The scalable pinacol coupling reaction utilizing the inorganic electride [Ca2N]+·e- as an electron donor

Article abstract of DOI:10.1039/c4cc00802b

The scalable pinacol coupling reaction is realized utilizing the inorganic electride [Ca₂N]⁺·e^- as an electron donor in organic solvents. The bond cleavages of the [Ca₂N] ⁺ layers by methanol play a vital role in transferring anionic electrons to electrophilic aldehydes, accompanying the formation of Ca(OMe) ₂ and ammonia. The Royal Society of Chemistry 2014.

Full text of DOI:10.1039/c4cc00802b

Showcasing research from Sung Wng Kim’s
Laboratory/Department of Energy Science, Sungkyunkwan
University, Suwon, Korea.
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The scalable pinacol coupling reaction utilizing the inorganic
electride [Ca2N]+⋅e− as an electron donor
The scalable pinacol coupling reaction can be achieved utilizing
the inorganic electride [Ca2N]+⋅e− as an electron donor in
alcoholic solvents. This suggests a possible milestone of electride
application as an efficient electron donor in synthetic organic
chemistry.
See Sung Wng Kim et al.,
Chem. Commun.,
2014, 50, 4791.
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The scalable pinacol coupling reaction utilizing
the inorganic electride [Ca2N]+ÁeÀ as an
electron donor†
Cite this: Chem. Commun., 2014,
50, 4791
Received 29th January 2014,
Accepted 18th March 2014
Ye Ji Kim,‡ab Sun Min Kim,‡a Hideo Hosono,c Jung Woon Yang*a and
Sung Wng Kim*ab
DOI: 10.1039/c4cc00802b
www.rsc.org/chemcomm
The scalable pinacol coupling reaction is realized utilizing the inorganic lattice framework composed of 3-dimensionally connected
electride [Ca2N]+ÁeÀ as an electron donor in organic solvents. The subnanometer-sized cages with an inner diameter of B0.4 nm.
bond cleavages of the [Ca2N]+ layers by methanol play a vital role This discovery accelerated the investigation of the physical proper-
in transferring anionic electrons to electrophilic aldehydes, accom- ties of the [Ca24Al28O64]4+Á4eÀ electride, revealing an extremely low
panying the formation of Ca(OMe)2 and ammonia.
work function of 2.4 eV (ref. 2c) and a metal–insulator transition,4
as well as superconductivity.5 Very recently, a two-dimensional (2D)
Electrides are ionic crystals with cavity-trapped electrons, which electride has been reported in a layered structure of dicalcium
serve as anions.1 In a complex array of subnanometer-sized nitride with a chemical formula of [Ca2N]+ÁeÀ.6 This 2D electride
cavities, channels or layers, anionic electrons localize and interact shows the characteristic feature of delocalized anionic electrons
mutually. These provide a rich area for theoretical studies of within the interlayer spacing of B0.4 nm, rendering the metallic
quantum confinement systems and have a broad range of state with the electron concentration of B1.37 Â 1022 cmÀ3, which
applications in chemical synthesis, catalysis, and electronic is comparable to typical alkali metals. As expected in electrides,
devices.1b,2 The first crystalline electride, Cs+ (18-crown-6)2ÁeÀ, the [Ca2N]+ÁeÀ also shows the low work function value of 2.6 eV
is the organic compound grown from the solution that contains along the in-plane direction.
solvated electrons in alkali metal–ammonia solutions and
It is intriguing to note that both the solvated electrons in
macrocyclic ligands, such as crown ethers or cryptands, strongly alkali metal–ammonia solutions and the anionic electrons in
binding to cations of alkali metals.1c Likewise for the solvated electrides have played an important role in synthetic organic
electrons, the organic electrides are also thermally and chemically chemistry as effective electron donors. From early years, solvated
unstable and decompose in an inert atmosphere and air above electrons have been applied to Birch7 and Bouveault–Blanc reduc-
approximately À30 1C, hampering the practical applications of tions8 as a potent reducing agent, forming free radical anions.
electrides as functional materials.
Recently, it has been demonstrated that the [Ca24Al28O64]4+Á4eÀ
In 2003, the first room temperature stable inorganic electride acts as an efficient electron donating promoter for metal
[Ca24Al28O64]4+Á4eÀ electride was synthesized by utilizing catalysts in ammonia synthesis. However, in contrast to the
the complex oxide 12CaOÁ7Al2O3,3 which is a constituent of solvated electrons, it is noted that the electrides can offer an
commercial alumina cements and has a positively charged interesting opportunity for chemical reactions at room temperature
and under mild reactive conditions upon selecting an appropriate
medium for electron transfer. Taking this into consideration, the
a Department of Energy Science, Sungkyunkwan University, Suwon 440-746,
[Ca24Al28O64]4+Á4eÀ electride was applied to the pinacol coupling
Republic of Korea. E-mail: jwyang@skku.edu, kimsungwng@skku.edu;
reaction in an aqueous media at room temperature.
Fax: +82-31-299-4279; Tel: +82-31-299-4276, +82-31-299-6274
b IBS Center for Integrated Nanostructure Physics, Institute for Basic Science,
Central to organic synthetic chemistry are the methods for
carbon–carbon bond formation associated with electron transfer
in a free radical process.9,10 Numerous reagents and catalysts for
carbon–carbon bond formations have been utilized as electron
donors. Generally, alkali and alkaline earth metals are regarded as
state-of-the-art electron sources to produce the solvated electrons.
As the surrogate of alkali and alkaline earth metals, the
[Ca24Al28O64]4+Á4eÀ electride was first employed in the pinacol
Daejeon 305-701, Republic of Korea
c Materials and Structures Laboratory, Tokyo Institute of Technology,
4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan
† Electronic supplementary information (ESI) available: Experimental procedures
for the pinacol coupling reactions, characterization of products, 1H NMR and
13C NMR spectra of the products, and calibrations and results of ion chromato-
graphy. See DOI: 10.1039/c4cc00802b
‡ These authors contributed equally to this work.
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coupling reaction.11,12 However, in such a reaction, water is
preferentially required for destroying the cage structure and
transferring anionic electrons. Although the electron released
from the cage structure initiates the reactions in aqueous media,
electrons are also partially consumed to generate H2 and OHÀ
from water, limiting reactivity, yield and even scalability. This
indicates that the selection of an appropriate solvent, according
to the type of electrides, is significantly important for an effective
electron transfer in a radical formation process.
Table 1 Optimization of the reaction conditions for the pinacol coupling
reaction utilizing [Ca2N]+ÁeÀ electridea
Electride
Time Yieldb
Entry (equiv.)
Solvent [M]
(h)
(%)
dl : mesoc
1
2
3
4
5
6
7
8
0.5
1
1.5
2
2
2
2
2
2
2
MeOH [0.5]
MeOH [0.5]
MeOH [0.5]
MeOH [0.5]
EtOH [0.5]
iPrOH [0.5]
tBuOH [0.5]
THF [0.5]
MeOH [0.25]
MeOH [0.125]
MeOH : THF (1 : 1) [0.125] 1.5
MeOH : THF (1 : 1) [0.125]
MeOH : THF (1 : 1) [0.125] 45
0.5
0.5
0.5
0.5
1.5
16
16
24
0.5
0.5
29
67
79
83
2.5 : 1
1.4 : 1
1.4 : 1
1.4 : 1
3.2 : 1
—
—
—
1.4 : 1
1.7 : 1
2 : 1
Meanwhile, there have been no reports on the application of
the 2D [Ca2N]+ÁeÀ electride in synthetic organic reactions. Since
the [Ca2N]+ÁeÀ electride has a low work function (2.6 eV) and a high
electron concentration of B1.37 Â 1022 cmÀ3, it would be effective
in transferring electrons into organic solvents. Furthermore, the
opened layer structured [Ca2N]+ÁeÀ electride can provide a better
accessibility to anionic electrons when compared to the closed cage
structured [Ca24Al28O64]4+Á4eÀ electride. Here, we demonstrate that
the 2D [Ca2N]+ÁeÀ electride is significantly effective in donating and
transferring the electrons to organic compounds in the presence of
alcoholic solvents with the formation of Ca(OMe)2 and evolution of
29
N.D.
N.D.
N.D.
82
84
499
24
9
10
11
12d
13e
2
2
2
1
—
—
N.D.
a
Reaction conditions: 1a (0.5 mmol), [Ca2N]+ÁeÀ (0.5–2.0 equiv.), solvent
ammonia, leading to the effective carbon–carbon bond formation (2–4 mL), rt. Isolated yield. Determined by 1H NMR spectro-
b
c
d
e
4+
scopy. Use of calcium metal. Use of [Ca24Al28O64
]
Á4eÀ electride.
in the pinacol coupling reaction (Fig. 1). Furthermore, an efficient
electron donating and transferring of the [Ca2N]+ÁeÀ electride in
alcoholic solvents allow for the gram-scale reaction.
Under dilute conditions, the dl-selectivity of the product slightly
We carried out the pinacol coupling reaction of p-chloro- improved while retaining chemical yield (Table 1, entries 9 and 10).
benzaldehyde 1a as an electron acceptor in alcoholic solvents at room Gratifyingly, the dramatically increased yield was achieved via the
temperature. During the reaction, the black colour of the [Ca2N]+ÁeÀ introduction of a mixed solvent system of THF and MeOH (Table 1,
electride powders gradually changed to grey, and finally to white. This entry 11). The potential [Ca2N]+ÁeÀ electride for both reactivity
reveals that the anionic electrons of the [Ca2N]+ÁeÀ electride are and selectivity was compared by employing calcium metal and
completely consumed by organic substrates. As shown in Table 1, the [Ca24Al28O64]4+Á4eÀ electride (Table 1, entries 12 and 13).
the reaction proceeded more efficiently as the electride equivalent(s) With calcium metal, a low yield of 24% was achieved, whereas the
increased (Table 1, entries 1–4). The reaction was sluggish when the [Ca24Al28O64]4+Á4eÀ electride was not able to participate in the
solvent was switched from methanol to ethanol, resulting in a lower co-organic solvent system, indicating no transfer of anionic
yield of 29% (Table 1, entry 5). Interestingly, the chemical yield of electrons (Table 1, entries 12 and 13). These observations clearly
product 2a increased with decreasing pKa values of alcohols in the indicate that the anionic electrons in the [Ca2N]+ÁeÀ electride are
following order: methanol 4 ethanol 4 iso-propanol = tert-butanol transferred to the p-chlorobenzaldehyde and are responsible for
(Table 1, entries 4–7).
the carbon–carbon bond formations. Importantly, the use of
Furthermore, no reaction took place in the absence of either dilute methanol as a co-solvent is the most critical reaction
methanol or ethanol. For example, no product was detected parameter for enhancing the reaction rate and chemical yield in
in an aprotic polar solvent such as THF (Table 1, entry 8). the use of the [Ca2N]+ÁeÀ electride.
Under the established optimal conditions, we examined the
substrate scope of both aromatic or aliphatic aldehydes and
ketones (Table 2). Aldehydes bearing an electron-deficient
substituent on aromatic rings gave high yields of products
2a–f (Table 2, entries 1–6). It is notable that the experimental
maximum yield (499%) of product 2a was obtained. In the case of
un-substituted aldehydes, a moderate yield of the corresponding
1,2-vic-diol products 2g and 2h was achieved (Table 2, entries 7
and 8). Electron-rich substrates also produced the corresponding
products 2i and 2j in moderate yields (Table 2, entries 9 and 10).
An aliphatic aldehyde such as pivalaldehyde can be also used for
this reaction with a higher equivalent of electrides (Table 2,
entry 11). Additionally, the reaction of a ketone, such as aceto-
phenone, which is a less reactive functional group than an
aldehyde, also smoothly proceeded to yield the 1,2-vic-diol
product 2l (74% yield, Table 2, entry 12).
Fig. 1 Schematic illustration of a plausible mechanism for the pinacol
coupling reaction utilizing [Ca2N]+ÁeÀ electride as an electron donor in
methanol, producing Ca(OMe)2 and NH3.
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Table
Communication
2
Reaction scope for the pinacol coupling reaction utilizing
[Ca2N]+ÁeÀ electride in THF–MeOH co-solventa
Entry R1
R2 Product Time (h) Yieldb (%) dl : mesoc
1
2
3
4
5
6
7
8
4-Cl-C6H4
H
H
H
H
H
H
H
H
H
H
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
1.5
9
2
9
8
8
3
9
9
499
71
81
61
79
78
63
51
63
66
38
74
1.5 : 1
1.9 : 1
1.7 : 1
1.8 : 1
1.5 : 1
1.2 : 1
2.4 : 1
5.9 : 1
1.6 : 1
1.8 : 1
1.1 : 1
2.5 : 1
4-F-C6H4
3-CF3-C6H4
3-Br-C6H4
3-Cl-C6H4
2-Cl-C6H4
Ph
2-Naphthyl
3-Me-C6H4
3-MeO-C6H4
Trimethyl
Ph
Fig. 2 Comparisons of reactivity and selectivity using alkali (Li), alkaline
earth (Mg) metals and [Ca2N]+ÁeÀ electride for carbon–carbon bond
forming reactions.
9
10
11d
12
2j
2k
8
0.5
6
Me 2l
a
Reaction conditions: aldehyde or ketone (0.5 mmol), [Ca2N]+ÁeÀ
(2 equiv.), THF : MeOH (v/v = 1 : 1, 0.125 M), rt. b Isolated yield. c Determined
by 1H NMR spectroscopy. d Varying reaction conditions {[Ca2N]+ÁeÀ (4 equiv.),
THF : MeOH (v/v = 1 : 3, 0.125 M), rt.}.
verify the superior performance of our protocols, we compared
them with previous reports that used alkali and alkaline earth
metals12e,13 as an electron source in pinacol coupling reactions
(Fig. 2). It is clear that the reaction using the [Ca2N]+ÁeÀ
electride is the most effective among the reactions in terms of
yield, selectivity and scalability.
We considered that the pinacol coupling reactions of aldehydes
or ketones with the [Ca2N]+ÁeÀ electride presumably proceeded
through the coupling of ketyl radical anions, which were generated
by electron transfer from electrides to carbonyl moieties. Most
importantly, the methanol of the co-solvent played vital roles in the
electron transfer by the cleavage of calcium–nitrogen bonds in the
[Ca2N]+ layer, producing two different outcomes: (i) formation
of Ca(OMe)2 by bonding of 2MeOÀ from methanol with Ca2+ of
[Ca2N]+ÁeÀ, (ii) formation of ammonia by bonding of protons from
methanol with N3À of [Ca2N]+ÁeÀ, simultaneously releasing the
anionic electrons. As shown in Fig. 3(a), it is verified that X-ray
diffraction (XRD) pattern of isolated Ca(OMe)2 after the completion
of the reaction is identical to that of the standard sample (Ca(OMe)2
was purchased from Sigma-Aldrich).
Scheme 1 Proposed mechanism for the selectivity in the pinacol
coupling reaction utilizing the [Ca2N]+ÁeÀ electride.
The observed moderate dl–meso selectivity results from the
dimerization of radical anions and the formation of the
strongly-bound ion-pairs between negatively charged oxygen and
calcium ions after the first electron transfer (Scheme 1). The
dl-product is slightly favoured compared to the meso-product
owing to minimize steric hindrance of R groups. Specifically,
2-naphthaldehyde gave the best dl-selectivity by the introduc-
tion of more bulky R groups.
To confirm the evolution of ammonia during the reactions,
we performed ion-chromatography (IC) measurements with the
completed reaction mixtures. Samples for IC measurements
Next, we expanded to the large-scale preparation of various
1,2-vic-diols (Scheme 2). Each reaction was repeated on a 10 mmol
scale (20 times greater than the experiments described in Table 2). It
is noteworthy that higher yields were achieved by modifying the
co-solvent ratio from MeOH : THF (1 : 1) to MeOH : THF (3 : 1) com-
pared to small-scale experiments described in Table 2. Moreover, to
Fig. 3 (a) XRD patterns of Ca(OMe)2 standard powders (black line) and the
resulting Ca(OMe)2 product from the reaction mixtures (red line). All
measurements are performed under nitrogen atmosphere. (b) IC analysis
of ammonia from the THF-mediated reaction mixture (top panel) and from
the THF–MeOH-mediated reaction mixture (bottom panel).
Scheme 2 Gram-scale synthesis of 2a, 2i, 2j, and 2l using [Ca2N]+ÁeÀ.
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4 S. W. Kim, S. Matsuishi, T. Nomura, Y. Kubota, M. Takata,
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were prepared by the following procedures: each sample was
taken from the individual reaction mixtures of THF and THF–MeOH
using micro-glass filters without the acidic work-up procedure. For a
more accurate analysis, they were diluted with deionized water.
+
As shown in Fig. 3(b), the ammonium ion (NH4 ) peak was detected
6 K. Lee, S. W. Kim, Y. Toda, S. Matsuishi and H. Hosono, Nature,
2013, 494, 336.
+
in the THF–MeOH co-solvent, whereas the NH4 peak was not
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detected in the pure THF solvent. These observations strongly
support a plausible mechanism (Fig. 1) for the donation of anionic
electrons of the [Ca2N]+ÁeÀ electride to the aldehydes.
In conclusion, we have demonstrated that the [Ca2N]+ÁeÀ
electride acts as an efficient electron donor for the carbon–
carbon bond forming reaction via a free radical process. The
appropriate solvent selection for the [Ca2N]+ÁeÀ electride allows
for the efficient electron transfer to aldehydes. Moreover, we
also identified the evolution of ammonia and the formation of
Ca(OMe)2 by the decomposition of the [Ca2N]+ÁeÀ electride, thereby
releasing anionic electrons to promote the pinacol coupling
reaction. Our protocols can be utilized for the large-scale
production of 1,2-vic-diol via ketyl radical anion dimerization
of aldehydes, which are governed by electron donation from the
[Ca2N]+ÁeÀ electride in alcoholic solvents.
This work was supported by the NRF grant (No.
2013R1A1A1008025), the Institute for Basic Science (IBS), the NRF
NanoÁMaterial Technology Development Program (2012M3A7B4-
049652), the JSPS FIRST Program and the ACCEL Program.
11 H. Buchammagari, Y. Toda, M. Hirano, H. Hosono, D. Takeuchi and
K. Osakada, Org. Lett., 2007, 9, 4287.
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4794 | Chem. Commun., 2014, 50, 4791--4794
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