Emergence of Homochiral Benzene-1,3,5-tricarboxamide Helical Assemblies and Catalysts upon Addition of an Achiral Monomer

Article abstract of DOI:10.1021/jacs.9b13157

Chirality amplification refers to the ability of a small chiral bias to fully control the main chain helicity of polymers and assemblies. Further implementation of functional chirally amplified helices as switchable asymmetric catalysts, chiral sensors, a

Full text of DOI:10.1021/jacs.9b13157

Subscriber access provided by Karolinska Institutet, University Library
Article
Emergence of homochiral benzene-1,3,5-tricarboxamide helical
assemblies and catalysts upon addition of an achiral monomer
Yan Li, Ahmad Hammoud, Laurent Bouteiller, and Matthieu Raynal
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b13157 • Publication Date (Web): 02 Mar 2020
Downloaded from pubs.acs.org on March 2, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 14
Journal of the American Chemical Society
1
2
3
4
5
6
Emergence of homochiral benzene-1,3,5-tricarboxamide helical
assemblies and catalysts upon addition of an achiral monomer
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Yan Li, Ahmad Hammoud, Laurent Bouteiller and Matthieu Raynal*
Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, Equipe Chimie des Polymères, 4 Place Jussieu, 75005
Paris (France) e-mail: matthieu.raynal@upmc.fr.
Supporting Information Placeholder
triggered by a small chiral bias at the molecular level. This minute
conformational preference is usually too small to be directly
ABSTRACT: Chirality amplification refers to the ability of a small
chiral bias to fully control the main chain helicity of polymers and
assemblies. Further implementation of functional chirally-
amplified helices as switchable asymmetric catalysts, chiral
sensors and circularly-polarized light emitters will require a
greater control of the energetics governing these chirality
amplification effects. In this work, we report on the
counterintuitive ability of an achiral molecule to suppress
conformational defects in supramolecular helices thus leading to
the emergence of homochirality in a system containing a very
small chiral bias. We focus our investigation on supramolecular
helices composed of an achiral benzene-1,3,5-tricarboxamide
-1
measured (with extreme values as low as a few J.mol per repeat
6
unit in the case of chiral isotopic substitution) but induces a
conformational bias that is amplified through the whole
nanostructure and may eventually lead to the formation of
homochiral structures. Dynamic helical covalent and
supramolecular polymers are particularly prone to chirality
amplification as demonstrated by the diversity of scaffolds in
4
c
which these phenomena have been expressed. The ultra high
sensitivity to a variety of chiral inducers (e.g. monomers, additives,
solvents, physical fields) has motivated the implementation of
functional helical nanostructures as switchable asymmetric
(
BTA) ligand, coordinated to copper, and an enantiopure BTA co-
monomer. Amplification of chirality as probed by varying the
amount (sergeants-and-soldiers effect) or the optical purity
7
8
catalysts, chiral stationary phases and as optical devices able to
9
10
emit or selectively reflect circularly-polarized light.
Green, Selinger and co-workers provided the experimental and
theoretical basis of amplification of chirality in covalent
poly(isocyanate)s, i.e. a class of stiff polymers in which the
backbone adopts a stable but dynamic helical conformation in
(
diluted majority-rules effect) of the enantiopure co-monomer,
are modest in this initial system. However, both effects are hugely
enhanced upon addition of a second achiral BTA monomer leading
to a perfect control of the helicity either by means of a remarkably
low amount of sergeants (0.5%) or a small bias from a racemic
mixture of enantiopure co-monomers (10% e.e.). Such an
enhancement in the amplification of chirality is only achieved by
mixing the three components, i.e. the two achiral and the
enantiopure co-monomers, highlighting a synergistic effect upon
co-assembly of the three monomers. Investigation of the role of
the achiral additive by multifarious analytical techniques supports
its ability to stabilize the helical co-assemblies and suppress helix
reversals i.e. conformational defects. Implementation of these
helical copper precatalysts in the hydrosilylation of 1-(4-
nitrophenyl)ethanone confirms that the effect of the achiral BTA
additive is also operative under the conditions of the catalytic
experiment. A highly enantioenriched product (90% e.e.) is
produced by a supramolecular catalyst operating with ppm levels
of chiral species.
4
a
solution. These authors notably reported the possibility of
controlling the backbone helicity by: (i) introducing a small
amount of chiral monomers (sergeants) to copolymers mainly
constituted of achiral monomers (soldiers) through the so-called
11
sergeants-and-soldiers (S&S) effect, (ii) mixing enantiopure co-
monomers in a non-equimolar ratio through the majority-rules
1
2
(MR) effect and (iii) combining both effects, i.e. adding a non-
equimolar ratio of enantiopure monomers to achiral monomers
1
3
thus forming a terpolymer (diluted MR effect). For all these
cases, the chiral bias imparted by the sergeant or by the majority
enantiopure monomer is transferred to soldiers (S&S), the
minority enantiomer (MR) or both (diluted MR) which remain
under its influence in between two helix reversals. Following these
pioneering studies, similar effects have been observed for other
4
b,14
covalent helical polymers
polymers.
and for supramolecular
4c,5b
Extremely high levels of chirality amplification, by means of a small
15
amount of sergeants (≤ 1%), by a mixture of enantiopure
monomers only moderately biased from the racemic mixture
Introduction
1
5i,16
17
(≤10% e.e.),
mirror-symmetry breaking phenomena
by chiral physical fields or through spontaneous
Asymmetric amplification refers to a quite large variety of topics
in chemical sciences such as non-linear effects in asymmetric
9
,15i,17b,18
have been
reported for a limited number of helical assemblies in solution or
in the gel state. N,N′,N′′-trialkylbenzene-1,3,5-tricarboxamides
1
2
catalysis, racemization/deracemization processes and chiral
3
replicators that may ultimately constitute a basis to understand
(
alkyl BTA) and their functional derivatives are ubiquitous
the elusive omnipresence of homochirality on Earth. In addition,
amplification of chirality in helical covalent molecules and
supramolecular aggregates deals with controlling helicity,
expressed at the macromolecular or supramolecular level, but
synthons in supramolecular chemistry as a result of their robust
assembly into dynamic helices stabilized by a threefold hydrogen-
bond network and aromatic interactions. S&S and MR
4
5
1
9
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 14
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 1 Schematic representation of the concept. Supramolecular stacks are composed of a first soldier (green) and a low amount of
sergeants (blue) (I) or a mixture of enantiopure monomers slightly biased from the racemic mixture (II). The stacks consist of a nearly equal
amount of left and right-handed helical parts. Upon addition of a second soldier (orange), these helices become homochiral (III and IV).
This soldier acts as a “rigidifier” by stabilizing the helical co-assemblies and removing helix reversals as indicated by the helix reversal
penalty (HRP) values. This concept also applies for the construction of helical catalysts in which the first soldier bears a catalytic site.
chiral
BTA comonomers
H
N
O
H
NR
achiral BTA ligands
achiral BTA additive
Ar2P
Cu]
PAr2
H
O
[
N
O
R
H
NR
CO2C12H25
CO2C12H25
O
NH
O
H
NR
O
NH
O
*
H O
N
NH
H
C12H25O2C
Ar P
O
N
O
2
H
RN
H
*
H
O
O
N
O
[Cu]
H
N
C12H25O2C
O
HN
NR
H
C8H17
H
O
HN
O
HN
*
C12H25O2C
O
N
O
C8H17
R
H
NR
*
C12H25O2C
Ar = Ph, l1-BTA
Ar = 3,5-Me C H , l2-BTA
a-BTA
O
H O
2
6
3
NR
*
*
RN
*
= (S), (S)-BTA
O
c-BTA
*
= (R), (R)-BTA
n
Scheme 2 Left: chemical structures of the BTA monomers used in this study. Right: representation of the helical co-assemblies,
preferentially right-handed, formed by mixing l1-BTA, [Cu(OAc) ∙H O], (S)-BTA and a-BTA (S&S type mixture). For a tentative molecular
2
2
representation of the concept shown in Scheme 1 with BTA co-assemblies, see Chart S1b.
ACS Paragon Plus Environment

Page 3 of 14
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2 2
Figure 1 Chirality amplification through the S&S effect as probed by CD spectroscopy (293K, toluene), [Cu]= [Cu(OAc) ∙H O]. a) CD spectra
of mixtures without a-BTA ([l1-BTA]/[Cu]= 4, [l1-BTA]= 5.80±0.04 mM, 0.006≤ [(S)-BTA]≤ 6.35 mM). b) CD spectra of mixtures with a-BTA
[l1-BTA]/[Cu]= 4, [l1-BTA]= 5.82±0.06 mM, [a-BTA]= 5.80±0.06 mM, 0.006≤ [(S)-BTA]≤ 6.39 mM). The superior maximal ellipticity reached
(
for S&S mixtures with a-BTA is related to an increase of the intensity of the main UV-Vis absorption band (vide infra). c) Kuhn anisotropy
factor (g) measured at = 295 nm as a function of the fraction of (S)-BTA in the mixtures. g295= θ /(32980 × Abs ) where θ and Abs are
295
295
the ellipticity and UV absorbance measured at = 295 nm, respectively. fc-BTA= [c-BTA]/([c-BTA]+[l1-BTA]+[a-BTA]). The data have been
20
fitted for the mixtures with and without a-BTA (red and black solid lines, respectively) according to Smulders et al. (see text).
effects exist in BTA helices20-21 but are not exceptional and their
enhancement would clearly be beneficial for a range of chirality-
driven applications. Meijer and co-workers probed the limits of
chirality amplification in BTA helical assemblies and their studies
revealed that optimization by subtle variation in the structure of
the monomer will improve the extent of amplification but solely
up to the limits fixed by the number of reversals present in the
helix. As this latter parameter is intrinsically related to the
stability of the BTA assemblies, the authors suggested that further
improvement would require changing the chemical structure of
the monomers (and thus the nature of the helix). We report herein
that, albeit counterintuitive at first sight, the addition of an achiral
BTA monomer switches the configurational state of BTA co-
assemblies from poorly helically biased to single handed, thus
leading to the emergence of homochirality in supramolecular
systems embedding a very small chiral bias. The S&S and diluted
MR effects are improved by two orders and one order of
magnitude, respectively, which is attributed to the stabilization of
the co-assemblies and the suppression of the helix reversals in
presence of the achiral additive (see a representation of the
present concept in Scheme 1). Furthermore, the copper atoms
supported by these BTA helical assemblies serve as catalytic sites
providing a highly enantio-enriched alcohol (>90% e.e.) despite
catalytic loading in chiral species being at ppm levels.
Results
Chirality amplification probed by CD spectroscopy. We previously
found that the mixture composed of the BTA ligand, l1-BTA, and
the chiral BTA co-monomer, c-BTA (Scheme 2) yields very long
2
0
n
one-dimensional co-assemblies in solution (DP ≈250) with a
radius corresponding to a single molecule of BTA in the cross-
22
section. c-BTA belongs to the family of BTAs derived from amino-
15g,23
esters (ester BTAs)
which were shown to be efficient chiral
inducers for asymmetric reactions performed with helical BTA
22,24
catalysts.
In order to induce a sufficient bias in the handedness
of these co-assemblies, an excess of c-BTA was employed
22,24b
relatively to l1-BTA.
We have now investigated the possibility
of generating homochiral helices with a lower amount of
enantiopure co-monomer. Firstly, mixtures of l1-BTA and (S)-BTA
in toluene are analyzed by CD spectroscopy with the presence of
copper coordinated to the BTA ligand in order to be as close as
26
possible to the catalytic conditions we established previously.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 14
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2 2
Figure 2 Chirality amplification through the diluted MR effect as probed by CD spectroscopy (293 K, toluene), [Cu]= [Cu(OAc) ∙H O]. a) CD
spectra of mixtures without a-BTA ([l1-BTA]/[Cu]= 4, [l1-BTA]= 5.78±0.07 mM, -100% e.e.≤ c-BTA.≤ 100% e.e., fc-BTA= 0.53±0.02). b) CD
spectra of mixtures with a-BTA ([l1-BTA]/[Cu]= 4, [l1-BTA]= 5.80±0.04 mM, [a-BTA]= 6.40±0.40 mM, -100% e.e.≤ c-BTA.≤ 100% e.e., fc-BTA
.34±0.02). The superior maximal ellipticity reached for diluted MR mixtures with a-BTA is related to an increase of the intensity of the
=
0
main UV-Vis absorption band (vide infra). c) Kuhn anisotropy factor (g) measured at = 295 nm as a function of the optical purity of c-BTA
in the mixtures. The data have been fitted for the mixtures with and without a-BTA (red and black solid lines, respectively) according to
2
5
van Gestel (see text).
CD analyses of sergeants-and-soldiers (S&S) type mixtures, in
which l1-BTA coordinated to Cu and (S)-BTA are the soldiers and
the sergeants, respectively, are shown in Figure 1a ([l1-BTA] and
since the cyclohexyl group attached on the amino-ester -carbon
is expected to reduce the conformational freedom of the amide
functions and thus to rigidify the hydrogen-bonded network
2
8
[
2
Cu(OAc) ∙H
2
O] are set constant at 5.80±0.04 mM and 1.46±0.02
between the complementary monomers in the co-assemblies. A
mM, respectively). Mixtures with more than 0.5% of sergeants
exhibit a Cotton effect with a maximum at ≈ 295 nm while no CD
signal is detected for mixtures containing a lower amount of
sergeant. The observed Cotton effect constitutes a direct probe of
the extent of chirality induction in the co-assemblies since only the
new set of mixtures has been analyzed by CD which differs from
the initial one only by the fact that the mixtures now contain two
soldiers: l1-BTA coordinated to Cu and a-BTA ([l1-BTA]/[a-BTA]=
1). The influence of a-BTA on the amplitude of the S&S effect is
dramatic (Figure 1b). The CD spectrum of the mixture with only
0.5% of sergeant is virtually identical to that of the mixtures
containing higher fractions of enantiopure co-monomers. The S&S
mixture with only 0.25% of (S)-BTA displays a g value which is
22,24b,27
soldier is UV active in this region (induced CD).
Accordingly,
plotting the Kuhn anisotropy values (g) at = 295 nm as a function
of the fraction of (S)-BTA in these mixtures (f(S)-BTA) provides the
amplitude of the S&S effect operating in this system (Figure 1c).
Even though the plot deviates from linearity, no obvious plateau
of the g value is reached meaning that a sizable fraction of
enantiopure co-monomers (f(S)-BTA≥ 52%) is required to get fully
biased co-assemblies.
-4
equal to 90% of the maximal g value (│gmax│= 6.9 × 10 ). A similar
max value is reached for S&S mixtures with and without a-BTA
corroborating the formation of similar homochiral, preferentially
g
2
4b
right-handed,
co-assemblies but for drastically different
fractions of sergeants, f(S)-BTA= 0.5% and 52% respectively. The S&S
effect is thus enhanced by two orders of magnitude in the
presence of a-BTA.
We previously reported that incorporating 1% of an ester BTA was
enough to fully bias the handedness of (otherwise racemic) helical
assemblies
tricarboxamide.
formed
by
N,N’,N’’-tris(octyl)benzene-1,3,5-
We have investigated whether a similar effect is operative on co-
assemblies obtained by mixing soldiers and non-equimolar
amounts of enantiopure sergeants, i.e. for amplification of
chirality through the diluted majority-rules effect. Mixtures
containing l1-BTA coordinated to Cu and c-BTA of various optical
purities (-100% e.e.→100% e.e.) have been analyzed in absence
and presence of a-BTA (Figures 2a and 2b, respectively). Without
15g
We therefore hypothesize that the limited
amplification of chirality observed in the present system is related
to defects induced by l1-BTA coordinated to Cu, i.e. this monomer
behaves as a “poor soldier”. We thus test the possibility of
inducing a conformational change in the co-assemblies upon
addition of a second achiral BTA. We selected a-BTA (Scheme 2)
ACS Paragon Plus Environment

Page 5 of 14
Journal of the American Chemical Society
additive, a nonlinear increase of the g value is observed as a
bonded stacks as the exclusively detected species thus indicating
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
function of the optical purity in c-BTA but no plateau is reached
indicating that the amplification of chirality is modest (Figure 2c).
Again, the addition of a-BTA has a huge effect on the extent of
amplification of chirality since homochiral co-assemblies are
obtained for scalemic mixtures only slightly biased from the
racemic mixture (10% e.e.). The diluted MR effect is thus increased
by one order of magnitude in the presence of a-BTA. A modulation
in the relative proportion of the enantiomers of only 10% around
the racemic composition produces homochiral helices with
opposite handedness.
that both monomers co-assemble into the same helical
assemblies. Conversely, the FT-IR spectrum of the 1:1 mixture
between a-BTA and (S)-BTA is virtually identical to the weighted
average of the spectra of the individual components (Figure 3b).
Also, CD analyses of their binary mixtures in various molar ratios
(Figure S3) reveal a CD signal which is closely proportional to the
amount of (S)-BTA in the sample, thus indicating that no
amplification of chirality occurs. These observations strongly
suggest that a-BTA and (S)-BTA, when mixed together,
preferentially tend to self-sort into their own self-assemblies (self-
segregation) rather than mix into the same aggregates (co-
aggregation).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
In the previous experiments, the addition of a-BTA induces an
increase of the total BTA concentration. To demonstrate the
robustness of our data and discard a possible influence of the
concentration, we have performed similar S&S and diluted MR
type experiments in which the total concentration in BTA
monomers has been kept constant to 5.84±0.2 mM (Figure S1).
Even in these conditions, upon partial substitution of l1-BTA by a-
BTA, a plateau of g values is obtained for mixtures containing 0.5%
of sergeants (S&S mixtures) or a 10% e.e. scalemic mixture (diluted
MR mixtures) inferring a similar enhancement of the amplification
of chirality in the helical co-assemblies. It is remarkable that this
simple strategy allows to reach extremely high levels of chirality
amplification for both the S&S and diluted MR effects with the
same sergeant, which outperforms those obtained for helical
Finally, the nature of the co-assembly formed by mixing l1-BTA
coordinated to Cu, (S)-BTA and a-BTA has been precisely
determined. The FT-IR spectrum of the three-component mixture
totally differs from the FT-IR spectra of its individual components
since it mainly consists of single band in the N−H and C=O regions
-1
(Figure 3c). These bands with a maxima at = 3239 cm and =
-1
1640 cm are the signature of hydrogen-bonded amide functions
in well-defined helical BTA stacks. The experimental spectrum is
virtually identical to the one simulated in case of full co-assembly
of the 3 BTA partners meaning that, a large fraction (≥ 90%) of (S)-
BTA and a-BTA monomers are incorporated into the stacks
formed by l1-BTA. This is further supported by SANS analysis of a
2
0-21
-1
assemblies of BTA monomers reported to date.
similar mixture which shows a q dependence of the scattered
Assembly behavior of the BTA partners. In order to unravel the
role of a-BTA, we started by determining whether the presence of
the three monomers was necessary to observe high amplification
of chirality in our above-mentioned helical BTA systems. We have
thus firstly characterized the self-assembly of the different BTA
monomers. We previously reported that l1-BTA monomers
aggregate through a cooperative pathway to form hydrogen
intensity at low q values which is indicative of the presence of
cylindrical and rigid objects in C D (Figure 3d). The SANS data can
7
8
be fitted by making the assumption of a full incorporation of (S)-
BTA and a-BTA into the stacks of l1-BTA. The excellent fit of the
3
0
SANS data with the form factor for rigid rods of infinite length
confirms that the self-assemblies contain a single BTA molecule in
the cross-section (r= 12.1 Å, n= 0.81) and that, indeed, stacks are
the main contributor of the SANS intensity with only a low content
(if any) of (S)-BTA and a-BTA self-assemblies. This full set of
analyses offers a precise picture of the assembly behavior of the
different BTA monomers: the small assemblies formed by (S)-BTA
and a-BTA in which there is no or little implication of the amide
carbonyls rearrange in the presence of amide-bonded stacks of l1-
BTA to generate long helical co-assemblies, while they self-
segregate in its absence. The presence of the three BTA partners
thus appears to be crucial to generate rigid helical assemblies
whose handedness can be fully biased by the enantiopure co-
monomer.
Rationalization of the role of the achiral BTA additive. CD
analyses have revealed the ability of a-BTA to promote the
formation of homochiral helical assemblies when the fraction of
sergeant is ≥ 0.5% (or its optical purity is ≥ 10% e.e.). We first
compare the FT-IR analyses of the mixtures with and without a-
BTA (Figure S4b). Both spectra are very similar indicating that the
helical assemblies display a similar hydrogen bond network.
Importantly, in both cases the incorporation of (S)-BTA into the
stacks can be estimated to be superior to 90% which discards a
potential bias in the l1-BTA/(S)-BTA ratio in the helical co-
assemblies as a result of the presence of a-BTA (Figure S4a). Also,
structural parameters determined above for the assemblies with
a-BTA (r= 12.1 Å, n= 0.81, l> 120 nm) are similar to those
determined previously for assemblies without a-BTA (r= 11.4 Å, n
= 0.6, l> 100 nm) confirming that the achiral BTA additive does not
significantly alter the geometry of
bonded stacks, similar to the ones described for N,N’,N’’-
29
tris(methoxyethyl)benzene-1,3,5-tricarboxamide
and other
19
BTAs in the literature, above a critical concentration of ca.
.5×10 M in toluene (see the FT-IR and SANS signatures in Figure
3a and 3d respectively). In the same solvent, c-BTA assembles
-3
0
2
4b
under the form of dimers only, the structure of which was
2
3d
unambiguously determined and revealed by the presence of
hydrogen bonds between amide N-H and ester (instead of amide)
carbonyls (see the FT-IR and SANS signatures in Figure 3b and 3d
respectively). We have now studied the structure of the self-
assemblies formed by a-BTA by means of FT-IR and SANS analyses.
The FT-IR spectrum recorded in toluene at 1.0 mM, shows the
presence of three broad bands in the N−H region with maxima at
-1
-1
-1

≈ 3448 cm , = 3402 cm and = 3293 cm which are attributed
to free N−H, N−H bonded to ester C=O, and N−H (weakly) bonded
to amide C=O, respectively (Figure S2a). A similar pattern is
observed at 5.8 mM (Figures 3a and 3b), except that the free N−H
band has decreased in intensity and the two others have become
more intense meaning that a transition occurs between two
species. However, the low intensity of the scattered intensity
observed in SANS analyses of a-BTA at both 5.4 mM and 9.0 mM
indicates that small assemblies are the dominant species in C
Figures 3d and S2b).
7 8
D
(
After determining the self-assembly behavior of l1-BTA (stacks), c-
BTA (dimers) and a-BTA (small objects), we have investigated their
co-assembly capability by analyzing their respective binary
mixtures. A 1:1 mixture of l1-BTA coordinated to Cu and a-BTA
analyzed by FT-IR (Figure 3a) reveals the presence of hydrogen-
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 14
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 3 Characterization of the assemblies (293 K, [Cu]= [Cu(OAc)
of the N−H and C=O bands according to literature.
2
∙H
a) FT-IR spectra of a-BTA (5.8 mM), {l1-BTA (5.8 mM) + [Cu] (1.45 mM)} and their
1:1 mixture in toluene. Simulated spectra for no and full co-assembly. The simulated spectrum for full co-assembly was obtained by
2
O]). For FT-IR spectra: Zoom on the N−H and C=O regions. Assignment
15g,23c
2
3c
considering that all a-BTA monomers adopt the conformation of BTA Aib monomers in the co-assembled helical stacks (i.e. that they
have the same IR spectrum). The good agreement of this simulation with the experimental spectrum means that most of the BTA
monomers stack into helical co-assemblies (fraction≥ 90% by considering the measurement uncertainty). b) FT-IR spectra of (S)-BTA (5.8
mM), a-BTA (5.8 mM) and their 1:1 mixture in toluene. Simulated spectrum for no co-assembly. The good agreement of this simulation
with the experimental spectrum means that a-BTA and (S)-BTA self-sort into their own co-assemblies. c) FT-IR spectra of the mixtures {l1-
BTA (5.8 mM) + [Cu] (1.45 mM)} and {l1-BTA (5.8 mM) + [Cu] (1.45 mM) + (S)-BTA (0.58 mM, f(S)-BTA= 0.048) + a-BTA (5.8 mM)} in toluene.
Simulated spectra for no and full co-assembly. The good agreement of the former simulation with the experimental spectrum means that
most of the BTA monomers stack into helical co-assemblies (fraction≥ 90% by considering the measurement uncertainty). d) SANS analyses:
-1
-1
22
-1
-1
scattered intensity (cm ) normalized by the total BTA concentration (g.L ) for (S)-BTA (19.9 g.L , 17.0 mM), a-BTA (9.83 g.L , 9.0 mM),
-1
-1
-1
-1
l1-BTA (5.98 g.L , 8.6 mM) and of the mixture {l1-BTA (3.94 g.L , 5.7 mM) + [Cu] (0.29 g.L , 1.45 mM) + (S)-BTA (0.68 g.L , 0.58 mM, f(S)-
-1
7 8
BTA= 0.062) + a-BTA (3.26 g.L , 2.99 mM)} in C D . The SANS data of the mixture is fitted by the form factor for rigid rods of infinite length,
assuming that all BTA monomers are co-assembled into the rods.
the supramolecular helices.22 We thus attribute the synergistic
effect observed upon co-assembly of the three partners to a
conformational change induced by a-BTA upon its incorporation
into the helical co-assemblies. Closer examination of the FT-IR
spectra of the mixtures with and without a-BTA (Figure S4b)
reveals the following differences: i) the maximum of the N−H band
UV absorption band is narrower and its intensity is significantly
increased when a-BTA monomers are incorporated into the stacks
despite the fact that a-BTA self-assemblies barely absorb in that
region. A similar change in the intensity and shape of the
corresponding Cotton effect is also seen. These observations infer
the formation of a stronger and more regular intermolecular
hydrogen bond network when a-BTA is present in the helical BTA
co-assemblies. One can thus expect a difference in the stability of
the respective co-
-1
is shifted from 3248 to 3239 cm and ii) the amide I band is
narrower. Notable differences are also observed in the CD and UV-
Vis absorption spectra of the same mixtures (Figure S5). The main
ACS Paragon Plus Environment

Page 7 of 14
Journal of the American Chemical Society
-1
Table 1 Helix reversal penalty (HRP) and mismatch penalty (MMP) (both in kJ.mol ) determined by simultaneously fitting CD data of
Figures 1 and 2 following procedures described by Smulders et al. (for S&S) and by van Gestel (for diluted MR). Comparison with the
values obtained for selected helical systems in the literature (293 K).
2
0
25
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Helical systems
Opt. S&S(a) Opt. diluted MR(b)
HRP
MMP
l1-BTA∙Cu + (S)-BTA
without a-BTA
with a-BTA
≥52%
≥50% e.e.
10% e.e.
11.0±2.5
0.4±0.4
(this work)
0.5%
22.1±0.5
0.3±0.2
Alkyl BTA (reference21e
)
5%
≥30% e.e.
nr
12.6±2.0(c) 1.9±0.2(c)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Triphenylamine trisamide
0
.3%
20.5(d)
19.5(e)
1.0(d)
1
5h
(reference
)
Bisurea (references16a,34
)
nr
10% e.e.
0.05(e)
(
a) Minimum amount of sergeants required to get homochiral helices in S&S experiments. (b) Minimal optical purity in sergeant required
to get homochiral helices in diluted MR experiments. (c) Obtained by fitting independently S&S and MR experiments yielding a precise
value for the HRP and MMP, respectively [conditions: 2×10 M in MCH]. (d) Obtained by fitting the S&S experiment [conditions: 3×10 M
in MCH]. (e) Obtained by fitting simultaneously the helicity and stability data [conditions: 10 M in cyclohexane]. nr: not reported.
-5
-5
-3
assemblies. Indeed, precisely probing the assembly process by VT-
CD spectroscopy shows that helical assemblies with a-BTA are
more stable (by ca. 20 K) than those lacking a-BTA (Figure S6).
Additional support towards the stabilization of the helical co-
assemblies when a-BTA is present comes from the quantification
of the conformational defects in the supramolecular helices.
Amplification of chirality in dynamic supramolecular systems has
Asymmetric catalysts built on an extremely chirally-amplified
helical backbone. We previously found that helical co-assemblies
with an excess of (S)-BTA relatively to l1-BTA provided 1-(4-
nitrophenyl)ethanol (NPnol) with 54±2% e.e. when applied in the
copper-catalysed hydrosilylation of 1-(4-nitrophenyl)ethanone
22,24b
(NPnone) at 293 K (reaction scheme in Figure 4).
We now
probe whether the generation of homochiral helices in the
presence of a-BTA as determined by CD spectroscopy also holds
for catalytic mixtures. Except otherwise stated, catalytic
experiments are implemented at a concentration in [l1-BTA] of
2
5,31
been consistently modelled by statistical mechanics.
The
statistical model developed by van Gestel and its adaptation by
2
0,21e
Smulders et al.
were successfully applied to quantify
3
1a
energetic parameters governing chirality amplification in S&S,
MR and diluted MR effects. Its robustness was demonstrated
for various BTA monomers
aggregating disk-like molecules.
16.1 mM, a catalytic loading of 3.0 mol% in [Cu(OAc)
2 2
∙H O], with
3
1b
25
PhSiH acting both as an activator of the copper precatalyst and as
3
6
b,20,21c,21e,32
35
as well as other types of
In order to allow a
a reducing agent. For S&S-type catalytic mixtures without a-BTA,
the optical purity in NPnol increases non linearly with the fraction
of (S)-BTA present in the catalytic mixture (16 µM≤ [(S)-BTA]≤ 18.4
mM), but no plateau is reached (│e.e.max│= 57.6%, Figure 4a, black
curve). Conversely, in presence of a-BTA ([l1-BTA]/[a-BTA]= 1), a
plateau is reached with a concentration in (S)-BTA of 160 µM (f(S)-
BTA= 0.50%,│e.e.max│= 51.4%), and 98% of the plateau value is
achieved with only 80 µM of sergeant (f(S)-BTA= 0.25%, │e.e.│=
50.4% Figure 4a, red curve). This is in good agreement with the
minimal fraction of (S)-BTA required to get homochiral helices as
probed by CD spectroscopy. This drastic effect of a-BTA on the
selectivity is not related to a change in the total BTA concentration
since doubling the concentration in l1-BTA (without additive) has
no significant influence (compare blue and black curves in Figure
4a). In fact, a remarkable correlation is found between the
selectivity and the optical purity of the supramolecular helices as
shown by the similarity of their curves as a function of f(S)-BTA
(Figures 4b). It demonstrates that the enhancement of the
enantioselectivity observed at low f(S)-BTA values in presence of a-
BTA is related to its ability to promote the formation of
homochiral helices. The only discrepancy arises for mixtures
containing a higher fraction of (S)-BTA since the optimal
selectivities with and without additive slightly differ, 51.4% and
57.6% e.e., respectively, despite the respective helices being
homochiral. We assume that this gap is related to a slight
1
5h,32-33
comparison of the present system with those described in the
literature, we have fitted the CD data of Figures 1 and 2
simultaneously by following procedures described by Smulders et
20
25
al. (for S&S) and by van Gestel (for diluted MR). It allows
extracting two energetic parameters: the helix reversal penalty
(HRP) that corresponds to the energy needed to reverse the
handedness of the supramolecular helix and the mismatch penalty
(
MMP) which is the energy paid for incorporating a monomer in a
helix of its nonpreferred helicity. The quality of the fits for the CD
data allows us to obtain a precise set of values for helical co-
assemblies with and without a-BTA and to compare them with the
data published in the literature for other helical systems (Table 1).
Strikingly, the value of HRP doubles in the presence of a-BTA (from
-1
1
1.0 to 22.1 kJ.mol ) while the MMP value is not impacted. The
energetic values determined from the fit are actually “effective
25
HRP and MMP values” which likely reflects the average of the
values of each BTA partner in the co-assemblies. Even though an
achiral monomer may be anticipated to lower the helicity as it
2
5
exhibits no chiral preference, our data show that the effective
HRP value in the presence of a-BTA is actually very high and this is
possibly due to (i) a high conformational rigidity and (ii) the
formation of strong intermolecular interactions with the other
BTA monomers. Compared to previously reported BTA mixtures,
the better chirality amplification properties observed in the
2
difference in the conformation of the PPh moiety and the related
present system is likely related to its higher HRP value (Table
copper catalyst that modifies the energetics of the
enantiodiscriminating event without affecting the optical purity of
the helical main chain.
20,21e
1
).
BTA helices embedding a-BTA exhibit a similar extent of
15h
amplification of chirality than triphenylamine trisamide and
16a,34
bisurea
based assemblies which is well substantiated by their
remarkably close energetic parameters.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 14
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 4 Asymmetric catalysis with S&S- and diluted MR-type helical catalysts (293K). a) Enantioselectivity in NPnol (±1%) versus the
fraction of (S)-BTA in the catalytic mixtures with and without a-BTA. Conditions: see the reaction scheme and SI. b) Plot of the
enantioselectivity in NPnol and of the Kuhn anisotropy factor versus the fraction of (S)-BTA in the catalytic mixtures. c) Enantioselectivity
in NPnol (±1%) versus the optical purity in c-BTA in the catalytic mixtures with and without a-BTA. Conditions: see the reaction scheme
and SI. d) Plot of the enantioselectivity in NPnol and of the Kuhn anisotropy factor versus the optical purity in c-BTA in the catalytic mixtures.
Zoom on the scalemic mixtures biased in (R)-BTA. Conversion >99% was obtained for all catalytic experiments as determined by GC and H
NMR analyses. The optical purity was determined by GC analysis, e.e. are set as positive and negative when (S)-NPnol and (R)-NPnol are
1
the major enantiomers, respectively. Lines are guides for the eye.
The effect of the achiral BTA additive on the selectivity was also
probed for diluted MR-type catalytic mixtures ([c-BTA]= 18.4 mM).
Whilst reaching the optimal selectivity requires a significantly
optically-enriched mixture of BTA enantiomers in absence of a-
BTA (e.e. in c-BTA≥ 50% e.e., black curve in Figure 4c), a plateau is
reached with a 20% e.e. scalemic mixture in presence of a-BTA
(│e.e.max│= 51.7%, red curve). A mixture in c-BTA slightly biased
from the racemic mixture (10% e.e.) yields (S)-NPnol (+44.0% e.e.)
and (R)-NPnol (-42.4% e.e.) when (R)-BTA and (S)-BTA are the
major enantiomers, respectively. The degree of selectivity
provided by the catalyst is directly related to the optical purity of
the supramolecular helices probed by CD spectroscopy, excepting
that, again, homochiral helices with and without a-BTA provide
slightly different selectivities (51.6% and 57.0% e.e. respectively,
Figure 4d).
monomers. More specifically, the addition of a-BTA to the mixture
with as low as 80 µM of sergeant (f(S)-BTA= 0.25%) switches the state
of the helical catalyst from non selective (e.e.< 1%) to significantly
selective (−50.4% e.e., entries 1 and 2). The fraction of (S)-BTA
(relatively to l1-BTA, 0.5%) and its catalytic loading (relatively to
NPnone, 0.06 mol% i.e. 600 ppm) are ca. fifty times and equal,
respectively, to the higher chirally-amplified helical catalysts
2
4a,36
reported in the literature.
Optimization of the catalytic
system was pursued by changing the nature of the BTA ligand and
the reaction temperature. A BTA ligand with methyl groups at the
meta positions of the aromatic rings attached to the phosphorus
atom, l2-BTA (Scheme 2), displays higher selectivity than l1-BTA
(entry 3) at 293 K. Upon lowering the temperature to
200 K, the effect of a-BTA on the selectivity provided by l2-BTA is
remarkable. Indeed, the selectivity rises from <3% e.e. to −90%
The results obtained with S&S-type helical catalysts have been
further investigated (Table 2). Significant selectivities are found
for catalytic mixtures containing very low amounts of (S)-BTA
ACS Paragon Plus Environment

Page 9 of 14
Journal of the American Chemical Society
Table 2 Optimization of S&S-type helical catalysts.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1. [Cu(OAc)2•H2O] 4.0 mM
l1-BTA or l2-BTA 16.1 mM
[(S)-BTA] 80 µM
a-BTA 16.1 mM when present
PhSiH3
O
OH
toluene, 293 K or 200 K
O2N
2. HCl
O2N
NPnone
37 mM - 1096 mM
NPnol
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Catalytic loading in (S)-BTA= [(S)-BTA]/[NPnone]. Conversion >99% was obtained for all catalytic experiments. The optical purity of NPnol
was determined by GC analysis, e.e. are set as positive and negative when (S)-NPnol and (R)-NPnol are the major enantiomers, respectively.
(a) (R)-BTA was used instead of (S)-BTA.
frozen state. The kinetics involved in the formation of the selective
helical catalysts were probed by performing a set of catalytic
experiments as follows: NPnone, toluene, l1-BTA, [Cu(OAc)
S)-BTA (80 µM, f(S)-BTA= 0.25%) and a-BTA which acts as a
rigidifier” of the assembly were mixed at 293 K followed by, after
2
]∙H
2
O,
(
“
a given aging time, PhSiH
3
which triggers the catalytic reaction. No
selectivity is observed without the achiral additive under these
conditions. A significant level of selectivity (−29% e.e.) is achieved
when the components are aged for 1 minute prior to the catalytic
event (Figure 5, red curve). From then, the selectivity increases
slowly but steadily until reaching −50.6% e.e. when the
3
components are aged for 30 minutes before PhSiH addition. This
selectivity is almost identical (−50.4% e.e) to the one obtained
when a solution of the same partners is heated prior to catalysis
indicating that the same thermodynamic state is reached from
molecularly dissolved BTAs (heated solution) or from assembled
BTAs (room temperature solution). The dramatic effect of the
additive on the selectivity is efficiently probed by these
experiments since it occurs on a much longer time scale (30
minutes) than the catalytic reaction (< 2s). This effect can also
be probed by means of CD and UV-Vis spectroscopy. a-BTA was
2 2
added to a mixture of l1-BTA, [Cu(OAc) ]∙H O and (S)-BTA (f(S)-BTA=
0.25%) in toluene, the solution was stirred for 20 seconds and full
CD (Figure S7a) and UV-Vis (Figure S7b) spectra were recorded at
Figure 5 Kinetics related to the emergence of selectivity and
homochirality. Plot of the enantioselectivity in NPnol (red curve)
2
95
and of the g values (blue curve) versus aging time for the
mixture with f(S)-BTA= 0.25%. Conditions for catalysis: see Table S9.
Conditions for CD analyses: see Table S5. The empty red square
and the empty blue circle correspond to the enantioselectivity and
295
24b
the g .value, respectively, of a solution of identical composition
but heated to reflux prior to analysis.
e.e. allowing both enantiomers of NPnol to be obtained with high
levels of enantiopurity (entries 4-6). The extent of selectivity that
emerges from this system (∆e.e.= 87%) is higher than that
observed for the reference ligand l1-BTA (∆e.e.= 69%) under the
same conditions (Table S8). The system remains active at
remarkably low loadings in Cu and BTA (S)-Cha (0.38 mol% and 75
2
95
regular times (0−1825 s). The evolution of the g
values
extracted from these spectra (Figure 5, blue curve) as a function
of the time of mixing is similar to that of the catalyst selectivity
indicating that emergence of chirality and selectivity are
concomitant phenomena. Conversely, all recorded UV-Vis
absorption spectra are virtually identical and similar to the one of
the heated solution with the same composition (Figure S7b). This
might be explained by a fast incorporation of a-BTA into the stacks
followed by a slower disappearance of the helix reversals.
Previously, exchange rate between sergeants and soldiers from
their individual helical BTA assemblies was reported to occur on
ppm, respectively) at the cost of
a limited drop in
enantioselectivity (−74% e.e., entry 7). Further data on this
optimization study are compiled in Table S8.
Probing the dynamics of the formation of chirally-amplified
helices. It might be questioned whether the amplification of
chirality that emerges after the addition of the achiral BTA is
dynamic in nature i.e. whether it simply occurs upon mixing the
different partners or whether it results from a complex kinetically
2
1d,24b
the time scale of seconds.
The slower kinetics associated
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 14
with the formation of highly chirally-amplified helices likely
inducers relatively to the catalytically active species (S&S ratio)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
originates from the fact that in the present system the additive
triggers a set of conformational changes including the removal of
the helix reversal(s) which requires an important reorganization of
the monomers within the co-assemblies.
and to the substrate (catalytic loading in mol%) can be drastically
reduced. Ultimately, asymmetric helical catalysts which get rid of
chiral inducers have been reported with the limitations that
degree of enantioinduction is low (e.e.≤ 46%) and that the
4
3,44
configuration of the major enantiomer is left to chance.
In the
Discussion
present system, the enantioselectivity provided by the copper
centres is greatly affected by the incorporation of the achiral
additive into the S&S-type and diluted MR-type helical assemblies.
For mixtures with 0.5% of sergeant, a-BTA switches the state of
the copper catalysts from non selective (< 3% e.e.) to selective (up
to 90% e.e.) and this can be directly related to the generation of
homochiral helices in which all copper centres are positioned in a
similar chirally biased environment. The co-assembly process
leading to the formation of the helical catalysts is under
thermodynamic control leading to excellent reproducibility of the
catalytic results and control of the configuration of the enantio-
enriched product by the nature of the sergeant. Both enantiomers
are accessed in highly enantio-enriched form (90% e.e.) with 600
ppm of sergeants (relatively to NPnone) and significant
enantioselectivity (74% e.e.) is still obtained with only 75 ppm of
sergeants. Long-range chiral information transfer in these helical
catalysts allows chirality inducers to be employed at drastically
lower amount than the catalytic sites thus offering a strategy that
circumvent the selectivity – activity paradigm, i.e. it paves the way
towards a new class of active asymmetric catalysts which operate
The importance of helix reversals in controlling the optical purity
of poly(isocyanate)s in dilute solutions had been recognized from
6
a
the seminal work of Green and co-workers. A steep increase in
the optical activity of an alkane solution of a S&S-type
poly(isocyanate) copolymer upon lowering the temperature was
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
6
a,37
attributed to a reduction of the helix reversal population.
Not
surprisingly, helix reversals also play a key role in determining the
extent of amplification of chirality in dynamic supramolecular
16a,20,21c,21e,25,31,33a
helices.
have
gels
Extremely high levels of amplification
been
reported
for
molecular
helices
in
1
5b,15e,15f,15i,16b,17f,18b,18c
38
and in liquid crystalline states or for
1
4f
one-dimensional assembly of covalent helices. It was surmised
that defects present in isolated helical chains would be excluded
6
a
upon interactions of the chains. Chirality amplification is
expected to be greater when both the HRP and the length of the
3
3
helices are large. However, few studies have addressed the
possibility of tuning the number of helix reversals in
15h,20,21e,32,33d,39
supramolecular systems,
mostly because
a
significant alteration would require changing the nature of the
3
b,45
20
at ppm levels of chiral species.
interactions governing the assemblies.
In the present system, amplification of chirality occurs in isolated
BTA helices for which the helix reversals are excluded upon
incorporation of the achiral BTA monomer. Comparison of
spectroscopic and scattering analyses with and without this BTA
additive are consistent with no or limited modification of the
geometry of the helices at the nm scale but subtle changes in the
Conclusion
In conclusion, we disclose the ability of an achiral BTA monomer
to fully bias the helicity of co-assemblies that are otherwise almost
racemic in its absence, and which contain as little as 0.5% of
sergeants (S&S effect) or a 10% e.e. scalemic mixture of
enantiopure co-monomers (diluted MR effect). This strategy,
albeit counterintuitive at first sight, improves both the S&S and
the diluted MR effect by two orders and one order of magnitude,
respectively, thus reaching levels of chirality amplification that
have been achieved by the best supramolecular single helices
reported to date. Precise investigation of the assembly behavior
of the different BTA partners by multifarious analytical techniques
reveals that each monomer plays a precise role towards the
generation of homochiral co-assembly: the BTA ligand forms long
but racemic and disordered stacks that favor the co-assembly of
the other BTA monomers, the enantiopure co-monomer imposes
a preferred-helical conformation to the BTA assemblies and finally
the achiral BTA additive reduces the number of defects in the co-
assembly. The last point is reflected by the higher stability of the
helices incorporating the achiral additive. The helical catalysts
generated from these homochiral co-assemblies display
significant selectivities (up to 90% e.e.) despite the limited amount
of sergeant (ppm levels relatively to the substrate) or low optical
purity of the sergeant (10−20% e.e.) present in the catalytic
mixture. Further work is directed towards further control of the
microstructure of supramolecular co-assemblies in order to get
structurally-complex multicomponent systems with increased
2
conformation of the amide functions and the PPh group are
detected which can be attributed to a more regular organization
of the monomers within the stacks in presence of the additive.
40
21d
Previous rheological and spectroscopic studies demonstrated
that homochiral BTA helical assemblies possess increased
correlation lengths (i.e. distance between defects/helix reversals)
and increased stability relatively to racemic mixtures of BTAs. The
stabilization of the helices incorporating a-BTA as determined by
VT-CD experiments (Figure S6) goes along this line except that
here the decreased number of defects is triggered by an achiral
monomer, not an enantiopure one. The relatively slow kinetics
associated with the emergence of homochirality can thus be
attributed to a series of conformational changes and monomer
reorganization within the stacks that are necessary for this
exclusion of the helix reversals. Compared to other amino acids,
quaternary amino acids (such as Aib, aminoisobutyric acid)


severely restrict the possible rotation about the N-C and C -C’
bonds and, as a consequence, promote helical conformation in
41
relatively short peptide sequences. We hypothesize that a-BTA
which also possesses an ,-dialkylated Aib type moiety has a
similar effect in restricting the conformation of the hydrogen-
bonded amide functions thus preventing the formation of the
defects in the supramolecular helical assemblies.
4
6
dynamicity and emerging functionalities.
Introducing intrinsically achiral catalytic monomers into the
preferred-handed helical scaffold of covalent or supramolecular
polymers enables the formation of an enantio-enriched product
whose configuration is determined solely by the handedness of
ASSOCIATED CONTENT
Supporting Information
7
,24,36,42
the helices.
A particularly remarkable advantage of such a
The Supporting Information is available free of charge on the ACS
Publications website.
catalytic system is that catalytic activity and selectivity arise from
different chemical species and, consequently, the amount of chiral
ACS Paragon Plus Environment

Page 11 of 14
Journal of the American Chemical Society
Chart S1, Figures S1-S7, Tables S1-S9, General procedures, Chiral
GC analyses, Synthetic procedures and NMR spectra. (PDF)
Thin Films of Helical Polymer Blends. Angew. Chem. Int. Ed. 2016, 55, 7126-
7130.
11) Green, M. M.; Reidy, M. P.; Johnson, R. J.; Darling, G.; Oleary, D. J.;
Willson, G.: Macromolecular Stereochemistry - the out-of-Proportion
Influence of Optically-Active Co-Monomers on the Conformational
Characteristics of Polyisocyanates - the Sergeants and Soldiers Experiment.
J. Am. Chem. Soc. 1989, 111, 6452-6454.
(12) Green, M. M.; Garetz, B. A.; Munoz, B.; Chang, H. P.; Hoke, S.; Cooks,
R. G.: Majority Rules in the Copolymerization of Mirror-Image Isomers. J.
Am. Chem. Soc. 1995, 117, 4181-4182.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
AUTHOR INFORMATION
Corresponding Author
*
matthieu.raynal@upmc.fr.
Author Contributions
(
13) a) Selinger, J. V.; Selinger, R. L. B.: Cooperative chiral order in
polyisocyanates: New statistical problems. Macromolecules 1998, 31,
488-2492; b) Jha, S. K.; Cheon, K. S.; Green, M. M.; Selinger, J. V.: Chiral
The manuscript was written through contributions of all authors.
All authors have given approval to the final version of the
manuscript.
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
optical properties of a helical polymer synthesized from nearly racemic
chiral monomers highly diluted with achiral monomers. J. Am. Chem. Soc.
Notes
The authors declare no competing financial interests.
1
999, 121, 1665-1673.
(14) a) Nagata, Y.; Yamada, T.; Adachi, T.; Akai, Y.; Yamamoto, T.;
Suginome, M.: Solvent-Dependent Switch of Helical Main-Chain Chirality
in Sergeants-and-Soldiers-Type Poly(quinoxaline-2,3-diyl)s: Effect of the
Position and Structures of the “Sergeant” Chiral Units on the Screw-Sense
Induction. J. Am. Chem. Soc. 2013, 135, 10104-10113; b) Maeda, K.;
Wakasone, S.; Shimomura, K.; Ikai, T.; Kanoh, S.: Chiral Amplification in
Polymer Brushes Consisting of Dynamic Helical Polymer Chains through
the Long-Range Communication of Stereochemical Information.
Macromolecules 2014, 47, 6540-6546; c) Bergueiro, J.; Freire, F.; Wendler,
E. P.; Seco, J. M.; Quiñoá, E.; Riguera, R.: The ON/OFF switching by metal
ions of the “Sergeants and Soldiers” chiral amplification effect on helical
ACKNOWLEDGMENT
This work was supported by the China Scholarship Council (CSC,
PhD grant of Y. L.) and by the French Agence Nationale de la
Recherche (project ANR-17-CE07-0002 AbsoluCat). Nicolas
Vanthuyne (iSm2, Aix-Marseille Université) is acknowledged for
performing preparative chiral HPLC. Jacques Jestin (LLB, Saclay) is
acknowledged for assistance with SANS experiment.
REFERENCES
poly(phenylacetylene)s. Chem. Sci. 2014, 5, 2170-2176;
d)
(1) a) Noyori, R.; Kitamura, M.: Enantioselective Addition of
Organometallic Reagents to Carbonyl-Compounds - Chirality Transfer,
Multiplication, and Amplification. Angew. Chem. Int. Ed. Engl. 1991, 30, 49-
Maeda, K.; Hirose, D.; Okoshi, N.; Shimomura, K.; Wada, Y.; Ikai, T.; Kanoh,
S.; Yashima, E.: Direct Detection of Hardly Detectable Hidden Chirality of
Hydrocarbons and Deuterated Isotopomers by a Helical Polyacetylene
through Chiral Amplification and Memory. J. Am. Chem. Soc. 2018, 140,
3270-3276; e) Ishidate, R.; Markvoort, A. J.; Maeda, K.; Yashima, E.:
Unexpectedly Strong Chiral Amplification of Chiral/Achiral and
Chiral/Chiral Copolymers of Biphenylylacetylenes and Further
Enhancement/Inversion and Memory of the Macromolecular Helicity. J.
Am. Chem. Soc. 2019, 141, 7605-7614; f) Ikai, T.; Okubo, M.; Wada, Y.:
Helical Assemblies of One-Dimensional Supramolecular Polymers
Composed of Helical Macromolecules: Generation of Circularly Polarized
Light Using an Infinitesimal Chiral Source. J. Am. Chem. Soc. 2020, 142,
3254-3261.
(15) a) Brunsfeld, L.; Lohmeijer, B. G. G.; Vekemans, J. A. J. M.; Meijer, E.
W.: Amplification of chirality in helical supramolecular columns. J. Incl.
Phenom. Macro. 2001, 41, 61-64; b) Haino, T.; Tanaka, M.; Fukazawa, Y.:
Self-assembly of tris(phenylisoxazolyl) benzene and its asymmetric
induction of supramolecular chirality. Chem. Commun. 2008, 468-470; c)
Nam, S. R.; Lee, H. Y.; Hong, J. I.: Control of macroscopic helicity by using
the sergeants-and-soldiers principle in organogels. Chem. Eur. J. 2008, 14,
6040-6043; d) Ishi-i, T.; Kuwahara, R.; Takata, A.; Jeong, Y.; Sakurai, K.;
Mataka, S.: An enantiomeric nanoscale architecture obtained from a
pseudoenantiomeric aggregate: Covalent fixation of helical chirality
formed in self-assembled discotic triazine triamides by chiral amplification.
Chem. Eur. J. 2006, 12, 763-776;e) Tanaka, M.; Ikeda, T.; Mack, J.;
Kobayashi, N.; Haino, T.: Self-Assembly and Gelation Behavior of
Tris(phenylisoxazolyl)benzenes. J. Org. Chem. 2011, 76, 5082-5091; f) Cao,
H.; Yuan, Q. Z.; Zhu, X. F.; Zhao, Y. P.; Liu, M. H.: Hierarchical Self-Assembly
of Achiral Amino Acid Derivatives into Dendritic Chiral Nanotwists.
Langmuir 2012, 28, 15410-15417; g) Desmarchelier, A.; Raynal, M.;
Brocorens, P.; Vanthuyne, N.; Bouteiller, L.: Revisiting the assembly of
amino ester-based benzene-1,3,5-tricarboxamides: chiral rods in solution.
Chem Commun 2015, 51, 7397-7400; h) Kim, T.; Mori, T.; Aida, T.;
Miyajima, D.: Dynamic propeller conformation for the unprecedentedly
high degree of chiral amplification of supramolecular helices. Chem. Sci.
2016, 7, 6689-6694; i) Karunakaran, S. C.; Cafferty, B. J.; Weigert-Munoz,
A.; Schuster, G. B.; Hud, N. V.: Spontaneous Symmetry Breaking in the
Formation of Supramolecular Polymers: Implications for the Origin of
Biological Homochirality. Angew. Chem. Int. Ed. 2019, 58, 1453-1457.
(16) a) Isare, B.; Linares, M.; Zargarian, L.; Fermandjian, S.; Miura, M.;
Motohashi, S.; Vanthuyne, N.; Lazzaroni, R.; Bouteiller, L.: Chirality in
Dynamic Supramolecular Nanotubes Induced by a Chiral Solvent. Chem.
Eur. J. 2010, 16, 173-177; b) Cao, H.; Zhu, X. F.; Liu, M. H.: Self-Assembly of
6
9; b) Satyanarayana, T.; Abraham, S.; Kagan, H. B.: Nonlinear Effects In
Asymmetric Catalysis. Angew. Chem. Int. Ed. 2009, 48, 456-494.
(2) Palmans, A. R. A.: Deracemisations under kinetic and thermodynamic
control. Mol. Syst. Des. Eng. 2017, 2, 34-46.
(
3) a) Storch, G.; Trapp, O.: By-design enantioselective self-amplification
based on non-covalent product-catalyst interactions. Nat. Chem. 2017, 9,
79-187; b) Soai, K.; Kawasaki, T.; Matsumoto, A.: Asymmetric
1
Autocatalysis of Pyrimidyl Alkanol and Its Application to the Study on the
Origin of Homochirality. Acc. Chem. Res. 2014, 47, 3643-3654.
(4) a) Green, M. M.; Park, J. W.; Sato, T.; Teramoto, A.; Lifson, S.; Selinger,
R. L. B.; Selinger, J. V.: The macromolecular route to chiral amplification.
Angew. Chem. Int. Ed. 1999, 38, 3139-3154; b) Yashima, E.; Maeda, K.; Iida,
H.; Furusho, Y.; Nagai, K.: Helical Polymers: Synthesis, Structures, and
Functions. Chem. Rev. 2009, 109, 6102-6211; c) Yashima, E.; Ousaka, N.;
Taura, D.; Shimomura, K.; Ikai, T.; Maeda, K.: Supramolecular Helical
Systems: Helical Assemblies of Small Molecules, Foldamers, and Polymers
with Chiral Amplification and Their Functions. Chem. Rev. 2016, 116,
1
3752-13990.
(5) a) Prins, L. J.; Timmerman, P.; Reinhoudt, D. N.: Amplification of
Chirality: The “Sergeants and Soldiers” Principle Applied to Dynamic
Hydrogen-Bonded Assemblies. J. Am. Chem. Soc. 2001, 123, 10153-10163;
b) Palmans, A. R. A.; Meijer, E. W.: Amplification of chirality in dynamic
supramolecular aggregates. Angew. Chem. Int. Ed. 2007, 46, 8948-8968.
(6) a) Green, M. M.; Peterson, N. C.; Sato, T.; Teramoto, A.; Cook, R.; Lifson,
S.: A Helical Polymer with a Cooperative Response to Chiral Information.
Science 1995, 268, 1860-1866; b) Cantekin, S.; Balkenende, D. W. R.;
Smulders, M. M. J.; Palmans, A. R. A.; Meijer, E. W.: The effect of isotopic
substitution on the chirality of a self-assembled helix. Nat. Chem. 2011, 3,
4
2-46.
(7) Li, Y.; Bouteiller, L.; Raynal, M.: Catalysts Supported by Homochiral
Molecular Helices: New Concept to Implement Asymmetric
Amplification in Catalytic Science. ChemCatChem 2019, 11, 5212-5226.
8) Shimomura, K.; Ikai, T.; Kanoh, S.; Yashima, E.; Maeda, K.: Switchable
A
(
enantioseparation based on macromolecular memory of
a helical
polyacetylene in the solid state. Nat. Chem. 2014, 6, 429-434.
(9) Shen, Z. C.; Wang, T. Y.; Shi, L.; Tang, Z. Y.; Liu, M. H.: Strong circularly
polarized luminescence from the supramolecular gels of an achiral gelator:
tunable intensity and handedness. Chem. Sci. 2015, 6, 4267-4272.
(
(
10) Nagata, Y.; Uno, M.; Suginome, M.: Three-Way-Switchable
Right/Left/OFF) Selective Reflection of Circularly Polarized Light on Solid
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 12 of 14
Racemic Alanine Derivatives: Unexpected Chiral Twist and Enhanced
Capacity for the Discrimination of Chiral Species. Angew. Chem. Int. Ed.
013, 52, 4122-4126.
17) a) El-Hachemi, Z.; Arteaga, O.; Canillas, A.; Crusats, J.; Escudero, C.;
Kuroda, R.; Harada, T.; Rosa, M.; Ribó, J. M.: On the mechano-chiral effect
of vortical flows on the dichroic spectra of 5-phenyl-10,15,20-tris(4-
sulfonatophenyl)porphyrin J-aggregates. Chem. Eur. J. 2008, 14, 6438-
L.; Troufflard, C.; Tessier, M.; Vanthuyne, N.; Ide, J.; Maistriaux, T.;
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Beljonne, D.; Brocorens, P.; Lazzaroni, R.; Raynal, M.; Bouteiller, L.: Tuning
the nature and stability of self-assemblies formed by ester benzene 1,3,5-
tricarboxamides: the crucial role played by the substituents. Soft Matter
2016, 12, 7824-7838; d) Caumes, X.; Baldi, A.; Gontard, G.; Brocorens, P.;
Lazzaroni, R.; Vanthuyne, N.; Troufflard, C.; Raynal, M.; Bouteiller, L.:
Tuning the structure of 1,3,5-benzene tricarboxamide self-assemblies
through stereochemistry. Chem. Commun. 2016, 52, 13369-13372; e)
Bejagam, K. K.; Remsing, R. C.; Klein, M. L.; Balasubramanian, S.:
Understanding the self-assembly of amino ester-based benzene-1,3,5-
tricarboxamides using molecular dynamics simulations. Phys. Chem. Chem.
Phys. 2017, 19, 258-266; f) Vantomme, G.; ter Huurne, G. M.; Kulkarni, C.;
ten Eikelder, H. M. M.; Markvoort, A. J.; Palmans, A. R. A.; Meijer, E. W.:
Tuning the Length of Cooperative Supramolecular Polymers under
Thermodynamic Control. J. Am. Chem. Soc. 2019, 141, 18278-18285.
(24) a) Desmarchelier, A.; Caumes, X.; Raynal, M.; Vidal-Ferran, A.; van
Leeuwen, P. W. N. M.; Bouteiller, L.: Correlation between the Selectivity
and the Structure of an Asymmetric Catalyst Built on a Chirally Amplified
Supramolecular Helical Scaffold. J. Am. Chem. Soc. 2016, 138, 4908-4916;
b) Zimbron, J. M.; Caumes, X.; Li, Y.; Thomas, C. M.; Raynal, M.; Bouteiller,
L.: Real-Time Control of the Enantioselectivity of a Supramolecular Catalyst
Allows Selecting the Configuration of Consecutively Formed Stereogenic
Centers. Angew. Chem. Int. Ed. 2017, 56, 14016-14019.
2
(
6
443; b) Crusats, J.; El-Hachemi, Z.; Ribó, J. M.: Hydrodynamic effects on
chiral induction. Chem. Soc. Rev. 2010, 39, 569-577; c) Micali, N.;
Engelkamp, H.; van Rhee, P. G.; Christianen, P. C. M.; Scolaro, L. M.; Maan,
J. C.: Selection of supramolecular chirality by application of rotational and
magnetic forces. Nat. Chem. 2012, 4, 201-207; d) Kim, J.; Lee, J.; Kim, W.
Y.; Kim, H.; Lee, S.; Lee, H. C.; Lee, Y. S.; Seo, M.; Kim, S. Y.: Induction and
control of supramolecular chirality by light in self-assembled helical
nanostructures. Nat Commun 2015, 6; e) Sun, J. S.; Li, Y. K.; Yan, F. S.; Liu,
C.; Sang, Y. T.; Tian, F.; Feng, Q.; Duan, P. F.; Zhang, L.; Shi, X. H.; Ding, B.
Q.; Liu, M. H.: Control over the emerging chirality in supramolecular gels
and solutions by chiral microvortices in milliseconds. Nat Commun 2018,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
9
, 2599, doi:10.1038/s41467-018-05017-7; f) Sang, Y. T.; Yang, D.; Duan, P.
F.; Liu, M. H.: Towards homochiral supramolecular entities from achiral
molecules by vortex mixing-accompanied self-assembly. Chem. Sci. 2019,
1
0, 2718-2724; g) Hu, J. G.; Xie, Y. F.; Zhang, H. L.; He, C. L.; Zhang, Q. J.;
Zou, G.: Chiral induction, modulation and locking in porphyrin based
supramolecular assemblies with circularly polarized light. Chem. Commun.
(25) van Gestel, J.: Amplification of Chirality of the Majority-Rules Type in
Helical Supramolecular Polymers: The Impact of the Presence of Achiral
Monomers. J. Phys. Chem. B 2006, 110, 4365-4370.
(26) CD spectroscopy analyses are performed with [l1-BTA] ≤5.8 mM to
limit the absorbance of the sample in toluene whilst catalytic experiments
are performed with [l1-BTA]= 16.1 mM
2
019, 55, 4953-4956.
(18) a) Stals, P. J. M.; Korevaar, P. A.; Gillissen, M. A. J.; de Greef, T. F. A.;
Fitie, C. F. C.; Sijbesma, R. P.; Palmans, A. R. A.; Meijer, E. W.: Symmetry
Breaking in the Self-Assembly of Partially Fluorinated Benzene-1,3,5-
tricarboxamides. Angew. Chem. Int. Ed. 2012, 51, 11297-11301; b) Shen, Z.
C.; Wang, T. Y.; Liu, M. H.: Macroscopic Chirality of Supramolecular Gels
(27) Allenmark, S.: Induced Circular Dichroism by Chiral Molecular
Interaction. Chirality 2003, 15, 409-422.
Formed
from
Achiral
Tris(ethyl
cinnamate)
Benzene-1,3,5-
tricarboxamides. Angew. Chem. Int. Ed. 2014, 53, 13424-13428; c) Shen, Z.
C.; Jiang, Y. Q.; Wang, T. Y.; Liu, M. H.: Symmetry Breaking in the
Supramolecular Gels of an Achiral Gelator Exclusively Driven by pi-pi
Stacking. J. Am. Chem. Soc. 2015, 137, 16109-16115; d) Sang, Y. T.; Liu, M.
H.: Symmetry Breaking in Self-Assembled Nanoassemblies. Symmetry
(28) Naphthalenediimides (NDI) derived from quaternary amino acids
were found to be adequate soldiers in S&S-type NDI co-assemblies:
Anderson, T. W.; Sanders, J. K. M.; Dan Pantoş, G.: The sergeants-and-
soldiers effect: chiral amplification in naphthalenediimide nanotubes. Org.
Biomol. Chem. 2010, 8, 4274-4280.
(29) Lightfoot, M. P.; Mair, F. S.; Pritchard, R. G.; Warren, J. E.: New
supramolecular packing motifs: pi-stacked rods encased in triply-helical
hydrogen bonded amide strands. Chem. Commun. 1999, 1945-1946.
(30) The deviation of the scattering intensity at low q values is either the
result of the finite length of the objects or of interactions between objects.
Accordingly, only a lower limit value of the length of the supramolecular
helices can be deduced (l> 120 nm).
(31) a) van Gestel, J.; van der Schoot, P.; Michels, M. A. J.: Amplification of
chirality in helical supramolecular polymers. Macromolecules 2003, 36,
6668-6673; b) van Gestel, J.: Amplification of chirality in helical
supramolecular polymers: The majority-rules principle. Macromolecules
2004, 37, 3894-3898; c) van Gestel, J.; van der Schoot, P.; Michels, M. A.
J.: Amplification of chirality in helical supramolecular polymers beyond the
long-chain limit. J Chem Phys 2004, 120, 8253-8261.
(32) Li, Y.; Dubreucq, L.; Alvarenga, B. G.; Raynal, M.; Bouteiller, L.: N-
Substituted Benzene-1-Urea-3,5-Biscarboxamide (BUBA): Easily Accessible
C-2-Symmetric Monomers for the Construction of Reversible and Chirally
Amplified Helical Assemblies. Chem. Eur. J. 2019, 25, 10650-10661.
(33) a) van Gestel, J.; Palmans, A. R. A.; Titulaer, B.; Vekemans, J. A. J. M.;
Meijer, E. W.: "Majority-rules" operative in chiral columnar stacks of C-3-
symmetrical molecules. J. Am. Chem. Soc. 2005, 127, 5490-5494; b)
Stals, P. J. M.; Everts, J. C.; de Bruijn, R.; Filot, I. A. W.; Smulders, M. M. J.;
Martin-Rapun, R.; Pidko, E. A.; de Greef, T. F. A.; Palmans, A. R. A.; Meijer,
E. W.: Dynamic Supramolecular Polymers Based on Benzene-1,3,5-
tricarboxamides: The Influence of Amide Connectivity on Aggregate
Stability and Amplification of Chirality. Chem. Eur. J. 2010, 16, 810-821; c)
Helmich, F.; Smulders, M. M. J.; Lee, C. C.; Schenning, A. P. H. J.; Meijer, E.
W.: Effect of Stereogenic Centers on the Self-Sorting, Depolymerization,
and Atropisomerization Kinetics of Porphyrin-Based Aggregates. J. Am.
Chem. Soc. 2011, 133, 12238-12246; d) Greciano, E. E.; Calbo, J.; Buendía,
J.; Cerdá, J.; Aragó, J.; Ortí, E.; Sánchez, L.: Decoding the Consequences of
Increasing the Size of Self-Assembling Tricarboxamides on Chiral
Amplification. J. Am. Chem. Soc. 2019, 141, 7463-7472.
2
019, 11, 950; doi:10.3390/sym11080950.
(19) Cantekin, S.; de Greef, T. F. A.; Palmans, A. R. A.: Benzene-1,3,5-
tricarboxamide: a versatile ordering moiety for supramolecular chemistry.
Chem. Soc. Rev. 2012, 41, 6125-6137.
(20) Smulders, M. M. J.; Stals, P. J. M.; Mes, T.; Paffen, T. F. E.; Schenning,
A. P. H. J.; Palmans, A. R. A.; Meijer, E. W.: Probing the Limits of the
Majority-Rules Principle in a Dynamic Supramolecular Polymer. J. Am.
Chem. Soc. 2010, 132, 620-626.
(21) a) Brunsveld, L.; Schenning, A. P. H. J.; Broeren, M. A. C.; Janssen, H.
M.; Vekemans, J. A. J. M.; Meijer, E. W.: Chiral amplification in columns of
self-assembled
N,N',N''-tris((S)-3,7-dimethyloctyl)benzene-1,3,5-
tricarboxamide in dilute solution. Chem. Lett. 2000, 292-293; b) Wilson, A.
J.; Masuda, M.; Sijbesma, R. P.; Meijer, E. W.: Chiral amplification in the
transcription of supramolecular helicity into a polymer backbone. Angew.
Chem. Int. Ed. 2005, 44, 2275-2279;
c) Wilson, A. J.; van Gestel, J.;
Sijbesma, R. P.; Meijer, E. W.: Amplification of chirality in benzene
tricarboxamide helical supramolecular polymers. Chem. Commun. 2006,
4
404-4406; d) Smulders, M. M. J.; Schenning, A. P. H. J.; Meijer, E. W.:
Insight into the Mechanisms of Cooperative Self-Assembly: The
Sergeants-and-Soldiers” Principle of Chiral and Achiral C3-Symmetrical
“
Discotic Triamides. J. Am. Chem. Soc. 2008, 130, 606-611; e) Smulders, M.
M. J.; Filot, I. A. W.; Leenders, J. M. A.; van der Schoot, P.; Palmans, A. R.
A.; Schenning, A. P. H. J.; Meijer, E. W.: Tuning the Extent of Chiral
Amplification by Temperature in a Dynamic Supramolecular Polymer. J.
Am. Chem. Soc. 2010, 132, 611-619.
(22) Li, Y.; Caumes, X.; Raynal, M.; Bouteiller, L.: Modulation of catalyst
enantioselectivity through reversible assembly of supramolecular helices.
Chem. Commun. 2019, 55, 2162-2165.
(23) a) de Loos, M.; van Esch, J. H.; Kellogg, R. M.; Feringa, B. L.: C-3-
symmetric, amino acid based organogelators and thickeners: a systematic
study of structure-property relations. Tetrahedron 2007, 63, 7285-7301;
b) Veld, M. A. J.; Haveman, D.; Palmans, A. R. A.; Meijer, E. W.: Sterically
demanding benzene-1,3,5-tricarboxamides: tuning the mechanisms of
supramolecular polymerization and chiral amplification. Soft Matter 2011,
7, 524-531; c) Desmarchelier, A.; Alvarenga, B. G.; Caumes, X.; Dubreucq,
(34) Jouvelet, B.; Isare, B.; Bouteiller, L.; van der Schoot, P.: Direct Probing
ACS Paragon Plus Environment

Page 13 of 14
Journal of the American Chemical Society
of the Free-Energy Penalty for Helix Reversals and Chiral Mismatches in
Chiral Supramolecular Polymers. Langmuir 2014, 30, 4570-4575.
35) Jordan, A. J.; Lalic, G.; Sadighi, J. P.: Coinage Metal Hydrides: Synthesis,
Characterization, and Reactivity. Chem. Rev. 2016, 116, 8318-8372.
36) a) Yamamoto, T.; Suginome, M.: Helical Poly(quinoxaline-2,3-diyl)s
breaking coupled to top-bottom chirality transfer: from porphyrin self-
assembly to scalemic Diels–Alder adducts. Chem. Commun. 2019, 55,
12219-12222.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
(45) a) Xyl-P-Phos is a remarkably active and selective covalent ligand for
thr copper-catalysed hydrosilylation of NPnone: Wu, J.; Ji, J. X.; Chan, A. S.
C.: A remarkably effective copper(II)-dipyridylphosphine catalyst system
for the asymmetric hydrosilylation of ketones in air. Proc. Natl. Acad. Sci.
U. S. A. 2005, 102, 3570-3575; Higher extent of chirality amplification is
achieved with asymmetric auto-catalysts: see reference 3b and: b) Soai, K.;
Shibata, T.; Morioka, H.; Choji, K.: Asymmetric Autocatalysis and
Amplification of Enantiomeric Excess of a Chiral Molecule. Nature 1995,
378, 767-768; c) Soai, K.; Sato, I.; Shibata, T.; Komiya, S.; Hayashi, M.;
Matsueda, Y.; Imamura, H.; Hayase, T.; Morioka, H.; Tabira, H.; Yamamoto,
J.; Kowata, Y.: Asymmetric synthesis of pyrimidyl alkanol without adding
chiral substances by the addition of diisopropylzinc to pyrimidine-5-
carbaldehyde in conjunction with asymmetric autocatalysis. Tetrahedron
Asymmetry 2003, 14, 185-188.
(
Bearing Metal-Binding Sites as Polymer-Based Chiral Ligands for
Asymmetric Catalysis. Angew. Chem. Int. Ed. 2009, 48, 539-542; b) Nagata,
Y.; Nishikawa, T.; Suginome, M.: Exerting Control over the Helical Chirality
in the Main Chain of Sergeants-and-Soldiers-Type Poly(quinoxaline-2,3-
diyl)s by Changing from Random to Block Copolymerization Protocols. J.
_
Am. Chem. Soc. 2015, 137, 4070 4073.
(37) Green, M. M.; Khatri, C. A.; Reidy, M. P.; Levon, K.: Dilute-Solution
Chiral Optical-Changes Signal the Thermally Reversible Gelation of Poly(N-
Hexyl Isocyanate) in Hydrocarbon Solvents. Macromolecules 1993, 26,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
723-4725.
(38) a) Tschierske, C.; Ungar, G.: Mirror Symmetry Breaking by Chirality
Synchronisation in Liquids and Liquid Crystals of Achiral Molecules.
ChemPhysChem 2016, 17, 9-26; b) Buchs, J.; Vogel, L.; Janietz, D.; Prehm,
M.; Tschierske, C.: Chirality Synchronization of Hydrogen-Bonded
Complexes of Achiral N-Heterocycles. Angew. Chem. Int. Ed. 2017, 56, 280-
(46) Adelizzi, B.; Van Zee, N. J.; de Windt, L. N. J.; Palmans, A. R. A.; Meijer,
E. W.: The future of supramolecular copolymers unveiled by reflecting on
covalent copolymerization. J. Am. Chem. Soc. 2019, 141, 6110-6121.
2
84.
(39) García, F.; Sánchez, L.: Structural Rules for the Chiral Supramolecular
Organization of OPE-based Discotics: Induction of Helicity and
Amplification of Chirality. J. Am. Chem. Soc. 2012, 134, 734-742.
(
40) Shikata, T.; Kuruma, Y.; Sakamoto, A.; Hanabusa, K.: Segment Sizes of
Supramolecular Polymers of N,N′,N′′-Tris(3,7-dimethyloctyl)benzene-
,3,5-tricarboxamide in n-Decane. J. Phys. Chem. 2008, 112, 16393-16402.
1
(41) a) Karle, I. L.; Balaram, P.: Structural Characteristics of Alpha-Helical
Peptide Molecules Containing Aib Residues. Biochemistry 1990, 29, 6747-
6
756; b) Clayden, J.; Castellanos, A.; Sola, J.; Morris, G. A.: Quantifying End-
to-End Conformational Communication of Chirality through an Achiral
Peptide Chain. Angew. Chem. Int. Ed. 2009, 48, 5962-5965.
(42) a) Megens, R. P.; Roelfes, G.: Asymmetric Catalysis with Helical
Polymers. Chem. Eur. J. 2011, 17, 8514-8523; b) Suginome, M.; Yamamoto,
T.; Nagata, Y.; Yamada, T.; Akai, Y.: Catalytic asymmetric synthesis using
chirality-switchable helical polymer as a chiral ligand. Pure Appl. Chem.
2
012, 84, 1759-1769; c) Jiang, J.; Ouyang, G. H.; Zhang, L.; Liu, M. H.: Self-
Assembled Chiral Nanostructures as Scaffolds for Asymmetric Reactions.
Chem. Eur. J. 2017, 23, 9439-9450; d) Ke, Y.-Z.; Nagata, Y.; Yamada, T.;
Suginome, M.: Majority-Rules-Type Helical Poly(quinoxaline-2,3-diyl)s as
Highly Efficient Chirality-Amplification Systems for Asymmetric Catalysis.
_
Angew. Chem. Int. Ed. 2015, 54, 9333 9337; e) Yamamoto, T.; Murakami,
R.; Komatsu, S.; Suginome, M.: Chirality-Amplifying, Dynamic Induction of
Single-Handed Helix by Chiral Guests to Macromolecular Chiral Catalysts
Bearing Boronyl Pendants as Receptor Sites. J. Am. Chem. Soc. 2018, 140,
3
867; f) Nagata, Y.; Takeda, R.; Suginome, M.: Asymmetric Catalysis in
Chiral Solvents: Chirality Transfer with Amplification of Homochirality
through a Helical Macromolecular Scaffold. ACS Cent. Sci. 2019, 5, 1235-
1
240.
(43) Shen, Z. C.; Sang, Y. T.; Wang, T. Y.; Jiang, J.; Meng, Y.; Jiang, Y. Q.;
Okuro, K.; Aida, T.; Liu, M. H.: Asymmetric catalysis mediated by a mirror
symmetry-broken helical nanoribbon. Nat Commun 2019, 10,
doi/10.1038/s41467-019-11840-3.
(44) Arlegui, A.; Soler, B.; Galindo, A.; Arteaga, O.; Canillas, A.; Ribó, J. M.;
El-Hachemi, Z.; Crusats, J.; Moyano, A.: Spontaneous mirror-symmetry
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 14 of 14
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
4
ACS Paragon Plus Environment