Nonclassical Mechanism in the Cyclodehydration of Diols Catalyzed by a Bifunctional Iridium Complex

Article abstract of DOI:10.1002/chem.201805460

1,4- and 1,5-diols undergo cyclodehydration upon treatment with cationic N-heterocyclic carbene (NHC)–Ir^III complexes to give tetrahydrofurans and tetrahydropyrans, respectively. The mechanism was investigated, and a metal-hydride-driven pathway was proposed for all substrates, except for very electron-rich ones. This contrasts with the well-established classical pathways that involve nucleophilic substitution.

Full text of DOI:10.1002/chem.201805460

A Journal of
Accepted Article
Title: Nonclassical mechanism in the cyclodehydration of diols
catalyzed by a bifunctional iridium complex
Authors: Greco González Miera, Aitor Bermejo López, Elisa Martínez-
Castro, Per-Ola Norrby, and Belén Martín-Matute
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To be cited as: Chem. Eur. J. 10.1002/chem.201805460
Link to VoR: http://dx.doi.org/10.1002/chem.201805460
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10.1002/chem.201805460
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Nonclassical mechanism in the cyclodehydration of diols
catalyzed by a bifunctional iridium complex
Greco González Miera,#[a] Aitor Bermejo López,# [a] Elisa Martínez-Castro,[a] Per-Ola Norrby,[b] and
Belén Martín-Matute*[a]
Abstract: 1,4- and 1,5-Diols undergo cyclodehydration upon
treatment with cationic N-heterocyclic carbene (NHC) Ir(III)
complexes to give tetrahydrofurans and tetrahydropyrans,
respectively. The mechanism was investigated, and a metal-hydride-
driven pathway is proposed for all substrates, with the exception of
very electron-rich ones. This contrasts with the well-established
classical pathways involving nucleophilic substitution.
The synthesis of this type of cyclic ethers from diols is a well-
established procedure that can be mediated by Brønsted [5] or
6
]
Lewis acids,[
and mechanisms involving nucleophilic
substitution have been proposed.[7 ] Cyclizations under basic
conditions have also been reported.[8] However, in those cases
where transition-metal complexes were used, the possibility that
an alternative hydrogen-borrowing (or hydrogen-autotransfer)
mechanism could be operating was not investigated; this
motivated us to study the mechanism of these formal
cyclodehydration reactions.[9] We foundthat the mechanism for
the dehydrogenation of benzylic alcohols by 1a involved an
initial hydrogen-transfer step with concomitant formation of an
iridium-hydride species.[2] The hydroxy/alkoxide functionality on
the carbene ligand participated in proton-transfer steps. We
were intrigued by the possibility that a similar hydrogen-transfer
mechanism could also be operating in the case of the diols, and
we have now studied the cyclodehydration reactions of 1,4- and
1,5-diols catalyzed by NHC–iridium complexes 1a–1c. In this
paper, we propose mechanistic pathways that are dependent on
the electronic properties of the diols, and also on whether the
substrate is a 1,4- or a 1,5-diol.
Introduction
NHC-Ir complexes have proven to be excellent catalysts in
numerous processes, particularly in dehydrogenations and
transfer-hydrogenations.[1 , 2 , 3 ] NHCs can be relatively easily
functionalized to provide the desired reactivity. Their versatility
has been recently highlighted by Peris in a recent review article,
[4] where the author refers to NHCs as “smart ligands”.
We have previously investigated the activity of Ir(III)
complexes bearing functionalized NHC ligands (1) in C-N bond-
forming reactions from anilines and alcohols. Mechanistic
investigations indicated that the oxygen functionality on the NHC
ligand is involved in proton transfer steps, enabling to perform
the reactions under base-free conditions.[3b] The binfunctional
nature of the NHC-Ir complexes (1) was also explored in the
acceptorless dehydrogenation of alcohols [2] (Scheme 1, top).
(1a). Here we observed that when two 1,4-diols, 1-phenyl-1,4-
pentanediol (2a) and 1,4-diphenyl-1,4-butanediol (2j), were
reacted with 1a, tetrahydrofurans were formed in very good
yields (Scheme 1, bottom), instead of the expected products
derived from a dehydrogenation process (Scheme 1, bottom).
Results
First, we tested a series of NHC–Ir(III) complexes in the
cyclodehydration reaction of 1-phenyl-1,4-pentanediol (2a; Table
1).[2] The optimized reaction conditions for the acceptorless
alcohol dehydrogenation (AAD) reaction (Scheme 1, top) had
previously been tested on 2a (i.e., iridium complex 1a, in a
mixture of toluene and t-butanol (2.6:1, v/v) under reflux), and
under these conditions, tetrahydrofuran 3a was formed in
excellent yield (91%, Table 1, entry 1). [2] In contrast, neutral
iridium dichloride complex 1b did not promote the cyclization,
and instead, mono- and dioxidized linear compounds 4a and 5a,
as well as deoxygenated ketone 6a (see Supporting
Information),[10 ] were detected in the crude mixture at 80%
conversion of 2a (Table 1, entry 2). Biscationic bifunctional
catalyst 1c, which has an NHC ligand with only one hydroxy-
functionalized wingtip, gave the tetrahydrofuran product (3a) in a
low yield of 31%, together with a mixture of oxidized linear
compounds (Table 1, entry 3). The commercially available
complex [Cp*IrCl2]2 (1d) was also tested, and this gave 3a in
only 11% yield (Table 1, entry 4), along with higher yields of
oxidized linear by-products. In a control experiment carried out
in the absence of any iridium complex under otherwise identical
reaction conditions, 2a did not undergo any reaction (Table 1,
entry 5). When toluene was used as the sole solvent, the
catalytic activity of 1a towards the formation of 3a decreased;
this product was formed in a lower yield of 70% (Table 1, entry 6
vs entry 1).
OH
O
1a (3 mol%)
2
H2
+
2BF4
R1 R2
R1 R2
toluene:t-BuOH
H
O
reflux
Ir
L
OH
OH
N
N
n
1a (3 mol%)
R2
n
+
H2O
R1
R1
R2
toluene:t-BuOH
1a
O
OH
reflux
Bifunctional catalyst
n = 1, 2
Scheme 1. Acceptorless dehydrogenation of alcohols (top) and redox
cyclization of diols (bottom) catalyzed by 1a.
[a]
[b]
Dr. G. González Miera, A. Bermejo López, Dr. E. Martínez-Castro,
Prof. B. Martín-Matute
Department of Organic Chemistry
Stockholm University
Stockholm 10691, Sweden
E-mail: belen.martin.matute@su.se
# Equal contribution
Prof. P.-O. Norrby,
Early Product Development, Pharmaceutical Sciences, IMED
Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Supporting information for this article is given via a link at the end of
the document.
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Table 1. Cyclodehydration of diols catalyzed by Ir(III) complexes.[a]
Table 2. Cyclodehydration of diols catalyzed by 1a.[a]
O
n
OH
Ph
[Ir] (1a, 3 mol%)
n
R2
R1
R1
R2
5a
O
OH
O
toluene, t-BuOH
reflux, 24 h
O
[Ir] (3 mol%)
OH
O
+
+
Ph
Ph
Ph
toluene:t-BuOH
reflux, 12 h
O
3a
2a-2p
3a-3p
n = 1, 2
Ph
OH
OH
2a
4a
6a
2
2
2BF4
2BF4
O
O
O
O
H
H
O
tBu
MeO
Cl
N
O
Ir
Ir
Ir
3a
L
L
Cl
N
[Cp*IrCl2]2
3b
3c
94% (84%)
3d
95% (72%)
OH
OH
HO
nBu
91% (62%)
>99% (90%)
[>99% at 80 °C]
N
N
N
N
[21% at 80 oC]
1d
1a
1c
1b
F
O
O
O
O
Cl
F
Br
Entry
[Ir]
2a [%]
3a [%]
4a [%]
5a [%]
6a [%]
3e
3g
3h
3f
84% (75%)
59% (50%)
86% (70%)
86% (71%)
[56% at 80 oC]
1
1a
1b
1c
1d
-
nd[b]
20
91
5
4
nd[b]
23
2
nd
45
30
26
nd[b]
3
13
Ph
O
Ph
Ph
H
O
O
O
3
8
31
13
18
3i
89% (80%)
3k
3l
24%
3j
70%o
88% (78%)
4
10
17
12
35
5
>95
14
nd[b]
70
nd[b]
14
nd[b]
nd[b]
Ph
O
Ph
O
Ph
3n'
54% (3n’: 23%; 3n: 18%)
Ph
O
Ph
6[c]
1a
3m
42% (34%)
+
3n
[a] Reaction conditions: diol (1 mmol), [Ir] (0.03 mmol, 3 mol%), toluene (2.6
mL), t-BuOH (1 mL), 80 °C or reflux, 24 h. Yield determined by 1H NMR
spectroscopy. [b] nd = not detected. [c] In toluene as the sole solvent.
[a] Reaction conditions: diol (1 mmol), 1a (0.03 mmol, 3 mol%), toluene (2.6
mL), t-BuOH (1 mL), 80 °C or reflux, 24 h. Yield determined by 1H NMR
spectroscopy. Isolated yields in parentheses.
Iridium complex 1a was then used as the catalyst in the
cyclodehydration of a series of 1,4-diols (2a–2l) and 1,5-diols
(2m–2n) using the conditions of Table 1, entry 1 (Table 2). For
1,4-diols containing only sec-alcohols, the corresponding
tetrahydrofurans 3a–3k were formed in good to excellent yields.
The 1H NMR spectra of the products indicated the presence of
diastereomeric mixtures (see Supporting Information). The
reaction even worked well for aliphatic biomass-derived 2,5-
hexanediol (2k), which gave 2,5-dimethyltetrahydrofuran (3k),
an important industrial additive.[11]
Crossover experiments were carried out to gain some insight
into the overall redox-neutral reaction of diols. When a 1:1
mixture of 2j and ketoalcohol 4a was subjected to the reaction
conditions, cyclic structures 3j and 3a were both obtained
(Scheme 2, top). The reaction mixture also contained oxidized
intermediates 2,3-dihydrofuran 3j’, ketoalcohol 4j, and diketone
5j. Similarly, a 1:1 mixture of 2j and diketone 5a was subjected
to the reaction conditions (Scheme 2, bottom), and after 24 h,
tetrahydrofurans 3j and 3a were obtained, along with the
corresponding oxidized intermediates 3j’, 4j, and 5j.
When 1,4-diol 2l, which contains a sec- and a primary
alcohol, was subjected to the reaction conditions, the yield
dropped dramatically to only 24%. This is consistent with our
observations on the AAD reactions of primary alcohols catalyzed
by 1a.[2] Unsaturated diols did not yield cyclic ether derivatives,
but mixtures of diketones and deoxygenated ketones (see the
Supporting Information). Importantly, when the reaction was
tested under milder reaction conditions (80 °C), good yields
were only obtained for the very electron-rich diol 2b (to give 3b;
3a and 3h were formed in lower yields). Interestingly, 1,5-diol
substrates (2m and 2n) reached full conversions to give
mixtures of products; the major products were six-membered-
ring compounds; both saturated cyclic ethers (3m and 3n) and
2,3-dihydropyrans (3m’ and 3n’) were observed. The presence
of the unsaturated products suggests a net loss of dihydrogen
for this family of substrates. Dihydropyran 3m’ was transformed
into the corresponding tetrahydropyran 3m in a subsequent
hydrogenation step (see Supporting Information).
Hammett studies on the cyclization of five different para-
functionalized 1-aryl-1,4-pentanediol substrates are shown in
Figure 1: 1-phenyl-1,4-pentanediol (2a), p-methoxyphenyl-1,4-
pentanediol (2b), p-tert-butylphenyl-1,4-pentanediol (2c), p-tolyl-
1,4-pentanediol (2d), p-chlorophenyl-1,4-pentanediol (2e), and
p-fluorophenyl-1,4-pentanediol (2f) (see also the Supporting
Information).[12] The conversions were monitored by in situ 1H
NMR spectroscopy. For electron-poor 1,4-diols and for 1,4-diols
with moderately electron-rich substituents, plots of [log(kX/kH)] vs
σ (Figure 1a) show a linear relationship with a negative slope of
-1.73 ± 0.22. The electron-rich para-methoxy-substituted diol 2b
deviates from this Hammett correlation, as it reacted ca. 104
times faster than extrapolated (Figure 1a).[13]
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O
OH
(a)
Ph
Ph
OH
Ph
Ph
Ph
Ph
Ph
O
Ph
O
O
O
2j
3j (30%)
3j' (<5%)
5j (13%)
1a (3 mol%)
toluene:t-BuOH
reflux, 24 h
O
Ph
Ph
Ph
3a (50%)
O
Ph
OH
4j (<5%)
OH
(100% conv.)
4a
(2j : 4a = 1:1)
O
OH
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
O
O
O
OH
2j
3j (12%)
3j' (ca. 5%)
5j (30%)
1a (3 mol%)
O
toluene:t-BuOH
reflux, 24 h
O
Ph
Ph
Ph
O
(b)
Ph
OH
3a (22%)
4j (<5%)
O
(72% conv.,
28% of 5a left)
5a
(2j : 5a = 1:1)
Scheme 2. Crossover experiments for the cyclization of 1,4-diol 2j in the
presence of ketoalcohol 4a (top) or diketone 5a (bottom).
Figure 1b also shows a plot of [log(kX/kH)] vs the Hammett–
Brown σ+ constants instead of the σ constants (see the
Supporting Information).[14]
Kinetic isotope effect (KIE) studies were then carried out.[15]
The cyclodehydration rate of 2a was compared to that of 2a-d2,
and a KIE of 2.94 ± 0.14 was observed (see Supporting
Information). This value suggests that the cleavage of the
C−H(D) bond at the benzylic position occurs in the rate
determining step. In contrast, a negligible KIE of 1.14 ± 0.08 was
obtained for the p-methoxy-substituted diols, 2b and 2b-d2 (see
the Supporting Information).
Figure 1. Hammett plots for the cyclodehydration of diols 2a–2f. (a)
log(kX/kH) versus σ, log(kX/kH) = (−1.7±0.2)σ, R2 = 0.94. (b) log(kX/kH) versus
σ+ log(kX/kH) = (-1.1±0.5)σ+, R2 = 0.59. The shaded regions show the
,
expected areas for log(kX/kH) if the substrates were to follow an SN2 (top, a)
or an SN1 (bottom, b) mechanism. Each point corresponds to an average of
three experiments. Note: 2b (red cross) is not used for the correlations, see
text.
all substrates, excluding 2b, in the Hammett plot (Figure 1a,
substituent constants σ, R2 = 0.94) compared with the Hammett-
Brown plot (Figure 1b, substituent constants σ+, R2 = 0.59), the
SN1 pathway (i.e. through a fully developed positive charge in
direct conjugation with the para substituent) can already be ruled
out for these substrates. Closer analysis of Figure 1b gives
further support to the absence of an SN1 pathway for 2a, and
2c–2f; In general, for an SN1 mechanism, we would expect a
linear fit with the σ+ values, and a ρ value of around −4.[14] In
Figure 1b, the shaded area shows the range of gradients for
typical ρ values in SN1 reactions, ranging from −3.5 to −4.5
(using the data point of 2b as a reference point). If diols 2a, 2c–
2f followed an SN1 pathway, their data points would fall within
this shaded region (Figure 1b), and this is in clear disagreement
with the experimental data; All substrates except 2b lie above
the expected SN1 plot bracket based on 2b (Figure 1b, shaded
region). In short, we can conclude that all the substrates except
p-MeO diol 2b follow a faster neutral pathway instead of the
alternative SN1 mechanism.
Discussion
Two possible mechanistic pathways are shown in Scheme 3.
Scheme 3a shows a mechanism that proceeds through acid
catalysis,[16] and that involves nucleophilic substitution (SN1 or
SN2). Scheme 3b shows
a redox-neutral mechanism with
carbonyl compounds and iridium hydrides as key intermediates.
The functionalized NHC ligand of 1a participates in proton-
shuffling steps.[ 3] The iridium complex acts in the first instance
as an acid catalyst, and in the second as a hydrogen-transfer
catalyst. When we investigated the scope of this reaction (vide
supra, Table 2), we found that diol 2b, which has an electron-
rich p-MeOC6H4 subtituent, gave the tetrahydrofuran product 3b
in excellent yield, even when a lower temperature of 80 °C was
used. Neither 2a nor 2b gave any product when the reaction
was carried out in the absence of an iridium catalyst (vide supra,
Table 1, entry 5), under otherwise identical reaction conditions.
The Hammett plots (Figure 1a and 1b) clearly show that the
p-MeO-substituted substrate (2b) reacts at a rate that is orders
of magnitude higher than what would be predicted based on the
log(kX/kH) of the other substrates. Due to the excellent fitting of
Thus, we now have to consider which of the alternative
neutral mechanisms, the SN2 and redox pathways (Scheme 3),
is operating for 2a, and for 2c–2f. If the reaction followed an SN2
mechanism, we would expect to see a correlation with σ with a
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small positive ρ value (typical ρ values for SN2 reactions range
from 0.1 to 1; Figure 1a, shaded area, using the data point of 2b
as a reference point).[14] Thus, 2a, 2c–2f would all be expected
to have reactivities equal to or higher than that of p-MeO diol 2b
Further support for the redox pathway (Scheme 3b) for
substrate 2a was obtained in the crossover experiments
(Scheme 2), as hydrogen was transferred between the diol
substrates and the diketone or ketoalcohol additives.
Furthermore, the cyclodehydration of 1,5-diols 2m–2n gave
mixtures of 2,3-dihydropyrans 3’ and tetrahydropyrans 3. The
former type of products (3’) could only be formed through a
mechanism involving hydrogen transfer.[18]
In an attempt to obtain further evidence for the formation of
carbocationic species in the cyclodehydration of 2b, we carried
out a number of experiments in the presence of nucleophiles
(see Supporting Information).[19] With 2b as a substrate, these
experiments only resulted in the formation of 3b. However, when
a model alcohol with identical electronic properties that is unable
(i.e.,
a positive ρ value, with substrates with electron-
withdrawing substituents having higher rates). This is once again
in clear disagreement with the observed results. In fact,
excluding cyclic ether 3b, which is obviously formed by a
different mechanism (c.f., KIE), the opposite reactivity trend is
observed, as the data fit well to standard Hammett σ values
(Figure 1a) with a negative ρ value of -1.7. This is very similar to
what we reported before for a rate-limiting Ir-catalyzed hydrogen
transfer from benzylic alcohols.[3b]
We may therefore conclude that there are two competing
mechanisms. Normally, this situation results in a Hammett plot
with two linear regions showing an upwards break, a so-called
“V” shape.[17] In the peculiar case described here, this should
instead be represented with two different Hammett plots, as the
SN1 pathway correlates with σ+ values, and the neutral-redox
pathway with the neutral substituent constants σ. The inflection
point can be estimated by looking into Figure 1b, at a σ+ value of
around −0.3 to −0.4, at the intersection between the shaded
region representing an SN1 mechanism from 2b and the
experimental Hammett–Brown plot (purple dashed line
constructed from 2a, 2c–2f).
to
undergo
intramolecular cyclization, namely (1-(p-
methoxyphenyl)-1-pentanol, 13b), was subjected to the same
reaction conditions, this substrate did react with the added
nucleophiles (e.g., MeOH, 5 equiv.). This result clearly supports
the idea of carbocationic intermediates in the cyclization of 2b.
In summary, we have reported the acid- and base-free
cyclodehydration of 1,4- and 1,5-diols catalyzed by NHC–
iridium(III) complex 1a. Supported by Hammett studies, KIE
investigations, and crossover and trapping experiments, we
found that the mechanism of the cyclization is highly dependent
on the electronic properties of the diol substrates. Very electron-
rich aromatic substrates follow an acid-catalyzed mechanistic
pathway, whereas substrates with no substituents on the
aromatic ring, or electron-withdrawing substituents, follow a
hydrogen-transfer mechanism. Both mechanisms may be
The substantial difference obtained in the KIE studies on diol
2a vs diol 2b (2.94 ± 0.14 vs 1.14 ± 0.08, respectively) also
supports the operation of two distinct mechanistic pathways,
depending on the electronic properties of the substrates. Thus,
in the case of 2a, the C-H bond is broken in the rate determining
step, in contrast to 2b.
operating
simultaneously
for
moderately
electron-rich
a) Acid catalysis mechanism:
H
H
[Y]
OH
O
n
[Y]
- [Y]
H
OH
H
n
n
R
R
Ar
R
Ar
Ar
O
Y = [Ir] or H+
Nucleophilic
Substitution
OH
OH
2
Cp*
3
H
O
Cp*
H
O
Ir
Ir
NHC
NHC
b) Transfer hydrogenation mechanism:
Cp*
H
n
n
H
Ar
Ar
R
H2O
H
R
Cp*
H
O
O
v
O
Ir
O
Ir
3a-3n
3'
NHC
NHC
iii
iv
OH
O
n
H
H
HO
Ar
n
n
R
H
R
Cp*
Cp*
Ar
Ar
R
O
O
Ir
O
ii
i
H
H
Ir
HO
HO
NHC
H2O
I
NHC
2a-2n
4
Cp*
n
O
n
H
O
Cp*
H
Ir
NHC
H
Ar
R
Ar
R
Ir
O
Cp*
H
O
vi
NHC
O
II
3a-3n
Ir
Cp*
H
vi
NHC
O
H
Cp*
Ir
NHC =
OH
N
N
O
H
NHC
Ir
NHC
vii
Cp*
O
Ir
O
n
NHC
R
Ar
O
O
5
n
R
Ar
(traces)
H
6
Scheme 3. Proposed mechanism for the formation of cyclic ethers 3 (n = 1,2).
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General procedure for NMR-scale experiments: Iridium complex 1b
(0.045 mmol, 27.5 mg) and anhydrous and degassed CH2Cl2 (4 mL)
were added to a vial containing AgBF4 (0.0945 mmol, 18.4 mg). The
reaction mixture was stirred for 2 h at room temperature. The mixture
was filtered through a pad of Celite® to remove the AgCl precipitate, and
the filtrate was distributed into 20 NMR tubes. The solvent was
evaporated under vacuum, and the NMR tubes could then be stored
under an inert atmosphere. Toluene-d8 (0.2 mL), tert-butanol (0.05 mL),
and a stock solution of a 1,4-diol 2 (0.075 mmol) were added to an NMR
tube containing 1a (0.00225 mmol). The NMR tube was then put into an
NMR spectrometer preheated to 100 °C. 1H NMR spectra were recorded
every 2 min.
substrates. From a synthetic point of view, the protocol reported
here using bifunctional NHC-iridium(III) complexes can be used
for the preparation of functionalized 2,6-disubstituted
dihydropyran or 2,5-disubstituted tetrahydrofuran building blocks
from diols under neutral reaction conditions.
Experimental Section
Synthesis of 1,4-diols: Commercially available 1,4-diols 2k and 2l were
purchased from Sigma–Aldrich, and were used as received. Non-
commercially-available 1,4-diols were obtained by reduction of 1,4-
diketone precursors. Commercially available 1,4-diketones 5a and 5j,
precursors of 1,4-diols 2a and 2j, respectively, were purchased from
Sigma–Aldrich, and were used as received. Non-commercially-available
1,4-diketones 5 were synthesized following reported procedures:
Acknowledgements
This project was generously supported by the Swedish
Research Council through Vetenskapsrådet (VR), and by the
Knut and Alice Wallenberg Foundation. The Wenner-Gren
foundation is gratefully acknowledged for a postdoctoral grant to
E.M.-C.
.
(a)
Cu(OTf)2
(5
mol%),
MnCl2 4H2O
(5
mol%),
1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU; 7.5 mmol, 1.5 equiv) and aqueous
tert-butyl hydroperoxide (TBHP; 20 mmol, 4 equiv; 70% in water) were
added to a round-bottom flask equipped with a condenser containing a
mixture of the corresponding vinylarene (7, 5 mmol) and acetone (8, 30
mL). The reaction mixture was stirred at reflux, and the reaction progress
was monitored by TLC. When the reaction was complete, the mixture
was diluted with CH2Cl2 (125 mL), and washed with water.The aqueous
phase was further extracted with CH2Cl2. The combined organic phases
were dried with MgSO4, filtered, and concentrated under vacuum. The
residue was purified by column chromatography using petroleum ether
Keywords: Hydrogen Transfer • Hammett-Brown • Kinetic
Isotope Effect • Cyclodehydration • Hydride
References
20
and ethyl acetate (9:1, v/v) as eluent to give the desired diketone 5.[
]
(b) In a sealed glass tube equipped with a stirrer bar, the corresponding
precursor benzaldehyde (9, 0.09 mol), triethylamine (19.5 mL, 0.14 mol),
methyl vinyl ketone (10, 0.09 mol), and 3-ethyl-5-(2-hydroxyethyl)-4-
methylthiazolium bromide (11, 3.53 g, 0.014 mol) were mixed together.
The flask was heated in the cavity of a microwave reactor for 15 min (150
W, internal temperature 70 °C, and internal pressure 60 psi). After this
time, the resulting mixture was stirred with aqueous HCl (2 M; 10 mL) for
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washed with aqueous sodium bicarbonate and brine. The organic
fractions were dried over Na2SO4, filtered, and concentrated to give a
crude orange liquid. Column chromatography (cyclohexane/ethyl acetate,
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10.1002/chem.201805460
Chemistry - A European Journal
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FULL PAPER
Greco González Miera, Aitor Bermejo
López, Elisa Martínez-Castro, Per-Ola
Norrby, and Belén Martín-Matute*
Ar
Hydrogen transfer vs acid catalysis:
Mechanistic studies on the iridium-
catalyzed cyclodehydration of a series of
diols have been carried out. Hammett and
Hammett–Brown analyses of the reactivity
data are compared, along with kinetic
isotope effect and crossover experiments.
In this way, we were able to elucidate the
reaction mechanisms, which were found to
be dependent on the electronic properties
of the substrates.
O
DEPARTURES)
GATE%
DESTINATION%
HAMMETT%
COMPANY%
Page No. – Page No.
0% 1%
T% H% F%
σ% +%
S% N% 1%
0% 2%
T% H% F%
σ% −%
σ%
S% N% 2%
Nonclassical mechanism in the
cyclodehydration of diols catalyzed
by a bifunctional iridium complex
OH
Ar
OH
3%
T% H%
r% −%
I%
H%
0%
F%
This article is protected by copyright. All rights reserved.