A pseudo multi-component electrochemical synthesis of spiro dihydrofuran derivatives

Article abstract of DOI:10.1016/j.tet.2013.10.056

An electrochemical strategy to the assembly of tricyclic spiro dihydrofuran scaffold via the reaction of aryl aldehyde and dimedone has been developed successfully. This protocol has the advantages of high yields, wide application scope and an environmental benign procedure compared with the reported methods.

Full text of DOI:10.1016/j.tet.2013.10.056

Accepted Manuscript
A Pseudo Multi-Component Electrochemical Synthesis of Spiro Dihydrofuran
Derivatives
Changsheng Yao, Ying Wang, Tuanjie Li, Chenxia Yu, Liang Li, Chao Wang
PII:
S0040-4020(13)01601-3
10.1016/j.tet.2013.10.056
TET 24931
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 August 2013
Revised Date: 26 September 2013
Accepted Date: 14 October 2013
Please cite this article as: Yao C, Wang Y, Li T, Yu C, Li L, Wang C, A Pseudo Multi-Component
Electrochemical Synthesis of Spiro Dihydrofuran Derivatives, Tetrahedron (2013), doi: 10.1016/
j.tet.2013.10.056.
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An electrochemical strategy to the assembly of tricyclic
A Pseudo Multi-Component Electrochemical
Synthesis of Spiro Dihydrofuran Derivatives
spiro dihydrofuran scaffold via the reaction of aryl aldehyde
and dimedone has been developed successfully. This
protocol has the advantages of high yields, wide application
scope and an environmental benign procedure compared
with the reported methods.
Changsheng Yao*, Ying Wang, Tuanjie Li, Chenxia Yu, Liang Li, Chao Wang*
School of Chemistry and Engineering, Key Laboratory of Biotechnology for Medicial Plant, Jiangsu Normal
University, Xuzhou, Jiangsu 221116, P R China

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1
Tetrahedron
journal homepage: www.elsevier.com
A Pseudo Multi-Component Electrochemical Synthesis of Spiro Dihydrofuran
Derivatives
Changsheng Yaoa,*, Ying Wangb, Tuanjie Lib, Chenxia Yub, Liang Lib, Chao Wangb,*
a School of Chemistry and Engineering, Key Laboratory of Biotechnology for Medicial Plant, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P R China
b School of Chemistry and Engineering, Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou
Jiangsu 221116, P R China
Fax: +86-516-83500365.
E-mail: csyao@jsnu.edu.cn.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An electrochemical strategy to the assembly of tricyclic spiro dihydrofuran scaffold via the
reaction of aryl aldehyde and dimedone has been developed successfully. This protocol has
the advantages of high yields, wide application scope and an environmental benign
procedure compared with the reported methods.
Available online
2013 Elsevier Ltd. All rights reserved.
Keywords:
Electrosynthesis
Spiro dihydrofuran
multi-component reaction
reaction of aldehydes with 5,5-dimethylcyclohexane-1,3-dione in the
presence of molecular iodine and dimethylaminopyridine could
Introduction
afford spiro dihydrofuran framework readily as well.12 The above-
mentioned methods could establish the spiro dihydrofuran skeleton
effectively. However, some external volatile oxidants, e.g.,
molecular iodine should be used to complete the assembly. Hence, it
is necessary to develop an efficient alternative strategy to construct
the framework considering the atom economy and environmental
concern.
The spiro dihydrofurans are frequently presented as core units in
diverse classes of natural products showing importantly biological
significance and pharmaceutical value.1 For example, coumestans,
isolated from plants of the family of fabaceae, are used in folk
medicine against snake poison.2 The spiro dihydrofuran diterpenoid
nepetaefolin exhibits biological activities such as anti-
hypertensiveness, sedativeness, bactericidality, insecticidality and
antivirality.3 In view of their biological importance, several
procedures for the synthesis of spiro dihydrofurans have been
developed for years. The majority of approaches for the assembly of
spiro dihydrofuran include the oxidative 1,3-dipolar cycloaddition of
1,3-dicarbonyl compounds with exocyclic alkenes,4 the three-step
protocol of addition, halogenation, cyclo-dehydrohalogenation of
cyclic 1,3-diones with aldehydes,5 and the N-heterocyclic carbeneꢀ
mediated cycloaddition.6 Very recently, one-pot synthesis of
substituted dihydrofurans through Lewis base-catalyzed three-
component condensation was reported by Shi’s group.7 The NaOH-
catalyzed splitting of dimedone fragment of spiran could also give
rise to the spiro dihydrofuran derivatives in aqueous dioxane.8
Sahu’s group put forward a route towards spiro dihydrofurans by the
reaction of dimedone and aldehydes mediated by iodine and
ammonium acetate through the sequence of Knoevenagel
The electrosynthesis has provided organic chemists with novel and
versatile synthetic protocols of great promise due to its prominent
advantages including high material utilization, mild reaction
condition, decreased energy requirement, ease of control of the
reaction, less hazardous process, and the ability to perform wide
range of precisely tunable oxidation and reduction reactions.13-14
Pronounced growth of investigations in organic electrochemistry
during last three decades has made electrosynthesis one of the most
competitive methods of modern organic chemistry.15 The multi-
component reactions (MCRs) have been employed for preparing
compound libraries by virtue of straightforward reaction condition,
atomic economy, high bond forming efficiency and great diversity
generating potential.16 Methods of organic transformations based on
electrochemically induced MCRs involving carbonyl compounds
have been extensively developed.17 To continue our work on the
multi-component synthesis of heterocyclic compound library,18
herein we shall report an electrochemical pseudo multi-component
procedure for the fabrication of tricyclic spiro dihydrofuran scaffold
through the reaction of dimedone and aldehydes in an undivided cell
(Sheme 1).
condensation,
Michael
addition,
iodination
and
cyclodehydroiodination.9 In addition, several reports described the
synthesis
of
spiro
dihydrofurans
promoted
by
1,4-
diazabicyclo[2.2.2]octane (DABCO),10 Dess-Martin periodinane
(DMP) and tetraethylammonium bromide (TEAB).11 The ball-milled

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2
Tetrahedron
Under the optimal conditions, the scope and generality of the
reaction was explored. A variety of aryl aldehydes were investigated
to react with dimedone, and the results are summarized in Table 2.
This protocol can be applied not only to electron-rich (entry 10 and
entry 13) and electron-deficient (entry 7 and entry 9) aryl aldehydes,
but also to heteroaromatic aldehydes (entry 14) with excellent yields
under the mild conditions, which highlighted the wide scope of this
pseudo multi-component electrosynthesis. However, when the
aliphatic aldehydes were employed in this reaction, no expected
product was obtained.
Scheme 1
Results and discussion
In an initial study, to optimize the electrolytic conditions, the
electrochemical multi-component transformation of dimedone 1
and 4-bromobenzaldehyde 2a into 3-(4-bromophenyl)-4',4',6,6-
tetramethyl-6,7-dihydro-3H-spiro[benzofuran-2,1'-cyclohexane]-
2',4,6'(5H)-trione 3a was studied using sodium bromide as
supporting electrolyte in ethanol (Table 1).
Table 2 Electrochemical transformation of cyclic 1,3-diketones 1,
aldehyde 2, into 3-substituted-4',4',6,6-tetramethyl-6,7-dihydro-3H-
spiro[benzofuran-2,1'-cyclohexane]-2',4,6'(5H)-trione 3a.
Table 1
The optimization of electrolysis conditions for the synthesis of
3aa
Entry
Product
R
Charge
passed
Current Yield
Yield(%) of 3
(F/mol)b
(%)c
1
2
4-BrC6H4
C6H5
2.10
2.10
2.10
2.10
2.33
2.56
2.56
2.33
2.56
2.33
2.56
2.10
2.33
2.80
2.00
95
95
95
95
86
78
78
86
78
86
78
95
86
71
—
94
95
96
95
93
92
96
90
96
88
93
90
90
89
—
3a
3b
3c
3d
3e
3f
3
4-ClC6H4
4
4-FC6H4
5
3-ClC6H4
Entry
I
Time Solvent
Charge
Current Yield
6
3,4-Cl2C6H3
3-NO2C6H4
3,4-Me2C6H3
4-NO2C6H4
4-Me2NC6H4
3-CH3OC6H4
4-CH3C6H4
4-CH3OC6H4
Thien-2-yl
n-C3H7–
(mA) (min)
passed Yield(%) of 3a
(F/mol)b
2.02
(%)c
72
7
3g
3h
3i
1
2
3
4
5
6
7
50
130
65
45
30
45
50
45
EtOH
EtOH
99
99
95
86
95
86
95
8
9
100
150
250
150
150
150
2.02
83
10
11
12
13
14
15
3j
EtOH
2.10
94
3k
3l
EtOH
2.33
87
3m
3n
3o
MeOH
i-PrOH
n-BuOH
2.10
84
2.33
89
2.10
75
[a] General procedure: 1 (4 mmol), 2 (2 mmol), NaBr (1 mmol), alcohol (20 mL), iron cathode (5
cm2), graphite anode (5 cm2), current density 30 mA/cm2, at room temperature.
[a] General procedure: 1 (4 mmol), 2a (2 mmol), NaBr (1 mmol), alcohol (20 mL), iron cathode (5 cm2),
graphite anode (5 cm2), at room temperature.
[b] Calculated for aryl aldehyde 2.
[c] Yield of isolated product.
[b] Calculated for 4-bromobenzaldehyde 2a.
[c] Yield of isolated product.
With the above results and related reference taken into
consideration,20 the plausible mechanism for the electrochemical
transformation of dimedone 1, aldehydes 2 into substituted spiro
dihydrofurans 3 was proposed. The initial formation of bromine
on the anode is a well-known process and the corresponding
halogen color was observed at the anode when the electrolysis
was conducted without stirring the reaction mixture. The solvent,
EtOH was reduced to EtO-, an electrochemically generated base
(EGB) on the cathode at the same time. The condensation of
aldehyde 2 and dimedone 1 initiated by the deprotonation of 1 by
As can be seen in Table 1, the reaction proceeded to provide the
desired product 3a smoothly when the reaction was carried out under
a constant current of 150 mA after 2.10 F/mol of electricity passed.
We were pleased to find that the current of 150 mA was optimal for
the electrochemical synthetic process for the desired product was
obtained in excellent yield. However, raising the current up to 250
mA resulted in a slight decrease in the reaction yield and it should be
attributed to the oligomerization of the starting material.19 Lately, we
examined the effect of alcoholic solvents on the reactions. This
electrochemical synthesis could be carried out in n-BuOH with
relatively low conversion of starting materials. The similar results
were found in the case of MeOH and i-PrOH. Thus EtOH was the
optimal solvent for this electrochemical reaction.
EGB
would
give
rise
to
2-(arylmethylene)-5,5-
dimethylcyclohexane-1,3-dione 4. The Michael addition of
dimedone 1 to 4 yielded anion 5 in the presence of EtO-. Then,
bromination of anion 5 led to the formation of substituted

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3
bromoadduct 6, which was further cyclized into 3-substituted-
4',4',6,6-tetramethyl-6,7-dihydro-3H-spiro[benzofuran-2,1'-
cyclohexane]-2',4,6'(5H)-trione 3 (Scheme 2).
(potassium bromide) (v, cm-1): 3430, 2957, 2872, 1737, 1713,
1643, 1456, 1391, 1203, 1183, 1042, 967, 739, 701, 547; HRMS
(ESI) m/z: Calcd. for [M+Na]+C23H26NaO4: 389.1729; found:
389.1728
Br2
anode:
2 Br - 2e
Compound 3c: White solid; M.P: 262-264 oC (reported 258-
260 oC[9]); 1H NMR (400 MHz, DMSO-d6): δ 7.39 (d, J = 8.0 Hz,
2H, ArH), 7.28 (d, J = 8.0 Hz, 2H, ArH), 4.83 (s, 1H, CH), 3.66
(d, J = 15.2 Hz, 1H, CH2), 2.71 (d, J = 18.0 Hz, 1H, CH2 ), 2.58
(d, J = 17.6 Hz, 1H, CH2), 2.42 (d, J = 14.8 Hz, 1H, CH2), 2.14
(d, J = 15.6 Hz, 2H, CH2), 2.09 (d, J = 4.4 Hz, 2H, CH2),1.08 (s,
6H, 2 × CH3), 1.07 (s, 3H, CH3), 0.69 (s, 3H, CH3); IR
(potassium bromide) (v, cm-1): 2964, 2871, 1742, 1711, 1640,
1393, 1203, 1142, 1092, 1044, 837, 650, 542; HRMS (ESI) m/z:
Calcd. for [M+Na]+C23H25ClNaO4: 423.1339; found: 423.1331.
cathode: 2 EtOH + 2e
2 EtO + H2
Ar
O
O
O
O
O
O
H
O
EtO
H
Ar
2
O
1
O
O
O
OH
Ar
- H2O
O
EtOH
O
Ar
O
O
O
4
o
O
Ar
Compound 3d: White solid; M.P: 242-243 C (reported 245-
Ar
O
Br
247 oC[9]); 1H NMR (400 MHz, DMSO-d6): δ 7.30 (t, J = 6.4 Hz,
2H, ArH), 7.16 (t, J = 8.8 Hz, 2H, ArH), 4.82 (s, 1H, CH), 3.66
(d, J = 15.2 Hz, 1H, CH2), 2.71 (d, J = 18.0 Hz, 1H, CH2), 2.58
(d, J = 17.6 Hz, 1H, CH2 ), 2.42 (d, J = 15.2 Hz, 1H, CH2), 2.16-
2.04 (m, 4H, 2 × CH2), 1.08 (s, 3H, CH3), 1.07 (s, 6H, 2 × CH3),
0.69 (s, 3H, CH3); IR (potassium bromide) (v, cm-1): 2956, 1741,
1712, 1648, 1512, 1390, 1235, 1164, 1045, 845, 627; HRMS
(ESI) m/z: Calcd. for [M+Na]+C23H25FNaO4: 407.1635; found:
407.1616.
Br2
O
O
O
O
6
5
O
Ar
O
Br
Ar
O
O
O
O
Ar
O
Br
- Br
EtO
O
O
O
O
3
HO
Scheme 2.
o
1
Compound 3e: White solid; M.P: 225-226 C; H NMR (400
MHz, DMSO-d6): 7.35 (d, J = 4.0 Hz, 3H, ArH), 7.21 (s, 1H,
Conclusions
δ
In conclusion, we have presented a novel, efficient, convenient and
electrochemical way to the construction of spiro dihydrofuran
skeleton. The ready availability of the simple equipment, the
environmental benignness and the useful skeleton of the products
would make this strategy quite attractive. More importantly, these
studies not only provide a new method to form the spiro
dihydrofuran scaffold but also expand the application scope of
electrosynthesis reactions.
ArH), 4.80 (s, 1H, CH), 3.69 (d, J = 15.2 Hz, 1H, CH2), 2.74 (d, J
= 18.0 Hz, 1H, CH2), 2.58 (d, J = 18.0 Hz, 1H, CH2), 2.43 (d, J =
14.4 Hz, 1H, CH2), 2.17-2.06 (m, 4H, 2 × CH2), 1.09 (s, 3H,
CH3), 1.08 (s, 6H, 2 × CH3), 0.69 (s, 3H, CH3); 13C NMR
(100MHz, DMSO-d6): 200.0, 198.8, 192.3, 176.9, 139.2, 133.0,
130.3, 128.6, 128.1, 127.4, 112.8, 103.0, 53.0, 51.6, 50.4, 49.1,
36.3, 34.0, 30.3, 29.3, 28.0, 27.8, 25.9; IR (potassium bromide)
(v, cm-1): 2959, 2871, 1747, 1718, 1643, 1472, 1429, 1390, 1317,
1191, 1078, 1040, 949, 798, 697; HRMS (ESI) m/z: Calcd. for
[M+Na]+C23H25ClNaO4: 423.1339; found: 423.1331.
Experimental section
o
General Procedure: A mixture of cyclic 1,3-diketone (4 mmol), aryl
aldehyde (2 mmol) and sodium bromide (1 mmol) in the ethanol solvent (20
mL) was electrolyzed in an undivided cell equipped with an iron cathode and
a graphite anode at room temperature under a constant current density of 30
mA/cm2 (I = 150 mA, electrodes square 5 cm2). When the electrolysis was
finished, the solution was concentrated to one-fifth of its initial volume to
crystallize the solid product. After filtration, the crude solid product was
washed with cold solution of ethanol-water (v/v:19:1), dried under reduced
pressure to give the pure product.
Compound 3f: White solid; M.P: 252-253 C (reported 251-
252 oC[12]); 1H NMR (400 MHz, DMSO-d6): δ 7.60 (t, J = 8.4 Hz,
2H, ArH), 7.22 (d, J = 8.0 Hz, 1H, ArH), 4.83 (s, 1H, CH), 3.70
(d, J = 15.2 Hz, 1H, CH2), 2.75 (d, J = 18.0 Hz, 1H, CH2 ), 2.58
(d, J = 17.6 Hz, 1H, CH2), 2.44 (dd, J1 = 1.6 Hz, J2 = 14.8 Hz, 1H,
CH2), 2.23- 2.17 (m, 1H, CH2), 2.12 (d, J = 3.2 Hz, 2H, CH2),
2.09 (d, J = 5.6 Hz, 1H, CH2), 1.10 (s, 3H, CH3), 1.07 (s, 6H, 2 ×
CH3), 0.70 (s, 3H, CH3); IR (potassium bromide) (v, cm-1): 2963,
2874, 1748, 1720, 1644, 1471, 1390, 1193, 1038, 948, 838, 675,
613; HRMS (ESI) m/z: Calcd. for[M+Na]+C23H24Cl2NaO4:
457.0949; found: 457.0974.
Compound 3g: White solid; M.P: 202-203oC (reported 201-
203 oC[12]); 1H NMR (400 MHz, DMSO-d6): δ 8.25 (s, 1H, ArH),
8.15 (d, J = 6.8 Hz, 1H, ArH), 7.64 (t, J = 7.2 Hz, 2H, ArH), 5.02
(s, 1H, CH), 3.77 (d, J = 15.2 Hz, 1H, CH2), 2.75 (d, J = 18.0 Hz,
1H, CH2), 2.63 (d, J = 18.0 Hz, 1H, CH2), 2.45 (d, J = 14.8 Hz,
1H, CH2), 2.15 (t, J = 16.0 Hz, 2H, CH2), 2.08 (d, J = 16.0 Hz,
2H, CH2), 1.09 (s, 9H, 3 × CH3), 0.70 (s, 3H, CH3); IR
(potassium bromide) (v, cm-1): 2959, 2874, 1743, 1714, 1640,
1532, 1397, 1352, 1189, 1103, 1043, 815, 732, 691; HRMS (ESI)
m/z: Calcd. for [M+Na]+C23H25NNaO6: 434.1580; found:
434.1562.
1
Compound 3a: White solid; M.P: 287-288 oC; H NMR (400
MHz, DMSO-d6): δ 7.53 (d, J = 8.0 Hz, 2H, ArH), 7.22 (d, J =
7.6 Hz, 2H, ArH), 4.81 (s, 1H, CH), 3.65 (d, J = 14.8 Hz, 1H,
CH2), 2.71 (d, J = 18.0 Hz, 1H, CH2 ), 2.61 (s, 1H, CH2), 2.43 (d,
J = 14.8 Hz, 1H, CH2), 2.15 (d, J = 15.6 Hz, 2H, CH2), 2.08 (d, J
= 16.0 Hz, 2H, CH2), 1.09 (s, 9H, 3 × CH3), 0.70 (s, 3H, CH3);
13C NMR (100MHz, DMSO-d6): 199.6, 198. 5, 191.7, 176.3,
135.9, 131.0, 130.6, 121.0, 112.5, 102.7, 52.9, 51.7, 50.4, 49.1,
36.2, 33.6, 29.8, 29.1, 27.8, 27.6, 25.6; IR (potassium bromide)
(v, cm-1): 2964, 2871, 1741, 1710, 1640, 1393, 1045, 1008, 834,
626; HRMS (ESI) m/z: Calcd. for [M+Na]+C23H25 BrNaO4:
467.0834; found: 467.0820.
o
Compound 3b: White solid; M.P: 222-224 C (reported 232
oC[9]); 1H NMR (400 MHz, DMSO-d6): δ 7.31-7.23 (m, 5H, ArH),
4.77 (s, 1H, CH), 3.63 (d, J = 15.2 Hz, 1H, CH2), 2.69 (d, J =
17.6 Hz, 1H, CH2 ), 2.57 (d, J = 17.6 Hz, 1H, CH2), 2.41 (d, J =
15.2 Hz, 1H, CH2), 2.15-2.05 (m, 4H, 2 × CH2), 1.08 (s, 3H,
CH3) , 1.07 (s, 3H, CH3), 1.06 (s, 3H, CH3), 0.67 (s, 3H, CH3); IR
o
Compound 3h: White solid; M.P: 245-247 C (reported 242-
243 oC[12]); 1H NMR (400 MHz, DMSO-d6): δ 7.05 (d, J = 7.6 Hz,
1H, ArH), 6.96 (t J = 12.4 Hz, 2H, ArH), 4.66 (s, 1H, CH), 3.63
(d, J = 15.2 Hz, 1H, CH2), 2.69 (d, J = 17.6 Hz, 1H, CH2), 2.57
(d, J = 17.6 Hz, 1H, CH2 ), 2.40 (d, J = 14.8 Hz, 1H, CH2), 2.16

ACCEPTED MANUSCRIPT
4
Tetrahedron
1369, 1231, 1093, 1041, 735, 674; HRMS (ESI) m/z: Calcd. for
(s, 6H, 2 × CH3), 2.11-2.03 (m, 4H, 2 × CH2), 1.09 (s, 3H, CH3),
[M+Na]+ C21H24NaO4S: 395.1293; found: 395.1295.
1.07 (s, 6H, 2 × CH3), 0.68 (s, 3H, CH3); IR (potassium bromide)
(v, cm-1): 3442, 2961, 2873, 1745, 1715, 1641, 1389, 1318, 1197,
1042, 833, 652; HRMS (ESI) m/z: Calcd. for
[M+Na]+C25H30NaO4: 417.2042; found: 417.2043.
Acknowledgments
We are grateful for financial support by NSFC (No. 21242014,
21073153 and 21173180), A Project Funded by the Priority
Academic Program Development of Jiangsu Higher Education
Institutions, and the Major Basic Research Project of the Natural
Science Foundation of the Jiangsu Higher Education Institutions
(09KJA430003). This project was also sponsored by Qing Lan
Project (10qlg005).
Compound 3i: Yellow solid; M.P: 269-270 oC (reported 265-
266 oC[12]); 1H NMR (400 MHz, DMSO-d6): δ 8.20 (d, J = 8.0 Hz,
2H, ArH), 7.56 (d, J = 8.4 Hz, 2H, ArH), 5.01 (s, 1H, CH), 3.71
(d, J = 14.8 Hz, 1H, CH2), 2.74 (d, J = 17.6 Hz, 1H, CH2 ), 2.62
(d, J = 17.6 Hz, 1H, CH2), 2.46 (dd, J1 = 1.6 Hz, J2 = 15.2 Hz, 1H,
CH2), 2.18-2.05 (m, 4H, 2 × CH2), 1.09 (s, 9H, 3 × CH3), 0.70 (s,
3H, CH3); IR (potassium bromide) (v, cm-1): 2960, 1746, 1717,
1665, 1645, 1519, 1393, 1346, 1040, 869; HRMS (ESI) m/z:
Calcd. for [M+Na]+C23H25NNaO6: 434.1580; found: 434.1582.
References and notes
o
Compound 3j: Pink solid; M.P: 251-252 C (reported 250
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[2] (a) Harbone, J. B.; Mabry, T. J.; Mabry, H. The Flavonoids: Chapman
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[3] Cousins, D. J.; Medicinal, Essential Oil, Culinary Herb, and Pesticidal
Plants of the Labiatae, CAB International: Wallingford, 1994, parts 1 and
2.
oC[9]); 1H NMR (400 MHz, DMSO-d6): δ 7.04 (d, J = 9.2 Hz, 2H,
ArH), 6.61 (d, J = 8.4 Hz, 2H, ArH), 4.65 (s, 1H, CH), 3.62 (d, J
= 15.2 Hz, 1H, CH2), 2.87 (s, 6H, 2 × CH3 ), 2.64 (t, J = 17.2 Hz,
2H, CH2), 2.39 (d, J = 15.6 Hz, 1H, CH2), 2.18-2.02 (m, 4H, 2 ×
CH2), 1.09 (s, 3H, CH3), 1.08 (s, 6H, 2 × CH3), 0.69 (s, 3H, CH3);
IR (potassium bromide) (v, cm-1): 2957, 1738, 1711, 1638, 1526,
1392, 1228, 1196, 1041, 817, 674;HRMS (ESI) m/z: Calcd. for
[M+Na]+C25H31NNaO4: 432.2151; found: 432.2153.
o
Compound 3k: White solid; M.P: 208-210 C (reported 215-
218 oC[9]); 1H NMR (400 MHz, DMSO-d6): δ 7.22 (t, J = 8.0 Hz,
1H, ArH), 6.83 (d, J = 9.2 Hz, 3H, ArH), 4.73 (s, 1H, CH), 3.71
(s, 3H, CH3), 3.65 (d, J = 15.2 Hz, 1H, CH2), 2.69 (d, J = 17.6 Hz,
1H, CH2 ), 2.58 (d, J = 17.6 Hz, 1H, CH2), 2.41 (d, J = 14.8 Hz,
1H, CH2), 2.17-2.05 (m, 4H, 2 × CH2), 1.09 (s, 3H, CH3), 1.08 (s,
6H, 2 × CH3), 0.68 (s, 3H, CH3); IR (potassium bromide) (v, cm-
1): 2953, 1722, 1609, 1495, 1467, 1385, 1291, 1250, 1100, 1067,
985, 742;HRMS (ESI) m/z: Calcd. for [M+Na]+C24H28NaO5:
419.1834; found: 419.1858.
[4] (a) Muthusamy, S.; Gunanathan, C.; Babu, S. A. Synlett. 2002, 787-789;
(b) Savitha, G.; Niveditha, S. K.; Muralidharan, D.; Perumal, P. T.
Tetrahedron. Lett. 2007, 48, 2943ꢀ2947.
[5] (a) Ohkata, K.; Sakai, T.; Kubo, Y. J. Org. Chem. 1978, 43, 3070; (b)
Fedotova, O. V.; Skuratova, M. I.; Reshetov, P. V. Heterocycl.
Compounds. 2005, 41, 1480ꢀ1483; (c) Jursic, B. S.; Stevens, E. D.
Synth. Commun. 2004, 34, 3915ꢀ3923..
[6] Nair, V.; Deepthi, A.; Poonoth, M.; Santhamma, B.; Vellalath, S.; Babu,
B. P.; Mohan, R.; Suresh, E. J. Org. Chem. 2006, 71, 2313ꢀ2319.
[7] Zhong, C.; Liao, T.; Tuguldur, O.; Shi, X. Org. Lett. 2010, 12, 2064-2067.
[8] Greenberg, F. H. J. Org. Chem. 1965, 30, 1251-1253.
[9] Sahu, D. P.; Giri, S. K.; Varshney, V.; Kumar, S.; Synth. Commun. 2009,
39, 3406-3419.
[10] Chen, J.; Shi, J.; Yan, C. G.; Chem. Res. Chin. Univ. 2011, 27, 49-53.
[11] Salgaonkar, P. D.; Shukla, V. G.; Akamanchi, K. G.; Synth. Commun.
2007, 37, 275-280.
[12] Wang, G. W.; Gao, J.; Org. Lett. 2009, 11, 2385-2388.
[13] (a) Frontana-Uribe, B. A.; Little, R. D.; Ibanez, J. G.; Palma, A.;
Vasquez-Medrano, R. Green Chem. 2010, 12, 2099-2119; (b) Schaefer,
H. J. C. R. Chim. 2011, 14, 745-765.
c
Compound 3l: White solid; M.P: 228-229 C (reported 233
oC[9]); 1H NMR (400 MHz, DMSO-d6): δ 7.07 (d, J = 7.2 Hz, 2H,
ArH), 6.83 (d, J = 7.2Hz, 2H, ArH), 4.42 (s, 1H, CH), 3.77 (s, 3H,
CH3), 3.07 (d, J = 14.4 Hz, 1H, CH2), 2.65 (s, 2H, CH2), 2.53 (d,
J = 14.4 Hz, 1H, CH2), 2.20 (t, J = 16.0 Hz, 2H, CH2), 2.14 (d, J
= 2.8 Hz, 1H, CH2), 2.00 (d, J = 14.4 Hz, 1H, CH2), 1.15 (s, 6H,
2 × CH3), 1.12 (s, 3H, CH3), 0.84 (s, 3H, CH3); IR (potassium
bromide) (v, cm-1): 2952, 2874, 1741, 1713, 1641, 1395, 1200,
1046, 835, 677, 545; HRMS (ESI) m/z: Calcd. for
[M+Na]+C24H28NaO4: 403.1885; found: 403.1880.
Compound 3m: White solid; M.P: 230-231 oC (reported 223-
224 oC[9]); 1H NMR (400 MHz, DMSO-d6): δ 7.17 (d, J = 8.0 Hz,
2H, ArH), 6.85 (d, J = 8.4 Hz, 2H, ArH), 4.73 (s, 1H, CH), 3.72
(s, 3H, CH3), 3.64 (d, J = 14.8 Hz, 1H, CH2), 2.68 (d, J = 17.6 Hz,
1H, CH2 ), 2.57 (d, J = 18.0 Hz, 1H, CH2), 2.41 (d, J = 15.2 Hz,
1H, CH2), 2.15-2.04 (m, 4H, 2 × CH2), 1.08 (s, 9H, 3 × CH3),
0.68 (s, 3H, CH3); IR (potassium bromide) (v, cm-1): 2961, 1741,
1712, 1640, 1512, 1393, 1243, 1182, 1043, 839, 546; HRMS
(ESI) m/z: Calcd. for [M+Na]+C24H28NaO5: 419.1834; found:
419.1832.
[14] Novel Trends in Electroorganic Synthesis, Torii, E. S. Springer, Berlin,
1998.
[15] Organic Electrochemistry, Lund, E. H. (4th ed.), Marcel Dekker Inc.,
New York, 2001.
[16] For recent reviews, please see: (a) Ramachary, D. B.; Jain, S. Org.
Biomol. Chem. 2011, 9, 1277-1300; (b) Eckert, H. Molecules 2012, 17,
1074-1102; (c) de Graaff, C.; Ruijter, E.; Orru, R. V. A. Chem. Soc. Rev.
2012, 41, 3969-4009; (d) Singh, M. S.; Chowdhury, S. RSC Adv. 2012, 2,
4547-4592; (e) Pellissier, H. Chem. Rev. 2013, 113, 442-524. For recent
examples, see: (a) Hasaninejad, A.; Firoozi, S.; Mandegani, F.
Tetrahedron Lett. 2013, 54, 2791-2794; (b) Ghandi, M.; Momeni, T.;
Nazeri, M. T.; Zarezadeh, N.; Kubicki, M. Tetrahedron Lett. 2013, 54,
2983-2985; (c) Jadhav, N. C.; Jagadhane, P. B.; Patile, H. V.; Telvekar,
V. N. Tetrahedron Lett. 2013, 54, 3019-3021.
Compound 3n: Yellow solid; M.P: 251-253oC (reported 246-
o
1
248 C[12]); H NMR (400 MHz, DMSO-d6): δ 7.44 (d, J = 4.8
Hz, 1H, ArH), 7.23 (d, J = 2.4 Hz, 1H, ArH), 6.98 (dd, J1 = 3.6
Hz, J2 = 5.2 Hz, 1H, ArH), 5.24 (s, 1H, CH), 3.69 (d, J = 15.2
Hz, 1H, CH2), 2.62 (s, 2H, CH2), 2.48 (s, 1H, CH2), 2.44 (d, J =
2.8 Hz, 1H, CH2), 2.42 (dd, J1 = 2.8 Hz, J2 = 14.8 Hz, 1H, CH2),
2.18 (d, J = 5.6 Hz, 1H, CH2), 2.07 (d, J = 16.0 Hz, 1H, CH2),
1.13 (s, 6H, 2 × CH3), 1.09 (s, 3H, CH3), 0.70 (s, 3H, CH3); IR
(potassium bromide) (v, cm-1): 2958, 2874, 1738, 1712, 1641,
[17] Ilovaisky, A. I.; Merkulova, V. M.; Elinson, M. N.; Nikishin, G. I. Russ.
Chem. Rev. 2012, 81, 381-396.
[18] (a) Yao, C. S.; Wang, C. H.; Jiang, B.; Tu, S. J. J. Comb. Chem. 2010,
12, 472-475; (b) Yao, C. S.; Lei, S.; Wang, C. H.; Yu, C. X.; Tu, S. J.
J. Heterocycl. Chem. 2008, 45, 1609-1613; (c) Yao, C. S.; Lei, S.;
Wang, C. H.; Yu, C. X.; Tu, S. J. Chin. J. Chem. 2008, 26, 2107-2111;
(d) Yao, C. S.; Wang, D. L; Lu, J.; Qin, B. B.; Zhang, H. H.; Li, T. J.;
Yu, C. X. Tetrahedron. Lett. 2011, 52, 6162-6165; (e) Yao, C. S.;
Jiang, B.; Li, T. J.; Qin, B. B.; Feng, X. D.; Zhong, H. H.; Wang, C. H.;

ACCEPTED MANUSCRIPT
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Tu, S J. Bioorg. Med. Chem. Lett. 2011, 21, 599-601; (f) Li, T. J.;
Feng, X. D.; Yao, C. S.; Yu, C. X.; Jiang, B.; Tu, S. J. Bioorg. Med.
Chem. Lett. 2011, 21, 453-455; (g) Yu, C. X.; Li, T. J.; Lu, J.; Wang,
D. L.; Qin, B. B.; Zhang, H. H.; Yao, C. S. Synlett. 2011, 2420-2424.
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A.; Nikishin, G. I. Tetrahedron 2012, 68, 1198-1206; (b) Vereshchagin,
A. N.; Elinson, M. N.; Dorofeeva, E. O.; Stepanov, N. O.;
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