An Aluminum Fluoride Complex with an Appended Ammonium Salt as an Exceptionally Active Cooperative Catalyst for the Asymmetric Carboxycyanation of Aldehydes

Article abstract of DOI:10.1002/anie.201612493

Al?F bonds are among the most stable σ bonds known, exhibiting an even higher bond energy than Si?F bonds. Despite a stability advantage and a potentially high Lewis acidity of Al?F complexes, they have not been described as structurally defined catalysts

Full text of DOI:10.1002/anie.201612493

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201612493
German Edition: DOI: 10.1002/ange.201612493
Cooperative Catalysis
Hot Paper
An Aluminum Fluoride Complex with an Appended Ammonium Salt
as an Exceptionally Active Cooperative Catalyst for the Asymmetric
Carboxycyanation of Aldehydes
Daniel Brodbeck, Florian Broghammer, Jan Meisner, Julian Klepp, Delphine Garnier,
Wolfgang Frey, Johannes Kꢀstner, and Renꢁ Peters*
Dedicated to Professor Yoshito Kishi on the occasion of his 80th birthday
loadings,[10] for carboxycyanations, the turnover numbers
(TONs) are lower, with catalyst loadings usually in the
range of 1–10 mol%.[2a,11] As a general
À
Abstract: Al F bonds are among the most stable s bonds
À
known, exhibiting an even higher bond energy than Si F
bonds. Despite a stability advantage and a potentially high
À
Lewis acidity of Al F complexes, they have not been described
as structurally defined catalysts for enantioselective reactions.
trend, cooperative catalysis has proven
to be beneficial for both carboxy- and
We show that Al F salen complexes with appended ammoni-
carbocyanations.[12–14]
À
um moieties give exceptional catalytic activity in asymmetric
carboxycyanations. In addition to aromatic aldehydes, enal
and aliphatic substrates are well accepted. Turnover numbers
up to around 104 were achieved, whereas with previous
catalysts 101–102 turnovers were typically attained. In contrast
In this Communication, we report
a new strategy for the carboxycyanation
of aldehydes, which permits unprece-
dented TONs.[2] In our approach,
a Lewis acid catalyst cooperates with
to Al Me and Al Cl salen complexes, the analogous Al F
species are remarkably stable towards air, water, and heat, and
can be recovered unchanged after catalysis. They possess
a considerably increased Lewis acidity as shown by DFT
calculations.
an internal ammonium salt moiety.[15]
À
À
À
The study was driven by the idea that
a “naked” cyanide would facilitate the 1,2-addition to
a simultaneously activated aldehyde while the ammonium
should promote a face-selective attack.[15] Key for the high
À
catalyst efficiency is a robust Al F unit that provides an
extraordinarily stable and active catalyst.
A
symmetric 1,2-additions of cyanide to aldehydes have been
intensively studied because the enantioenriched cyanohydrin
products are valuable chiral building blocks.[1–3] Although it is
industrially employed in enzymatic processes,[4,5] the direct
use of HCN is difficult for safety reasons and thus less volatile
HCN equivalents are often utilized, in particular trimethyl-
silyl cyanide and ethyl cyanoformate.[2,6,7] Whereas addition
of HCN is reversible, the O-protected products formed from
Initial experiments (0.1 mmol scale) were conducted with
ligands like 4 (5 mol%), which bear two ammonium units
(Table 1, entry 1). The Al catalysts were formed in situ using
AlMe3. However, activity and ee were poor in CH2Cl2 at
À508C. To improve the catalyst solubility, ligand 5 was
studied, which bears a single ammonium unit (entry 2). The
reactivity was massively improved by using KCN as an
additive, which also has a positive impact on the ee (entry 3).
A further ee enhancement was achieved with ligand 6, which
has a Et2MeN+CH2 residue (entry 4), and with BF4À as XÀ in 7
(entry 5). The influence of longer linkers between the salen
core and the ammonium group were studied (entries 6 and 7),
and the best results were obtained with the (CH2)3 unit in
ligand 9.
=
TMSCN and EtO(C O)CN are stable towards the reverse
reaction and hence less prone to racemization.[2] On a pro-
=
duction scale, the use of EtO(C O)CN appears more
attractive for practical, safety, and cost reasons.[8] The
installed carboxy groups were also used for elegant further
transformations like [3,3]-rearrangements.[9]
Although very active catalysts have been developed that
can be applied to cyanosilylations with very small catalyst
“Non-nucleophilic” counterions XÀ initially had an unex-
pected impact. With triflate in ligand 10 (and also PF6 ) in
À
place of BF4À, the enantioselectivity was nearly completely
lost (entry 8). In contrast, when using ligand 10 but with
Me2AlCl for complexation, it was largely regained (entry 9).
Solvent screening using the catalyst formed from 9 and AlMe3
revealed that slightly better enantioselectivity is attained in
CHCl3. The amount of 2 and KCN could then be lowered
without any negative effect (entry 10).
[*] M. Sc. D. Brodbeck, Dipl.-Chem. F. Broghammer, M. Sc. J. Klepp,
Dr. D. Garnier, Dr. W. Frey, Prof. Dr. R. Peters
Universitꢀt Stuttgart, Institut fꢁr Organische Chemie
Pfaffenwaldring 55, 70569 Stuttgart (Germany)
E-mail: rene.peters@oc.uni-stuttgart.de
M. Sc. J. Meisner, Prof. Dr. J. Kꢀstner
Universitꢀt Stuttgart, Institut fꢁr Theoretische Chemie
Pfaffenwaldring 55, 70569 Stuttgart (Germany)
The so far most selective catalyst formed in situ from 9
À
(XÀ = BF4 ) and AlMe3 proved to be a complex mixture of
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
http://dx.doi.org/10.1002/anie.201612493.
1
several species as judged by H-/19F NMR. Our speculation
À
that a much more active {Al F} catalyst might have been
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Table 1: Development of the model reaction.
(see the Supporting Information) confirm a monomeric
[17]
À
structure for the {Al F}X complexes.
À
{Al F}OTf provided 3a in a quantitative yield with good
ee (entry 11). Its superior performance permitted us to
employ a catalytic amount of KCN (0.1 equiv) and obviated
the need for an excess of 2, while at the same time improving
the ee through a reduced catalyst load (entry 12). A quanti-
À
tative yield was still obtained with 0.1 mol% of {Al F}OTf
À
(TON = 1000, entry 13). A comparison of {Al F}OTf with its
À
Al Cl counterpart revealed that the latter is much less active
(entry 14).
À
The optimized conditions with a standard {Al F}OTf
loading of 0.1 mol% were applied to various aldehydes
(Table 2).[18] Both s and p donors on aromatic aldehydes were
well tolerated (entries 2, 4–7, 9–11). In the case of an ortho-
positioned donor, the ee was slightly reduced, but the
reactivity was still useful to high (entries 6, 9). Substrates
bearing s or p acceptors (entries 8, 12–14), as well as 2-
furylcarbaldehyde (entry 15), furnished nearly quantitative
yields. The catalyst performance is thus not very sensitive
towards electronic effects.
Entry Ligand (x) R2Al-Y
2 (equiv)
y
Yield [%][a] ee [%][b]
1
2
3
4
5
6
7
8
9
4 (5.0)
5 (5.0)
5 (5.0)
6 (5.0)
7 (5.0)
8 (5.0)
9 (5.0)
10 (5.0)
10 (5.0)
9 (5.0)
10 (5.0)
10 (1.0)
Me2Al-Me
Me2Al-Me
Me2Al-Me
Me2Al-Me
Me2Al-Me
Me2Al-Me
Me2Al-Me
Me2Al-Me
Me2Al-Cl
Me2Al-Me
Me2Al-F
4
4
4
4
4
4
4
4
4
2
2
1
1
1
0
0
2
2
2
2
2
2
2
1
1
9
12
15
39
53
85
66
88
12
79
90
90
92
93
69
20
100
100
100
63
High yields and ee values were also attained with enals.
With (E)-cinnamaldehyde, the product was formed in more
100
99
99
10[c]
11[c,d]
12[c,d]
100
100
Table 2: Investigation of the substrate scope.
Me2Al-F
Me2Al-F
0.1 100
0.1 100
0.1 12
13[c,d,e] 10 (0.1)
14[c,d]
10 (1.0)
Me2Al-Cl
[a] Determined by 1H-NMR of the crude product using an internal
standard. [b] Determined by HPLC. [c] The reaction was performed in
CHCl3. [d] Preformed catalyst was used. [e] Reaction time: 48 h.
À
formed in the presence of a BF4 counterion through
a methyl/fluoride exchange was supported by HR-MS and
X-ray crystal structure analysis of one of these species
(Figure 1, left), which revealed a dimeric aggregate with an
anionic F-Al-F-Al-F axis.
Entry 1/3 R-
x
t [h] Yield [%][a] ee [%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18[c]
19[d]
20[c]
21[c]
22[c]
a
b
c
d
e
f
g
h
i
2-naphthyl-
6-MeO-2-naphthyl-
Ph-
0.1 24
0.1 24
0.1 24
0.1 72
0.1 48
0.1 48
0.5 72
0.1 24
0.1 48
0.1 72
0.5 72
0.1 48
0.1 48
0.1 48
0.1 48
0.1 48
>99
92
93
93
91
88
90
82
93
92
84
86
96
89
89
80
82
96
97
94
93
81
90
78
À
A monomeric {Al F}OTf salen complex featuring a free
99
85
98
99
coordination site was then synthesized from ligand 10 and
Me2AlF.[16] X-ray crystal structure analysis (Figure 1, right)
and PGSE (Pulsed Gradient Spin Echo) NMR experiments
4-Me-C6H4-
3-Me-C6H4-
2-Me-C6H4-
4-MeO-C6H4-
3-MeO-C6H4-
2-MeO-C6H4-
3,4-Me2-C6H3-
3,4-(MeO)2-C6H3-
4-Cl-C6H4-
78
>99
61
j
k
l
74
97
>99
>99
99
m
n
o
p
q
r
4-F-C6H4-
3-MeO2C-C6H4-
2-furyl-
(E)-Ph-CH CH-
(E)-4-MeO-C6H4-CH CH- 0.1 48
98
>99
90
=
=
=
=
(E)-Me-CH CH-
0.1 72
0.01 72
0.1 72
0.1 72
0.1 72
96
98
99
99
r
(E)-Me-CH CH-
s
t
u
Et-
PhCH2CH2-
tBu-
99
Figure 1. X-ray crystal structure analyses of dimeric {Al2F3}BF4 (a) and
À
monomeric {Al F}PF6 (b) complexes. H atoms, included solvent
molecules and a second monomer per unit cell (for (b); see the
Supporting Information) are omitted for clarity.
[a] Yield of isolated product after column chromatography. [b] Deter-
mined by HPLC. [c] Reaction in CH2Cl2/CHCl3 (1:1) at À808C.
[d] 0.05 equiv of KCN.
2
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than 99% yield and in highly enantioenriched form
Scheme 1 shows a possible mechanism. Addition of KCN
[20,21]
À
(entry 16). A p donor slightly affected the product yield
(entry 17). Moreover, the small, linear g-acidic crotonalde-
hyde was well accepted (entry 18). It was shown that even
lower catalyst loadings are possible without disturbing the
catalyst performance. When using as little as 0.01 mol% of
likely improves the reactivity by generating {Al F}CN.
1 is activated through coordination to the Al center, thereby
facilitating a quasi-intramolecular attack by cyanide.[22] Prod-
uct release and catalyst regeneration are achieved through
carboxylation by 2.
À
{Al F}OTf, a highly enantioenriched product was formed in
an almost quantitative yield (TON = 9800, entry 19). The
method is also applicable to enolizable substrates like
propanal and dihydrocinnamaldehyde (entries 20–21), as
well as bulky aliphatic substrates like pivaldehyde (entry 22).
À
To study the preparative value of {Al F}OTf, gram-scale
experiments were conducted using cinnamaldehyde in anal-
ogy to Table 2, entry 16. The product was again isolated in
quantitative yield and with 96% ee. Efficient stirring proved
to be essential to maintain high yields, which is ascribed to the
À
phase-transfer catalysis (PTC) character of this reaction. {Al
F}OTf was recovered unchanged (characterized again by 1H-/
19F-NMR and HR-MS) in 72% yield through precipitation
from the reaction mixture and reused under identical
conditions, providing 3p in 88% yield and with 95% ee.
The lower yield is ascribed to an incomplete precipitation of
the tiny catalyst amount. The catalyst recycling needs to be
technically optimized, but the data establish a proof of
principle.
Scheme 1. Possible mechanism.
À
The superior performance of {Al F}OTf is ascribed to two
À
factors: increased stability and Lewis acidity. Al F bonds are
Moreover, five additional experiments were conducted on
among the most stable s bonds, with reported bond energies
À
a 200 mg scale at À508C using 0.1 mol% {Al F}OTf and
of 659–672 kJmolÀ1.[23] This stability is reflected by the high
À
almost identical results were obtained as on the 0.1 mmol
scale reported in Table 2 [1a (72 h): 100%, 93% ee; 1c (72 h):
98%, 91% ee; 1e (48 h): 100%, 90% ee; 1p (72 h): 100%,
96% ee; 1q (72 h): 92%, 96% ee].
robustness of {Al F}OTf, which is remarkably stable to water,
air (over several months at room temperature), and melted
without decomposition (judged by 1H-/19F NMR) at 2218C. In
contrast to the related {Al Cl} and {Al Me} catalysts, it can
be recovered unchanged after the title reaction.
À
À
Control experiments were conducted with the chiral Al
salen complex 11, which lacks an appended ammonium
moiety (Table 3).[19] 11 furnished very small amounts of nearly
racemic 3a, even at high catalyst loadings and working with
an excess of 2 and relatively large amounts of KCN (entry 1).
By adding [Et4N]OTf, the reactivity was increased. However,
nearly no enantioselectivity was found and the reactivity was
À
The Al F bond was investigated by means of density
functional theory (DFT)[24] and intrinsic bond orbitals
(IBOs)[25] which lead to useful Lewis structures and are
appropriate to interpret quantum chemical calculations.[26]
The structurally reduced Al salen complexes 12 were studied
to describe the binding situation around the aluminum center
for X = F, Cl and Me (Figure 2).
À
much lower than with the bifunctional {Al F}OTf (entry 2).
À
[Et4N]OTf also catalyzed the reaction in the absence of 11,
but with decreased activity (entry 3). The results support the
essential role of the ammonium moiety in the dual activation
The calculated Al F distance of 1.69 ꢀ is in very good
agreement with the crystal structure (1.688–1.702 ꢀ). The
IBO analysis shows that the Al F s bond is strongly polarized
towards the F atom: only 0.23 of the corresponding bond
charge (12%) is located at the Al atom (for Cl 0.38, for Me
À
À
catalyst {Al F}OTf.
Table 3: Control experiments.
Entry
x
2 (equiv) y (equiv) additive (mol%) Yield [%][a] ee [%][b]
1
2
3
5
2.0
0.5
0.2
0.2
–
12
17
2
–
0.1 1.0
1.0
[Et4N]OTf (0.1) 31
[Et4N]OTf (0.1) 23
–
[a] Determined by 1H-NMR of the crude product using an internal
standard. [b] Determined by HPLC.
Figure 2. Intrinsic bond orbitals for the Al X bonds in complexes 12:
À
À
À
À
top right: Al F; bottom left: Al Cl; bottom/right: Al Me.
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À
Kurono, T. Yoshikawa, M. Yamasaki, T. Ohkuma, Org. Lett.
2011, 13, 1254.
[6] Early asymmetric carboxycyanation with ethyl cyanoformate: S.-
K. Tian, L. Deng, J. Am. Chem. Soc. 2001, 123, 6195.
[7] An interesting alternative is cyanophosphorylation: A. Baeza, J.
Casas, C. Nꢂjera, J. M. Sansano, J. M. Saꢂ, Angew. Chem. Int. Ed.
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0.50). It follows that the Al atom in the Al F complex
possesses a higher partial charge (+ 1.26) than in the
respective Cl and Me complexes (+ 1.09 and + 1.11), thus
confirming a higher Lewis acidity. A Mulliken population
analysis shows the same trend, as shown in the Supporting
À
Information. This suggests that the Al F bond is more ionic
than the Al Cl and Al C bonds. This is supported by the
lower Wiberg bond order of 0.58 for the Al F bond compared
to 0.77 and 0.74 for the Al Cl and Al C bonds.
In conclusion, we have reported an exceptionally active,
broadly applicable catalyst for the asymmetric carboxycya-
nation of aldehydes, which gives unprecedented TONs of up
to around 104. Our results suggest that a Lewis acidic Al
center cooperates with an internal ammonium salt moiety.
Key for the high efficiency is the Al F unit. This is explained
by 1) a high Lewis acidity as found by DFT studies and 2) a
remarkable catalyst stability, which also allows catalyst
À
À
À
À
À
[9] J. Tian, N. Yamagiwa, S. Matsunaga, M. Shibasaki, Org. Lett.
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[10] Highly active catalysts (loadings ꢀ 0.2 mol%) for highly enan-
tioselective cyanosilylations: a) Y. N. Belokonꢃ, S. Caveda-
Cepas, B. Green, N. S. Ikonnikov, V. N. Khrustalev, V. S.
Larichev, M. A. Moscalenko, M. North, C. Orizu, V. I. Tararov,
M. Tasinazzo, G. I. Timofeeva, L. V. Yashkina, J. Am. Chem. Soc.
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T. Ohkuma, Adv. Synth. Catal. 2012, 354, 2023.
À
À
recovery. As a result of these advantages, {Al F} catalysts
might be of technical interest. To our knowledge, this is the
first application of a structurally defined Al catalyst contain-
À
ing an Al F s bond in asymmetric catalysis. Even higher
enantioselectivity might be possible with alternative catalyst
cores. We expect that Al F catalysts will find wide applica-
À
tion.
[11] High TONs were achieved in carbocyanations with NaCN and
acetic anhydride: see Ref. [10f].
Acknowledgments
[12] Selected studies: a) J. Tian, N. Yamagiwa, S. Matsunaga, M.
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buck, M. North, Org. Lett. 2003, 5, 4505; c) J. Casas, A. Baeza,
J. M. Sansano, C. Nꢂjera, J. M. Saꢂ, Tetrahedron: Asymmetry
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Shibasaki, J. Am. Chem. Soc. 2005, 127, 3413; e) S. Lundgren, E.
Wingstrand, M. Penhoat, C. Moberg, J. Am. Chem. Soc. 2005,
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North, Chem. Commun. 2006, 1775; g) S. Gou, X. Chen, Y.
Xiong, X. Feng, J. Org. Chem. 2006, 71, 5732; h) S. Gou, J. Wang,
X. Liu, W. Wang, F.-X. Chen, X. Feng, Adv. Synth. Catal. 2007,
349, 343; i) Y. N. Belokonꢃ, W. Clegg, R. W. Harrington, E.
Ishibashi, H. Nomura, M. North, Tetrahedron 2007, 63, 9724;
j) with a-ketonitriles: S. Lundgren, E. Wingstrand, C. Moberg,
Adv. Synth. Catal. 2007, 349, 364; k) ref. [10f]; l) J. Wang, W.
Wang, W. Li, X. Hu, K. Shen, C. Tan, X. Liu, X. Feng, Chem. Eur.
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R. I. Kureshy, S. H. R. Abdi, S. Saravanan, H. C. Bajaj, Tetrahe-
dron 2011, 67, 7073; n) E. Wingstrand, C. Moberg, Synlett 2010,
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[13] Interesting results were also obtained with chiral bisammonium
salts: R. Chinchilla, C. Nꢂjera, F. J. Ortega, S. Tarꢄ, Tetrahedron:
Asymmetry 2009, 20, 2279.
[14] Cooperative Catalysis—Designing Efficient Catalysts for Syn-
thesis (Ed.: R. Peters), Wiley-VCH, Weinheim, 2015.
[15] Our research group has introduced the strategy of cooperative
asymmetric intramolecular Lewis acid/aprotic onium salt catal-
ysis: a) T. Kull, R. Peters, Angew. Chem. Int. Ed. 2008, 47, 5461;
Angew. Chem. 2008, 120, 5541; b) T. Kull, J. Cabrera, R. Peters,
Chem. Eur. J. 2010, 16, 9132; c) P. Meier, F. Broghammer, K.
Latendorf, G. Rauhut, R. Peters, Molecules 2012, 17, 7121; d) F.
Broghammer, D. Brodbeck, T. Junge, R. Peters, Chem.
Commun. 2017, 53, 1156; related catalyst systems: e) M.
Mechler, R. Peters, Angew. Chem. Int. Ed. 2015, 54, 10303;
Angew. Chem. 2015, 127, 10442; f) this concept is also very useful
in macromolecular chemistry see, e.g.: M. Winnacker, S. Vagin,
The Carl-Zeiss-Stiftung is gratefully acknowledged for
a Ph.D. fellowship to D.B. We thank Dr. Josꢁ Cabrera-
Crespo for initial studies on asymmetric cyanations.
Conflict of interest
The authors declare no conflict of interest.
À
Keywords: Al F bond · cyanide · dual activation · ion pairs ·
phase transfer catalysis
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4
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Angewandte
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2015; g) another application: K. Ohmatsu, S. Kawai, N. Imag-
awa, T. Ooi, ACS Catal. 2014, 4, 4304.
side. This is also the reason why {Al-F}OTf is recovered
À
unchanged after the catalytic reaction. {Al F}CN is probably
À
short-lived but much more reactive than {Al F}OTf.
[22] The absence of a non-linear effect supports a mechanism in
which only one catalyst molecule is involved (see the Supporting
Information).
[16] Me2AlF: K. Ziegler, R. Kçster, Justus Liebigs Ann. Chem. 1957,
608, 1.
[17] T. Augenstein, F. Dorner, K. Reiter, H. E. Wagner, D. Garnier,
W. Klopper, F. Breher, Chem. Eur. J. 2016, 22, 7935.
[18] The (R)-configuration of 3 was determined by comparison to
published optical rotation data (see the Supporting Informa-
tion).
[23] a) R. T. Sanderson, Polar Covalence, Academic Press, New
York, 1983, p. 155; b) L. Pauling, The Nature of The Chemical
Bond, Cornell University Press, Ithaca, New York, 1960, p. 85.
[24] A detailed description of the computational details is given in
the Supporting Information.
[19] Early applications of homochiral Al salen complexes: a) M. S.
Sigman, E. N. Jacobsen, J. Am. Chem. Soc. 1998, 120, 5315;
b) J. K. Myers, E. N. Jacobsen, J. Am. Chem. Soc. 1999, 121, 8959.
[20] Reviews on asymmetric onium salt catalysis: a) S. Shirakawa, K.
Maruoka, Angew. Chem. Int. Ed. 2013, 52, 4312; Angew. Chem.
2013, 125, 4408; b) K. Maruoka, Org. Process Res. Dev. 2008, 12,
679.
[25] G. Knizia, J. Chem. Theory Comput. 2013, 9, 4834.
[26] G. Knizia, J. E. M. N. Klein, Angew. Chem. Int. Ed. 2015, 54,
5518; Angew. Chem. 2015, 127, 5609. For an application, see: M.
Ayerbe Garcia, W. Frey, M. Ringenberg, M. Schwilk, R. Peters,
Chem. Commun. 2015, 51, 16806.
À
À
[21] We tried to detect {Al F}CN, after prestirring {Al F}OTf with
KCN, by IR, 1H-NMR, 13C-NMR (K13CN), and MS, but it could
Manuscript received: December 29, 2016
À
not be detected so far. The equilibrium is far on the {Al F}OTf
Final Article published: && &&, &&&&
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
À
Cooperative Catalysis
AlF has landed: In comparison to its{Al
À
Me} and {Al Cl} analogues, a structurally
À
D. Brodbeck, F. Broghammer, J. Meisner,
J. Klepp, D. Garnier, W. Frey, J. Kꢁstner,
defined {Al F} complex is unusually
stable towards air, moisture and heat,
À
R. Peters*
&&& — &&&
probably as a result of the very strong Al
F bond. In asymmetric carboxycyana-
À
An Aluminum Fluoride Complex with an
Appended Ammonium Salt as an
Exceptionally Active Cooperative Catalyst
for the Asymmetric Carboxycyanation of
Aldehydes
tions, the {Al F} complex shows extra-
ordinary catalytic activity.
6
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
These are not the final page numbers!