Classical Example of Total Kinetic and Thermodynamic Control: The Diels-Alder Reaction between DMAD and Bis-furyl Dienes

Article abstract of DOI:10.1021/acs.joc.8b00336

A rare example of chemospecificity in the tandem Diels-Alder reaction of activated alkynes and bis-dienes has been revealed. The reaction between bis-furyl dienes and DMAD occurs at 25-80 °C and leads to kinetically controlled pincer adducts, 4a,8a-disubstituted 1,4:5,8-diepoxynaphthalenes. On the contrary, only thermodynamically controlled domino adducts (2,3-disubstituted 1,4:5,8-diepoxynaphthalenes) are formed in the same reaction at 140 °C. The pincer adducts can be transformed to the domino adducts at heating. The rate constants for reactions of both types were calculated using dynamic ¹H NMR spectroscopy.

Full text of DOI:10.1021/acs.joc.8b00336

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pubs.acs.org/joc
Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX
Classical Example of Total Kinetic and Thermodynamic Control: The
Diels−Alder Reaction between DMAD and Bis-furyl Dienes
Kseniya K. Borisova,† Elizaveta A. Kvyatkovskaya,† Eugeniya V. Nikitina,† Rinat R. Aysin,‡
Roman A. Novikov,§ and Fedor I. Zubkov*,†
†Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, Moscow 117198, Russian Federation
‡Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov Street, Moscow, 119991, Russian
Federation
§V. A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov Street, Moscow, 119991, Russian
Federation
S
* Supporting Information
ABSTRACT: A rare example of chemospecificity in the tandem Diels−Alder reaction of activated alkynes and bis-dienes has
been revealed. The reaction between bis-furyl dienes and DMAD occurs at 25−80 °C and leads to kinetically controlled “pincer”
adducts, 4a,8a-disubstituted 1,4:5,8-diepoxynaphthalenes. On the contrary, only thermodynamically controlled “domino” adducts
(2,3-disubstituted 1,4:5,8-diepoxynaphthalenes) are formed in the same reaction at 140 °C. The “pincer” adducts can be
transformed to the “domino” adducts at heating. The rate constants for reactions of both types were calculated using dynamic 1H
NMR spectroscopy.
he phenomenon of thermodynamic and kinetic control is
view, tandem and domino reactions involving several
Tunique in organic chemistry, and it is the easiest method consecutive [4+2] cycloaddition steps are the most attractive
and widely used in the total synthesis of natural products, due
to the possibility of a simultaneous creation of four or more
new σ-bonds with the controlled stereochemistry.3
However, a limited number of examples of the intramolecular
Diels−Alder (IMDA) reactions that can lead to either
kinetically or thermodynamically controlled products, depend-
ing on temperature, are currently known.4 To the best of our
knowledge, there are only two examples of full kinetic and
thermodynamic control in the IMDA reaction.5
The impetus for the present study was given by the article by
Lautens and Fillion published in 1997, which described the
tandem [4+2] cycloaddition between dimethyl acetylenedicar-
boxylate (DMAD) and bis-furyl dienes (1a−c,e) at rt (Scheme
1), leading to the formation of compounds 3a−c,e only.6a
Later, some useful transformations of the obtained pincer
adducts 3 were demonstrated.6b
for the control of stereo-, regio-, or chemoselectivity, since it
allows alteration the direction of the reaction pathway by
varying only temperature and keeping the rest of the
parameters unchanged.
A very limited set of reactions illustrate this principle to a full
extent. Among them, textbook examples of the sulfonation of
phenol, aniline, and naphthalene are worth citing here.
However, even in these simplest examples, no full kinetic (or
vice versa thermodynamic) control is achieved since mixtures of
regioisomeric arenesulfonic acids are formed both at high and
especially low temperatures. In more complicated cases, the
practical application of the kinetic/thermodynamic control is
seriously hindered or rendered impossible by the formation of
isomers.
Woodward and Baer were first to report the formation of
kinetically and thermodynamically controlled adducts in the
Diels−Alder reaction as early as 1948.1 Since then, a significant
amount of information about the reversibility of the [4+2]
cycloaddition has been obtained.2 From a practical point of
Received: February 5, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.8b00336
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Scheme 1. Temperature Control in the Course of the Tandem IMDA Reaction between 1 and DMAD
a
Scheme 2. Gibbs Free Energy Profile for the Reaction between 1f and DMAD
a
Computed potential energy surfaces (ΔG°) for pathways to 3f and 4f at the M06-2X/6-311++G(d,p) level are shown.
A theoretical study concerning the mechanism of the
reaction between acetylenedicarboxylic acid and 1,3-bis(2-
furyl)propane (1a) using DFT methods with the B3LYP
functional and the 6-31G* basis set was carried out.6c These
computations theoretically explained the exclusive formation of
exo,exo-adduct similar to 3 (with the cis-oriented oxo-bridges)
within the IMDA reaction6a and mentioned a high energy
barrier for the retro Diels−Alder reaction of the pincer
cycloadduct that prevents the domino-adduct formation.
Comparing the data6 with earlier works5 and taking into
account the possibility of an equilibrium between products of
kinetic and thermodynamic control in the IMDA reactions, we
were encouraged to study of this phenomenon in more detail.
First of all, quantum-chemical calculations were needed to
assign unambiguously the forms of adducts 3 and 4 to
kinetically and thermodynamically controlled products. DFT
calculations of reaction paths for five bis-dienes (1a−d,f) with a
rather diverse X were performed by using the M06-2X
functional and 6-311++G(d,p) basis set (Scheme 2, Table 2,
and Supporting Information). The M06-2X results seems to be
reliable and agree well with the thermodynamic/kinetic control
notion and are presented in Table 2. The tandem reaction
begins with the intermolecular [4+2] cycloaddition of DMAD
at one of the furan ring of bis-diene 1, which occurs via TS1
(Scheme 2) and leads to the intermediate 2 (INTk and INTt).
TS1 formation is the rate limiting step of the reaction; the
activation barrier of which is ∼29 kcal/mol. Subsequently, the
intermediate 2, undergoes the IMDA reaction via TS3 or TS2
to give corresponding cycloadducts 3 or 4. The calculated
energetic parameters show that the domino adducts 4a−d,f are
slightly (by 3.8−4.3 kcal/mol) more stable energetically, than
the pincer adducts 3a−d,f for any X. However, activation
energies for the pincer adducts 3 (energy values for “TS3 to 3”
in Table 2) are smaller than those of the domino adducts 4
lying in the range 3.4−5.6 kcal/mol. Consequently, the
theoretical calculation clearly established that adducts 3 are
kinetically controlled and that adducts 4 are thermodynamically
controlled products of the reaction. The geometrical parame-
ters of the two target compounds 3f and 4f were refined based
on X-ray diffraction data.7
B
DOI: 10.1021/acs.joc.8b00336
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The Journal of Organic Chemistry
Note
Table 1. Yields of Adducts 3 and 4 and Conditions of Kinetic and Thermodynamic Control
a
c
d
e
f
e
entry
X
conditions
yield 3 (%)
conditions
ratio of 3/4
yield 3 (%)
conditions
yield 4 (%)
b
a
b
c
d
e
f
CH2
O
Et2O, 21 days
Et2O, 21 days
Et2O, 21 days
62, 71
PhH, 20 h
PhH, 20 h
PhH, 20 h
PhH, 20 h
PhH, 20 h
PhH, 30 h
PhH, 30 h
PhH, 30 h
PhH, 25 h
PhH, 24 h
94:6
89:11
97:3
86:14
95:5
94:6
95:5
85:15
98:2
56
58
60
54
67
61
62
56
77
52
Me2C6H4, 6 h
Me2C6H4, 6 h
Me2C6H4, 4 h
Me2C6H4, 4 h
Me2C6H4, 5 h
Me2C6H4, 3 h
Me2C6H4, 5 h
Me2C6H4, 7 h
Me2C6H4, 6 h
68
75
93
70
73
87
93
73
87
54
b
67, 76
b
S
64, 71
SO2
b
N-Bn
Et2O, 21 days
Et2O, 21 days
Et2O, 21 days
64, 72
N-Ac
54
57
g
h
i
N-COCF3
N-COCCl3
N-Bz
j
N-Boc
91:9
Me2C6H4, 3 h
a
b
c
All reactions were carried out with 1.1 mol excess of DMAD in Et2O at rt for 3 weeks. According to the published data.6a Compounds 1 were
d
1
heated at reflux in PhH with 1.5 mol excess of DMAD. Isomer ratio was determined using H NMR analysis of the solids precipitating from
reaction mixtures at cooling. (The mother liquors do not contain the target cycloadducts 3 and 4.) When adducts 3 did not precipitate from the
reaction solutions, the volatiles were removed under reduced pressure and the obtained crude solids were analyzed by NMR. Isolated yield after
e
f
recrystallization. Compounds 1 were heated at reflux in o-Me2C6H4 with 1.1 mol excess of DMAD.
After theoretical calculations, experiments were carried out.
Initial bis-furyl dienes 1a−j were prepared according to
standard procedures6a (Supporting Information). All prelimi-
nary experiments to optimize the reaction conditions were
carried out using bis-furans 1b (X = O) and 1f (X = N-Ac) as
model compounds.
Bis-dienes 1b,f react slowly with DMAD under reflux in
THF. Under these conditions, the completion of the reaction
required from 4 days (when 1.5 equiv of DMAD was used) to
10 days (an equimolar quantity of DMAD). When the
experiments were carried out in MeCN or toluene at reflux,
the reactions proceeded faster (1−2 days), but the process
chemoselectivity decreased: mixtures of 3/4 were formed in the
ratio from 75:25 to 82:18.
Benzene turned out to be the best solvent for the preparation
of pincer adducts 3; in PhH, the tandem [4+2] cycloaddition
was complete within 20−30 h in rather good yields and with a
satisfactory chemoselectivity. The ratio of pincer 3/domino 4
adducts exceeded 85:15 in all cases. Kinetically controlled
products 3 can be easily isolated by one-fold recrystallization
(Table 1). In comparison with the conditions described
earlier,6a our approach has an evident time advantage (1−2
days instead of 21 days) giving comparable yields of the target
products 3. To confirm this conclusion we reproduced
experiments in Et2O at rt (entries a−c and e−g, Table 1).
All experiments at 80 °C also gave byproducts 4. Obviously,
the raise of temperature would have to shift the equilibrium
toward the thermodynamically controlled adducts 4. Therefore,
when o-xylene was chosen as a solvent, only domino adducts 4
were isolated in excellent yields (Table 1). In these cases, an
excess of DMAD (varied from 1.1 to 1.5 equiv) does not affect
the reaction rate.
Table 2. Apparent Gibbs Free Energy ΔG° Values (kcal/
mol) for Reactions of 1 with DMAD at M06-2X/6-311+
a
+G** Level of Theory (Gas Phase)
X
2
TS3 to 3 (Eact
)
TS2 to 4 (Eact
)
3
4
CH2 (a)
−1.9a
−2.9b
−1.1a
−3.1b
−1.9a
−1.2b
0.7a
13.0
(14.9)
13.9
18.3
(21.2)
19.5
−16.2
−20.0
O (b)
−14.6
−14.1
−9.5
−18.7
−18.2
−13.8
−18.8
(15.0)
15.4
(22.6)
20.5
S (c)
(17.3)
20.6
(21.7)
25.4
SO2 (d)
NAc (f)
3.9b
(21.7)
15.3
(29.3)
18.7
−2.1a
−14.5
−3.2b
(17.4)
(21.9)
a
ΔG° values of the reaction products are referenced to the sum of
energies of reactants. TS stands for transition state. Eact is an ΔG°
activation energy. Energy values for conformers formed via the pincer-
and domino-reaction pathways are labeled by superscript indices a and
b, respectively (Scheme 2).
out in an NMR tube in C2D2Cl4 at 140 °C that allowed us to
determine the reaction rate constants (Supporting Informa-
tion). The solvent selection was stipulated by its high boiling
point (∼145 °C). The half-life (τ1/2) of the reactions varied
within the range 11.5−22 min, which corresponds to the first-
order reaction rate constants of 0.031−0.060 min−1. The
transformation of 3b to 4b (X = O) was the quickest one along
the series.
The analogical dynamic NMR experiments were also used to
determine the reaction rates of the first step of the reaction,
involving the interaction of alkynes with bis-dienes 1b,c,g.
Dimethyl and diethyl acetylenedicarboxylates were chosen as
dienophiles (Scheme 3). These reactions were carried out in
C2D2Cl4 at 80 °C, and the half-lives for the cycloaddition of
DMAD were 128, 228, and 564 min for X = S, O, and COCF3,
respectively. For diethyl ester (E = CO2Et), τ1/2 were 270 and
390 min for 1c and 1b, respectively. The interaction of
EtO2CCCCO2Et with amide 1g proceeded so slowly that it
was impossible to measure the reaction half-life with a sufficient
accuracy. The reaction rate with the more sterically demanding
diethyl ether was roughly twice as slow than that with dimethyl
ether. The formation of the impurity 4 complicated the
calculation of the reaction rate constants for compounds 3b,c,g.
As already mentioned, products of the thermodynamic
control 4 were formed by the retro-DA/DA sequence from
products of kinetic control 3 through the transition state 2. We
were unable to detect open-chain intermediates 2 in reaction
1
mixtures using H NMR analysis. This observation suggests
that the first step of the tandem process, i.e., the intermolecular
[4+2] cycloaddition (1 → 2), proceeds much slower than the
second one, viz., the IMDA reaction (2 → 3 or 4), which is in a
good correlation with the theoretical predictions (Scheme 2,
Table 2).
Dynamic 1H NMR experiments to monitor transformation of
adducts 3b,c,g into 4b,c,g (X = O, S, NCOCF3) were carried
C
DOI: 10.1021/acs.joc.8b00336
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Scheme 3. Interaction of Bis-dienes 1b,c,g with Dialkyl
Acetylenedicarboxylates
EXPERIMENTAL SECTION
■
General Methods. All commercially available reagents and
solvents were used without further purification. Melting points were
measured on a capillary point apparatus equipped with a digital
thermometer and were uncorrected. Mass spectra were obtained using
the Supporting Information method. H NMR, 13C NMR, and 19F
1
NMR spectra were recorded on 400, 600 (for 1H), 100, 150 (for 13C),
and 282 (for 19F) MHz spectrometers, with TMS (1H and 13C NMR)
and CCl3F (19F NMR) as the internal standard, using CDCl3, DMSO-
1
d6, and C2D2Cl4 (for kinetic experiments) as solvents. Data for H
NMR spectra are reported as follows: chemical shift δ (ppm),
referenced to TMS; multiplicities are indicated as the following: s,
singlet; d, doublet; t, triplet; q, quartet; m, multiplet; dd, doublet of
doublets; coupling constants (Hz), and integration. Data for 13C NMR
spectra are reported in terms of chemical shift δ (ppm) relative to
residual solvent peak. Data for 19F NMR spectra are reported as
follows: chemical shift δ (ppm), referenced to CCl3F; multiplicities are
indicated as the following: s, singlet and coupling constants (Hz).
Effect of the steric volume of the ester group in the
dienophilic part was investigated in the final part of the work
(Scheme 3). In general, this influence is difficult to predict
precisely; however, it is possible to derive some conclusions.
On going from methyl to ethyl ester of acetylene dicarboxylic
acid, the chemoselectivity of the kinetically controlled reactions
decreases distinctly (entries b/k and c/n, Table 3). The pincer
1
Assignments of H and 13C signals were made with the aid of COSY,
NOESY, and HSQC NMR spectra where necessary. IR spectra were
recorded in thin films (for oils) or KBr pellets (for solids) using an
FTIR Infralum FT-801 spectrometer in range 400−4000 cm−1. Mass
spectra were taken either on Thermo Focus DSQ II (electron
ionization, 70 eV, ion source temperature 200 °C, gas chromato-
graphic inlet with Varian FactorFour VF-5 ms column) or Thermo
Trace DSQ (electron ionization, 70 eV, ion source temperature was
200 °C, direct inlet probe) spectrometers. HRMS spectra were
recorded on an LC TOF (ES). Analytical TLC was performed on silica
plates, Sorbfil.
Table 3. Yields and Conditions of the Synthesis of Esters 3
and 4
b
80 °C,
a
ratio and yield
140 °C,
yield 4
d
c
entry
X
E
(h)
3/4 (%)
(h)
(%)
General Procedure for the Synthesis of the Initial Bis-furyl Dienes
(1). 1,3-Bis(2-furyl)propane 1a (X = CH2) and di-α-furfuryl ether 1b
(X = O) were obtained as described previously.6a Difurfuryl sulfide 1c
(X = S) is a commercially available product. Difurfuryl sulfone 1d (X =
SO2) and N-benzyldifurfuryl amine 1e (X = NBn) are known
compounds,6a,8 but they were synthesized by modified methods as
described below. All other N-acyl derivatives 1f−j are new.
b
k
l
O
O
O
O
S
CO2Me
CO2Et
20
32
42
47
20
30
31
31
89:11 (67)
84:16 (61)
75:25 (54)
71:29 (72)
99:1 (73)
4
24
8
75
71
56
e
CO2iPr
CO2tBu
CO2Me
CO2Et
m
c
10
4
93
95
72
e
n
o
p
S
75:25 (81)
86:14 (83)
88:12 (57)
4
S
CO2iPr
CO2tBu
4
2-2′-(Sulfonyldimethanediyl)difuran (1d). A suspension of meta-
chloroperoxybenzoic acid (m-CPBA, 70% in water) (15.86 g, 0.064
mol) was added in portions to a solution of difurfuryl sulfide (5.0 g,
0.026 mol) in CH2Cl2 (200 mL) at 0 °C within 15 min. The mixture
was stirred for another 24 h at rt. (Precipitation of m-chlorbenzoic acid
was observed.) The reaction mixture was poured into water (100 mL)
and basified to pH 8−9 with a 25% solution of NH3 in H2O; the
organic layer was separated, and the water layer was extracted with
CH2Cl2 (4 × 100 mL). The combined organic layers were washed
with a saturated solution of Na2CO3 (4 × 100 mL), dried over MgSO4,
filtered, and concentrated. Recrystallization of the residue from
hexane/EtOAc gave sulfone 1d as a colorless powder (3.02 g, 0.014
mol, 53%). Rf 0.56 (EtOAc/hexane, 1:6, Sorbfil). 1H NMR (600 MHz,
CDCl3): δ 7.51 (2H, d, J = 1.8 Hz, H-5 and H-5′-Furyl), 6.58 (2H, br
d, J = 3.2 Hz, H-3 and H-3′-Furyl), 6.45 (2H, dd, J = 1.8 and J = 3.2
Hz, H-4 and H-4′-Furyl), 4.30 (4H, s, CH2−N−CH2). 13C NMR (150
MHz, CDCl3): δ 144.2 (C-5 and C-5′), 142.3 (C-2 and C-2′), 112.7
(C-4 and C-4′), 111.5 (C-3 and C-3′), 51.4 (CH2−S(O2)-CH2). IR
νmax/cm−1 (KBr): 3142, 2974, 1274, 754, 491. HRMS (ESI-TOF):
calcd for C10H10O4S [M + H]+, 226.0300; found, 226.0314.
S
4
b
a
Heating at reflux in PhH with 1.5 mol excess of alkyne. According to
1H NMR analysis of reaction mixtures (solids obtained after solvent
c
removing). Heating at reflux in o-Me2C6H4 with 1.1 mol excess of
alkyne. Yields are given for crude reaction mixtures before
crystallization. Adducts 4m,p were not isolated due to polymerization
of the reaction mixtures.
d
e
adducts 3 predominated in the reaction mixtures even in the
case of cycloaddition of bulky tert-butyl ester. The reaction of
bis-dienes 1b,c with tert-butyl ester at 80 °C (entries m and p)
demonstrated a rather good chemoselectivity; the ratio of 3m/
4m and 3p/4p was 88:12 and 71:29.
Under thermodynamic conditions, the steric volume of the
ester groups does not play any crucial role. The domino
adducts 4 form in good yields, except for the tert-butyl ethers
4m,p. At 140 °C, due to lability of the tert-butyl ester groups,
both reactions were accompanied by a degradation of the
starting materials. (We could not isolate adducts 4m,p.)
In conclusion, this work is a logical extension of the
preceding researches by Lautens and Fillion,6a,b and it
demonstrates unique chemospecificity in the tandem IMDA
reaction. The above-mentioned reactions can be considered as
an illustrative example of the total kinetic and thermodynamic
control and can be useful both for educational and theoretical
purposes.
N-Benzyl-1-(furan-2-yl)-N-(furan-2-ylmethyl)methanamine (1e).
Powdered LiAlH4 (3.80 g, 0.10 mol) was added in small portions to
a stirred solution of amide 1i (9.40 g, 0.0335 mol) in absolute THF
(100 mL) at +10 °C under an argon atmosphere. The reaction mixture
was heated at reflux for 12 h. Then EtOAc (30 mL) was added to the
mixture at reflux; the reaction was cooled to 0 °C, and H2O (20 mL)
was carefully added. After additional stirring at constant reflux (∼10
min) and following cooling to rt, the resulting suspension was filtered
through silica gel, concentrated, and purified by silica gel column
chromatography (Et2O) to give tertiary amine 1e as a yellow oil (6.87
1
g, 0.0257 mol, 77%). Rf 0.56 (EtOAc/hexane, 1:3, Sorbfil). H NMR
(600 MHz, CDCl3): δ 7.40−7.32 (5H, m, H-Ph), 7.31−7.23 (2H, m,
H-5-Furyl and H-5′-Furyl), 6.33 (2H, br dd, J = 3.2 and J = 1.8 Hz, H-
D
DOI: 10.1021/acs.joc.8b00336
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The Journal of Organic Chemistry
Note
4-Furyl and H-4′-Furyl), 6.23 (2H, br d, J = 3.2 Hz, H-3-Furyl and H-
3′-Furyl), 3.66 (4H, s, CH2−N−CH2), 3.61 (2H, s, NCH2Ph). HRMS
(ESI-TOF): calcd for C17H17NO2 [M + H]+, 267.1259; found,
267.1271.
intensive stirring within 15 min. The mixture was stirred for another
30 min at rt, poured into water (150 mL), and extracted with CH2Cl2
(3 × 80 mL). The combined organic layers were dried over MgSO4,
filtered, and concentrated under reduced pressure. Flash chromatog-
raphy purification of the residue on silica gel (Et2O) yielded amide 1i
as a light-yellow viscous oil (13.89 g, 0.050 mol, 89%). Rf 0.68
N,N-Bis(furan-2-ylmethyl)acetamide (1f). Acetic anhydride (Ac2O,
18.70 mL, 0.197 mol) was added dropwise under intensive stirring to a
solution of difurfuryl amine (10.0 g, 0.056 mol) in PhH (30 mL) at 0
°C within 30 min. The mixture was heated at reflux for 1 h and then
was poured into water (100 mL) and basified to pH 8−9 with a 25%
solution of NH3 in H2O. The organic layer was separated, and the
water layer was extracted with EtOAc (3 × 50 mL). The combined
organic layers were dried over MgSO4, filtered, and concentrated. The
residue was purified by silica gel column chromatography (Et2O) to
give amide 1f as a light-brown viscous oil (10.58 g, 0.048 mol, 86%). Rf
1
(EtOAc/hexane, 1:2, Sorbfil). H NMR (600 MHz, CDCl3): δ 7.57−
7.55 (2H, m, H-5 and H-5′-Furyl), 7.42−7.41 (5H, m, H-Ph), 6.35−
6.20 (4H, m, H-3, H-4, H-3′, H-4′-Furyl), 4.70 (2H, br s, CH2−N),
4.39 (2H, br s, CH2−N). 13C NMR (100 MHz, CDCl3): δ 171.8
(COPh), 150.7 and 149.9 (C-2 and C-2′), 142.9 and 142.5 (C-5 and
C-5′), 135.9 (C-1-Ph), 129.8 (C-4-Ph), 128.5 (2C, C-3-Ph and C-5-
Ph), 127.3 (2C, C-2-Ph and C-6-Ph), 110.5 (C-3 and C-3′), 109.1 (C-
4 and C-4′), 45.4 (CH2−N), 40.4 (CH2−N). IR νmax/cm−1 (thin film):
1640, 1013, 739. HRMS (ESI-TOF): calcd for C17H15NO3 [M + H]+,
281.1052; found, 281.1066.
1
0.76 (EtOAc/hexane, 1:2, Sorbfil). H NMR (600 MHz, CDCl3): δ
7.38 (1H, dd, J = 0.8 and J = 1.7 Hz, H-5-Furyl), 7.35 (1H, dd, J = 0.8
and J = 1.7 Hz, H-5′-Furyl), 6.33 (1H, dd, J = 1.7 and J = 3.2 Hz, H-4-
Furyl), 6.31 (1H, dd, J = 1.7 and J = 3.2 Hz, H-4′-Furyl), 6.25 (1H, br
d, J = 3.2 Hz, H-3-Furyl), 6.20 (1H, br d, J = 3.2 Hz, H-3′-Furyl), 4.58
(2H, s, CH2−N), 4.42 (2H, s, N−CH2), 2.26 (3H, s, CH3). 13C NMR
(150 MHz, CDCl3): δ 170.3 (COCH3), 150.6 and 149.7 (C-2′ and C-
2), 142.4 and 142.0 (C-5 and C-5′), 113.6 and 110.1 (C-4 and C-4′),
108.5 and 107.9 (C-3 and C-3′), 44.2 and 40.4 (CH2−N−CH2), 21.4
(CH3). IR νmax/cm−1 (thin film): 2920, 1645. HRMS (ESI-TOF):
calcd for C12H13NO3 [M + H]+, 219.0895; found, 219.0879.
tert-Butyl Bis(furan-2-ylmethyl)carbamate (1j). Di-tert-butyl dicar-
bonate ((Boc)2O, 40.6 mL, 0.19 mol) was added dropwise under
intensive stirring to a solution of bis(furan-2-ylmethyl)amine (30 g,
0.17 mol) in CH2Cl2 (250 mL) at rt within 30 min. The mixture was
stirred for another 2 h at rt. The reaction mixture was poured into
water (100 mL) and basified to pH 8−9 with a 25% solution of NH3 in
H2O. The organic layer was separated, and the water layer was
extracted with CH2Cl2 (3 × 50 mL). The combined organic layers
were dried over MgSO4, filtered, and concentrated. The residue was
purified by silica gel column chromatography (Et2O) to give amide 1j
as a bright-yellow viscous oil (41.1 g, 0.15 mol, 87%). Rf 0.72 (EtOAc/
hexane, 1:6, Sorbfil). 1H NMR (400 MHz, CDCl3): δ 7.34 (2H, d, J =
1.8 Hz, H-5 and H-5′-Furyl), 6.31−6.29 (2H, m, H-4 and H-4′-Furyl),
6.20−6.14 (2H, m, H-3 and H-3′-Furyl), 4.41−4.34 (4H, m, CH2−N−
CH2), 1.47 (9H, s, C(CH3)3). 13C (150 MHz, CDCl3): δ 155.3
(COC(CH3)3), 151.9 and 151.6 (C-2′ and C-2), 142.3 and 142.1 (C-5
and C-5′), 110.4 (2C, C-4 and C-4′), 108.4 and 107.6 (C-3 and C-3′),
80.4 (COC(CH3)3), 42.9 (CH2−N), 42.4 (CH2−N), 28.5 (C(CH3)3).
IR νmax/cm−1 (thin film): 1699, 1163, 1011, 735. HRMS (ESI-TOF):
calcd for C15H19NO4 [M + H]+, 277.1314; found, 277.1329.
General Procedure for the Synthesis of the Pincer Adducts 3
(Method A). Dimethyl acetylenedicarboxylate (DMAD, 1.84 mL,
0.015 mol) was added to a solution of the appropriate bis-diene 1
(0.01 mol) in PhH (30 mL). The mixture was heated at reflux for
15.5−40 h at 80 °C (GC−MS monitoring until disappearance of the
starting material). The reaction mixture was cooled and left overnight
at room temperature. Further treatment of the resulting mixtures is
given below.
2,2,2-Trifluoro-N,N-bis(furan-2-ylmethyl)acetamide (1g). Tri-
fluoroacetic anhydride (9.4 mL, 0.068 mol) was added dropwise
under intensive stirring to a mixture of bis(furan-2-ylmethyl)amine
(10.0 g, 0.056 mol) and NEt3 (17.1 mL, 0.12 mol) in CH2Cl2 (80 mL)
at 0 °C within 20 min. The mixture was stirred for another 2 h at rt.
The reaction mixture was poured into a 2% solution of HCl in H2O
(150 mL). The organic layer was separated, and the water layer was
extracted with CH2Cl2 (3 × 100 mL). The combined organic layers
were dried over MgSO4, filtered, and concentrated. The residue was
purified by silica gel column chromatography (hexane/Et2O) to give
amide 1g as a brown viscous oil (13.72 g, 0.050 mol, 89%). Rf 0.80
1
(EtOAc/hexane, 1:2, Sorbfil). H NMR (600 MHz, CDCl3): δ 7.42
(1H, br d, J = 2.1 Hz, H-5-Furyl), 7.39 (1H, br d, J = 2.1 Hz, H-5′-
Furyl), 6.38 (1H, dd, J = 2.1 and J = 3.4 Hz, H-4-Furyl), 6.35−6.32
(3H, m, H-3, H-3′and H-4′-Furyl), 4.60 (2H, s, N−CH2), 4.57 (2H, s,
N−CH2). 13C NMR (150 MHz, CDCl3): δ 156.8 (q, J = 36.1 Hz,
CO−CF3), 148.4 (2C, C-2 and C-2′), 143.3 (2C, C-5 and C-5′), 116.5
(q, J = 287.6 Hz, CF3), 110.6 (2C, C-3 and C-3′), 110.0 (2C, C-4 and
C-4′), 43.2 (2C, CH2−N−CH2). 19F NMR (282 MHz, CDCl3): δ
−68.1 (s, CF3). IR νmax/cm−1 (thin film): 1670, 2941, 1146. HRMS
(ESI-TOF): calcd for C12H10F3NO3 [M + H]+, 273.0613; found,
273.0621.
1
The isomer ratio of 3/4 (Table 1) was determined using H NMR
analysis of the solids precipitating from reaction mixtures at cooling.
(The mother liquors do not contain the target cycloadducts.) When
adducts 3 did not precipitate from the reaction solutions, the volatiles
were removed under reduced pressure and the obtained crude solids
were analyzed by NMR.
2,2,2-Trichloro-N,N-bis(furan-2-ylmethyl)acetamide (1h). 2,2,2-
Trichloroacetyl chloride (6.2 mL, 0.055 mol) was added dropwise
under intensive stirring to a solution of bis(furan-2-ylmethyl)amine
(8.85 g, 0.05 mol) and NEt3 (8.3 mL, 0.06 mol) in CH3CN (100 mL)
at 0 °C within 10 min. The mixture was stirred for another 30 min at
rt. The reaction mixture was poured into a 2% solution of HCl in H2O
(150 mL). The organic layer was separated, and the water layer was
extracted with EtOAc (3 × 80 mL). The combined organic layers were
dried over MgSO4, filtered, and concentrated. The residue was purified
by aluminum oxide column chromatography (hexane/Et2O) to give
amide 1h as a colorless oil (13.2 g, 0.041 mol, 82%). Rf 0.43 (EtOAc/
Dimethyl (1RS,3aSR,6aRS,9SR)-5,6-Dihydro-1H,4H,9H-1,3a:6a,9-
diepoxyphenalene-9a,9b-dicarboxylate (3a). The precipitated crys-
tals were filtered off and recrystallized from hexane/EtOAc to give
compound 3a as a white powder (1.78 g, 5.6 mmol, 58%). Rf 0.62
(EtOAc/hexane, 1:3, Sorbfil). Mp: 151.8−153.4 °C (from hexane/
EtOAc). 1H NMR (600 MHz, CDCl3): δ 6.55 (2H, dd, J = 1.5 and J =
5.3 Hz, H-2 and H-8), 6.47 (2H, d, J = 5.3 Hz, H-3 and H-7), 5.05
(2H, d, J = 1.5 Hz, H-1 and H-9), 3.61 (3H, s, CO2Me), 3.60 (3H, s,
CO2Me), 2.16 (4H, dd, J = 3.8 and J = 8.8 Hz, H-4 and H-6), 2.01−
1.93 (1H, m, H-5A), 1.72−1.68 (1H, m, H-5B). 13C NMR (150 MHz,
CDCl3): δ 171.0 (CO2Me), 170.8 (CO2Me), 142.2 (2C, C-3 and C-7),
138.4 (2C, C-2 and C-8), 90.0 (2C, C-3a and C-6a), 83.5 (2C, C-1
and C-9), 73.4 and 68.6 (2C, C-9b and C-9a), 52.0 (CO2Me), 51.9
(CO2Me), 25.7 (2C, C-4 and C-6), 17.1 (C-5).
Dimethyl (3aRS,6SR,7RS,9aSR)-6H,7H-3a,6:7,9a-Diepoxybenzo-
[de]isochromene-6a,9b(1H,3H)-dicarboxylate (3b). The precipitated
crystals were filtered off and recrystallized from EtOH (30 mL) to give
the pure compound 3b as colorless prisms (1.86 g, 5.8 mmol, 58%). Rf
0.64 (EtOAc/hexane, 1:1, Sorbfil). Mp: 168.4−169.2 °C (from
EtOH). 1H NMR (600 MHz, DMSO-d6): δ 6.63 (2H, dd, J = 2.1 and J
1
hexane, 1:2, Sorbfil). H NMR (600 MHz, CDCl3): δ 7.39 (2H, br s,
H-5 and H-5′-Furyl), 6.35−6.29 (4H, m, H-3, H-3′, H-4 and H-4′-
Furyl), 4.94 (2H, br s, N−CH2), 4.58 (2H, br s, N−CH2). 13C NMR
(100 MHz, CDCl3): δ 160.4 (NCOCCl3), 149.2 and 148.6 (C-2 and
C-2′), 143.1 and 143.0 (C-5 and C-5′), 110.7 and 110.6 (C-3 and C-
3′), 109.8 (C-4 and C-4′), 93.0 (NCOCCl3), 46.1 (NCH2), 43.7
(NCH2). IR νmax/cm−1 (thin film): 1686, 2930, 1149. HRMS (ESI-
TOF): calcd for C12H10Cl3NO3 [M + H]+, 320.9726; found, 320.9738.
N,N-Bis(furan-2-ylmethyl)benzamide (1i). NaOH (2.68 g, 0.067
mol) was added to a suspension of bis(furan-2-ylmethyl)amine (10.0
g, 0.056 mol) in water (40 mL). The mixture was cooled to 0 °C, and
benzoyl chloride (7.2 mL, 0.062 mol) was added dropwise under
E
DOI: 10.1021/acs.joc.8b00336
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
= 5.5 Hz, H-5 and H-8), 6.42 (2H, d, J = 5.5 Hz, H-4 and H-9), 5.14
(2H, d, J = 2.1 Hz, H-6 and H-7), 4.13 (2H, d, J = 13.1 Hz, H-1A and
H-3A), 4.03 (2H, d, J = 13.1 Hz, H-1B and H-3B), 3.51 (6H, s, 2 ×
CO2Me). 13C NMR (150 MHz, DMSO-d6): δ 170.5 (CO2Me), 170.3
(CO2Me), 141.9 (2C, C-5 and C-8), 138.2 (2C, C-4 and C-9), 87.5
(2C, C-6 and C-7), 83.6 and 83.5 (2C, C-3a and C-9a), 71.0 and 64.3
(2C, C-6a and C-9b), 67.6 (2C, C-1 and C-3), 52.6 (CO2Me), 52.4
(CO2Me). IR νmax/cm−1 (KBr): 3055, 2956, 1736, 1715. HRMS (ESI-
TOF): calcd for C16H16O7 [M + H]+, 320.0896; found, 320.0889.
Dimethyl (3aRS,6SR,7RS,9aSR)-6H,7H-3a,6:7,9a-Diepoxybenzo-
[de]isothiochromene-6a,9b(1H,3H)-dicarboxylate (3c). The precipi-
tated crystals were filtered off and recrystallized from an EtOAc/EtOH
mixture to give the pure compound 3c as colorless needles (2.01 g, 6.0
mmol, 60%). Rf 0.53 (EtOAc/hexane, 1:2, Sorbfil). Mp: 177.3−178.4
°C (with decomp from EtOAc/EtOH). 1H NMR (600 MHz, DMSO-
d6): δ 6.58 (2H, dd, J = 1.4 and J = 5.5 Hz, H-5 and H-8), 6.42 (2H, d,
J = 5.5 Hz, H-4 and H-9), 5.09 (2H, d, J = 1.4 Hz, H-6 and H-7), 3.52
(3H, s, CO2Me), 3.51 (3H, s, CO2Me), 3.48 (2H, d, J = 15.1 Hz, H-1A
and H-3A), 2.84 (2H, d, J = 15.1 Hz, H-1B and H-3B). 13C NMR (150
MHz, DMSO-d6): δ 170.5 (CO2Me), 170.4 (CO2Me), 141.9 (C-4),
141.8 (C-9), 139.7 (2C, C-5 and C-8), 87.2 (2C, C-6 and C-7), 83.1
and 83.0 (2C, C-3a and C-9a), 73.4 and 67.4 (2C, C-9b and C-6a),
52.5 (CO2Me), 52.4 (CO2Me), 26.8 (2C, C-1 and C-3). IR νmax/cm−1
(KBr): 2983, 2948, 1740, 1706, 1091, 1010. HRMS (ESI-TOF): calcd
for C16H16SO6 [M + H]+, 336.0668; found, 336.0679.
and H-7), 4.25 (1H, dd, J = 1.4 and J = 14.8 Hz, H-3A), 4.00 (1H, d, J
= 14.8 Hz, H-3B), 3.62 (6H, s, 2 × CO2Me), 3.34 (1H, d, J = 14.8 Hz,
H-1B), 2.17 (3H, s, N−Ac). 13C NMR (100 MHz, CDCl3): δ 170.9 (2
× CO2Me), 170.3 (N-COMe), 140.9 (C-5 and C-8), 137.9 (C-4 and
C-9), 87.7 (C-3a and C-9a), 83.6 (C-6 and C-7), 71.3 and 68.8 (C-6a
and C-9b), 52.3 (2 × CO2Me), 45.7 and 40.6 (C-1 and C-3), 22.0 (N-
COMe). IR νmax/cm−1 (KBr): 3096, 3009, 3010, 1711, 1640. HRMS
(ESI-TOF): calcd for C18H19NO7 [M + H]+, 361.1162; found,
361.1179.
Dimethyl (3aRS,6SR,7RS,9aSR)-2-(Trifluoroacetyl)-2,3-dihydro-
1H,6H,7H-3a,6:7,9a-diepoxybenzo[de]isoquinoline-6a,9b-dicarbox-
ylate (3g). The solvent was removed under reduced pressure. The
residue (brown oil) was triturated with ether. Obtained crystals were
filtered off and recrystallized from hexane/EtOAc to give the pure
compound 3g as a white powder (2.57 g, 6.2 mmol, 62%). Rf 0.56
(EtOAc/hexane, 2:1, Sorbfil). Mp: 194.2−194.9 °C (from hexane/
EtOAc). 1H NMR (400 MHz, CDCl3): δ 6.74−6.71 (2H, m, H-4 and
H-9), 6.46 (2H, dd, J = 2.3 and J = 5.5 Hz, H-5 and H-8), 5.14 (2H, br
s, H-6 and H-7), 5.10 (1H, d, J = 14.9 Hz, H-1A), 4.43 (1H, br d, J =
14.9 Hz, H-3A), 4.08 (1H, d, J = 14.9 Hz, H-3B), 3.64 (6H, s, 2 ×
CO2Me), 3.59 (1H, d, J = 14.9, H-1B). 13C NMR (100 MHz, CDCl3):
δ 170.1 (2 × CO2Me), 157.2 (q, J = 35.5 Hz, F3C-C), 141.2 (C-5 and
C-8), 137.5 (C-4 and C-9), 116.4 (q, J = 288.1 Hz, CF3), 87.1 (C-3a
and C-9a), 83.8 (C-6 and C-7), 71.4 and 68.8 (C-9 and C-6a), 52.4 (2
× CO2Me), 44.8 (q, J = 3.8 Hz, C-1), 42.4 (C-3). 19F NMR (282
MHz, CDCl3): δ −67.7 (s, CF3). IR νmax/cm−1 (KBr): 3109, 3055,
2956, 1713, 1688, 1197. HRMS (ESI-TOF): calcd for C18H16F3NO7
[M + H]+, 415.0879; found, 415.0889.
Dimethyl (3aRS,6SR,7RS,9aSR)-2-(Trichloroacetyl)-2,3-dihydro-
1H,6H,7H-3a,6:7,9a-diepoxybenzo[de]isoquinoline-6a,9b-dicarbox-
ylate (3h). The solvent was removed under reduced pressure.
Obtained crystals were recrystallized from an EtOAc/DMF mixture
to give the pure compound 3h as coarse colorless prisms (2.59 g, 5.6
mmol, 56%). Rf 0.55 (from EtOAc/hexane, 1:2, Sorbfil). Mp: 194.8−
195.2 °C (with decomp, EtOAc/DMF). 1H NMR (400 MHz,
CDCl3): δ 6.72 (2H, dd, J = 1.4 and J = 5.6 Hz, H-5 and H-8),
6.47 (2H, d, J = 5.6 Hz, H-4 and H-9), 5.14 (2H, br d, J = 1.4 Hz, H-6
and H-7), 5.11 (2H, d, J = 14.5 Hz, H-1 and H-3), 3.85 (2H, br d, J ∼
14.5 Hz, H-1 and H-3), 3.63 (6H, s, 2 × CO2Me). 13C NMR (100
MHz, DMSO-d6): δ 170.1 (CO2Me), 170.0 (CO2Me), 160.9 (N-
COCCl3), 141.0 (C-5 and C-8), 137.8 (C-4 and C-9), 92.9 (N-
COCCl3), 87.2 (C-3a and C-9a), 83.9 (C-6 and C-7), 71.3 and 68.4
(C-6a and C-9b), 52.4 (CO2Me), 52.3 (CO2Me), 46.6 and 44.4 (C-1
and C-3). IR νmax/cm−1 (KBr): 2997, 2951, 1741, 1686, 1288. HRMS
(ESI-TOF): calcd for C18H16Cl3NO7 [M + H]+, 462.9992; found,
462.9977.
Dimethyl (3aRS,6SR,7RS,9aSR)-2-Benzoyl-2,3-dihydro-1H,6H,7H-
3a,6:7,9a-diepoxybenzo[de]isoquinoline-6a,9b-dicarboxylate (3i).
The precipitated crystals were filtered off and recrystallized from an
EtOH/DMF mixture to give the pure compound 3i as a colorless
powder (3.25 g, 7.7 mmol, 77%). Rf 0.71 (EtOAc, Sorbfil). Mp:
174.3−175.1 °C (from EtOH/DMF). 1H NMR (400 MHz, CDCl3): δ
7.53−7.52 (2H, m, H-2′ and 6′-Ph), 7.38−7.36 (3H, m, H-3′, H-4′, H-
5′-Ph), 6.70 (1H, br s, H-5), 6.67 (1H, br s, H-8), 6.51 (1H, br s, H-4),
6.35 (1H, br s, H-9), 5.33 (1H, d, J = 14.0 Hz, H-1A), 5.16−5.13 (2H,
m, H-6 and H-7), 4.31 (1H, d, J = 14.0 Hz, H-3A), 3.90 (1H, d, J =
14.0 Hz, H-3B), 3.62 (6H, s, 2 × CO2Me), 3.63 (1H, br d, J = 14.0 Hz,
H-1B). 13C NMR (150 MHz, CDCl3): δ 172.1 (CO-Ph), 170.2 (2 ×
CO2Me), 140.8 (C-4), 140.6 (C-9), 138.4 (C-5), 138.0 (C-8), 135.7
(C-1′-Ph), 129.7 (C-4′-Ph), 128.4 (C-3′-Ph and C-5′-Ph), 127.8 (C-
2′-Ph and C-6′-Ph), 87.6 (C-3a and C-9a), 83.8 (C-6 and C-7), 70.3
(C-6a and C-9b), 52.3 (2 × CO2Me), 46.7 and 41.2 (C-1 and C-3). IR
νmax/cm−1 (KBr): 2954, 1736, 1749, 1631, 1077, 1055. HRMS (ESI-
TOF): calcd for C23H21NO7 [M + H]+, 423.1318; found, 423.1326.
2-tert-Butyl 6a,9b-Dimethyl (3aRS,6SR,7RS,9aSR)-1H,6H,7H-
3a,6:7,9a-Diepoxybenzo[de]isoquinoline-2,6a,9b(3H)-tricarboxylate
(3j). The solvent was removed under reduced pressure. The residue
was purified by silica gel flash chromatography (hexane/EtOAc = 9:1)
to give compound 3j as a colorless powder (2.09 g, 5.2 mmol, 52%). Rf
0.72 (EtOAc/hexane, 1:6, Sorbfil). Mp: 117.7−118.3 °C (from
Dimethyl (3aRS,6SR,7RS,9aSR)-6H,7H-3a,6:7,9a-Diepoxybenzo-
[de]isothiochromene-6a,9b(1H,3H)-dicarboxylate 2,2-Dioxide (3d).
The precipitated crystals were filtered off and recrystallized from
EtOH (∼60 mL) to give the pure compound 3d as colorless needles
(1.99 g, 5.4 mmol, 54%). Rf 0.47 (EtOAc/EtOH, 1:2, Sorbfil). Mp:
274.2−276 °C (with decomp from EtOH). 1H NMR (600 MHz,
DMSO-d6): δ 6.65 (2H, dd, J = 1.6 and J = 5.5 Hz, H-5 and H-8), 6.42
(2H, d, J = 5.5 Hz, H-4 and H-9), 5.19 (2H, d, J = 1.6 Hz, H-6 and H-
7), 4.10 (2H, d, J = 15.1 Hz, H-1A and H-3A), 3.80 (2H, d, J = 15.1
Hz, H-1B and H-3B), 3.57 (3H, s, CO2Me), 3.53 (3H, s, CO2Me). 13
C
NMR (150 MHz, DMSO-d6): δ 168.6 (CO2Me), 168.5 (CO2Me),
139.4 (C-4 and C-5), 138.9 (C-5 and C-8), 87.9 (C-3a and C-9a), 83.1
(C-6 and C-7), 72.8 and 67.0 (C-9b and C-6a), 51.5 (C-1 and C-3),
51.3 (2 × CO2Me). IR νmax/cm−1 (KBr): 2993, 2949, 1735, 1711,
1129. HRMS (ESI-TOF): calcd for C16H16SO8 [M + H]+, 368.0566;
found, 368.0553.
Dimethyl (3aRS,6SR,7RS,9aSR)-2-Benzyl-2,3-dihydro-1H,6H,7H-
3a,6:7,9a-diepoxybenzo[de]isoquinoline-6a,9b-dicarboxylate (3e).
The precipitated crystals were filtered off and recrystallized from
hexane/EtOAc to give the pure compound 3e as a light-brown powder
(2.74 g, 6.7 mmol, 67%). Rf 0.56 (EtOAc/hexane, 2:1, Sorbfil). Mp:
161.7−162.0 °C (from hexane/EtOAc). 1H NMR (400 MHz,
CDCl3): δ 7.37−7.22 (5H, m, H-Ph), 6.59 (2H, dd, J = 1.6 and J =
5.6 Hz, H-5 and H-8), 6.42 (2H, d, J = 5.6 Hz, H-4 and H-9), 5.12
(2H, d, J = 1.6 Hz, H-6 and H-7), 3.81 (2H, br s, NCH2Ph), 3.60 (3H,
s, CO2Me), 3.54 (3H, s, CO2Me), 3.32 (2H, d, J = 13.1 Hz, H-1A and
H-3B), 3.00 (2H, br d, J = 13.1 Hz, H-1B and H-3B). 13C NMR (100
MHz, CDCl3): δ 170.5 (CO2Me), 170.4 (CO2Me), 139.8 (C-5 and C-
8), 139.1 (C-4 and C-9), 137.0 (C-1-Ph), 129.4 (C-2-Ph and C-6-Ph),
128.2 (C-3-Ph and C-5-Ph), 127.2 (C-1-Ph), 88.4 (C-3a and C-9a),
83.8 (C-6 and C-7), 72.0 and 67.8 (C-9b and C-6a), 62.5 (NCH2Ph),
52.0 (CO2Me), 51.9 (CO2Me), 50.7 (C-1 and C-3). IR νmax/cm−1
(KBr): 3447, 2951, 2782, 1734, 1708, 1237. HRMS (ESI-TOF): calcd
for C23H23NO6 [M + H]+, 409.1525; found, 409.1517.
Dimethyl (3aRS,6SR,7RS,9aSR)-2-Acetyl-2,3-dihydro-1H,6H,7H-
3a,6:7,9a-diepoxybenzo[de]isoquinoline-6a,9b-dicarboxylate (3f).
The solvent was removed under reduced pressure. The residue
(brown oil) was triturated with ether. The obtained crystals were
filtered off and recrystallized from an EtOAc/EtOH mixture to give
the pure compound 3f as light-brown rhombic crystals (2.20 g, 6.1
mmol, 61%). Rf 0.49 (EtOAc/EtOH, 8:1, Sorbfil). Mp: 144.7−145.3
1
°C (from EtOAc/EtOH). H NMR (600 MHz, CDCl3): δ 6.70 (1H,
dd, J = 1.4 and J = 5.5 Hz, H-5), 6.67 (1H, dd, J = 1.4 and J = 5.5 Hz,
H-8), 6.49 (1H, d, J = 5.5 Hz, H-4), 6.44 (1H, d, J = 5.5 Hz, H-9), 5.25
(1H, dd, J = 1.4 and J = 14.8 Hz, H-1A), 5.10 (2H, d, J = 1.4 Hz, H-6
F
DOI: 10.1021/acs.joc.8b00336
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
hexane/EtOAc). 1H NMR (400 MHz, CDCl3): δ 6.67 (2H, dd, J = 1.4
and J = 5.5 Hz, H-5 and H-8), 6.46 (2H, d, J = 5.5 Hz, H-4 and H-9),
5.10 (2H, br s, H-6 and H-7), 4.73 (1H, br d, J = 14.0 Hz, H-1A), 4.57
(1H, br d, J = 14.0 Hz, H-3A), 3.66 (1H, br d, J = 14.0 Hz, H-3B), 3.61
(6H, s, 2 × CO2Me), 3.51−3.47 (1H, d, J = 14.0 Hz, H-1B), 1.46 (9H,
s, CO2C(CH3)3). 13C NMR (150 MHz, CDCl3): δ 170.5 (CO2Me),
170.3 (CO2Me), 155.6 (NCO2tBu), 140.4 (C-4), 140.3 (C-9), 138.7
(C-5 and C-8), 87.5 (NCO2C(CH3)3), 83.8 (C-6 and C-7), 80.5 (C-3a
and C-9a), 71.7 and 68.4 (C-9b and C-6a), 52.3 (CO2Me), 52.2
(CO2Me), 43.4 and 42.2 (C-1 and C-3), 28.3 (NCO2C(CH3)3). IR
νmax/cm−1 (KBr): 2971, 1710, 1694, 1284. HRMS (ESI-TOF): calcd
for C21H25NO8 [M + H]+, 419.1580; found, 419.1591.
General Procedure for the Synthesis of the Pincer Adducts 3a−c
and 3e−g (Method B). Cycloadducts 3a−c and 3e−g were also
obtained according to the procedure described previously.6a A solution
of DMAD (1.47 mL, 0.012 mol) and 3 (0.010 mol) in Et2O (10.0 mL)
was left at rt for 3 weeks. The precipitated crystals were filtered off and
washed with Et2O. According to the 1H NMR data, the obtained
powders did not need additional purification.
Yields of compounds 3f and 3g are given below as an example. The
yields of the remaining adducts 3a−c and 3e are given in Table 1.
Dimethyl (3aRS,6SR,7RS,9aSR)-2-Acetyl-2,3-dihydro-1H,6H,7H-
3a,6:7,9a-diepoxybenzo[de]isoquinoline-6a,9b-dicarboxylate (3f).
The precipitate from Et2O crystals were filtered off and recrystallized
from an EtOAc/EtOH mixture to give compound 3f as light-yellow
crystals (1.95 g, 5.4 mmol, 54%).
Dimethyl (3aRS,6SR,7RS,9aSR)-2-(Trifluoroacetyl)-2,3-dihydro-
1H,6H,7H-3a,6:7,9a-diepoxybenzo[de]isoquinoline-6a,9b-dicarbox-
ylate (3g). The precipitate from Et2O crystals were filtered off and
recrystallized from hexane/EtOAc to give compound 3g as a white
powder (2.37 g, 5.7 mmol, 57%).
General Procedure for the Synthesis of the Domino Adducts 4.
Dimethyl acetylenedicarboxylate (DMAD, 1.35 mL, 0.011 mol) was
added to a solution of the appropriate diene 1 (0.010 mol) in o-
Me2C6H4 (30 mL). The mixture was heated at reflux for 3−7 h at 140
°C (TLC monitoring). The reaction mixture was cooled and left
overnight at room temperature. Further treatment of the resulting
mixtures is given below.
Dimethyl (1RS,3aSR,6aSR,9RS,9aSR,9bRS)-5,6,9a,9b-Tetrahydro-
1H,4H,9H-1,3a:6a,9-diepoxyphenalene-2,3-dicarboxylate (4a). The
solvent was removed under reduced pressure. The residue was purified
by silica gel column chromatography (hexane/EtOAc = 5:1) to give
compound 4a as colorless prisms (2.16 g, 6.8 mmol, 68%). Rf 0.62
(EtOAc/hexane, 2:5, Sorbfil). Mp: 138.1−139.3 °C (hexane/EtOAc).
1H NMR (400 MHz, CDCl3): δ 6.43 (1H, dd, J = 1.8 and J = 5.6 Hz,
H-8), 6.27 (1H, d, J = 5.6 Hz, H-9), 5.09 (1H, s, H-1), 4.88 (1H, d, J =
1.8 Hz, H-9), 3.78 (3H, s, CO2Me), 3.73 (3H, s, CO2Me), 2.23−2.17
(3H, m, H-4A, H-6A and H-9a), 2.00−1.88 (4H, m, H-4B, H-6B, H-
5A and H-9b), 1.71−1.68 (1H, m, H-5B). 13C NMR (100 MHz,
CDCl3): δ 164.7 (CO2Me), 162.6 (CO2Me), 150.6 (C-3), 143.8 (C-
2), 140.8 (C-7), 138.5 (C-8), 89.3 (C-3a), 85.8 (C-6a), 81.3 (C-1),
80.5 (C-9), 52.2 (C-9a), 52.0 (2 × CO2Me), 49.8 (C-9b), 26.7 (C-9),
25.0 (C-6), 17.2 (C-5). IR νmax/cm−1 (KBr): 1709, 1628, 1284, 1261.
HRMS (ESI-TOF): calcd for C17H18O6 [M + H]+, 318.1103; found,
318.1125.
1712, 1272, 975. HRMS (ESI-TOF): calcd for C16H16O7 [M + H]+,
320.0896; found, 320.0883.
Dimethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-6a,9b-Dihydro-6H,7H-
3a,6:7,9a-diepoxybenzo[de]isothiochromene-4,5-(1H,3H)-dicarbox-
ylate (4c). The precipitated crystals were filtered off and recrystallized
from DMF (∼25 mL) to give the pure compound 4c as small colorless
needles (3.12 g, 9.3 mmol, 93%). Rf 0.75 (EtOAc, Sorbfil). Mp: 216.3-
217.8 °C (with decomp from DMF). 1H NMR (600 MHz, DMSO): δ
6.53 (1H, br d, J = 4.8 Hz, H-8), 6.31 (1H, d, J = 4.8 Hz, H-9), 5.13
(1H, s, H-6), 4.90 (1H, s, H-7), 3.70 (6H, s, 2 × CO2Me), 3.41 (1H,
d, J = 15.1 Hz, H-1A), 3.38 (1H, d, J = 15.1 Hz, H-3A), 2.83 (2H, m,
H-1B and H-3B), 2.15 and 1.83 (2H, d, J = 5.5 Hz, H-6a and H-9b).
13C NMR (100 MHz, CDCl3): δ 164.2 (CO2Me), 162.5 (CO2Me),
148.7 (C-5), 145.8 (C-4), 139.9 (C-8), 140.0 (C-9), 86.5 and 83.3 (C-
9a and C-3a), 81.6 (C-6), 80.7 (C-7), 52.9 (CO2Me), 52.7 (CO2Me),
52.6 and 48.8 (C-9b and C-6a), 28.8 and 27.0 (C-3 and C-1). IR νmax
/
cm−1 (KBr): 1732, 1715, 1277, 984. HRMS (ESI-TOF): calcd for
C16H16O6S [M + H]+, 336.0668; found, 336.0684.
Dimethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-6a,9b-Dihydro-6H,7H-
3a,6:7,9a-diepoxybenzo[de]isothiochromene-4,5-(1H,3H)-dicarbox-
ylate 2,2-Dioxide (4d). The precipitated crystals were filtered off and
recrystallized from DMF (∼20 mL) to give adduct 4d as a white
powder (2.58 g, 7.0 mmol, 70%). Rf 0.42 (EtOAc/EtOH, 2:1, Sorbfil).
Mp: 268.4−269.6 °C (with decomp from DMF). 1H NMR (600 MHz,
DMSO-d6): δ 6.61 (1H, dd, J = 1.4 and J = 5.7 Hz, H-8), 6.37 (1H, d, J
= 5.7 Hz, H-9), 5.20 (1H, s, H-6), 4.99 (1H, d, J = 1.4 Hz, H-7), 4.18
(1H, d, J = 14.6 Hz, H-1A), 4.08 (1H, d, J = 14.6 Hz, H-3A), 3.78 (3H,
s, CO2CH3), 3.76 (3H, s, CO2CH3), 3.70 (1H, dd, J = 2.5 and J = 14.6
Hz, H-1B), 3.63 (1H, dd, J = 2.5 and J = 14.6 Hz, H-3B), 2.38 and
2.32 (2H, d, J = 6.4 Hz, H-9b and H-6a). 13C NMR (100 MHz,
CDCl3): δ 161.7 (2 × CO2Me), 152.5 (C-4), 146.1 (C-5), 138.8 (C-
8), 138.5 (C-9), 86.3 (C-6), 83.9 (C-7), 81.0 and 79.8 (C-3a and C-
9a), 52.2 (2 × CO2CH3), 51.6 (C-1), 51.5 and 50.2 (C-6a and C-9b),
47.4 (C-3). IR νmax/cm−1 (KBr): 1734, 1717, 1278, 1133. HRMS
(ESI-TOF): calcd for C16H16O8S [M + H]+, 368.0566; found,
368.0538.
Dimethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-2-Benzyl-2,3,6a,9b-tet-
rahydro-1H,6H,7H-3a,6:7,9a-diepoxybenzo[de]isoquinoline-4,5-di-
carboxylate (4e). The solvent was removed under reduced pressure.
The residue was purified by silica gel column chromatography
(hexane/EtOAc = 3/1) to give compound 4e as light-yellow crystals
1
(2.99 g, 7.3 mmol, 73%). Rf 0.51 (EtOAc/hexane, 1:1, Sorbfil). H
NMR (600 MHz, CDCl3): δ 7.36 (2H, br d, J = 7.4 Hz, H-2-Ph and
H-6-Ph), 7.32 (2H, t, J = 7.4 Hz, H-3-Ph and H-5-Ph), 7.25 (1H, br t,
J = 7.4 Hz, H-4-Ph), 6.48 (1H, dd, J = 1.4 and J = 6.2 Hz, H-8), 6.31
(1H, d, J = 6.2 Hz, H-9), 5.22 (1H, s, H-6), 5.01 (1H, d, J = 1.4 Hz, H-
7), 3.84 (1H, d, J = 13.4 Hz, N-CH2A−Ph), 3.82 (1H, d, J = 13.4 Hz,
N-CH2B−Ph), 3.80 (3H, s, CO2Me), 3.76 (3H, s, CO2Me), 3.44 (1H,
d, J = 13.1 Hz, H-1A), 3.42 (1H, d, J = 13.1 Hz, H-3A), 2.85 (1H, d, J
= 13.1 Hz, H-1B), 2.73 (1H, d, J = 13.1 Hz, H-3B), 2.25 and 1.96 (1H
and 1H, d and d, J = 6.2 Hz, H-6a and H-9b). 13C NMR (100 MHz,
CDCl3): δ 164.1 (CO2Me), 162.6 (CO2Me), 149.0 (C-4), 144.7 (C-
5), 139.2 (C-9), 138.8 (C-8), 136.6 (C-1-Ph), 129.4 (C-2-Ph and C-6-
Ph), 128.3 (C-3-Ph and C-5-Ph), 127.4 (C-4-Ph), 87.6 and 84.5 (C-3a
and C-9a), 81.7 (C-6), 80.8 (C-7), 62.4 (N-CH2−Ph), 52.3 (CO2Me),
52.2 (CO2Me), 51.9 (C-1), 50.8 and 49.3 (C-6a and c-9b), 50.2 (C-3).
IR νmax/cm−1 (KBr): 1726, 1627, 1316, 1142. HRMS (ESI-TOF):
calcd for C23H23NO6 [M + H]+, 409.1525; found, 409.1539.
Dimethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-6a,9b-Dihydro-6H,7H-
3a,6:7,9a-diepoxybenzo[de]isochromene-4,5(1H,3H)-dicarboxylate
(4b). The precipitated crystals were filtered off and recrystallized from
EtOH (30 mL) to give the pure compound 4b as bright-yellow
needles (2.40 g, 7.5 mmol, 75%). Rf 0.66 (EtOAc, Sorbfil). Mp:
Dimethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-2-Acetyl-2,3,6a,9b-tet-
rahydro-1H,6H,7H-3a,6:7,9a-diepoxybenzo[de]isoquinoline-4,5-di-
carboxylate (4f). The precipitated crystals were filtered off and
recrystallized from DMF to give the pure compound 4f as a bright-
yellow powder (3.14 g, 8.7 mmol, 87%). Rf 0.44 (EtOAc/EtOH, 8:1,
1
167.9−169.1 °C (from EtOH). H NMR (600 MHz, DMSO-d6): δ
6.53 (1H, dd, J = 2.0 and J = 5.8 Hz, H-8), 6.41 (1H, d, J = 5.8 Hz, H-
9), 5.19 (1H, s, H-6), 4.97 (1H, d, J = 2.0 Hz, H-7), 4.15 (1H, d, J =
13.1 Hz, H-3A), 4.11 (1H, d, J = 12.4 Hz, H-1B), 4.03 (1H, d, J = 12.4
Hz, H-1B), 3.98 (1H, d, J = 13.1 Hz, H-3B), 3.73 (6H, s, 2 × CO2Me),
2.15 and 2.01 (2H, d, J = 6.2 Hz, H-6a and H-9b). 13C NMR (150
MHz, CDCl3): δ 163.5 (CO2Me), 162.8 (CO2Me), 146.9 (C-4), 146.5
(C-5), 139.4 (C-8), 137.7 (C-9), 86.5 and 83.8 (C-3a and C-9a), 82.3
(C-6), 81.1 (C-7), 66.2 and 64.6 (C-1 and C-3), 52.6 (CO2Me), 52.4
(CO2Me), 50.4 and 48.8 (C-6a and C-9b). IR νmax/cm−1 (KBr): 1731,
1
Sorbfil). Mp: 126.9−127.6 °C (from DMF). H NMR (600 MHz,
CDCl3), the mixture of amide rotamers in the ratio 1:1.1: δ 6.57 and
6.51 (1H, dd, J = 0.6 and J = 6.2 Hz, H-8), 6.39 and 6.38 (1H, d, J =
6.2 Hz, H-9), 5.34 (1H, d, J = 14.4 Hz, H-1A), 5.18 and 5.17 (1H, s,
H-6), 5.01 (1H, br d, J = 0.6 Hz, H-7), 4.37 and 4.34 (1H, d, J = 14.4
Hz, H-3A), 3.92 and 3.72 (1H, d, J = 14.4 Hz, H-1B), 3.84 and 3.82
(3H, s, CO2Me), 3.81 and 3.79 (3H, s, CO2Me), 3.33 and 3.15 (1H, d,
J = 14.4 Hz, H-3B), 2.30, 2.27, 2.15, and 2.13 (2H, d, J = 6.2 Hz, H-6a
G
DOI: 10.1021/acs.joc.8b00336
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
and 6−9b), 2.19 and 2.18 (3H, s, CO2Me). 13C NMR (150 MHz,
CDCl3), the mixture of amide rotamers: δ 171.0 and 170.8 (N-
COCH3), 163.7 and 163.3 (CO2Me), 162.7 and 162.6 (CO2Me),
147.1 and 147.2 (C-5), 146.2 and 146.1 (C-4), 139.9 and 139.8 (C-9),
138.2 and 137.9 (C-8), 86.8, 86.7, and 83.9 (C-3a and C-9a), 82.1 and
81.8 (C-6), 80.9 and 80.7 (C-7), 52.6 and 52.5 (CO2Me), 52.5 and
52.4 (CO2Me), 50.7 and 50.1 (C-9b and C-6a), 46.7, 45.5, 41.8, and
40.3 (C-1 and C-3), 21.9 (N-COMe). IR νmax/cm−1 (KBr): 2956,
1714, 1736, 1640, 1302, 1248. HRMS (ESI-TOF): calcd for
C18H19NO7 [M + H]+, 361.1162; found, 361.1140.
3.80 (3H, s, CO2Me), 3.76 (1H, br d, J = 13.5 Hz, H-1B), 3.57−3.35
(1H, m, H-3B), 2.31 and 2.18 (1H and 1H, d and d, J = 6.2 Hz, H-6a
and H-9b). 13C NMR (150 MHz, CDCl3), the mixture of amide
rotamers: δ 172.1 (CO-Ph), 163.8 and 163.4 (2 × CO2Me), 162.7 and
162.6 (2 × CO2Me), 147.5 and 147.3 (C-4), 146.2 and 146.1 (C-5),
139.8 and 139.5 (C-8), 138.4 and 137.9 (C-9), 135.6 and 135.5 (C-1-
Ph), 129.8 (C-4-Ph), 128.4 (C-3-Ph and C-5-Ph), 127.9 (C-2-Ph and
C-6-Ph), 86.7, 86.5, 82.1, and 81.0 (C-3a and C-9a), 83.8 (C-6), 80.9
(C-7), 52.6 and 52.5 (C-6a and C-9b), 50.9 (CO2Me), 50.5 (CO2Me),
47.8, 46.3, 42.5, and 41.0 (C-1 and C-3). IR νmax/cm−1 (KBr): 2954,
1714, 1628, 1272, 1076. HRMS (ESI-TOF): calcd for C23H21NO7 [M
+ H]+, 423.1318; found, 423.13135.
2-tert-Butyl 4,5-Dimethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-6a,9b-
dihydro-1H,6H,7H-3a,6:7,9a-diepoxybenzo[de]isoquinoline-
2,4,5(3H)-tricarboxylate (4j). The solvent was removed under reduced
pressure. The residue (viscous light-brown oil) was triturated with
hexane/Et2O, and the obtained solid was recrystallized from hexane/
EtOAc to give adduct 4j as a colorless powder (2.18 g, 5.4 mmol,
54%). Rf 0.35 (EtOAc/hexane, 1:1, Sorbfil). Mp: 148.7−149.2 °C
(from hexane/EtOAc). 1H NMR (600 MHz, CDCl3): δ 6.53 (1H, d, J
= 5.5 Hz, H-8), 6.37 (1H, d, J = 5.5 Hz, H-9), 5.18 (1H, s, H-7), 4.99
(1H, s, H-6), 4.82 (1H, br d, J = 12.9 Hz, H-1A), 4.66 (1H, br d, J =
12.9 Hz, H-3A), 3.83 (3H, s, CO2Me), 3.79 (3H, s, CO2Me), 3.57−
3.42 (1H, m, H-1B), 3.41−3.26 (1H, m, H-3B), 2.28 and 2.08 (1H
and 1H, d and d, J = 6.0 Hz, H-9b and H-6a), 1.46 (9H, s, C(CH3)3).
13C NMR (150 MHz, CDCl3), the mixture of amide rotamers: δ 163.9
Dimethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-2-(Trifluoroacetyl)-
2,3,6a,9b-tetrahydro-1H,6H,7H-3a,6:7,9a-diepoxybenzo[de]-
isoquinoline-4,5-dicarboxylate (4g). The solvent was removed under
reduced pressure. The residue (viscous brown oil) was triturated with
Et2O. Obtained crystals were filtered off and recrystallized from
hexane/EtOAc to give the pure compound 4g as a bright-yellow
powder (3.86 g, 9.3 mmol, 93%). Rf 0.57 (EtOAc/hexane, 2:1, Sorbfil).
1
Mp: 146.7−147.9 °C (from EtOAc). H NMR (400 MHz, CDCl3),
the mixture of amide rotamers in the ratio 1:1: δ 6.60 and 6.66 (1H, br
dd, J = 1.6 and J = 5.5 Hz, H-8), 6.41 and 6.39 (1H, d, J = 5.5 Hz, H-
9), 5.23 and 5.17 (1H, d, J = 14.7 Hz, H-1A), 5.20 and 5.19 (1H, s, H-
6), 5.03 (1H, br s, H-7), 4.54 and 4.50 (1H, d, J = 14.7 Hz, H-3A),
4.06 and 3.79 (1H, d, J = 14.7 Hz, H-1B), 3.84 and 3.83 (3H, s,
CO2Me), 3.82 and 3.81 (3H, s, CO2Me), 3.64 and 3.39 (1H, d, J =
14.7 Hz, H-3B), 2.36, 2.34, 2.20, and 2.19 (2H, d, J = 6.4 Hz, H-6a and
H-9b). 13C NMR (100 MHz, CDCl3), the mixture of amide rotamers:
δ 163.2 and 163.0 (CO2Me), 162.6 and 162.5 (CO2Me), 157.2 and
157.1 (q, J = 36.4 Hz, N-COCF3), 147.9 and 147.1 (C-5), 145.7 and
145.0 (C-4), 140.1 and 139.7 (C-9), 137.6 and 137.3 (C-8), 116.3 (q, J
= 288.5 Hz, N-COCF3), 85.9, 85.6, 83.3, and 83.2 (C-3a and C-9a),
82.1 and 82.0 (C-6), 80.9 and 80.8 (C-7), 52.6 and 52.5 (CO2Me),
52.4 and 52.3 (CO2Me), 51.0, 50.9, and 50.1 (C-3 and C-1), 45.8, 44.5,
43.7, and 42.3 (C-9b and C-6a). 19F NMR (282 MHz, CDCl3),
and 162.7 (CO2Me), 155.5 (C-5), 147.9 and 147.5 (C-4), 146.3 and
145.6 (N-CO2tBu), 139.5 and 139.4 (C-9), 138.4 (C-8), 85.6 (C-2),
83.7 and 80.5 (C-3a and C-9a), 81.9 (C-6), 80.9 (C-7), 52.5 (CO2Me),
52.4 (CO2Me), 50.9 and 49.7 (C-9b and C-6a), 44.5, 43.3, 42.0, and
41.8 (C-1 and C-3), 28.4 (NCO2C(CH3)3). IR νmax/cm−1 (KBr):
2960, 1697, 1623, 1273, 1152. HRMS (ESI-TOF): calcd for
C21H25NO8 [M + H]+, 419.1580; found, 419.1565.
mixture of amide rotamers: δ −68.4 (s, CF3), −68.5 (s, CF3). IR νmax
/
General Procedure for the Synthesis of the Pincer Adducts 3k−
m. The appropriate alkyne (7.50 mmol) was added to a solution of
difurfuryl ether 1b (0.89 g, 5.00 mmol) in PhH (15 mL). The mixture
was heated at reflux for 32−47 h (Table 3). The solvent was removed
under reduced pressure. The residue (viscous yellow oil) was dissolved
in Et2O (15 mL) and left for 48 h at −14 °C. Further treatment of the
resulting mixtures is given below.
Diethyl (3aRS,6SR,7RS,9aSR)-6H,7H-3a,6:7,9a-Diepoxybenzo[de]-
isochromene-6a,9b-(1H,3H)-dicarboxylate (3k). After cooling, the
solid was filtered off and recrystallized from hexane/EtOAc to give
compound 3k as a white powder (0.85 g, 2.45 mmol, 49%). Rf 0.59
(EtOAc, Sorbfil). Mp: 113.7−114.9 °C (from hexane/EtOAc). 1H
NMR (600 MHz, CDCl3): δ 6.69 (2H, dd, J = 1.5 and J = 5.5 Hz, H-5
and H-8), 6.41 (2H, d, J = 5.5 Hz, H-4 and H-9), 5.16 (2H, d, J = 1.5
Hz, H-6 and H-7), 4.28 (2H, d, J = 12.3 Hz, H-1A and H-3A), 4.25
(2H, d, J = 12.3 Hz, H-1B and H-3B), 4.09 (4H, q, J = 7.4 Hz, 2 ×
OCH2Me), 1.25 (3H, t, J = 7.4 Hz, OCH2Me), 1.22 (3H, t, J = 7.4 Hz,
OCH2Me). 13C NMR (150 MHz, CDCl3): δ 169.9 and 169.7 (2 ×
CO2Et), 140.5 (C-4 and C-9), 137.6 (C-5 and C-8), 87.7 (C-3a and C-
9a), 84.1 (C-6 and C-7), 71.4 and 67.6 (C-9b and C-6a), 64.8 (C-1
and C-3), 61.4 and 61.3 (2 × OCH2CH3), 14.1 and 14.0 (2 ×
OCH2CH3). IR νmax/cm−1 (KBr): 2840, 1742, 1731, 1075, 1003.
HRMS (ESI-TOF): calcd for C18H20O7 [M + H]+, 348.1209; found,
348.1234.
cm−1 (KBr): 2955, 1739, 1690, 1333, 1245. HRMS (ESI-TOF): calcd
for C18H16F3NO7 [M + H]+, 415.0879; found, 415.0855.
Dimethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-2-(Trichloroacetyl)-
2,3,6a,9b-tetrahydro-1H,6H,7H-3a,6:7,9a-diepoxybenzo[de]-
isoquinoline-4,5-dicarboxylate (4h). The solvent was removed under
reduced pressure. The residue was purified by silica gel column
chromatography (hexane/EtOAc = 2:1) to give the title compound as
a brown solid. The obtained crystals were recrystallized from EtOAc to
give adduct 4h as small colorless needles (3.38 g, 7.31 mmol, 73%). Rf
0.41 (EtOAc/hexane, 1:2, Sorbfil). Mp: 179.8−181.0 °C (from
hexane/EtOAc). 1H NMR (600 MHz, DMSO-d6): δ 6.57 (1H, dd, J =
1.4 and J = 5.3 Hz, H-8), 6.51 (1H, d, J = 5.3 Hz, H-9), 5.20 (1H, s, H-
6), 4.96 (1H, d, J = 1.4 Hz, H-7), 4.93 (1H, br d, J = 14.4 Hz, H-3A),
4.87 (1H, br d, J = 14.4 Hz, H-1A), 4.13 (1H, br d, J = 14.4 Hz, H-3B),
3.77 (1H, br d, J = 14.4 Hz, H-1B), 3.75 (3H, br s, CO2Me), 3.73 (3H,
br s, CO2Me), 2.22 and 2.13 (1H and 1H, d and d, J = 6.2 Hz, H-6a
and H-9b). 13C NMR (100 MHz, CDCl3): δ 163.2 (CO2Me), 162.6
(CO2Me), 160.9 (N-COCCl3), 146.9 (C-4), 145.9 (C-5), 139.7 (C-8),
137.9 (C-9), 92.9 (N-COCCl3), 86.0 and 83.5 (C-3a and C-9a), 81.1
(C-6), 80.9 (C-7), 52.6 (CO2Me), 52.5 (CO2Me), 50.8 and 49.9 (C-6a
and C-9b), 46.7 and 45.1 (C-1 and C-3). IR νmax/cm−1 (KBr): 2954,
1741, 1711, 1676, 1238. HRMS (ESI-TOF): calcd for C18H16Cl3NO7
[M + H]+, 462.9992; found, 462.9976.
Dipropan-2-yl (3aRS,6SR,7RS,9aSR)-6H,7H-3a,6:7,9a-
Diepoxybenzo[de]isochromene-6a,9b(1H,3H)-dicarboxylate (3l).
After cooling, the white powder of byproduct 4l (0.17 g, 0.45 mmol,
9%) was filtered off. The mother liquid was concentrated and purified
by silica gel column chromatography (petroleum ether/Et2O) to give
compound 3l as colorless prisms (0.50 g, 1.33 mmol, 27%). Rf 0.61
(hexane/EtOAc, 8:1, Sorbfil). Mp: 114.4−115.7 °C (from hexane/
Dimethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-2-Benzoyl-2,3,6a,9b-
tetrahydro-1H,6H,7H-3a,6:7,9a-diepoxybenzo[de]isoquinoline-4,5-
dicarboxylate (4i). The solvent was removed under reduced pressure.
The residue (viscous brown oil) was triturated with Et2O. The
precipitated crystals were filtered off and recrystallized from an EtOH/
DMF mixture to give the pure compound 4i as a bright-yellow powder
(3.68 g, 8.7 mmol, 87%). Rf 0.36 (EtOAc/hexane, 4:1, Sorbfil). Mp:
1
1
193.0−194.1 °C (from EtOH/DMF). H NMR (600 MHz, CDCl3),
Et2O). H NMR (600 MHz, CDCl3): δ 6.68 (2H, dd, J = 1.4 and J =
all signals broaden due to restricted C−N amide bond rotation: δ
7.56−7.54 (2H, m, H-2-Ph and H-6-Ph), 7.38−7.37 (3H, m, H-3-Ph,
H-4-Ph and H-5-Ph), 6.54 (1H, br d, J = 5.5 Hz, H-8), 6.44−6.27 (1H,
m, H-9), 5.41 (1H, d, J = 13.5 Hz, H-1A), 5.22 (1H, s, H-6), 5.04 (1H,
s, H-7), 4.42 (1H, br d, J = 13.5 Hz, H-3A), 3.85 (3H, br s, CO2Me),
5.5 Hz, H-5 and H-8), 6.42 (2H, d, J = 5.5 Hz, H-4 and H-9), 5.14
(2H, d, J = 1.4 Hz, H-6 and H-7), 4.98−4.91 (2H, m, 2 × OCHMe2),
4.28 (2H, d, J = 12.4 Hz, H-1A and H-3A), 4.23 (2H, d, J = 12.4 Hz,
H-1B and H-3B), 1.24 and 1.22 (12H, d, J = 6.2 Hz, 2 × OCHMe2).
13C NMR (100 MHz, CDCl3): δ 168.8 and 168.7 (2 × CO2CHMe2),
H
DOI: 10.1021/acs.joc.8b00336
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
140.0 (C-4 and C-9), 137.3 (C-5 and C-8), 87.4 (C-3a and C-9a), 83.8
(C-6 and C-7), 71.5 and 67.4 (C-9b and C-6a), 69.1 and 68.8 (2 ×
(3p). According to 1H NMR analysis, the resulting solid was the
mixture of 3p/4p (1.20 g, 2.86 mmol, 57%) in the ratio 88:12.
Recrystallization of this solid from hexane/EtOAc gave the mixture of
3p/4p in the ratio 82:18 as colorless needles (0.61 g, 1.45 mmol,
29%). Rf 0.64 (hexane, Sorbfil). 1H NMR for 3p (600 MHz, CDCl3): δ
6.60 (2H, dd, J = 1.7 and J = 5.0 Hz, H-5 and H-8), 6.45 (2H, d, J =
5.0 Hz, H-4 and H-9), 5.05 (2H, d, J = 1.7 Hz, H-6 and H-7), 3.57
(2H, d, J = 14.9 Hz, H-1A and H-3A), 2.90 (2H, d, J = 14.9 Hz, H-1B
and H-3B), 1.44 (9H, s, CO2tBu), 1.42 (9H, s, CO2tBu). 13C NMR for
3p (100 MHz, CDCl3): δ 168.6 and 168.5 (2 × CO2tBu), 141.4 (C-4
and C-9), 138.7 (C-5 and C-8), 87.2 (C-3a and C-9a), 83.5 (C-6 and
C-7), 74.3 and 67.9 (C-9b and C-6a), 28.1 (2 × CO2tBu), 27.4 (C-1
and C-3). IR νmax/cm−1 (KBr): 2981, 1728, 1709, 1008, 969. HRMS
(ESI-TOF): calcd for C22H28SO6 [M + H]+, 420.1607; found,
420.1622.
CHMe2), 64.7 (C-1 and C-3), 21.6 and 21.5 (2 × CHMe2). IR νmax
/
cm−1 (KBr): 2981, 1744, 1727, 1101, 1073. HRMS (ESI-TOF): calcd
for C20H24O7 [M + H]+, 376.1522; found, 376.1501.
Di-tert-butyl (3aRS,6SR,7RS,9aSR)-6H,7H-3a,6:7,9a-
Diepoxybenzo[de]isochromene-6a,9b(1H,3H)-dicarboxylate (3m).
After cooling, light-brown prisms of byproduct 4m (0.40 g, 1.0
mmol, 20%) were filtered off. The mother liquid was concentrated and
purified by silica gel column chromatography (petroleum ether/Et2O)
to give compound 3m as colorless needles (0.94 g, 2.32 mmol, 46%).
Rf 0.52 (hexane/EtOAc, 2:1, Sorbfil). Mp: 132.8−139.4 °C (from
hexane). 1H NMR (600 MHz, CDCl3): δ 6.66 (2H, dd, J = 1.5 and J =
5.5 Hz, H-5 and H-8), 6.42 (2H, d, J = 5.5 Hz, H-4 and H-9), 5.09
(2H, d, J = 1.5 Hz, H-6 and H-7), 4.27 (2H, d, J = 12.7 Hz, H-1A and
H-3A), 4.22 (2H, d, J = 12.7 Hz, H-1B and H-3B), 1.44 (9H, s,
CO2tBu), 1.43 (9H, s, CO2tBu). 13C NMR (100 MHz, CDCl3): δ
168.4 and 168.3 (2 × CO2tBu), 139.6 (C-4 and C-9), 137.6 (C-5 and
C-8), 87.4 (C-3a and C-9a), 83.9 (C-6 and C-7), 82.1 and 81.7 (2 ×
CO2CMe3), 72.2 and 67.5 (C-9b and C-6a), 64.8 (C-1 and C-3), 28.1
(2 × CO2CMe3). IR νmax/cm−1 (KBr): 2980, 1724, 1707, 1172, 1092.
HRMS (ESI-TOF): calcd for C22H28O7 [M + H]+, 404.1835; found,
404.1858.
General Procedure for the Synthesis of the Domino Adducts 4k−
m. The appropriate alkyne (5.50 mmol) was added to a solution of
difurfuryl ether 1b (0.89 g, 5.00 mmol) in o-Me2C6H4 (15 mL). The
mixture was heated at reflux for 4−7 h (Table 3), then was cooled to
rt, and was left for 24 h at −14 °C. The obtained solids were filtered
off and washed with Et2O to give compounds 4k−m.
Diethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-6a,9b-Dihydro-6H,7H-
3a,6:7,9a-diepoxybenzo[de]isochromene-4,5(1H,3H)-dicarboxylate
(4k). White prisms (1.23 g, 3.54 mmol, 71%). Rf 0.52 (EtOAc/hexane,
1:4, Sorbfil). Mp: 158.6−159.2 °C (from EtOH). 1H NMR (600 MHz,
CDCl3): δ 6.54 (1H, dd, J = 1.7 and J = 5.8 Hz, H-8), 6.35 (1H, d, J =
5.8 Hz, H-9), 5.23 (1H, s, H-6), 5.04 (1H, d, J = 1.7 Hz, H-7), 4.41
(1H, d, J = 12.4 Hz, H-1A), 4.39 (1H, d, J = 13.2 Hz, H-3A), 4.28−
4.24 (4H, m, 2 × OCH2Me), 4.15 (1H, d, J = 12.4 Hz, H-1B), 3.99
(1H, d, J = 13.2 Hz, H-3B), 2.30 and 2.13 (1H and 1H, d and d, J = 6.6
Hz, H-6a and H-9b), 1.32 (3H, t, J = 7.4 Hz, OCH2Me), 1.31 (3H, t, J
= 7.4 Hz, OCH2Me). 13C NMR (150 MHz, CDCl3): δ 163.2 and
162.6 (2 × CO2CHMe2), 146.6 (C-5), 146.4 (C-4), 139.5 (C-8), 137.7
(C-9), 86.5 and 83.9 (C-9a and C-3a), 82.3 and 81.2 (C-6 and C-7),
66.3 and 64.7 (2 × CH2Me), 61.7 and 61.5 (C-3 and C-1), 50.5 and
48.9 (C-6a and C-9b), 14.2 and 14.1 (2 × CHMe2). IR νmax/cm−1
(KBr): 2824, 1716, 1702, 1102, 1027. HRMS (ESI-TOF): calcd for
C18H20O7 [M + H]+, 348.1209; found, 348.1232.
General Procedure for the Synthesis of the Pincer Adducts 3n−p.
The corresponding alkyne (7.50 mmol) was added to a solution of
bis(furan-2-ylmethyl)sulfane 1c (1.0 g, 5.0 mmol) in PhH (20 mL).
The mixture was heated at reflux for 30−31 h (GC−MS monitoring
until disappearance of the starting material). The solvent was removed
under reduced pressure. The residue (viscous light-brown oil) was
triturated with hexane, and the obtained solid was filtered off and
recrystallized to give compounds 3n−p as colorless needles.
Diethyl (3aRS,6SR,7RS,9aSR)-6H,7H-3a,6:7,9a-Diepoxybenzo[de]-
isothiochromene-6a,9b-(1H,3H)-dicarboxylate (3n). According to
1H NMR analysis, the resulting solid was the mixture of 3n/4n (1.44 g,
4.00 mmol, 81%) in the ratio 75:25. Recrystallization from a DMF/
EtOH mixture gave the mixture of 3n/4n = 20:80 as colorless needles
(1.08 g, 2.96 mmol, 60%, partial isomerization observed at
1
recrystallization). Rf 0.59 (hexane/EtOAc, 4:1, Sorbfil). H NMR for
Dipropan-2-yl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-6a,9b-Dihydro-
6H,7H-3a,6:7,9a-diepoxybenzo[de]isochromene-4,5(1H,3H)-dicar-
boxylate (4l). Light-brown powder (1.05 g, 2.79 mmol, 56%). Rf 0.47
(hexane, Sorbfil). Mp: 138.1−139.4 °C (from EtOH). H NMR (600
3n (600 MHz, CDCl3): δ 6.62 (2H, dd, J = 1.7 and J = 5.0 Hz, H-5
and H-8), 6.46 (2H, d, J = 5.0 Hz, H-4 and H-9), 5.13 (2H, d, J = 1.7
Hz, H-6 and H-7), 4.11−4.05 (4H, m, 2 × OCH2Me), 3.58 (2H, d, J =
14.9 Hz, H-1A and H-3A), 2.93 (2H, d, J = 14.9 Hz, H-1B and H-3B),
1.23 (6H, dt, J = 2.5 and J = 7.4 Hz, 2 × OCH2Me). 13C NMR for 3n
(150 MHz, CDCl3): δ 168.9 and 168.7 (2 × CO2Et), 141.4 (C-4 and
C-9), 138.1 (C-5 and C-8), 87.3 (C-3a and C-9a), 83.6 (C-6 and C-7),
73.8 and 67.5 (C-9b and C-6a), 61.4 and 61.3 (2 × OCH2CH3), 27.4
(C-1 and C-3), 14.2 and 14.1 (2 × OCH2CH3). IR νmax/cm−1 (KBr):
2870, 1737, 1720, 1098, 1022. HRMS (ESI-TOF): calcd for
C18H20SO6 [M + H]+, 364.0981; found, 364.0993.
Dipropan-2-yl (3aRS,6SR,7RS,9aSR)-6H,7H-3a,6:7,9a-
Diepoxybenzo[de]isothiochromene-6a,9b(1H,3H)-dicarboxylate
(3o). According to 1H NMR analysis, the resulting solid was the
mixture of 3o/4o (1.60 g, 4.15 mmol, 83%) in the ratio 86:14.
Recrystallization of this solid from hexane/EtOAc gave the mixture
3o/4o in the ratio 91:9 as colorless needles (0.88 g, 2.25 mmol, 45%).
Rf 0.53 (hexane, Sorbfil). 1H NMR for 3o (600 MHz, CDCl3): δ 6.62
(2H, dd, J = 1.7 and J = 5.8 Hz, H-5 and H-8), 6.46 (2H, d, J = 5.8 Hz,
H-4 and H-9), 5.10 (2H, d, J = 1.7 Hz, H-6 and H-7), 4.96 (1H,
heptet, J = 6.4 Hz, OCHMe2), 4.91 (1H, heptet, J = 6.4 Hz,
OCHMe2), 3.57 (2H, d, J = 14.9 Hz, H-1A and H-3A), 2.93 (2H, d, J
= 14.9 Hz, H-1B and H-3B), 1.25 and 1.23 (6H and 6H, d and d, J =
6.4 Hz, 2 × OCHMe2). 13C NMR for 3o (150 MHz, CDCl3): δ 168.9
and 168.7 (2 × CO2CHMe2), 141.3 (C-4 and C-9), 138.9 (C-5 and C-
8), 87.2 (C-3a and C-9a), 83.5 (C-6 and C-7), 73.9 and 69.2 (C-9b
and C-6a), 68.9 and 67.5 (2 × CHMe2), 27.4 (C-1 and C-3), 21.7 (2 ×
CHMe2). IR νmax/cm−1 (KBr): 2936, 1727, 1709, 1085, 1051. HRMS
(ESI-TOF): calcd for C20H24SO6 [M + H]+, 392.1294; found,
392.1275.
1
MHz, CDCl3): δ 6.55 (1H, dd, J = 2.0 and J = 6.2 Hz, H-8), 6.35 (1H,
d, J = 6.2 Hz, H-9), 5.20 (1H, s, H-6), 5.11 (2H, heptet, J = 6.5 Hz, 2
× OCHMe2), 5.04 (1H, d, J = 2.0 Hz, H-7), 4.41 (1H, d, J = 13.1 Hz,
H-1A), 4.39 (1H, d, J = 13.1 Hz, H-3A), 4.11 (1H, d, J = 13.1 Hz, H-
1B), 3.98 (1H, d, J = 13.1 Hz, H-3B), 2.30 and 2.12 (1H and 1H, d
and d, J = 6.2 Hz, H-6a and H-9b), 1.32−1.28 (12H, m, 2 ×
OCHMe2). 13C NMR (100 MHz, CDCl3): δ 162.8 and 162.1 (2 ×
CO2iPr), 146.8 (C-5), 145.9 (C-4), 139.4 (C-8), 137.6 (C-9), 86.4 and
83.8 (C-9a and C-3a), 82.2 and 81.2 (C-6 and C-7), 69.7 and 69.3 (2
× CO2CHMe2), 66.3 and 64.7 (C-3 and C-1), 50.5 and 28.8 (C-6a and
C-9b), 21.8 and 21.7 (2 × CO2CHMe2). IR νmax/cm−1 (KBr): 2981,
1726, 1709, 1260, 1107, 1075. HRMS (ESI-TOF): calcd for C20H24O7
[M + H]+, 376.1522; found, 376.1501.
Di-tert-butyl (3aRS,6SR,6aS,7SR,9aRS,9bSR)-6a,9b-Dihydro-
6H,7H-3a,6:7,9a-diepoxybenzo[de]isochromene-4,5(1H,3H)-dicar-
boxylate (4m). Light-brown prisms 4m (0.40 g, 1.0 mmol, 20%). Rf
0.41 (hexane/EtOAc, 1:4, Sorbfil). Mp: 142.1−143.6 °C (from
hexane/EtOAc). 1H NMR (600 MHz, CDCl3): δ 6.54 (1H, dd, J = 1.4
and J = 6.2 Hz, H-8), 6.33 (1H, d, J = 6.2 Hz, H-9), 5.14 (1H, s, H-6),
5.02 (1H, d, J = 1.4 Hz, H-7), 4.40 (1H, d, J = 13.0 Hz, H-1A), 4.38
(1H, d, J = 13.0 Hz, H-3A), 4.08 (1H, d, J = 13.0 Hz, H-1B), 3.97 (1H,
d, J = 13.0 Hz, H-3B), 2.29 and 2.10 (1H and 1H, d and d, J = 6.2 Hz,
H-6a and H-9b), 1.51 and 1.49 (18H, s, 2 × CO2tBu). 13C NMR (100
MHz, CDCl3): δ 162.1 and 161.6 (2 × CO2tBu), 146.7 (C-5), 145.9
(C-4), 139.3 (C-8), 137.4 (C-9), 86.1 and 83.7 (C-9a and C-3a), 83.0
and 82.4 (2 × CO2CMe3), 82.2 and 81.0 (C-6 and C-7), 66.2 and 64.7
(C-1 and C-3), 50.3 and 48.7 (C-6a and C-9b), 28.1 and 28.0 (2 ×
CO2CMe3). IR νmax/cm−1 (KBr): 2973, 1732, 1700, 1258, 1160, 1132.
Di-tert-butyl (3aRS,6SR,7RS,9aSR)-6H,7H-3a,6:7,9a-
Diepoxybenzo[de]isothiochromene-6a,9b(1H,3H)-dicarboxylate
I
DOI: 10.1021/acs.joc.8b00336
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
HRMS (ESI-TOF): calcd for C22H28O7 [M + H]+, 404.1835; found,
404.1807.
Notes
The authors declare no competing financial interest.
General Procedure for the Synthesis of the Domino Adducts
4n,o. The appropriate alkyne (5.50 mmol) was added to a solution of
bis(furan-2-ylmethyl)sulfane 1c (1.00 g, 5.00 mmol) in o-Me2C6H4
(20 mL). The mixture was heated at reflux for 4 h (∼140 °C), and
then the reaction mixture was cooled to +4 °C. The solvent was
decanted, and the obtained solids were washed with hexane and dried
in air to give compounds 4n,o.
Diethyl (3aRS,6SR,6aRS,7SR,9aRS,9bSR)-6a,9b-Dihydro-6H,7H-
3a,6:7,9a-diepoxybenzo[de]isothiochromene-4,5(1H,3H)-dicarboxy-
late (4n). White powder (1.72 g, 4.75 mmol, 95%). Rf 0.53 (hexane/
EtOAc, 4:1, Sorbfil). Mp: 192.8−193.7 °C (with decomp from DMF).
1H NMR (600 MHz, CDCl3): δ 6.56 (1H, dd, J = 1.7 and J = 5.8 Hz,
H-8), 6.29 (1H, d, J = 5.8 Hz, H-9), 5.22 (1H, s, H-6), 5.02 (1H, d, J =
1.7 Hz, H-7), 4.31−4.22 (4H, m, 2 × OCH2Me), 3.48 (1H, d, J = 14.0
Hz, H-1A), 3.35 (1H, d, J = 14.0 Hz, H-3A), 3.02 (2H, dd, J = 1.6 and
14.0 Hz, H-1B and H-3B), 2.34 and 2.03 (1H and 1H, d and d, J = 6.3
Hz, H-6a and H-9b), 1.32 (3H, t, J = 7.4 Hz, OCH2Me), 1.30 (3H, t, J
= 7.4 Hz, OCH2Me). 13C NMR (150 MHz, CDCl3): δ 163.8 and
162.2 (2 × CO2CHMe2), 148.5 (C-5), 145.4 (C-4), 139.9 (C-8), 139.7
(C-9), 86.4 and 83.1 (C-9a and C-3a), 81.5 and 80.6 (C-6 and C-7),
61.7, 61.4, 52.9, and 48.8 (2 × CH2Me, C-9b and C-6a), 28.7 and 26.8
(C-3 and C-1), 14.1 and 14.0 (2 × CHMe2). IR νmax/cm−1 (KBr):
2833, 1727, 1709, 1091, 984. HRMS (ESI-TOF): calcd for C18H20SO6
[M + H]+, 364.0981; found, 364.0969.
ACKNOWLEDGMENTS
■
The authors are grateful to Dr. Victor N. Khrustalev (RUDN
University) for the X-ray diffraction study. (This part of the
research was prepared with the support of the “RUDN
University Program 5-100”.) Funding for this research was
provided by the Ministry of Education and Science of the
Russian Federation (award no. 4.1154.2017/4.6). R.A.N. thanks
the Program of Fundamental Research for state academies for
years 2013−2020 (no. 01201363817) for support of NMR
studies (Engelhardt Institute of Molecular Biology, Russian
Academy of Sciences).
REFERENCES
■
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= 6.6 Hz, OCHMe2), 1.30 (6H, d, J = 6.6 Hz, OCHMe2). 13C NMR
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139.8 (C-4), 129.6 (C-8), 125.8 (C-9), 86.3 (C-9a), 83.1 (C-3a), 81.4
and 80.6 (C-6 and C-7), 69.7, 69.3, and 52.8 (2 × CO2CHMe2 and C-
9b), 48.8 (C-6a), 28.7 and 26.9 (C-3 and C-1). IR νmax/cm−1 (KBr):
2878, 1729, 1706, 1036, 984. HRMS (ESI-TOF): calcd for C20H24SO6
[M + H]+, 392.1294; found, 392.1311.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.8b00336.
■
S
Copies of NMR spectra, details of kinetic and quantum-
chemical calculations, and X-ray crystallography data for
compounds 3f and 4f (PDF)
Crystal data of 3f (CIF)
Crystal data of 4f (CIF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: fzubkov@sci.pfu.edu.ru. Fax: +7 495-952-2644. Tel:
+7 495-955-0779.
■
ORCID
Rinat R. Aysin: 0000-0003-1402-9878
Roman A. Novikov: 0000-0002-3740-7424
Fedor I. Zubkov: 0000-0002-0289-0831
Author Contributions
(4) (a) Cram, D. J.; Knox, G. R. A cross-breeding reaction, a bent
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1961, 83, 2204−2205. (b) Cram, D. J.; Montgomery, C. S.; Knox, G.
R. Macro rings. XXXIII. A 1,6 to 1,6 cycloaddition reaction, a Diels−
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
J
DOI: 10.1021/acs.joc.8b00336
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Alder insertion reaction, and bent benzene rings. J. Am. Chem. Soc.
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simultaneous double Diels−Alder addition of 1,1-bis(3,5-dimethylfur-
2-yl)ethane; toward a new, asymmetric synthesis of long-chain
polypropionate fragments and analogues. Tetrahedron Lett. 1996, 37,
4149−4152. (d) Schwenter, M.-E.; Schenk, K.; Scopelliti, R.; Vogel, P.
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(5) For researches closely related to the subject of this work, see:
(a) Paquette, L. A.; Wyvratt, M. J.; Berk, H. C.; Moerck, R. E. Domino
Diels−Alder reactions. 6. Domino Diels−Alder cycloadditions to 9,10-
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cycloadducts from the condensation of N,N′-dipyrrolylmethane with
acetylenic dienophiles: synthesis of the 10,12-diazapentacyclo-
[7.3.1.04,12.05,13.06,10]trideca-2,7-diene ring system. J. Chem. Soc.,
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(7) Full crystallographic data for structures 3f and 4f have been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication numbers CCDC 970102 and 970101.
Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK. (Fax: +44 (0)1233
336033. E-mail: deposit@ccdc.cam.ac.uk.)
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K
DOI: 10.1021/acs.joc.8b00336
J. Org. Chem. XXXX, XXX, XXX−XXX