Table 1, entries 14-15). Based on the above results, we then
understood that the base shouldn’t be too strong or weak, because the
formation of cyclopropene intermediate and deprotonation of the
phenol should be kinetically compatible, or cyclopropene
intermediate will proceed with polymerization reactions. Therefore,
Cs CO was chosen as the best base. Further study about the loadings
[
11]
electron-deficient cyclopropenes,
4+2] cycloaddition reaction can take place between ethyl 2-
aroyl-1-chlorocyclopropanecarboxylates and (E)-3-(2-
we envisage that a formal
[
1
hydroxyaryl)-1-arylprop-2-en-1-ones 2, affording the desired
cyclopropylchromenes 3.
2
3
of Cs CO revealed that the 2 eq. gave the highest yield as well as
2
3
diastereoselectivity (Table 1, entries 2 and 16-18).
Table 1. Optimization of the reaction conditions

3
O
O
ACCEPTED MANUSCRIPT
O
O
Ar2
O
O
Ph
O
O
Ar1
Cs2CO3 (2 eq.)
DMF, rt, 6 h
Cl
Ph
Ar2
Base
Cl
+
Ar1
+
CO2Et
Solvent, T, time
CO2R
OH
OH
2
O
3aa
O
3
CO2Et
1
CO2R
1a
2a
1
Ar2
yield (%)b (cis:trans)c
entrya
base
solvent
T ( oC)
t (h)
b
c
entry
Ar /R
y
i
e
l
d
(
%
)
(
c
i
s
:
t
r
a
n
s
)
1
2
3
4-MeC6H4/Et, 1b
4-MeOC6H4/Et, 1c
4-ClC6H4/Et, 1d
4-BrC6H4/Et, 1e
Ph, 2a
Ph, 2a
Ph, 2a
3ba, 74 (2.8:1)
3ca, 80 (2.9:1)
3da, 62 (1.8:1)
3ea, 72 (3.3:1)
1
2
3
Cs2CO3
Cs2CO3
Cs2CO3
DMSO
DMF
25
25
60
6
6
56 (3.4:1)
88 (3.5:1)
83 (4:1)
CH3CN
12
4
5
6
Ph, 2a
Ph, 2a
Ph, 2a
4
5
6
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
1,4-dixoane
THF
60
25
25
12
12
12
68 (1:2.3)
77 (2.5:1)
73 (1.1:1)
2-ThioC6H4/Et, 1f
4-PhC6H4/Et, 1g
Ph/Et, 1a
3fa, 50 (3.3:1)
3ga, 74 (3.2:1)
3ab, 91 (3.2:1)
3ac, 50 (3.0:1)
3bb, 79 (3:1)
CH2Cl2
7
8
9
4-MeC6H4, 2b
7
8
9
Toluene
1,2-DCE
DMF
60
25
25
25
25
12
12
24
24
12
61 (1:2.5)
57 (1:1)
Ph/Et, 1a
1-Naphthyl, 2c
4-MeC6H4, 2b
4-MeC6H4, 2b
4-MeC6H4, 2b
4-MeC6H4, 2b
4-MeC6H4, 2b
Ph, 2a
Cs2CO3
K2CO3
K3PO4
4-MeC6H4, 1b
4-MeOC6H4, 1c
4-ClC6H4, 1d
4-BrC6H4, 1e
2-ThioC6H4,1f
Ph/Me, 1h
49 (3.7:1)
78 (3.7:1)
30 (2.9:1)
1
1
1
1
1
1
0
1
2
3
4
5
3cb, 84 (2.9:1)
3db, 91 (3.1:1)
3eb, 83 (3.3:1)
3fb, 72 (2.1:1)
3ha, 74 (2.5:1)
3hb, 75 (2.0:1)
10
DMF
11
KOH
DMF
12
13
14
LiOH
DMF
DMF
DMF
25
80
25
12
24
24
51 (2.8:1)
48 (2:1)
ND
Mg(OEt)2
Et3N
DBU
Ph/Me, 1h
4-MeC6H4, 2b
15
16
17
DMF
DMF
DMF
25
25
25
24
24
6
< 5
d
e
81 (3:1)
Cs CO3
2
2
Cs CO3
85 (3:1)
a
Reaction conditions: 1 (0.2 mmol), 2a (0.2 mmol), DMF (2.0
18
2
Cs CO3
f
DMF
25
6
56 (2.9:1)
mL), 6 h.
b
a
Isolated yields of the diastereomers.
Reaction conditions: 0.2 mmol (1.0 eq.) of 1a, 0.2 mmol (1.0
eq.) of 2a, and 0.4 mmol (2.0 eq.) of base in 2.0 mL of solvent at
c
1
Determined by H NMR of crude 3.
the specified temperature for the given time.
[
11a, 11b]
b
Based on the above results and our previous work,
a
Isolated total yields of the diastereomers.
c
d
e
f
1
plausible mechanism was proposed in Scheme 2. Initially, in the
presence of Cs CO , 1 was converted to the cyclopropene
Determined by H NMR of crude 3aa.
.2 mmol of base (1.0 eq.).
.3 mmol of base (1.5 eq.).
.5 mmol of base (2.5 eq.).
0
0
0
2
3
intermediate A, meanwhile, 2 was deprotonated to form anion B.
Next, an oxa-Michael addition takes place to generate
intermediate C. Following by another Michael addition in enolate
C, the corresponding diastereoisomers are formed after
protonation with cis-3 as the major product. Strong base KOH or
DMSO = Dimethyl sulfoxide, DMF = Dimethylformamide, THF
=
tetrahydrofuran, 1,2-DCE = 1,2-dichlorethane.
With the best reaction conditions in hand, we next turned our
relatively weak organic bases such as DBU and Et N are not
3
interest to study the generality of this reaction. As can be seen from
table 2, the reactions of 2a with various 1b-1g all went smoothly to
give the corresponding products in moderate to good yields and
moderate diastereoselectivities with no significant electronic effect
effective in our reaction, probably due to that in the presence of
such bases the speeds for formation of intermediate A and B do
not match and A may decompose during the reaction process.
(Table 2, entries 1-6). In case of 2-thiophenyl group substituted
substrate 1f, lower yield of 3fa was obtained probably because of the
steric hindrance (Table 2, entry 5). Next, taking 1a as a model
substrate, different ortho-hydroxy chalcones 2 were investigated. As
for substrates 2b and 2c, the reactions delivered the desired products
3
ab and 3ac in moderate to good yields (Table 2, entries 7-8),
surprisingly, in case of substrate 2b with a 4-methyl group, the
reaction gave the best yield (91%) (Table 2, entry 7). Though the
reason was not clear at this stage, we were eager to known the
reaction performance of 2b with other cyclopropene precursors 1. To
our delight, as for substrates 1b-1f (Table 2, entries 9-13), all the
reactions furnished higher yields than those reactions with 2a (Table
2
, entries 1-5). The ester group R was found to have no obvious
Scheme 2. A plausible reaction mechanism.
influence on the reaction outcomes, as for substrate 1h, the
corresponding products 3ha and 3hb were obtained in 74% and 75%
yields with moderate diastereoselectivities, respectively (Table 2,
entries 14 and 15).
Interestingly, the stereoselectivity in this reaction is different
[11b]
from our previous report,
in which the trans-isomers were
obtained as the major products. Though the reason for such
different stereoselectivities still need further evaluation, we
propose a possible rationale herein (Scheme 3). As carefully
looking into the 6-membered-ring transition state in intermediate
C, the steric hindrance in cis-transition state is smaller than that
in trans-transition state because the bulky unsaturated ketone
moiety stretched out, thus leading to the fast formation of cis-3
products. Even though trans-3 are more stable than cis-3 due to
the less steric hindrance, however, kinetic control plays a more
important role to determine the stereochemistry of the reaction.
Table 2. Generality of this reaction.

4
Tetrahedron
ACCEPTED MA 11 3
NU
3.0,
S
o
12
C
9
R
.1,IP12
T
9.0, 128.8, 128.6, 128.4, 127.9, 126.2, 123.3,
18.4, 64.8, 61.9, 43.3, 43.0, 36.5, 18.9, 13.9. trans-3aa: m.p. =
1
4
7
5-47 C. H NMR (400 MHz, CDCl ) δ 7.92 (d, J = 7.2 Hz, 2H),
.81 (d, J = 7.2 Hz, 2H), 7.58-7.49 (m, 1H), 7.44 (d, J = 7.6, 7.6
3
Hz, 2H), 7.36 (d, J = 7.6, 7.6 Hz, 2H), 7.23 (d, J = 7.2 Hz, 1H),
7
1
.16 (d, J = 7.2 Hz, 1H), 7.00-6.93 (m, 2H), 4.41 (t, J = 6.0 Hz,
H), 3.93-3.79 (m, 2H), 3.48 (dd, J = 18.0, 6.4 Hz, 1H), 3.33 (dd,
J = 18.0, 6.4 Hz, 1H), 2.29 (d, J = 6.8 Hz, 1H), 1.69 (d, J = 6.8
13
Scheme 3. 6-membered ring transition states (intermediate C).
Hz, 1H), 0.88 (t, J = 7.2 Hz, 3H). C NMR (101 MHz, CDCl
3
) δ
1
1
6
97.1, 194.5, 168.3, 151.1, 136.4, 134.5, 133.4, 133.3, 128.74,
3
. Conclusion
28.68, 128.64, 128.5, 128.4, 128.1, 123.3, 123.0, 118.1, 64.9,
1
1.8, 44.0, 42.5, 31.2, 18.2, 13.6. mix 3aa: H NMR (400 MHz,
In conclusion, we have developed a tandem oxa-Michael
CDCl ) δ 7.92-7.84 (dd, J = 25.1, 7.8 Hz, 2H), 7.75-7.66 (dd, J =
3
addition and Michael addition reaction of 2-hydroxychalcones
with ethyl 2-benzoylcycloprop-1-enecarboxylate intermediate,
affording a facile excess to diversified polyfunctionalized
chromenes, which may have biologically activities as well as
potential applications in organic synthesis. Moreover, the
products contains several different functional groups, which may
have potential applications for useful chemical modification.
Considering that the study of the electron sufficient
2
6
7
6.3, 7.8 Hz, 2H), 7.52-7.49 (t, J = 7.3 Hz, 1H), 7.40-7.37 (t, J =
.7 Hz, 3H), 7.31-7.25 (q, J = 7.9 Hz, 2H), 7.21 – 7.03 (m, 2H),
.20 – 7.06 (m, 2H), 4.36-4.32 (t, J = 6.3 Hz, 1H), 4.23 – 3.62
(m, 2H), 3.64 – 3.31 (m, 1H), 3.31 – 3.11 (m, 1H), 2.11 (d, J =
1
1
1
1
1
6
1
1.7 Hz, 1H), 1.93 (d, J = 7.0 Hz, 1H). 1.18-1.12 (t, J = 7.0 Hz,
13
H). C NMR (101 MHz, CDCl ) δ 197.5, 197.1, 194.8, 194.5,
3
68.7, 168.3, 151.1, 150.9, 136.7, 136.4, 135.0, 134.5, 133.5,
33.4, 133.3, 133.0, 129.1, 129.0, 128.8, 128.7, 128.68, 128.64,
28.5, 128.4, 128.1, 127.9, 126.2, 123.3, 123.0, 118.4, 118.2,
4.87, 64.79, 61.9, 61.8, 43.9, 43.3, 43.0, 42.5, 36.5, 31.3, 18.9,
cyclopropenes, this work make
a good contribution to
cyclopropene chemistry. Further investigation to study more
intensively of the mechanism and application of this method in
natural products or drug candidates are currently undergoing in
our laboratory.
-1
8.2, 13.9, 13.6. IR (KBr): ν 3456, 1742, 1450, 1249 cm .
+
HRMS (ESI) m/z calcd. for: C H O 441.1697, found
4
28
25
5
41.1708.
4
. Experimental section
Ethyl-7a-(4-methylbenzoyl)-7-(2-oxo-2-phenylethyl)-7,7a-
4
.1 General remarks
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate(3ba)
1
White solid (67 mg, total yield 74%), NMR (400 MHz, CDCl )
3
Dichloromethane was freshly distilled from calcium hydride;
δ 7.93-7.87 (m, 2H), 7.75 – 7.70 (m, 2H), 7.56 (t, J = 7.2 Hz,
THF, Et O and toluene were distilled from sodium (Na) under
argon (Ar) atmosphere. Melting points were determined on a
digital melting point apparatus and temperatures were
uncorrected. H NMR and C NMR spectra were recorded on a
Bruker AM-400 spectrophotometers. Infrared spectra were
recorded on a Perkin-Elmer PE-983 spectrometer with absorption
in cm- . Flash column chromatography was performed using 300-
4
gel plates (Huanghai GF254) were used. Mass spectra were
recorded by EI, and HRMS were measured on a HP-5989
instrument.
2
0
7
.3H), 7.48 – 7.42 (m, 1.2H), 7.33 (t, J = 7.6 Hz, 1.5H), 7.26-
.21 (m, 2H), 7.19 – 7.12 (m, 2H), 7.04 – 7.93 (m, 2H), 4.42 –
1
13
4.38 (m, 1H), 4.22 – 4.17 (m, 1.5H), 3.90 – 3.80 (m, 0.5H), 3.62
–
2
3.56 (m, 0.7H), 3.50 – 3.44 (m, 0.3H), 3.36 – 3.21 (m, 1H),
.41 (s, 2.2H), 2.36 (s, 0.8H), 2.26 (d, J = 6.4 Hz, 0.3H), 2.16 (d,
1
J = 6.4 Hz, 0.7H), 1.99 (d, J = 7.2 Hz, 0.7H), 1.68 (d, J = 6.4 Hz,
13
0
.3H ), 1.20 (t, J = 7.2 Hz, 2.3H), 0.90 (t, J = 7.2 Hz, 0.7H).
C
00 mesh silica gel. For thin-layer chromatography (TLC), silica
NMR (101 MHz, CDCl ) δ 197.6, 197.1, 194.3, 194.2, 168.8,
3
1
1
1
6
1
68.3, 151.0, 150.9, 144.5, 144.2, 136.7, 136.4, 133.3, 133.0,
32.4, 131.9, 129.4, 129.2, 129.0, 128.9, 128.8, 128.6, 128.4,
28.1, 128.0, 126.3, 123.4, 123.2, 122.9, 118.4, 118.1, 64.8, 64.7,
1.8, 61.7, 43.9, 43.3, 43.0, 42.6, 36.5, 31.3, 21.7, 21.6, 18.9,
-
1
8.0, 13.9, 13.5. IR (KBr): ν 3456, 1741, 1404, 1248 cm .
4
.2 General procedure
+
HRMS (ESI) m/z calcd.for: C H O
455.1853, found
29
27
5
Using 3aa as an example. To a 25 mL flame-dried reaction tube
were added cyclopropane 1a (0.2 mmol, 50 mg), 2a (0.2 mmol,
455.1832.
4
4 mg) and Cs CO (0.4 mmol, 130 mg), followed by addition of
Ethyl-7a-(4-methoxybenzoyl)-7-(2-oxo-2-phenylethyl)-7,7a-
2
3
DMF (2 mL) via syringe. The reaction mixture was stirred at
room temperature (25 C) for 6 h, TLC showed that all starting
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate (3ca)
White solid (75 mg, yield 80%); H NMR (400 MHz, CDCl
o
1
) δ
3
material 1a was consumed, the reaction mixture was filtered and
diluted with water. Then extracted by EA (3X20 mL), the organic
layers were combined and dried over MgSO4, filtered and
concentrated in vacuo. The residue was purified by silica gel
chromatography to give 3aa as a white solid (77 mg, yield 88%).
7.97 – 7.91 (m, 2H), 7.93 – 7.73 (m, 2H), 7.56 – 7.32 (m, 3H),
7.27 – 7.12 (m, 2H), 7.04 – 6.83 (m, 4H), 4.43 – 4.35 (m, 1H),
4.24 – 4.15 (m, 1.5H), 3.91 – 3.78 (m, 3.5H), 3.58 (dd, J = 17.6,
5.6 Hz, 0.74H), 3.48 (dd, J = 17.6, 5.6 Hz, 0.26H), 3.35 (dd, J =
17.6, 5.6 Hz, 0.26H), 3.25 (dd, J = 17.6, 5.6 Hz, 0.74H), 2.24 (d,
J = 6.4 Hz, 0.24H), 2.16 (d, J = 6.4 Hz, 0.76H), 2.00 (d, J = 6.4
Hz, 0.76H), 1.69 (d, J = 6.4 Hz, 0.24 H), 1.20 (t, J = 7.2 Hz,
o
White solid (77 mg, total yield 88%); cis-3aa: m.p. = 38-40 C.
1
2.22H), 0.90 (d, J = 7.2 Hz, 0.78H), 1.92 (d, J = 6.8 Hz, 1H),
H NMR (400 MHz, CDCl ) δ 7.90 (d, J = 8.1 Hz, 2H), 7.66 (d, J
13
3
1
1
1
1
1
.11 (t, J = 7.1 Hz, 3H). C NMR (101 MHz, CDCl ) δ 197.6,
3
=
7
7.5 Hz, 2H), 7.49 (t, J = 7.4 Hz, 1H), 7.37 (t, J = 7.5 Hz, 3H),
.26 (t, J = 7.7 Hz, 2H), 7.11 (t, J = 7.7 Hz, 1H), 7.05 (d, J = 7.4
Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 6.87 (t, J = 7.4 Hz, 1H), 4.33
t, J = 6.4 Hz, 1H), 4.11-4.06 (m, 2H), 3.53 (dd, J = 18.0, 6.4 Hz,
97.2, 193.1, 168.8, 168.3, 163.8, 163.6, 150.9, 136.7, 136.4,
33.3, 133.0, 131.4, 131.0, 129.0, 128.7, 128.6, 128.4, 128.3,
28.0, 127.9, 127.3, 126.3, 123.2, 122.9, 118.4, 118.1, 113.9,
13.8, 64.7, 61.8,61.7, 55.4, 55.3, 43.9, 43.2, 42.9, 42.4, 36.5,
(
1
1
H), 3.17 (dd, J = 18.0, 6.4 Hz, 1H), 2.10 (d, J = 7.0 Hz, 1H),
.92 (d, J = 7.0 Hz, 1H), 1.12 (t, J = 7.1 Hz, 3H). C NMR (101
13
31.4, 18.9, 17.8, 13.9, 13.6. IR (KBr): ν 3456, 1740, 1399, 1253
-
1
+
cm . HRMS (ESI) m/z calcd.for: C H O 471.1802, found
29
27
6
MHz, CDCl ) δ 197.5, 194.8, 168.7, 150.9, 136.7, 135.0, 133.5,
3
4
71.1818.

5
ACCEPTED MA13
N
9.
U
8,
S
13
C
9.
R
68
I
,
P
136.65, 136.4, 133.7, 133.4, 133.2, 133.0, 129.6,
T
Ethyl-7a-(4-chlorobenzoyl)-7-(2-oxo-2-phenylethyl)-7,7a-
129.3, 129.0, 128.91, 128.87, 128.83, 128.6, 128.5, 128.4, 128.3,
128.1, 128.0, 127.28, 127.25, 127.18, 126.3, 123.33, 123.0,
118.4, 118.1, 64.9, 64.8, 61.9, 61.8, 44.0, 43.3, 43.1, 42.6, 36.5,
31.3, 19.0, 18.3, 14.0, 13.6. IR (KBr): ν 3451, 1700, 1399, 1211
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate(3da)
1
White solid (59 mg, yield 62%); H NMR (400 MHz, CDCl ) δ
3
7
7
4
6
1
.92 – 7.90 (m, 2H), 7.76 – 7.71 (m, 2H), 7.68 – 7.34 (m, 5H),
.27 – 7.11 (m, 2H), 7.05 – 6.95 (m, 2H), 4.41 – 4.32 (m, 1H),
.24 – 4.15 (m, 1.3H), 3.92 – 3.84 (m, 0.7H), 3.67 (dd, J = 18.0,
.4 Hz, 0.66H), 3.45 (dd, J = 18.0, 6.4 Hz, 0.34H), 3.19 (dd, J =
8.0, 6.4 Hz, 0.66H), 2.30 (d, J = 6.8 Hz, 0.34H), 2.18 (d, J = 6.8
-
1
+
cm . HRMS (ESI) m/z calcd.for: C H O 517.2010, found
34
29
5
517.2015.
Ethyl-7a-benzoyl-7-(2-oxo-2-(p-tolyl)ethyl)-7,7a-
Hz, 0.66H), 1.96 (d, J = 6.8 Hz, 0.66H), 1.67 (d, J = 6.8 Hz,
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate (3ab)
White solid (83 mg, yield 91%); H NMR (400 MHz, CDCl ) δ
13
1
0
.34H), 1.21 (t, J = 7.2 Hz, 2H), 0.94 (t, J = 7.2 Hz, 1H). C
3
NMR (101 MHz, CDCl ) δ 197.5, 197.0, 193.8, 193.4, 168.7,
7.99 – 7.97 (m, 1.5H), 7.83 – 7.80 (m, 1H), 7.64 (d, J = 8.4 Hz,
1.5H), 7.59 – 7.55 (m, 1H), 7.51 – 7.43 (m, 1.5H), 7.36 (d, J =
3
1
1
1
6
1
68.2, 151.2, 150.9, 140.0, 139.66, 136.59, 136.3, 133.5, 133.1,
33.0, 130.4, 130.1, 128.99, 128.90, 128.8, 128. 7, 128.6, 128.44,
28.37, 128.1, 127.9, 126.1, 123.5, 123.4, 123.1, 118.45, 118.2,
4.9, 64.8, 61.96, 61.89, 43.9, 43.2, 43.1, 42.4, 36.3, 31.2, 19.1,
1
3
8.0 Hz, 0.5H), 7.24 – 7.12 (m, 4H), 7.05 – 6.93 (m, 2H).
C
NMR (101 MHz, CDCl ) δ 197.1, 196.7, 194.8, 194.5, 168.8,
3
168.3, 151.0, 150.9, 144.2, 143.8, 134.9, 134.4, 134.2, 133.9,
133.5, 133.2, 129.3, 129.0, 128.9, 128.74, 128.70, 128.63,
128.59, 128.42, 128.39, 128.2, 128.1, 126.3, 123.4, 123.3, 122.9,
118.4, 118.1, 64.8, 64.7, 61.8, 61.7, 43.8, 43.3, 42.8, 42.5, 36.5,
-
1
8.5, 13.9, 13.6. IR (KBr): ν 3458, 1741, 1366, 1248 cm .
+
HRMS (ESI) m/z calcd.for: C H ClO 475.1307, found
28
27
5
4
75.1298.
3
1.2, 21.6, 21.5, 18.9, 18.1, 13.9, 13.5. IR (KBr): ν 3468, 1745,
-
1
+
Ethyl-7a-(4-bromobenzoyl)-7-(2-oxo-2-phenylethyl)-7,7a-
1407, 1248 cm . HRMS (ESI) m/z calcd. for: C H O
29 27 5
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate (3ea)
White solid (74 mg, yield 72%); H NMR (400 MHz, CDCl ) δ
455.1853, found 455.1859.
1
3
7
2
–
.92 – 7.81 (m, 2.2H), 7.76 – 7.73 (m, 1.5H), 7.66 – 7.56 (m,
Ethyl-7a-benzoyl-7-(2-(naphthalen-1-yl)-2-oxoethyl)-7,7a-
H), 7.51 – 7.42 (m, 1.8H), 7.36 (dd, J = 7.6, 7.6 Hz, 1.5 H), 7.25
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate (3ac)
13
1
7.11 (m, 2H), 7.05 – 6.96 (m, 2H). C NMR (101 MHz,
White solid (49 mg, yield 50%); H NMR (400 MHz, CDCl ) δ
3
CDCl ) δ 197.5, 196.9, 194.0, 193.6, 168.6, 168.2, 151.2, 150.9,
8.54 (d, J = 8.4 Hz, 0.25H), 8.24 – 8.21 (m, 0.75H), 8.05 – 8.02
(m, 1.5H), 7.98 – 7.78 (m, 3H), 7.62 – 7.57 (m, 2H), 7.55 – 7.44
(m, 4.5H), 7.26 – 7.26 (m, 2H), 7.12 – 7.04 (m, 1H), 7.00 – 6.95
(m, 1H), 4.54 – 46 (m, 1H), 4.26 – 4.13 (m, 1.5H), 3.91 – 3.78
(m, 0.5H), 3.70 (dd, J = 17.6, 6.4 Hz, 0.75H), 3.54 (dd, J = 17.6,
6.4 Hz, 0.25H), 3.40 (dd, J = 17.6, 6.4 Hz, 0.25H), 3.33 (dd, J =
17.6, 6.4 Hz, 0.75H), 2.32 (d, J = 7.2 Hz, 0.25H), 2.23 (d, J = 7.2
Hz, 0.75H), 2.02 (d, J = 7.2 Hz, 0.75H), 1.69 (d, J = 7.2 Hz,
0.25H), 1.20 (t, J = 7.2 Hz, 2.25H), 0.88 (t, J = 7.2 Hz, 0.75H).
3
1
1
1
4
36.5, 136.2, 133.8, 133.5, 133.4, 133.1, 132.2, 131.9, 130.4,
30.2, 128.9, 128.8, 128.7, 128.7, 128.6, 128.43, 128.36, 128.1,
27.9, 126.1, 123.5, 123.1, 118.4, 118.2, 64.9, 64.8, 61.9, 61.9,
3.9, 43.3, 43.0, 42.4, 36.3, 31.2, 19.1, 18.5, 13.9, 13.7. IR
-
1
(
KBr): ν 3464, 1744, 1453, 1275 cm . HRMS (ESI) m/z
+
calcd.for: C H BrO 519.0802, found 519.0808.
28
27
5
Ethyl-7-(2-oxo-2-phenylethyl)-7a-(thiophene-2-carbonyl)-7,7a-
13
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate(3fa)
C NMR (101 MHz, CDCl ) δ 201.4, 200.9, 194.9, 194.5, 168.7,
3
1
White solid (44 mg, yield 50%); H NMR (400 MHz, CDCl ) δ
168.3, 151.2, 150.8, 135.5, 135.2, 134.9, 134.5, 133.9, 133.7,
133.6, 133.3, 133.0, 132.6, 130.0, 129.8, 129.2, 129.0, 128.9,
128.7, 128.69, 128.67, 128.5, 128.4, 128.2, 128.1, 127.65,
127.61, 126.5, 126.2, 126.0, 125.7, 125.5, 124.24, 124.22, 123.4,
123.2, 123.0, 118.5, 118.2, 64.8, 64.7, 61.9, 61.8, 47.3, 46.7,
43.2, 42.5, 36.8, 31.7, 18.8, 18.3, 13.9, 13.5. IR (KBr): ν 3434,
3
7
1
7
4
.94 – 7.91 (m, 0.4H), 7.79 – 7.77 (m, 1.6H), 7.66 (d, J = 5.2 Hz,
H), 7.60 – 7.42 (m, 2H), 7.36 (dd, J = 8.0, 8.0 Hz, 2H), 7.25 –
.05 (m, 4H), 6.99 – 6.94 (m, 1H), 4.48 (t, J = 6.4 Hz, 0.22H),
.32 (t, J = 6.4 Hz, 0.78H), 4.21 – 4.14 (m, 1.55H), 3.94 – 3.80
(m, 0.45H), 3.61 (dd, J = 18.0, 5.2 Hz, 0.78H), 3.48 (dd, J = 18.0,
-
1
+
5
2
2
.2 Hz, 0.22H), 3.36 – 3.25 (m, 1H), 2.29 (d, J = 6.8 Hz, 0.22H),
.16 (s, 1.56H), 1.72 (d, J = 6.8 Hz, 0.22H), 1.87 (t, J = 7.2 Hz,
.34H), 0.93 (t, J = 7.2 Hz, 0.66H). C NMR (101 MHz, CDCl3)
1699, 1410, 1240 cm . HRMS (ESI) m/z calcd.for: C H O
32 27 5
491.1853, found 491.1858.
13
δ 197.5, 197.0, 187.5, 168.6, 168.3, 151.6, 151.3, 142.2, 142.1,
Ethyl-7a-(4-methylbenzoyl)-7-(2-oxo-2-(p-tolyl)ethyl)-7,7a-
1
1
1
3
36. 7, 136.4, 134.7, 134.2, 133.4, 133.1, 132.4, 128.8, 128.7,
28.6, 128.4, 128.2, 128.1, 128.0, 126.5, 124.2, 123.3, 123.1,
18.5, 118.2, 64.9, 64.8, 61.9, 61.8, 44.1, 43.8, 43.6, 42.5, 36.5,
1.9, 19.5, 18.8, 13.9, 13.5. IR (KBr): ν 3465, 1741, 1412,
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate(3bb)
White solid (74 mg, yield 79%); H NMR (400 MHz, CDCl ) δ
7.87 (d, J = 8.0 Hz, 1.45H), 7.82 (d, J = 8.0 Hz, 0.5H), 7.71 (d, J
= 8.0 Hz, 0.5H), 7.64 (d, J = 8.0 Hz, 1.5H), 7.26 – 7.12 (m, 6H),
7.04 – 7.93 (m, 2H), 4.42 – 4.37 (m, 1H), 4.24 – 4.15 (m, 1.5H),
3.91 – 3.77 (m, 0.5H), 3.58 – 3.40 (m, 1H), 3.33 – 3.19 (m, 1H),
1
3
-
1
+
1
252cm . HRMS (ESI) m/z calcd.for: C H O S 447.1261,
26 23 5
found 447.1273.
2
.41 – 2.33 (m, 6H), 2.25 (d, J = 6.0 Hz, 0.3H), 2.16 (d, J = 6.0
Ethyl-7a-([1,1'-biphenyl]-4-carbonyl)-7-(2-oxo-2-phenylethyl)-
,7a-dihydrocyclopropa[b]chromene-1a(1H)-carboxylate (3ga)
Hz, 0.7H), 1.99 (m, 0.7H), 1.68 (m, 0.3H), 1.19 (t, J = 7.2 Hz,
13
7
2.4H), 0.89 (t, J = 7.2 Hz, 0.6H). C NMR (101 MHz, CDCl ) δ
3
1
White solid (76 mg, yield 74%); H NMR (400 MHz, CDCl ) δ
197.1, 196.7, 194.3, 194.2, 168.8, 168.3, 151.0, 150.9, 144.4,
144.2, 144.1, 143.8, 134.2, 133. 9, 132.4, 131.9, 129.4, 129.3,
129.2, 129.1, 129.02, 128.98, 128.8, 128.7, 128.4, 128.2, 128.1,
126. 5, 123. 5, 123.2, 122.9, 118.4, 118.0, 64.7, 64.7, 61.76,
61.69, 43.7, 43.3, 42.8, 42.9, 36.5, 31.3, 21.7, 21.59, 21.57,
21.50, 18.9, 17.9, 13.9, 13.5. IR (KBr): ν 3470, 1744, 1407, 1251
3
8
6
1
–
.05 (d, J = 8.0 Hz, 1.5H), 7.94 – 7.87 (m, 1H), 7.77 – 7.54 (m,
H), 7.49 – 7.32 (m, 6H), 7.27 – 7.14 (m, 1.5H), 7.06 – 7.01 (m,
H), 6.97 (dd, J = 7.2, 7.2 Hz, 1H), 4.45 (t, J = 6.4 Hz, 1H), 4.29
4.17 (m, 1.5H), 3.94 – 3.82 (m, 0.5H), 3.66 (dd, J = 18.0, 6.4
Hz, 0.77H), 3.50 (dd, J = 18.0, 6.4 Hz, 0.23H), 3.33 (dd, J =
8.0, 6.4 Hz, 0.23H), 3.27 (dd, J = 18.0, 6.4 Hz, 0.77H), 2.31 (d,
-
1
+
1
cm . HRMS (ESI) m/z calcd.for: C H O 469.2010, found
30 29 5
J = 6.4 Hz, 0.23H), 2.21 (d, J = 6.4 Hz, 0.77H), 2.04 (d, J = 6.4
Hz, 0.77H), 1.71 (d, J = 6.4 Hz, 0.23), 1.22 (t, J = 7.2 Hz, 2.3H),
469.2027.
13
0
1
.92 (t, J = 7.2 Hz, 0.7H). C NMR (101 MHz, CDCl ) δ 197.6,
97.1, 194.4, 194.1, 168.8, 168.3, 151.1, 150.9, 146.1, 145.8,
Ethyl-7a-(4-methoxybenzoyl)-7-(2-oxo-2-(p-tolyl)ethyl)-7,7a-
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate (3cb)
3

6
Tetrahedron
1
White solid (81 mg, yield 84%); H NMR (40
.95 (d, J = 8.8 Hz, 1.5H), 7.84 – 7.79 (m, 1H), 7.64 (d, J = 8.8
Hz, 1.5H), 7.24 – 7.12 (m, 4H), 7.04 – 6.83 (m, 4H), 4.43 – 4.35
m, 1H), 4.24 – 4.15 (m, 1.5H), 3.91 – 3.76 (m, 3.5H), 3.54 (dd, J
18.0, 5.2 Hz, 0.75H), 3.44 (dd, J = 18.0, 5.2 Hz, 0.25H), 3.32
dd, J = 18.0, 5.2 Hz, 0.25H), 3.23 (dd, J = 18.0, 5.2 Hz, 0.75H),
.39 – 2.32 (m, 3H), 2.24 (d, J = 6.8 Hz, 0.23), 2.16 (d, J = 6.8
Hz, 0.77H), 2.00 (d, J = 6.8 Hz, 0.77H), 1.69 (d, J = 6.8 Hz,
A
0
C
M
C
Hz
E
, C
P
D
T
C
l
3
ED
) δ MA0.
NU
38
H)
S
, 2
C
.1
R
6
I
(s, 1.24H), 1.72 (d, J = 6.8 Hz, 0.38H), 1.18 (t, J =
P
T
13
7
7.2 Hz, 2H), 0.92 (t, J = 7.2 Hz, 1H). C NMR (101 MHz,
CDCl ) δ 197.0, 196.6, 187.5, 168.6, 168.3, 151.5, 151.3, 144.3,
3
(
=
(
2
143.9, 142.2, 142.0, 134.6, 134.2, 134.1, 133.9, 133.4, 132.4,
129.3, 129.1, 128.7, 128.5, 128. 5, 128.21, 128.18, 128.1, 126.6,
124.3, 123.3, 123.1, 118.4, 118.2, 64.9, 64.8, 61.9, 61.8, 44.1,
43.6, 42.2, 36.5, 31.9, 21.6, 21.5, 19.5, 18.8, 13.9, 13.5. IR
-
1
(KBr): ν 3454, 1739, 1408, 1180 cm . HRMS (ESI) m/z
calcd.for: C H O S 461.1417, found 461.1431.
13
+
0
.23H), 1.19 (d, J = 6.8 Hz, 2.3H), 0.90 (t, J = 6.8 Hz, 0.7H).
C
27
25
5
NMR (101 MHz, CDCl ) δ 197.2, 196.8, 193.1, 168.9, 168.4,
3
1
1
1
1
4
63.8, 163.6, 150.9, 144.2, 143.8, 134.2, 133.9, 131.4, 131.3,
31.0, 129.7, 129.3, 129.1, 129.0, 128.95, 128.67, 128.62, 128.4,
28.3, 128.2, 128.0, 127.9, 127.3, 126.4, 123.3, 123.2, 122.9,
18.3, 118.0, 113.9, 113.8, 64.7, 61.7, 61.7, 55.4, 55.4, 43.7,
3.3, 42.7, 42.4, 36.5, 31.4, 21.6, 21.5, 19.0, 17.8, 13.9, 13.5. IR
Methyl-7a-benzoyl-7-(2-oxo-2-phenylethyl)-7,7a-
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate(3ha)
1
White solid (63 mg, yield 74%); H NMR (400 MHz, CDCl ) δ
3
8.01 – 7.91 (m, 2H), 7.81 – 7.73 (m, 2H), 7.61 – 7.32 (m, 6H),
7.24 – 7.15 (m, 2H), 7.03 – 6.94 (m, 2H), 4.46 – 4.39 (m, 1H),
3.77 (s, 2.2H), 3.64 – 3.45 (m, 1H), 3.39 (m, 0.7H), 3.36 – 3.23
(m, 1H), 2.31 – 3.20 (m, 1H), 1.99 (d, J = 7.2 Hz, 0.8H), 1.71 (d,
-
1
(
KBr): ν 3468, 1745, 1408, 1260 cm . HRMS (ESI) m/z
+
calcd.for: C H O 485.1959, found 485.1968.
30
29
6
13
J = 7.2 Hz, 0.2H). C NMR (101 MHz, CDCl ) δ 197.5, 197.1,
3
Ethyl-7a-(4-chlorobenzoyl)-7-(2-oxo-2-(p-tolyl)ethyl)-7,7a-
194.97, 194.63, 169.2, 168.8, 150.9, 150.5, 136.5, 136.2, 134.8,
134.3, 133.6, 133.4, 133.3, 133.0, 129.2, 129.0, 128.9, 128.7,
128.7, 128.6, 128.6, 128.6, 128.5, 128.4, 128.4, 128.2, 127.9,
125.9, 123.4, 123.2, 123.0, 118.3, 118.0, 65.0, 64.8, 52.7, 52.4,
43.9, 43.3, 43.2, 42.5, 36.4, 31.1, 18.6, 18.3. IR (KBr): ν 3478,
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate (3db)
1
White solid (89 mg, yield 91%); H NMR (400 MHz, CDCl ) δ
3
7
8
1
6
3
1
.90 (d, J = 8.8 Hz, 1.5H), 7.81 (d, J = 8.8 Hz, 0.5H), 7.73 (d, J =
.0 Hz, 0.5H), 7.65 (d, J = 8.0 Hz, 1.5H), 7.41 (d, J = 8.0 Hz,
.5H), 7.33 (d, J = 8.0 Hz, 0.5H), 7.26 – 7.11 (m, 4H), 7.05 –
.95 (m, 2H), 4.41 – 4.32 (m, 1H), 4.24 – 4.14 (m, 1.5H), 3.94 –
.83 (m, 0.5H), 3.64 (dd, J = 18.0, 6.8 Hz, 0.75H), 3.42 (dd, J =
8.0, 6.8 Hz, 0.25H), 3.27 (dd, J = 18.0, 6.8 Hz, 0.25H), 3.17
-
1
+
1734, 1399, 1232 cm . HRMS (ESI) m/z calcd.for: C H O
2
7
23
5
427.1540, found 427.1560.
Methyl-7a-benzoyl-7-(2-oxo-2-(p-tolyl)ethyl)-7,7a-
(
(
dd, J = 18.0, 6.8 Hz, 0.75H), 2.39 (s, 0.7H), 2.34 (s, 2.3H), 2.29
d, J = 6.8 Hz, 0.25H), 2.19 (d, J = 6.8 Hz, 0.75H), 1.96 (d, J =
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate(3hb)
White solid (66 mg, yield 75%); H NMR (400 MHz, CDCl ) δ
1
3
6
2
1
1
1
1
4
.8 Hz, 0.75H), 1.67 (d, J = 6.8 Hz, 0.25H), 1.20 (t, J = 7.2 Hz,
8.00 (d, J = 6.8 Hz, 1.5H), 7.82 (t, J = 8.0 Hz, 1H), 7.65 – 7.35
(m, 4.5H), 7.26 – 7.12 (m, 4H), 7.03 – 6.94 (m, 2H), 4.46 – 4.39
(m, 1H), 3.77 (s, 2.2H), 3.59 – 3.41 (m, 1H), 3.39 (s, 0.8H), 3.33
– 3.21 (m, 1H), 2.39 (s, 0.8H), 2.33 (s, 2.2H), 2.29 (d, J = 6.8 Hz,
0.25H), 2.20 (d, J = 6.8 Hz, 0.75H), 1.99 (d, J = 6.8 Hz, 0.75H),
13
.3H), 0.93 (t, J = 7.2 Hz, 0.7H). C NMR (101 MHz, CDCl ) δ
3
97.0, 196.5, 193.7, 193.4, 168.6, 168.2, 151.2, 150.9, 144.3,
43.9, 139.9, 139.6, 134.0, 133.8, 133.4, 133.0, 130.3, 130.1,
29.3, 129.1, 128.9, 128.8, 128.8, 128.5, 128.4, 128.2, 128.0,
26.2, 123.4, 123.1, 118.4, 118.1, 64.9, 64.8, 61.9, 61.8, 43.7,
3.03, 42.99, 42.4, 36.3, 31.2, 21.6, 21.5, 19.1, 18.4, 13.9, 13.6.
13
1.71 (d, J = 6.8 Hz, 0.25H). C NMR (101 MHz, CDCl ) δ
3
197.1, 196.7, 194.9, 194.6, 169.3, 168.8, 150.9, 150.5, 144.3,
143.8, 134.8, 134.3, 134.1, 133.8, 133.5, 133.2, 129.3, 129.2,
129.04, 129.02, 128.8, 128.7, 128.62, 128.56, 128.44, 128.39,
-
1
IR (KBr): ν 3468, 1745, 1408, 1260 cm . HRMS (ESI) m/z
calcd.for: C H ClO 489.1463, found 489.1478.
+
29
26
5
1
28.2, 128.0, 126.0, 123.3, 123.0, 118.3, 117.9, 65.0, 64.8, 52.7,
Ethyl-7a-(4-bromobenzoyl)-7-(2-oxo-2-(p-tolyl)ethyl)-7,7a-
52.4, 43.7, 43.3, 42.9, 42.5, 36.4, 31.2, 21.6, 21.5, 18.7, 18.2. IR
-
1
dihydrocyclopropa[b]chromene-1a(1H)-carboxylate (3eb)
(KBr): ν 3390, 1699, 1397, 1222 cm . HRMS (ESI) m/z
1
+
White solid (88 mg, yield 83%); H NMR (400 MHz, CDCl ) δ
calcd.for: C H O 441.1702, found 441.1688.
3
28 25
5
7
2
1
1
.84 – 7.80 (m, 2H), 7.65 (d, J = 8.0 Hz, 2H), 7.59 – 7.48 (m,
H), 7.26 – 7.10 (m, 4H), 7.05 – 6.95 (m, 2H), 4.41 – 4.32 (m,
H), 4.23 – 4.14 (m, 1.5H), 3.94 – 3.82 (m, 0.5H), 3.64 (dd, J =
8.0, 6.8 Hz, 0.76H), 3.41 (dd, J = 18.0, 6.8 Hz, 0.24H), 3.27
Acknowledgments
We are grateful for the financial support from the National
Natural Science Foundation of China (21472053, 21172082).
(
2
dd, J = 18.0, 6.8 Hz, 0.24H), 3.16 (dd, J = 18.0, 6.8 Hz, 0.76H),
.39 – 2.34 (m, 3H), 2.29 (d, J = 6.8 Hz, 0.24H), 2.18 (d, J = 6.8
Hz, 0.76H), 1.96 (d, J = 6.8 Hz, 0.76H), 1.67 (d, J = 6.8 Hz,
Appendix A. Supplementary data
13
0
.24), 1.20 (t, J = 7.2 Hz, 2.2H), 0.94 (t, J = 7.2 Hz, 0.7H).
C
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tet.2017.xx.xxx.
NMR (101 MHz, CDCl ) δ 197.0, 196.5, 193.9, 193.5, 168.6,
3
1
1
1
1
4
3
68.1, 151.2, 150.8, 144.3, 143.9, 134.0, 133.8, 133.7, 133.4,
31.9, 130.6, 130.4, 130.1, 129.3, 129.2, 129.1, 128.9, 128.9,
28.73, 128.65, 128.5, 128.33, 128.31, 128.14, 127.99, 126.1,
23.4, 123.1, 118.3, 118.1, 64.9, 64.8, 61.9, 61.8, 43.7, 43.0,
2.4, 36.3, 31.2, 21.6, 21.5, 19.1, 18.4, 13.9, 13.6. IR (KBr): ν
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ACCEPTED MANUSCRIPT
Table 1. Optimization of the reaction conditions
O
O
O
Ph
O
Cl
Ph
Base
+
CO2Et
Solvent, T, time
OH
O
CO2Et
1a
2a
3aa
a
o
b
entry
base
solvent
T ( C)
t (h)
Yield (%)
c
(
cis: trans)
56 (3.4:1)
88 (3.5:1)
83 (4:1)
68 (1:2.3)
77 (2.5:1)
73 (1.1:1)
61 (1:2.5)
57 (1:1)
49 (3.7:1)
78 (3.7:1)
30 (2.9:1)
51 (2.8:1)
48 (2:1)
ND
1
2
3
4
5
6
7
8
9
Cs
Cs
Cs
Cs
Cs
Cs
Cs
Cs
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
CO
3
DMSO
DMF
25
25
60
60
25
25
60
25
25
25
25
25
80
25
25
25
25
25
6
3
3
3
3
3
3
3
6
CH
3
CN
12
12
12
12
12
12
24
24
12
12
24
24
24
24
6
1,4-dioxane
THF
2 2
CH Cl
Toluene
1,2-DCE
DMF
K
2
CO
3
1
0
1
2
3
4
5
6
7
8
K
3
PO
4
DMF
1
1
1
1
1
1
1
1
KOH
LiOH
DMF
DMF
Mg(OEt)
2
DMF
Et
3
N
DMF
DBU
DMF
< 5
d
Cs
2
CO
3
DMF
81 (3:1)
85 (3:1)
56 (2.9:1)
e
Cs
2
CO
3
DMF
f
Cs
2
CO
3
DMF
6
a
Reaction conditions: 0.2 mmol (1.0 eq.) of 1a, 0.2 mmol (1.0
eq.) of 2a, and 0.4 mmol (2.0 eq.) of base in 2.0 mL of solvent at
the specified temperature for the given time.
b
Isolated total yields of the diastereomers.
c
d
e
f
1
Determined by H NMR of crude 3aa.
.2 mmol of base (1.0 eq.).
.3 mmol of base (1.5 eq.).
.5 mmol of base (2.5 eq.).
0
0
0
DMSO = Dimethyl sulfoxide, DMF = Dimethylformamide, THF
tetrahydrofuran, 1,2-DCE = 1,2-dichlorethane.
=

ACCEPTED MANUSCRIPT
Table 2. Generality of this reaction.
a
1
2
b
entry
Ar /R
Ar
Yield (%)
c
(
cis: trans)
1
2
3
4
5
6
7
8
9
4-MeC
4-MeOC
4-ClC
4-BrC
2-ThioC
4-PhC
6
H
4
/Et, 1b
/Et, 1c
/Et, 1d
/Et, 1e
/Et, 1f
/Et, 1g
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
Ph, 2a
3ba, 74 (2.8:1)
3ca, 80 (2.9:1)
3da, 62 (1.8:1)
3ea, 72 (3.3:1)
3fa, 50 (3.3:1)
3ga, 74 (3.2:1)
3ab, 91 (3.2:1)
3ac, 50 (3.0:1)
3bb, 79 (3:1)
6
H
4
6
H
4
6
H
4
6
H
4
6
H
4
Ph/Et, 1a
Ph/Et, 1a
4-MeC
6 4
H , 2b
1-Naphthyl, 2c
4-MeC
4-MeOC
4-ClC
4-BrC
2-ThioC
6
H
4
/Et, 1b
/Et, 1c
/Et, 1d
/Et, 1e
/Et, 1f
4-MeC
4-MeC
4-MeC
4-MeC
4-MeC
6
6
6
6
6
H
4
H
4
H
4
H
4
H
4
, 2b
, 2b
, 2b
, 2b
, 2b
1
0
1
2
3
4
5
6
H
4
3cb, 84 (2.9:1)
3db, 91 (3.1:1)
3eb, 83 (3.3:1)
3fb, 72 (2.1:1)
3ha, 74 (2.5:1)
3hb, 75 (2.0:1)
1
1
1
1
1
6 4
H
6
H
4
6
H
4
Ph/Me, 1h
Ph/Me, 1h
Ph, 2a
4-MeC
6
H
4
, 2b
a
Reaction conditions: 1 (0.2 mmol), 2a (0.2 mmol), DMF (2.0
mL), 6 h.
b
Isolated yields of the diastereomers.
Determined by H NMR of crude 3.
c
1