Highly Stereoselective Intermolecular Haloetherification and Haloesterification of Allyl Amides

Article abstract of DOI:10.1002/anie.201502341

An organocatalytic and highly regio-, diastereo-, and enantioselective intermolecular haloetherification and haloesterification reaction of allyl amides is reported. A variety of alkene substituents and substitution patterns are compatible with this chemistry. Notably, electronically unbiased alkene substrates exhibit exquisite regio- and diastereoselectivity for the title transformation. We also demonstrate that the same catalytic system can be used in both chlorination and bromination reactions of allyl amides with a variety of nucleophiles with little or no modification. A highly regioselective intermolecular haloetherification that proceeds with excellent enantioselectivity, catalyzed by cinchona alkaloid dimers, is reported. The regioselectivity is preserved for unbiased alkyl substituted allyl amides with either E or Z geometry. (DHQD)₂PHAL=hydroquinidine 1,4-phthalazinediyl diether.

Full text of DOI:10.1002/anie.201502341

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201502341
German Edition: DOI: 10.1002/ange.201502341
Organocatalysis
Highly Stereoselective Intermolecular Haloetherification and
Haloesterification of Allyl Amides**
Bardia Soltanzadeh, Arvind Jaganathan, Richard J. Staples, and Babak Borhan*
Abstract: An organocatalytic and highly regio-, diastereo-, and
enantioselective intermolecular haloetherification and haloes-
terification reaction of allyl amides is reported. A variety of
alkene substituents and substitution patterns are compatible
with this chemistry. Notably, electronically unbiased alkene
substrates exhibit exquisite regio- and diastereoselectivity for
the title transformation. We also demonstrate that the same
catalytic system can be used in both chlorination and
bromination reactions of allyl amides with a variety of
nucleophiles with little or no modification.
Figure 1. Enantioselective intra- and intermolecular haloetherification
of alkenes. It should be noted that the bridged halonium is used as
only a demonstration of a putative intermediate, although in many
instances the open carbocation would predominate. The nature of the
intermediate is highly dependent on the nature of the olefin and the
halogen.
T
he field of catalytic asymmetric alkene halogenation has
witnessed an explosive growth in recent years, with tremen-
dous advances being made both in terms of new reaction
discovery as well as mechanistic understanding. Two of the
major issues that have thwarted the development of asym-
metric alkene halogenations are the rapid stereochemical
degradation of chiral halonium ions by olefin-to-olefin
halenium transfer,[1] and isomerization of halonium ions to
the open b-halocarbenium ions.[2] Not surprisingly, most early
examples have reported on the intramolecular capture of
halonium ions via tethered nucleophiles;[3] the proximity-
driven rate enhancement of the cyclization step presumably
outcompetes any stereorandomizing events. Enantioselectiv-
ities of more than 95:5 are routinely obtained with a variety of
halenium precursors and nucleophiles.
afford poor or moderate levels of enantioselectivity at best.[8]
Third, substrate scope studies have been limited to electroni-
cally biased alkenes and hence possible regioselectivity issues
have remained unaddressed.[9] Finally, none of the catalytic
systems were demonstrated to be promiscuous enough to
allow for the use of different halenium sources and nucleo-
philes with the same substrates.
We sought to develop an enantioselective intermolecular
haloetherification reaction with the intention of both dem-
onstrating the feasibility of this unprecedented transforma-
tion as well as to address some of the limitations detailed
above. We report herein the enantio-, diastereo-, and
regioselective intermolecular haloetherification, haloesterifi-
cation and halohydrin synthesis of a variety of alkenes,
including those with no dominant bias for regioselectivity
(that is, alkenes with alkyl substituents).
In our prior work, we had demonstrated that the non-
nucleophilic CF3CH2OH was crucial for obtaining high yields
and enantioselectivities for intramolecular cyclization of allyl
amides,[3i] although traces of intermolecular incorporation of
CF3CH2OH were still observed in a few cases. Crucially, these
chloroether by-products were formed with exquisite dia-
stereo- and regioselectivity (see the Supporting Information,
Scheme S1 for an example). As such, this result represented
a good starting point for developing a practical and general
intermolecular chlorofunctionalization reaction of alkenes.
We chose the intermolecular reaction of E-1b-Br[10] with
a chlorenium source and MeOH as the test bed to optimize
the process. The p-bromobenzamide group was retained in
these orienting studies based on our prior results.[3i]
More recently, the development of enantioselective
intermolecular alkene halofunctionalization reactions has
come into focus.[4] A number of excellent reports have
shown a great deal of progress in this area.[4a,5] Intermolecular
aminohalogenation,[5b–e] haloesterifications,[5g,h,k] halohy-
drin[5l,6] synthesis, and dihalogenation[5i,m] have all been
reported.
Despite this progress, numerous shortcomings are appar-
ent. First, alcohols are yet to be demonstrated as viable
nucleophiles in this chemistry despite the success seen in halo-
cycloetherification reactions (Figure 1A and B).[7] Second,
substrates with alkyl substituents on the alkene are known to
[*] B. Soltanzadeh, Dr. R. J. Staples, Prof. Dr. B. Borhan
Department of Chemistry, Michigan State University
E. Lansing, MI 48824 (USA)
E-mail: babak@chemistry.msu.edu
Dr. A. Jaganathan
Engineering and Process Sciences, Core R&D
The Dow Chemical Company, Midland, MI 48674 (USA)
[**] We are grateful to the NSF (CHE-1362812) and NIH (GM110525)
for funding.
(DHQD)2PHAL
diether; 10 mol%) was employed as the catalyst along with
(hydroquinidine
1,4-phthalazinediyl
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201502341.
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Table 1: Orienting studies for the enantioselective intermolecular chloroetherification of E-1b-(Br/OMe/NO2).
Entry
Substrate
Solvent
Conc. [m]
Temp. [8C]
Yield [%][a]
ratio
d.r.
e.r.
e.r.
2b:3b[b]
(a-2b:s-2b)[b]
(2b)[c]
(3b)[c]
1
2
3
E-1b-Br
E-1b-Br
E-1b-Br
E-1b-Br
E-1b-OMe
E-1b-NO2
MeOH
MeOH
MeOH
MeOH/MeCN
MeOH/MeCN
MeOH/MeCN
0.03
0.03
0.01
0.01
0.01
0.01
24
À30
À30
À30
À30
À30
93
94
76
76
86
85
1.8:1
1.8:1
1.8:1
1.3:1
1.3:1
1.1:1
6.8:1
6.8:1
5.7:1
5.8:1
5.0:1
3.4:1
67:33
73:27
71:29
85:15
83:17
92:8
96:4
98:2
98:2
99:1
97:3
96:4
4[d]
5[d]
6[d]
[a] Combined yield of a-2b, s-2b, and 3b as determined by NMR analysis with MTBE as added external standard. [b] Determined by NMR spectroscopy.
[c] Determined by chiral-phase HPLC. [d] MeOH/MeCN ratio was 3:7.
2.0 equiv of 1,3-dichloro-5,5-dimethylhydantoin (DCDMH)
Table 2: Reaction optimization for aliphatic substrates.[a]
as the chlorenium source.[11] At ambient temperature both the
desired chloroether product a-2b-OMe-Br and the cyclized
product t-3b-Br were observed (93% combined yield) in
a 1.8:1 ratio. In line with our prior studies, the cyclized
product t-3b-Br had excellent enantioselectivity (96:4 e.r.),
whereas the desired product a-2b-OMe-Br exhibited a lower
67:33 e.r. Lower temperatures and lower concentration led to
slightly improved enantioselectivity for a-2b-OMe-Br while
not significantly improving the d.r. or the 2b:3b ratio
(Table 1, entries 2 and 3). Further experimentation revealed
Entry Substrate Temp [8C] Product
Yield [%][b]
e.r.[d]
that employing MeOH as a co-solvent in MeCN led to
a significant improvement in the enantioselectivity of a-2b-
OMe-Br (Table 1, entry 4).
1
2
3
E-1c-Br
À30 a-2c-OMe-Br
À30 a-2c-OMe-NO2
À30 s-2c-OMe-NO2
24 s-2c-OMe-NO2
À30 s-2c-OMe-NO2
92[c]
86
87
75
81:19
87:13
99.5:0.5
97:3
E-1c-NO2
Z-1c-NO2
Z-1c-NO2
Z-1c-NO2
Other studies focused on varying the expendable amide
moiety. While the 4-methoxybenzamide gave practically
identical results (Table 1, entry 5), the electron-deficient 4-
NO2-benzamide gave a significant improvement in the
enantioselectivity of a-2b-OMe-NO2 (92:8 e.r.; Table 1,
entry 6). As evident from these preliminary results, although
useful levels of enantioinduction was seen for the intermo-
lecular chloroetherification of E-1b-NO2, the d.r. (3.4:1) as
well the ratio of 2b:3b (ca. 1:1) were not ideal. Gratifyingly,
on replacing the aryl substituent on the alkene with an
aliphatic group, the desired intermolecular products were
obtained with near complete diastereo- and regioselectivity.
For example, the reaction of E-1b-Br, bearing n-C3H7 as the
alkene substituent, led to the production of a-2c-OMe-Br
with more than 99:1 d.r. and r.r. (Table 2, entry 1). More
importantly, a-2c-OMe-Br was formed in 92% yield and
81:19 e.r., and the formation of the cyclized product was
suppressed to a mere 5%. Employing the less nucleophilic 4-
NO2-benzamide in afforded exclusively a-2c-OMe-NO2
(Table 2, entry 2) in 86% yield, 87:13 e.r., more than 20:1
r.r., and more than 99:1 d.r.[12] cis-Allylic amides were even
better substrates for this chemistry as compared to the trans-
allylic amide counterparts. Substrate Z-1c-NO2 gave the
corresponding product s-2c-OMe-NO2 in 87% yield and
99.5:0.5 e.r. (Table 2, entry 3). Reactions that were run at
ambient temperatures or with lower catalyst loadings showed
4
5[e]
79
97:3
[a] The r.r. (defined as ratio of 2:5, see Table 4) was more than 20:1 and
d.r. was more than 99:1 in all instances. [b] Determined by NMR using
MTBE as added external standard. [c] 5% of cyclized product was also
seen by NMR. [d] Determined by chiral-phase HPLC. [e] 2 mol% catalyst
was used.
no loss in the diastereo- and regioselectivity and only a small
decrease in the enantioselectivity (97:3 e.r.; Table 2, entries 4
and 5). Nonetheless, the yields were lower (75–79%) owing to
the formation of side products arising from the competing
addition of MeCN across the alkene.[13]
In an effort to map out the generality of this trans-
formation, a number of trans-disubstituted allyl amides were
initially exposed to the optimized reaction conditions. Com-
pounds E-1b-NO2 and E-1d-NO2 (Table 3, entries 1 and 2)
with aryl substituents on the alkene gave moderate yields of
isolated product (due to competing chlorocyclization) and fair
diastereoselectivity for the corresponding products a-2b-
OMe-NO2 and a-2d-OMe-NO2 (56% and 64% yields,
respectively; ca. 3.3:1 d.r., mass balance in both cases was
the cyclized product; Table 3, entries 1 and 2). Nonetheless,
the chloroether products were formed with good enantiose-
lectivity. Trans substrates with alkyl substituents on the olefin
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Table 3: Substrate scope of intermolecular chloroetherification.
Entry
Starting material
R1
R2
Product
Yield [%][a]
d.r.
r.r.[b]
e.r.[c]
[e]
[e]
1
2
3
4
5
6
7
8
E-1b-NO2
E-1d-NO2
E-1c-NO2
E-1a-NO2
E-1e-NO2
Z-1b-NO2
Z-1 f-NO2
Z-1g-NO2
Z-1h-NO2
Z-1c-NO2
Z-1i-NO2
Z-1e-NO2
Z-1j-NO2
1k-NO2
Ph
pF-Ph
n-C3H7
CyHex
H
H
H
H
a-2b-OMe-NO2
56 (49)[d]
64 (58)[d]
86 (79)
70
3.4:1
3.3:1
>99:1
>99:1
>99:1
3.3:1
>99:1
>99:1
>20:1
>20:1
7:1
>99:1
>99:1
>99:1
>20:1
>20:1
>20:1
7:1
>20:1
na
>99:1
>99:1
>20:1
92:8
90:10
87:13
75:25
89:11
a-2d-OMe NO2
a-2c-OMe-NO2
a-2a-OMe-NO2
a-2e-OMe-NO2
s-2b-OMe-NO2
s-2 f-OMe-NO2
s-2g-OMe-NO2
s-2h-OMe-NO2
s-2c-OMe-NO2
s-2i-OMe-NO2
s-2e-OMe-NO2
s-2j-OMe-NO2
2k-OMe-NO2
BnOCH2
H
Ph
pMe-Ph
pMeO-Ph
C2H5
62 (57)
93 (82)[d]
87[d]
H
H
H
H
H
H
H
H
Me
Ph
H
H
99.5:0.5 (90:10)[f]
98:2 (97:3)[f]
99:1 (92:8)[f]
98:2
1.3:1
1:1
80[d]
9
83 (77)
87 (79) g
83 (74)
60 (53)
79
>99:1
>99:1
>99:1
>99:1
>99:1
na
6.2:1
1.2:1
>99:1
10
11
12
13
14
15 [h]
16 [h]
17 [h]
C3H7
99.5:0.5 (99.5:0.5)[g]
95:5
C5H11
BnOCH2
TBDPSOC2H4
Me
99.5:0.5
99.5:0.5
59 (53)
99:1
75:25
[e]
E-1b-NO2
Z-1 f-NO2
Z-1c-NO2
H
ent-a-2b-OMe-NO2
ent-s-2 f-OMe-NO2
ent-s-2c-OMe-NO2
42[d]
pMe-Ph
C3H7
82
69
99.5:0.5 (96:4)[f]
95:5
[a] Yield determined by NMR with MTBE as standard. Numbers in parentheses reflect yields of isolated product on a 0.1 mmol scale. [b] r.r.
(regioselectivity) is defined as ratio of 2:5, see Table 4. [c] Enantioselectivity determined by chiral-phase HPLC. [d] Combined yield of diastereomers,
Li2CO3 (15 equiv) was used as additive. [e] Mass balance was the cyclized product; [f] The e.r. values are for the minor diastereomer. [g] The result in
parenthesis is from a 1 g reaction scale, illustrating the scalability of the method. The corresponding Ritter product[13] (6%) was also isolated. [h] The
reactions in entries 15–17 were performed with the quasi enantiomeric (DHQ)2PHAL catalyst, yielding the enantiomeric product in each case.
(Table 3, entries 3–5) predictably gave products with exqui-
site levels of diastereo- and regioselectivity. Additionally, high
yield and e.r. was observed for a-2c-OMe-NO2 (R1 = n-C3H7).
The e.r. dropped significantly on introduction of the bulky
cyclohexyl group (see a-2a-OMe-NO2, 75:25 e.r.). The
benzyloxy substituted compound gave only moderate yields
and r.r. (62%, 7:1 r.r.), although the enantioselectivity was
good (see a-2e-OMe-NO2, 89:11 e.r.).
alcohols, carboxylic acids, and water may be employed as
viable nucleophiles in this chemistry with little or no
modification of the optimized reaction conditions. Replacing
MeOH with other alcohols such as ethanol, allyl alcohol, and
propargyl alcohol as the co-solvents cleanly afford the desired
products in more than 20:1 d.r. and more than 98:2 e.r. (see s-
2c-OEt-NO2, s-2c-OAllyl-NO2 and s-2c-OPropargyl-NO2 in
Scheme 1). These results demonstrate the feasibility of
introducing diverse functional handles into the products
using this chemistry, along with the highly stereoselective
Aryl-substituted Z-alkenes were exceptional substrates,
leading to the intermolecular product exclusively, in good
yields (73% to 80%), excellent regioselectivity (> 99:1 r.r.),
and high enantioselectivity (ꢀ 98:2 e.r.; Table 3, entries 6–8).
The diastereoselectivities for these entries, however, were
poor (ranging from 1:1 to 3.3:1), which was presumably due to
the increased carbocation character at the benzylic position.
Z-alkyl-substituted olefins afforded the desired products in
near complete regio-, diastereo-, and enantioselectivity
(Table 3, entries 9–13). Trisubstituted alkene 1k-NO2 pro-
vides the desired product in moderate yield and excellent
enantioselectivity (59%, 99:1 e.r.). The quasi-enantiomeric
catalyst, (DHQ)2PHAL, was also evaluated with four differ-
ent substrates, yielding the enantiomeric products in compa-
rable yields and selectivities (Table 3, entries 15–17, and last
entry in Scheme 1). The exception was the results with the
least successful category of substrates (trans-substituted
aryls), which does not mirror the (DHQD)2PHAL catalyzed
the reaction well (Table 3, entries 1 and 15), yielding products
with lower than expected enantioselectivity.
À
À
C Cl and C O bond installations during the course of the
reaction.
Acetic acid can be employed also as the nucleophilic co-
solvent to furnish the corresponding chloroacetates with
excellent enantioselectivity with Z-, E-, as well as trisubsti-
tuted alkene substrates (ꢀ 93:7 e.r., see s-2c-OAc-NO2, a-2c-
OAc-NO2, and 2k-OAc-NO2 in Scheme 1). Employing water
as the nucleophile leads directly to the corresponding chlor-
ohydrins in excellent yields and e.r. values (see s-2c-OH-NO2
and s-2h-OH-NO2 in Scheme 1). Finally, employing NBS in
lieu of DCDMH leads to the corresponding bromoether and
bromohydrin products in good yields and e.r. (see s-2c’-OMe-
NO2, s-2c’-OH-NO2, a-2c’-OH-NO2, and 2k’-OMe-NO2 in
Scheme 1). The quasi-enantiomeric (DHQ)2PHAL catalyst
gave practically identical results favoring the opposite enan-
tiomeric product (Scheme 1, ent-2k’-OMe-NO2). It warrants
emphasis that a large excess of the nucleophile (> 100 equiv) is
currently required to prevent predominant formation of
cyclized products. Our lab is currently in the process of
addressing this limitation to enable the use of highly function-
alized nucleophiles in this chemistry.
Finally, we sought to explore the scope of this reaction
with regards to the nucleophilic and electrophilic components
(Scheme 1). We were delighted to discover that a variety of
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A comparison of the non-catalyzed and catalyzed chlor-
oetherification of E-1c-NO2 and Z-1c-NO2 is illuminating
(Table 4). Meticulous characterization of the products of the
non-catalyzed reaction revealed a poor regioselectivity (3:1
and 4:1, respectively, for E-1c-NO2 and Z-1c-NO2) and only
a marginal preference for the intermolecular capture of the
putative chloriranium ion over the intramolecular capture by
the amide (ca. 3:2 for E-1c-NO2 and ca. 3:1 ratio for Z-1c-
NO2 substrates). Under catalyzed reaction conditions, how-
ever, the regioselectivity was superb for both E-1c-NO2 and
Z-1c-NO2 (> 20:1 r.r.). Additionally, the intermolecular
chloroetherification product was predominant in both instan-
ces (by a ratio of 10:1 and more than 99:1 respectively, for E-
1c-NO2 and Z-1c-NO2). These results underscore the exqui-
site levels of catalyst control in these reactions (see the
Supporting Information for HPLC traces of the crude
reaction mixtures). It is noteworthy that the diastereoselec-
tivity is > 99:1, even for non-catalyzed reactions. Two other
facts are highly significant to report. First, the face selectivity
in chlorenium delivery for the intramolecular process is the
same for both E and Z substrates (see the Supporting
Information, Figure S3 for chemical transformations).[12]
Second, surprisingly, the olefin face selectivity of chlorenium
transfer for the intramolecular process is opposite that of the
intermolecular reaction (Supporting Information, Figure S4).
These results lead us to conclude that two distinct mecha-
nisms are in play that leads to either the cyclized dihydroox-
azine products or the desired intermolecular addition of the
nucleophile and halenium ion across the alkene in the same
reaction.
Scheme 1. Nucleophile scope of intermolecular chlorofunctionalizatio-
n.[a,b] [a] The r.r. was more than 20:1 and d.r. was more than 99:1 in all
instances. [b] Yield determined by NMR with MTBE as standard.
Numbers in parentheses reflect yields of isolated products on
a 0.1 mmol scale. Enantioselectivity determined by chiral-phase HPLC.
[c] Reaction was run under nitrogen in the presence of molecular
sieves. [d] The ratio of MeCN:H2O was 9:1, reaction temperature was
À108C. [e] The results reflect a 1 g scale reaction. The corresponding
Ritter product (10%) was also isolated. [f] The prime symbol refers to
Br instead of Cl in the product. [g] Results with the quasi enantiomeric
(DHQ)2PHAL catalyst (ent-2k’-OMe-NO2 was the product).
A complete mechanistic picture that accounts for this
nucleophile-dependent stereodivergence is yet to emerge.
Nonetheless, we have recently demonstrated the importance
of the nucleophile in modulating the ease of chlorenium
capture by the alkene functionality by means of an anchimeric
assistance.[3ac] This aspect among others is currently being
looked into for explaining the observed stereoselectivity.
Keywords: chloroetherification · enantioselectivity ·
halogenation · organocatalysis · regioselectivity
Table 4: Demonstration of catalyst control in the intermolecular chloroetherification of allyl amides.[a]
Substrate
Catalyst
ratio
2c:5c:3c:4c
r.r.
ratio
d.r.
(s-2c:a-2c)
d.r.
(s-5c:a-5c)
d.r.
(s-4c:a-4c)
(2c:5c)[a]
(2c+5c):(3c+4c)
E-1c-NO2
E-1c-NO2
Z-1c-NO2
Z-1c-NO2
none
43:15:26:16
87:4:7:2
57:16:0:27
96:4:0:0
3:1
21:1
4:1
3:2
10:1
3:1
<1:99
<1:99
>99:1
>99:1
<1:99
<1:99
>99:1
>99:1
<1:99
<1:99
>99:1
>99:1
10% (DHQD)2PHAL
none
10% (DHQD)2PHAL
24:1
>99:1
[a] Regioselectivity (r.r.) and ratio of uncyclized to cyclized products was determined by HPLC.
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[8] For example, the best enantioselectivities seen for aliphatic
substrates in vicinal dihalogenation: 78:22 e.r. (Ref. [5i]);
haloesterification: 60:40 e.r. (Ref. [5k]); halohydrin synthesis:
84:16 e.r. (one example, Ref. [5l]).
[9] Where such substrates have been studied, the reason for poor
stereoselectivity and yields has not been established. For an
elegant description of the role of regioselectivity in eroding
enantioselectivity in vicinal dihalogenation, see Ref. [5i].
[10] We have opted to use a systematic naming system that enables
the reader to identify the relevant components of the starting
materials and products easily. Since all starting materials are
substituted allyl amides, they are defined as E or Z (where
appropriate), followed by a number (1a, 1b,…) that is unique to
the substitution on the olefin. The naming is completed by
defining the phenyl substituent of the amide moiety (NO2,
Br,…), which is always on the para position. The naming of the
intermolecular products precede by a or s (anti or syn), followed
by a number (2a, 2b,…) that corresponds to the substituent on
the parent olefin. The third component (in italics) is the identity
of the nucleophile (OMe, OH,…), followed by the substituent on
the phenyl group of the amide. The six-membered-ring intra-
molecular products are identified as either cis or trans (c or t),
followed by the number that corresponds to the substituent on
the parent olefin (3a, 3b,…), and then the identifier of the
phenyl substituent for the amide. The five-membered-ring
products are named as above, with the exception of having
a or s (anti or syn) that precedes the numbering (4a, 4b,…).
[11] See the Supporting Information for detailed DCDMH loading
studies and optimization of other variables.
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[12] The absolute stereochemistry of s-2h-OH-NO2 and s-2c-OMe-
NO2, and the relative stereochemistry of a-2c-OH-NO2, were
established by single-crystal X-ray diffraction. Since the absolute
Angew. Chem. Int. Ed. 2015, 54, 9517 –9522
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stereochemistry of a-2c-OH-NO2 could not be determined from
X-ray analysis, we resorted to the chemical transformations
detailed in the Supporting Information, Figure S3 for confirma-
tion of the structure. The absolute stereochemistry of the
following compounds was determined by single-crystal X-ray
diffraction (their corresponding Cambridge Structural Database
deposition numbers are provided following each compound
name). These are: s-4c-NO2 (1039232), s-2h-OH-NO2 (994564),
a-2c-OH-NO2 (1039233), s-2c’-OMe-NO2 (1039234), t-3c-NO2
(1039235), and s-2c-OMe-NO2 (994565).
[13] Structure of the “Ritter-type” addition product is depicted in the
Supporting Information (see 2c-NHAc-NO2). Solvents other
than MeCN were also evaluated as co-solvents; significantly
inferior results were obtained in all instances.
Received: March 14, 2015
Published online: June 25, 2015
9522
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Angew. Chem. Int. Ed. 2015, 54, 9517 –9522