Zeolites Catalyze the Nazarov Reaction and the tert -Butylation of Alcohols by Stabilization of Carboxonium Intermediates

Article abstract of DOI:10.1055/s-0039-1690896

Zeolites are the most used catalysts worldwide in petrochemistry processes, with particular ability to stabilize carbocations. However, the use of zeolites in organic synthesis is still scarce. We show here that representative carboxonium-mediated organic

Full text of DOI:10.1055/s-0039-1690896

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–G
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M. Tejeda-Serrano et al.
Feature
Synthesis
Zeolites Catalyze the Nazarov Reaction and the tert-Butylation of
Alcohols by Stabilization of Carboxonium Intermediates
María Tejeda-Serrano
stabilized carboxonium
O
O
Sergio Sanz-Navarro
Finn Blake
R1
R2
R1
R2
OH
R1
R2
R1
R2
R1
R2
R1
R2
Antonio Leyva-Pérez*
0
0
0
0-0
0
0
3-
1
0
6
3-5
8
1
1
Nazarov
cyclization
Instituto de Tecnología Química, Universidad Politècnica de
València, Consejo Superior de Investigaciones Científicas (ITQ,
UPV-CSIC), Avda. de los Naranjos s/n, 46022 Valencia, Spain
anleyva@itq.upv.es
O
tert-butylation
of alcohols
R1 OH
+
Me
O
H
O
R1
O
Me
O
acid zeolite
Received: 31.01.2020
Accepted after revision: 26.03.2020
Published online: 20.04.2020
pens when the success of the organic reaction not only re-
lies on the first protonation of the substrate, but also on the
lifetime of the positively charged intermediates.4 If so, a sol-
id having a negatively charged, highly delocalized frame-
work, can readily interact with the flourishing (oxo)carbo-
cation intermediate and catalyze the reaction to the final
product under much milder reaction conditions than solu-
ble superacids.
Zeolites are crystalline microporous aluminosilicates
with the general formula shown in Figure 1.5 The isomor-
phic substitution of Si4+ by Al3+ atoms, generates a defect of
positive charges in the framework that must be balanced
with external cations, and if these cations are protons, the
zeolite shows Brönsted acidity. The negatively charged zeo-
lite framework acts as a very diffuse macroanion, in analo-
gy with low-coordinating anions in solution. Thus, a zeolite
may be active as acid catalyst in relatively complex organic
reactions involving positively charged intermediates, and
substitute very strong soluble acids. Indeed, this strategy
has proved efficient in organic reactions involving highly
delocalized aromatic carbocations.4,6 However, it is difficult
to find in the literature simple solid acids that catalyze rela-
tively complex organic reactions involving carboxonium
intermediates.7
Two representative organic reactions involving carboxo-
nium intermediates are the Nazarov cyclization (Scheme
1B)8 and the tert-butylation of alcohols (Scheme 1C).9 The
former is typically catalyzed by very strong soluble acids,
for instance TfOH,10 and starts with the protonation of a di-
enone in trans-trans configuration, which after several de-
localizations of the positive charge evolves to the cyclized
product. The very strong acid catalyst not only triggers the
reaction, but also may isomerize the starting dienone into
other conformations than the required trans-trans configu-
ration.11 While a zeolite will not trigger so efficiently the
reaction, it may stabilize the different positively charged
DOI: 10.1055/s-0039-1690896; Art ID: ss-2020-z0061-fa
Abstract Zeolites are the most used catalysts worldwide in petro-
chemistry processes, with particular ability to stabilize carbocations.
However, the use of zeolites in organic synthesis is still scarce. We show
here that representative carboxonium-mediated organic reactions,
such as the Nazarov cyclization and the tert-butylation of alcohols with
tert-butyl acetate, typically performed with very strong acid catalysts in
solution such as triflic acid, can be catalyzed by simple zeolites with
high yield and selectivity. The aluminosilicate framework stabilizes the
intermediate carboxonium species and overrides the need for superacid
protons in solution.
Key words zeolites, solid catalyst, Nazarov reaction, tert-butylation
reaction, carboxonium, heterogeneous catalysis
Organic reactions catalyzed by very strong acids in solu-
tion, either Brønsted acids composed of protons loosely
bound to low-coordinating anions, such as sulfuric acid
(H2SO4), phosphoric acid (H3PO4), and triflic acid (TfOH), or
Lewis acids, such BF3 and AlCl3, are recurrent in organic
synthesis.1 In many cases, the substrates evolve to carboca-
tions and carboxoniums (if the positive charge is stabilized
and can delocalize into an adjacent oxygen atom) after the
initial protonation, and these charged intermediates are of-
ten the key intermediate of the reaction.2 Thus, one must
accept that the strong acid in solution not only triggers the
reaction, but also stabilizes intermediate (oxo)carbocations
with the low-coordinating anion left behind, which makes
them, on the one hand, very efficient and somewhat unique
for certain organic reactions while, on the other hand, un-
suitable to provide mild reaction conditions.
The catalytic and stabilizing effect of strong acids in
solution for (oxo)carbocations can be somehow mimicked
by simple solid acids (Scheme 1A), despite the fact that
acidity of the latter is orders of magnitude lower.3 This hap-
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
M. Tejeda-Serrano et al.
Feature
Synthesis
intermediate species formed during reaction, in such a way
to perform the cyclization efficiently.12
Catalytic results for the Nazarov cyclization with H-USY
zeolite (commercially available as CBV-720), a standard acid
zeolite of Si/Al ratio = 15, pore diameter of ~10 Å, and acidi-
ty of 444.5 mol H+/g according to amine-probe titrations
are given in Scheme 2 and Table S1.4,13a It can be seen that
dienones 2a–c cyclize in high yields with just 0.5 mol% solid
acid sites (10 wt% in zeolite) after 2 h reaction time at 75 °C
M2/nO·Al2O3·xSiO2·yH2O
Figure 1 General formula for zeolites; M = hydrogen, alkali metal, or
alkaline earth atom, n = charge of that atom, x = ratio of SiO2/Al2O3, and
y = number of water molecules.
Biographical Sketches
Maria Tejeda-Serrano de-
fended her master thesis in
2015 focused on the synthesis
of ionic liquids as sustainable or-
ganic catalysts. Then she moved
to Instituto de Tecnología
Química (UPV-CSIC) in Valencia
for a Ph.D. in Sustainable Chem-
istry under the supervision of
Dr. Antonio Leyva-Pérez, fo-
cused on the substitution of ho-
ect between ITQ and a multina-
tional company, Schimmer &
Schwarz, supervised by Dr.
Antonio Leyva-Pérez. Currently,
she is a postdoc at the ETH Zu-
rich under the supervision of
Prof. Christophe Copéret.
mogeneous
catalysts
for
heterogeneous catalysts in or-
ganic reactions of industrial in-
terest. Furthermore, she worked
on a RETOS Collaboration proj-
Sergio Sanz Navarro was
born in Valencia (Spain). He ob-
tained a Bachelor’s degree in
Chemistry and a Master’s de-
gree in Organic Chemistry at
the University of Valencia. He
developed his degree and Mas-
ter’s degree projects under the
supervision of Dr. Carlos del
Pozo in the Organic Chemistry
Department of the University of
Valencia, working on the asym-
metric synthesis of pharmaco-
logical compounds. Currently
he is carrying out a Ph.D. on
heterogeneous catalysis under
the supervision of Dr. Antonio
Leyva-Pérez at the Universitat
Politècnica de València.
Finn Blake grew up in Aber-
deen, Scotland. He graduated
ceived the opportunity through
the Erasmus program to spend
Leyva-Perez and Dr. Maria
Tejeda to complete his master’s
thesis. Since completing his
studies Finn has spent the last 2
years working as a Process Engi-
neer in the energy industry.
from
the
University
of
a
semester
studying
at
Strathclyde with a Master’s de-
gree in Chemical and Process
Engineering in 2017. As part of
his university studies he re-
the Universitat Politècnica de
València, working at the Institu-
to de Tecnología Química under
the stewardship of Dr. Antonio
Antonio Leyva-Pérez was
born and grew up in Seville
(Spain). He carried out his Ph.D.
research on heterogeneous ca-
talysis under the supervision of
Prof. Hermenegildo García at
the Universitat Politècnica de
València. After a short stay at
M.I.T. in Prof. Steven L.
Buchwald’s laboratories, work-
ing in organometallics, he did
post-doctoral studies in the
Chemistry Department of the
University of Cambridge in Prof.
Steven Ley’s group, working on
the total synthesis of the
Prof. Avelino Corma. After re-
ceiving a Ramon y Cajal re-
search contract in 2014 and a
Distinguished Research perma-
nent position in 2016, he start-
ed the Catalysis for Sustainable
Organic Synthesis at CSIC,
which he currently leads.
complex
natural
products
bongkrekic and isobongkrekic
acids and epyriculol. In 2008, he
returned to the ITQ to work with
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

C
M. Tejeda-Serrano et al.
Feature
Synthesis
H+X– (cat.)
Substrate
[Substrate-H]+ X–
[Substrate]+-H X–
A)
+
[Substrate]+
Substrate-
B) Nazarov cyclization
OH
O
O
OH
O
OH
R1
R2
R1
R2
R1
R1
R2
R1
R2
R1
R2
H+
R1
R2
R1
R2
R1
R2
R1
R2
R1
R2
R1
R2
+ R2
H
Different carboxonium and carbocation intermediates
C) tert-Butylation of alcohols
O
R3
O
O
, H+
OH
R2
O
R3
R1OR3
+
R3
R1OH
R2
O
R2 OH
R2
O
H
H+
Carboxonium intermediates, R3 = tert-butyl
Scheme 1 Carboxonium stabilization in solid catalysts. (A) Schematic representation of the catalytic action of a soluble superacid and a solid during
protonation and (oxo)carbocation stabilization; X– = low-coordinating anion. (B) Carboxonium and carbocation intermediates during the Nazarov cy-
clization. (C) Carboxonium intermediates during the tert-butylation of alcohols.
(see comments for products 2d,e below). Remarkably, the
cis-cis isomer was obtained as the major product, since ki-
netic results by gas chromatography coupled to mass spec-
trometry (GC-MS) show that the other isomers appear at
the very beginning of the reaction, but evolve progressively
to the cis-cis isomer, as assessed with independently syn-
thesized pure samples of the product.11 It must be recog-
nized that the substrate scope is quite narrow, however, not
far from other catalytic system based on stronger acids.13b
Figure 2 shows a plot where the activation energy (Ea)
for the Nazarov cyclization of dienone 1a is represented vs.
the acidity (tabulated pKa values) of different soluble and
solid acids.4,6c The activation energy was calculated from
the initial rate of the cyclization at different temperatures,
which was obtained by linear regression of the first points
of the corresponding kinetics (Figure S1), then applying the
Arrhenius equation. The results clearly show that, for solu-
ble acids, the activation energy correlates linearly with the
pKa of the acid, as it would be expected for general acid ca-
talysis where the protonation step is the limiting step of the
reaction (see Scheme 1A). In striking contrast, different
O
O
H-USY zeolite
(0.5 mol%, Si/Al = 15)
Me
R1
Me
R1
Me
R1
Me
R1
1,2-dichloroethane, 75 °C, 2 h
2a–e
1a–e
O
O
O
Me
Me
Me
Me
Me
Me
S
Me
S
Cl Cl
2a, 85%
2b, 94%
2c, 97%
O
O
Me
Cl
Me
Me
Cl
Cl Cl
Cl
Cl
2d, 13%
2e, 11%
Figure 2 Activation energy (Ea) for the Nazarov cyclization of dienone
1a as a function of the acidity (pKa) of different soluble and solid acids.
The Si/Al ratios for the different zeolites are: HY-720, beta-H, and
ZSM-5 ~15, HY-740 ~20, and HY-760 ~30. Error bars account for a
5% uncertainty.
Scheme 2 Nazarov cyclization catalyzed by H-USY zeolite under the re-
action conditions indicated; GC yields. Only the cis-cis product is shown,
since it typically accounts for >90% of the total isomeric mixture.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

D
M. Tejeda-Serrano et al.
Feature
Synthesis
zeolites show much lower activation energy than that ex-
pected from their corresponding pKa values, at least 40 kcal
lower. This decrease in activation energy is more pro-
nounced as the acid strength of the zeolite increases (i.e.,
compare H-USY 720 with 760) and it does not depend on
zeolite pore size or topology, since the beta-H and ZSM-5-H
zeolites also catalyze the cyclization.
lene (4) gives directly the all-carbon products, indenes 6a–
c, in 42–69% yields, without the need to isolate intermedi-
ates 5 is shown in Scheme 3.6a,18 These results illustrate the
potential of zeolites as catalysts for the Nazarov reaction.
However, it must be noticed that, while intermediate 5a is
formed with just 1 mol% of acid zeolitic sites in 78% under
similar reaction conditions,19 the cyclization needs 10 mol%
of zeolite to convert ~80% of this intermediate, even with
the more active H-USY (Si/Al = 20) zeolite.
When the activation energy is decoupled into the en-
thalpic and entropic contributions (Figures S2 and S3), it
can be seen that the decrease in the activation energy is en-
thalpic in nature.14 Comparison of the activation energies
for 1a–c, with different zeolites (Figures S4–S7), shows an
increase with the electron-withdrawing nature of the sub-
stituents, in other words, the more delocalized dienones re-
act worse. This can be the reason why dienones 1d,e did
not cyclize significantly under all conditions tested. Single
crystal X-ray crystallography of dienone 1e (Figure S8) did
not show any particular structural issue to justify such a
huge difference in reactivity, and the use of the aluminosili-
cate MCM-22 as a catalyst (the non-porous analogue of H-
USY) did not improve the yield of 2d (Figure S9). These re-
sults confirm that the catalytic action of the zeolites for the
Nazarov reaction depends on electronics rather than ster-
ics, and that very subtle changes in the electronics of the di-
enone dramatically changes the cyclization outcome. In-
deed, in the case of 1d, only the isomerization of the start-
ing dienone to non-productive isomers, was found, and
calculation of the dynamic radii by molecular mechanics
(MM2) at minimized energy for this and other dienone iso-
mers, gives values of ~15 Å, nearly one and a half times
higher than the pore diameter of H-USY zeolite (Figure S9).
Thus, the Nazarov cyclization must occur outside the pores,
on the outer surface of the microporous of the zeolite. To
check this, the aluminosilicate MCM-22 was used as a cata-
lyst for 1a, and a similar activation energy to H-USY was ob-
tained. These results strongly support that the Nazarov cy-
clization is catalyzed on the negatively charged surface of
the zeolite by electronic stabilization of the carboxonium
and carbocations intermediates during reaction, and not to
confinement effects within the pores.15
Me
resonant
H-USY Zeolite
propargyl cation
(10 mol%, Si/Al = 20)
for 3a
Me
OH
Me
Me
R2
Me
R1
Me
Me
Me
Me
4 (solvent)
3a, R1 = Ph, R2 = H
3b, R1 = R2 = Ph
3c, R1 = R2 = H
130 °C, 24 h
6a, 61%
5a
Me
Me
Me
Me
6b, 69%
6c, 42%
Me
Me
Scheme 3 One-pot Friedel–Crafts/Nazarov cyclization of propargyl al-
cohols 3a–c to indenes 6a–c catalyzed by H-USY zeolite (CBV740). GC
yields.
The tert-butylation of benzyl alcohols 7a–j with tert-
butyl acetate (8), another representative carboxonium-
mediated organic reaction (see Figure 1C), was then
attempted with zeolite catalysts (Scheme 4).9 Different ben-
zyl alcohols give a variety of tert-butylated products con-
taining halide (9b–g), trifluoromethyl (9b), alcohol (9d),
thioether (9h), and cyano (9j) functional groups, in differ-
ent positions of the aromatic ring in good yields, when a
H-USY catalyst was employed; 2-thienylmethanol also gave
the corresponding product 9i . Not only that, alkyl (prod-
ucts 9k–o) and homobenzyl (products 9p–s) alcohols also
engage in the reaction, although the latter provided some-
what lower yields due to extensive dehydration to the cor-
responding styrene derivatives, under the indicated reac-
tion conditions.
Figure 3 shows a plot with the calculated activation en-
ergies for the tert-butylation of benzyl alcohol (7a) with
tert-butyl acetate (8), in the presence of different soluble
and solid acids. As for the Nazarov reaction, the solid acids
show a significant decrease in the activation energy com-
pared to soluble acids, the latter showing a linear correla-
tion. As it occurs in the Nazarov reaction, not only zeolites,
but also other aluminosilicates, such as MCM-22 and the
The catalytic zeolite was recovered and recycled after
the Nazarov cyclization of 1a (Figure S10). Thermogravi-
metric analysis of the used solid catalyst showed a signifi-
cant amount (~8%) of non-volatile carbonaceous substances
retained in the zeolite, even after extensive washings (Fig-
ure S11), and Fourier-transformed infrared spectroscopy
(FT–IR, Figure S12) of the used catalyst showed the appear-
ance of new signals around 1650–1700 cm–1, which corre-
sponds to entrapped aromatic organic compounds.16 These
results, together, indicate the strong adsorption of colored
aromatic intermediates, most probably positively charged
species, on the zeolitic surface.
A one-pot Friedel–Crafts/Nazarov cyclization17 cata-
lyzed by the most active H-USY zeolite (CBV740), where the
dihydroxylation of propargyl alcohols 3a–c with mesity-
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

E
M. Tejeda-Serrano et al.
Feature
Synthesis
H-USY
(5 mol%, Si/Al = 20)
O
R1 OH
+
R1
O
Me
O
toluene, 75 °C
– MeCOOH
8
9a–s
7a–s
I
F3C
F
O
O
O
O
I
I
OH
9a
9b
9c
85%
9d
79%
83%
55%
I
F
Br
O
O
O
O
O
MeS
I
Br
9h
9e
9f
9g
51%
80%
72%
63%
NC
O
O
O
O
S
9l
85%
9k
55%
9i
65%
9j
79%
O
O
O
O
9m
9p
70%
9o
79%
9n
65%
75%
O
O
O
O2N
9q
9s
65%
9r
55%
45%
Scheme 4 tert-Butylation of benzyl, alkyl, and homobenzyl alcohols 7a–s with tert-butyl acetate (8) catalyzed by H-USY zeolite (CBV740).
mesoporous material MCM-41, efficiently catalyze the re-
action, which suggests that the reaction occurs on the ex-
ternal surface of the zeolite.
In conclusion, carboxonium and carbocation-mediated
reactions are efficiently catalyzed by acid aluminosilicates,
particularly zeolites, under relatively mild conditions. The
catalysis occurs on the surface of the zeolite, thus molecular
size is not a restriction and the most important factor gov-
erning the reactions is the electronics of the substrate.
These results open new opportunities in the design of or-
ganic reactions based on cheap, widely available, and envi-
ronmentally friendly solid catalysts to substitute corrosive
soluble acids.20
All chemicals were of reagent grade quality. They were purchased
from commercial sources and used as received. Gas chromatographic
analyses were performed in an instrument equipped with a 25-m
capillary column of 5% phenylmethylsilicone. n-Dodecane was used
as an external standard. GC/MS analyses were performed on a spec-
trometer equipped with the same column as the GC and operated un-
der the same conditions. 1H, 13C, and DEPT NMR spectra were record-
ed at r.t. on a Bruker AC 300 using the appropriate solvent containing
TMS as an internal standard. FT-IR spectra were recorded on a Perkin-
Elmer 882 spectrophotometer as KBr pellets or on a Thermo Nicolet
iS10 after deposition and evaporation of a solution of the compound
over a germanium wafer. Absorption spectra were recorded on a Cary
300 UV-Vis spectrophotometer (Varian). The thermogravimetric
analyses were performed under a dry N2 atmosphere with a Mettler
Figure 3 Correlation between the activation energy (Ea) and the acidi-
ty (pKa) of different soluble and solid acids for the tert-butylation of
benzyl alcohol (7a) with tert-butyl acetate (8) to give the ether product
9a. Error bars account for a 5% uncertainty.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

F
M. Tejeda-Serrano et al.
Feature
Synthesis
Toledo TGA/STDA851e thermobalance operating at a heating rate of
10 °C min–1. CCDC 1981152 contains the supplementary crystallo-
graphic data for 1e for this paper. The data can be obtained free of
charged from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
1,5-Bis(4-chlorophenyl)-2,4-dimethylpenta-1,4-dien-3-one (1e)
White solid.
IR: 1678, 1622, 1487 cm–1
.
1H NMR (CDCl3, 300 MHz):  = 7.37 (s, 8 H), 7.12 (s, 2 H), 2.18 (s, 6 H).
13C NMR (CDCl3, 75 MHz):  = 201.49, 137.70, 137.50, 137.42, 134.38,
130.97, 128.84, 15.05.
MS: m/z (%) = 330 (M+, 3), 295 (45), 150 (70), 115 (100).
1,5-Disubstituted 2,4-Dimethylpenta-1,4-dien-3-ones 1a–e; Gen-
eral Procedure13b,20c
To distilled water (20 mL) in a beaker was slowly added KOH pellets
(6.9 g); the mixture was stirred to dissolve the KOH. This solution was
added to a second flask equipped with a magnetic stirrer and contain-
ing MeOH (40 mL), pentan-3-one (6.15 mL), and aldehyde (122
mmol). The conical flask was then placed into a silicone bath set at
100 °C and connected to a condenser to achieve reflux. The reaction
was refluxed overnight and allowed to cool. The solution was neutral-
ized by slow addition of 2 M HCl (61 mL). After neutralization, the
solution was poured into a separatory funnel along with CH2Cl2 (20
mL) and shaken to allow the phases to mix. The aqueous phase was
discarded, the process was repeated (2 ×), and also with aq NaHCO3
soln (20 mL), water (40 mL), and finally brine (20 mL). The final or-
ganic solution was dried (Na2SO4), filtered, and concentrated under
vacuum. The product was purified by crystallization (MeOH, cool
overnight). The pure crystals examined by GC using a general 10-min
method with single injection of 3 L. The products were character-
ized by 1H and 13C NMR, MS, and analysis.
Anal. Calcd for C19H16Cl2O: C, 68.07; H, 6.01. Found: C, 69.01; H, 4.78.
Zeolite-Catalyzed Nazarov Cyclization
The corresponding amount of dienone 1a–e (0.2 mmol) was weighed
and diluted with DCE (1 mL) in a test tube. A 50 L sample was taken
as the zero-time sample and diluted in a vial with EtOAc (1 mL) to be
analyzed using GC with n-dodecane (22 L, 0.1 mmol) as the external
standard. The substrate and DCE were then added to a vial containing
0.5 mol% H+ of the zeolite (5 wt% for 1a) and a magnetic stirrer. The
vial was placed in a silicone bath at the required reaction tempera-
ture, ranging from 25 to 75 °C. The reaction was typically run for 120
min and 50 L samples were taken throughout the reaction, and each
was added to a vial containing EtOAc (1 mL). Each sample was then
filtered to remove any solid catalyst in the sample, and then analyzed
by GC with n-dodecane (22 L, 0.1 mmol) as an internal standard. All
the products are reported and characterized in the literature: 2a–d,13b
2e.21a
2,4-Dimethyl-1,5-diphenylpenta-1,4-dien-3-one (1a)
Recovery and Reuse of the Catalyst
White solid.
The Nazarov cyclization was performed using the same method as
above except with double the amount of catalyst (1 mol%, 10 wt%) to
ensure a good recovery. The reaction chosen to test the reusability of
the catalyst was the cyclization of 2c at 75 °C. After 60 min, the reac-
tion was stopped and the zeolite separated from the solution using a
centrifuge at 6000 rpm. After separation, the zeolite was cleaned with
a solvent and separated again in the centrifuge. The process was re-
peated twice. Then, the zeolite was left to dry overnight, weighed and
used again in reaction, adjusting the mass of substrate and volume of
DCE to keep the same final concentration.
IR: 1606, 1441 cm–1
1H NMR (CDCl3, 300 MHz):  = 7.46–7.32 (m, 10 H), 7.23 (s, 2 H), 2.23
.
(s, 6 H).
13C NMR (CDCl3, 75 MHz):  = 202.14, 139.09, 137.04, 136.10, 129.74,
128.58, 128.40, 15.04.
MS: m/z (%) = 262 (M+, 60), 116 (100).
Anal. Calcd for C19H18O: C, 85.67; H, 8.32. Found: C, 85.85; H, 6.82.
1,5-Bis(2-chlorophenyl)-2,4-dimethylpenta-1,4-dien-3-one (1c)
White solid.
Zeolite-Catalyzed One-Pot Friedel–Crafts/Nazarov Cyclization
IR: 1635, 1470, 1435 cm–1
1H NMR (CDCl3, 300 MHz):  = 7.35 (t, J = 9.8 Hz, 6 H), 7.24–7.18 (m, 4
.
Alcohol 3 (32 mg, 0.125 mmol) was weighed into a 2-mL vial and di-
luted with mesitylene (4; 1 mL). The corresponding zeolite (10 mol%,
100 wt%) was added and the vial was capped and placed in a steel
heat block at 130 °C. A 50 L sample was taken after 30, 60, and 90
min and then the reaction was left to run overnight. The samples
were diluted with DCE (1 mL), filtered to remove any solid catalyst in
the sample and analyzed by GC after addition of n-dodecane (22 L,
0.1 mmol) as an internal standard. All the products are reported and
characterized in the literature: 6a–c.17c
H), 2.00 (s, 6 H).
13C NMR (CDCl3, 75 MHz):  = 201.54, 138.87, 136.87, 135.10, 134.61,
130.88, 130.15, 129.91, 127.05, 15.12.
MS: m/z (%) = 330 (M+, 3), 295 (45), 150 (70).
Anal. Calcd for C19H16Cl2O: C, 68.07; H, 6.01. Found: C, 69.01; H, 4.78.
1,5-Bis(2,6-dichlorophenyl)-2,4-dimethylpenta-1,4-dien-3-one
(1d)
Zeolite-Catalyzed tert-Butylation Of Alcohols
Alcohol 7a–s (0.4 mmol) was weighed in a test tube, then the corre-
sponding amount of tert-butyl acetate (8; 68 L, 0.5 mmol) and tolu-
ene (0.5 mL) were added. A 20 L sample was taken as the zero-time
sample and diluted in a vial with EtOAc (1 mL) to be analyzed using
GC, with n-dodecane (22 L, 0.1 mmol) as an internal standard. The
mixture was then added to a vial containing 5 mol% H+ of the zeolite
(50 wt% for 7a) and a magnetic stirrer. The vial was placed in a sili-
cone bath at 75 °C. The reaction was typically run for 240 min and 20
L samples were taken throughout the reaction, and each was placed
in a vial with EtOAc (1 mL). Each sample was then filtered to remove
White solid.
IR: 1718, 1642, 1423 cm–1
.
1H NMR (CDCl3, 300 MHz):  = 7.31 (s, 1 H), 7.29 (s, 2 H), 7.20–7.12
(m, 5 H), 1.79 (s, 6 H).
13C NMR (CDCl3, 75 MHz):  = 199.39, 141.10, 134.49, 134.40, 134.29,
129.55, 128.09, 14.80.
MS: m/z (%) = 400 (M+, 2), 277 (100), 199 (50).
Anal. Calcd for C19H14Cl4O: C, 56.47; H, 4.49. Found: C, 57.10; H, 3.28.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

G
M. Tejeda-Serrano et al.
Feature
Synthesis
any solid catalyst in the sample, and then analyzed by GC with n-do-
decane (22 mL, 0.1 mmol) as an external standard. Most of the prod-
ucts are reported and characterized in the literature: 9a,21b 9g,21c
9h,21d 9i,21e 9k–l,n,21f 9m,21g 9o,21h 9p,s,21i 9q,21j 9r.21k
(8) (a) He, W.; Sun, X.; Frontier, A. J. J. Am. Chem. Soc. 2003, 125,
14278. (b) Alachouzos, G.; Frontier, A. J. Angew. Chem. Int. Ed.
2017, 56, 15030.
(9) Lloret, V.; Rivero-Crespo, M. A.; Vidal-Moya, J. A.; Wild, S.;
Domenech-Carbo, A.; Heller, B. S. J.; Shin, S.; Steinrueck, H.-P.;
Maier, F.; Hauke, F.; Varela, M.; Hirsch, A.; Leyva-Perez, A.;
Abellan, G. Nat. Commun. 2019, 10, 1.
(10) Vaidya, T.; Eisenberg, R.; Frontier, A. J. ChemCatChem 2011, 3,
1531.
(11) He, W.; Herrick, I. R.; Atesin, T. A.; Caruana, P. A.; Kellenberger,
C. A.; Frontier, A. J. J. Am. Chem. Soc. 2008, 130, 1003.
(12) Lewis, J. D.; Van de Vyver, S.; Román-Leshkov, Y. Angew. Chem.
Int. Ed. 2015, 54, 9835.
Funding Information
This work was supported by the MINECO (Spain) (Projects CTQ 2017-
86735-P, RTC-2017-6331-5, and Severo Ochoa program SEV-2016-
0683)
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Acknowledgment
(13) (a) Derouane, E.; Védrine, J.; Pinto, R.; Borges, P.; Costa, L.;
Lemos, M.; Lemos, F.; Ribeiro, F. Catal. Rev. 2013, 55, 454.
(b) Daneshfar, Z.; Rostami, A. RSC Adv. 2015, 5, 104695.
(14) Kadam, S. A.; Li, H.; Wormsbecher, R. F.; Travert, A. Chem. Eur. J.
2018, 24, 5489.
(15) (a) Huang, C.; Zhang, Y.; Yang, H.; Wang, D.; Mi, L.; Shao, Z.; Liu,
M.; Hou, H. Crystal Growth Design 2018, 18, 5674. (b) Shao, Z.;
Liu, M.; Dang, J.; Huang, C.; Xu, W.; Wu, J.; Hou, H. Inorg. Chem.
2018, 57, 10224.
(16) Reale, E.; Leyva, A.; Corma, A.; Martinez, C.; Garcia, H.; Rey, F.
J. Mater. Chem. 2005, 15, 1742.
(17) (a) Liu, R.; Abu Sohel, S.; Lin, S. Synlett 2008, 745. (b) Somai
Magar, K.; Lee, Y. Org. Lett. 2013, 15, 4288. (c) Morita, N.;
Miyamoto, M.; Yoda, A.; Yamamoto, M.; Ban, S.; Hashimoto, Y.;
Tamura, O. Tetrahedron Lett. 2016, 57, 4460.
M.T.-S. thanks ITQ for the concession of a contract. S.S.-N thanks
MINECO for the concession of a FPI fellowship. F.B. acknowledges fi-
nancial support from the Erasmus programme and is grateful to the
University of Strathclyde for a short stay at ITQ. Authors would like to
thank the use of RIAIDT–USC analytical facilities.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690896.
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G