Gold-silver catalyzed straightforward one pot synthesis of pyrano[3,4-: B] pyrrol-7(1 H)-ones

Article abstract of DOI:10.1039/c7ob01849e

Pyrano[3,4-b]pyrrol-7(1H)-one is a bicyclic structure that is rarely described in the literature but is found in numerous polycyclic natural products as lamellarins. This work presents a one-pot synthesis of pyrano[3,4-b]pyrrol-7(1H)-one substituted in the 2- and 5-position. The reaction proceeds via a one-pot two step 5-endo-dig and 6-endo-dig cyclization catalyzed by a cationic gold complex with high regioselectivity.

Full text of DOI:10.1039/c7ob01849e

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Gold-silver catalyzed straightforward one pot synthesis of
pyrano[3,4-b]pyrrol-7(1H)-ones.
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
a*
P.-O. Delaye, J. Petrignet, E. Thiery and J. Thibonnet
Pyrano[3,4-b]pyrrol-7(1H)-one is a bicyclic structure that is rarely described in the literature but found in numerous
polycyclic natural products as Lamellarins. This work presents a one-pot synthesis of pyrano[3,4-b]pyrrol-7(1H)-one
substituted in 2- and 5-position. The reaction proceeds via a one-pot two steps 5-endo-dig and 6-endo-dig cyclization
catalyzed by a cationic gold complex with high regioselectivity.
DOI: 10.1039/x0xx00000x
www.rsc.org/
structures starting from 1-methypyrrole-2-carboxylic acid, pyranone
ring being formed by annulation with alkynes in presence of
Introduction
9
b,c
ruthenium or rhodium catalysts.
Herein, the development of a
Pyrano[3,4-b]pyrrol-7(1H)-one is a bicyclic structure found in many
polyheterocyclic molecules and natural compounds as Ningalin B
and Lamellarins (Figure 1). Ningalin B is a marine natural product,
and is a potent multidrug resistance reversal agents of cancer cells
Ningalin B is a marine natural product, and is a potent reversal
new synthetic pathway to access both pyrrole and pyranone cycles
in a one-pot process is highly challenging.
1
agent of multidrug resistance cancer cells. Pentacyclic Lamellarin D
O
is one of the first example of Lamellarins alkaloids isolated from
various marine organisms such as mollusks, sponges and
N
H
O
pyrano[3,4,b]pyrrol-7(1H)-one
2
,3
ascidians. Since their discovery in 1985, about 50 new Lamellarins
have been isolated and interest in these molecules has been
growing due to their cytotoxicity and antitumor activities,
multidrugs resistance reversal activity, HIV-1 integrase inhibition,
O
O
O
4
and immunomodulatory activity. Due to their various biological
N
N
N
H
O
H
O
H
O
properties and the difficulty in obtaining large quantities of natural
resources, many total syntheses of various Lamellarins have been
chromeno[3,4-b]-
pyrrol-4(3H)-one
chromeno[3,4-b]- pyrano[3,4-b]indol-
indol-6(7H)-one
1(9H)-one
3
,5
published in the last decade. The preparation of analogs of these
alkaloids has also been studied as an issue for pharmaco-
OH
HO
HO
MeO
MeO
HO
MeO
HO
OH
OH
6
modulating the Lamellarin core and for designing structures that
are easier to access. Thus, diversely substituted molecules with
7
O
O
tricyclic chromeno[3,4-b]-pyrrol-4(3H)-one and chromeno[3,4-b]-
8
N
N
indol-6(7H)-one scaffold were prepared. The latter showed
O
O
inhibitory activities of DYRK1A kinase. However, the bicyclic
pyrano[3,4-b]pyrrol-7(1H)-one is rarely described in the literature,
and to the best of our knowledge, only few examples have been
NingalinB
OH
Lamellarin D
9
reported. Indeed, most recent works proposed an access to those
OH
Figure 1.
Over the past ten years, our group has been developing
methodologies based on electrophilic or transition metal-catalyzed
cyclization. We reported various approaches for the synthesis of
1
0
biologically interesting heterocycles, such as tricyclic pyrano[3,4-
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b]indol-1(9H)-ones synthetized by a copper (I) catalyzed domino Figure 2. Retrosynthetic pathways for the synthesis of pyrano[3,4-
1
0d
reaction. The strategy we envision here for the preparation of b]pyrrol-7(1H)-ones.
pyrano[3,4-b]pyrrol-7(1H)-ones 3 is based on a double alkyne
11
12
activation of diynes 2 (Figure 2), catalyzed by platinum or gold
Results and discussion
13
salts which are known for their remarkable activation of alkynes.
The compound 3 could be formed via heterocycle rings obtained
through 5-endo-dig and 6-endo-dig cyclization modes. The latter
First, β,β-dibromodehydroalanine derivatives
1 and 1’ were
competes with the 5-exo mode—the regioselectivity is known to be prepared according to procedures previously described in the
1
5
dependent on the chain length, on the substitution pattern on the literature (four steps from Serine (Scheme 1)). Compounds 2 were
1
4
chain, and on the transition metal chosen. The diynes 2 can be then prepared in average to good yields using a double Sonogashira
prepared via double Sonogashira cross coupling from β,β- cross coupling between compound 1 and various alkynes using a
1
5c
dibromodehydroalanine derivatives 1 (Figure 2).
modified procedure from the literature. Derivative of compound
1
were prepared by replacing tert-butoxycarbonyl group by
benzyloxycarbonyl group. Unfortunately, we did not succeed in
carrying out the double Sonogashira coupling with such a protective
group. Mono coupling debrominated product was obtained.
a
Table 1. Optimization of reaction conditions
b
b
Entry
1
Substrate
Catalysts
Additive
-
Conditions
3
-
4
2’a
PtCl
PtCl
PtCl
4
2
2
, 5 mol%
, 5 mol%
, 5 mol%
Toluene, 90°C,
overnight
4’a, 64 %
4’a, 84 %
4a, 70 %
4a, 70 %
4’a, 52 %
2
3
4
5
6
7
8
9
2’a
2a
2a
2’a
2’a
2a
2a
2a
2a
2a
2a
-
-
-
-
Toluene, 90°C,
overnight
-
-
-
-
Toluene, 90°C,
overnight
PtCl , 5 mol%
Toluene, 75°C,
overnight
2
PPh
AgBF
PPh AuCl, 5 mol%,
AgBF , 5 mol%
3
AuCl, 5 mol%,
CH
2
Cl
2
, 50°C,
4
, 6 mol%
24 h
c
c
3
t-BuOH
(3 equiv.)
t-BuOH
Benzene, rt,
overnight
nd
nd
4
PPh
AgBF
3
AuCl, 5 mol%,
, 5 mol%
Benzene, rt,
overnight
3a, 52 %
3a, 72 %
3a, 60 %
3a, 41 %
-
-
-
-
-
-
4
(3 equiv.)
PPh AuCl, 10 mol%, t-BuOH
Benzene, rt,
overnight
3
AgBF
PPh AuCl, 10 mol%, t-BuOH
AgBF , 10 mol% (3 equiv.)
PPh AuCl, 10 mol%, t-BuOH
AgBF , 10 mol%
4
, 10 mol%
(3 equiv.)
3
Toluene, rt,
overnight
4
1
1
1
0
1
2
3
2 2
CH Cl , rt,
overnight
(3 equiv.)
4
PPh
3
AuCl, 5 mol%,
t-BuOH
Toluene, rt,
overnight
(
3equiv.)
t-BuOH
3 equiv.)
c
c
AgBF , 10 mol%
Benzene, rt,
nd
nd
4
(
overnight
a
b
c
Reactions were typically performed with 0.5 mmol of substrate. Isolated yield. Inseparable mixture.
2
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a
Table 2. Synthesis of pyrano[3,4-b]pyrrol-7(1H)-ones 3.
Scheme 1. Synthesis of compounds 2.
We investigated the use of platinum (II) and (IV) salts in toluene for
the cyclization of compounds 2'a (Table 1, entries 1 and 2) and 2a
b
(entries 3 and 4). In all cases, we observed only the sole nitrogen
Entry
1
2
Products
Yield (%)
cyclization via 5-endo-dig pathway that leads to pyrroles 4'a and 4a
with good yields. We then considered the use of gold (I) salts
associated with silver salts in order to facilitate the formation of
cationic gold. Compound 2'a in the presence of
2a
3a, 72%
3b, 82%
3c, 45%
O
Boc
(triphenylphosphine)gold (I) chloride and silver tetrafluoroborate in
N
O
dichloromethane at 50 °C, leads to pyrrole 4'a (entry 5). According
to the conditions described by Asao et al., we used tert-butanol as
MeO
2
3
2b
2c
1
OMe
an additive to promote the living of R group of the ester and
1
6
formation of the lactone ring. The addition of t-BuOH to the
reaction mixture entails a loss of reactivity (conversion = 50%) and
an inseparable mixture of 3a and 4'a in 40:60 proportions (entry 6).
On the other hand, under the same conditions, substrate 2a will
form the compound 3a with no trace of formation of the pyrrole 4a
in the crude product and in modest yield (52%; entry 7). The
pyrano[3,4-b]pyrrol-7(1H)-one structure of compound 3a was
determined by NMR experiments (see SI-S15). We thus confirmed
the regioselectivity of the 6-endo-dig cyclization between the alkyne
and the ester. The cyclization product from 5-exo-dig cyclization
was never observed. The amounts of catalysts (entries 8) and
solvents (entries 8-10) are then optimized from 2a. The use of gold
salts as catalysts and silver salts as co-catalysts is required. Indeed,
no conversion is observed without silver salts (entry 11). Without
gold catalysts, the conversion is not complete, and a mixture of 3a,
4
5
2d
2e
4d, 58%
3e, 72%
6
7
2f
3f, 66%
3g, 75%
4'a, and a third indeterminate compound was obtained (entry 12).
The products could not be separated. The use of silver triflate
instead of silver tetrafluoroborate allows the formation of 3a in
similar yields.
2g
a
Conditions: 2 (0.5 mmol), (Ph
3 4
P)AuCl (0.05 mmol), AgBF or AgOTf
We then prepared a series of bicyclic compounds using our method
with gold catalysis (Table 2). The preparation of these compounds
also appeared including aryls (entries 1-3 and 5) and alkyls (entries
b
(
0.05 mmol), t-BuOH (1.5 mmol), benzene (2 mL), rt, overnight.
Isolated yields.
6
and 7) with yields of up to 82%. Here we also noted less efficient
What is worthy of note is that the synthesis of compound 3 can be
accomplished in a two steps sequence because platinum (II)
chloride allowed selective pyrrole synthesis. Trisubstituted pyrroles
cyclization with electron-poor aryls (entry 3). This result can be
explained by the fact that the position attacked on the alkyne
moiety was less electrophilic due to the electron-poor substituent.
The efficiency of gold was reduced by the amino substituted aryl.
This resulted in the only example without closing of both cycles
4
were synthesized from 2a in the presence of platinum (II) chloride
in toluene at 75 °C (Scheme 2). These compounds, in presence of
gold (I) and silver (I) salts, led to the formation of pyrano[3,4-
b]pyrrol-7(1H)-ones 3 according to a 6-endo-dig cyclization. We
(entry 4). In this case, pyrrole 4d was the only product.
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have noted that the yields are lower than those obtained by the evaluating these compounds for their biological effects. Moreover,
one-pot procedure (Table 2).
studies to extend the scope of the synthetic utility of this one-pot
reaction are underway in our laboratory.
Experimental
All reactions were carried out under argon atmosphere in
dried glassware. Toluene and benzene were dried and freshly
distilled from sodium. Acetonitrile was dried and freshly
distilled from CaH
purchased from Sigma-Aldrich , in
purity respectively. (Ph P) PdCl was prepared from PdCl
PPh . Reactions were monitored by TLC with Merck Silica gel
According to our results and the literature, we propose a 60 F254. Purifications by flash chromatography were carried out
2
. (Ph
3
P)AuCl, AgOTf, AgBF
4
and CuI were
99.95% and 98%
and
®
≥
99.9%, ≥
Scheme 2. Synthesis of compounds 3 in two steps.
3
2
2
2
®
3
®
®
1
mechanism based on gold catalysis (Scheme 3). First, silver (I) will using Merck Geduran Si 60 silica gel (40-63 µm). H NMR
®
make it possible to form cationic gold (I), which interacts with the π- spectra were recorded on a Bruker Avance 300 (300 MHz)
system of the substrate to form intermediate A. The nucleophilic
attack of the nitrogen then proceeds via 5-endo-dig cyclization to
form the vinylgold species B. The protodemetallation of B liberated
the pyrrole compound and the gold catalyst, which can then
interact with the second alkyne to form the intermediate C. The
nucleophilic attack of oxygen, according to a 6-endo-dig cyclization,
leads to organogold D, which liberates compound 3 and gold (I)
catalyst by protodemetallation.
NMR spectrometer, using CDCl
using Me Si (δ = 0.00 ppm) as internal reference, were as
follows (in order): chemical shift (δ in ppm relative to Me Si),
3
as solvent. Data, reported
4
H
4
multiplicity (s, d, t, q, m, br for singlet, doublet, triplet, quartet,
13
multiplet, broad) and coupling constants (J in Hz). C NMR was
recorded at 75 MHz on the same instrument, using the CDCl
3
1
9
solvent peak at (δ
recorded at 282 MHz on the same instrument, using the CClF
peak at (δ = 0.0 ppm) as internal reference. Mass spectra
C
= 77.16 ppm) as reference. F NMR was
3
F
were obtained on a Hewlett Packard (engine 5988A) by direct
inlet at 70eV. IR spectra were recorded on a Perkin-Elmer
Spectrum One spectrophotometer. Melting points were
uncorrected.
Preparation of starting materials
1
5c
Compound 2’ was prepared by the reported procedure.
Preparation of compounds
supporting information.
1, 2a-g is reported in the
General procedure for the synthesis of compounds (3)
AgBF (10 mol%, 0.05 mmol, 10 mg) or AgOTf (10 mol%, 0.05
mmol, 13 mg) was added to a solution of (Ph P)AuCl (10 mol%, 0.05
mmol, 25 mg) in freshly distilled benzene (2 mL). After 2 minutes, 2
0.5 mml) was added, followed by t-BuOH (3 equiv., 1.5 mmol, 138
4
3
(
µL). The reaction was then stirred overnight at room temperature
before it was filtered through a pad of celite with EtOAc. The filtrate
Scheme 3. Proposed reaction mechanism.
was then washed with a saturated aqueous solution of NaHCO
3
,
dried over MgSO and solvents were evaporated under vacuum.
4
Conclusions
Residues were purified by flash chromatography on silica gel to give
compounds 3.
In summary, we developed
pyrano[3,4-b]pyrrol-7(1H)-one derivatives from benzyl β,β- tert-Butyl-7-oxo-2,5-diphenylpyrano[3,4-b]pyrrole-1(7H)-
4
diacetylenic dehydroalanine esters. The substrates can easily be carboxylate (3a): Eluant: PE/Et O 80/20, yield = 72%; C24H21NO ; Rf
a gold-catalyzed synthesis of
2
prepared by Sonogashira coupling, and this reaction offers a two- (PE/AcOEt : 90/10) = 0.30 ; yellow solid; m.p.: 135-137 °C , IR (ATR):
1
steps and rapid access to various new pyrano-pyrroles resulting ν = 2979, 2928, 1761, 1727, 1285, 1259, 1146, 1124, 690; H NMR
from double intramolecular nucleophilic 5-endo and 6-endo- (300 MHz, CDCl
additions to a carbon˗carbon triple bond. We are currently 7.51 (m, 8H), 7.84-7.87 (m, 2H) ; C NMR (75 MHz, CDCl
3
): δ = 1.54 (s, 9H), 6.40 (s, 1H), 6.97 (s, 1H), 7.26-
1
3
3
): δ = 27.3
4
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(
CH
CH), 128.6 (CH), 128.8 (CH), 129.2 (CH), 129.5 (CH), 131.1 (Cq), (CH
32.4 (Cq), 134.4 (Cq), 144.6 (Cq), 148.4 (Cq), 153.9 (Cq), 154.6 (CH), 104.6 (CH), 116.1 (Cq), 135.9 (Cq), 147.5 (Cq), 148.9 (Cq),
3
), 86.4 (Cq), 97.5 (CH), 106.5 (CH), 117.7 (Cq), 125.2 (CH), 128.5 CDCl
3
): δ = 13.89 (CH
3
), 13.95 (CH
3
), 22.2 (CH
2
), 22.5 (CH
2
), 27.6
(
3
), 27.7 (CH
2
), 29.4 (CH
2
), 31.0 (CH
2
), 33.3 (CH
2
), 85.6 (Cq), 98.3
1
+
(Cq) ; HRMS (ESI) calcd. for C24
H
22NO
4
[M+H]+: 388.15433; found: 154.6 (Cq), 159.6 (Cq) ; HRMS (ESI) calcd. for C20
348.21693; found: 348.21698.
4
H30NO [M+H] :
3
88.15441.
tert-Butyl-2,5-bis(4-methoxyphenyl)-7-oxopyrano[3,4-b]pyrrole-
(7H)-carboxylate (3b): Eluant: PE/AcOEt 70/30, yield = 82%; carboxylate (3g): Eluant: PE/Et
; Rf (PE/Et O: 70/30) = 0.16 ; yellow solid; m.p.: 131- (PE/Et O: 95/5) = 0.20; yellow oil; IR (ATR): ν = 2956, 2928, 2870,
33 °C; IR (ATR): ν = 2941, 2842, 1748, 1724, 1608, 1291, 1249, 1729 (br), 1304, 1150, 841; H NMR (300 MHz, CDCl
tert-Butyl-2,5-diisopentyl-7-oxopyrano[3,4-b]pyrrole-1(7H)-
1
2
O 95/5, yield = 75%; C22
4
H33NO ; Rf
26
C H
25NO
6
2
2
1
1
1
3
2
3
): δ = 0.93 (app.
3
): δ = 1.57 (s, 9H), 3.85 (s, 3H), t, J = 6.3 Hz, 12H), 1.50-1.61 (m, 6H), 1.65 (s, 9H), 2.50 (t, J = 7.2 Hz,
1
025, 817; H NMR (300 MHz, CDCl
.86 (s, 3H), 6.31 (s, 1H), 6.83 (s, 1H), 6.94-9.98 (m, 4H), 7.42 (m, 2H), 2.84 (t, J = 7.5 Hz, 2H), 6.02 (s, 1H), 6.17 (s, 1H); C NMR (75
13
13
H), 7.79 (m, 2H) ; C NMR (75 MHz, CDCl
), 55.52 (CH ), 86.3 (Cq), 96.0 (CH), 106.0 (CH), 114.0 (CH), (CH), 27.9 (CH), 31.6 (CH
14.3 (CH), 123.5 (Cq),125.3 (Cq), 126.8 (CH), 130.2 (CH), 135.0 (CH), 104.4 (CH), 116.1 (Cq), 135.8 (Cq), 147.7 (Cq), 148.8 (Cq),
3
): δ = 27.5 (CH
3
), 55.49 MHz, CDCl
3
): δ = 22.4 (CH
3
), 22.5 (CH
3
), 25.9 (CH
2
3
), 27.5 (CH ), 27.6
(CH
3
3
2
), 36.3 (CH
2
), 37.8 (CH
2
), 85.6 (Cq), 98.2
1
+
4
(Cq), 144.8 (Cq), 148.7 (Cq), 154.1 (Cq), 154.9 (Cq), 160.5 (Cq), 160.8 154.5 (Cq), 159.8 (Cq); HRMS (ESI) calcd. for C22H34NO [M+H] :
+
(
Cq); HRMS (ESI) calcd. for C26
48.17540.
6
H26NO [M+H] : 448.17546; found: 376.24824; found: 376.24749.
4
General procedure for the synthesis of pyrroles (4)
PtCl (5 mol%, 0.025 mmol, 6.6 mg) was added to a solution of 2
(7H)-carboxylate (3c): Eluant: PE/AcOEt 80/20, yield = 45%; (0.5 mmol) in toluene (5 mL). Reaction mixture was stirred at 75 °C
NO ; Rf (PE/Et O: 80/20) = 0.27; yellow solid; m.p.: 138- overnight, and then filtrated on a pad of celite with EtOAc. The
40 °C IR (ATR): ν = 3078, 2985, 2933, 1762, 1731, 1291, 1156, filtrate was evaporated under vacuum, and the residues were
tert-Butyl-2,5-bis(4-fluorophenyl)-7-oxopyrano[3,4-b]pyrrole-
2
1
24
C H
19
F
2
4
2
1
1
1
2
1
1
141, 1125, 828; H NMR (300 MHz, CDCl
3
): δ = 1.54 (s, 9H), 6.36 (s, purified by flash chromatography on silica gel to give compounds 4.
H), 6.88 (s, 1H), 7.09-7.17 (m, 4H), 7.44-7.49 (m, 2H), 7.80-7.84 (m,
1
3
H); C NMR (75 MHz, CDCl
3
): δ = 27.4 (CH
3
), 86.7 (Cq), 97.2 (CH), 1-(tert-Butyl) 2-methyl 5-phenyl-3-(phenylethynyl)-1H-pyrrole-1,2-
2
2
06.7 (CH), 115.7 (d, JC-F = 21.9 Hz, CH), 116.0 (d, JC-F = 22.0 Hz, dicarboxylate (4’a): Eluant: PE/AcOEt 95/5→80/20, yield = 64%;
CH), 117.6 (Cq), 127.2 (d, JC-F = 3.4 Hz, Cq), 127.3 (d, JC-F = 8.3 Hz, white solid; m.p.: 97-99 °C; C25
4
3
H
23NO
4
; Rf (PE/Et
2
O: 90/10) = 0.32; IR
4
3
1
CH), 128.7 (d, JC-F = 3.2 Hz, Cq), 130.8 (d, JC-F = 8.4 Hz, CH), 134.4 (ATR): ν = 3028, 2956, 1761, 1705, 1450, 1152, 760; H NMR (300
1
(
Cq), 143.8 (Cq), 148.3 (Cq), 153.7 (Cq), 154.0 (Cq), 163.4 (d, JC-F
=
MHz, CDCl
49.8 Hz, Cq), 163.6 (d, JC-F = 250.2 Hz, Cq) ; F NMR (282 MHz, 3H), 7.38-7.46 (m, 5H), 7.52-7.57 (m, 2H); C NMR (75 MHz, CDCl
): δ = -111.9, -111.5; HRMS (ESI) calcd. for C24 NO δ = 27.3 (CH ), 52.0 (CH ), 82.9.0 (Cq), 85.9 (Cq), 93.5 (Cq), 113.0
(Cq), 114.2 (CH), 123.5 (Cq), 125.7 (Cq), 128.3 (CH), 128.43 (CH),
28.45 (CH), 128.84 (CH), 129.1 (CH), 131.2 (Cq), 131.7 (Cq), 138.4
3
): δ = 1.40 (s, 9H), 3.96 (s, 3H), 6.38 (s, 1H), 7.32-7.36 (m,
1
19
13
2
3
):
CDCl
3
H
20
F
2
4
3
3
+
[
M+H] : 424.13549; found: 424.13553.
1
+
tert-Butyl-2,5-bis(4-tert-butylphenyl)-7-oxopyrano-[3,4-b]pyrrole-
(7H)-carboxylate (3e): Eluant: PE/Et 95/5, yield = 72% ; 402.16998; found: 402.16917.
; Rf (PE/Et O: 80/20) = 0.38; colorless oil; IR (ATR): ν =
960, 2903, 2870, 1765, 1728, 1477, 1285, 1148, 824; H NMR (300
4
(Cq), 148.9 (Cq), 160.5 (Cq). HRMS (ESI) calcd. for C25H24NO [M+H] :
1
2
O
32
C H
37NO
4
2
1
2
3
MHz, CDCl ): δ = 1.34 (s, 9H), 1.35 (s, 9H), 1.55 (s, 9H), 6.37 (s, 1H), 2-Benzyl 1-tert-butyl 5-phenyl-3-(phenylethynyl)-1H-pyrrole-1,2-
1
3
6
.93 (s, 1H), 7.40-7.47 (m, 6H), 7.79 (m, 2H); C NMR (75 MHz, dicarboxylate (4a): Eluant: PE/AcOEt 95/5→90/10, yield = 70%;
CDCl ): δ = 27.4 (CH ), 31.29 (CH ), 31.34 (CH ), 34.8 (Cq), 86.2 (Cq), yellow oil; C31 ; Rf (PE/Et O: 90/10) = 0.22; IR (ATR): ν = 3063,
6.9 (CH), 106.2 (CH), 117.5 (Cq), 125.0 (CH), 125.4 (CH), 125.8 (CH), 3034, 2981, 2937, 1767, 1698, 1277, 1251, 1216, 1149, 1122, 1070,
3
3
3
3
H
27NO
4
2
9
1
1
3
28.2 (Cq), 128.4 (CH), 129.7 (Cq), 134.6 (Cq), 144.8 (Cq), 148.5 752, 691; H NMR (300 MHz, CDCl ): δ = 1.37 (s, 9H), 5.39 (s, 2H),
1
3
(
Cq), 152.4 (Cq), 152.9 (Cq), 154.1 (Cq), 154.8 (Cq); HRMS (ESI) 6.38 (s, 1H), 7.23-7.30 (m, 8H), 7.38-7.50 (m, 7H); C NMR (75 MHz,
+
calcd. for C32
H
38NO
4
[M+H] : 500.27954; found: 500.27966.
CDCl
13.1 (Cq), 114.4 (CH), 123.4 (Cq), 125.3 (Cq), 128.2 (CH), 128.28
CH), 128.32 (CH), 128.4 (CH), 128.6 (CH), 128.8 (CH), 129.1 (CH),
131.1 (Cq), 131.7 (Cq), 135.8 (Cq), 138.6 (Cq), 148.9 (Cq), 160.0 (Cq);
3 3 2
): δ = 27.3 (CH ), 67.0 (CH ), 83.0 (Cq), 86.0 (Cq), 93.6 (Cq),
1
(
tert-Butyl-2,5-dibutyl-7-oxopyrano[3,4-b]pyrrole-1(7H)-
carboxylate (3f): Eluant: PE/Et O 95/5; yield = 66%; C20
PE/Et O: 80/20) = 0.39; yellow oil; IR (ATR): ν = 2957, 2931, 2872, 478.20191.
+
2
4 4
H29NO ; Rf HRMS (ESI) calcd. for C31H28NO [M+H] : 478.20128; found:
(
2
1
1
6
2
729 (br), 1305, 1150, 840; H NMR (300 MHz, CDCl
3
): δ = 0.93 (m,
H), 1.33-1.44 (m, 4H), 1.59-1.72 (m, 13H), 2.50 (t, J = 7.4 Hz, 2H), 2-Benzyl 1-tert-butyl 5-(4-methoxyphenyl)-3-((4-methoxyphenyl)-
1
3
.84 (t, J = 7.4 Hz, 2H), 6.01 (s, 1H), 6.16 (s, 1H); C NMR (75 MHz, ethynyl)-1H-pyrrole-1,2-dicarboxylate (4b): Eluant : PE/AcOEt
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DOI: 10.1039/C7OB01849E
ARTICLE
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8
0/20, yield = 68%; beige solid; m.p.: 74-76°C; C33
H
31NO
6
; Rf
1
(a) D. L. Boger, D. R. Soenen, C. W. Boyce, M. P. Hedrick, Q.
Jin, J. Org. Chem., 2000, 65, 2479; (b) D. L. Boger, PCT Int.
Appl. 20à1, WO 2001064635 A1 20010907; (c) P. Y. Zhang, I.
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S. B. Wan, J; Med. Chem., 2010, 53, 5108; (d) J. W. Bin, I. L. K.
Wong, X. Hu, Z. X. Yu, L. F. Xing, T. Jiang, L. M. C. Chow, W. S.
Biao, J. Med. Chem., 2013, 56, 9057; (e) C. Yang, I. L. K.
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(a) R. J. Andersen, D. J. Faulkner, H. Cun-beng, G. D. Van
Duyne, J. Clardy, J. Am. Chem. Soc., 1985, 107, 5492; (b) A. R.
Carroll, B. F. Bowden, J. C. Coll, Aust. J. Chem., 1993, 46, 489;
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Prod., 1999, 62, 419.
(PE/AcOEt: 80/20) = 0.46; m.p.: 91-93°C; IR (ATR): ν = 2979, 2935,
1
2837, 2215, 1764, 1697, 1606, 1245; H NMR (300 MHz, CDCl
3
): δ =
1.39 (s, 9H), 3.80 (s, 3H), 3.82 (s, 3H), 5.38 (s, 2H), 6.31 (s, 1H), 6.77
(m, 2H), 6.92 (m, 2H), 7.16 (m, 2H), 7.24-7.29 (m, 3H), 7.36 (m, 2H),
1
3
7.49 (m, 2H); C NMR (75 MHz, CDCl
55.43 (CH ), 66.8 (CH ), 81.8 (Cq), 85.8 (Cq), 93.7 (Cq), 113.6 (Cq),
113.7 (CH), 113.9 (CH), 114.1 (CH), 115.6 (Cq), 123.4 (Cq), 124.7
3 3 3
): δ = 27.3 (CH ), 55.38 (CH ),
3
2
2
(Cq), 128.1 (CH), 128.3 (CH), 128.6 (CH), 130.5 (CH), 133.2 (CH),
135.9 (Cq), 138.7 (Cq), 149.2 (Cq), 159.6 (Cq), 160.1 (Cq); HRMS
+
(ESI) calcd. for C33
H
32NO
6
[M+H] : 538.22241; found: 538.22246.
3
4
For reviews on Lamellarins, see: (a) H. Fan, J. Peng, M. T.
Hamann, J.-F. Hu, Chem. Rev., 2008, 108, 264; (b) D. Pla, F.
Albericio, M. Alvarez, MedChemComm, 2011, 2, 689.
2
-Benzyl
1-tert-butyl 5-(4-(dimethylamino)phenyl)-3-((4-
(dimethylamino)phenyl)ethynyl)-1H-pyrrole-1,2-dicarboxylate
(4d): Eluant: PE/AcOEt 50/50, yield 36%;
(PE/AcOEt : 50/50) = 0.61; orange oil; IR (ATR): ν = 2978, 2888,
=
35
C H
37
N
3
O
4
; Rf
):
(a) C. Bailly, Curr. Med. Chem.: Anti-Cancer Agents, 2004, 4,
363; (b) M. Vanhuyse, J. Kluza, C. Tardy, G. Otero, C. Cuevas,
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Kluza, M.-A. Gallego, A. Loyens, J.-C. Beauvillain, J.-M.
Fernandez Sousa-Faro, C. Cuevas, P. Marchetti, C. Bailly,
Cancer Res., 2006, 66, 3177; (d) D. Baunbaek, N. Trinkler, Y.
Ferandin, O. Lozach, P. Ploypradith, S. Rucirawat, F. Ishibashi,
1
2802, 2208, 1762, 1695, 1606, 1149, 812; H NMR (300 MHz, CDCl
3
δ = 1.42 (s, 9H), 2.97 (s, 6H), 2.98 (s, 6H), 5.39 (s, 2H), 6.27 (s, 1H),
6
2
6
1
.57 (m, 2H), 6.70 (m, 2H), 7.15 (m, 2H), 7.25-7.33 (m, 5H), 7.51 (m,
13
H); C NMR (75 MHz, CDCl
6.6 (CH ), 81.4 (Cq), 85.4 (Cq), 95.0 (Cq), 110.5 (Cq), 111.7 (CH),
11.8 (CH), 113.6 (CH), 114.4 (Cq), 118.7 (Cq), 127.9 (CH), 128.2
3 3 3 3
): δ = 27.4 (CH ), 40.4 (CH ), 40.5 (CH ),
M. Iwato, L. Meijer, Mar. Drugs, 2008,
Chittchang, P. Batsomboon, S. Ruchirawat, P. Ploypradith,
ChemMedChem, 2009, , 457; (f) C. Ballot, J. Kluza, S. Lancel,
6, 514; (e) M.
2
4
(CH), 128.6 (CH), 130.0 (CH), 132.9 (CH), 136.2 (Cq), 139.8 (Cq),
A. Martoriati, S. M. Hassoun, L. Mortier, J. C. Vienne, G.
Briand, P. Formstercher, C. Bailly, R. Nevière, P. Marchetti,
Apoptosis, 2010, 15, 769; (g) S. Khiati, Y. Seol, K. Agama, I. D.
Rosa, S. Agawal, K. Fesen, H. Zhang, K. C. Neuman, Y.
Pommier, Mol. Pharmacomol., 2014, 86, 193; (h) C. Ballot, A.
Martoriati, M Jendoubi, S. Buche, P. Formstecher, L. Mortier,
J. Kluza, P. Marchetti, Mar. Drugs, 2014, 12, 779.
149.6 (Cq), 150.1 (Cq), 150.7 (Cq), 160.3 (Cq); HRMS (ESI) calcd. for
+
35 38 3 4
C H N O [M+H] : 564.28568; found: 564.28601.
2
-Benzyl
dicarboxylate (4f): Eluant: PE/Et
PE/Et O: 80/20) = 0.45; yellow oil; IR (ATR): ν = 2956, 2931, 2872,
1-tert-butyl
5-butyl-3-(hex-1-ynyl)-1H-pyrrole-1,2-
2
O 95/5; yield = 48% ; C27 ; Rf
H35NO
4
(
2
5
6
(a) Q. Li, J. Jiang, A. Fan, Y. Cui, Y. Jia, Org. Lett., 2011, 13,
1
2
0
7
235, 1755, 1704, 1226, 1158; H NMR (300 MHz, CDCl
3
): δ = 0.85-
312; (b) A. Theppawong, P. Ploypradith, P. Chuawong, S.
Ruchiawat, M. Chittchang, Chem. Asian J., 2015, 10, 2631; (c)
D. M. Lade, A. B. Pawar, P. S. Mainkar, S. Chandrasekhar, J.
Org. Chem., 2017, 82, 4998; K.-L. Zheng, M.-Q. You, W.-M.
Shu, Y.-D. Wu, A.-X. Wu, Org. Lett., 2017, 19, 2262.
(a) L. Shen, N. Xie, B. Yang, Y. Hu, Y. Zhang, Eur. J. Med.
Chem., 2014, 85, 807; (b) K. B. Manjappa, J.-R. Syu, D.-Y.
Yang, Org. Lett., 2016, 18, 332.
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C. Neagoie, E. Vedrenne, F. Buron, J.-Y. Mérour, S. Rosca, S.
Bourg, O. Lozach, L. Meijer, B. Baldeyrou, A. Lansiaux, S.
Routier, Eur. J. Med. Chem., 2012, 49, 379.
.94 (m, 6H), 1.33-1.62 (m, 17H), 2.28 (t, J = 6.9 Hz, 2H), 2.67 (t, J =
13
.2 Hz, 2H), 5.32 (s, 2H), 5.97 (s, 1H), 7.31-7.48 (m, 5H); C NMR (75
): δ = 13.7 (CH ), 13.9 (CH ), 19.5 (CH ), 22.1 (CH ), 22.4
), 27.1 (CH ), 27.5 (CH ), 30.79 (CH ), 30.84 (CH ), 66.5 (CH ),
MHz, CDCl
3
3
3
2
2
(CH
2
2
3
2
2
2
73.9 (Cq), 85.2 (Cq), 95.1 (Cq), 112.8 (CH), 114.6 (Cq), 125.0 (Cq),
128.0 (CH), 128.2 (CH), 128.5 (CH), 136.2 (Cq), 140.6 (Cq), 149.2
+
7
8
(Cq), 160.3 (Cq); HRMS (ESI) calcd. for
C
27
H
36NO
4
[M+H] :
438.26389; found: 438.26384.
9
1
(a) T. A. Bryson, G. A. Roth, Tetrahedron Lett., 1986, 27
685. (b) M. Shimizu, K. Hirano, T. Satoh, M. Miura, J. Org.
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Abarbri, Synthesis, 2005, 2349; (b) K. Cherry, J.-L. Parrain, J.
,
3
Acknowledgements
8
We gratefully acknowledge Département d’Analyse Chimique,
Biologique et Médicale of Tours University for high-resolution
mass spectrum analysis and Johnson Matthey Company for the
generous gift of palladium and platinum metal salts.
Thibonnet, A. Duchêne, M. Abarbri, J. Org. Chem., 2005, 70
,
6669; (c) S. Inack-Ngi, R. Rahmani, L. Commeiras, G.
Chouraqui, J. Thibonnet, A. Duchêne, M. Abarbri, J.-L.
Parrain, Adv. Synth. Catal., 2009, 351, 779; (d) S. Inack-Ngi, V.
Guilloteau, M. Abarbri, J. Thibonnet, J. Org. Chem., 2011, 76,
376; (e) S. Inack-Ngi, J. Petrignet, R. Duwald, E. M. El Hilali,
Notes and references
8
‡
Footnotes relating to the main text should appear here. These
M. Abarbri, A. Duchêne, J. Thibonnet, Adv. Synth. Catal.
2013, 355, 2936; (f) J. Petrignet, S. Inack-Ngi, M. Abarbri, J.
Thibonnet, Tetrahedron Lett. 2014, 55, 982.
might include comments relevant to but not central to the
matter under discussion, limited experimental and spectral data,
and crystallographic data.
6
| J. Name., 2012, 00, 1-3
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DOI: 10.1039/C7OB01849E
Journal Name
ARTICLE
1
1
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2 For recent reviews and selected examples of gold-catalyzed
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3 A. Kumar, D. D. Vachhani, S. G. Modha, S. K. Sharma, V. S.
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b) J. E. Baldwin, J. Cutting, W. Dupont, L. Kruse, L.
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5 (a) P. M. T., Ferreira, H. L. S., Maia, L. S. Monteiro, J.
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