Diversity oriented approach to phenylalanine derivatives via the dielsalder reaction involving sulfolene intermediates

Article abstract of DOI:10.3987/COM-14-S(K)9

We report a new synthetic approach to highly functionalized phenylalanine derivatives via sulfolenes as latent diene equivalents. Here, the DielsAlder reaction has been used as a key step to assemble diverse unusual amino acid derivatives.

Full text of DOI:10.3987/COM-14-S(K)9

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HETEROCYCLES, Vol. 90, No. 1, 2015
HETEROCYCLES, Vol. 90, No. 1, 2015, pp. 226 - 237. © 2015 The Japan Institute of Heterocyclic Chemistry
Received, 18th February, 2014, Accepted, 9th May, 2014, Published online, 19th May, 2014
DOI: 10.3987/COM-14-S(K)9
DIVERSITY
ORIENTED
APPROACH
TO
PHENYLALANINE
DERIVATIVES VIA THE DIELSALDER REACTION INVOLVING
SULFOLENE INTERMEDIATES†
Sambasivarao Kotha* and Vijayalakshmi Bandi
Department of Chemistry, Indian Institute of Technology-Bombay, Powai,
Mumbai-400076, India, Fax: +91(22)-2572 7152; E-mail: srk@chem.iitb.ac.in
th
†This paper is dedicated to Prof. Isao Kuwajima on the occasion of his 77
birthday.
Abstract – We report a new synthetic approach to highly functionalized
phenylalanine derivatives via sulfolenes as latent diene equivalents. Here, the
DielsAlder reaction has been used as a key step to assemble diverse unusual
amino acid derivatives.
INTRODUCTION
Unusual α-amino acids (AAAs) play a critical role in modulating the stability and the activity of
1
therapeutically useful peptides. In this regard, development of general methods to a library of unusual
AAA derivatives with varied electronic and steric properties is warranted for structure activity or
2
-4
conformational activity relationships. In view of limited reports available for the synthesis of unusual
AAA derivatives using DielsAlder (DA) reaction as a key step, we envisioned a major program based on
5
-7
DA approach that can deliver a series of unusual AAA derivatives. Sulfolene derivatives are known to
8
be useful for the synthesis of natural products. For example, alkylation of 3-sulfolenes followed by
desulfonylation generate a facile stereoselective method for the synthesis of (E)-, (E)(Z)-, and
9
,10
(
E)(E)-conjugated dienes.
Although, a number of methods are available to generate conjugated dienes
11
based on organometallic reagents, thermal desulfonylation of 3-sulfolenes has been a well established
1
2
method for this purpose. Here, we report a new method to generate phenylalanine derivatives using
sulfolenes as a diene equivalent.

HETEROCYCLES, Vol. 90, No. 1, 2015
227
RESULTS AND DISCUSSION
Two sulfolene based AAA derivatives 1, and 2 were chosen as our initial targets. These sulfolene
derivatives on DA reaction with a suitable dienophile followed by aromatization can deliver highly
functionalized phenylalanine based AAA derivatives (Figure 1).
Figure 1. Sulfolene based AAA derivatives
We have shown that the (dibromomethyl)sulfolene 3 on coupling with ethyl isocyanoacetate (EICA) in
the presence of 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP)
gave the isonitrile derivative 4 in low yields (Scheme 1). Efforts to improve the yields of the coupling
1
3
product 4 were not successful.
Scheme 1. Alkylation of dibromide 3 with ethyl isocyanoacetate
In another occasion, attempts to alkylate ethyl isocyanoacetate with 2-bromomethyl-1,3-butadiene 5 or
(
bromomethyl)sulfolene 7 failed to give the alkylated product, and therefore, the amino acid based diene
1
4
6
could not be realized (Scheme 2).
Scheme 2. Attempted synthesis of amino acid based diene 6
Although sulfolene involvement in DA chemistry is well established, from the two examples 3 and 7
discussed earlier it is clear that attaching amino acid fragment to sulfolene moiety is not a simple task.
Therefore, the challenge is: creation of C-C bond with glycine equivalent and sulfolene moiety.

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HETEROCYCLES, Vol. 90, No. 1, 2015
To begin with, cheleotropic addition of SO
2
to 2-methyl-1,3-butadiene 8 gave the known sulfolene
derivative 9 in 83% yield. Allylic bromination of the sulfolene 9 with N-bromosuccinimide (NBS) in
dry CHCl in the presence of benzoyl peroxide gave the bromo compound 7 (47%), which on treatment
with K CO in dry acetonitrile furnished the unsaturated compound 10 via an intermediate 7A. Since most
of the reactions of 7 with base resulted in the low yields of 10 caused to the side-reaction. Coupling of
sulfone 10 with diethyl acetamidomalonate (DEAM) in the presence of
,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave the corresponding conjugate addition product 1 in 14%
1
5
3
2
3
1
yield. Several other reaction conditions to obtain amino acid derivative 1 or its equivalent involving
various bases and other glycine equivalents were not successful. After considerable amount of
experimentation, we found that the bromo derivative 7 on treatment with DEAM in the presence of
1
,1,3,3-tetramethylguanidine (TMG) in dry acetonitrile gave the required product 1 in 34% yield. During
this sequence, we obtained the formation of 10 as an intermediate which is indicated by TLC. However,
0 have been used to generate 1 (Scheme 3).
1
Scheme 3. Synthetic route to the amino acid derivative 1
Sulfolene based amino acid derivative 1 on DA reaction under microwave conditions with dimethyl
acetylenedicarboxylate (DMAD) in 1,2-dichlorobenzene at 150 C gave 12. However, naphthoquinone 14,
and anthraquinone 17 on DA with 1 in 1,2-dichlorobenzene at 160 C furnished the corresponding DA
adducts 15 and 18 under microwave irradiation conditions. We did not characterize the DA adducts,
because some of these adducts were contaminated with partially aromatized products. Therefore, these
DA adducts were directly treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to deliver the
corresponding aromatized products 13, 16, and 19 respectively (Table 1).

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229
Table 1. List of unusual AAA derivatives prepared by DA strategy via 1
S. No
Dienophile
DA adduct
Aromatised product Yield
CO Me
CO Et
2
CO Et
2
2
MeO C
MeO C
2
2
CO Et
CO Et
2
1
2
NHCOMe
NHCOMe
MeO C
MeO C
2
CO Me
2
2
1
3, (56%)
1
2
11
O
O
O
CO Et
O
2
CO Et
2
CO Et
2
CO Et
2
2
NHCOMe
NHCOMe
O
O
16,
(
57%)
14
15
O
O
O
O
CO Et
2
CO Et
2
CO Et
2
CO Et
2
3
NHCOMe
NHCOMe
17
O
19, (61%)
18
O
Along similar lines, the reaction of 2,3-dimethyl-1,3-butadiene 20 with SO
2
in the presence of
hydroquinone in dry methanol gave the (dimethyl)sulfolene 21 (96%) which on allylic bromination with
16
3
NBS in dry CHCl in the presence of benzoyl peroxide gave the dibromide 3 in 36% yield. Later,
2 3
treatment of the dibromide 3 with DEAM in the presence of K CO in dry acetonitrile gave the
unsaturated compound 22 in 33% yield.
Scheme 4. Synthetic route to amino acid derivative 2
Coupling of the conjugated sulfolene 22 with DEAM in the presence of DBU in dry acetonitrile gave the
coupling product 2 (16%). To improve the yield of the desired bis armed amino acid derivative 2, we had
investigated an alternate protocol and found that the dibromide 3 on coupling with DEAM in the presence
of TMG in dry acetonitrile gave the dialkylated product 2 in a better yield (Scheme 4).

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HETEROCYCLES, Vol. 90, No. 1, 2015
Table 2. List of unusual AAA derivatives prepared by DA strategy via 2
DA reaction of sulfolene derivative 2 on DA reaction under microwave conditions with DMAD 11 in
1
,2-dichlorobenzene at 150 C gave 23, whereas naphthoquinone 14 and anthraquinone 17 on DA with 2
in 1,2-dichlorobenzene at 160 C furnished the corresponding DA adducts 25 and 27, these DA adducts
were contaminated with aromatized products, respectively. The corresponding mixtures were
subsequently treated with DDQ to obtain 24, 26, and 28, respectively (Table 2).
Although the yields of the alkylation step are somewhat low, the starting materials are readily available
and also inexpensive, the overall process to prepare unusual AAA derivatives is a useful addition to the
existing methods to prepare these unusual AAA derivatives. Moreover, the length of the sequence
involved to assemble the key building blocks 1 and 2 is short. In view of these considerations, our DA
approach to unusual AAA is likely to play important role in design of peptidomimetics.
In summary, we have synthesized a series of highly functionalized unusual phenylalanines by DA reaction
of sulfolenes derived from DEAM as the glycine equivalent. Various points for diversification are
embedded in our strategy and thus provide opportunity to generate a library of unusual phenylalanine
derivatives. By our methodology, these unusual AAAs are readily accessible from easily available starting
materials such as 3 and 7 in three steps. The strategy demonstrated here can provide access to bis-armed
AAA derivatives such as 24, which are not accessible by conventional coupling strategies. For example,
dibromo compound 29 on coupling with DEAM gave 1,2,3,4-tetrahydroisoquinoline- 3-carboxylic acid
1
7
(
Tic) derivative 30. DA strategy can deliver bis armed AAA derivatives such as 24.

HETEROCYCLES, Vol. 90, No. 1, 2015
231
Scheme 5. Preparation of Tic containing AAA derivatives
EXPERIMENTAL
All the reactions were monitored by using TLC technique with appropriate solvents for the development.
Oxygen sensitive reagents reactions were performed in dry solvents. Acetonitrile was distilled over CaH
2
.
Dry toluene was obtained by distillation over sodium benzophenone ketyl freshly prior to use. Reported
yields are isolated yields of the products after purification. All the commercial grade reagents were used
without any further purification. Generally NMR samples were made in chloroform-d solvent and chemical
shifts were reported in  scale using tetramethylsilane (TMS) as an internal standard. The standard
abbreviation s, d, t, q and m, refer to singlet, doublet, triplet, quartet, and multiplet, respectively. Coupling
constants (J) were reported in Hertz. All microwave irradiated reactions were performed with a Discover
SP CEM Microwave apparatus. The reactions were carried out in 10 mL glass tubes, sealed with Teflon™
septum and placed in the microwave cavity. The reaction mixture was irradiated at a required ceiling
temperature using maximum power for the stipulated time; the reaction mixture temperatures were
measured by an external IR sensor.
Compound 1
Procedure A. To a solution of diethyl acetamidomalonate (108 mg, 0.49 mmol) in dry MeCN (5 mL) was
added DBU (88 mg, 0.57 mmol) at 0 C and was added compound 10 (50 mg, 0.38 mmol) in dry MeCN
(
5 mL) and the reaction mixture was stirred at rt for 4 h. At the conclusion of the reaction (TLC
monitoring), MeCN was removed and the reaction mixture was quenched with cold water. The product
was extracted with CHCl and the organic layer was dried over MgSO . The crude product was purified
3
4
by silica gel column chromatography. Elution of the column with 40% EtOAc/petroleum ether gave the
desired product (18 mg, 14%) as a colorless solid.
Procedure B. To a solution of diethyl acetamidomalonate (372 mg, 1.71 mmol) in MeCN (10 mL) was
added 1,1,3,3-tetramethylguanidine (362 mg, 3.14 mmol) and then the compound 7 (300 mg, 1.42 mmol)
dissolved in MeCN (5 mL) was added drop wise and the reaction mixture was stirred at rt for 48 h. At the
conclusion of the reaction (TLC monitoring), the MeCN was removed and the reaction mixture was
quenched with cold water. The product was extracted with EtOAc and the organic layer was dried over
MgSO . The crude product was purified by silica gel column chromatography. Elution of the column with
4
4
0% EtOAc/ petroleum ether gave the desired product 1 (168 mg, 34%) as a colorless solid.

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1
Mp 102 C; H-NMR (400 MHz, CDCl )  = 1.27 (t, J = 7.1 Hz, 6H), 2.05 (s, 3H), 3.30 (s, 2H), 3.63 (s,
3
1
3
2
1
1
H), 3.75 (s, 2H), 4.23-4.30 (m, 4H), 5.77 (s, 1H), 6.85 (s, 1H); C-NMR (100 MHz, CDCl
3
)  = 169.8,
67.4, 133.4, 122.8, 65.8, 63.3, 58.0, 56.6, 36.5, 23.1, 14.1; IR (KBr): max = 3403, 3054, 2986, 1740,
-1
7
684, 896, 740 cm ; “accurate mass” electrospray ionization (ESI), (Q-Tof) calculated for C14H22NO S
+
[
M+H] 348.1111, found: 348.1119.
Compound 13
To a solution of compound 1 (100 mg, 0.28 mmol) in 1,2-dichlorobenzene (1.3 mL) was added DMAD 11
245 mg, 1.72 mmol) and was irradiated in a microwave oven at 150 C for 15 min. At the conclusion of
(
the reaction (TLC monitoring), the crude product was purified by column chromatography to give the
mixture of DA adduct and aromatized product (90 mg). The adduct was dissolved in dry toluene (10 mL),
added DDQ (96 mg) and then refluxed for 22 h. At the conclusion of the reaction (TLC monitoring),
toluene was removed and the reaction mixture was quenched with 2% KOH solution. The product was
extracted with EtOAc and the organic layer was washed with water and brine solution. The organic layer
4
was dried over MgSO and the crude product was purified by silica gel column chromatography. Elution
of the column with 40% EtOAc/ petroleum ether gave the aromatized product 13 (68.4 mg, 56%).
1
Mp 98 C; H-NMR (400 MHz, CDCl
3
)  = 1.30 (t, J = 7.1 Hz, 6H), 2.04 (s, 3H), 3.73 (s, 2H), 3.89 (s,
= 7.9 Hz, J = 1.6 Hz, 1H), 7.37 (d, J
1.5 Hz, 1H), 7.62 (d, J = 7.8 Hz, 1H); C-NMR (100 MHz, CDCl )  = 168.2, 166.6, 166.5, 165.9,
3
H), 3.90 (s, 3H), 4.27 (q, J = 7.1 Hz, 4H), 6.54 (s, 1H), 7.17 (dd, J
1
2
1
3
=
3
1
2
37.9, 131.3, 130.8, 129.6, 129.2, 127.8, 65.7, 61.8, 51.4, 36.2, 21.8, 12.8; IR (KBr): max = 3401, 3019,
-1
977, 1739, 1675, 1216, 760, 669 cm ; “accurate mass” electrospray ionization (ESI), (Q-Tof) calculated
+
for C20
H26NO
9
[M+H] 424.1602, found: 424.1613.
Compound 16
To a solution of compound 1 (30 mg, 0.08 mmol) in 1,2-dichlorobenzene (1.2 mL) was added
naphthoquinone 14 (20.7 mg, 0.13 mmol) and was irradiated in a microwave oven at 160 C for 15 min.
At the conclusion of the reaction (TLC monitoring), the crude product was purified by column
chromatography to give a mixture of partially aromatized DA adduct (24 mg). The adduct was dissolved
in dry toluene (10 mL), added DDQ (49.3 mg) and the reaction mixture was refluxed for 24 h. At the
conclusion of the reaction (TLC monitoring), toluene was removed and the reaction mixture was
quenched with 2% KOH solution. The product was extracted with EtOAc and the organic layer was
washed with water and brine solution. The organic layer was dried over MgSO and the crude product
4
was purified by silica gel column chromatography. Elution of the column with 40% EtOAc/ petroleum
ether gave the aromatized product 16 (21.6 mg, 57%) as a colorless solid.
1
Mp 209 C; H-NMR (400 MHz, CDCl
3
)  = 1.34 (t, J = 7.1 Hz, 6H), 2.09 (s, 3H), 3.85 (s, 2H), 4.31 (q,

HETEROCYCLES, Vol. 90, No. 1, 2015
233
J = 7.1 Hz, 4H), 6.57 (s, 1H), 7.45 (dd, J
1 2
= 7.9 Hz, J = 1.6 Hz, 1H), 7.79-7.83 (m, 2H), 7.96 (d, J = 1.4
13
Hz, 1H), 8.22 (d, J = 7.8 Hz, 1H), 8.27-8.32 (m, 2H); C-NMR (100 MHz, CDCl )  = 183.1, 183.0,
3
1
3
69.6, 167.3, 142.6, 135.9, 134.4, 134.3, 133.6, 133.5, 133.5, 132.6, 128.4, 127.5, 127.4, 127.3, 67.1, 63.3,
-1
8.0, 29.8, 23.2, 14.2; IR (KBr): max = 3406, 3019, 2950, 1735, 1679, 758, 1216, 669 cm ; “accurate
+
mass” electrospray ionization (ESI), (Q-Tof) calculated for C24
38.1549.
Compound 19
H24NO
7
[M+H] 438.1547, found:
4
To a solution of compound 1 (30 mg, 0.08 mmol) in 1,2-dichlorobenzene (1.2 mL) was added
anthraquinone 17 (36 mg, 0.17 mmol) and was irradiated in a microwave oven at 160 C for 15 min. At
the conclusion of the reaction (TLC monitoring), the crude product was purified by column
chromatography to give the mixture of DA and partially aromatized adduct (29 mg), which was dissolved
in dry toluene (10 mL), added DDQ (53.4 mg) and the reaction mixture was irradiated in a microwave
oven at 120 C for 1 h. At the conclusion of the reaction (TLC monitoring), toluene was removed and
quenched with 2% KOH solution. The product was extracted with EtOAc and the organic layer was
4
washed with water and brine solution. The organic layer was dried over MgSO and the crude product
was purified by silica gel column chromatography. Elution of the column with 50% EtOAc/ petroleum
ether gave the aromatized product 19 (26 mg, 61%) as a yellow solid.
1
Mp 265 C; H-NMR (400 MHz, CDCl
3
)  = 1.36 (t, J = 7.1 Hz, 6H), 2.11 (s, 3H), 3.86 (s, 2H),
= 7.9 Hz, J = 1.6 Hz, 1H), 7.69-7.71 (m, 2H), 8.04-8.12 (m,
4
3
1
3
.34-4.31 (m, 4H), 6.60 (s, 1H), 7.47 (dd, J
H), 8.29 (d, J = 7.9 Hz, 1H), 8.83 (d, J = 8.3 Hz, 2H); C-NMR (100 MHz, CDCl
69.7, 167.3, 142.7, 136.0, 135.3, 135.3, 134.5, 133.6, 130.3, 129.9, 129.8, 129.7, 128.7, 127.8, 67.2, 63.3,
1
2
1
3
3
) = 183.0, 182.8,
-1
8.1, 29.8, 23.2, 14.2; IR (KBr): max 3247, 3049, 2928, 1745, 1668, 758, 702 cm ; “accurate mass”
+
electrospray ionization (ESI), (Q-Tof) calculated for C28
H
25NNaO
7
[M+Na] 510.1523, found: 510.1519.
Compound 22
To a solution of diethyl acetamidomalonate (360 mg, 1.65 mmol) in dry MeCN (20 mL) was added
K CO (565 mg, 4.09 mmol) and refluxed for 15 min. Then compound 3 (250 mg, 0.82 mmol) was added
2
3
and refluxed for 4 h. At the conclusion of the reaction (TLC monitoring), the reaction mixture was filtered
through celite pad and acetonitrile was removed to get the crude compound, which was purified by silica
gel column chromatography. Elution of the column with 40% EtOAc/ petroleum ether gave the desired
product 22 (98 mg, 33%).
1
Mp 123 C; H-NMR (400 MHz, CDCl
3
) = 1.27 (t, J = 7. 1 Hz, 6H), 2.03 (s, 3H), 3.55 (s, 2H), 3.91 (s,
13
2
H), 4.19-4.31 (m, 4H), 5.36 (s, 1H), 5.59 (s, 1H), 6.41 (s, 1H), 6.84 (s, 1H); C-NMR (100 MHz,
CDCl ) = 170.1, 167.0, 145.6, 137.0, 131.5, 114.6, 65.5, 63.5, 53.9, 29.4, 23.1, 14.1; IR (KBr): max
3

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HETEROCYCLES, Vol. 90, No. 1, 2015
-1
3
407, 3019, 1741, 1680, 851, 759, 669 cm ; “accurate mass” electrospray ionization (ESI), (Q-Tof)
+
calculated for C15
Compound 2
7
H21NNaO S [M+Na] 382.0931, found: 382.0932.
Procedure A. To a solution of diethyl acetamidomalonate (26.5 mg, 0.12 mmol) in dry MeCN (10 mL)
was added DBU (20.3 mg, 0.13 mmol) at 0 C and then added compound 22 (40 mg, 0.11 mmol)
dissolved in dry MeCN drop wise and stirred the reaction mixture for 5 h. At the conclusion of the
reaction (TLC monitoring), MeCN was removed and quenched with cold water. The product was
4
extracted with EtOAc and the organic layer dried over MgSO . The crude product was purified by silica
gel column chromatography. Elution of the column with 40% EtOAc/ petroleum ether gave the desired
product 2 (10 mg, 16%) as a colorless solid.
Procedure B. To a solution of diethyl acetamidomalonate (428 mg, 1.97 mmol) and MeCN (10 mL) was
added 1,1,3,3-tetramethylguanidine (303 mg, 2.63 mmol). Then, the compound 3 (200 mg, 0.65 mmol)
dissolved in MeCN (5 mL) was added drop wise and the reaction mixture was stirred at rt for 2.5 days. At
the conclusion of the reaction (TLC monitoring), MeCN was removed and quenched with cold water. The
4
product was extracted with EtOAc and the organic layer dried over MgSO . The crude product was
purified by silica gel column chromatography. Elution of the column with 40% EtOAc/ petroleum ether
gave the desired product 2 (136 mg, 38%) as a colorless solid.
1
Mp 178 C; H-NMR (400 MHz, CDCl
3
)  = 1.27 (t, J = 7. 1 Hz, 12H), 2.05 (s, 6H), 3.25 (s, 4H), 3.65 (s,
1
3
4
5
H), 4.21-4.32 (m, 8H), 6.85 (s, 2H); C-NMR (100 MHz, CDCl  = 170.0, 167.3, 130.6, 65.7, 63.4,
3
-1
8.6, 31.8, 23.1, 14.0; IR (KBr): max = 3405, 3020, 1740, 1680, 858, 758, 669 cm . “accurate mass”
+
electrospray ionization (ESI), (Q-Tof) calculated for C24
H
37
N
2
O
12S [M+H] 577.2067, found: 577.2078.
Compound 24
To a solution of compound 2 (50 mg, 0.08 mmol) in 1,2-dichlorobenzene (1.2 mL) was added DMAD 11
24.62 mg, 0.17 mmol) and was irradiated in a microwave oven at 150 C for 15 min. At the conclusion
(
of the reaction (TLC monitoring), crude product was purified by stirring with 20 mL of petroleum ether
and kept in refrigerator for 10 h followed by decantation and reprecipitated the product with
EtOAc/petroleum ether to give the mixture of DA and aromatized adducts (41 mg). The adduct was
dissolved in dry toluene (10 mL), added DDQ (24.4 mg) and the reaction mixture was refluxed for 27 h.
At the conclusion of the reaction (TLC monitoring), the toluene was removed and quenched with 2%
KOH solution. The product was extracted with DCM and the organic layer was washed with water and
brine solution. The organic layer dried over MgSO and the crude product was purified by silica gel
4
column chromatography. Elution of the column with 45% EtOAc/ petroleum ether gave the aromatized
product 24 (36.9 mg, 65%) as a colorless solid.

HETEROCYCLES, Vol. 90, No. 1, 2015
235
1
Mp 166 C; H-NMR (400 MHz, CDCl )  = 1.30 (t, J = 3.5 Hz, 12H), 2.07 (s, 6H), 3.63 (s, 4H), 3.87 (s,
3
1
3
6
H), 4.24-4.30 (m, 8H), 6.45 (s, 2H), 7.26 (s, 2H); C-NMR (100 MHz, CDCl
3
) = 169.8, 167.6, 167.2,
1
38.2, 132.2, 130.4, 66.5, 63.2, 52.8, 33.2, 23.0, 14.0; IR (KBr): max 3368, 2925, 2851, 1738, 1666, 741
-1
+
cm ; “accurate mass” electrospray ionization (ESI), (Q-Tof) calculated for C30
53.2552, found: 653.2556.
Compound 26
41 2
H N O14 [M+H]
6
To a solution of compound 2 (40 mg, 0.06 mmol) in 1,2-dichlorobenzene (1.2 mL) was added
naphthoquinone 14 (14.2 mg, 0.09 mmol) and was irradiated in a microwave oven at 160 C for 20 min.
At the conclusion of the reaction (TLC monitoring), the crude product was purified by column
chromatography to give the mixture of DA adduct and partially aromatized adduct (36 mg). The mixture
was dissolved in dry toluene (1.2 mL), added DDQ (16.4 mg) and the reaction mixture was irradiated in a
microwave oven at 120 C for 1 h. At the conclusion of the reaction (TLC monitoring), toluene was
removed and quenched with 2% KOH solution. The product was extracted with EtOAc and the organic
4
layer was washed with water and brine solution. The organic layer dried over MgSO and the crude
product was purified by silica gel column chromatography. Elution of the column with 50% EtOAc/
petroleum ether gave the aromatized product 26 (25.9 mg, 56%) as a pale yellow solid.
1
Mp 228 C; H-NMR (400 MHz, CDCl
3
) = 1.26 (t, J = 7.1 Hz, 12H), 2.06 (s, 6H), 3.72 (s, 4H),
= 5.8 Hz, J = 3.3 Hz, 2H), 7.84 (s, 2H), 8.19 (dd, J = 5.7
= 3.3 Hz, 2H); C-NMR (100 MHz, CDCl ) = 182.9, 169.9, 167.3, 141.8, 134.3, 133.6, 131.8,
4
.18-4.26 (m, 8H), 6.43 (s, 2H), 7.72 (dd, J
1
2
1
1
3
Hz, J
2
3
-1
1
30.1, 127.3, 66.7, 63.3, 33.5, 23.1, 14.0; IR (KBr): max = 3379, 3054, 2851, 1749, 1673, 803, 743 cm ;
+
“
39 2
accurate mass” electrospray ionization (ESI), (Q-Tof) calculated for C34H N O12 [M+H] 667.2498,
found: 667.2494.
Compound 28
To a solution of compound 2 (50 mg, 0.08 mmol) in 1,2-dichlorobenzene (1.3 mL) was added
anthraquinone 17 (36 mg, 0.17 mmol) and was irradiated in a microwave oven at 160 C for 30 min. At
the conclusion of the reaction (TLC monitoring), the crude product was purified by column
chromatography (60% EtOAc/petroleum ether) to give the mixture of DA adduct and partially aromatized
product (45 mg). The mixture was dissolved in dry toluene (2 mL), added DDQ (50.3 mg) and the
reaction mixture was irradiated in a microwave oven at 120 C for 2 h. At the conclusion of the reaction
(
TLC monitoring), toluene was removed and quenched with 2% KOH solution. The product was
extracted with EtOAc and the organic layer was washed with water and brine solution. The organic layer
dried over MgSO and the crude product was purified by silica gel column chromatography. Elution of
4
the column with 60% EtOAc/ petroleum ether gave the aromatized product 28 (36 mg, 58%) as a yellow

236
HETEROCYCLES, Vol. 90, No. 1, 2015
solid.
Mp decomposed at 262 C; H-NMR (400 MHz, CDCl
1
3
) = 1.28 (t, J = 7 Hz, 12H), 2.09 (s, 6H), 3.74 (s,
= 3.1 Hz, J = 6.2 Hz, 2H), 7.93 (s, 2H), 8.02 (dd, J
= 6.2 Hz, 2H), 8.75 (s, 2H); C-NMR (100 MHz, CDCl ) = 182.7, 169.9, 167.3, 141.9, 135.3,
32.7, 130.4, 130.3, 129.9, 129.7, 66.8, 63.3, 33.6, 23.1, 14.0; IR (KBr): max = 3362, 2956, 2923, 1739,
4
3
1
1
H), 4.20-4.27 (m, 8H), 6.45 (s, 2H), 7.64 (dd, J
1
2
1
=
1
3
.1 Hz, J
2
3
-1
670, 877, 762 cm ; “accurate mass” electrospray ionization (ESI), (Q-Tof) calculated for
+
C H N NaO [M+Na] 739.2473, found: 739.2477.
3
8
40
2
12
ACKNOWLEDGEMENTS
We thank Department of Science and Technology and Council for Scientific and Industrial Research, New
Delhi for financial support. S. K. thanks DST-New Delhi for the award of a J. C. Bose fellowship.
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