Synthesis of Polycyclic Spironaphthofuran Derivatives by Acid-Catalyzed Domino Reaction of 2-Naphthols with Tetraarylbut-2-yne-1,4-diols

Article abstract of DOI:10.1002/ejoc.201800612

The acid-catalyzed condensation of 2-naphthols with tetraphenylbut-2-yne-1,4-diols affords a mixture of spiro[indene-1,1′-naphthofurans] and dinaphthofurans through a cascade of intramolecular reactions, whereas using the more reactive thienyltriphenylbut

Full text of DOI:10.1002/ejoc.201800612

A Journal of
Accepted Article
Title: Synthesis of polycyclic spiro naphthofuran derivatives via acid-
catalyzed domino reaction of 2-naphthol with tetraarylbut-2-
yne-1,4-diols
Authors: Paulo Jorge Coelho, Jerome Berthet, Stephanie Delbaere,
and Ceu Sousa
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800612
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800612
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European Journal of Organic Chemistry
10.1002/ejoc.201800612
1
Synthesis of polycyclic spiro naphthofuran derivatives via acid-catalyzed domino
reaction of 2-naphthol with tetraarylbut-2-yne-1,4-diols
1
2
2
1
Cꢀu M. Sousa, Jerome Berthet, Stephanie Delbaere and Paulo J. Coelho*
1
Centro de Química-Vila Real, Universidade de Trás-os-Montes e Alto Douro, 5000-801
Vila Real, Portugal
2
Facultꢀ́ des Sciences Pharmaceutiques et Biologiques, Universitꢀ́ Lille Nord de France,
UDSL, CNRS UMR 8516, F-59006 Lille, France
Email: Paulo J. Coelho – pcoelho@utad.pt
URL: www.cqvr.purpleprofile.pt/applied-organic-chemistry/
*
Corresponding author
Abstract:
The acid-catalyzed condensation of 2-naphthols with tetraphenylbut-2-yne-1,4-diols affords
a mixture of spiro[indene-1,1'-naphthofurans] and dinaphthofurans through a cascade of
intramolecular reactions, whereas using the more reactive thienyltriphenylbut-2-yne-1,4-diol
leads to the formation of a single spiranic compound joining a cyclopenta[b]thiophene to a
naphtho[2,1-b]furan.
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European Journal of Organic Chemistry
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Keywords: Acid catalysis; cyclopenta[b]thiophene; domino reaction; naphthofuran; spiro
compounds.
Short text to go with the table of contents
An easy synthesis of complex spiro compounds was developed using the acid-catalyzed
condensation of 2-naphthols with tetraphenylbut-2-yne-1,4-diols. The reaction proceeds
through a cascade of intramolecular reactions.
Topic Key
Domino reactions
Polycyclic spiro compounds
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Introduction
Domino reactions are quite common in nature. The biosynthesis of complex
compounds through a series of successive reactions enchants any organic chemist,
although, usually, each step is catalyzed by a different enzyme 1-8. Whilst common
synthetic procedures routinely involve the stepwise formation of each bond in the target
molecule, in domino reactions, several bonds are formed and different reactions occur
successively, without the need to isolate the intermediates, change the reaction conditions
or add more reagents. There are many examples of such transformations developed in the
laboratories, most of them involving 2-3 reactions, which allows the preparation of complex
molecules from simple reagents 9-14. The acid-catalysed synthesis of vinylidene-
naphthofurans from 2-naphthols and tetraphenylbut-2-yne-1,4-diols, at room temperature,
is an example of such domino reactions involving 3 steps 15 (Scheme 1).
Scheme 1: Synthesis of vinylidene-naphthofuran from 2-naphthol and tetraphenylbut-2-yne-
1
,4-diol.
Vinylidene-naphthofurans show acidochromic properties being converted, after
adding trifluoroacetic acid (TFA), into a violet cationic species formed through the addition
of one proton to the allene group and overture of the furan ring (Scheme 2). The process is
reversible and upon NEt addition, the initial uncoloured vinylidene-naphthofurans are
3
recovered. These molecules show also photochromic properties when they come in contact
with an acidic environment and exposed to the UV light. The process originates the same
coloured species and is reversible, in the absence of light, the coloured species returns
thermally to the initial uncoloured compound 16.
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Scheme 2: Acidochromic behavior of vinylidene-naphthofurans
However, the opened coloured species has a cationic character and can undergo
intramolecular reactions. We have observed that these species evolve slowly and
irreversibly, at room temperature, into a new compound which is not photochromic. Since
both the synthesis of the vinylidene-naphthofurans and this side reaction are promoted by
acid, we made the hypothesis that the acid-catalyzed reaction of 2-naphthols with
tetraphenylbut-2-yne-1,4-diols, performed at an higher temperature, could led directly to this
new compound.
Results and Discussion
To check the foregoing hypothesis, the reaction between 2-naphthol 1a and
tetraarylbut-2-yne-1,4-diol 2a was reproduced in CHCl
3
under reflux, in the presence of p-
TsOH.H O. It led to the initial formation of the expected photochromic vinylidene-
2
naphthofuran, which is progressively converted into new compounds, having the same
polarity, but without any photochromic activity. In one hour, the reaction is complete. After
column chromatography and recrystallization a yellowish product was obtained in good yield
(87%). Spectroscopic analysis of the solid shows that it is a 2:1 mixture of two polycyclic
aromatic compounds, that were assigned to the spiranic structure 3a, joining a naphthofuran
to an indene, along with the unexpected 7a,13a-dihydrodinaphthofuran 4a (Scheme 3).
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Scheme 3: Acid-catalyzed reaction of naphthols 1a-c with tetraphenylbut-2-yne-1,4-diol 2a.
The molecular structures of 3a and 4a were elucidated by NMR spectroscopy. For
3
a, 2D NMR COSY highlighted scalar correlations between protons H2' at 7.58 ppm, H3' at
.17 ppm, H4' at 6.81 ppm and H5' at 6.57 ppm (Figure 1, see Supporting Information for full
7
experimental data). In addition, long-range correlations in HMBC (Figure 2) between H5'
(
6.57 ppm) and H
between protons H
6.82 ppm proved the bond formation between carbons C
with the proposed structure.
2
(6.61 ppm) with the aliphatic quaternary carbon C
3
at 70.6 ppm and
at
3
2
, H2"=6" (7.34 ppm), H2"a=6"a (7.49 ppm) and the sp pyran carbon C
4
9
3
and C6' and are in agreement
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1
1
Figure 1: H- H NMR COSY experiment of 3a and 4a in CDCl
3
1
13
Figure 2: H- C NMR HMBC experiment of 3a and 4a in CDCl
3
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European Journal of Organic Chemistry
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For 4a, the mono-subtituted phenyl group attached to carbon C
3
was evidenced by
the scalar correlations between protons H2'=6' at 6.69 ppm, H3'=5' at 6.93 ppm and H4' at 7.00
1
13
ppm (Figure 1) and by the scalar H- C long-range correlations in HMBC, between protons
3
H
2'=6' and H
2
at 6.62 ppm with the aliphatic quaternary carbon C
at 96.79 ppm is also correlated through three bonds with protons H
.44 ppm (Figure 2).
3
at 61.2 ppm. The sp pyran
carbon C
4
2
and H2" at
7
The formation of the spiro compound 3a and the fused naphthofuran 4a can be
explained by a series of cascade reactions 17]. Thus, under acid-catalysis the diol 2a is
converted into the propargylic carbocation A, which upon reaction with 2-naphthol 1a
provides the propargylic aryl ether B. This intermediate performs a 3,3]-sigmatropic Claisen
rearrangement followed by enolization and acid-catalysed intramolecular dehydration
affording the vinylidene-naphthofuran C detected as intermediate in this reaction 15. Then,
proton addition to the allene group followed by the opening of the dehydrofuran ring provides
the coloured carbocation D. This species is then converted into the conjugated tertiary
carbocation E which can perform an intramolecular electrophilic aromatic substitution
reaction (EAS) giving the spiro[indene-1,1'-naphthofuran] 3a, or an 1,2-aryl shift may occur
in E providing the carbocation F which then performs an intramolecular electrophilic aromatic
substitution, providing the polycyclic dinaphthofuran 4a (Scheme 4).
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European Journal of Organic Chemistry
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Scheme 4: Proposed mechanism for the formation of the polycyclic spiroindene 3a and
dinaphthofuran 4a from 2-naphthol 1a and tetraphenylbut-2-yne-1,4-diol 2a, under acidic
conditions.
The same behavior was observed starting from substituted naphthols. Thus, the
reaction of the diol 2a with the commercially available 7-methoxynaphthol 1b and ethyl 6-
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hydroxy-2-naphthoate 1c afforded the expected mixtures of the two corresponding
polycyclic compounds 3b/4b (40%, 1:0.8 mixture) and 3c/4c (87%, 2:1 mixture) (Scheme
3
). In HMBC experiments (Figure 3), the C
with long range correlations with H5' and H
long range correlations with H2'=6' and H
3
carbon in 3b/3c, is observed at about 70 ppm
2
, whereas, in 4b/4c, it is at about 60 ppm with
2
.
Figure 3: Part of HMBC experiments of a) 3b/4b and b) 3c/4c in CDCl
3
Since the presence of more reactive aromatic rings on the diol 2 could influence the
selectivity of this domino reaction and favor the formation of the spiranic compound, three
new diols 2b-d were prepared through the reaction of 1,1-diphenylpropynol with n-BuLi
followed by the addition of 4-methoxybenzophenone, 4-bromobenzophenone and thienyl
phenyl ketone, respectively (Scheme 5). In fact, the reaction of 2-naphthol 1a with methoxy
substituted diol 2b afforded mainly a 2:1 mixture of two spiranic compounds 3d/3d’ (70%)
that differ on the position of the methoxy group (Scheme 6). In addition, a very weak amount
of two isomers of dinaphthofuran is observed. The amount of each of them is around 5%.
The presence of the methoxy group creates an asymmetry in the diol 2b. In this case
the protonation of the diol should afford a carbocation A with the charge near the activated
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European Journal of Organic Chemistry
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0
aromatic ring. Therefore, according to the proposed mechanism (Scheme 4) this substituent
should end in the phenyl group attached to the allene in the intermediate C. Then, after
proton addition the carbocation E may be attacked by the phenyl or the methoxypheny rings
affording mainly a mixture of the spirocompounds 3d/3d’ with the expected predominance
of compound 3d.
Scheme 5: Synthesis of tetraarylbut-2-yne-1,4-diols 2a-d.
Scheme 6: Acid-catalyzed reaction of naphthol 1a with the diol 2b.
In the 2D-COSY experiment (Figure 4) the main spiranic isomer 3d is identified by
scalar coupling pattern between protons H5' at 6.08 ppm, H3' in the meta position at 6.71
ppm and H2' at 7.47 ppm, formed after carbons C
3
and C6' bond formation. The second
isomer 3d' is identified by scalar coupling pattern between protons H5'a at 6.56 ppm, H4'a at
6
.79 ppm, H3'a at 7.14 ppm and H2'a at 7.57 ppm. The structures of the spiranic structures
3
d and 3d' were confirmed in the HMBC experiment (Figure 5) by long range correlations
between the carbons C
3
at about 70 ppm with protons H
2
and H5' for 3d and with protons H
2
2
and H5'a for 3d'. In this HMBC experiment, characteristic correlations between protons H
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1
and protons H2'=6' with carbons C at 60 ppm pointed also to the possible presence of two
3
minor isomers of the dinaphthopyran derivatives 4d/4d’’.
Figure 4: COSY experiment of 3d and 3d' in CDCl .
3
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European Journal of Organic Chemistry
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2
Figure 5: Part of HMBC experiment of 3d/3d' and 4d/4d' in CDCl .
3
The presence of an electron withdrawing bromine atom in the diol 2c, leads to a
different reactivity. In this case the protonation of the diol 2c should afford a carbocation with
the charge far from the bromophenyl group. Therefore, according to the proposed
mechanism, the bromine atom should appear in the phenyl group attached to the C-O sp3
3
carbon atom in the intermediate C and end up in the C-O sp phenyl groups of the
spirocompound 3. In fact the reaction of diol 2c with the naphthol 1c affords a complex
mixture of 4 compounds (75% yield): two diastereoisomers of the spiranic structure 3e
(80%) along with two isomeric dinaphthofurans 4e/4e' (20%) (Scheme 7).
Scheme 7: Acid-catalyzed reaction of naphthol 1c with the diol 2c.
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In the 2D-COSY experiment (Figure 6) the two diastereoisomers of 3e are identified
by the splitting of the scalar coupling between protons H5' at 6.49/6.57 ppm via H4' at
6
.81/6.86 ppm, H3' at 7.18/7.20 ppm and H2' at 7.59 ppm, indicative of the coupling between
carbons C and C6'. In addition in the HMBC experiment (Figure 7) long range correlations
between the carbons C at about 70 ppm with protons H and H5' are observed. Moreover,
the two minor isomers of the dinaphthopyran 4e and 4e' were identified by long range
correlation with the carbons C at about 60 ppm.
3
3
2
3
Figure 6: 2D-COSY experiment of 3e in CDCl
3
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European Journal of Organic Chemistry
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Figure 7: Part of HMBC experiment of 3e and 4e/4e' in CDCl .
3
The use of the diol 2d, presenting a thiophene ring, led to the formation of a unique
product. In fact, heating a mixture of diol 1d and 2-naphthol 1a gave only the
cyclopenta[b]thiophene spiranic compound 3f (46% yield after column chromatography),
due to the higher reactivity of the thiophene ring in the intramolecular electrophilic
substitution reaction (Scheme 8).
Scheme 8: Acid-catalyzed reaction of naphthol 1a with the diol 2d.
In 2D HMBC experiment (Figure 8), the structure of 3f was confirmed by long range
correlations between the proton H
2
at 6.67 ppm with the aliphatic carbon C at 69.0 ppm.
3
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5
5
Due to the cyclization, a long range scalar coupling J = 1.4 Hz between proton H
2
and
proton H3' at 7.00 ppm is observed.
Figure 8: Part of HMBC experiment of 3f in CDCl .
3
The formation of these polycyclic compounds by intramolecular cyclization of the
coloured conjugated cation D (Scheme 4) may constitute a problem for the use of vinylidene-
naphthofurans as photochromic molecules, due to fatigue under strong acidic conditions.
However, this limitation may be overcome by the use of weaker acids, sufficient to observe
the photochromic behavior of these molecules, at ambient temperatures. On the other hand,
although the mixtures of spiroindenes 3 and dinaphthofurns 4 are quite difficult to separate,
the formation of a single spiroproduct 3f, using the more reactive thiophene ring in the diol,
may open a way to the straightforward formation of cyclopenta[b]thiophene spiranic
compounds which have structural resemblance with some pharmaceutical important
molecules incorporating this motif 18-21.
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Conclusion
The acid-catalysed reaction of 2-naphthols with tetraarylbut-2-yne-1,4-diols,
performed under CHCl reflux, affords a mixture of polycyclic naphthofuran derivatives
3
whose structures were unambiguously established by 2D NMR analysis. The transformation
occurs through a cascade of reactions involving the intermediate formation of vinylidene-
naphthofurans which upon addition of one proton to the allene group affords a delocalized
conjugated carbocation that undergoes two competitive intramolecular electrophilic
reactions leading to the formation of two polycyclic isomeric compounds with spiroindene
and dinaphthofuran strutures. However, the use of thienyltriphenylbut-2-yne-1,4-diol leads
to the formation of a single spiranic compound joining a cyclopenta[b]thiophene to a
naphtho[2,1-b]furan.
Supporting Information
Supporting information features experimental procedures plus full spectroscopic data for
diols 2a-c and spiro compounds 3a-f/4a-e.
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Experimental Section
General remarks: All reaction were monitored by thin-layer chromatography on aluminum
plates coated with Merck silica gel 60 F254 (0.25mm). IR spectra were obtained in a
Shimadzu IRAffinity spectrometer using an ATR mode. Melting point were determined using
1
13
a microscope URAC with a heating plate and are uncorrected. The H and C NMR spectra
were recorded at 298K on a Bruker ARX 400 spectrometer (at 400.13 and 100.62 MHz).
High resolution electrospray ionization time-of-flight (ESI-TOF) mass spectra and electron
impact time-of-flight mass spectra were determined with a VG AutoSpec M spectrometer.
General Procedure for the Synthesis of diols 2a-d: n-Butyllithum (2 eq) was added
dropwise to a solution of 1,1-diarylprop-2-yn-1-ol (2.5 g) in dry THF (30 mL) at 0ºC. After
complete addition, the cold mixture was maintained under constant stirring for 30 min. The
adequate benzophenone (1.1 eq) was added at once to the solution, and the resulting
mixture stirred at room temperature for 22 hours. The solvent was removed, water was
added and the aqueous phase was extracted with ethyl acetate (3x30mL). The combined
organic phases were dried (Na
2
SO ) and the solvent removed under reduced pressure to
4
give an oil which was purified by recrystallization.
−
1
1
3
1
,1,4,4-Tetraphenylbut-2-yne-1,4 diol 2a. 81%. Mp: 201.4−203.0 °C. IR (KBr, cm ): 3532,
456, 3061, 3019, 2918, 2843, 2364, 2339, 1600, 1499,1448, 1331, 1213, 1138, 1070,
1
028, 995, 911, 886, 776, 743, 693, 642, 609. H NMR (400 MHz, CDCl
3
): 7.59 (d, J = 7.9
Hz, 8H), 7.39−7.23 (m, 12H), 2.86 (s, 2H, OH). EI-MS (TOF) m/z (%): 372 (32), 371 (11),
70 (14), 356 (28), 344 (22), 267 (22), 265 (27), 252 (11), 208 (10), 207 (14), 182 (64), 181
10), 179 (13), 178 (17), 165 (19), 05 (100), 77 (50). HRMS calcd for C28 O):
3
(
H20O (M − H
2
3
72.1514. Found: 372.1503.
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1
-(p-Methoxyphenyl)-1,4,4-triphenylbut-2-yne-1,4-diol 2b. 77%. Mp 107.5−109.5°C. IR
−1
(
KBr, cm ): 3375, 1590, 1509, 1446, 1362, 1241, 1174, 996, 892, 839, 778, 691. EI-MS
(TOF) m/z (%): 420 (M+, 0.18), 225 (31), 386 (100), 374 (28), 143 (47), 265 (31), 252 (26),
1
2
37 (26), 207 (14), 182 (14), 165 (38). H NMR (400 MHz; CDCl
3
): 7.59-7.50 (m, 6H), 7.35
), 3.03-2.90
): 159.1, 144.8, 144.7, 137.0, 128.3, 128.7, 127.8, 127.7,
27.4, 126.0, 125.9, 113.6, 90.2, 89.8, 74.5, 74.2, 55.3. HRMS calcd for C29
20.1725, found: 420.1724.
(
d, J=7.1 Hz, 2H), 7.32-7.26 (m, 9H), 6.85 (d, J=8.6 Hz, 2H), 3.79 (s, 3H, OCH
3
13
(m, 2H). C NMR (100 MHz; CDCl
3
1
4
H O :
24 3
1
-(p-Bromophenyl)-1,4,4-triphenylbut-2-yne-1,4-diol 2c. 67%. Mp 116.8−118.8°C. IR
−1
(
KBr, cm ): 3408, 1596, 1492, 1442, 1395, 1208, 1127, 1073, 1013, 986, 892, 818, 745,
6
2
91, 611. EI-MS (TOF) m/z (%): 450 (M+, 8), 436 (31), 434 (35), 347 (8), 276 (15), 267 (10),
1
65 (35), 263 (14), 207 (22), 189 (15), 184 (18), 182 (18), 178 (28), 165 (19), 105 (100). H
NMR (400 MHz, CDCl
3
): 7.60-7.50 (m, 6H), 7.50-7.40 (m, 4H), 7.35-7.20 (m, 9H), 3.11 (s,
1
1
H), 3.05 (s, 1H). 13C NMR (100 MHz; CDCl
3
):144.5, 144.2, 143.8, 131.4, 128.4, 128.3,
28.0, 127.9. 127.8, 125.9, 125.8, 121.8, 90.3, 89.4, 74.5, 74.1. HRMS calcd for C28
H19OBr
2
(M-H O): 450.0619, found: 450.0619.
1
.4. 1-Thienyl-1,4,4-triphenylbut-2-yne-1,4 diol 2d. 18%. Mp 172.6−174.5°C. IR (KBr,
−1
cm ): 3509, 1596, 1489, 1449, 1342, 1215, 1073, 1027, 979, 912, 832, 778, 739, 698, 644.
EI-MS (TOF) m/z (%): 378 (M+, 14), 362 (100), 350 (17), 285 (10), 273 (31), 271 (17), 239
1
(
(
(
15), 213 (14), 184 (39), 152 (15), 110 (20), 105 (38). H NMR (400 MHz; CDCl
3
): 7.67-7.60
13
m, 7H), 7.40-7.20 (m, 9H), 7.03 (m, 1H), 6.89 (m, 1H), 3.28 (s, 1H), 3.08 (s, 1H). C NMR
100 MHz; CDCl ): 149.9, 144.5, 143.9, 128.3, 128.2, 127.8, 126.6, 126.0, 125.7, 125.4,
9.3, 89.3, 74.6, 72.0. HRMS calcd for C26 18OS (M-H O): 378.1078, found: 378.1083.
3
8
H
2
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European Journal of Organic Chemistry
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General procedure for the synthesis of the spirocompounds 3-4: To a solution of
naphthol 1a-c (100 mg) and tetraarylbut-2-yn-1,4-diol 2a-d (1 eq) in CHCl (5 mL) was added
3
APTS (catalytic) and the mixture was heated under reflux. TLC examination indicated the
initial formation of the less polar and photochromic vinylidene-naphthofuran. After 1-2.5 h at
reflux TLC examination indicated the absence of the diol and naphthol and the formation of
a non-photochromic compound with the same polarity as the intermediate vinylidene-
naphthofuran. The solution was cooled to room temperature and the solvent removed under
reduced pressure. The residual product was purified by column chromatography (silica, 0-5
%
ethyl acetate/petroleum ether).
The reaction of 2-naphthol 1a with diol 2a afforded a mixture of spironaphthofuran 3a and
−1
dihydrodinaphthofuran 4a: 87%. IR (KBr, cm ): 2959, 1624, 1596, 1496, 1436, 1375, 1275,
1
3
020, 972, 805, 768, 739, 698. EI-MS (TOF) m/z (%): 498 (M+, 100), 422 (21), 421 (63),
93 (12), 356 (15), 331 (33), 327 (22), 315 (60), 313 (59), 307 (41), 300 (15), 267 (16), 239
(25), 149 (26), 137 (69), 127 (55), 99 (28), 81 (22), 69 (73). HRMS calcd for C38H26O:
4
98.1984, found: 498.1987. For NMR details see the supplementary information.
The reaction of 7-methoxy-2-naphthol 1b with diol 2a afforded a mixture of
-1
spironaphthofuran 3b and dihydrodinaphthofuran 4b: 40%. IR (KBr, cm ): 2959, 1624,
1
5
516, 1469, 1439, 1375, 1275, 1227, 1127, 1033, 972, 825, 751, 698. EI-MS (TOF) m/z (%):
+
29 (M +1, 28), 528 (M+, 100), 451 (35), 337 (17), 302 (20), 300 (17), 165 (17). HRMS calcd
for C36H24OS: 528.2089. Found: 528.2072. For NMR details see the supplementary
information.
The reaction of ethyl 6-hydroxy-2-naphthoate 1c with diol 2a afforded a mixture of
-1
spironaphthofuran 3c and dihydrodinaphthofuran 4c: 87%. IR (KBr, cm ): 2985, 1711, 1621,
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European Journal of Organic Chemistry
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0
1
5
474, 1442, 1362, 1275, 1241, 1187, 1093, 1020, 946, 809, 751, 698. EI-MS (TOF) m/z (%):
+
71 (M +1, 38), 570 (M+, 100), 493 (41), 379 (34), 315 (38), 313 (63). HRMS calcd for
41 30
C H O
3
: 570.2195. Found: 570.2180. For NMR details see the supplementary information.
The reaction of 2-naphthol 1a with diol 2b afforded a mixture of spironaphthofurans 3d/3d'.
−
1
7
7
0%. IR (KBr, cm ): 2945, 1596, 1509, 1442, 1348, 1268, 1239, 1174, 1033, 979, 939, 812,
+
45, 698. EI-MS (TOF) m/z (%): 529 (M +1, 38), 528 (M+, 100), 451 (42), 361 (34), 307
(43), 302 (52), 300 (33), 165 (39). HRMS calcd for C36H24OS: 528.2089. Found: 528.2078.
For NMR details see the supplementary information.
The reaction of 2-naphthol 1a with diol 2c afforded a mixture of Spironaphthofuran 3e and
−1
dihydrodinaphthofurans 4e/4e': 75%. IR (KBr, cm ): 2959, 1711, 1627, 1469, 1355, 1268,
+
1
234, 1187, 1093, 1013, 972, 812, 745, 691. EI-MS (TOF) m/z (%): 650 (M +2, 62), 648
(
M+, 59), 573 (17), 493 (20), 457 (24), 403 (21), 375 (27), 359 (22), 313 (100), 300 (25), 265
28), 165 (60). HRMS calcd for C41 Br: 648.1300. Found: 648.1274. For NMR details
(
29
H O
3
see the supplementary information.
The reaction of 2-naphthol 1a with diol 2d afforded the Spironaphthofuran 3f. 46% IR (KBr,
−1
cm ): 2952, 1630, 1596, 1489, 1446, 1369, 1248, 1237, 1006, 939, 805, 751, 691. EI-MS
+
(
TOF) m/z (%): 505 (M +1, 31), 504 (M+, 100), 427 (33), 337 (28), 321 (33), 319 (25), 307
(22), 186 (82), 105 (32). HRMS calcd for C36H24OS: 504.1548. Found: 504.1545. For NMR
details see the supplementary information.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201800612
2
1
Acknowledgments
We acknowledge the FCT (Portugals Foundation for Science and Technology) and FEDER
program COMPETE) for financial support through research project POCI-01-0145-FEDER-
16726 and PTDC/QEQQOR/0615/2014. The 300 and 500 MHz NMR facilities were funded
(
0
by the Rꢀgion Nord-Pas de Calais (France), the Ministꢁre de la Jeunesse de l’education
Nationale et de la Recherche (MJENR) and the Fonds Europꢀens de Dꢀveloppement
Rꢀgional (FEDER).
References
1
.
T.W. Christopher, T. Yi, In Natural Product Biosynthesis: Chemical Logic and
Enzymatic Machinery. Royal Society of Chemistry. London, 2017.
2
3
4
5
.
.
.
.
D.J. Tantillo, J. Phys. Org. Chem. 2008, 21, 561-570.
H. Li, Y. Sun, Q. Zhang, Y. Zhu, S.M. Li, A. Li, C. Zhang, Org Lett. 2015, 17(2), 306-9.
B.T. Ueberbacher, M. Hall, K. Faber, Nat. Prod. Rep. 2012; 29(3), 337-50.
E.R. Strieter, A. Koglin, Z.D. Aron, C.T. Walsh, J. Am. Chem. Soc. 2009, 131(6), 2113-
5
.
6
.
J. Bai, D. Yan, T. Zhang, Y. Guo, Y. Liu, Y. Zou, M. Tang, B. Liu, Q. Wu, S. Yu, Y.
Tang, Y. Hu, Angew. Chem. 2017, 129, 4860-4864.
7
8
.
.
B. Baskar, P. Dakas, K. Kumar, Org. Lett. 2011, 13 (8), 1988-1991.
M. Ohashi, F. Liu, Y. Hai, M. Chen, M.C. Tang, Z. Yang, M. Sato, K. Watanabe, K. N.
Houk, Y. Tang, Nature 2017, 549, 502-506.
9
.
K.C. Nicolaou, J.S. Chen, Chem. Soc. Rev. 2009, 38, 2993-3009.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201800612
2
2
1
0. K.C. Nicolaou, D.J. Edmonds, P.G Bulger, Angew. Chem. Int. Ed. 2006, 45, 7134-
186.
7
1
1
1
1. C. Grondal, M. Jeanty, D. Enders, Nat. Chem. 2010, 2(3), 167-178.
2. L.F Tietze, A. Modi, Med. Res. Rev. 2000, 20(4), 304-22.
3. S.B. Jones, B. Simmons, A. Mastracchio, D.W.C. MacMillan, Nature 2011, 475, 183-
88.
1
1
1
1
1
1
4. T. Broja, P.J.W. Fuchs, K. Zeitler, Nat. Chem. 2015, 7, 950-951.
5. C. M. Sousa, J. Berthet, S. Delbaere, P.J. Coelho, J. Org. Chem. 2013, 78, 6956-6961.
6. C. M. Sousa, J. Berthet, S. Delbaere, P.J. Coelho, Dyes Pigm. 2017, 137, 593-600.
7. C. M. Sousa, J. Berthet, S. Delbaere, P.J. Coelho, J. Org. Chem. 2013, 79, 5781-5786.
8. J. Schripsema, G.P. Caprini, R. van der Heijden, R. Bino, R. de Vos, D. Dagnino, J.
Nat. Prod. 2007, 70, 1495-1498.
1
2
2
9. N. Watanabe, H. Nakagawa, A. Ikeno, H. Minato, C. Kohayakawa, J. Tsuji, Bioorganic
Med. Chem. Lett. 2003, 13, 4317-320.
0. N. Watanabe, A. Ikeno, H. Minato, H. Nakagawa, C. Kohayakawa, J. Tsuji, J. Med.
Chem. 2003, 46, 3961-3964.
1. T.A. Blizzard, J.D. Morgan, R.T. Mosley, E.T. Birzin, K. Frisch, S.P. Rohrer, M.L.
Hammond, Bioorganic Med. Chem. Lett. 2003, 13, 479-483.
This article is protected by copyright. All rights reserved.