Triphenylacetic acid amides: Molecular propellers with induced chirality

Article abstract of DOI:10.1002/ejoc.201403182

The combination of electronic circular dichroism spectroscopy (ECD), X-ray diffraction, and theoretical calculations permitted a detailed description of an unexpected chirality transfer in triphenylacetamides, which is achieved solely through weak intramolecular interactions. The observed phenomenon proceeds as a cascade process. The triphenylacetamide chromophore is sensitive to even small changes in the relative size of the substituent attached to the stereogenic center. Substitution at the stereogenic center influences helicity of the distal trityl chromophore but does not affect its propeller shape. Deformation of the propeller shape and consequent loss of its C3 symmetry results mainly from substitution of the amide hydrogen and is connected with an increase in steric hindrance. As an outcome of our studies, a model of optical activity of chiral triphenylacetamides is proposed. The performed X-ray studies revealed that this novel class of chiral compounds is likely to be of additional value due to the porosity of the crystals.

Full text of DOI:10.1002/ejoc.201403182

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FULL PAPER
DOI: 10.1002/ejoc.201403182
Triphenylacetic Acid Amides: Molecular Propellers with Induced Chirality[‡]
[a]
[a]
[a]
´
Natalia Prusinowska, Wioletta Bendzinska-Berus, Maciej Jelecki,
Urszula Rychlewska,*[a] and Marcin Kwit*[a,b]
Keywords: Conformation analysis / Chirality / Configuration determination / Circular dichroism / Density functional
calculations / X-ray diffraction
The combination of electronic circular dichroism spec-
troscopy (ECD), X-ray diffraction, and theoretical calcula-
tions permitted a detailed description of an unexpected
chirality transfer in triphenylacetamides, which is achieved
solely through weak intramolecular interactions. The ob-
served phenomenon proceeds as a cascade process. The tri-
phenylacetamide chromophore is sensitive to even small
changes in the relative size of the substituent attached to the
stereogenic center. Substitution at the stereogenic center in-
fluences helicity of the distal trityl chromophore but does not
affect its propeller shape. Deformation of the propeller shape
and consequent loss of its C3 symmetry results mainly from
substitution of the amide hydrogen and is connected with an
increase in steric hindrance. As an outcome of our studies,
a model of optical activity of chiral triphenylacetamides is
proposed. The performed X-ray studies revealed that this
novel class of chiral compounds is likely to be of additional
value due to the porosity of the crystals.
compounds. Wang et al. recently identified S-trityl-(S)-
cysteine and related analogues as potent selective inhibitors
of the human mitotic kinesin Eg5.[10] An enantiomer, S-
trityl-(R)-cysteine, is an efficient chiral selector that is
highly effective in both analytical and preparative-scale
separation of enantiomers of some natural and synthetic
underivatized amino acids.[11] The trityl group is often used
as a synthon in the construction of supramolecular archi-
tecture, molecular devices such as molecular rotaxanes,
gyroscopes,[12,13] compasses,[14–16] and molecular glasses
with nonlinear optical activity.[17]
Recently, Megumi and co-workers examined salts of
some N-tritylamino acids (Ala, Val, Leu, Ile, Phe, and
phenylglycine) and tert-butylamine in terms of inclusion
ability for chiral alcohols.[18] An extensive X-ray crystallo-
graphic study showed that both the steric bulk of the trityl
group and the hydrogen-bonding donor ability of the
primary ammonium cation were essential for making a new
host–guest hydrogen-bond network.
Introduction
Since pioneering studies of Mislow and co-workers, the
fascinating stereochemistry of molecular propellers – both
static and dynamic – have attracted a lot of attention in the
last two decades.[1,2] Irrespective of the substitution pattern
in the aromatic skeleton, the triarylmethyl system exists in
solution as an equimolar mixture of enantiomers, in which
all aryl rings have the same sense of twist (for a given mol-
ecule), either P or M. The simplest example of such system
is the triphenylmethyl (trityl) group (Tr, Ph3C-), which is
widely used in organic chemistry. Nowadays, exploitation of
the Tr group is not only limited to the protection of primary
alcohols (or other polar groups) in carbohydrates and
nucleosides.[3] Carbocations generated from simple deriva-
tives of the trityl group can catalyze important reactions
such as Diels–Alder, Michael addition, and others.[4–8] The
trityl group constitutes part of the thiourea organocatalysts,
which have a broad spectrum of application in stereoselec-
tive synthesis.[6–9]
The structure of the trityl group depends on the type of
the attached substituent. Its conformational freedom stems
not only from rotation around the bond connecting the Tr
group to the molecular framework but also from rotation
The hydrophobic properties of triaryl groups have been
utilized in the construction of several biologically active
[‡] This contribution celebrates the International Year of
Crystallography IYCr2014
[a] Department of Chemistry, A. Mickiewicz University,
Grunwaldzka 6, 60780 Poznan´, Poland
E-mail: urszular@amu.edu.pl
marcin.kwit@amu.edu.pl
www.amu.edu.pl
[b] Institute of Organic Chemistry, Polish Academy of Science,
Kasprzaka 44/52, 01224 Warszawa, Poland
E-mail: mkwit@icho.edu.pl
3
of each phenyl ring around the Cipso–Csp bond (slippage).
The Tr group connected to the achiral spherical substituent
forms a propeller of formal C3 symmetry, which is dynami-
cally racemic and generates no electronic circular dichroism
(ECD) signal.[19] Gawronski et al. demonstrated for the first
time that the ECD spectra of trityl-protected monoalcohols
are highly sensitive to the chirality (absolute configuration)
of the alcohol and this allowed the transmission of chirality
from an alcohol chiral center to the trityl group through a
www.icho.edu.pl
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403182.
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U. Rychlewska, M. Kwit et al.
FULL PAPER
molecular “bevel gear” mechanism to be observed.[20] DFT hydrocarbon surfaces”.[26] The lack of involvement of the
calculations show that the triphenylmethyl group in chiral NH amide group in hydrogen-bonding was also noticed in
molecules does not form a regular C3-symmetry propeller, one of the Mosher’s amides.[27] Moreover, the hydrogen-
but adopts the lowest (C1) symmetry, with a low-energy bonding scheme in 2,2,2-triphenyl-N-(2-pyridylmethyl)acet-
barrier of a two-ring flip through a Cs-symmetry transition amide featured a dimeric N–H···N interaction instead of
state. Based on conformational space analysis for low-en- the expected hydrogen-bonded amide chains that occur in
ergy diastereoisomers and on TD-DFT computation of phenylmethyl-substituted pyridyl amide, again demonstrat-
ECD spectra, Gawronski et al. proposed a simple model for ing the role of the bulky triphenylmethyl group in pre-
the determination of the absolute configuration of trityl- venting amide groups from getting close enough to form
protected alcohols.
amide hydrogen bonds.[28] Zhu at al. studied the hydrogen-
ECD spectroscopy seems to be a method of choice for bonding pattern in chloro-, bromo-, and iodo-substituted
the detection of residual stereoisomerism in such chiral aromatic amides containing bulky substituents. Introduc-
systems in solution.[21,22] In their recent study, Gawronski tion of a large unit increases the stability of the intramolec-
and Sciebura showed that in chiral N-tritylamines the per- ular NH···halogen hydrogen bonding over competitive
manent chirality of the carbon atom is efficiently trans- intermolecular NH···O=C hydrogen bonding.[29] Recently,
mitted through the nitrogen atom to the trityl group.[23] Du at al. revealed the existence of similar intramolecular
Comparison of the calculated diastereoisomer population hydrogen bonds between NH amide protons and a weak
and the Boltzmann averaged ECD spectra with the experi- acceptor such as a sulfur atom.[30] Although the conforma-
mental results demonstrates that dynamic configurational tion of the trityl moiety has not so far been a subject of
change at the nitrogen atom is correlated with permanent much interest, a brief survey of reported structures of tri-
chirality at the carbon atom and to dynamic helicity of the phenylacetamide derivatives (Ph3CCONHR) determined by
trityl group. In 2013 Gawronski and Sciebura introduced a X-ray diffraction methods[31] show that some derivatives
new chromophore for stereochemical studies – a diphenyl- with formal C3 symmetry (R = Me, 4-MeOC6H4, 2-ClC6H4,
methyl group (benzhydryl, Bh) – as a receptor system to 2-MeSC6H4, CH2C5H4N, Table 1) indeed have the struc-
report the chirality of a nearby stereogenic center. As in the tures of molecular propellers [dihedral angles (O=)C–C–
case of the trityl group, the permanent chirality of a
Cipso–Cortho are of the same sign, which is indicative of
molecule is transmitted to the diphenylmethyl reporting either M or P helicity].[26,28–30,32–34] This is not true for
group, shifting the equilibrium in the direction of either the other derivatives [e.g., R = 2,3-(iPrS)2C6H3], for which a
M or P helical propeller.[24]
breakdown of C3 symmetry is observed (two dihedral
Although results obtained to date for chiral N-trityl de- angles are of opposite sign to the sign of the third). In the
rivatives have been spectacular, it was not possible to estab- case of 2,6-bis(triphenylacetylamino)phenol, both irregular
lish the order of events; that is, in which way the chiral MPP and propeller-like PPP structures are present in the
information is transferred from the permanent stereogenic crystal.[33] This suggests that in the case of triphenylacet-
center to the conformationally labile trityl chromophore. To amides, the energy barrier to stereoisomer interconversion
resolve this issue, we looked for molecules that were de- is rather low and even a small difference in the relative size
prived of the dynamic stereogenic center at the nitrogen of substituents at the chiral center might affect the helicity
atom and in which the trityl chromophore was distant from of the trityl moiety. On the other hand, a relatively long
the permanent stereogenic center at the carbon atom. It distance between the chiral center and the trityl substituent
soon became apparent that simple derivatization of chiral might render the chirality transmission impossible.
primary or secondary amines by triphenylacetic acid might
Table 1. Dihedral angles (O=)C–C–Cipso–Cortho (γ1–γ3) in selected
Ph3CCONHR structures determined by X-ray diffraction studies.
To distinguish between two ortho positions ,the angles were restric-
provide suitable model molecules. In triphenylacetamides
the chiral center and the reporter (trityl) part of a molecule
are connected by a rigid amide spacer, which should not be
able to transfer the chirality information from inductor to
reporter through the sp2 nitrogen atom.
ted to lie in the range from –90 to 90°.
R
γ1
γ2
γ3
Ref.
[26]
[29]
[32]
[30]
[28]
[26]
[34]
Me
2-ClC6H4
4-MeOC6H4
2-MeSC6H4
(2-C5H4N)CH2
PhCH(CH3)
2,3-(iPrS)2C6H3
–28.9
–10.1
–25.2
–16.4
22.8
10.8
8.0
–55.3
–53.5
–56.8
–51.4
49.7
50.4
–58.5
55.1
–59.3
–63.5
–57.6
–59.3
61.3
57.4
–62.0
63.9
Despite biological activity studies of triphenylacetamide
entities, little is known about their structural properties.[25]
McQuade et al. used the N–H stretch region in the IR spec-
tra to probe the hydrogen-bond-donating properties of
structurally related secondary amides in which the amide
group is flanked by sterically bulky groups.[26] The IR and
crystallographic data indicated that intermolecular
hydrogen-bonding is not obligatory among secondary
amides derived from triphenylacetic acid or its saturated an-
alogue. The authors pointed out that most of the packing
–7.5
[33]
2-HOC6H3
29.5
–13.9
50.2
52.7
59.2
66.0
To test the two scenarios, we examined triphenylacetic
energy in the molecules studied probably arises from disper- acid derivatives 1–11 (Figure 1) of representative chiral
sion interactions and it is energetically advantageous “to amines. We also attempted to correlate the dynamic struc-
forgo hydrogen bonds in favour of superior contact among ture of the triphenylmethyl chromophore with the observed
2
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Molecular Propellers with Induced Chirality
chiroptical phenomena by means of a combined experimen- arches for all molecules were performed with Scigress soft-
tal/theoretical protocol. This required an extensive compu- ware.[36] Preliminary calculations for all conformers gener-
tational study to determine the conformation of these com- ated at the molecular mechanics level were carried out at
pounds. Another point was to determine to what extent the the B3LYP/6-31G(d) level, followed by higher accuracy cal-
bulky aryl and alkyl substituents influence the solid-state culations with the use of B3LYP,[37] LC-wPBE,[38] and
structure of secondary amides; in particular, their ability to M06–2X[39] hybrid functional, and pure B97-D functional
pack efficiently and to utilize intermolecular amide including empirical long-range correction;[40] all in conjunc-
hydrogen bonds for their packing.
tion with the enhanced 6-311++G(d,p) basis set.[41] The
structures thus obtained were the real minimum energy con-
formers (no imaginary frequencies were found). The total
and free energy values were used to obtain the Boltzmann
population of conformers at 298.15 K. For density func-
tional theory (DFT) calculations, by following a generally
accepted protocol, only the conformers that differ from the
most stable by less than 2 kcalmol–1 were taken into ac-
count. Relative energies (in kcalmol–1) discussed here refer
to Gibbs free energies (ΔG°) computed at the B3LYP/6-
311++G(d,p) level.
ECD spectra for all structures optimized at the DFT/6-
311++G(d,p) level were calculated by employing PBE0,[42]
CAM-B3LYP,[43] B2LYP,[44] LC-wPBE,[38] and M06–2X[39]
hybrid functional; all in conjunction with the 6-
311++G(d,p) basis set.[41,45] The calculated ECD spectra
were Boltzmann averaged by taking into account conform-
ers of 1–11 ranging from 0 to 2.0 kcalmol–1 in relative ener-
gies, by following a generally accepted protocol.[35]
Rotatory strengths were calculated by using both length
and velocity representations. In the present study, the differ-
ences between the length and velocity calculated values of
rotatory strengths were quite small; for this reason, only the
velocity representations were further used. The ECD spec-
tra were simulated by overlapping Gaussian functions for
each transition, according to the procedure previously de-
scribed by Harada and Stephens.[46]
Figure 1. (a) Structures of amides under study. (b) Schematic repre-
sentation of N-substituted triphenylacetamide and definition of the
dihedral angles that characterize the conformation of the molecule.
Solvent effects on the structure and ECD spectra were
not taken into account because the measurements for
amides 1–11 were conducted in nonpolar cyclohexane.
To keep the discussion as simple as possible, we focus
Results and Discussion
Materials, Experimental, and Computational Details
Triphenylacetamides 1–11 (Figure 1, a) were obtained in here only on the structures obtained through the use of the
high yields by reactions of the respective primary or second- B3LYP/6-311++G(d,p) method and ECD spectra calcu-
ary amines with triphenylacetoyl chloride (detailed experi- lated at the M06–2X/6-311++G(d,p) level, because the re-
mental procedures and full spectroscopic characterization sults of these calculations were in best agreement with ex-
for all new compounds have been deposited as Supporting periment results.
Information). Crystals suitable for X-ray diffraction were
Given that is was not possible to address the question of
obtained by slow evaporation of diethyl ether from a solu- conformational equilibria of 1–11 experimentally, the
tion of the respective amide in a mixture of diethyl ether choice of the best method of geometry/energy determi-
and n-hexane. ECD spectra of amides 1–11 were measured nation was done indirectly by comparing the calculated
in cyclohexane and in acetonitrile solutions. For compari- ECD with the experimental data. In the case of tri-
son of the sensitivity of chirogenesis, selected diphenylacet- phenylacetamides 1–11, the proposed protocol gave almost
amides 12–17 were also synthesized. Given the insolubility perfect reproduction of experimental data.[35]
of diphenylacetamides 12–17 in nonpolar media, ECD
For further computational results and short comments
spectra for these compounds were measured in acetonitrile on the performance of the computational methods, see the
only.
Computational studies on possible mechanisms of chiral-
ity transmission were conducted by followed the previously
proposed protocol.[23,24] This allowed a rational study of
the relationship between structure and chiroptical proper-
Supporting Information.
Structure of Amides 1–11 as Revealed by DFT Calculations
and X-ray Diffraction Studies
The structures of the amides under study are deceptively
ties with avoiding incidental effects. Conformational se- simple. There are at least seven torsion angles, for which
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FULL PAPER
the expected barriers of rotation are low. The structures and
relative positions of the trityl groups in the amide deriva-
tives can be described by a set of pseudotorsion angles
showing the relative orientation of each of the three phenyl
groups, as defined previously.[20] Alternatively, the confor-
mation of the trityl group may be characterized by a set of
three torsion angles γ1–γ3 (C(=O)–C–Cipso–Cortho) lying in
the range of –90 to 90°, as applied in this study.
The angles α (H–C*–N–C(=O)) and β1–β3 (O=C–C–
C
ipso) characterize the spatial arrangement of atoms around
the amide group (see Figure 1, b).
To determine the factors responsible for chirality induc-
tion in the trichromophore, we have performed extensive
experimental and theoretical studies on the structures of
amides 1–11 and performed a crystal structure database
(CSD) search for related compounds.[31] Additionally N-
methyl- and N,N-dimethyltriphenylacetamides have been
chosen as model molecules for calculations of conforma-
tional dynamics. Available crystallographic data for tri-
phenylacetic acid NH amides suggest that the β1–β3 torsion
angles concentrate in regions corresponding to two synclinal
(sc) and one antiperiplanar (ap) orientation of the trityl
phenyl rings with respect to the carbonyl bond. Based on
this observation, we have limited calculations for model
compounds to rotamers in which one of the β angles
adopted either 180 or 0°, with the other two being either sc
or anticlinal (ac), respectively. The energy-structure relation-
ships for model amides were obtained by systematical scan
of γ1–γ3 torsion angles with 10 degrees step by use of the
B3LYP/6-311++G(d,p) method. All of the obtained energy
maps have been deposited in the Supporting Information;
here we show only two representative examples; that is, the
global energy minima for the two model molecules (Fig-
ure 2 and the Supporting Information).
The arrangement of twist angles γ1–γ3 and hence the con-
formation of the trityl group was different in the two model
amides. For the lowest-energy conformer of the secondary
N-methyl amide, the values of twist angles γ1–γ3 were char-
acterized by the same sign and measured 60, 30, and 40°,
whereas for the lowest-energy conformer of tertiary N,N-
dimethyl amide, two of the twist angles (γ1 and γ2) were
characterized by the same sign and the same value of 50°,
whereas the third angle (γ3) was 0°. The β angle changed
Figure 2. Examples of potential energy maps (in kcalmol–1) as a
function of angles γ1–γ3 (in degrees) calculated for (a) N-methyltri-
phenylacetamide and (b) N,N-dimethyltriphenylacetamide at the
B3LYP/6-311++G(d,p) level. Marks represent global energy min-
ima.
from 180° to 0° when an additional methyl group was intro- ual conformers for amides 1–11 are collected in Table 2.
duced at the nitrogen atom. The maximum energy struc- Even a cursory reading of energetic data reveals that the
tures were found for the conformation in which all twist number of low-energy conformers is substantially lower
angles γ1–γ3 were close to 90°, regardless of the substitution than that established previously for chiral trityl ethers or
pattern on the nitrogen atom.
chiral N-tritylamines.[20,23] The number of structures within
In model molecules, rotation around the γ angles in one the 2 kcalmol–1 energy bracket is further reduced to only
or the other direction provides respective conformers as one conformer in amides bearing bulky aliphatic substitu-
mirror images. The situation changes if a chiral substituent ents at the stereogenic center (e.g., the tert-butyl group in
is introduced on to the nitrogen atom, as in compounds 1– 3) or in a bicyclic system such as 7. Despite the attractive-
11. However, before we comment on the structure of the ness of this proposal, no general rule that combines the
investigated compounds, a few words about energetic rela- number of low-energy conformers with the size of the re-
tionships between conformers of chiral amides 1–11 are spective substituents could be derived.
necessary.
More interesting was to collate the energetic data from
The relative energies calculated at the B3LYP/6- Table 2 with the structural data provided in Table 3 (see also
311++G(d,p) level and percentage populations of individ- the full version of Table 3 in the Supporting Information).
4
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Molecular Propellers with Induced Chirality
Table 2. Total energies (in Hartree), relative energies (ΔE, ΔG° in interactions in crystals are provided in Table S2 in the
kcalmol–1) and percentage populations calculated for individual
conformers of amides 1–11 at the B3LYP/6-311++G(d,p) level.
Supporting Information.
As observed for the model achiral compounds, the con-
Amide Conf.[a] Energy
ΔE
–1059.877204 0.24
–1059.8767 0.56
–1059.877586 0.00
–1059.877 0.43
Pop.
ΔG°
Pop.
formation defined by a set of β angles depended mainly on
the substitution at the nitrogen atom. In secondary amides,
the carbonyl group was oriented synclinally (sc) with respect
to two phenyl rings of the trityl moiety and ap relating to
the third phenyl ring (β3 value approximated 180°), leading
to the parallel orientation of the N–H bond with respect to
one of the C–Cipso bonds. When a methyl group was intro-
duced at the nitrogen atom, as in tertiary amides 8–11, the
carbonyl group became sp (β3 value approximated 0°) and
the amide methyl ap with respect to one of the phenyl rings,
and in bisecting position with respect to the remaining two
phenyl substituents. For tertiary amides, the values of the
smallest β angles, which are indicative of the sp conforma-
tion, ranged from –8.7° (in the case of 11) to 6.7° in the
case of the lowest-energy conformer number 1 of amide 10.
In crystals, the respective values varied from –7.9(2)° (in 8)
to 4.7(2)° (in 11). The conformational changes taking place
upon N-methylation, as observed in crystals, are illustrated
in Figure 3.
In contrast to the previously studied chiral N-trityl-
amines and O-trityl ethers, for which the overall conforma-
tion of the trityl group was described as “similar to Cs”, in
chiral secondary triphenylacetic acid amides 1–7 it approxi-
mated to C3 symmetry, both in the isolated state and in
crystals. It could be qualitatively described as MMM (M in
short) or PPP (P in short) (see Table 3 and the Supporting
Information). The latter appeared only in the calculated
structures of 5 and 7 and in the highest-energy conformers
of amides 2 and 4 (respectively conformers no. 6 and 7). In
crystals of 1 and 5, containing only one molecule in the
asymmetric unit (ZЈ = 1), the S configuration at the
stereogenic center was combined with P helicity of the Tr
chromophore. Consequently, crystals of 1 and 5 contained
solely molecules of S absolute configuration at the
stereogenic center and P helicity. However, in all crystals
with ZЈ = 2 (2, 3, and 6), the two independent molecules
always displayed opposite helicity forced by the favorable
pseudocentrosymmetric-type packing (Table 3), which com-
1
1
1
1
1
2
4
6
26
15
39
20
0.72
1.48
0.00
0.49
16
5
55
24
2
2
2
2
1
3
4
6
–1099.200621 0.00
–1099.200602 0.01
34
33
31
2
0.00
1.02
0.76
3.05
69
12
19
–1099.20054
0.05
–1099.197525 1.94
3
1
–1138.522729
0
100
0
100
4
4
4
4
4
2
3
4
6
7
–1215.96348
–1215.96434
–1215.96351
–1215.96175
–1215.96163
0.54
0.00
0.52
1.62
1.70
21
52
21
3
0.89
1.02
0.00
1.52
1.83
15
11
66
5
3
3
5
5
1
2
–1212.33319
–1212.33297
0.00
0.14
56
44
0.04
0.00
48
52
6
6
1
2
–1366.008309 0.00
–1366.005291 1.89
96
4
0.00
1.68
94
6
7
2
–1293.381933 0.00
100
100
0.00
100
8
8
1
3
–1177.818209 0.00
–1177.814364 2.41
0.00
1.82
96
4
9
9
9
9
9
1
2
3
4
9
–1255.264192 0.00
–1255.261883 1.45
–1255.261233 1.86
–1255.261608 1.62
80
7
3.
5
0.00
1.90
2.84
1.64
1.68
86
4
5
5
–1255.2615
1.69
5
10
10
1
6
–1251.634699 0.00
–1251.633761 0.59
73
27
0.00
0.01
51
49
11
1
–1405.30908
0.00
100
0.00
100
[a] Conformers are numbered according to their appearance during
the conformational search.
It was clear that any deviation from the syn orientation of pensates for a small but real energy difference between the
C*–H bond with respect to the carbonyl bond measured by two types of helicities. In cases in which ZЈ = 2, adoption
the value of the α angle (H–C*–N–C(=O)) caused a signifi- of opposite helicity (signaled by changes in sign of the non-
cant increase in energy. For example, in the case of the low- zero γ angles) was accompanied by changes in the sign of
energy conformers of 2, a change in the conformation from those β angles that differed significantly from 180 and 0°.
synperiplanar (sp) to antiperiplanar (ap) increased the free This was a clear indication of an exchange of information
energy of the molecule by approximately 3 kcalmol–1. The between the Tr chromophore and the amide fragment.
value of the α angle ranged from –34° to 33° for all calcu-
As one could expect, the conformation of the trityl group
lated low-energy conformers of amides 1–11. One could say in tertiary amides 8–11 differed from that of secondary
that the C*–H bond was balanced around a position typi- amides. From the formal point of view, within the calcu-
fied by its sp orientation with respect to the carbonyl group. lated low-energy structures of amides 8–11, all possible
This nearly parallel orientation of the amide C=O bond combinations of phenyl group helicities were found. How-
with respect to the C*–H bond at the stereogenic center ever, in all of these cases, one of the γ twist angles always
was also seen in all of the investigated crystal structures, assumed a value close to 0°. Strictly speaking, the values
suggesting the presence of an intramolecular hydrogen balanced around 0°, ranging from –4.5° to 4.7° (the helicity
CH···O(=C) bond that linked the amide unit with the is denoted as 0) and the remaining twist angles γ were char-
stereogenic center. Geometrical parameters describing these acterized by the same sense of helicity, either PP or MM,
Eur. J. Org. Chem. 0000, 0–0
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U. Rychlewska, M. Kwit et al.
FULL PAPER
Table 3. Dihedral angles α, β, γ, τ, ω (in degrees) and helicity of the trityl group observed in the crystal structures and calculated at the
B3LYP/6-311++G(d,p) level for individual low-energy conformers of amides 1–11. Angles β and γ can have three different values β1, β2,
and β3, and γ1, γ2, γ3, where 1, 2, and 3 refer to the phenyl groups of the trityl moiety numbered, respectively, from C11 to C16, C21 to
C26, and C31 to C36.
Amide[a]
α[b]
β1
β2
β3
γ1
γ2
γ3
τ
ω[e]
Helicity
[c]
[c]
[c]
[d]
[d]
[d]
1 (X-ray)
1 (conf. 1)
1 (conf. 2)
1 (conf. 4)
1 (conf. 6)
–29.5
–31.9
29.5
34.0
–33.1
68.6(1)
–87.2
–85.5
–79.7
–85.1
–49.9(1)
29.6
31.4
37.3
32.1
–171.8(1)
151.7
153.6
159.7
154.2
38.2(1)
–16.4
–18.9
–22.4
–22.5
42.3(1)
–56.3
–56.1
–54.9
–57.1
61.3(1)
–59.4
–58.7
–59.6
–57.3
–175.5(2)[f]
–170.2[f]
59.6[f]
–178.9
–179.0
–176.0
–175.0
–176.4
PPP
MMM
MMM
MMM
MMM
–66.5[f]
–62.5[f]
2 (X-ray)
–6.9
–8.8
5.1
33.5
–7.4
–179.8
61.5(2)
–72.4(2)
65.9
–79.6
66.3
–57.8(2)
46.7(2)
–52.6
37.4
–52.1
52.8
–178.2(1)
168.2(1)
–173.0
159.9
–172.7
173.2
–14.2(2)
16.5(2)
–27.6
–21.1
–28.4
32.1
–49.4(2)
49.0(2)
–39.3
–54.3
–40.2
37.3
–67.6(2)
70.8(2)
–72.2
–60.3
–71.6
71.0
–56.4[g]
–56.5[g]
–53.7[g]
174.0[g]
65.0[g]
174.7
–174.4
176.3
–177.3
176.2
–178.4
MMM
PPP
MMM
MMM
MMM
PPP
2 (conf. 1)
2 (conf. 3)
2 (conf. 4)
2 (conf. 6)
–65.3
62.2[g]
3 (X-ray)
–4.6
–19.7
–0.2
–82.3(2)
70.7(2)
65.2
36.3(2)
–47.8(2)
–53.4
157.6(2)
–168.0(2)
–173.8
24.4(2)
–26.4(3)
–28.0
46.2(2)
–43.6(2)
–39.9
72.1(2)
–70.6(2)
–71.6
–174.1
175.0
175.3
PPP
MMM
MMM
3 (conf. 1)
4 (conf. 1)
4 (conf. 3)
4 (conf. 4)
4 (conf. 6)
4 (conf. 7)
–31.0
31.4
–33.2
–2.1
–88.1
–79.8
–82.8
67.1
28.7
37.2
34.4
–51.4
52.3
150.9
159.8
156.6
–172.0
172.8
–17.4
–22.3
–24.4
–27.4
31.0
–56.9
–54.7
–55.2
–39.9
38.9
–58.9
–59.7
–59.3
–71.8
71.0
67.1[h]
179.8
MMM
MMM
MMM
MMM
PPP
–65.8[h]
–172.4[h]
–172.4[h]
–179.2[h]
–177.1
–179.8
177.1
179.8
–65.9
–178.5
5 (X-ray)[i]
5 (conf. 1)
5 (conf. 2)
34.1
–32.4
18.0
85.2
85.1
79.9
–30.4
–32.3
–37.3
–152.8
–154.3
–159.7
10.8
24.6
23.7
50.4
56.7
55.3
57.4
56.9
58.8
170.1
176.7
178.6
PPP
PPP
PPP
6 (X-ray)
–11.1
–24.4
–8.8
67.7(2)
–55.9(2)
–79.7
–49.7(2)
62.9(2)
37.4
–170.8(2)
–176.3(2)
159.6
–32.1(3)
31.1(3)
–25.5
–48.9(2)
49.8(2)
–56.7
–63.4(2)
60.5(2)
–57.0
–174.9
–169.1
–175.0
–170.3
MMM
PPP
MMM
MMM
6 (conf. 1)
6 (conf. 2)
–32.8
–83.8
33.3
155.4
–22.0
–56.9
–57.1
7 (X-ray)
7 (conf. 1)
8 (X-ray)
0.1
–42.8
11.3
61.0(3)
–74.6(3)
–83.6
–56.2(3)
43.1(3)
33.2
–178.4(3)
165.4(3)
155.7
23.2(3)
–25.3(3)
–18.7
51.4(4)
–59.1(3)
–55.7
63.2(2)
–60.1(2)
–59.7
–168.0
175.9
–179.3
PPP
MMM
MMM
–0.7
–6.3
3.5
–111.8(2)
108.2(2)
–112.0
124.6(3)
–126.1(2)
121.5
3.4(2)
–7.9(2)
2.6
–2.8(2)
4.7(2)
2.5
–47.7(4)
44.3(2)
–51.4
–55.2(1)
57.2(2)
–58.5
–176.4
–178.2
–176.6
–176.6
0MM
0PP
0MM
0MM
8 (conf. 1)
8 (conf. 2)
–165.7
114.2
–118.9
–0.5
–3.9
50.4
58.3
9 (X-ray)
–29.3
–13.2
–179.9
–11.0
31.9
114.5(4)
–111.7
115.9
–111.5
–111.9
–115.5
–118.8(4)
121.8
–118.3
–122.1
121.8
–1.4(5)
3.1
–2.7
3.3
3.2
–0.4
–4.2(5)
3.4
1.5
2.1
–0.1
2.2
44.7(4)
–51.6
–49.3
–51.4
–48.3
–47.8
63.2(4)
–58.1
–59.5
–58.4
–60.0
–59.2
–178.4[h]
–176.6[h]
174.7[h]
179.7[h]
–66.1[h]
–64.9[h]
174.8
178.1
–174.3
178.9
–175.5
–179.8
0PP
9 (conf. 1)
9 (conf. 2)
9 (conf. 3)
9 (conf. 4)
9 (conf. 9)
0MM
0MM
0MM
0MM
0MM
32.7
117.8
10 (conf. 1)
10 (conf. 6)
3.0
–17.0
109.1
–109.4
–125.0
124.6
–6.2
5.7
1.4
–0.1
47.7
–49.1
61.1
–59.8
–178.2
178.1
0PP
0MM
11 (X-ray)
11 (conf. 1)
–20.2
–8.8
–109.8(2)
–106.6
123.1(2)
127.8
4.7(2)
8.7
3.5(2)
–4.7
–50.8(2)
–46.4
–55.9(2)
–62.6
176.9
179.5
0MM
0MM
[a] Conformers are numbered according to their appearance during the conformational search. [b] α = H–C*–N–C(=O). [c] β = O=C–C–
Cipso. [d] γ = C(=O)–C–Cipso–Cortho (of the two possibilities the absolute values Յ 90° has been chosen). [e] ω = H(Me)–N–C=O. [f] τ =
C–C*–C–C. [g] τ = C–C*–C–H. [h] τ = H–C*–C–H. [i] X-ray data adopted from Ref.[26]
with the calculated values differing over |18°|. Exactly the
In all investigated derivatives 1–11, the amide group can
same trend was maintained in the crystal structures of com- be considered as planar. In the calculated structures, the
pounds 8, 9, and 11, for which the values of the γ1 angle values of the ω (H(Me)–N–C=O) angle balance around
ranged from –4.2(5)° in 9 to 4.7(2)° in 8, and the γ2 and γ3 180°, ranging from –175° to 175° and there are no visible
angles differed by no more than 13°.
trends that allow the helicity of the trityl moiety to be corre-
6
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Molecular Propellers with Induced Chirality
Figure 3. Illustration of conformational change taking place upon
N-methylation of the amide fragment. The picture displays mo-
lecules (a) 6 and (b) 11 as present in the crystal. Hydrogen atoms
attached to the aromatic rings are omitted for clarity.
lated with a slight distortion from planarity of the amide
linker. In crystals, deviations from 180° are more severe for
5, 6, and 7, and concern molecules in which trityl group
adopts P helicity. Interestingly, in tertiary amides 8 and 11,
the planarity of the amide group is maintained despite the
steric hindrance introduced by a methyl group.
Is worth mentioning that rotation around the dihedral
angle τ, which characterizes the conformation of the chiral
substituent in 1, 2, 4, and 9, had no effect on the conforma-
tion of the trityl group, however, it could have an impact
on the calculated relative energies (see Tables 2 and 3).
Figure 4. Calculated structures of the lowest energy conformers of
triphenylacetamides (a) 3 and (b) 8. Arrows indicate possible at-
tractive interactions (distances in Å). (c) Intramolecular interac-
tions as seen in crystals of 1. Geometrical parameters describing
these interactions are listed in Table S2 in the Supporting Infor-
mation. Some hydrogen atoms are omitted for clarity.
C=O···H(Cortho) interactions. The shortest distance between
these atoms was estimated to be 2.544 Å. Involvement of
one of the phenyl groups present in the trityl chromophore
in C=O···H–Cortho hydrogen-bonding fixes the orientation
of the remaining phenyl groups. In total, the conformation
of the trityl group seemed to be determined by C=O···H–
Factors Affecting the Molecular Conformation and Packing
of Molecules in Crystals
A detailed look at the calculated low-energy structures Cortho and by multiple attractive CH···π or electrostatic
of amides 1–11 and those present in crystals allowed us to interactions between the positively charged ortho–H
C
determine the factors that affect the molecular conforma- hydrogen atom and the negatively charged Cipso carbon
tion. Considering that an in-depth elaboration of each cal- atom from the neighboring phenyl group. This is particu-
culated structure may obscure the problem, we have limited larly well seen in the crystal structure of 1, shown in Fig-
our detailed discussion to two important representatives ure 4c.
differing only in the substitution at the amide nitrogen
atom; that is, amides 3, and to the lowest-energy conformer positely oriented dipoles formed by the C=O group and the
of 8 (shown in Figure 4) and their crystal counterparts. H–C* bond. These interactions appeared in all calculated
Other stabilizing interactions were found between the op-
The conformation of the TrCONH-fragment of 3 is de- structures of amides 1–11 and in all investigated crystal
termined by electrostatic interaction between positively structures 1–3, 5–9, and 11, and were characterized by a
charged (0.409) amide proton and one of the electron-rich close to zero value of the α angle (Table 3). In the case of
phenyl groups. The calculated distance between this par- the discussed amides 3 and 8, the distances between O and
ticular proton and the negatively charged ipso carbon atom the methine H(C*) protons were 2.320 and 2.106 Å, respec-
in one of the phenyl rings is 2.289 Å. Another stabilizing tively. Note that there was a general trend observed among
interaction is observed between negatively charged (–0.694) respective secondary and tertiary amides. For tertiary
oxygen atom and one of the ortho protons from the other amides, the calculated distances between O and H(C*)
phenyl ring (the calculated charge is 0.241). The calculated methine protons were shorter by approximately 0.2 Å than
distance is 2.148 Å. Based on the well-known scalar form those calculated for their secondary amide counterparts.
of Coulomb’s law and neglecting the influence of other Geometrical parameters describing the intramolecular in-
charges, we were able to estimate the relative strength of teractions mentioned above in crystals are provided in
both types of interactions. Mutual O···H(Cortho) electro- Tables S2 and S3.
static interactions are almost twelvefold stronger than
Note that in none of the investigated crystal structures
attractive (N)H···Cipso interaction.
of secondary amides was the NH group available for any
In the lowest-energy conformer of 8, the structure of the intermolecular interactions; in all cases, the amide carbonyl
trityl group seemed to be affected solely by the oxygen acted only as an acceptor of weak intermolecular
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U. Rychlewska, M. Kwit et al.
FULL PAPER
CH···O(=C) hydrogen bonds, and only a few of the phenyl
rings acted as acceptors of very weak CH···π interactions.
One consequence of the absence of strong intermolecular
interactions is the observed substantial solubility of com-
pounds 1–11 in nonpolar hydrocarbon solvents. The inter-
molecular hydrogen-bond parameters are listed in Table S4
in the Supporting Information.
Densities of the investigated crystals differ considerably
(Table S1, Supporting Information), ranging from
1.11 gcm–3 for 3 to 1.23 gcm–3 for 6 and 11. In the homolo-
gous series 1–3, the crystal density diminishes in the order
ethyl Ͼ isopropyl Ͼ tert-butyl and eventually leads to slight
microporosity of the crystals of 3. The microporosity is also
present in crystals of 7 and achieves the highest value in 9,
which demonstrates empty cavities with a void space per
cavity of 21 Å3, calculated by using the solvent accessible
surface method in the program Mercury[47] with a probe
radius of 1.1 Å. A guiding principle for the design of porous
materials within this novel class of chiral compounds seems
to be the presence of alicyclic groups and the lack of aro-
matic substituents.
Electronic Circular Dichroism
The validity of the structural studies discussed above may
be ultimately confirmed by comparison of the experimen-
tally measured ECD spectra with those calculated for the
low-energy conformers of amides 1–11. Examples of the
ECD spectra measured and calculated for arbitrarily chosen
amides 1–3 and 8 are presented in Figure 5 (see the
Supporting Information for the remaining results).
A number of triphenylacetic acid amides 1–11 prepared
for this study, displayed characteristic Cotton effects in their
ECD spectra in the 250–185 nm range (see Table 4 and a
full version of in the Supporting Information). The deriva-
tives with S configuration at the stereogenic center exhib-
1
ited a positive Cotton effect within the Lb transition range
(ca. 225 nm) and a negative CD couplet within the strong
1B band (205–185 nm). The sequence of signs of Cotton
effects was reversed in the case of 10, when an aliphatic
substituent at the stereogenic center was replaced by a
phenyl ring. In this particular case, the observed and calcu-
lated sequence of signs of Cotton effects is negative at
around 230 nm and positive at around 200 nm. To explain
this incoherence, we have initially compared the ECD spec-
tra of 5 and 10 with that measured for a model compound
in which the trityl group has been replaced by the tert-butyl
moiety. This was done to verify whether the initial sub-
Figure 5. Examples of experimental (solid lines) and calculated
(dashed lines) ECD spectra of triphenylacetamides 1–3 and 8.
strate, which contained an aromatic ring, was optically differs markedly from the ECD spectrum of 10, and shows
active without a reporter unit and showed intrinsic Cotton only one strong negative Cotton effect at 197 nm (see the
effects in a close or similar region of absorption as the acyl- Supporting Information), exactly in the spectral region
ated derivative. If such phenomenon had taken place, the where the positive Cotton effect for 10 was found. This
ECD spectra for 5 and 10 and for other derivatives contain- suggests a dominant role of induced over intrinsic Cotton
ing the aromatic moiety would have exhibited Cotton ef- effects in the net ECD spectrum of 10. However, for amide
fects originating from intrinsic and/or induced chirality that 5 the separation of the intrinsic and induced Cotton effects
appear in a similar or identical spectral region. The ECD is not possible and the overall ECD spectrum is rather
spectrum of N-pivaloyl amide of (S)-1-phenylethylamine dominated by the intrinsic Cotton effects.
8
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Molecular Propellers with Induced Chirality
Table 4. Short-wavelength ECD and UV data for triphenylacet-
amides 1–11 (measured in cyclohexane solution) and diphenylacet-
amides 12–17 (measured in acetonitrile solution).
Amide
Δε [nm]
Δε [nm]
ε [nm]
1
2
3
4
5
5
6
1.5 (229)
3.2 (227)
4.0 (228)
4.8 (228)
4.8 (228)
2.9 (210)
64.2 (227)
–5.0 (205)
–9.7 (204)
–13.6 (203)
–11.4 (204)
–32.7 (193)
81200 (192)
81200 (192)
81000 (191)
80100 (191)
114100 (189)
Figure 6. Structures of the lowest-energy conformers of amides (S)-
1 (a) and (S)-5 (b) characterized by opposite helicities of the trityl
groups.
–25.0 (197)
73200 (225) 88000
(192)
7
3.5 (228)
6.9 (234)
5.7 (232)
–4.6 (232)
96.5 (226)
–8.3 (199)
–24.5 (205)
–21.1 (205)
13.4 (198)
–35.0 (195)
83900 (192)
82700 (191)
84700 (192)
108900 (189)
76500 (225) 91600
(192)
65700 (191)
65700 (191)
67200 (191)
64500 (191)
95500 (189)
65000 (190)
8
9
Revisiting the analysis of the ECD spectra, we noted that
an increase in the size of the aromatic ring, as in the case
of 6, does not affect the sequence of signs of Cotton effects,
which is positive at 225 nm and negative at 205 nm. How-
ever, in the case of amides 6 and 11, the magnitudes of the
long-wavelength Cotton effects are higher than observed
and calculated for other molecules under study and result
from interchromophoric trityl-naphthyl rather than intra-
chromophoric interactions within the trityl group. Notably,
the ECD spectrum measured for a model (S)-N-pivaloyl-1-
10
11
12
13
14
15
16
17
0.2 (228)
0.5 (231)
0.3 (227)
1.7 (192)
1.7 (197)
3.8 (200)
2.1 (198)
–17.9 (194)
–2.2 (207)
–9.3 (214)
1.6 (230)
We then looked again at the calculated structures of indi- naphthylethylamine shows negative Cotton effect at 225 nm
vidual low-energy conformers of 1–11. For all aliphatic sec- and positive short-wavelength Cotton effect at 192 nm (see
ondary triphenylacetamides, the equilibrium between the the Supporting Information). Thus, in amides 6 and 11, the
trityl group conformers was shifted into MMM dia- intrinsic circular dichroism is overwhelmed by Cotton
stereoisomer in secondary amides, and into 0MM dia- effects generated by interchromophoric interactions.
stereoisomer, in tertiary amides. Furthermore, within each
The spectacular sensitivity of the triphenylacetic acid
of the two groups the orientation of the phenyl rings of the probe to remote molecular chirality is illustrated with the
Tr chromophore with respect to the alkylamide fragment derivative of (S)-2-aminobutane. Although the difference
followed the same pattern (see Figure 6, a). Upon replace- between methyl and ethyl substituents flanking the
ment of the l-alkyl substituent by the phenyl ring (5 and its stereogenic center is very small, the signs of the observed
N-methyl analogue 10) mutual orientation of the trityl Cotton effects follow the configurational scheme mentioned
phenyl rings in relation to the L- and M-substituents at the above. Increase of the substituent size gradually enhances
stereogenic center was reversed – the phenyl ring was situ- the amplitudes of the respective Cotton effects. Introduc-
ated in an environment previously occupied by the methyl tion of a methyl group at the nitrogen atom additionally
group (see Figure 6, b). For a molecule of defined chirality, increases the amplitudes of both long- and short-wave-
this event could easily take place upon a change of helicity length Cotton effects, keeping the same order of signs (i.e.,
of the Tr group from MMM to PPP (see Table 3), which +/–/+ for amines of S absolute configuration at the
indeed is observed in the CD spectra. This observation can stereogenic center, with the exception of 10). The UV ab-
be interpreted as an indication that the phenyl group is seen sorption maxima appear at approximately 195 nm and, in
by the system as smaller than the methyl group and that general, their positions are not affected by solvent, similar
the receptor group is very sensitive to even subtle changes to that observed in the case of ECD spectra.
in the size and electronic properties of the substituents at
Compared with amides 1–11, derivatives of diphenyl-
the chiral center. The overall molecular conformation of 5 acetic acid 12–17 are less suitable for stereochemical studies.
and 10 is stabilized by CH···π intramolecular interactions Although helicity enhancement was observed, the response
between a pair of nearly perpendicular phenyl rings, of measured by means of electronic circular dichroism spec-
which one is situated at the chirality center and the second troscopy was not as clear as that recorded in the case of the
is a constituent of the trityl group.
trityl group. The observed Cotton effects were weak and
To sum up, the polar amide group determines the helicity did not allow such simple structure-chiroptical property
of the trityl group, which may be either MMM/0MM or correlations to be obtained, as was possible for amides 1–
PPP/0PP, but the chiral substituent decides which dia- 11 (Table 4). This suggests that the trityl chromophore is
stereoisomer is energetically preferred. In other words, indeed exceptional.
chirality transmission proceeds through the cascade mode,
As an outcome of our study, we propose a simple model
in which the rigid amide group plays a role of a neutral of optical activity of chiral secondary and tertiary tri-
(configurationally stable) transmitter of chirality from a phenylacetic acid amides. The analysis of chirality trans-
permanent stereogenic center to a reporter group.
mission from the stereogenic center to the trityl group
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FULL PAPER
through the difference of steric bulk of the groups attached (MMM) and differ only in the conformation of the
to the chiral carbon atom allows the ECD spectrum to be aliphatic backbone, which does not affect the chiroptical
correlated with the substitution pattern within a molecule properties of the chromophore.
(Figure 7). An additional benefit of this analysis is the pos-
sibility to estimate the relative size of the substituents. Our
results suggest that the steric and/or electronic power of
substituents in the dynamic induction of chirality rises as
follows: Me Ͻ Et Ͻ iPr Ͻ tBu Յ cyclohexyl. Due to dif-
ferent mode of generation of Cotton effects, the aromatic
substituents form a separate group in which the steric and/
or electronic power of the naphthyl group for induction of
dynamic chirality is significantly larger than that of the
phenyl group. In terms of sensitivity, where only the abso-
lute values of the respective Cotton effects are considered,
the order rises as: Me Ͻ Et Ͻ iPr Ͻ tBu Յ cyclohexyl Ͻ
phenyl ϽϽ naphthyl.
Conclusions
We have demonstrated that effective chirality trans-
mission is not reserved for systems in which the inductor
and the receptor (trityl) are in immediate proximity, but
extends over a distance of about 4 Å utilizing a rigid amide
frame and weak intramolecular interactions between C–H/
C=O(amide) local dipoles. The triphenylacetic acid
chromophore displayed high sensitivity to relatively subtle
changes in the size of the substituent at the stereogenic cen-
ter. Comparable sensitivity in chirogenesis was reported for
a supramolecular system based on the formation of a com-
plex between chiral amines and the ethane-bridged
bis(zincporphyrin) and for readily available N-(1,8-
naphthaloyl)-2-aminobenzoyl (NAB) derivatives.[22a,48] X-
ray studies demonstrated that this novel class of chiral com-
pounds are likely to be of additional value because of the
porosity of their crystals, which can be rationally designed
by using appropriate functional groups.
A significant feature of the experimental and computed
ECD spectra for chiral triphenylacetamides is the uniformly
identical sequence of signs of Cotton effects for aliphatic
amides of S absolute configuration at the stereogenic cen-
ter; that is, positive at around 225 nm and negative at
around 200 nm, despite different populations of the con-
formers.
The study on chirality transmission within triphenyl-
acetic acid derivatives has been extended to bis(triphenyl-
acetamides) and the results will be published in due course.
Figure 7. Correlation model of ECD spectrum with the dominant
conformation for chiral secondary (a) and tertiary (b) tri-
phenylacetamides [projection down the N–C(=O) bond].
Experimental Section
Thus, for effective chirality transmission from the chiral
center to the reporter part of a molecule, the bent molecular
structure is not compulsory, as was required for O-trityl
ethers and N-tritylamines. One of the measures of the effec-
tiveness of the trityl-based receptor systems is a distance
between stereogenic center and the sp3 hybridized carbon
atom of the trityl group. Analysis of the available data
shows that the average C*···C(Ph3) distances for chiral O-
trityl ethers and N-tritylamines range from 2.44 to 2.50 Å,
whereas the analogous average distance estimated for
amides 1–11 is over 1.5 times longer and equal to 3.89 Å.
The dissymmetry factors (Δε/ε), estimated for a series of
structurally related chiral N-tritylamines [TrNHCH(Me)R]
and triphenylacetamides [TrCONHCH(Me)R] differing in
size of the R substituent are comparable. In the case of the
most important example of N-tritylamines, (R)-N-trityl-2-
aminobutane, the observed partial cancelation of the chir-
optical spectra has been rationalized by the equilibrium of
participating pseudoenantiomeric trityl structures, MPM
and PMP.[23] This is in contrast to amide 1, for which all
four low-energy conformers found computationally are
General: 1H and 13C NMR spectra were recorded with a Varian
VNMR-S 400 MHz instrument. Chemical shifts (δ) are reported in
ppm relative to SiMe4, and coupling constants (J) are given in Hz.
HRMS spectra were obtained with a Bruker 320 MS spectrometer.
UV and ECD spectra were recorded in spectroscopic grade cyclo-
hexane or acetonitrile with a JASCO J-810 instrument. FTIR spec-
tra were measured with a Bruker FTIR IFS 66/s in KBr pellets. A
Perkin–Elmer 341 polarimeter was used for optical rotation
([α]D) measurements (ca. 20 °C). Flash column chromatography
was performed on Merck Kieselgel type 60 (250–400 mesh). Merck
Kieselgel type 60F254 analytical plates were employed for TLC.
Melting points were measured with Büchi Melting Point B-545 and
are uncorrected. All reagents were used as purchased from com-
mercial suppliers. All solvents were provided by a local supplier
and were purified by conventional methods prior to use.
N-Methylamines and model N-pivaloylamides were prepared ac-
cording to previously published procedures.[49,50]
General Procedure for Synthesis of Triphenylacetamides 1–11: To
a suspension of triphenylacetic acid (1.2–1.5 mmol) in anhydrous
toluene (2 mL) containing one drop of DMF, thionyl chloride (0.6–
1.0 mL) was added dropwise. The mixture was heated to gentle
characterized by the same sense of chromophore helicity reflux at 80 °C for 3 h. After evaporation of all volatiles under re-
10 Eur. J. Org. Chem. 0000, 0–0
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Pages: 13
Molecular Propellers with Induced Chirality
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(S)-N-sec-Butyl-2,2,2-triphenylacetamide (1): Yield 83%; white so-
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(300 MHz, CDCl3, TMS): δ = 0.78 (t, J = 7.5 Hz, 3 H), 1.07 (d, J
= 6.6 Hz, 3 H), 1.28–1.45 (m, 2 H), 3.96–4.07 (m, 1 H), 5.49 (d, J
= 7.7 Hz, 1 H), 7.21–7.36 (m, 15 H) ppm. 13C NMR (100 MHz,
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X-ray Diffraction Studies: X-ray diffraction studies were performed
under standard conditions for compounds 1–3, 6–9, and 11, which
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was reported previously.[26] Crystal data are provided in the Sup-
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(for 2), -1010219 (for 3), -1010220 (for 6), -1010221 (for 7),
-1010222 (for 8), -1010223 (for 9), -1010224 (for 11), contain the
supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic
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[11]
[12]
Figures displaying the molecular structures as found in crystals are
included in the Supporting Information (Figures S1 and S2). All
investigated crystals were enantiomerically pure and contain
molecules with S configuration. Consequently, all the compounds
crystallize in one of the 65 Sohncke space groups lacking any
improper symmetry operations. Of the nine crystal structures for
which the X-ray data are available, five display doubling of the
asymmetric unit (ZЈ = 2).
[13]
Supporting Information (see footnote on the first page of this arti-
cle): Synthesis and spectroscopic data for compounds 1–17, details
of crystal structure determination, details of calculation procedures
and comments on the performance of the DFT methods, Cartesian
coordinates of all calculated compounds, full version of Tables 3
and 4, full version of Figure 6, Figures S1–S28 and ECD spectra
of model N-pivaloylamides.
[14]
[15]
Acknowledgments
This work was supported by a research grant from the National
Science Center (NCN), Poland (UMO-2011/03/ST5/01011). All cal-
culations were performed at the Poznan Supercomputing and Net-
working Center (grant number 217).
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/KAP1
Date: 16-12-14 13:51:54
Pages: 13
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Received: September 12, 2014
Published Online: ᭿
12
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O43182
/KAP1
Date: 16-12-14 13:51:54
Pages: 13
Molecular Propellers with Induced Chirality
Conformation Analysis
Weak but cooperative intramolecular inter-
actions, either CH···O hydrogen bonds or
local CH/CO dipole/dipole interactions,
play a key role in the process of spectacular
chirality transfer in triphenylacetamides.
N. Prusinowska, W. Bendzin´ska-Berus,
M. Jelecki, U. Rychlewska,*
M. Kwit* ......................................... 1–13
Triphenylacetic Acid Amides: Molecular
Propellers with Induced Chirality
Keywords: Conformation analysis / Chiral-
ity / Configuration determination / Circu-
lar dichroism / Density functional calcu-
lations / X-ray diffraction
Eur. J. Org. Chem. 0000, 0–0
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13