Transition-Metal-Free Catalytic Formal Hydroacylation of Terminal Alkynes

Article abstract of DOI:10.1021/acscatal.8b02832

Although hydroacylation is a very useful reaction for producing ketones from aldehydes with 100% atom efficiency, classical Rh-catalyzed hydroacylation presents several problems, including the need for transition metal catalysts, unwanted decarbonylation of aldehydes, and difficulty in regioselectivity control. However, formal hydroacylation utilizing the nucleophilicity of terminal alkynes can avoid these problems. In this work, we have achieved transition-metal-free formal hydroacylation of terminal alkynes using an Mg₃Al-CO₃-layered double hydroxide as a heterogeneous catalyst. This system was applicable to the efficient synthesis of α,β-unsaturated ketones with various substituents, and the catalyst can be reused without a significant loss of catalytic performance.

Full text of DOI:10.1021/acscatal.8b02832

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Letter
Transition-Metal-Free Catalytic Formal Hydroacylation of Terminal Alkynes
Takafumi Yatabe, Noritaka Mizuno, and Kazuya Yamaguchi
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b02832 • Publication Date (Web): 05 Nov 2018
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Transition-Metal-Free Catalytic Formal Hydroacylation of Terminal
Alkynes
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Takafumi Yatabe,† Noritaka Mizuno,† and Kazuya Yamaguchi*,†
†Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-
8656, Japan
ABSTRACT: Although hydroacylation is a very useful reaction for producing ketones from aldehydes with 100% atom efficiency,
classical Rh-catalyzed hydroacylation presents several problems, including the need for transition metal catalysts, unwanted de-
carbonylation of aldehydes, and difficulty in regioselectivity control. However, formal hydroacylation utilizing the nucleophilicity
of terminal alkynes can avoid these problems. In this work, we have achieved transition-metal-free formal hydroacylation of termi-
nal alkynes using an Mg3Al–CO3-layered double hydroxide as a heterogeneous catalyst. This system was applicable to the efficient
synthesis of
α,β-unsaturated ketones with various substituents, and the catalyst can be reused without a significant loss of catalytic
performance.
KEYWORDS: Hydroacylation • Alkynes • Layered double hydroxide • Transition-metal-free • Heterogeneous catalysis
Hydroacylation, which is the transformation of aldehydes into
ketones without any byproducts, is an extremely important,
efficient, and environmentally friendly method of C–C bond
formation from C–H bonds.1 Particularly, many examples of
alkynes/alkenes hydroacylation using transition metals, mainly
Rh, as catalysts have been reported (Figure 1a).1–3 However,
this system still presents several problems, especially for in-
termolecular hydroacylation, owing to the intrinsic mechanism
of Rh-catalyzed hydroacylation; a) competing decarbonylation
of acylrhodium intermediates and b) difficulty in controlling
the regioselectivity of insertion into alkynes/alkenes.1 Accord-
ingly, the development of alternative catalytic hydroacylation
systems is required to avoid these problems.1d
terminal alkynes catalyzed by a commercially available
Mg3Al–CO3-layered double hydroxide
(Mg6Al2(OH)16(CO3)·4H2O, hereafter termed Mg3Al–
CO3 LDH) through nucleophilic addition/prototropy utilizing
the unique basicity and ionicity of Mg3Al–CO3 LDH
(Figure 1c). Mg3Al–CO3 LDH is well known as a solid base
catalyst and is composed of cationic metal hydroxide layers
([Mg6Al2(OH)16]2+)
and
hydrated
anion
layers
([(CO3)·4H2O]2−).10 However, to the best of our knowledge,
nucleophilic addition of alkynes or prototropy in propargylic
alcohols promoted by Mg3Al–CO3 LDH has not been reported.
Mg3Al–CO3 LDH shows moderate basicity10 compared to the
strong bases typically used for the Favorskii reaction. This
indicates a broad substrate scope in this system, which we
have demonstrated using 22 examples. In this method,
products possessing substituent patterns opposite to those
Recently, Hashmi et al. pioneered formal hydroacylation4
of terminal alkynes catalyzed by Au utilizing their
nucleophilicity through aldehyde–alkyne–amine coupling (A3-
coupling) and hydration (work-up), which is completely
different from classical Rh-catalyzed hydroacylation
(Figure 1b).5,6 Since this formal hydroacylation does not
involve an oxidative addition step or an insertion step, no
decarbonylation or regioselectivity problems are observed.
Since then, precious-metal-free formal hydroacylation
reactions using Cu catalysts have been developed.7 However,
these A3-coupling systems require the use of transition-metal
catalysts and (super)stoichiometric amounts of amines.
Interestingly, when the Favorskii reaction,8 i.e., the addition of
terminal alkynes to carbonyl compounds to afford propargylic
alcohols using strong bases, e.g., KOH,8a,b tBuOK,8c,e and
Bu4NOH,8f is performed using an aromatic aldehyde as the
substrate, the side reaction to produce an α,β-unsaturated
carbonyl compound occurs.9 This side reaction can be
regarded as a transition-metal-free formal hydroacylation;
however, these systems require strong basic conditions, and
the substrate scopes are quite limited.
obtained
through
hydration/aldol
condensation,4a–c
nucleophilic addtion/Meyer–Schuster rearrangement,4d,e or
aldehyde–alkyne metathesis4f–i are produced (Figure S1). In
addition, the present catalysis is truly heterogeneous and the
LDH catalyst can be reused without severe loss of its catalytic
activity; thus, the system is also environmentally friendly.
Initially, the synthesis of (E)-4'-methoxychalcone (3aa)
from p-anisaldehyde (1a) and phenylacetylene (2a), i.e., the
formal hydroacylation of 2a using 1a, was carried out in the
presence of various solid base catalysts in toluene at 100 °C
under an Ar atmosphere (Table 1). Surprisingly, of the cata-
lysts examined, namely Mg3Al–CO3 LDH (Mg/Al = 3), HAP,
Mg(OH)2, Ca(OH)2, MgO, CaO, ZnO, Al2O3, CeO2, ZrO2, and
TiO2, 3aa was afforded only when Mg3Al–CO3 LDH was used
(Table 1, entries 1 and 3–12). An LDH with an Mg/Al ratio of
2 also showed the catalytic activity whereas the use of an LDH
with an Mg/Al ratio of 4 or Mg3Al–CO3 LDH calcined at 200,
300, or 400 °C hardly afforded 3aa, indicating that
In the present study, we successfully achieved, for the
first time, transition-metal-free formal hydroacylation of
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Table 1. The effect of solid catalysts on the synthesis of 3aa
starting from 1a and 2aa
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entry
catalyst
conv. (%)
yield (%)
3aa
42
87
<1
<1
<1
<1
<1
<1
<1
<1
<1
1a
55
99
<1
<1
4
2a
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1
Mg3Al–CO3 LDH
Mg3Al–CO3 LDH
HAP
Mg(OH)2
Ca(OH)2
MgO
CaO
ZnO
Al2O3
CeO2
52
96
1
3
8
2b
3
4
5
6
7
8
9
10
11
12
1
5
<1
<1
10
6
2
<1
6
1
ZrO2
TiO2
5
<1
<1
3
<1
aReaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), base catalyst
(100 mg), toluene (2 mL), Ar balloon (1 atm), 100 °C, 5 h. Yields and
conversions were determined by GC using biphenyl as an internal stand-
ard. bCatalyst (130 mg), 120 °C, 15 h. HAP = hydroxyapatite.
examined (Scheme 1 and Figure S3). When the solid bases
were stirred with 2a under the optimal reaction conditions for
2 h, those that exhibited the catalytic activity became colored,
whereas the others exhibited no apparent change (except for
CeO2). Conversely, when diphenylacetylene, an internal
alkyne, was stirred with Mg3Al–CO3 LDH or CeO2, the color
of Mg3Al–CO3 LDH did not change, whereas that of CeO2
became almost the same as when CeO2 interacted with 2a,
demonstrating the interaction between CeO2 and the C≡C
bond of alkynes (Figure S4).11 Therefore, the coloring
interaction of Mg3Al–CO3 LDH with 2a likely occurred
through alkynyl species generated by deprotonation of
terminal alkynes. When Mg3Al–CO3 LDH (100 mg) was
stirred with 2a (0.5 mmol) for 16 h (termed LDH–2a, colored
reddish),12 the amount of 2a incorporated into the LDH was ca.
3 µmol (determined by GC analysis after dissolution of LDH–
2a with 1 M HCl followed by extraction of 2a with CHCl3).
When the reaction of 1a and LDH–2a was conducted under
the optimized conditions, 3aa was formed in 67% yield based
on the amount of 2a contained in LDH–2a (Figure S8). In
addition, 1H NMR analysis indicated that H/D exchange
Figure 1. Hydroacylation of alkynes/alkenes. (a) Classical hy-
droacylation catalyzed by Rh. (b) Formal hydroacylation of ter-
minal alkynes via A3-coupling. (c) This work: Transition-metal-
free formal hydroacylation of terminal alkynes catalyzed by an
Mg3Al–CO3-layered double hydroxide.
the ionic layered structure of the LDH is important for the
present formal hydroacylation (Table S1, entries 1–5, XRD
patterns presented in Figure S2). The partial exchange of inter-
Scheme 1. H/D exchange of 2a with D2O using Mg3Al–
CO3 LDH or Al2O3 and their images before/after stirring
a
with 2a.
2−
layer anions from CO3 to Cl− decreased the yield of 3aa,
aReaction conditions: 2a (0.5 mmol), base catalyst (100 mg), toluene-d8
(2 mL), D2O (50 µL), Ar (1 atm), 100 °C, 2 h.
indicating that the basicity of the interlayer anion also affected
the catalytic activity (Table S1, entry 6). Moreover, in the
presence of K2CO3, Na2CO3, or iPr2EtN, the formal hydroac-
ylation did not proceed at all (Table S1, entries 7–9). The ef-
fect of solvents on the formal hydroacylation was found to be
remarkable, with low-polarity solvents such as methoxycyclo-
pentane, PhCF3, and toluene being effective (Table S2, entries
1–15). Once the temperature, the amount of the catalyst, and
the reaction time had been optimized, the yield of 3aa reached
87% (Table 1, entry 2 and Table S2, entries 16–18).
To investigate the notable effect of catalysts on 3aa syn-
thesis, the interaction between the solid bases and 2a was
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between 2a and D2O occurred using either Mg3Al–CO3 LDH
or Al2O3, regardless of their catalytic activities for 3aa synthe-
sis (Scheme 1 and Figure S9). Considering these results, cata-
lytic amounts of alkynyl nucleophilic species are probably
formed by the basicity and stabilized by the ionicity of
Mg3Al–CO3 LDH, which promotes the nucleophilic addition
of alkynes to aldehydes unlike other solid catalysts13.
To establish whether the observed catalysis occurred het-
erogeneously on Mg3Al–CO3 LDH or arose from leached spe-
cies in the solution, the catalyst was removed by hot filtration
during the reaction, and the reaction was restarted with the
filtrate under the same conditions. As expected, the production
of 3aa immediately ceased upon removing the catalyst (Fig-
ure S11). Additionally, after the reaction, the filtrate was ana-
lyzed using inductively coupled plasma-atomic emission spec-
troscopy (ICP-AES), and Mg and Al species were hardly de-
tected (Mg < 4 × 10−6%, Al < 4 × 10−3%). Thus, the observed
catalysis for the present formal hydroacylation is truly hetero-
geneous. Furthermore, the Mg3Al–CO3 LDH can be easily
retrieved from the reaction mixture by simple filtration. The
retrieved Mg3Al–CO3 LDH can be reused after washing the
catalyst with acetone for the reaction of 1a and 2a at least
three times without significant loss of catalytic activity (Ta-
ble S4).14
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Figure 2. Mechanistic studies on the present formal hydroacyla-
tion. Reaction conditions are indicated, and yields were deter-
mined by GC. (a) Nucleophilic addition of 2a to 1n. (b) Rear-
rangement from 4da. (c) LDH-catalyzed formal hydroacylation
using D-2a. (d) LDH-catalyzed formal hydroacylation using D-1d
Table 2. Substrate scope under the optimized conditionsa
.
Next, the substrate scope of the present system was inves-
tigated. Under the optimized reaction conditions, the formal
hydroacylation using various aromatic aldehydes (1) and aro-
matic alkynes (2) proceeded efficiently to produce α,β-
unsaturated ketones (3) in an (E)-selective fashion (Table 2).15
The desired products were isolated by simple column chroma-
tography on silica gel (see Supporting Information).16 When
benzaldehydes substituted with a methoxy group at the o-, m-,
or p-position were used as the substrates, the formal hydroac-
ylation proceeded efficiently to give the corresponding chal-
cones in high yields (3aa–3ca). Naturally, benzaldehyde can
also be used as the substrate (3da). The use of benzaldehydes
with different substituents, including methyl, trifluoromethyl,
chloro, bromo, and amino groups, was also possible with this
system (3ea–3ia). Moreover, owing to the mild basicity of
Mg3Al–CO3 LDH,10 benzaldehydes possessing cyano or ester
groups, for which it is difficult to react efficiently in strongly
basic media, can be utilized (3ja and 3ka). When furfural was
used as the substrate, the corresponding enone was obtained
(3la). As well as 2a, a range of aromatic terminal alkynes can
also be used for the present formal hydroacylation. Phenyla-
cetylenes with a chloro group at the o-, m-, or p-position and
benzaldehyde were successfully converted into the corre-
sponding chalcones (3db–3dd). The formal hydroacylation
proceeded efficiently even when using phenylacetylenes bear-
ing a bromo, fluoro, methoxy, or pentyl group as the substrates
(3de–3dh).
Furthermore,
2-ethynylpyridine
or
3-
ethynylthiophene can be formally hydroacylated by benzalde-
hyde (3di and 3dj). Using 4-formylbenzonitrile and 1-ethynyl-
4-methoxybenzene, the corresponding multi-substituted chal-
cone can be synthesized (3jg). However, this system could not
be applied to aliphatic aldehydes or aliphatic alkynes (3ma
and 3dk).17
The most likely reaction mechanism of the present formal
hydroacylation is the nucleophilic addition of the alkyne to the
aldehyde to produce a propargylic alcohol followed by the
aReaction conditions:
(130 mg), toluene (2 mL), Ar balloon (1 atm), 120 °C, 15 h. GC Yields of
the ( ) isomers are displayed below chemical structures without parenthe-
ses. The values in parentheses are isolated yields. bThe average value of
1 (0.5 mmol), 2 (0.6 mmol), Mg3Al–CO3 LDH
E
c
d
e
two or three runs is displayed. 16 h. 24 h. Mg3Al–CO3 LDH (200 mg).
fThe isolated yield includes the (
Z
) isomer (2–6%).
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Fax: +81-3-5841-7220
alcohol’s rearrangement into an α,β-unsaturated carbonyl
compound. However, no propargylic alcohol was detected
during any of these formal hydroacylations. Thus, to investi-
gate the reaction path, the reaction of 2,2,2-
trifluoroacetophenone (1n) and 2a was carried out under the
optimized conditions (Figure 2a). Consequently, the corre-
sponding propargylic alcohol (4na) was produced in moderate
yield because the final rearrangement did not occur as it is a
tertiary propargylic alcohol. In addition, using 1,3-
diphenylprop-2-yn-1-ol (4da) as the substrate, the correspond-
ing α,β-unsaturated carbonyl compound (3da) was obtained in
59% yield less than 10 min after the reaction started (Fig-
ure 2b).18,19 At the same time, 4da was quantitatively convert-
ed (i.e., it was undetectable by GC), and the Mg3Al–CO3 LDH
became colored, suggesting that 4da was rapidly deprotonated
and adsorbed onto the Mg3Al–CO3 LDH. These results are
consistent with the fact that propargylic alcohols cannot be
observed when the present formal hydroacylation is conducted.
Thus, the nucleophilic addition/rearrangement mechanism was
strongly supported. Furthermore, when the reaction of 1a and
phenylacetylene-d1 (D-2a) was carried out under the optimized
conditions, no deuterated 3aa was produced (Figure 2c and 1H
NMR spectra in Figure S14); when the reaction of benzalde-
hyde-α-d1 (D-1d) and 2b was carried out under the optimized
conditions, α-deuterated 3db was produced, for which the H/D
Notes
The authors declare no competing financial interests.
ASSOCIATED CONTENT
Supporting Information
The supporting information is available free of charge on the ACS
Publication website: experimental details and compound charac-
terization, aldehyde–alkyne coupling schemes, XRD patterns,
photo images, NMR spectra, DR UV-vis spectra, FT-IR spectra,
reaction using LDH–2a, reaction profiles, the proposed mecha-
nism, tables presenting the effect of catalysts, solvents, and tem-
peratures as well as results of reuse tests (PDF).
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ACKNOWLEDGMENTS
We thank Dr. Xiongjie Jin (the University of Tokyo) for his help-
ful discussion. The authors would like to thank Enago
(www.enago.jp) for the English language review. This work was
financially supported by JSPS KAKENHI Grant No. 15H05797 in
Precisely Designed Catalysts with Customized Scaffolding. T. Y.
was supported by the JSPS through the Research Fellowship for
Young Scientists (Grant No. 17J08127) and the Program for
Leading Graduate Schools (MERIT program).
1
ratio determined by H NMR was 60:40 (Figure 2d and Fig-
REFERENCES
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catalyzed by Mg3Al–CO3 LDH most likely occurred through
prototropy9b,c,20 rather than hydride transfer.9a
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Given previous reports9b,c,20 and the results above, we
propose a plausible reaction mechanism of the present Mg3Al–
CO3 LDH-catalyzed formal hydroacylation as follows (Fig-
ure S16). Nucleophilic addition of the alkynyl species catalyti-
cally produced owing to the basicity and ionicity21 of Mg3Al–
CO3 LDH to the aldehyde affords a propargylic alcohol. Then,
a delocalized carbanion species is produced through deproto-
nation of the propargylic alcohol by Mg3Al–CO3 LDH. Subse-
quently, this species is protonated to produce an allenol, which
immediately tautomerizes to give the formally hydroacylated
product.
In summary, we have developed the first transition-metal-
free/additive-free formal hydroacylation of terminal alkynes
catalyzed by a commercially available Mg3Al–CO3 LDH. This
efficient transformation is enabled by the unique ionicity and
basicity of Mg3Al–CO3 LDH, which promotes both the nucle-
ophilic addition of terminal alkynes and prototropy of propar-
gylic alcohols effectively. This system is applicable to various
combinations of substrates, even including those with cyano or
ester groups, to produce a range of substituted α,β-unsaturated
ketones. The present catalysis was confirmed to be truly heter-
ogeneous, and the catalyst can be reused several times without
loss of its catalytic activity. Considering the fact that hydroac-
ylation is highly atomically economical, the present formal
hydroacylation is clearly environmentally friendly. In addition,
we believe that this novel catalysis that exploits the unique
properties of Mg3Al–CO3 LDH will allow the development of
novel organic reactions that utilize the specific properties of
solid catalysts.
(3) For examples of hydroacylation catalyzed by transition metal
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Nakao, Y.; Idei, H.; Kanyiva, K. S.; Hiyama, T. Hydrocar-
bamoylation of Unsaturated Bonds by Nickel/Lewis-Acid Catalysis. J.
Am. Chem. Soc. 2009, 131, 5070–5071. (c) Hatanaka, S.; Obora, Y.;
AUTHOR INFORMATION
Corresponding Author
*E-mail: kyama@appchem.t.u-tokyo.ac.jp
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(4) In this manuscript, formal hydroacylation is defined as the
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catalyzed by Rh, i.e., NOT enone synthesis via hydration of
alkynes/aldol condensation, nucleophilic addtion/Meyer–Schuster
rearrangement, or aldehyde–alkyne metathesis as the following reports
(Figure S1 can be also referred); for examples on hydration of
alkynes/aldol condensation, see: (a) Jia, H.-P.; Dreyer, D. R.;
Bielawski, C .W. Graphite Oxide as an Auto-Tandem Oxidation–
Hydration–Aldol Coupling Catalyst. Adv. Synth. Catal. 2011, 353,
528–532. (b) Mameda, N.; Peraka, S.; Kodumuri, S.; Chevella, D.;
Banothu, R.; Amrutham, V.; Nama, N. Synthesis of α,β-Unsaturated
Ketones from Alkynes and Aldehydes over Hβ Zeolite under Solvent-
Free Conditions. RSC Adv. 2016, 6, 58137–58141. (c) Zhou, Y.; Li,
Z.; Yang, X.; Chen, X.; Li, M.; Chen, T.; Yin, S.-F. Phosphorous
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Synthesis 2016, 48, 231–237. For examples on nucleophilic
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(5) In the pioneering work, only gloxyals can be used as the substrate
of aldehydes, see: Shi, S.; Wang, T.; Weingand, V.; Rudolph, M.;
Hashmi, A. S. K. Gold(I)-Catalyzed Diastereoselective Hydroacyla-
tion of Terminal Alkynes with Glyoxals. Angew. Chem. Int. Ed. 2014,
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(6) Before Hashmi’s report,4 the literature contains one report for Cu
nanoparticles-catalyzed formal hydroacylation; however, the substrate
scope was only limited to 2-formyl pyridine (or quinoline) and the
reaction mechanism was unknown. For the report, see: Albaladejo, M.
J.; Alonso, F.; Yus, M. Synthesis of Indolizines and Heterocyclic
Chalcones Catalyzed by Supported Copper Nanoparticles. Chem. Eur.
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(7) (a) Chen, S.; Li, X.; Zhao, H.; Li, B. CuBr-Promoted Formal Hy-
droacylation of 1-Alkynes with Glyoxal Derivatives: An Unexpected
Synthesis of 1,2-Dicarbonyl-3-enes. J. Org. Chem. 2014, 79, 4137–
4141. (b) Albaladejo, M. J.; Alonso, F.; González-Soria, M. J. Syn-
thetic and Mechanistic Studies on the Solvent-Dependent Copper-
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(12) XRD patterns, DR UV-Vis spectra, and FT-IR spectra of LDH–
2a (stirred for 15 h) and Mg3Al–CO3 LDH were shown in Figure S5–
S7.
(13) When the reaction from 1a and 2a with benzoic acid was con-
ducted under the conditions where 3aa yield reached 87% as of 24 h
without benzoic acid, an induction period was observed, which was
likely derived from the formation of alkynyl nucleophilic species on
Mg3Al–CO3 LDH (Figure S10a). Also, when the amount of benzoic
acid was increased from 20 mol% to 40 mol%, the initial rate after the
induction period decreased linearly (Figure S10b,c). With 50 mol% of
benzoic acid, the initial rate became close to zero, and the yield of 3aa
was only 5% after 50 h, which was the same as that as of 24 h (Table
S3), indicating that this system is catalytic.
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(14) The change of XRD patterns and appearances through the repeat-
ing use of Mg3Al–CO3 LDH indicated that the slight decrease of the
catalytic performance was possibly caused by the adsorption of organ-
ic compounds (Figure S12).
(15) A larger scale (5 mmol) α,β-unsaturated ketone synthesis was
also effective to produce 3aa in 67% yield from 1a and 2a under the
conditions described in Figure S13.
(16) The isolation of (E)-4ʹ-(methoxycarbonyl)chalcone (3ka) as the
sole compound was unsuccessful because the separation of 3ka and
methyl 4-formylbenzoate (1k) was quite difficult.
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(17) When using cyclohexanecarboxaldehyde (1m) as the substrate, a
byproduct that seemed to be the corresponding propargylic alcohol
was obtained in 38% GC yield. When using 1-octyne (2k) as the sub-
strate, 2k was hardly converted and no byproducts were also detected.
(18) The E/Z ratio of 3da was 86/14 as of 10 min. After 3 h, the E/Z
ratio became >99/<1 as with the present formal hydroacylation from
aldehydes and alkynes (the yield of 3da also increased from 59% to
77%).
(19) Without any catalysts, neither the nucleophilic addition of 2a to
1n nor the rearrangement of 4da proceeded at all.
(20) For the reports on base-catalyzed isomerization of propargylic
alcohols with electron withdrawing groups to enones, see: (a) Nine-
ham, A. W.; Raphael, R. A. J. Chem. Soc. 1949, 0, 118–121. (b)
Sonye, J. P.; Koide, K. Organic Base-Catalyzed Stereoselective Isom-
erizations of 4-Hydroxy-4-phenyl-but-2-ynoic Acid Methyl Ester to
(E)-and (Z)-4-Oxo-4-phenyl-but-2-enoic Acid Methyl Esters. Synth.
Commun. 2006, 36, 599–602. (c) Sonye, P.; Koide, K. Base-
Catalyzed Stereoselective Isomerization of Electron-Deficient Pro-
pargylic Alcohols to E-Enones. J. Org. Chem. 2006, 71, 6254–6257.
(d) Sonye, P.; Koide, K. Sodium Bicarbonate-Catalyzed Stereoselec-
tive Isomerizations of Electron-Deficient Propargylic Alcohols to (Z)-
Enones. J. Org. Chem. 2007, 72, 1846–1848.
(21) The basicity necessary for the deprotonation of alkynes is
derived from the metal hydroxide cationic layer ([Mg6Al2(OH)16]2+)
and/or the anionic hydrated layer ([(CO3)·4H2O]2−). The ionicity nec-
essary for the stabilization of nucleophilic alkynyl anionic species is
also derived from the metal hydroxide cationic layer
([Mg6Al2(OH)16]2+) and/or the anionic hydrated layer protonated from
alkynes ([(HCO3)·4H2O] −).
TOC graphic
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