Transamidation of: N -acyl-glutarimides with amines

Article abstract of DOI:10.1039/c7ob02874a

The development of new transamidation reactions for the synthesis of amides is an important and active area of research due to the central role of amide linkage in various fields of chemistry. Herein, we report a new method for transamidation of N-acyl-glutarimides with amines under mild, metal-free conditions that relies on amide bond twist to weaken amidic resonance. A wide range of amines and functional groups, including electrophilic substituents that would be problematic in metal-catalyzed protocols, are tolerated under the reaction conditions. Mechanistic experiments implicate the amide bond twist, thermodynamic stability of the tetrahedral intermediate and leaving group ability of glutarimide as factors controlling the reactivity of this process. The method further establishes the synthetic utility of N-acyl-glutarimides as bench-stable, twist-perpendicular, amide-based reagents in acyl-transfer reactions by a metal-free pathway. The origin of reactivity of N-acyl-glutarimides in metal-free and metal-catalyzed processes is discussed and compared.

Full text of DOI:10.1039/c7ob02874a

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PAPER
Transamidation of N-Acyl-Glutarimides with Amines
Yongmei Liu,a,b,† Marcel Achtenhagen,b,†,§ Ruzhang Liua and Michal Szostakb,*
Received 00th January 20xx,
Accepted 00th January 20xx
The development of new transamidation reactions for the synthesis of amides is an important and active area of research
due to the central role of amide linkage in various fields of chemistry. Herein, we report a new method for transamidation
of N-acyl-glutarimides with amines under mild, metal-free conditions that relies on amide bond twist to weaken amidic
resonance. A wide range of amines and functional groups, including electrophilic substituents that would be problematic
in metal-catalyzed protocols, are tolerated under the reaction conditions. Mechanistic experiments implicate the amide
bond twist, thermodynamic stability of the tetrahedral intermediate and leaving group ability of glutarimide as factors
controlling the reactivity of this process. The method further establishes the synthetic utility of N-acyl-glutarimides as
bench-stable, twist-perpendicular, amide-based reagents in acyl-transfer reactions by a metal-free pathway. The origin of
reactivity of N-acyl-glutarimides in metal-free and metal-catalyzed processes is discussed and compared.
DOI: 10.1039/x0xx00000x
www.rsc.org/
R1
O
O
N
H
1. Introduction
R2
2
R'
R2
R
N
R
N
New methods for constructing amide bonds are of
fundamental interest due to the central role of amide linkage
in various fields of chemistry, including drug discovery,
materials science and chemical manufacturing.1–3 In this
context, site-selective transamidation reactions under mild
conditions represent one of the most useful transformations in
organic synthesis (Fig. 1).4,5 However, these broadly applicable
processes suffer from the high stability of amide linkages due
1
3
R1
R''
R1
R'
H
R'
HO
R''
N
N
H
R''
R2
R2
N
nucleophilic
addition
R
N
thermodynamic
collapse
R1
Fig. 1 Proposed mechanism for metal-free transamidation.
to amidic resonance (Er
= 15-20 kcal/mol, nN→
π*
C=O
been established as the most reactive amide-based reagents in
transition-metal-catalyzed amide N–C bond activation12 owing
to three synergistic factors (Fig. 3): (1) perpendicular twist of
the amide bond (τ = 85.7°; χN = 5.6°
);13a,b (2) high stability of
conjugation, planar amides),6 and generally high temperatures,
long reaction times and metal-promoters are necessary.7
From a practical standpoint, metal-free transamidations
are vastly preferred due to high cost of metal catalysis,
problems associated with removal of toxic metal waste and
metal contamination of the amide products.8 Furthermore, the
development of chemoselective methods for amide formation
has had a continuous impact on organic synthesis, especially in
the context of pharmaceutical industry,9 wherein a number of
activating reagents and protocols for acylation of amines with
carboxylic acids has been developed over the past decades
(Fig. 2).10
the amide linkage under the reaction conditions; and (3) high
selectivity for the acyl N–C cleavage imparted by the activating
effect of the N-glutarimide substituent. Within this theme, our
laboratory has introduced N-acyl-glutarimides to accomplish a
range of acyl- and decarbonylative cross-coupling reactions
with exquisite selectivity using Pd, Ni and Rh catalysis (Suzuki-
Miyaura,14 Negishi,15 Heck,16 biaryl Suzuki,17 C–H arylation,18
cyanation,19 phosphorylation20) (Fig. 3). Mechanistic studies on
the effect of amide bond distortion demonstrated that N-acyl-
glutarimides contain the most distorted amide bond in any
amide derivative to date.13 More recently, Rueping et al.
reported elegant methods for Ni-catalyzed decarbonylative
Since the first report in 2015,11 N-acyl-glutarimides have
aCollege of Chemistry and Chemical Engineering, Yangzhou University, 180
Siwangting Road, Yangzhou 225002, China.
amination,21
reduction,22
alkynylation,23
cyanation,24
bDepartment of Chemistry,Rutgers University, 73 Warren Street, Newark, NJ 07102,
USA. E-mail: michal.szostak@rutgers.edu.
†These authors contributed equally.
silylation25 and borylation25 of N-acyl-glutarimides triggered by
amide distortion. A complementary approach was reported by
Han et al. on the Ni-catalyzed reductive coupling of N-acyl-
glutarimides,26 thus introducing the reductive manifold to the
area of amide bond coupling.27-29
§Present address: Department of Chemistry and Biochemistry, University of
Delaware, Newark, Delaware 19716, USA.
†Electronic Supplementary Information (ESI) available: Experimental details and
characterization data. See DOI: 10.1039/x0xx00000x
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Our laboratory has been interested in amide bond N–C
functionalization due to the pivotal role of amide linkages in
living organisms, and the untapped potential to exploit amide
bond destabilization as an enabling feature in organic
synthesis. We have demonstrated N-acyl-glutarimides in
metal-free Friedel-Crafts arylation and tandem transacylation
for the synthesis of anhydrides.32 We hypothesized that N-
acyl-glutarimides might be directly employed in synthetically
valuable transamidation reactions via nucleophilic addition
under mild, metal-free conditions that relies on twisting of the
amide bond to weaken amidic resonance (Fig. 1).35
Fig. 2 Selected amide bond coupling reagents.
The desired transamidation reaction was initially optimized
using N-benzoylglutarimide and benzylamine as model
substrates (Tables 1-3). Throughout the manuscript the new
amide bond formed is denoted in red colour, the N-acyl-
glutarimide bond is denoted in blue. This is justified by vastly
different properties of the amide bond in these compounds.
We
determined
that
transamidation
of
N-
benzoylglutarimide proceeds in excellent yield at room
temperature (Table 1, entry 6: Et3N, CH2Cl2, amine, 3.0 equiv).
The effect of amine and triethylamine stoichiometry on the
reaction is presented in Table 1. The stoichiometry of both
amine and triethylamine could be decreased to close to
equimolar ratio, however, at the expense of the reaction
efficiency (entry 1), while increasing the stoichiometry
improved the reactivity (entries 1-6). This is likely due to low
stability of the acylammonium species under the reaction
conditions. Importantly, the reaction showed good efficiency
at various temperatures (entries 7-8). Furthermore,
triethylamine could be omitted from the reaction set-up
altogether, albeit the product was formed in lower yield (entry
9). We note that under the optimized conditions, opening of
the glutarimide ring to give benzamide or the open-chain
transamidation product was not observed.10d
Fig. 3 N-Acyl-glutarimides in amide bond cross-coupling.
Important from the practical point of view, N-acyl-
glutarimides are bench-stable, crystalline solids that can be
routinely prepared from the corresponding acyl chlorides or
carboxylic acids in >80% yields on a gram scale.30 The high
stability of N-acyl-glutarimides, resulting from delocalization of
the Nlp into the carbonyl groups in the glutarimide ring,31
renders these reagents very attractive for applications in both
transition-metal catalysis and metal-free reactions,32 wherein
the reactivity is controlled by amide bond twist.33
As part of our interest in amide bond N–C
functionalization, herein, we describe a new method for
transamidation of N-acyl-glutarimides with amines under mild,
metal-free conditions that relies on amide bond twist to
weaken amidic resonance. The following features of our
findings are notable: (1) A wide range of amines and functional
groups, including electrophilic substituents that would be
problematic in metal-catalyzed protocols, are tolerated under
the reaction conditions. (2) Mechanistic experiments implicate
the amide bond twist, thermodynamic stability of the
tetrahedral intermediate and leaving group ability of
glutarimide as factors controlling the reactivity of this process.
(3) The method further establishes the synthetic utility of N-
acyl-glutarimides as bench-stable, twist-perpendicular, amide-
based reagents in acyl-transfer reactions by metal-free
pathway. Most importantly, this approach provides direct
access to a diverse range of amides by transamidation of
readily available N-acyl-glutarimides as novel acyl-transfer
reagents for amines in organic synthesis.1–7
The effect of solvent on the reaction is summarized in
Table 2. While, dichloromethane proved to be optimal (entry
1), other solvents, such as DMF (entry 2), THF (entry 4) and
DCE (entry 6), provided the transamidation product with
promising efficiency. While low conversion was observed
under aqueous conditions (entry 7), performing the reaction
under high dilution conditions (entry 8) resulted in a good
reactivity.35
Finally, among the bases tested, triethylamine was
identified as the optimal base (Table 3, entry 1), while pyridine
(entry 2), Hünig’s base (entry 3) and NaHCO3 gave lower
conversions but still afforded the desired product (cf.
background reaction, Table 1, entry 9).
Table 1 Development of transamidation of N-acyl-glutarimides with
amines: stoichiometry optimizationa
2. Results and discussion
2 | J. Name., 2012, 00, 1-3
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Amine
(x equiv)
1.1
1.1
1.5
1.5
2.0
3.0
3.0
Et3N
(y equiv)
1.0
3.0
2.0
3.0
2.0
3.0
3.0
Yield
(%)b
61
63
69
72
75
91
77
and secondary amines (3g-3n) (Table 4). We determined that
Entry
for more sterically-demanding amines (3b
catalytic DMAP 3b to facilitate the formation of
acylammonium,10b or increasing the reaction temperature to
80 C (3m) gives optimum results, presumably to facilitate
, 3m) addition of
1
2
3
4
5
(
)
°
nucleophilic addition of the amine. Furthermore, while the
very sterically-hindered tert-butylamine was ineffective under
standard conditions, we found that the reactivity could be
restored by increasing the electrophilicity of N-acyl-glutarimide
6
7c
8d
9
3.0
3.0
3.0
-
86
53
(
3f).36 Finally, we note that the very sterically-hindered di-
isopropylamine was unreactive under our reaction conditions
3o). In this case complete recovery of the staring material was
aConditions: amide (1.0 equiv), amine (x equiv), Et3N (y equiv),
CH2Cl2 (0.25 M), 23 °C, 15 h. Determined by H NMR and/or
GC, internal standard, nitromethane. c0 to 23°C. d80°C.
(
b
1
observed, which should prove useful in selective
transamidations with this class of amides.37
We next focused on the scope of N-acyl-glutarimides that
can participate in this protocol (Table 5). As expected, the
scope with respect to the amide substitution is also very
broad. Electron-poor (3p) and electron-rich (3q) substituents
on the aromatic ring are readily tolerated (see mechanistic
studies, Fig. 4). Importantly, this metal-free method tolerates
several functional groups that would be problematic using
Table 2 Development of transamidation of N-acyl-glutarimides with
amines: solvent optimizationa
Yield
Entry
Solvent
metal-catalysis, such as chloro
(3r) and bromo (
3s).7c,d
(%)b
91
47
26
52
42
72
<5
73
1
2
3
4
5
CH2Cl2
DMF
MeOH
THF
DME
DCE
Furthermore, fluorinated aromatics relevant from the
medicinal chemistry standpoint are competent substrates for
the reaction (3t).38 Other electrophilic functional groups, such
as esters (3u) are also tolerated on the amide component.
Finally, we were pleased to find that transamidation of
6
aliphatic N-acyl-glutarimides is also feasible
(
3v-3w).39
7c
8d
MeOH/H2O
CH2Cl2
Interestingly, N-acyl-glutarimides permit for selective
transamidation of aliphatic amides bearing primary and
aAmide (1.0 equiv), amine (3.0 equiv), Et3N (3.0 equiv), solvent
(0.25 M), 23 °C, 15 h. bDetermined by 1H NMR and/or GC,
internal standard, nitromethane c1:1 v/vol. d0.025 M.
secondary
α
while amides bearing
-carbon substituents by N-acyl cleavage (3v-3w),
-carbon tertiary substituents such as 3x
α
are recovered unchanged from the reaction conditions. This
unusual chemoselectivity (cf. Yamada amides)40 may lead to
chemoselective transamidations. Moreover, it should be noted
that while the substrate scope of these mild metal-free
conditions is broad, less nucleophilic amines, such as anilines,
are incompatible with the reaction conditions. In contrast,
anilines, including sterically-hindered examples, have been
shown to participate in metal-catalyzed Buchwald-Hartwig
acyl-type amination by N–C cleavage.7a,b This divergent
selectivity opens the door for the development of
chemoselective protocols for transamidation of non-planar
amides.
Table 3 Development of transamidation of N-acyl-glutarimides with
amines: base optimizationa
Yield
Entry
Base
(%)b
91
1
2
3
4
Et3N
Pyridine
DIPA
60
62
NaHCO3
47
aAmide (1.0 equiv), amine (3.0 equiv), base (3.0 equiv), CH2Cl2
(0.25 M), 23 °C, 15 h. bDetermined by 1H NMR and/or GC,
internal standard, nitromethane.
Table 4 Transamidation of N-acyl-glutarimides with amines: amine
scopea
With the optimized conditions in hand, the scope and
generality of this novel transamidation protocol was next
explored (Tables 4-5). As shown, N-acyl-glutarimides react with
a broad range of amines to afford synthetically valuable
amides in good to excellent yields. Importantly, the
transamidation accommodates simple alkyl (3a
-3b), benzyl
(
3c), allyl (3d), sterically-hindered α-branched amines (3d-3f),
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Table 5 Transamidation of N-acyl-glutarimides with amines: amide
scopea
Yield
(%)b
Entry
Amine
3
Product
1
2c
3
3a
61
75
91
81
63
3b
3c
3d
3e
Yield
(%)b
Entry
1
Amide (R)
3
Product
3p
66
80
88
94
84
86
4
2
3
4
5
6
3q
3r
3s
3t
3u
5
6d
3f
78
7
8
3g
3h
3i
95
91
98
90
94
95
9
7
8
9
3v
3w
3x
80
79
<5
10
11
12
3j
3k
3l
aConditions: amide (1.0 equiv), amine (3.0 equiv), Et3N (3.0
equiv), CH2Cl2 (0.25 M), 23 °C, 15 h. bIsolated yields. See ESI for
details.
13e
3m
90
A series of studies was performed to provide insight into
the reaction mechanism. Specifically, we sought to address the
role of amide bond twist in N-acyl-glutarimides as the driving
force for metal-free transamidation.
14
15
3n
3o
95
<5
(1)
transamidation of differently substituted aromatic amides with
benzylamine, showed a large positive Hammett-Brown ρ+
value of 1.43 (R2 = 0.94) (Fig. 4), which can be compared with
the
-value of 2.01 (R2 = 0.74). This suggests that resonance
A
Hammett
correlation
study, employing
-
aConditions: amide (1.0 equiv), amine (3.0 equiv), Et3N (3.0
ρ
equiv), CH2Cl2 (0.25 M), 23 °C, 15 h. bIsolated yields. DMAP
c
effects are involved in stabilization of the reactive center, and
that electron-deficient arenes are inherently more reactive
substrates, consistent with the relative electrophilicity of the
amide bond.
(0.20 equiv). d4-CF3-C6H4 amide. DMAP (1.0 equiv). eDCE, 80 °C.
(2) During the reaction development, we observed that the
reactivity was strongly dependent on the amine used. A series
of competition studies established the following relative order
of reactivity: pyrrolidine > n-BuNH2 > BnNH2 > Et2NH ≈ i-PrNH2
4 | J. Name., 2012, 00, 1-3
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> anisidine >> t-BuNH2 (Table 6). The observed reactivity is reactivity of N-acyl-glutarimides in metal-catalyzed N–C cross-
consistent with the relative basicity41 and steric hindrance of coupling,11-26 we conclude that the present metal-free
amine nucleophiles used in the reaction.
transamidation is controlled mainly by the thermodynamic
collapse of the tetrahedral intermediate (vs. kinetic activation
of the amide bond by twist and Nlp to glutarimide
conjugation).
Table
6 Transamidation of N-acyl-glutarimides with amines:
selectivity studies – effect of aminesa
Hammett Plot Analysis: Amides
1.0
CF3
0.5
H
Cl
0.0
-0.5
-1.0
-1.5
F
Entry
1
Amine
3
RVb
pKBH+
Me
3i
3.71
11.3
2
3
4
3a
3c
3h
2.50
1.0
10.6
9.3
y = 1.425x + 0.001, R2 = 0.938 (σ+
y = 2.006x - 0.233, R2 = 0.741 (
)
OMe
σ)
0.38
11.0
NH2
-0.8
-0.6
-0.4
-0.2
0.0
0.2
0.4
0.6
0.8
5
3y
0.05
5.4
σ+
MeO
6
7
3f
0.004
0.39
10.7
10.7
Fig. 4 Plot of log k vs. σ+ for transamidation of N-acyl-glutarimides
with PhCH2NH2: effects of substituents on aryl amide.
3e
(3) Hitchcock et al. reported an elegant study on the
synthesis and transamidation of N-acyl-succinimides.10c These
five-membered analogues of N-acyl-glutarimides contain much
aConditions: amide (1.0 equiv), amine (3.0 equiv), Et3N (3.0
b
equiv), CH2Cl2 (0.25 M), 23 °C, 15 h. Relative reactivity values
determined from product distribution by 1H NMR and/or GC of
crude reaction mixtures. RV = reactivity values vs. the
corresponding N-benzylbenzamide are shown.
less distorted amide bond (τ = 46.1°; χN = 9.5°), as a result of
decreased steric interactions between exo- and endo-cyclic
oxygens in the five-membered framework.13 As a consequence,
while N-acyl-succinimides have been routinely tested as
substrates in all N–C cross-coupling reactions, the reactivity of
these half-twisted amides is inferior to N-acyl-glutarimides in
metal-catalyzed protocols.11,12 However, succinimide is a much
better leaving group than glutarimide (pKa = 9.5 vs. pKa = 11.4,
also note phthalimide, pKa = 8.3).42 To address the role of twist
vs. leaving group ability, we established the relative order of
amine reactivity in transamidation using N-benzoyl-succinimde
as the electrophilic component (Table 7). Interestingly, we
found an excellent correlation between the reactivity of N-
acyl-glutarimides and N-acyl-succinimides. Furthermore, a plot
of log of relative reactivity of N-acyl-glutarimides vs. log of
Table
7 Transamidation of N-acyl-succinimides with amines:
selectivity studies – effect of aminesa
Entry
1
Amine
3
RVb
pKBH+
3i
6.81
11.3
2
3
4
3a
3c
3h
2.90
1.0
10.6
9.3
relative reactivity of N-acyl-succinimides gave
correlation with a slope of 0.93 (R2 = 0.99) (Fig. 5).
a linear
0.34
11.0
(4) To further explore the effect of twist on the
transamidation reactivity in N-acyl-glutarimides vs. N-acyl-
succinimides, a series of competition studies was conducted
(Table 8). As shown, we found that N-acyl-glutarimides are
significantly more selective acylating reagents than N-acyl-
succinimides, and this reactivity is consistent with the leaving
group ability in the transamidation reaction.43 It may be thus
expected that they are more selective for certain applications.
Thus, on the basis of these results and the well-established
NH2
5
3y
0.05
5.4
MeO
6
7
3f
0.003
0.36
10.7
10.7
3e
aConditions: amide (1.0 equiv), amine (3.0 equiv), Et3N (3.0
equiv), CH2Cl2 (0.25 M), 23 °C, 15 h. Relative reactivity values
b
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determined from product distribution by 1H NMR and/or GC of
crude reaction mixtures. RV = reactivity values vs. the
corresponding N-benzylbenzamide are shown.
applications in metal-free transformations. Furthermore, our
results support amine nucleophilicity as the driving force for
nucleophilic addition to the weakened amide bond. In both
cases, amide bond destabilization occurs by amide bond twist
and electronic nN
→
π* conjugation into the carbonyl groups
C=O
Plot of Amidation Selectivity 1a vs. 1k
1.0
of the activating ring.
pyrrolidine
0.5
n-BuNH2
0.0
BnNH2
Et2NH
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
i-PrNH2
anisidine
t-BuNH2
y = 0.932x - 0.058, R2 = 0.994
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
0.5
1.0
Fig. 6 Selectivity studies in transamidation of N-acyl-glutarimides
log(RV1k
)
and N-acyl-succinimides.
Fig. 5 Plot of log RV-glutarimide (Table 6) vs. log RV-succinimide
(Table 7) for transamidation with amines: effects of amines.
3. Conclusions
Table
8 Selectivity studies in the transamidation of N-acyl-
glutarimides and N-acyl-succinimides: effect of aminesa
In summary, through exploiting amide bond twist and
electronic activation, we have developed a new method for
transamidation of N-acyl-glutarimides with amines under mild,
metal-free conditions. The method tolerates a wide range of
amides and functional groups, including electrophilic
substituents that would be problematic in metal-catalyzed
protocols, delivering important amide products in good to
excellent yields. The high reactivity of N-acyl-glutarimides
relies on weakening of amidic resonance through steric and
electronic activation of the amide bond. Mechanistic studies
demonstrated amide bond weakening and thermodynamic
collapse of the tetrahedral intermediate as decisive factors
controlling the reactivity of this process. In a broader context,
the method further establishes the utility of N-acyl-
glutarimides as bench-stable, twist-perpendicular, amide-
based reagents in acyl-transfer reactions by a metal-free
pathway.
Entry
1
Amine
3
3B:3Ab
pKBH+
3i
54.7
11.3
2
3
4
3a
3c
3h
22.5
8.7
10.6
9.3
30.5
11.0
NH2
5
6
3y
3f
11.0
33.5
5.4
MeO
In the last two years, N-acyl-glutarimides have
spearheaded the development of novel metal-catalyzed acyl
and decarbonylative cross-coupling reactions by N–C
activation.11–26 The high stability, ready availability and
distortion-tuneable reactivity of perpendicularly twisted N-
acyl-glutarimides should enable the development of practical
protocols for other metal-free functionalizations in organic
synthesis. Studies in this direction are underway and will be
reported in due course.
10.7
aConditions: amide (2.0 equiv), amine (1.0 equiv), Et3N (3.0
equiv), CH2Cl2 (0.25 M), 23 °C, 15 h. Relative reactivity values
b
determined from product distribution by 1H NMR and/or GC of
crude reaction mixtures.
(5) Moreover, we found that O-nucleophiles such as alcohols
and water are ineffective as nucleophiles with both N-acyl-
glutarimides and N-acyl-succinimdes under the developed
conditions (Fig. 6). In this case, full recovery of amide starting
materials was observed. In contrast, bridged lactams, another
class of non-planar amides, are notorious to suffer from rapid
hydrolysis/alcoholysis.34 Thus, it is clear that despite the
Acknowledgements
Rutgers University and the NSF (CAREER CHE-1650766) are
gratefully acknowledged for support. Y.L. thanks for
a
scholarship from the Priority Academic Program Development
of Jiangsu Higher Education-Yangzhou University (BK2013016)
and the National Natural Science Foundation of China
significant twist, N-acyl-glutarimides (
13
succinimides (τ = 46.1°)
τ
are sufficiently robust for general
= 85.7°) and N-acyl-
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10 For excellent reviews, see: (a) Ref. 1c and 1f. For selected
examples, see: (b) Y. Liu, S. Shi, M. Achtenhagen, R. Liu and
M. Szostak, Org. Lett., 2017, 19, 1614; For an elegant study
on using N-acylsuccinimides, see: (c) C. A. Goodman, J. B.
Eagles, L. Rudahindwa, C. G. Hamaker and S. R. Hitchcock,
Synt. Commun., 2013, 43, 2155; See, also: (d) C. A. Goodman,
C. G. Hamaker and S. R. Hitchcock, Tetrahedron Lett., 2013,
54, 6012; (e) C. A. Goodman, E. M. Janci, O. Onwodi, C. C.
Simpson, C. G. Hamaker and S. R. Hitchcock, Tetrahedron
Lett., 2015, 56, 4468; (f) J. E. Taylor, M. D. Jones, J. M. J.
Williams and S. D. Bull, J. Org. Chem., 2012, 77, 2808, and
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11 (a) G. Meng and M. Szostak, Org. Lett., 2015, 17, 4364; (b) G.
Meng and M. Szostak, Org. Biomol. Chem., 2016, 14, 5690.
12 Reviews: (a) R. Takise, K. Muto and J. Yamaguchi, Chem. Soc.
Rev., 2017, 46, 5864; (b) G. Meng, S. Shi and M. Szostak,
Synlett, 2016, 27, 2530; (c) C. Liu and M. Szostak, Chem. Eur.
J., 2017, 23, 7157; (d) Y. Gao, C. L. Ji and X. Hong, Sci. China
Chem., 2017, 60, 1413.
(21472161). M.A. thanks the Chemistry Department (Rutgers
University) for a Summer Undergraduate Fellowship. The
Bruker 500 MHz spectrometer used in this study was
supported by NSF-MRI (CHE-1229030).
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