Dynamic Induction of Optical Activity in Triarylmethanols and Their Carbocations

Article abstract of DOI:10.1021/acs.joc.0c02289

A series of artificial triarylmethanols has been synthesized and studied toward the possibility of exhibiting an induced optical activity. The observed chiroptical response of these compounds resulted from the chiral conformation of a triarylmethyl core.

Full text of DOI:10.1021/acs.joc.0c02289

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Dynamic Induction of Optical Activity in Triarylmethanols and Their
Carbocations
Bartosz Stasiak,* Agnieszka Czapik, and Marcin Kwit*
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sı Supporting Information
ABSTRACT: A series of artificial triarylmethanols has been
synthesized and studied toward the possibility of exhibiting an
induced optical activity. The observed chiroptical response of these
compounds resulted from the chiral conformation of a triarylmethyl
core. The chirality induction from a permanent chirality element to
the liable triarylmethyl core proceeds as a cooperative and cascade
process. The OH···O(R) and/or (H)O···HorthoC hydrogen bond
formation along with the C−H···π interactions seem to be the most
important factors that control efficiency of the chirality induction. The
position of chiral and methoxy electron-donating groups within a trityl
skeleton affects the amplitude of observed Cotton effects and stability
of the trityl carbocations. In the neutral environment, the most intense
Cotton effects are observed for ortho-substituted derivatives, which
undergo a rapid decomposition associated with the complete decay of ECD signals upon acidification. From all of the in situ
generated stable carbocations, only two exhibit intense Cotton effects in the low energy region at around 450 nm. The formation of
carbocations is reversible; after alkalization, the ions return to the original neutral forms. Unlike most triarylmethyl derivatives known
so far, in the crystal, the triarylmethanol, para-substituted with the chiral moiety, shows a propensity for a solid-state sorting
phenomenon.
INTRODUCTION
The exceptional structural features and a wide-scope of
applications make triphenylmethane (TrH), and related
forming into one another; hence, neither trityl nor its ionized
■
12
forms are optically active. The induction of an optical activity
revealed in the appearance of non-zero Cotton effects (CEs) in
electronic circular dichroism (ECD) is achieved by linking
compounds of the general Ar X formula, interesting and still
3
3
chiral substituents to the central sp -hybridized carbon atom.
intensively explored objects of study. Besides being able to
protect a polar functional group and supramolecular synthons,
the presence of trityl(s) in a given molecular system is utilized
in molecular tectonics for construction of the 3D networks and
is crucial for the effective operation of some molecular
Adaptation of trityl to the structure of chiral secondary
alcohols, through the bevel-gear mechanism, was demonstrated
13
for the first time by Gawronski. Since then, a process of
chirality transmission from the permanent chirality element to
the stereodynamic trityl has been exploited by us and others
for stereochemical assignments of alcohols, amines, sulfides,
1
−3
devices.
The trityl-containing amino acids are promising
4
candidates for the lead structures in medicinal chemistry. The
tritylium ion, one of the first ever discovered, was recognized
for ages as an isolated curiosity of chemistry. Now, the
tritylium (triarylium) ions are employed as Lewis acid in
14
and selenides. For all systems studied so far, the final,
observed effects have provided evidence for a dynamic
5
15
induction of the optical activity, the detailed mechanism of
the chirality transfer phenomenon is rather case sensitive.
In contrast to the trityl radicals, the chiroptical properties of
6
synthesis, including catalytic stereoselective transfomations.
While early attempts to employ asymmetric catalysis with the
use of optically active carbocations provided unsatisfactory
results in terms of enantioselectivity, recent studies have
indicated an advantage of latent trityl cations in the catalytic
tritylium cations have not been yet the subject of an in-depth
16−18
study.
This remains rather an unexpected conclusion
7
−9
reactions.
Received: September 25, 2020
Published: December 22, 2020
Apart from applications in synthesis, the pioneering works of
Mislow and Iwamura on the triaryl molecular propellers,
exhibiting so-called residual stereochemistry, are considered
10,11
one of the foundations of dynamic stereochemistry.
In the
parent TrH, the aryl rings adapt the twisted C -symmetrical
3
conformation of either P or M helicity, dynamically trans-
©
2020 American Chemical Society
https://dx.doi.org/10.1021/acs.joc.0c02289
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when one takes into account the significance of tritylium (and
related) cations in chemistry and, especially, the growing
importance of these compounds in stereoselective synthesis
and in material chemistry. Recently, Suzuki and co-workers
have reported systems based on biphenyl-2,2′-diyl-type
carbocationthe latter may be useful at the next stage of
studies.
The synthetic routes to the 3−7 involved Mitsunobu
reaction between racemic or optically active 1-phenylethanol
and commercial hydroxyesters 1a−1c, followed by the
additions of respective Grignard reagents to ethers 2a−2c.
For comparison purposes, we have synthesized triarylmethanol
7 from ether 2d and chiral benzyl alcohols 8a−8c. To study
the effect of the optical purity of the sample on the possible
association mode in the solid state, the selected racemic
triarylmethanol rac-3a has been synthesized according to the
above-mentioned procedure.
19
dicationic dyes as those exhibiting strong chiroptical signals.
However, it can be supposed that the optical activity of
dication was due to the hindered rotation around the aryl−aryl
bond rather than to the specific helicity of the trityl fragments.
Hence, this and related molecules cannot be regarded as
systems dynamically adapting to the chiral environment.
With the exception of 4a, the 1H NMR spectra of
RESULTS AND DISCUSSION
■
As has been mentioned above, the importance of trityls and
trityliums in various aspects of chemistry is not related to the
growing interest in their dynamic stereochemistry. In fact, this
is somewhat understandable due to the complexity of the
problems to be solved. Therefore, continuing our interest in
the dynamic stereochemistry of chiral compounds, we have
decided to expand our study on triarylmethyl systems that may
exhibit an induced optical activity in the neutral and in the
cationic form. The systems planned to study should constitute
latent tritylium-based carbocations, easily transformed into
respective ions. Such derivatives would not constitute parts of
larger molecular or supramolecular systems, and the source of
optical activity will originate from the single chiral substituent
attached to the trityl core. This assumption excludes molecules
studied previously, as they do not form carbocations or the
generated trityliums did not show optical activity in the ECD.
The chiral substituent may stabilize the carbocation, and this
effect can be additionally supported by the presence of other
triarylmethanols, measured in CDCl , showed sharp signals,
3
which indicated a free rotation around C−C bonds. This fact
might suggest that these molecules are capable of adapting a
number of easily interconverting conformations differing in the
chromophore helicity, thus, of mutually canceling contribu-
tions to the CD spectra. However, despite our fears, the ECD
spectra of 3−6 exhibited CEs in the region of trityl absorption
(230−185 nm, Table 1, see the examples in Figure 1). For 3a−
1
3c, the first low energy CEs associated with L
electronic
b
transitions appear at around 225 ± 6 nm, whereas the second
1
intense ECD bands of B type are found at around 200 nm.
The third CEs of variable intensity appeared at a high energy
region. Both the sequence and intensity of the CEs are a
function of the position of a chiral substituent within skeleton
(vide infra). Introduction of additional chromophoric methoxy
group made very weak long-wavelength CEs (between 260 and
275 nm) visible, whereas for most of the cases 4−6, the higher
energy region of the spectra resemble the ECD spectra typical
of chiral trityl-containing systems.
20
electron donating groups. In this study, we have focused on
the chirality transfer phenomenon taking place in readily
available triarylmethanol alkoxyethers 3−7 (Scheme 1). As
As one can deduct from the data juxtaposed in Table 1, the
amplitudes of the most intense CEs, appearing at around 200
nm, ranged from rather small, Δε = −7 ((R)-6b) to high ones,
21
Scheme 1. Synthesis of Chiral Triarylmethanols 3−7 and
Structures of Model Compounds 8
|Δε| = 80 (for (R)-3a and (S)-6a). Thus, the dynamic
induction of an optical activity is a function of the substitution
pattern within the given triarylmethyl system. As expected, the
ortho-substitution with the chiral group is reflected in the most
intense CEs. Having neglected the differences resulting from
the opposite absolute configuration at the stereogenic centers,
the direct comparison showed a significant degree of similarity
between shapes of the ECD spectra of 3a, 4a, 5a, 6a (see
Figure S68 showing an overlay of the traces of the
corresponding ECD spectra). In these particular cases, the
effect of methoxy substituents os revealed in the magnitude of
the respective CEs only, and the largest steric congestion (as in
the case of 4a) was unrelated to the largest CE amplitudes. On
the opposite pole, there are derivatives in which the chiral
substituent occupies a para-position. In such cases, the effect of
chiral environment on the dynamic structure of triarylmethyl
chromofore, even supported by methoxy groups in ortho
positions, could be considered rather weak. Note that the
impacts of the chiral substituent in the para or meta positions
on the dynamic induction of optical activity, estimated based
on the CEs amplitude, were comparable.
mentioned before, these compounds are characterized by the
presence of a chiral substituent in one of the aryl rings, in
either an ortho, meta, or para position to the ipso carbon
attached to the “hub” of the propeller. This structural
differentiation was supposed to show the relationship between
the position of the chiral substituent (being the chirality
inducer) and the efficiency of the chirality transfer process. On
the other hand, methoxy substituents may play a 2-fold role
to increase steric congestion and/or to stabilize the forming
Since some of these derivatives contain proton-donating and
proton-accepting groups in the close proximity, one would
expect the strong influence of the solvent polarity on the
measured ECD spectra. However, the ECD spectra measured
for model compounds 3a, 3b, and 7 in cyclohexane,
acetonitrile, methanol, and acetonitrile containing up to 10%
(v/v) of hexafluoro-2-propanol did not exhibit substantial
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3
−1
−1
3
−1
−1
Table 1. UV (ε, in dm ·mol ·cm ) and ECD (Δε, in dm ·mol ·cm ) Data for 3−6 Measured in Acetonitrile and Acidified
Acetonitrile Solution
a
a
acetonitrile
acidified acetonitrile
4
4
compd
ε × 10 (nm)
10.5 (190)
Δε (nm)
−9.8 (221.5), −80.0 (198),
ε × 10 (nm)
Δε (nm)
3a
3b
3c
4a
4b
4c
5a
5b
n.a.
n.a.
n.a.
+
92 (188)
−2.7 (220.5), +16.5 (202),
6.4 (190)
−3.2 (231.5), −8.8 (215), + 26.0 n.a.
189)
9.9 (189)
n.a.
n.a.
n.a.
−
10.0 (189)
(
0.6 (273), 10.2 (197),
−2.9 (282), +2.5 (268), +66.3
n.a.
1
0.3 (191)
(200), −42.3 (190)
0.7 (274), 9.3 (198),
0.0 (189)
0.7 (273), 10.2 (199),
0.4 (190)
0.7 (281), 0.7 (274), 9.1
200), 9.2 (191)
0.6 (282), 0.7 (275), 8.9
201), 9.3 (189)
−1.9 (276), −2.5 (231), −13.1
0.4 (520.5), 0.7 (404), 0.7 +2.9 (517), +2.2 (486), +1.5 (403), −2.9 (260), −1.2
(271), 8.7 (201) (234), +1.5 (217), −8.4 (207), −6.3 (199), +2.8 (193)
1
(205), +13.9 (192)
−0.9 (254), +8.8 (217),
2.6 (508.5), 1.4 (431), 1.1 −1.6 (263.5), −1.3 (256), +8.9 (219), −24.3 (189)
b
1
−18.7 (193)
(269), 12 (185)
−2.0 (264), +2.2 (237), −58.1
n.a.
n.a.
n.a.
(
(202.5), +71.5 (189)
−1.2 (272.5), −1.3 (235), +1.1 n.a.
(218), −12.2 (207),
(
+
7.5 (191)
5
c
0.7 (282), 0.7 (275), 7.5
201), 7.9 (189)
−0.9 (272), +3.3 (215), −12.0
(191.5), −12.3 (189)
0.6 (560), 0.6 (479), 0.6
+2.4 (217), −7.7 (192), −6.9 (187)
(
(274), 8.0 (202),
b
1
2 (185)
6
6
6
a
b
c
0.7 (275), 3.1 (288),
0.8 (191)
+12.5 (226.5), +82.8 (201),
4.3 (503.5), 0.8 (396.5), 1.2 −3.6 (501.5), −1.6 (402), +2.0 (355), +3.1 (270), −6.2
b
1
−74.6 (190)
(271), 12 (185)
(222), +26.5 (199), −11.8 (188)
0.5 (283), 0.6 (276), 2.9
227), 11 (189)
−1.1 (277), −1.3 (233), +1.8
4.9 (503), 1.5 (405.5), 1.2 +11.3 (508), +8.0 (408), −2.8 (353), +1.6 (269), −2.0
b
(
(219), −6.7 (207), +1.8 (193)
(270), 12 (185)
(235), −4.0 (215), −10.6 (197), +7.5 (189)
0.5 (284), 0.5 (277), 3.0
232), 8.5 (198),
.5 (190.5)
−0.5 (271), +4.4 (216), +4.3
(204), −15.7 (194),
−17.0 (192)
8 (484), 1.8 (268),
+1.6 (478), +1.4 (449), +6.5 (218), −13.1 (190)
b
(
9
12 (185)
a
The concentration of analytes ranged from 1.0 to 2.0 × 10−4 mol L . The spectra were recorded in pure acetonitrile or in acetonitrile containing
up to 10 equiv of trifluoroacetic acid per 1 equiv of the alcohol (see the Experimental Section for details), from 600 to 185 nm, with a scan speed of
00 nm min and with 16 accumulations. The end of the measuring range.
−1
−
1
b
1
relation to the ECD spectra measured for their triarylmethanol
counterparts. Thus, in the triarylmethanols 3−6, the intrinsic
CD is overwhelmed by the CEs generated by the chiral
structure of the trityl chromophore. The ultimate confirmation
of the ongoing chirality transfer process was the ECD spectrum
of 7. The compound 7 does not contain any additional
aromatic chromophore; thus, the observed induced optical
activity originated solely from the chiral structure of the
triarylmethyl moiety.
Having confirmed the dominant role of the conformation of
the triarylmethyl moiety in generating a dynamic optical
activity, we will give a rationale on the possible chirality
transmission mechanism in compounds of this type. This can
be done by two ways: either experimentally by careful analysis
of X-ray data (if available) or by using theoretical calculations
at a suitable level of theory. The latter approach seems to be
more versatile as it allows not only for the determination of the
preferred structures but also for the calculation of the ECD
spectra.
Figure 1. ECD spectra of (R)-3a, (S)-3b, (S)-3c, and (R)-7 measured
in acetonitrile (solid black lines) and calculated at the IEFPCM/TD-
CAM-B3LYP/6-311++G(2d,2p)//IEFPCM/B3LYP/6-311++G(d,p)
level (dashed blue lines). The calculated ECD spectra were
Boltzmann-averaged based on ΔΔG values. Wavelengths were
corrected to match the experimental UV maxima.
The comparison and, more importantly, compliance of the
experimental and theoretical ECD spectra allows, among
others, for the determination of conformational equilibria,
differences. Thus, we can conclude that the effect of the
solvent on the observed Cotton effects can be considered as
negligible for neutral species 3−7.
The naturally emerging question is the one about the origin
of the observed optical activity in triarylmethanols. First, we
had to verify whether the 1-phenylethanoxy moiety exhibits
intrinsic Cotton effects in a similar region of absorption as the
trityl group. For this purpose, the model compounds 8a−8c
were synthesized. The ECD spectra measured for 8a−8c
showed the CEs of lower amplitudes and blue-shifted in
22
albeit not directly. Since the experimental X-ray data are
limited (vide infra) and the direct relationship between the
structure in the solid state and structure in solution is
sometimes questionable, at first we will focus on the results of
the theoretical calculations. To avoid overloading the text with
unnecessary details, which in turn obscure the problem, we
would point out some generalities. The remaining theoretical
results, less relevant to the discussion, available in the SI.
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The theoretical calculations, performed at the IEFPCM/
Table 2. ΔΔG-Based Percentage Populations (Pop.) and
Helicities of Trityl Chromophore Calculated for the Lowest
Energy Conformers of 3a−6c at the IEFPCM/B3LYP/6-
311++G(d,p) Level of Theory
23,24
B3LYP/6-311++G(d,p) level,
preceded by the systematic
conformational search, allowed us to determine structures of
thermally accessible conformers of compounds 3−7 and
establish structure-forming factors. The number of conformers
with relative Gibbs energy values (ΔΔG) ranging from 0 to 2
a
b
compd
pop.
helicity
−
1
3a (conf 58)
58
28
28
32
17
20
32
15
17
43
20
78
PPP
PPP
MMM
PPP
MMM
MMM
PPP
MMM
MMM
MMM
MMM
MMM
kcal mol vary in the number and position of the substituents.
Triarylmethanols 3a, 6a, and 6c are characterized by the lowest
number of stable conformers, 3, 4, and 4, respectively.
Introducing methoxy groups in the meta positions results in
a significant increase of the number of thermally accessible
conformers, up to 29 for 5b. In general, the triarylmethanols
having a chiral substituent on the meta position are
characterized by the highest number of conformers in
comparison to their ortho- and para-substituted counterparts
3
3
4
4
4
5
5
5
6
6
6
b (conf 28)
c (conf 24)
a (conf 18)
b (conf 34)
c (conf 1)
a (conf 12)
b (conf 26)
c (conf 44)
a (conf 13)
b (conf 17)
c (conf 49)
(
3b, 8; 4b, 28; 5b, 29; 6b, 10 conformers). It was well-
established that one of the consequences of the structural
diversity, manifested, inter alia, by a large number of
conformers, is the deletion of mutual contributions to the
overall CD spectra by the respective conformational stereo-
a
The conformers are numbered according to their appearance during
b
the conformational search. Helicity was determined on the basis of
the value of O−C−C −C
angles (of the two possibilities the
absolute values ≥90° has been chosen).
ipso
ortho
2
2
isomers. The measured chiroptical properties are linear
combinations of the contribution of each species present in the
sample to the total observed value. The parameter that needs
to be taken into account as well is the population of a given
species (conformer) in the equilibrium. Remaining in the field
of ECD spectroscopy and limited the discussion to the
compounds studied here, the actual contribution of individual
conformational diastereoisomers to the overall spectrum is a
function of the specific helicity of the chromophore, the
generated rotator strengths and, last but not least, their
population. Therefore, for meta-substituted triarylmethanols,
the large number of conformers close in relative energy and
characterized by opposite helicities of the chromophore
resulted in deterioration of observed and calculated CEs
compared to that observed in the case of compounds ortho-
substituted by chiral moiety.
From the point of view of the possibility of exhibiting the
induced optical activity, the β −β torsion angles which
1
3
determine the helicity of the trityl chromophore, either M
−90° < β < 0°) or P (0° < β < 90°) are the most important
(
ones. This particular structural feature may be further
correlated to chiroptical properties, namely the sequence of
the Cotton effect appearing in the spectral region of the trityl
UV absorption. Investigation of the data (Table 2, see the SI
for the remaining data) led to conclusion that in the majority
of cases, the trityl chromophore exhibits a tendency for
adapting homohelical (quasi-symmetrical) conformation,
25
either MMM or PPP. The exceptions to adapt heterohelical
conformations (MMP or MPP) are scarce. However, even
when considering the lowest energy conformers only, there is
no direct relationship between preferred chromophore helicity
and the absolute configuration at the stereogenic center of the
chiral substituent.
The substitution in para position limits the number of
possible interactions between chiral fragment and remaining
aryl rings in triarylmethanols 3c, 4c, 5c, and 6c. Both sides of
the phenyl ring, para-substituted by the chiral moiety, are
undistinguishable, which in turns reduces the number of
possible conformers. Only in the cases of 3a and 6c does the
population of the ΔΔG-based lowest energy conformers
exceed 50% (see Table 2). For compounds characterized by
much higher number of thermally available conformers, the
populations of the lowest energy one does not exceed 20%.
However, it is worth noting that for the specific case, the
highest abundance of a given conformer does not necessarily
translate into its greatest effect on the overall ECD spectrum
As far as possible, the overall helical structure of the
chromophore in the isolated molecules is determined by the
OH···O(R) hydrogen bond (see example structures in Figure
2
a and Figures S1−S15). In turn, the OH···O(R) hydrogen
bond formation controls conformation of one of the aryl rings.
The (H)O···HorthoC and C−H···π interactions stabilize the
conformation of the second aryl ring, whereas the third one
adjusts its conformation to the conformation of the remaining
two that is stabilized by CH···π interactions. Thus, one would
say that the structural information is transferred by the cascade
process, which is, in general, similar to the recently proposed
process of chirality transfer taking place in trityl-containing
(
vide infra).
The conformation of each conformer can be determined by
26
a set of torsional angles α (H−O−C −C ), β -β (O−
sp3
ipso
1
3
alcohols. In the cases where OH···O(R) hydrogen bonding is
not present in the molecule, the (H)O···HorthoC interactions
constitute the most important conformation-controlled factor.
The presence or absence of an OH···O(R) hydrogen bond in a
given conformer reflects in the values of the α angle. Since the
general definition of the α angle is not so precise (there are
three ipso and six ortho carbon atoms in the triarylmethane),
we found the chiral substituent to be more important than the
MeO group or the proton regardless of its position within the
ring. Consistently, we have decided to prioritize the aromatic
ring, substituted by the chiral moiety. Therefore, the α angle
C −C −C ), γ (C −O−C*−H) and ω (O−C*−C
ortho
−
sp3
ipso
ortho
ipso
ipso
C
). The latter two torsion angles determine the
conformation of the chiral substituent with regard to the
aromatic ring to which it is attached. In the majority of cases,
the position of proton attached to the stereogenic center,
described by the γ angle, remains either (+)- or (−)-synclinal
(
sc). The electrostatic C H···O interactions between the
ortho
proton from the ortho positions of an aromatic ring from the
chiral moiety and the ether oxygen atom enforced the ω angle
to adapt (+)- or (−)-sc conformation.
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conformational equilibrium is shown by those conformers in
which the OH···OMe hydrogen bonding controls the
structure.
The O−H···O distances are rather short and range from
.834 to 1.945 Å. On the other hand, in the case of no
1
possibility to form the intramolecular hydrogen bond, the
optimal conformation of the hydroxyl group is the one that
minimizes sterical interactions and at the same time allowing
the (H)O···HorthoC interactions. The examples of low-energy
structures of triarylmethanols of conformations controlled by
OH···O(R*), OH···OMe, or sterical interactions are shown in
Figure 2.
A high compatibility between the experimental and
theoretical ECD spectra (calculated at the IEFPCM/TD-
2
3,24
CAM-B3LYP/6-311++G(2d,2p) level)
confirmed that
both structures and relative energies of conformers have
been correctly estimated. The additional value of these studies
is the correlation between the signs of the Cotton effect
sequence and the helicity of triarylmethyl chromophore as well
as determining the particular conformer which influences the
overall ECD spectrum most. As we have mentioned above, the
simple relationshipthe higher abundance of a given con-
former, the greater effect on the overall ECD spectrumis not
always fulfilled.
For example, such counterintuitive results have been
obtained for the simplest case of 3a. As the computational
analyses performed for 3a have revealed, there are only three
thermally available conformers, nos. 1, 10, and 18 (shown in
Figure 3a), and each of which is stabilized by the OH···O(R)
hydrogen bond along with the (H)O···HorthoC and C−H···π
interactions. The lowest energy conformer no. 10 of alcohol 3a
is the most abundant among all thermally accessible con-
formers (58% based on ΔΔG values). The PPP helicity of the
chromophore corresponds to the rather unexpected negative,-
positive/negative,positive/negative (∓/ ∓ /−) sequence of
Cotton effects appearing in the spectral range between 230 and
Figure 2. Examples of the low energy structures of triarylmethanols
calculated at the IEFPCM/B3LYP/6-311++G(d,p) level, having
conformation controlled by (a) OH···O(R*); (b) OH···OMe; and
(
c) sterical and (H)O···HorthoC interactions. Dashed lines indicate
possible attractive interactions. Distances are in angstroms. The inset
shows the values of the α (H−O−C −Cipso) angles, which determine
sp3
the conformation of OH group in relation to the aromatic ring having
chiral substituent.
always adopts the (+)- or (−)-sc conformation, with respect to
the aromatic ring containing “chiral” hydrogen bond acceptor.
However, in the case of competitive OH···OMe interactions
with the oxygen atom from the methoxy group, the α angle is
either (+)- or (−)-antiperiplanar (ap) or in the selected cases,
(
+)- or (−)-sc, depending on the spatial relation of OH group
and aromatic rings with chiral and MeO substituents.
Noticeably, in the particular case of 4a, the predominance in
Figure 3. (a) Calculated at the IEFPCM/B3LYP/6-311++G(d,p) level low-energy conformers of 3a, stabilized by the OH···O(R) hydrogen bond
and by the (H)O···HorthoC and C−H···π interactions (indicated by dashed lines). Distances are in angstroms. (b) ECD spectra calculated for
individual conformers of 3a at the IEFPCM/TD-CAM-B3LYP/6-311++G(2d,2p) level. Vertical bars represent calculated rotatory strengths.
Wavelength were not corrected.
6
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The Journal of Organic Chemistry
80 nm (see Figure 3b). The same spectral pattern is found for
pubs.acs.org/joc
Article
1
the PPP-helical conformer no. 18, characterized by the 12% of
abundance. Although both conformers 0 and 18 strongly
prevail in the equilibrium (in total 70%), it is conformer no. 1
that determines the shape of the overall CD spectrum. This
particular conformer is characterized by the MMM helicity of
the chromophore, which corresponds to the ±/+ sequence of
Cotton effects in the calculated ECD spectrum (see Figure
3
b).
Conformer no. 1 of 3a is characterized by the highest values
of calculated Cotton effects among all thermally accessible
species, which overwhelm the CEs calculated for the more
abundant conformer no. 10 and for conformer no. 18. After
having averaged the calculated ECD spectra accordingly to the
relative populations of respective conformers, the resultant
ECD spectrum has reproduced well the experimental one.
The observed induction of an optical activity provides
evidence for the concept of chirality induction within
triarylmethyl derivatives. However, it is more interesting to
demonstrate the induced optical activity in triarylmethyl
cations generated from 3−6 by in situ treatment of the
acetonitrile solution of the respective alcohol by trifluoroacetic
acid (TFA). The ECD spectra were to have shown induced
CEs in the long-wavelength region, between 600 and 350 nm.
Unfortunately, in the case of the most promising derivatives 3a
and 4a, our expectations collided with reality, as we observed
the complete decay of the ECD signals after acidification.
Although we observed a very fast reversible color change to
red, even by increasing the scanning speed to 20000 nm
1
Figure 4. Traces of H NMR (400 MHz, CDCl ) spectra of (a) 4a;
(
3
b) 4a measured immediately upon acidification by anhydrous
trifluoroacetic acid; and (c) isolated decomposition product 9b.
Arrows indicate acetophenone proton signals. Asterisks indicate trace
solvent peaks. Note that the green peak appearing at 3.72 ppm (b) is
obscured by the high-intensity blue peak from the lower spectrum of
b. Both peaks originate from OCH3 protons. (d) Possible
decomposition mechanism of ortho-substituted derivatives 3a and
−
1
min ,we were not able to record any ECD spectrum for an
acidified sample of 3a and 4a. The subsequent study revealed
that the carbocations generated from 3a and 4a rapidly
underwent cleavage of the C−O ether bond, providing the
respective o-hydroxytriphenylmethane derivatives 9a and 9b
9
1
4a upon acidification.
and acetophenone, as indicated by H NMR (400 MHz,
CDCl ) measurements (see Figure 4a−c). Just after addition
3
of anhydrous TFA to the test NMR tube, the OMe singlets,
formed as a result of the nucleophilic attack of the water
molecule on the positively charged benzyl carbon atom. Acidic
hydrolysis of the hemiacetal led to formation of acetophenone
and the respective o-hydroxytriphenylmethane derivatives 9a
and 9b.
1
visible at around 3.5 ppm in H NMR (400 MHz, CDCl )
3
spectrum of 4a (shown in Figure 4a), vanished. Instead, two
sharp singlets originating from CH CO and OCH protons
3
3
have appeared at 2.73 and 3.72 ppm, respectively. Additionally,
the aromatic region of the NMR spectrum has changed, and
three sets of multiplets, of the relative integration 2:1:2, have
appeared at 7.51, 7.66, and 8.05 ppm, respectively (Figure 4b).
All of the signals appeared at δ 2.73, 7.51, 7.66, and 8.05 and as
observed in NMR spectrum shown in Figure 4b have
originated from acetophenone protons, whereas the remaining
Fortunately, the other substitution patterns make the formed
species more stable. The possibility for generation and the
stability of the given carbocation is not directly reflected in the
intensity of Cotton effects in the ECD spectra. For example, in
the case of the para-substituted carbocation generated from 6c,
the most intense (within the compounds studied) long-
wavelength UV band is observed at around 470 nm, while the
ECD spectrum in this spectral region remains flat. In contrast,
for all-meta-substituted 5b we did not observe the generation
of carbocation under these conditions. Thus, the effective
induction of an optical activity is the resultant of the
substituents ability to stabilize carbocation and efficiency of
chirality transmission from the permanent stereogenic center
to the tritylium chromophore.
1
signals are ascribed to the decomposition product 9b (the H
NMR, 400 MHz, CDCl ; spectrum of isolated 9b is shown in
3
Figure 4c). To explain this phenomenon, we have referred to
the available literature precedents. Starnes studied kinetics and
mechanism of thermal or acid-promoted decomposition of,
27
inter alia (o-benzyloxypheny)diphenylmethanol. After treat-
ment of the compound with TFA, the ether was cleaved and
provided benzaldehyde and o-hydroxytriphenylmethane. Hy-
dride transfer from the benzyl position to the positively
charged carbon atom was considered a key step for the entire
process. Subsequent studies by Lomas and co-workers
The most intense chiroptical responses within the whole
series were observed for carbocations generated from 6a and
+
+
6b (denoted here as 6a and 6b , respectively, see Table 1). In
both species, the methoxy groups are placed in para positions,
whereas the chiral substituent occupies either the ortho or meta
position. In particular, the induced CEs observed for
carbocation generated from 6b are exceptional. It should be
emphasized that that acidification, except the generation of
2
8
confirmed this hypothesis. Thus, on the basis of the
literature evidence, we have proposed a possible decom-
position mechanism of 3a and 4a upon acidification with TFA
(Figure 4d). The reaction involves formation of the tritylium
cation, and then, after [1,5]-hydride shift, a hemiacetal is
6
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carbocation, did not lead to other changes in the constitution
of the molecule of 6a and 6b in the time-scale of standard H
NMR measurements (see Figure 5). The appearance of signals
chiral ones, did not change the shape of the measured spectra
of generated carbocations (see Figures S63 and S64).
Therefore, even the use of both enantiomeric forms of chiral
acids did not affect the chirality transfer in tritylium ions.
1
+
Unfortunately, the attempts made for isolation of 6a and
+
6
b in analytically pure form have been unsuccessful so far.
The DFT calculations (IEFPCM/TD-CAM-B3LYP/6-311+
23,24
+
G(2d,2p)//IEFPCM/B3LYP/6-311++G(d,p) level)
al-
lowed to shed light on the origin of the observed CEs for the
+
most interesting example carbocation 6b .
First, despite the large diversity of thermally accessible
structures, one of the conformers found (no. 40) is dominant
(
the most abundant). Second, as expected, this particular
conformer has also a dominant contribution to the overall UV
and ECD spectra. Thus, it seems to be justified to describe the
+
chiroptical properties of 6b based on this particular structure.
Third, the tendency to flatten the carbocation structure does
not disturb the overall propeller structure. In other words,
while the central and the ipso carbon atoms lie in one plane,
the aromatic rings, as a whole, are twisted relatively to each
+
other. In the case of the lowest energy conformer of 6b , which
1
+
Figure 5. Traces of H NMR (400 MHz) spectra of (a) 6a, measured
is discussed here, the twist angles ω = Cipso−C −C −Cortho,
ipso
in CDCl ; (b) 6a, measured in CDCl containing 1 equiv of
anhydrous TFA; (c) 6a, measured in CDCl containing 2 equiv of
anhydrous TFA; (d) 6b, measured in CDCl ; (e) 6b, measured in
CDCl containing 2 equiv of anhydrous TFA. Asterisks indicate trace
are negative and ranged from −40 to −34°. Fourth, sterical
interactions between the aromatic rings of the chiral
substituent and one of the phenyl ring from the triarylmethyl
core induce propensity to the conformational diastereoisomer-
ism. Fifth, the lowest energy UV absorption band, appearing at
around 500 nm, is due to the HOMO−LUMO and
HOMO(−1)-LUMO electronic transitions that involve
orbitals from triarylmethyl core (see Figure 6). The former
3
3
3
3
3
solvent peaks.
at 192.8 and 194.6 ppm, for 6a+ and 6b , respectively)
+
(
13
characteristic for trityliums, observed in the C{1H} NMR
101 MHz, CDCl ) spectra originating from charged “central”
(
3
carbon atom, has additionally confirmed formation of
2
9
carbocations.
We emphasize that the formation of the carbocation is fully
reversible. After adding DMSO-d containing some water to
6
1
the NMR test tube, the measured H NMR (400 MHz, CDCl
3
+
TFA) spectra remain in full accordance with that measured
previously for neutral 6a and 6b. Moreover, the ECD spectra
measured for 6b, in alternately acidified and alkalized
acetonitrile solution, confirm almost perfect reversibility of
30
the process, up to three cycles (see the SI). Subsequent ECD
measurements have shown that the shape of the spectrum of
+
6
b did not change within 2 weeks of in situ generating the
carbocation in solution.
The results of measurements in other freshly distilled and
anhydrous solvents (dichloromethane, dimethylformamide,
tetrahydrofuran, and DMSO) and with the use of TFA as
acidifying agent, have indicated some solvent effect (see
Figures S61 and S62) on ECD spectra of 6a and 6b. The ECD
measurements performed in dichloromethane and acetonitrile
have provided convergent results; generation of carbocation
was observed. On the contrary, in other used solvents, we did
Figure 6. (a) UV (upper panel) and ECD (lower panel) spectra of
6b measured in the acidified acetonitrile (solid black lines) and
calculated at the IEFPCM/TD-CAM-B3LYP/6-311++G(2d,2p) level
+
(
blue lines). The calculated ECD spectra were Boltzmann-averaged
based on ΔΔG values. The wavelengths were corrected to match
experimental UV maxima. Insets shows the UV and ECD spectra
calculated for the lowest energy conformer of 6b . The vertical bars
+
represent oscillatory or rotatory strengths, respectively. (b) Molecular
orbitals involved in the low energy electronic transitions in the lowest
+
+
not observe generation of carbocations 6a and 6b . Although
the detailed mechanism according to which the solvent may
inhibit the carbocation formation is not known, it can be
+
energy conformer no. 40 of 6b .
31
assumed, based on previous work, that basic solvents of the
THF type form oxonium compounds with triarylmethane
derivatives.
electronic transition generates positive rotatory strength,
visible in the ECD spectrum as positive low-energy CE at
around 500 nm, whereas the latter electronic transition is
associated with small negative rotatory strength insignificant
with respect to their contribution to the overall CE. The next
rotatory strength, responsible for generating the second
positive CE, results from electronic transitions that mainly
To establish the counteranion effect during acid treatment,
we have used acidifying agents other than TFA, namely acetic
acid, methanesulfonic acid, HBF , and both enantiomers of
4
camphorsulfonic acid. With the exception of acetic acid, which
has turned out inefficient, the use of other acids, including the
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involve the π orbitals of the chiral substituent and the LUMO
orbital. The higher energy spectral region is again dominated
by the transitions that involve triarylmethyl core orbitals.
At the last stage of this study, we have referred again to the
calculation results. By comparing the respective neutral and
charged structures, we wanted to show the factors that
determine the efficiency of the chirality transfer and thus the
induction of optical activity in carbocations. The overlays o+f
found in the Supporting Information). Recently, it was found
that some racemic trityl-containing compounds are prone to
26,32
crystallize as solid solutions of enantiomers.
The trityl
substituent can act as a supramolecular protecting group for
the stereogenic center in triphenylacetyl acid derivatives, and
the solid solution of enantiomers can be formed. The
phenomenon of formation of solid solutions of enantiomers
in organic crystals is not frequent; according to the literature
33
the lowest energy conformers of 6a (conf no. 13) and 6a
data, it concerns less than 1% of racemic crystals. To check
the possibility to form solid solution, we have examined rac-3a
as a representative example.
+
(
conf no. 29), 6b (conf no. 17) and 6b (conf no. 40),
respectively, have shown changes, or lack thereof, in the
structure upon the ionization (Figure 7).
In accordance to the theoretical results, the predilection to
the OH···O(R) hydrogen bond formation is also seen in these
crystal structures. With the exception of 4c, conformation of
the molecule is additionally stabilized by intramolecular edge-
to-face interactions between one aryl ring from the triaryl-
methane and the substituent’s phenyl ring. The dihedral angle
value between suitable aryl rings is in the range of 56.69° (for
(
S)-6a) and 87.51° (for (R)-3a) and the distance of the
hydrogen atom from the plane designated via C atoms is in the
range of 2.696 Å (for rac-3a) and 2.879 Å (for (S)-4a) (see
Figure 8a). There are no strong intermolecular O−H···O
Figure 7. Overlays of the lowest energy conformers of (a) 6a (conf
+
no. 13, blue) and 6a (conf no. 29, red); (b) 6b (conf no. 17, green)
and 6b+ (conf no. 40, deep yellow), calculated at the IEFPCM/
B3LYP/6-311++G(d,p) level. The oxygen atoms are shown as balls,
hydrogen atoms have been omitted for clarity.
In the case of the lowest energy conformers of neutral and
positively charged 6a, ionization did not cause drastic changes
in the structure. The conformation of the lowest energy
conformer no. 13 of 6a is controlled by the OH···O(R*)
hydrogen bond. Upon ionization, the conformation of the
+
lowest energy conformer no. 29 of 6a retained more or less
the same as in its neutral counterpart. In the absence of the
+
hydrogen bond, the structure of conformer no. 29 of 6a is
+
controlled by the electrostatic interactions (R*)O···C and by
steric repulsions between the protons in ortho positions of
phenyl rings forming tritylium ion as well as between methyl
group of chiral substituent and one of the phenyl ring from the
propeller. As a consequence, the chirality transfer in such
neutral and charged species proceeds in a similar cascade
manner as described above.
Even at first glance, the ionization of 6b triggered significant
changes in the structure of the cation. The conformation of the
lowest energy conformer no. 17 of 6b is determined by the set
of the (H)O···HorthoC and C−H···π interactions, responsible
for the chirality transfer from permanent stereogenic center to+
the propeller. In the lowest energy conformer no. 40 of 6b
these interactions lost their importance or were not present at
all. As mentioned above, the propeller structure was flattened
upon ionization; however, due to the inevitable steric
repulsions between the protons in ortho positions, the phenyl
rings are forced to be twisted relatively to each other. The
sense of the propeller twist is determined by the interactions
between the aromatic rings, one from the chiral substituent
and one from the triarylmethyl core.
Figure 8. (a) Intramolecular edge-to-face interaction in molecular
structure of compound 3a; the C−H···π interactions and intra-
molecular O−H···O hydrogen bond are indicated as dashed lines. The
distance is in angstroms. (b) C−H···π interactions found in the crystal
of 4a. (c) Overlay of X-ray diffraction determined solid-state
structures of the conformational diastereoisomers (PPP)-A (green)
and (P0P)-B (blue) of 4c. (d) Folded, alternating layers of A and B
molecules found in the crystal of 4c.
hydrogen bonds in the structures of studied crystal. The van
der Waals and electrostatic interactions along with directional
interactions, such as weak C−H···O and C−H···π intermo-
lecular interactions, predominate in the solid state (Figure 8b
and Figure S136).
Using the rac-3a as the example, we have intended to
investigate the effect of the presence of an inversion center on
the intermolecular interactions in the crystal, as well as on the
geometry of the molecule. From the point of view of potential
applications of this and related compounds in crystal
engineering, the formation of a mixed crystal would be of
particular interest. However, rac-3a crystallized as racemic
Although most of the derivatives studied here did not form
crystals suitable for X-ray diffraction measurements, there are
some exceptions, though. Slow evaporation of the solvents
allowed to obtain crystals of (R)-3a, (S)-4a, (R)-4c, and (S)-6a
(
details on the crystallization of individual compounds can be
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crystals, which means that the enantiodiscrimination in crystal
structure is not disturbed. Moreover, the molecular geometry
observed in crystals of (R)-3a is preserved, which confirms that
the intramolecular O−H···O hydrogen bond and edge-to-face
interaction are essential for maintaining molecular conforma-
tion.
measured on a Nicolet iS 50 spectrometer using ATR module. A
JASCO P-2000 polarimeter was used for specific optical rotation
(
[α] ) measurements (carried out at ca. 20 °C).
D
Column chromatography was performed on J.T. Baker silica gel 40
μm (chromatography grade). Merck Kieselgel type 60F254 analytical
plates were used for TLC analyses. Melting points were measured on
̈
Buchi Melting Point B-545 and uncorrected. All reagents were used as
In the exceptional case of triarylmethanol 4c, two
independent molecules denoted as A and B have been found
in the asymmetric unit (Figure 8c). In the crystal, the
conformational diastereoisomers (PPP)-A and (P0P)-B form
separate layers, so in this particular case, one can say about a
solid-state sorting phenomenon. Such sorting may be found in
crystal structures, where the Z′ number is multiplied. In that
case, however, we expected pseudosymmetry between the
molecules to occur, which is not observed here. The surface of
these layers is folded, which allows them to interpenetrate and
the whole supramolecular structure is stabilized by the sets of
C−H···π interactions (Figure 8d).
purchased from commercial suppliers. All solvents were provided by a
local supplier and were purified by conventional methods prior to use.
The starting esters 1a-1c are commercial and have been purchased
from Sigma-Aldrich.
General Procedure for Synthesis of Chiral Hydroxy-
Substituted Salicylic Esters Using m-Salicylic Ester As an
Example. Under an argon atmosphere, ethyl 3-hydroxybenzoate (1 g,
6.02 mmol, 1 equiv), triphenylphosphine (2.15 g, 8.2 mmol, 1.36
equiv), and (R)-1-phenylethanol (1 g, 8.2 mmol, 1.36 equiv) were
dissolved in 50 mL of freshly distilled THF. The reaction mixture was
stirred for 5 min and then placed in an ice bath and cooled to 0 °C.
Then DIAD (1.6 mL, 8.2 mmol, 1.36 equiv) was added dropwise over
30 min. After 15 min, the ice bath was removed and the mixture was
stirred overnight at room temperature. Then THF was removed
under reduced pressure, and the residue was dissolved in a mixture of
diethyl ether and hexane. After a few minutes, white precipitate was
formed, which was removed by filtration. The filtrate was evaporated
to dryness and the crude product was purified by column
chromatography on silica gel (eluent: hexane).
CONCLUSIONS
■
In conclusion, we have designed and proven the possibility of
the dynamic induction of the optical activity in readily available
latent trityl-based carbocations. These compounds are
smoothly converted into corresponding cations through
acidification. However, the position of the chiral substituent
is crucial for the stability of the ion. The ortho-substituted
chiral alkoxy group triarylmethanols are prone to rapid
decomposition in the acidic environment.
Methyl (R)- or (S)-2-(1-phenylethoxy)benzoate (2a). rac-2a:
isolated yield, 1.5 g, 61%, colorless oil (eluent: hexane). (R)-2a:
isolated yield, 0.87 g, 69%, colorless oil (eluent: hexane). (S)-2a:
1
isolated yield, 0.92 g, 73%, colorless oil (eluent: hexane). H NMR
(
7
(
300 MHz, CDCl ) δ 7.75 (d, J = 7.6 Hz, 1H), 7.67−7.16 (m, 6H),
3
.16−6.66 (m, 2H), 5.38 (q, J = 12.7, 6.3 Hz, 1H), 3.91 (s, 3H), 1.67
The process of chirality transmission is demonstrated by the
rise in the CEs originating mainly from the twisted form of the
triarylmethyl core. The observed chirogenesis is primarily a
function of the position of the chiral substituent within the
triarylmethyl core. For neutral species, the ortho-substitution
affects the structure and the ECD spectra most. As it was
mentioned above, ionization may cause the cleavage of C−
O(R*) bond between the chiral substituent and the phenyl
ring. This is hampered by the introduction of an additional
electron donating methoxy groups in para position of
remaining aromatic rings of the chromophore.
In the cations, the combination of chiral group in meta and
methoxy groups in para positions of the aryl rings forming
chromophore led to the most intense chiroptical response
within the whole series. The para- and the meta-substitution
turned out inefficient in generation of optical activity in
carbocations, within the compounds studied here.
13
d, J = 6.4 Hz, 3H). C{1H} NMR (101 MHz, CDCl ) δ 167.0,
3
1
5
1
57.2, 142.8, 132.9, 131.4, 128.6, 127.5, 125.6, 121.2, 120.18, 115.3,
1.9, 24.3. ATR-IR 3062, 3029, 2979, 2949, 1726, 1599, 1486, 1448,
−1
432, 1300, 1240, 1080, 751, 699 cm . ESI HRMS m/z calcd for
+
C H O Na [M + Na] : 279.0992, found 279.0988. (R)-2a: [α] =
1
6
16
3
D
−28.9 (c 1.44, MeCN). (S)-2a: [α] = +37.8 (c 0.48, MeCN).
D
Ethyl (R)- or (S)-3-(1-Phenylethoxy)benzoate (2b). (S)-2b:
isolated yield, 1.4 g, 78%, colorless oil (eluent: hexane). (R)-2b:
1
isolated yield, 2.6 g, 82%, colorless oil (eluent: hexane). H NMR
(
400 MHz, CDCl ) δ 7.62−7.48 (m, 2H), 7.41−7.19 (m, 6H), 7.07−
3
6
.96 (m, 1H), 5.36 (q, J = 6.4 Hz, 1H), 4.32 (q, J = 7.1 Hz, 2H), 1.65
1
3
(
d, J = 6.4 Hz, 3H), 1.36 (t, J = 7.1 Hz, 3H). C{1H} NMR (101
MHz, CDCl ) δ 166.4, 157.8, 142.6, 131.6, 129.2, 128.6, 127.5, 125.6,
3
1
2
21.8, 120.5, 116.7, 76.1, 60.9, 24.3, 14.3. ATR-IR 3063, 3031, 2979,
931, 2903, 1714, 1582, 1486, 1442, 1271, 1213, 1098, 1068, 1025,
−
1
956, 752, 682 cm . ESI HRMS m/z calcd for C H NaO [M +
H] : 293.1148, found 293.1139. (R)-2b: [α] = +5.1 (c 1.1, MeCN).
1
7
18
3
+
D
(S)-2b: [α] = −4.7 (c 1.23, MeCN).
D
Ethyl (R) or (S)-4-(1-Phenylethoxy)benzoate (2c). (R)-2c: isolated
Although the initial attempts to the use of similar
34
yield, 1.8 g, 56%, colorless oil (eluent: hexane). (S)-2c, isolated yield,
compounds in asymmetric synthesis were unsuccessful, we
further study that is in progress in our laboratory that we
believe will lead to chiral structures stable enough for efficient
application as chiral Lewis acids.
1
1
.5 g, 84%, colorless oil (eluent: hexane). H NMR (300 MHz,
CDCl ) δ 7.90 (d, J = 8.9 Hz, 2H), 7.44−7.14 (m, 5H), 6.86 (d, J =
3
8
.9 Hz, 2H), 5.38 (q, J = 6.4 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 1.66
13
(
d, J = 6.4 Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H). C{1H} NMR (101
MHz, CDCl3) δ 166.3, 161.6, 142.4, 131.3, 128.7, 127.6, 125.4, 122.7,
15.3, 76.1, 60.5, 24.4, 14.3. ATR-IR 3062, 3029, 2979, 2930, 2903,
1707, 1604, 1580, 1507, 1450, 1366, 1272, 1243, 1165, 1100, 1066,
EXPERIMENTAL SECTION
1
■
General Information. H and 13C{1H} NMR spectra were
recorded on Bruker Ultrashield 300 MHz or Varian VNMR-S 400
MHz instruments. Chemical shifts (δ) are reported in ppm relative to
1
−
1
1010, 930, 846, 768, 696 cm . ESI HRMS m/z calcd for
C
+
H
17
18NaO
[M + Na] : 293.1148, found 293.1143. (R)-2c: [α]
3
D
SiMe or trace solvent signals. HR-MS spectra were obtained with the
= +3.9 (c = 1.15, MeCN). (S)-2c: [α] = −5.1 (c = 1.08, MeCN).
D
4
use of a Bruker Impact HD, QTOF MS spectrometer. The ECD and
UV spectra were measured using a JASCO J-810 spectropolarimeter
at room temperature in acetonitrile and acidified acetonitrile solutions
and with the use of a quartz cell of optical lengths 0.1 cm. The
(R)-1-Bromo-2-(octan-2-yloxy)benzene (2d). Isolated yield, 0.78
1
g, 72%, colorless oil (eluent: hexane). H NMR (300 MHz, DMSO) δ
7.60−7.46 (m, 1H), 7.31 (ddd, J = 8.9, 7.4, 1.6 Hz, 1H), 7.11 (dd, J =
8.3, 1.2 Hz, 1H), 6.85 (td, J = 7.8, 1.4 Hz, 1H), 4.64−4.33 (m, 1H),
−
4
−1
13
concentration of analytes ranged from 1.0 to 2.0 × 10 mol L .
1.85−1.04 (m, 13H), 0.84 (t, J = 6.7 Hz, 3H). C{1H} NMR (101
Background spectra of the pure solvents were recorded from 600 to
85 nm with the scan speed of 100 nm min . The ECD spectra of
MHz, CDCl ) δ 154.8, 133.4, 128.2, 121.6, 115.2, 113.5, 75.8, 36.4,
3
−
1
1
31.8, 29.2, 25.4, 22.6, 19.7, 14.1. ATR-IR 3063, 2952, 2927, 2856,
1585, 1572, 1474, 1442, 1377, 1273, 1244, 1162, 1127, 1047, 1029,
analytes were measured with 16 accumulations. FT-IR spectra were
6
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https://dx.doi.org/10.1021/acs.joc.0c02289
J. Org. Chem. 2021, 86, 643−656

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
−
1
−1
+
9
74, 937, 743,664 cm . ESI HRMS m/z calcd for C H NaO [M +
748 699 cm . ESI HRMS m/z calcd for C H O Na [M + Na] :
1
7
18
3
29 28
4
+
Na] : 307.0668, found 307.0665. [α] = −16.7 (c 1.02, MeCN).
General Procedure for Synthesis of Triarylmethanol
Derivatives Using 6a as an Example. Under an argon atmosphere,
magnesium turnings (0.135 g, 5.56 mmol, 2.85 equiv) were added to a
463.1880, found 463.1893. [α] = +52.4 (c 0.55, MeCN). Mp 144−
D
D
146 °C.
(R)-Bis(2-methoxyphenyl)(3-(1-phenylethoxy)phenyl)methanol
(4b). Isolated yield, 0.19 g, 22%, colorless oil, slowly solidifying after a
few weeks, eluent: hexane/AcOEt, 9:1. H NMR (300 MHz, CDCl )
1
5
0 mL two-neck round-bottomed flask, equipped with a reflux
3
condenser and containing 25 mL of a freshly distilled THF. To the
mixture 4-bromoanisole (1.04 g, 5.56 mmol, 2.85 equiv) was added
dropwise via syringe in a few portions. After the first addition of 4-
bromoanisole, the reaction mixture was placed in an ultrasonic bath
and sonicated until the reaction was started. Then the ultrasonic bath
was replaced with a heating mantle and a magnetic stirrer. The
remaining amount of aryl bromide was added for over 15 min and
refluxed until all the magnesium dissolved. The reaction was cooled to
the room temperature, and (S)-2-(1-phenylethoxy)benzoate (2a, 0.5
g, 1.95 mmol, 1 equiv) was added dropwise to a vigorously stirred
solution. After 30 min, the reaction was heated up and refluxed
overnight. After cooling to the room temperature, a saturated solution
of ammonium chloride was added to the reaction mixture and the
whole suspension was stirred for 15 min. The organic layer was
separated, and an aqueous phase was extracted with diethyl ether (3 ×
δ 7.37−7.13 (m, J = 8.3, 4.7 Hz, 7H), 7.08 (t, J = 7.9 Hz, 1H), 6.94−
6.62 (m, 9H), 5.35−5.04 (m, J = 13.6, 7.2 Hz, 2H), 3.44 (d, J = 6.2
1
3
Hz, 6H), 1.56 (d, J = 6.4 Hz, 3H). C{1H} NMR (75 MHz, CDCl )
3
δ 157.5, 157.4, 157.1, 148.1, 143.3, 134.2, 133.9, 129.6, 128.6, 128.4,
125.8, 120.3, 114.7, 112.4, 81.2, 75.6, 55.5, 24.3. ATR-IR 3511, 3061,
2976, 2931, 2835, 1736, 1597, 1581, 1484, 1455, 1434, 1371, 1284,
−
1
1231, 1024, 915, 751, 699, 638 cm . ESI HRMS m/z calcd for
+
C H O Na [M + Na] : 463.1880, found 463.1871. [α] = +5.4 (c
2
9
28
4
D
0.53, MeCN). Mp 55−55.5 °C.
(R)-Bis(2-methoxyphenyl)(4-(1-phenylethoxy)phenyl)methanol
(4c). Isolated yield, 0.12 g, 12% (eluent: hexane/AcOEt, 9:1), white
1
crystals. H NMR (300 MHz, CDCl ) δ 7.33−7.08 (m, 7H), 7.00 (d,
3
J = 8.7 Hz, 2H), 6.89 (td, J = 7.5, 1.6 Hz, 2H), 6.78 (dd, J = 13.8, 7.8
Hz, 4H), 6.68 (d, J = 8.8 Hz, 2H), 5.23 (q, J = 6.4 Hz, 1H), 5.15 (s,
1H), 3.39 (d, J = 9.2 Hz, 6H), 1.55 (d, J = 6.4 Hz, 3H). C{1H}
1
3
10 mL). The combined organic layers were washed with brine and
NMR (75 MHz, CDCl ) δ 157.4, 156.6, 143.4, 138.5, 134.6, 129.4,
3
dried over anhydrous Na SO . The drying agent was removed by
128.9, 128.5, 125.6, 120.3, 114.8, 112.4, 80.8, 75.9, 55.6, 24.5. ATR-IR
3490, 3059, 2987, 2967, 2933, 2835, 1597, 1582, 1505, 1484, 1448,
1434, 1370, 1282, 1239, 1175, 1019, 1006, 916, 763, 750, 703, 625,
2
4
filtration, the filtrate was evaporated to dryness, and the crude product
was purified by a column chromatography on silica gel (eluent:
hexane/AcOEt, 9:1). Resulting white solid was crystallized from the
mixture of toluene and hexane.
rac- or (R)-Diphenyl(2-(1-phenylethoxy)phenyl)methanol (3a).
rac-3a: isolated yield, 0.37 g, 61% (eluent: hexane/AcOEt, 9:1),
−1
+
516 cm . ESI HRMS m/z calcd for C H O Na [M + Na] :
2
9
28
4
463.1880, found 463.1882. [α] = −21.9 (c 0.5, MeCN). Mp 117−
D
118 °C.
(R)-Bis(3-methoxyphenyl)(2-(1-phenylethoxy)phenyl)methanol
colorless crystals. (R)-3a: isolated yield, 0.73 g, 49% (eluent: hexane/
(5a). Isolated yield, 0.49 g, 28% (eluent: hexane/AcOEt, 9:1),
1
1
AcOEt, 9:1), colorless crystals. H NMR (300 MHz, CDCl ) δ 7.44−
colorless crystals. H NMR (300 MHz, CDCl ) δ 7.31−6.37 (m,
3
3
6
1
5
.98 (m, 14H), 6.95−6.83 (m, J = 6.7, 2.8 Hz, 2H), 6.82−6.64 (m, J =
1.1, 6.1, 2.3 Hz, 2H), 6.52 (dd, J = 7.6, 1.7 Hz, 1H), 5.49 (s, 1H),
.21 (q, J = 6.4 Hz, 1H), 1.25 (d, J = 6.4 Hz, 3H). 13C{1H} NMR
17H), 5.49 (s, 1H), 5.22 (q, J = 6.4 Hz, 1H), 3.76 (d, J = 5.9 Hz, 6H),
1.28 (d, J = 6.4 Hz, 3H). C{1H} NMR (75 MHz, CDCl ) δ 159.3,
1
3
3
155.3, 148.1, 147,9, 142.1, 135.4, 130.1, 128.6, 125.3, 120.6, 120.2,
113.5, 112.7, 82.0, 55.2, 23.9. ATR-IR 3506, 3060, 3025, 2924, 2852,
1595, 1581, 1484, 1448, 1434, 1371, 1284, 1235, 1026, 1010, 933,
(
101 MHz, CDCl ) δ 155.3, 146.6, 146.3, 142.1, 135.6, 130.0, 128.6,
3
1
8
1
1
28.6, 127.8, 127.8, 127.7, 127.6, 127.0, 126.9, 125.2, 120.0, 113.5,
2.0, 76.6, 23.9. ATR-IR 3508, 3087, 3063, 3026, 2980, 2885, 1597,
580, 1477, 1447, 1359, 1349, 1284, 1228, 1163, 1120, 1065, 1017,
−
1
909, 748, 730, 698 cm . ESI HRMS m/z calcd for C H O Na [M +
2
9
28
4
+
Na] : 463.1880, found 463.1873. [α] = −29.3 (c 0.63, MeCN). Mp
D
−1
007, 996, 930, 887, 760, 746, 695 cm . ESI HRMS m/z calcd for
145−147 °C.
+
C H O Na [M + Na] : 403.1669, found 403.1658. (R)-3a: [α] =
(R)-Bis(3-methoxyphenyl)(3-(1-phenylethoxy)phenyl)methanol
(5b). Isolated yield, 0.42 g, 40%, yellow oil, eluent: hexane/AcOEt,
9:1. H NMR (300 MHz, CDCl
(m, 8H), 5.18 (q, J = 6.4 Hz, 1H), 3.72 (d, J = 4.6 Hz, 6H), 2.72 (s,
27
24
2
D
−
51.4 (c 1.45, MeCN). rac-3a: Mp 127−128 °C. (R)-3a; Mp 110−
12 °C.
S)-Diphenyl(3-(1-phenylethoxy)phenyl)methanol (3b). Isolated
1
1
) δ 7.41−7.05 (m, 9H), 6.85−6.65
3
(
1
13
yield, 0.70 g, 35%, colorless oil, eluent: hexane/AcOEt, 9:1. H NMR
1H), 1.57 (d, J = 6.4 Hz, 3H). C{1H} NMR (75 MHz, CDCl ) δ
3
(
(
300 MHz, CDCl ) δ 7.33−7.06 (m, 17H), 6.89−6.65 (m, 3H), 5.18
159.2, 157.5, 148.2, 148.1, 142.9, 128.8, 128.5, 125.6, 120.4, 120.2,
114.9, 112.5, 81.8, 55.2, 24.3. ATR-IR 3342, 3061, 2977, 2835, 1596,
1485, 1449, 1434, 1372, 1287, 1239, 11147, 1041, 881, 769, 699
3
1
3
q, J = 6.4 Hz, 1H), 2.71 (s, 1H), 1.57 (d, J = 6.4 Hz, 3H). C{1H}
NMR (101 MHz, CDCl ) δ 157.4, 148.2, 146.7, 146.5, 142.9, 128.8,
3
−
1
+
1
1
1
9
28.5, 127.8, 127.8, 127.7, 127.3, 127.1, 127.1, 125.6, 120.2, 116.0,
14.8, 81.8, 75.8, 24.3. ATR-IR 3557, 3466, 3058, 3026, 2976, 2927,
595, 1578, 1484, 1445, 1372, 1312, 1285, 1242, 1144, 1068, 1011,
cm . ESI HRMS m/z calcd for C H O Na [M + Na] : 463.1880,
29 28 4
found 463.1874. [α] = +1.3 (c 0.54, MeCN).
D
(R)-Bis(3-methoxyphenyl)(4-(1-phenylethoxy)phenyl)methanol
−
1
69, 928, 903, 753, 695 cm . ESI HRMS m/z calcd for C H O Na
(5c). Isolated yield, 0.18 g, 17%, colorless oil, eluent: hexane/AcOEt,
2
7
24
2
+
1
[
M + Na] : 403.1669, found 403.1666. [α] = +13.3 (c 1.05, MeCN).
9:1. H NMR (300 MHz, CDCl
3
) δ 7.33 (m, 4H), 7.20 (m, 3H), 7.06
D
(
S)-Diphenyl(4-(1-phenylethoxy)phenyl)methanol (3c). Isolated
(d, J = 8.8 Hz, 2H), 6.90−6.68 (m, 8H), 5.27 (q, J = 6.4 Hz, 1H),
1
13
yield, 0.17 g, 9%, colorless oil, eluent: hexane/AcOEt, 9:1. H NMR
(
3.71 (s, 6H), 2.70 (s, 1H), 1.62 (d, J = 6.4 Hz, 3H). C{1H} NMR
400 MHz, CDCl ) δ 7.48−6.63 (m, 19H), 5.28 (q, J = 6.5 Hz, 1H),
(101 MHz, CDCl ) δ 159.1, 157.2, 148.5, 143.1, 138.8, 129.0, 128.7,
3
3
1
3
2
.70 (s, 1H), 1.67−1.50 (d, 3H). C{1H} NMR (101 MHz, CDCl )
128.6, 127.4, 125.5, 120.4, 115.1, 113.7, 112.3, 75.9, 55.1, 29.7, 24.5.
ATR-IR 3396, 2973, 2834, 1596, 1504, 1487, 1450, 1450, 1433, 1372,
1313, 1286, 1240, 1171, 1146, 1039, 945, 930, 833, 773, 761, 699
3
δ 157.1, 147.0, 143.1, 139.0, 129.1, 128.6, 127.8, 127.4, 127.0, 125.4,
1
2
1
15.0, 81.6, 75.9, 24.5. ATR-IR 3551, 3461, 3059, 3029, 2977, 2929,
890, 1605, 1583, 1505, 1446, 1372, 1291, 1240, 1176, 1155, 1067,
−
1
+
cm . ESI HRMS m/z calcd for C29
H O Na [M + Na] : 463.1880,
28 4
−1
030, 1008, 930, 894, 828, 756, 696, 627 cm . ESI HRMS m/z calcd
found 463.1872. [α] = +1.6 (c 0.48, MeCN).
D
+
for C H O Na [M + Na] : 403.1669, found 403.1668. [α] = +10.5
(S)-Bis(4-methoxyphenyl)(2-(1-phenylethoxy)phenyl)methanol
27
24
2
D
(
c 0.5, MeCN).
S)-Bis(2-methoxyphenyl)(2-(1-phenylethoxy)phenyl)methanol
4a). Isolated yield, 0.14 g, 16% (eluent: hexane/AcOEt, 9:1),
(6a). Isolated yield, 0.23 g, 27% (eluent: hexane/AcOEt, 9:1),
1
(
colorless crystals. H NMR (300 MHz, CDCl
3
) δ 7.25−7.15 (m, 7H),
(
7.08 (dt, J = 7.9, 1.7 Hz, 1H), 6.92 (dd, J = 6.6, 2.9 Hz, 2H), 6.89−
6.79 (m, 4H), 6.77−6.65 (m, 2H), 6.54 (dd, J = 7.6, 1.6 Hz, 1H), 5.45
(s, 1H), 5.22 (q, J = 6.4 Hz, 1H), 3.82 (d, J = 6.4 Hz, 6H), 1.30 (d, J =
1
colorless crystals. H NMR (300 MHz, CDCl ) δ 7.48−6.41 (m,
3
1
3
1
1
2
7H), 5.53 (s, 1H), 5.15 (s, 1H), 3.47 (d, J = 17.3 Hz, 6H), 1.26 (s,
H). 13C{1H} NMR (101 MHz, CDCl ) δ 157.7, 143.1, 133.2, 130.7,
13
6.4 Hz, 3H). C{1H} NMR (75 MHz, CDCl ) δ 158.5, 155.4, 142.2,
3
3
29.9, 129.7, 128.3, 127.6, 127,1, 125.3, 120.4, 119.9, 119.3, 119.3,
12.6, 80.3, 75.3, 55.8, 55.6, 24.5. ATR-IR 3494, 3060, 3026, 2926,
853, 1596, 1582, 1485, 1449, 1434, 1372, 1284, 1233, 1025, 908,
139.3, 139.0, 136.0, 130.1, 129.0, 128.6, 125.3, 120.1, 113.5, 113.0,
81.6, 55.3, 24.1. ATR-IR 3534, 2997, 2953, 2930, 2894, 2833, 1655,
1597, 1580, 1505, 1480, 1448, 1296, 1242, 1227, 1176, 1105, 1067,
6
52
https://dx.doi.org/10.1021/acs.joc.0c02289
J. Org. Chem. 2021, 86, 643−656

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
−
1
1
031, 935, 831, 813, 755, 704, 606 cm . ESI HRMS m/z calcd for
1588, 1487, 1451, 1371, 1284, 1232, 1112, 1067, 1028, 1009, 997,
+
−1
C H O Na [M + Na] : 463.1880, found 463.1888. [α] = +59.5 (c
933, 748, 697 cm . ESI HRMS m/z calcd for C H O Na [M +
29
28
4
D
15 16
2
+
0
.43, MeCN). Mp 171−172 °C.
R)-Bis(4-methoxyphenyl)(3-(1-phenylethoxy)phenyl)methanol
6b). Isolated yield, 0.31 g, 36%, colorless oil, eluent: hexane/AcOEt,
Na] : 251.1043, found 251.1044. [α] = +4.3 (c 0.64, MeCN).
D
(
(R)-(3-(1-Phenylethoxy)phenyl)methanol (8b). Isolated yield, 0.18
1
(
9
(
1
g, 79%, colorless oil, eluent: dichloromethane. H NMR (300 MHz,
1
:1. H NMR (300 MHz, CDCl ) δ 7.39−7.18 (m, 6H), 7.16−6.96
CDCl ) δ 7.46−7.07 (m, 6H), 7.00−6.81 (m, 2H), 6.77 (dd, J = 8.2,
3
3
m, 5H), 6.89−6.67 (m, 7H), 5.19 (q, J = 6.4 Hz, 1H), 3.80 (d, J =
2
.3 Hz, 1H), 5.33 (q, J = 6.4 Hz, 1H), 4.59 (s, 2H), 1.63 (m, 4H).
13
1
3
.9 Hz, 6H), 2.63 (s, 1H), 1.57 (d, J = 6.5 Hz, 3H). C{1H} NMR
C{1H} NMR (101 MHz, CDCl ) δ 158.1, 143.1, 142.3, 129.4,
3
(
75 MHz, CDCl ) δ 158.5, 158.5, 157.4, 148.7, 143.0, 139.4, 139.2,
3
128.6, 127.4, 125.5, 119.1, 114.9, 114.4, 75.8, 65.1, 24.4. ATR-IR
1
3
1
29.0, 128.5, 125.7, 120.1, 116.0, 113.1, 81.3, 75.9, 55.2, 24.3. ATR-IR
481, 2929, 2834, 1605, 1580, 1507, 1481, 1439, 1293, 1243, 1173,
3
1
321, 3061, 3030, 2977, 2927, 2867, 1583, 1486, 1446, 1372, 1256,
−1
151, 1067, 1011, 998, 952, 879, 760, 747, 696 cm . ESI HRMS m/z
−
1
068, 1029, 830, 813, 790, 760, 698 cm . ESI HRMS m/z calcd for
+
calcd for C H O Na [M + Na] : 251.1043, found 251.1040. [α] =
1
5
16
2
D
+
C H O Na [M + Na] : 463.1880, found 463.1972. [α] = +1.6 (c
29
28
4
D
+15.1 (c 0.47, MeCN).
1
.12, MeCN).
R)-Bis(4-methoxyphenyl)(4-(1-phenylethoxy)phenyl)methanol
6c). Isolated yield, 0.32 g, 31%, colorless oil, eluent: hexane/AcOEt,
:1. H NMR (300 MHz, CDCl ) δ 7.40−7.19 (m, 5H), 7.18−6.99
m, 6H), 6.78 (dd, J = 8.6, 7.1 Hz, 6H), 5.27 (q, J = 6.4 Hz, 1H), 3.78
s, 6H), 2.62 (s, 1H), 1.61 (d, J = 6.4 Hz, 3H). C{1H} NMR (75
MHz, CDCl ) δ 158.5, 157.1, 143.2, 139.7, 139.6, 129.0, 128.6, 125.5,
15.0, 113.1, 81.1, 76.0, 55.2, 24.5. ATR-IR 3481, 3032, 2976, 2930,
903, 2835, 1605, 1581, 1504, 1452, 1372, 1295, 1239, 1173, 1030,
25, 760, 699, 607, 583 cm . ESI HRMS m/z calcd for C H O Na
(
R)-(4-(1-Phenylethoxy)phenyl)methanol (8c). Isolated yield, 0.17
(
1
g, 75%, colorless oil, eluent: dichloromethane. H NMR (300 MHz,
(
9
(
(
CDCl ) δ 7.47−7.02 (m, 7H), 6.84 (d, J = 8.6 Hz, 2H), 5.30 (q, J =
1
3
3
6
.4 Hz, 1H), 4.55 (s, 2H), 1.63 (d, J = 6.4 Hz, 3H), 1.54 (s, 1H).
13
C{1H} NMR (101 MHz, CDCl ) δ 157.5, 143.0, 133.0, 128.6,
1
3
3
1
2
1
28.5, 127.4, 125.5, 115.9, 75.9, 65.0, 24.4. ATR-IR 3319, 3061, 3030,
977, 2927, 2869, 1610, 1585, 1508, 1449, 1372, 1298, 1234, 1172,
3
1
2
8
−
1
068, 1027, 1008, 997, 930, 819, 759, 698 cm . ESI HRMS m/z
+
−
1
calcd for C15
H O Na [M + Na] : 251.1043, found 251.1040. [α] =
1
6
2
D
2
9
28
4
+
−16.1 (c 0.47, MeCN).
[
M + Na] : 463.1880, found 463.1876. [α]D = −18.2 (c 0.38,
General Procedure for the Synthesis of Derivatives 9. In a
5 mL round-bottomed flask, 0.25 mmol of the respective
MeCN).
2
(
R)-(3-(Octan-2-yloxy)phenyl)diphenylmethanol (7). Under an
triarylmethanol derivative was dissolved in 5 mL of CDCl . To the
3
argon atmosphere, (R)-1-bromo-2-(octan-2-yloxy)benzene (2d, 0.33
g, 1.16 mmol, 1 equiv) was dissolved in 10 mL of a freshly distilled
THF. The reaction was cooled to −78 °C, and n-BuLi (0.46 mL, 1.16
mmol, 1 equic, 2.5 M solution in hexanes) was slowly added dropwise
to the mixture. The mixture was being stirred for 0.5 h in dry ice/
acetone bath. Benzophenone (0.219 g, 1.16 mmol, 1 equiv) dissolved
in 10 mL of dry THF was added dropwise over 15 min. The cooling
bath was then removed, and the reaction was left stirring overnight.
The saturated solution of ammonium chloride (20 mL) was added
and the mixture was extracted with diethyl ether (3 × 10 mL). The
combined organic phases were washed with brine (20 mL) and dried
over anhydrous sodium sulfate. The drying agent was removed by
filtration. The solvent was evaporated under reduced pressure, and the
crude product was purified using a column chromatography on silica
gel (eluent: hexane/AcOEt, 9:1) resulting in the desired product.
flask, trifluoroacetic acid (19 μL, 1 mmol, 4 equiv) was added using an
automatic pipet. The initial, intense color of the resulting mixture
disappeared within seconds. The subsequent thin layer chromatog-
raphy of reaction mixture revealed total conversion of the substrate.
The solvent was evaporated under reduced pressure and the crude
product was purified using a column chromatography on silica gel
(
eluent: hexane/AcOEt, 95:5).
-(Diphenylmethyl)phenol (9a).
eluent: hexane/AcOEt, 95:5), white solid. H NMR (300 MHz,
2
7a
2
Isolated yield, 45 mg, 70%
1
(
CDCl ) δ 7.44−7.19 (m, 6H), 7.15 (dd, J = 9.9, 4.5 Hz, 5H), 6.94−
3
1
3
6
.68 (m, 3H), 5.74 (s, 1H), 4.65 (s, 1H). C{1H} NMR (101 MHz,
CDCl ) δ 153.3, 142.5, 130.4, 129.3, 128.5, 127.9, 126.6, 120.7, 116.0,
3
5
1
0.7. ATR-IR 3513, 3060, 3022, 2923, 2851, 1595, 1489, 1446, 1325,
266, 1173, 1086, 1042, 1030, 942, 921, 877, 814, 747, 725, 697
−
1
+
1
cm . ESI HRMS m/z calcd for C H ONa [M + Na] : 283.1093,
Isolated yield, 0.14 g, 32%, colorless oil. H NMR (300 MHz,
19 16
found 283.1093. Mp 121−124 °C.
DMSO-d ) δ 7.58−6.60 (m, 14H), 5.63 (s, 1H), 4.48−4.23 (m, 1H),
6
1
3
2
-(Bis(2-methoxyphenyl)methyl)phenol (9b). Isolated yield, 63
1
1
1
1
1
.15 (m, 8H), 0.87 (m, 8H). C{1H} NMR (101 MHz, CDCl ) δ
3
1
mg, 79% (eluent: hexane/AcOEt, 95:5), white solid. H NMR (400
55.3, 146.6, 146.5, 135.9, 130.3, 128.6, 127.8, 127.7, 127.6, 127.5,
26.9, 126.8, 119.6, 112.6, 82.0, 73.6, 36.1, 31.6, 29.2, 24.9, 22.6, 18.9,
4.1. ATR-IR 3508, 3058, 3026, 2953, 2926, 2855, 1597, 1582, 1481,
MHz, CDCl ) δ 7.24 (ddd, J = 8.4, 6.7, 2.4 Hz, 2H), 7.15−7.07 (m,
3
1H), 6.92−6.84 (m, 6H), 6.84−6.76 (m, 2H), 6.73 (dd, J = 7.6, 1.8
−1
13
446, 1377, 1284, 1225, 1119, 1018, 750, 698 cm . ESI HRMS m/z
Hz, 1H), 6.26 (s, 1H), 4.90 (s, 1H), 3.71 (s, 6H). C{1H} NMR
+
calcd for C H O Na [M + Na] : 411.2295, found 411.2311. [α] =
(101 MHz, CDCl ) δ 157.2, 153.5, 130.4, 129.8, 129.4, 127.8, 127.4,
3
27
32
2
D
−
19.4 (c 1.19, MeCN).
General Procedure for Reduction of Salicylic Esters. Under
120.4, 120.3, 115.8, 110.9, 55.7, 37.2. ATR-IR 3524, 3011, 2931,
2836, 1583, 1487, 1452, 1435, 1328, 1287, 1236, 1182, 1165, 1104,
−
1
an argon atmosphere, lithium aluminum hydride (0.15 g, 4 mmol, 3
equiv) was slowly added to freshly distilled THF (10 mL) at 0 °C.
The respective salicylic ester 2 (0.36 g, 1.3 mmol, 1 equiv) dissolved
in THF (10 mL) was added dropwise to the suspension. The progress
of the reaction was monitored by TLC. When the conversion of
substrate was completed, water (20 mL) was added slowly at 0 °C,
and the reaction mixture was extracted with diethyl ether (3 × 10
mL). The combined organic layers were washed with brine, dried over
anhydrous sodium sulfate and evaporated under reduced pressure
after removing the drying agent by filtration. The crude product was
purified by flash chromatography on silica gel (eluent: dichloro-
methane).
1087, 1049, 1026, 938, 878, 854, 813, 790, 754, 651 cm . ESI HRMS
+
m/z calcd for C21
H O Na [M + Na] : 343.1305, found 343.1303.
20 3
Mp 155−156 °C.
General Procedure for in Situ Generation of Carbocations
from Triarylmethanol Derivatives. In a 10 mL volumetric flask, 1
mg of triarylmethanol derivative was dissolved in 10 mL of dry
MeCN. To the flask was added 20 μL of 0.1 M solution of
trifluoroacetic acid (TFA) in MeCN containing 10% mol of
trifluoroacetic anhydride (in relation to TFA) as an additive. The
ECD spectra were measured directly after an addition of each portion
of acid. The addition of acid was continued until there was no
observable change in the ECD spectra or the analyzed compound
decomposed.
(
S)-(2-(1-Phenylethoxy)phenyl)methanol (8a). Isolated yield, 0.2
1
The NMR spectra of in situ generated carbocations 6a and 6b+
+
g, 88%, colorless oil, eluent: dichloromethane. H NMR (300 MHz,
CDCl ) δ 7.44−7.19 (m, 6H), 7.11 (dt, J = 8.0, 1.7 Hz, 1H), 6.88 (t, J
were measured in dry CDCl and with the use of TFA as acidifying
3
3
=
(
7.4 Hz, 1H), 6.73 (d, J = 8.2 Hz, 1H), 5.38 (q, J = 6.4 Hz, 1H), 4.77
agent. After dissolving respective triarylmethanol 6a or 6b in dry
q, 2H), 2.42 (s, 1H), 1.67 (d, J = 6.4 Hz, 3H). 13C{1H} NMR (101
MHz, CDCl ) δ 155.7, 142.6, 129.5, 128.7, 127.6, 125.3, 120.6, 113.0,
CDCl and under an inert atmosphere, two equivalents of TFA were
3
added in one portion. The NMR spectra were measured directly after
addition of the acid.
3
76.1, 62.4, 24.4. ATR-IR 3347, 3062, 3030, 2976, 2927, 2868, 1601,
6
53
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J. Org. Chem. 2021, 86, 643−656

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
+
+
+
NMR Data for in Situ Generated Carbocations 6a and 6b . 6a :
DEDICATION
1
■
8
H NMR (400 MHz, CDCl ) δ 7.74−7.68 (dd, 1H), 7.66 (d, J = 9.1
3
Dedicated to Prof. Bogdan Marciniec on the occasion of his
0th birthday.
Hz, 2H), 7.57 (d, J = 8.6 Hz, 2H), 7.29−7.21 (m, 5H), 7.19−7.10 (m,
3
1
H), 7.08−7.03 (m, 2H), 6.98−6.92 (m, 2H), 5.22 (q, J = 6.4 Hz,
13
H), 4.10 (d, J = 20.7 Hz, 6H), 1.21 (d, J = 6.4 Hz, 3H). C{1H}
NMR (101 MHz, CDCl ) δ 192.8, 172.1, 159.7, 143.3, 140.8, 139.2,
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AUTHOR INFORMATION
Corresponding Authors
Bartosz Stasiak − Faculty of Chemistry, Adam Mickiewicz
University, 61 614 Poznań, Poland; orcid.org/0000-
■
0
001-6884-3256; Email: bartosz.stasiak@amu.edu.pl
Marcin Kwit − Faculty of Chemistry and Centre for Advanced
Technologies, Adam Mickiewicz University, 61 614 Poznań,
Poland; orcid.org/0000-0002-7830-4560;
Email: marcin.kwit@amu.edu.pl
Author
Agnieszka Czapik − Faculty of Chemistry, Adam Mickiewicz
University, 61 614 Poznań, Poland
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02289
1
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ACKNOWLEDGMENTS
■
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1
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6
(
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https://dx.doi.org/10.1021/acs.joc.0c02289
J. Org. Chem. 2021, 86, 643−656