N-Silylation of Amines Mediated by Et3SiH/KOtBu

Article abstract of DOI:10.1002/hlca.201900235

Silylation of primary and secondary amines is reported, using triethylsilane as the silylating reagent in the presence of potassium tert-butoxide (KO^tBu). The reaction proceeds well in the presence of 0.2 equiv. of KO^tBu. In competit

Full text of DOI:10.1002/hlca.201900235

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chimica acta
Accepted Article
Title: N-Silylation of Amines Mediated by Et3SiH/KOtBu
Authors: John Murphy, Simon Rohrbach, Fabrizio Palumbo, and Tell
Tuttle
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10.1002/hlca.201900235
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HELVETICA
N-Silylation of Amines Mediated by Et3SiH/KOtBu
Fabrizio Palumbo, Simon Rohrbach, Tell Tuttle* and John A. Murphy*
Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom,
e-mail: tell.tuttle@strath.ac.uk; john.murphy@strath.ac.uk
Dedicated to Professor Philippe Renaud on the occasion of his 60th birthday
Silylation of primary and secondary amines is reported, using triethylsilane as the silylating reagent in the presence of potassium tert-butoxide (KOtBu).
The reaction proceeds well in the presence of 0.2 equiv of KOtBu. In competition experiments, aniline is selectively silylated over aliphatic amines.
Computational studies support a catalytic mechanism which is initiated by KOtBu interacting with the silane to form KH and silylated amine. The KH
then takes over the role of base in the propagation of the cyclic mechanism, and deprotonates the amine. This reacts with R3SiH to afford the product
R3SiNR’R” and regenerate KH.
Keywords: KOtBu • N-silylation • dehydrogenation • transition metal-free • catalysis
S and C-O bonds in aryl thioethers and aryl ethers, respectively.[26-31] The
Introduction
combination of Et3SiH and KOtBu leads to triethylsilyl radicals which are
Silicon chemistry plays a significant role in modern industry, with silicon
being used extensively to make silicones as well as alloys, including
aluminum-silicon and iron-silicon. It is also widely used as a semiconductor
in electronic devices. [1] Recently, significant attention has focused on the
formation of silicon-heteroatom (nitrogen, oxygen, sulfur) bonds.
Silazanides, featuring silicon-nitrogen bonds, have been used as bases,[2]
ligands in coordination chemistry[3] and protecting groups in chemical
synthesis.[4-7] Historical approaches for formation of silazanides, based on
condensation between chlorosilanes and amines, present the drawback of
generating corrosive HCl as by-product and considerable amounts of
salts.[8] In recent years, these methods are complemented by protocols
based on a cross-dehydrogenative coupling of hydrosilanes and amines,
with H2 being the exclusive by-product of the catalytic process. In this
regard, a comprehensive review of catalytic bond formation reactions for
silicon-nitrogen (and other heteroatoms) has been published by Kuciński
and Hreczycho in 2017.[9] Several catalytic processes have been developed
over the years to obtain compounds containing the Si-N bond. These
include processes mediated by alkali metals and alkaline earth metals
(such as Ba, Mg, Ca and Sr)[10-16] transition metals (Rh, Zn, Ru),[5,6,17] metal
nanoparticles[18,19] and main group compounds.[20,21] Generating O-Si
bonds by mild cross dehydrogenative methods has also been the focus of
recent attention. Weickgenannt and Oestreich showed in 2009 that
potassium tert-butoxide can act catalytically in the dehydrocoupling of
hydrosilanes with alcohols[22] while Grubbs et al have exploited similar
couplings with NaOH[23,24] and Vanucci et al. have likewise used K2CO3.[25]
The most intriguing recent development in silicon chemistry may well be
the use of the Et3SiH/KOtBu system, which has been extensively
developed by Stoltz, Grubbs et al. to address a number of remarkable
reactions, such as the conversion of arenes and heteroarenes into
regioselectively silyl-substituted products and the reductive cleavage of C-
very likely to play a major role in these reactions, although non-radical
routes may also contribute, especially in the silylation process. Although a
broad network of reactions involving several intermediates and
mechanisms has been proposed, the mechanistic diversity of this pair of
reagents is still puzzling. We recently reported the Et3SiH/KOtBu reagent
in reductions of arenes and in cleavage of C-N bonds.[32] In this paper, we
report our experimental and computational studies on the use of this
reagent pair to silylate amines. Our publication at this stage is prompted
by the appearance of a very recent patent in this area.[33]
Results and Discussion
Initially, representative (aliphatic, aromatic and heterocyclic) primary and
secondary amines (substrates 1-4, Scheme 1, inset) were treated with
Et3SiH and KOtBu at 130 oC for different durations. All amines were
silylated on the N atom in good yields (55 - 64 %) after 18 h using 3 equiv.
of both KOtBu and Et3SiH. The products are known to be unstable to
routine chromatography and so they were characterized by NMR, GC-MS
and IR spectroscopy.
The cross-dehydrogenative coupling of triethylsilane and all the substrates
also took place when only 0.2 equiv. of KOtBu were used, indicating that
the tert-butoxide base acts catalytically or acts as initiator of a chain
reaction. In these cases, higher yields were obtained (70-87 %), but as the
lower quantity of base allows the reaction mixture to be more easily
stirred (less solid is present), this may be due to a more effective stirring of
the reaction mixture.
N-silylation of 1-4 also occurred on decreasing reaction time to 3 h (Table
1). Interestingly, disilylation of the nitrogen atom on primary amines 2 and
4 was possible, but was not observed in any case under our conditions, as
confirmed by GCMS and 1H NMR. The 1H NMR signals corresponding to N-
1
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H were seen in the spectra of silyl-2 and silyl-4 and the integrals of the silyl
groups indicate monosilylated product.
When the reactions were carried out with NaOtBu as base, no silylated
products were produced, while NaH was found to be effective, although in
low-to-moderate yields (see Table S1 in SI file). Interestingly, KH was also
ineffective in producing silylated products and this point comes up for
comment later in the paper.[34-36]
Figure 1. Conversion profiles displayed by amines 1-4, and followed by 1H-
NMR, using 3 equiv. of Et3SiH and 0.2 equiv. of KOtBu.
To probe for selective silylations, competitive reactions using two
different amines from our list were carried out. The results are shown in
Table 2. When aniline 2 (1 equiv) was mixed with any other amine (1 equiv),
KOtBu (0.2 equiv) and silane (3 equiv), only aniline was silylated (Entries 1-
3). To check whether a rapidly silylated aliphatic amine could transfer a
silyl group to aniline in these mixtures, competitive reactions were
Scheme 1. Potassium tert-butoxide-mediated N-silylation of amines 1-4[1]
Table 1. N-silylation of amines by the Et3SiH/KOtBu system.
performed involving (silyl-1 or silyl-4) together with aniline
2 to
investigate a possible transfer of the triethylsilyl group from silyl-1 or silyl-
4 to 2. However, the desilylation of piperidine or cyclohexylamine and the
subsequent silylation of aniline did not occur.
Entry
Substrate
Time
Base
Silylated
product[a]
Remaining
substrate
equiv.
1
1
1
1
2
2
2
3
3
3
4
4
4
18 h
18 h
3 h
3
64 %
75 %
66 %
62 %
87 %
74 %
58 %
80 %
67 %
55 %
72 %
71%
-
Table 2. Competitive reactions between two substrates using 3 equiv. of
Et3SiH and 0.2 equiv. of KOtBu, 3h, 130 oC
2
0.2
0.2
3
-
3
traces
Entry
Amine A
Amine B
Silylated
Silylated
4
18 h
18 h
3 h
-
amine A
amine B
5
0.2
0.2
3
-
1
2
3
4
5
6
2
2
2
1
1
3
1
3
4
3
4
4
73 %
68 %
78 %
76 %
74 %
72 %
0 %
6
7
traces
0 %
18 h
18 h
3 h
-
-
-
-
-
-
0 %
8
0.2
0.2
3
74 %
77 %
63 %
9
10
11
18 h
18 h
3 h
0.2
0.2
12
The proposed mechanisms for the silylation of amines with alkaline earth
metal catalysts typically include a deprotonation step of the amine
substrate before the nitrogen-silicon bond is formed.[7] In analogy to this
class of reactions, several pathways leading to the deprotonation of the
aliphatic amine substrates were investigated computationally (Scheme 2;
as a starting point trimethylsilane was used instead of triethylsilane for
computational economy). It was found, as expected, that the direct
deprotonation of aliphatic amines with KOtBu is thermodynamically
unfavourable[37] (Scheme 2 ‘Direct Deprotonation’ and Table S3). A more
accessible energy profile was identified for the reaction of potassium tert-
butoxide 8 with trimethylsilane 5 to generate potassium hydride 9. The
subsequent deprotonation of the amine substrates 6 with this hydride is
[a]
Conversion of substrates was determined by 1H-NMR using 1,3,5-
trimethoxybenzene as an internal standard.
The conversion of the amines 1-4 to silyl derivatives as a function of time
in the presence of KOtBu (0.2 equiv), was monitored by 1H-NMR. Different
reaction profiles were observed for the various amines (Figure 1) with
piperidine 1 and morpholine 3 being fully converted into silyl-1 and silyl-3,
respectively, within
1 h of reaction start, whereas it took 2 h for
cyclohexylamine, 4, to be completely monosilylated.
2
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10.1002/hlca.201900235
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highly efficient (Step A in Scheme 2). (The direct deprotonation of an
amine with potassium tert-butoxide
8 is only possible for aniline
substrates, see SI). This finding suggests that the silylation of aliphatic
amines with the KOtBu-Et3SiH reagent system critically hinges on
potassium hydride. Thus, it appears plausible to draw the mechanism of
this reaction with potassium hydride as the actual catalytic species. This
may initially seem curious, as commercial KH was not effective in
promoting the reactions in the laboratory. However, a strong difference in
reactivity between a free KH molecule and the commercial solid aggregate
is expected.[34-36]
The energy profile of the proposed mechanism has been calculated for
four model substrates, 2 and 6a-c. Aniline 2 and dimethylamine 6a
represent typical aromatic and aliphatic amines, while the silylated amines
6b , 6c can be used to explore the energetics of further silylation.
PhNH2
Me2NH
(Me3Si)MeNH
(Me3Si)PhNH
Amine
2
6a
R1=R2=Me
6b
R1=Me;
R2=SiMe3
7.2
6c
R1=SiMe3,
R2=Ph
2.0
2
6a
6b
6c
Step A
R1=H;
R2=Ph
2.7
As has been discussed, potassium hydride 9 efficiently deprotonates the
amine substrates 6. The potassium amide 10 then adds to the silane
reagent 5 (step B) to form the pentavalent silicate species 11. After an
isomerization that features a nearly thermoneutral Berry pseudorotation
(which moves the attacking amide nitrogen atom out of the axial position
and the leaving hydrogen atom of the departing hydride into an axial
position) to 12, this species eliminates potassium hydride 9. Thereby, the
silylated product 7 is formed and the catalytic cycle is closed.
9.8
0.2
G*
G
-18.2
-7.6
-18.3
Step B
G*
G
16.1
15.6
7.9
2.2
13.9
12.4
No T.S.
11c not
stable
Step C
G*
-
-
Comparing the energy profiles for the model substrates 2 and 6a (Table 3)
gives a clear explanation for the selective silylation of aniline reported
above. The silylation of each aliphatic amine is dependent on the
formation of the corresponding potassium amide. The deprotonation of
aniline 2 is much more favourable than the deprotonation of 6a and can
even be achieved by KOtBu. In a direct competition experiment between
aniline and an aliphatic primary or secondary amine, it is aniline 2 that is
deprotonated and subsequently silylated.
5.9
1.8
2.3
-6.4
-11.7
-13.3
G
Overall Reaction
20.1
-9.8
9.8
15.4
-7.6
n.a.
-6.3
G*
G
-7.9
(All energies are in kcal mol-1).
Scheme 2 and Table 3. Proposed mechanism for the silylation of amines
with the KOtBu-Et3SiH reagent system. [a] 11c is not a stable structure.
Thus, the reaction cannot proceed.
The computational model based on the simple substrates provides
interesting information. For anilines, while the first silylation to give 6c +
KH from 2 is possible, no feasible energy profile was found for the second
silylation to give 7c (R1 = Ph, R2 = SiMe3) + KH. In fact, the intermediate 11c
is not a stable structure (i.e. there is no local minimum on the hyper energy
surface that would correspond to 11c). This implies that the reaction
cannot proceed. On the other hand, in relation to the aliphatic amine,
methylamine, conversion of its monosilylated derivative 6b to its
disilylated derivative 7b + KH is shown. Step B is endergonic but it features
a valid transition state, and rapid subsequent use of KH in the next cycle
can make it viable.
aliphatic amines, a more extensive computational model was employed
(see Figure 2 and also Figure S2 and S5). It was found that steric factors
have a critical impact on the reaction. As can be expected, the energy
barrier increases with increasing steric bulk. But only a moderate increase
was observed when increasing the steric bulk on the silyl groups; changing
the methyl groups for ethyl groups led to a moderate increase of the rate
determining step from 15.4 kcal/mol to 17.6 kcal/mol, respectively [Path (i)
and Path (ii)]. A marked increase of the rate-determining barrier height
was observed for n-propyl (iii) as a larger aliphatic residue on the amine.
The activation barrier for the analogous reaction with i-propylamine (iv)
was found to be even higher. In fact, the second silylation of the i-
propylamine substrate is predicted to have a barrier that is 5.1 kcal/mol
These experimental findings indicate that it depends on the exact nature
of the amine substrate whether the reaction stops after the first silylation
or proceeds to a second silylation. To better understand the factors
influencing the balance between mono and double silylation of primary
3
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higher than the second silylation of the n-propylamine substrate, which
Mass Spectrometry Centre, Swansea. Accurate mass was obtained using
atmospheric pressure chemical ionisation (APCI), electron ionisation (EI)
and nanospray ionisation (NSI) with an LTQ Orbitrap XL mass
spectrometer.
makes this reaction >500-times slower.
General procedure for N-silylation of substrates 1-4
The amine (0.50 mmol, 1.0 equiv.), triethylsilane (0.24mL, 1.5mmol,
3.0equiv.) and potassium tert-butoxide (168 or 11 mg , 1.50 or 0.1 mmol,
3.0 or 0.2 equiv.) were sealed in a pressure tube in a glove box under
nitrogen. The tube was removed and heated at 130 °C for different
durations behind a safety shield. After cooling to room temperature, the
mixture was diluted with water and extracted into diethyl ether. The
combined organic layers were dried over Na2SO4, filtered and
concentrated under reduced pressure. When only 0.2 equiv. of the base
were used, reactions were quenched by addition to CDCl3 without doing
any extraction with water in order to obtain more accurate conversion
values.
This general procedure has been also followed when other bases (NaH, KH,
NaOtBu) were used in place of KOtBu. Samples for GCMS experiments
were prepared by dissolving a small amount (< 1 mg/mL) of the crude
reaction mixture in chloroform.
Figure 2. The four most accessible energy profiles for the key steps B and
C as shown in Scheme 2 for substrates with increasing steric bulk; (i):
Me3SiN(Me)H and Me3SiH, (ii): Et3SiH and Et3SiN(Me)H (iii): Et3SiH and
Et3SiN(nPr)H, (iv): Et3SiN(iPr)H and Et3SiH
Procedure for N-silylation of amines 1-5 as a function of time followed by
1H-NMR
In summary, computational studies align with laboratory experiments in
supporting the feasibility of silylation of primary and secondary amines
with KOtBu as base and with a trialkylsilane as silylating agent. The
reaction is somewhat sensitive to steric effects and likely proceeds
through a catalytic cycle in which KH is generated.
The amine (0.50 mmol, 1.0 equiv.), triethylsilane (0.24mL, 1.5mmol,
3.0equiv.) and potassium tert-butoxide (11 mg , 0.1 mmol, 0.2 equiv.) were
sealed in a pressure tube in a glove box under nitrogen. The reaction was
entirely performed in the glovebox at 130 oC and 1H-NMR spectra of
reaction mixture aliquots were acquired every 30 min.
Experimental Section
General Text
Procedure for competitive reactions
All chemicals were commercially available and used without additional
purification.1H NMR and 13C NMR spectra were recorded in CDCl3 as
solvent on a Bruker AV3 at 400 and 100 MHz, respectively, and the NMR
chemical shifts are referenced in ppm from an internal solvent peak. Signal
multiplicities are abbreviated as: s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet; bs, broad singlet. Coupling constants are given in Hertz (Hz)
Amine A (0.50 mmol, 1.0 equiv.), amine B (0.50 mmol, 1.0 equiv.),
triethylsilane (0.24mL, 1.5mmol, 3.0equiv.) and potassium tert-butoxide
(11 mg , 0.1 mmol, 0.2 equiv.) were sealed in a pressure tube in a glove box
under nitrogen. The tube was removed and heated at 130 °C for different
durations behind a safety shield. After cooling to room temperature, the
mixture was diluted with water and extracted into diethyl ether. The
combined organic layers were dried over Na2SO4, filtered and
concentrated under reduced pressure.
The silylation reactions were performed in
a glove box (Innovative
Technology Inc., USA) under nitrogen atmosphere (O2 < 1 ppm). All
reagents introduced into the glove box were transferred through the port,
which was evacuated and purged with nitrogen ten times before entry.
The mass spectra were recorded by gas-phase chromatography (GC-MS)
using electron ionization (EI). Low resolution GC-MS data were recorded
using an Agilent Technologies 7890A GC system coupled to a 5975C inert
XL EI/CI MSD detector. Separation was performed using the DB5MS-UI
column (30 m x 0.25 mm x 0.25 μm) at a temperature of 320 oC, using
helium as the carrier gas. Chloroform was used as a solvent in all GC-MS
analyses.
Procedure for competitive reactions involving (silyl-1 or silyl-4) together
with aniline 2
Silyl-1 or silyl-4 (1 mmol, 2.0 equiv.), aniline 2 (0.50 mmol, 1.0 equiv.),
and potassium tert-butoxide (11 mg , 0.1 mmol, 0.2 equiv.) were sealed in a
pressure tube in a glove box under nitrogen. The tube was removed and
heated at 130 °C for different durations behind a safety shield. After
cooling to room temperature, the mixture was diluted with water and
extracted into diethyl ether. The combined organic layers were dried over
Na2SO4, filtered and concentrated under reduced pressure.
Infra-Red spectra were recorded on an ATR-IR spectrometer. High-
resolution mass spectrometry (HRMS) was performed at the National
4
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10.1002/hlca.201900235
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Conversion of substrates
0.79 (6H, q, J = 8.0 Hz, 3 × CH2). C (100 MHz, CDCl3): 4.1, 6.5, 115.6, 116.9,
128.7, 147.2. IR (NEAT) (cm-1) = 671, 691, 720, 746, 770, 887, 997, 1290,
1385, 1476, 1497, 1601, 2874, 2953. GC-MS [m/z (%)]: 207.2 (43, M+), 178.2
(100), 150.1 (68), 122.1 (70), 120.1 (76), 92.2 (18), 79.1 (30), 59.1 (15). The
data are consistent with the literature.[39]
Conversion of substrates was determined by 1H-NMR using 1,3,5-
trimethoxybenzene (10 %) as internal standard. Reactions were directly
quenched by adding to CDCl3. The quantity of each product was
determined as follows:
- (example calculation Table 1, Entry 2): for the product silyl-1 the
N-triethylsilylmorpholine (Silyl-3). The general procedure was followed,
using morpholine 3 (43.6 mg, 43.7 L). H (400 MHz, CDCl3): 3.58 – 3.55 (4H,
m, 2 × CH2), 2.88-2.90 (4H, m, 2 × CH2), 0.95 (9H, t, J = 8.0 Hz, 3 × CH3), 0.56
(6H, q, J = 8.0 Hz, 3 × CH2). C (100 MHz, CDCl3): 3.3, 6.7, 45.5, 68.2. IR
(NEAT) (cm-1) = 677, 723, 839, 970, 1015, 1101, 1238, 1458, 2874, 2911,
2953. GC-MS [m/z (%)]: 201.2 (16, M+), 172.2 (100), 144.1 (19), 114.1 (45),
87.1 (70), 59.1 (91). The data are consistent with the literature.[40]
1
integration of the methoxy signals of the internal standard in the H-NMR
spectrum (δ3.78 ppm) was set to 9 units.
The integration of the signal corresponding to the two methylene groups
next to the N atom of silyl-1 at δ2.85 ppm (2 × CH2, 4 H) was then
measured and the following calculation gave the amount of silyl-1
present: (30.15/4) x 10 = 75 %
- (example calculation Table 1, Entry 5): for the product silyl-2 the
1
integration of the methoxy signals of the internal standard in the H-NMR
N-triethylsilylcyclohexylamine (Silyl-4). The general procedure was
followed, using cyclohexylamine 4 (49.6 mg, 57.2 L). H (400 MHz,
CDCl3): 2.57 – 2.49 (1H, m, CH), 1.85 – 1.82 (1H, m, CH), 1.81 – 1.79 (1H, m,
CH), 1.72 – 1.71 (1H, m, CH), 1.69 – 1.67 (1H, m, CH), 1.59 – 1.54 (1H, m, CH),
1.31 – 1.27 (1H, m, CH), 1.25 – 1.21 (1H, m, CH), 1.17 - 1.09 (1H, m, CH), 1.07
- 1.02 (2H, m, 2 × CH), 0.95 (9H, t, J = 8.0 Hz, 3 × CH3), 0.52 (6H, q, J = 8.0 Hz,
3 × CH2), 0.33 (1H, bs, NH). C (100 MHz, CDCl3): 4.6, 6.7, 25.2, 25.4, 38.6,
50.1. IR (NEAT) (cm-1) = 667, 685, 715, 724, 822, 858, 1011, 1117, 1234,
1406, 1449, 2851, 2874, 2926, 2949. GC-MS [m/z (%)]: 213.3 (15, M+), 184.2
(100), 170.2 (48), 142.1 (6), 128.1 (8), 115.2 (7), 100.1 (7), 87.1 (14), 59.1 (15).
HRMS (APCI) calcd for C12H26NSi [M-H]+: 212.1829, found: 212.1828.
spectrum (δ3.78 ppm) was set to 9 units.
The integration of the signal corresponding to the two ortho aromatic
protons of silyl-2 at δ7.18 – 7.14 ppm (2 H) was then measured and the
following calculation gave the amount of silyl-2 present: (17.45/2) x 10 =
87 %
- (example calculation Table 1, Entry 8): for the product silyl-3 the
1
integration of the methoxy signals of the internal standard in the H-NMR
spectrum (δ3.78 ppm) was set to 9 units.
The integration of the signal corresponding to the two methylene groups
next to the O atom of silyl-3 at δ3.58 – 3.55 ppm (2 × CH2, 4 H) was then
measured and the following calculation gave the amount of silyl-3
present: (31.84/4) x 10 = 80 %
Supplementary Material
- (example calculation Table 1, Entry 11): for the product silyl-4 the
1
integration of the methoxy signals of the internal standard in the H-NMR
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/MS-number.
spectrum (δ3.78 ppm) was set to 9 units.
The integration of the signal corresponding to proton next to the amino
group of silyl-4 at δ2.57 – 2.49 ppm (1 H) was then measured and the
following calculation gave the amount of silyl-4 present: (7.18/1) x 10 =
72 %
Acknowledgements
We thank the Generalitat Valenciana (Spain) for funding a postdoctoral
fellowship (to F.P.). the University of Strathclyde and GlaxoSmithKline for
funding. Computational results were obtained using the ARCHIE-WeSt
High Performance Computer (www.archie-west.ac.uk) based at the
University of Strathclyde.
Characterisation of products
N-triethylsilylpiperidine (Silyl-1). The general procedure was
followed ,using piperidine 1 (42.6 mg, 49.4 L). H (400 MHz, CDCl3): 2.85
– 2.82 (4H, m, 2 × CH2), 1.59 – 1.55 (2H, m, CH2), 1.43 – 1.37 (4H, m, 2 × CH2),
0.94 (9H, t, J = 7.6 Hz, 3 × CH3), 0.54 (6H, q, J = 8.0 Hz, 3 × CH2). C (100 MHz,
CDCl3): 3.6, 6.8, 25.2, 27.6, 46.3. IR (NEAT) (cm-1) = 667, 688, 725, 851,
949, 1003, 1059, 1236, 2874, 2911, 2932, 2951. GC-MS [m/z (%)]: 199.2 (20,
M+), 170.2 (100), 142.2 (22), 112.1 (11), 87.1 (37), 59.1 (63). The data are
consistent with the literature.[38]
Author Contribution Statement
FP performed the laboratory experiments and SR performed the
computational experiments. JAM and TT supervised the work. FC, SR and
JAM wrote the article. All authors commented on the manuscript.
References
[1]
J. Emsley, Nature’s Building Blocks: An A-Z Guide to the Elements, Oxford
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7
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