Chiral Triphenylacetic Acid Esters: Residual Stereoisomerism and Solid-State Variability of Molecular Architectures

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Chiral Triphenylacetic Acid Esters: Residual Stereoisomerism and

Solid-State Variability of Molecular Architectures

Natalia Prusinowska, Agnieszka Czapik, and Marcin Kwit*

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ABSTRACT: We have proven the usability and versatility of chiral triphenyl-

acetic acid esters, compounds of high structural diversity, as chirality-sensing

stereodynamic probes and as molecular tectons in crystal engineering. The low

energy barrier to stereoisomer interconversion has been exploited to sense the

chirality of an alkyl substituent in the esters. The structural information are

cascaded from the permanently chiral alcohol (inducer) to the stereodynamic

chromophoric probe through cooperative interactions. The ECD spectra of

triphenylacetic acid esters are highly sensitive to very small structural diﬀerences

in the inducer core. The tendencies to maximize the C−H···O hydrogen bonds,

van der Waals interactions, and London dispersion forces determine the way of

packing molecules in the crystal lattice. The phenyl embraces of trityl groups allowed, to some extent, the control of molecular

organization in the crystal. However, the spectrum of possible molecular arrangements is very broad and depends on the type of

substituent, the optical purity of the sample, and the presence of a second trityl group in the proximity. Racemates crystallize as the

solid solution of enantiomers, where the trityl group acts as a protecting group for the stereogenic center. Therefore, the absolute

conﬁguration of the inducer is irrelevant to the packing mode of molecules in the crystal.

activity induction. The initially established “bevel-gear”

mechanism of chirality induction is dominant for O-trityl

ethers,⁹N-trityl amines,¹⁰O-triphenylsilyl ethers,¹⁶and 3,3,3-

triphenylpropionic acid derivatives¹⁷(see Figure 1b,c). For

other derivatives studied so far, the established mechanisms of

chirality induction are rather case-sensitive and generally

proceed through a set of cooperative interactions.^18,19The

involvement of the triarylmethyl moiety into the rigid

triptycene skeleton eliminates any conformational changes of

the propeller. In such cases, the chirality of the whole

triptycene system is achieved by proper functionalization of

benzene rings.²⁰

The intensively studied triphenylacetamides can be consid-

ered the counterpart of N-trityl amines. A rigid amide spacer

linking the inductor and the chromophore part of the molecule

does not signiﬁcantly disturb the chirality induction process¹⁹

(Figure 1d). However, the dynamic stereochemistry of

triphenylacetic acid esters being chiral congeners of O-trityl

ethers has not been a subject of interest. As early as in 1912,

Chugayev reported the optical rotation of menthyl tripheny-

lacetate, the ﬁrst chiral ester derivative of triphenylacetic

INTRODUCTION

■

The dynamic stereochemistry and residual stereoisomerism of

molecular propellers were the subjects of intense studies

initiated by Mislow in the early 1970s.¹⁻³Then, after a nearly

20 year period of freezing activity in the ﬁeld, there was

renewed interest in molecular propellers associated with their

increasing number of applications. One of the simplest entities

showing propensity to residual stereoisomerism, namely, the

triphenylmethyl group (CPh₃, Tr, trityl), is currently used in

organic synthesis as protecting devices, catalysts,^4,5construc-

tion of molecular machines,⁶medical chemistry,⁷and

bioimaging.⁸

From the stereochemical point of view, the trityl moiety

represents an unique example of stereodynamic system that

resembles a macroscopic rotor with variable blades geometry.

Due to a low enantiomerization barrier, the parent triphenyl-

methane and related systems exist as a mixture of quickly

interconverting enantiomers, characterized by the same sense

of blade’s twist, either P and M, as well as by the highest

available C₃symmetry (Figure 1a).

Not until recently has Gawronski demonstrated usefulness

of the trityl as a stereodynamic chirality sensor for alcohols and

amines.⁹⁻¹³The mutual matching between the permanently

chiral part of the molecule (usually called “the inducer”) and

the stereodynamic probe has resulted in the appearance of

nonzero Cotton eﬀects (CEs) in electronic circular dichroism

(ECD).^14,15It should be emphasized that the similarities in the

patterns of the ECD spectra of trityl derivatives do not directly

translate into the similarities in the mechanisms of the optical

Received: February 4, 2021

Published: April 28, 2021

American Chemical Society

https://doi.org/10.1021/acs.joc.1c00279

J. Org. Chem. 2021, 86, 6433−6448

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Figure 1. (a) Extreme C₃-symmetric conformers of triphenylmethane propeller. The “bevel gear” mechanism of chirality induction for (b) O-trityl

ethers and (c) N-trityl amines, and correlation of the shape of ECD spectrum with dominant conformation of O-trityl ethers and N-trityl amines,

respectively (projections dawn the O−CPh₃or N−CPh₃bond). (d) Mechanism of chirality induction and correlation between the shape of ECD

spectrum and the dominant conformation of chiral secondary and tertiary triphenylacetamides (projection down the N−C(O) bond).

acid.²¹However, neither this nor the later works contributed

much to understanding the mechanism of inducing the optical

activity in such compounds.²²Thus, being for ages isolated

curiosities of chemistry, the chiral mono- and diesters of

triphenylacetic acid constitute the missing pieces of the jigsaw

puzzle showing dynamic stereochemistry of trityl-containing

compounds.

In addition to synthetic and stereochemical applications,

trityl and related groups are widely utilized in crystal

engineering to construct inclusion crystals.²³Akazome has a

proven propensity of N-tritylamino acids to the solid-state

enantiodiscrimination of chiral guests.^24,25The presence of

trityl groups in the amino acid core has prevented the

formation of inherent hydrogen bonds, and the loss of

hydrogen bonds was compensated for by an inclusion of

guest molecules. In the secondary amides of triphenylacetic

acid, the trityl group has played the role of supramolecular

protecting group for the amide N−H hydrogen bond

functionality.²⁶However, the presence of additional supra-

molecular synthons within the N-triphenylacetylamino acid

skeleton allowed for the back-activation of the N−H group,

then for the formation of associates of the wheel-and-axle

structure and/or various multicomponent crystals.^26,27

The presence of π-electron fragments enables various intra-

and intermolecular interactions. Therefore, the trityl group

itself and its analogues are considered useful building blocks

(tectons) in molecular tectonics.^28,29In principle, the multiple

phenyl embraces are engaged in simultaneous attractive

(mostly the dispersive) interactions³⁰which would allow for

the control over the molecular organization in the materi-

als.^29,31,32After analyzing the available data and based on his

own research, Wuest very recently outlined the key require-

ments for the use of the triarylmethyl groups to control

molecular organization.²⁹One of the most important

conclusions of Wuest’s study, showing the diﬃculties in

predicting material structure, was as follows: “strong direc-

tional intermolecular interactions will be most eﬀective when

closely related alternatives of similar energy are absent”.²⁹Due

to the multiple and concerted edge-to-face interactions

between interdigitating trityl (and related) groups of opposite

helicity, the 6-fold phenyl embraces are considered to be an

attractive supramolecular motif. However, even for predis-

posed trityl-containing compounds the a priori prediction of

the occurrence of this form is burdened with considerable

risk.^29,31

In contrast, the presence of the highly polar groups in salts

of triphenylacetic acid and primary amines allowed for the

formation of multicoordinated polyhedrons exhibiting a novel

supramolecular chirality in the solid state.³³In such crystals,

the phenyl−phenyl interactions gave a small or even negligible

impact to have control over molecular organization. Despite

the hundreds of crystal structures of trityl-containing

derivatives reported so far, it is worth emphasizing that no

crystal structure of a triphenylacetic acid ester had been

deposited in The Crystal Structure Database until this

manuscript was written.³⁴

Feeling that there are still some unresolved issues in the ﬁeld

of dynamic stereochemistry and molecular tectonics of trityl-

containing compounds, which might be properly addressed, we

have decided to direct our attention to chiral triphenylacetic

acid esters. The structural dynamics of these compounds has

never been the subject of an in-depth study. Additionally, little

to nothing is known about a possibility of and, thus mechanism

of, chirogenesis in chiral esters of triphenylacetic acid.

Demonstration of similarities and diﬀerences in chirogenesis

occurring in triphenylacetic acid amides, esters, and respective

O-trityl ethers would constitute an outcome of this part of the

study.

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a

Chart 1. Structures of Compounds under Study

a

Values in parentheses refer to the isolated yield of the given product.

The chosen research objects are characterized by the

absence of supramolecular synthons in the skeleton and by

the presence of a chiral side chain (the inducer part) in the

molecule. These two factors can aﬀect not only the structural

dynamics of the isolated molecule but the association mode

and thus the material structure. The possible competition

between intra- and intermolecular interactions make the

compounds in which more than one trityl groups exist in

proximity especially interesting in the context of self-

organization of molecules in the crystal. Thus, in the absence

of supramolecular synthons that allowed for the long-range

order of molecules in the crystal lattice (e.g., formation of the

hydrogen bonds cascades), we expect the dominant impact of

the phenyl−phenyl interactions on the organization mode of

the entities.

The choice of the chiral inducer has been dictated by the

availability and the structural variability of a given alcohol.

Apart from 5 and 7, the compounds under study do not

contain any other aromatic chromophore, which may, although

not necessarily, disturb the chiroptical phenomena. The

inducers can be considered as ECD-silent in the region of

the trityl group absorption. Therefore, the possibly observed

phenomena will result from the generation of optical activity in

the chromophore and will have their source in the chirality

transfer from the inducer to the probe. Additionally, diesters

20−22 give us a chance to study the competitive or

cooperative eﬀects on chirality inductions and association.

Since they are deceptively simple, the compounds under

study are characterized by rather complex conformational

dynamics. In each molecule, there are at least ﬁve torsion

angles for which rotation barriers are expected to be low. The

¹H NMR spectra of 1−22 show only sharp signals, which

suggest rather high structural dynamics, associated with a

number of easily interconverted conformations. This, in turn,

might lead to mutually canceling contributions of conforma-

tional diasteoisomers to the overall ECD spectra; therefore, no

rise or very weak CEs will be observed. However, the ECD

spectra measured in cyclohexane solution of 1−22 with no

exceptions show CEs in the region of trityl UV absorption,

thus conﬁrming the ongoing chirogenesis in a way that leaves

no doubt (Table 1 and see Figure 2 for examples of measured

ECD spectra). Lowering the concentration of the sample (up

to 10⁻⁶mol L⁻¹) has no eﬀect on the observed phenomena. In

fact, with the exception of increasing the noise level, we did not

see any changes in the shape of respective ECD spectra.

Therefore, a possible aggregation has not played a role at the

concentration range between 10⁻⁴and 10⁻⁶mol L⁻¹.

RESULTS AND DISCUSSION

■

Chirogenesis and Molecular Dynamics of Esters 1−

22. Although initial attempts to synthesize chiral esters in the

reaction of an alcohol with the acid chloride were unsuccessful,

the fusion of a triphenylacetyl chloride with an excess of

respective alcohol provided compounds 1−22 (Chart 1) with

yields ranging from 12 to 95%. The reactions in solution that

are a natural choice for this type of synthesis either led to the

formation of only small quantities of the esters, or in our

hands, the reactions were ineﬃcient. We have not observed

any racemization nor epimerization in the products.²²

However, in the particular case of citronellol, during the

course of the esteriﬁcation reaction, migration of a double

bond took place. This is most likely due to the reversible

addition−elimination of hydrochloride and is not hampered by

the addition of the base. Unfortunately, these compounds are

not separable from each other, and the isolated yield of 9 refers

to the sum of isomers diﬀering in the position of a double

bond.

We add that the change of the solvent to more polar

acetonitrile has resulted in small or negligible changes in the

observed chiroptical phenomena. In fact, only for 5 and 18

could the overall shape of the ECD spectra measured in polar

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Table 1. UV (ε, in dm³·mol⁻¹·cm⁻¹) and ECD (Δε, in dm³·

mol⁻¹·cm⁻¹) Data for 1−22 Measured in Cyclohexane

This simple relationship (the higher structural diﬀerence

between the substituents ﬂanking stereogenic center, the more

intense the CEs) can be assigned with a great deal of caution

for acyclic derivatives 1−4 and 6. For these compounds, the

steric power of aliphatic substituents in the dynamic chirality

induction rises as follows: Me < Et < n-C₅H₁₁< n-Pr < i-Pr <

Cy. For cyclic monoesters, such a simple relationship is not

seen. In menthol derivatives 10 and 11, the change of the

absolute conﬁguration at the C1 carbon atom (from R to S),

associated with the change of position of the ester group from

equatorial to axial, led to the signiﬁcant decrease of the CEs

amplitudes. The highest amplitude of CEs has been found for

14, which can make an impression that the impact of gem-

dimethyl group on the ECD spectrum overwhelms that of the

carbonyl group.

In the context of eﬃciency of the dynamic induction of

optical activity, the derivatives 12 and 15, where there is no

signiﬁcant diﬀerence between the substituents’ ﬂanking

chirality element, deserve special attention. In the former

case, the probe stereodiﬀerentiates the CH₂and the CH₂C*H-

(C) groups in the β position. In the case of the latter,

tetrahydrofuran derivative 15, the structural diﬀerence between

the −O− and −CH₂− groups is even more subtle. However,

the eﬃciency of the chirogenesis, as estimated on the basis of

CEs amplitudes, is higher than that observed for more

structurally diversiﬁed 12. Quantitatively, for derivative 15,

the low-energy CE appearing at around 227 nm is over 2-fold

higher in intensity than that measured for 12 (Δε = −1.57 vs

Δε = −0.67). However, the higher-energy CD band, located at

around 200 nm, is only 1.2 times higher for 15 (Δε = 5.80)

than the respective CE that has been found experimentally for

12 (Δε = 4.80).

As the structure and the energy relationships between

conformers of the given compound cannot be determined

experimentally, we have conducted calculations at the

appropriate DFT level for the representative examples 1, 4,

6, 10, 11, 14, 15, 18, and 20−22.³⁵⁻³⁸Eventually, this could

shed light on the mechanism of chirality induction (for details

regarding the calculation methodology, see the Supporting

Information). Since the detailed elaboration of each structure

might obscure the basic problem, we will discuss here some

generalities. The best combination of methods for structure/

spectra prediction has been chosen by comparison of

experimental and Boltzmann averaged CD spectra calculated

for the structures optimized with the use of diﬀerent density

functionals. In the cases discussed here and for the same

method used for geometry optimization, the results of ECD

calculations with the use of the M06-2X hybrid functional only

slightly outperforms results obtained with the use of CAM-

B3LYP hybrid functional. Therefore, the method of geometry

optimization seemed to be crucial for the correctness of the

ﬁnal results.^14,36While for esters 1, 4, 10, 11, and 14 the

“classical” B3LYP hybrid functional gave the best results,³⁷the

conformational dynamic and structure of individual con-

formers of 6 and 15, aﬀected by CH···O interactions between

inductor and acceptor, were better reproduced by the newer

M06-2X hybrid functional. The empirical correction for

dispersion that was added to the B3LYP functional was only

relevant in the cases of 18, 20, and 21 having the ester groups

in the close proximity.³⁹However, for the remaining diester,

22, the London dispersive interactions did not much aﬀect the

structure of the compound. For a given compound, the

wavelengths in UV and ECD calculated spectra (overlapped by

a

Solution

b

compd.

Δε (nm)

ε (nm)

c

1

2

3

4

5

−2.30 (226); 11.31 (200); −7.46 (185)

75400 (197)

75800 (197)

73400 (197)

74300 (197)

121000 (189)

c

4.16 (226); −13.90 (199); 12.79 (185)

c

1.19 (224); −2.76 (202); 3.86 (185)

−3.24 (225); 14.16 (200); −9.08 (185)

−1.00 (225); 2.55 (211); 2.87 (205);

8.14 (191)

c

6

7

8

9

10

11

11.03 (229); −49.85 (200); 29.32 (185)

18.53 (222); 13.88 (200); −45.59 (189)

−0.39 (216); −1.04 (205); −0.60 (194)

74900 (197)

116200 (192)

74300 (197)

66400 (196)

72400 (197)

72800 (196)

c

0.50 (225); −1.43 (196); 1.61 (185)

c

−11.37 (225); 46.38 (200); −36.50 (185)

−2.90 (221); −3.41 (210); −2.31 (200);

4.12 (191)

12

13

14

15

16

17

−0.67 (227); 4.82 (200)

−0.96 (340); 8.89 (228); 7.09 (191)

18.40 (227); −74.45 (200); 43.76 (185)

−1.57 (228); 5.80 (200); −0.8 (185)

74100 (196)

65700 (197)

72600 (196)

66100 (197)

69800 (197)

147700 (190)

d

c

0.63 (224); −5.14 (195); 1.17 (185)

11.32 (231); −37.30 (210); −36.62 (198);

c

29.60 (185)

18

2.55 (231); −7.23 (208); 3.02 (196);

141200 (196)

c

−1.65 (185)

c

19

20

21

22

−13.35 (219); 47.84 (197); −30.06 (185)

−9.02 (226); 33.91 (201); −25.59 (185)

−1.40 (221); 13.11 (196); −7.69 (185)

−11.89 (227); 49.16 (201); −35.73 (185)

140800 (195)

142700 (196)

143900 (194)

141200 (196)

c

a

The concentration of analytes ranged from 1.52 to 2.91 × 10⁻⁴mol

L⁻¹. The spectra were recorded in pure cyclohexane, from 400 to 185

nm, with a scan speed of 50 nm min⁻¹and 8 accumulations (see the

b

Experimental Section). Only well-established absorption bands of ε

c

d

> 2000 were reported. End of measuring range. Partially insoluble in

cyclohexane.

solvent be considered diﬀerent from those measured in a

nonpolar environment, whereas for 2-7, 12, 14, 15, and 19, an

increase of the solvent polarity has caused a decrease of CEs

amplitudes while retaining the same shape of the ECD

spectrum (see Table SI_2, and see copies of ECD spectra

posted in Supporting Information).

1

The low-energy CEs associated with L_belectron transition

appear at around 225

6 nm, whereas the second more

1

intense and opposite-sign ECD bands of B type are found at

around 200 5 nm. The third, higher-energy CEs reach their

maxima usually bellow 185 nm. Those associated the UV

spectra are dominated by strong absorption maximum at

around 195 5 nm. Other transitions do not form any well-

distinguished shoulder peaks apart from the lowest energy ones

appearing at around 260−280 nm. Strictly speaking, for the

majority of cases this particular band is hardly visible, and the

extinction coeﬃcient (ε) does not exceed 2000. The presence

of an additional chromophore of the ketone, enone, and

COOR type does not disturb this pattern, although additional

CEs are visible in the region of the n−π* electron transition.

Replacing of an aliphatic substituent at stereogenic center by

the aromatic phenyl group makes the ECD spectra of 5 and 7

more complex. As one might expect, the weakest induced CEs

are found for derivatives 8 and 9, in which the ester group is

spaced from the stereogenic center. The existence of 9 as the

mixture of isomers has not aﬀected the observed phenomena.

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Figure 2. Examples of the ECD spectra of 1, 6, 10, 14, 15, and 20−22 measured in cyclohexane (solid black lines) and calculated at the TD-M06-

2X/6-311++G(2d,2p) level (solid blue lines). The calculated ECD spectra were Boltzmann-averaged based on ΔΔG values. Wavelengths were

corrected to match the experimental UV maxima. With an exception of 10, for which only one low-energy conformer has been found, inserts show

the comparison between the ECD spectra calculated for the lowest energy conformer of a given compound (dashed blue lines) and the ΔΔG-based

and Boltzmann averaged (solid blue lines).

Gaussian function) were multiplied by the same scaling factors

obtained from a simple equation: UV λ_max(exp)/UV λ_max(calcd). In

the cases discussed here, the scaling factors were ca. 1.05,

which means that the calculated spectra were blue-shifted with

respect to the experimental ones.

and 20−22 have been juxtaposed in Table 2; Figure 3 shows

the example structures. All remaining theoretical results are in

the Supporting Information.

The structure of each individual conformer might be

described by a set of torsion angles α, β₁−β₃, γ₁−γ₃, δ, and

ζ. The angles α = C_Tr−C(O)−O−C*and δ = C(O)−O−

C*−H are, to some extent, correlated and describe the

conformation of TrCOOC*H(R₁,R₂) fragment. Without

exception, the α angles adapt an antiperiplanar (ap)

conformation. The position of the CO group and the

C*−H bond are the best described by the δ angle. Only for a

few higher-energy structures did the conformation of the δ

angle deviate from either synperiplanar (sp) or synclinal (sc).

The favored syn position of the CO and C*−H bonds is

caused by the interaction of the opposite polarized dipoles;

hence, any deformation of the δ angle toward the parallel

arrangement of the dipoles will increase the energy of the

entire molecular system.

The number of thermally available conformers that need to

be taken into account during further analysis varies, depending

on the structure of the ester. For a highly structurally

diversiﬁed ester, such as 10, there was only one low-energy

conformer found. In contrast are the highly ﬂexible diester

molecules. In the example case of 22, we found 12 conformers

(at the B3LYP/6-311G(d,p) level) that ranged in relative

energies by less than 2 kcal mol⁻¹. Among these individuals,

the lowest-energy conformer No. 3 was found almost 2-fold

more abundant than the second lowest energy conformer No.

1. The estimated ΔΔG-based populations for these two species

were 15 and 28%, respectively, for conformers Nos. 1 and 3 of

22.

The selected structural, energetic, and spectral data found

for the lowest energy conformers of 1, 4, 6, 10, 11, 14, 15, 18,

The ζ torsion angle (ζ = O−C*−C−C or O−C*−C−C*)

describes the conformation of the chiral backbone. The values

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Table 2. ΔΔG-Based Percentage Populations (pop), Values of the γ₁−γ₃Angles (deg), Helicities of Trityl Chromophore, and

Sequences of Cotton Eﬀects (CEs) and Similarity Index (∑) Calculated for the Lowest Energy Conformers of 1, 4, 6, 10, 11,

14, 15, 18, and 20−22

a

b

c

d

e

compd.

pop.

γ₁

γ₂

γ₃

helicity

CEs

∑

f

1 (38)

37

27

63

100

59

78

67.69

−41.80

4.70

66.50

66.14

6.55

64.95

42.22

43.58

78.94

50.87

−86.04

11.74

−13.15

−66.71

−63.15

−11.31

42.20

−63.59

−12.48

84.16

55.81

−28.17

51.46

39.98

69.89

47.65

−34.96

−52.11

49.05

37.34

−51.80

49.42

−25.96

52.07

37.85

47.58

26.47

PMP

MMM

0MM

PMP

PPP

∓/−

0.97

0.92

0.95

0.98

0.91

0.98

0.95

f

4 (46)

g

6 (1)

/+

∓/−

/+

∓/−

/+

f

10 (1)

f

11 (56)

f

14 (1)

PMM

PMP

PPM

PPP

PMP

PPP

g

15 (20)

18 (32)

31

30

h

20 (22)

30

∓/−

0.96

h

21 (1)

75

28

∓/−

0.85

0.97

MPP

PPM

ij

22 (3) ^,

−16.19

a

The number of the lowest energy conformer is given in parentheses (conformers are numbered according to their appearance during

b

c

conformational search). γ = (O)C−C_Tr−C_ipso−C_ortho(of the two possibilities the absolute values ≤ 90° has been chosen). Helicity of the

d

phenyl rings is deﬁned as M (−90° < γ < 0°), P (0° < γ < 90°) or 0 (for γ angles deviating from zero by less than |5°|). Calculated at the TD-M06-

e

2X/6-311++G(2d,2p) level for the given the lowest energy conformer sequence of Cotton eﬀects. Similarity between ECD spectra: experimental

f

g

and the calculated for the given lowest energy conformer. Optimized at the B3LYP/6-311++G(d,p) level. Optimized at the M06-2X/6-311+

+G(d,p) level. Optimized at the B3LYP-GD3BJ/6-311G(d,p) level; Optimized at the B3LYP/6-311G(d,p) level. C₂symmetry.

h

i

j

of the ζ angle vary for these compounds, where the carbon

chain has the possibility of free rotation or for those in which

the ring undergoes pseudorotation.⁴⁰For example, for 1 the ζ

angle adapts either a sc or an ap conformation, but for the

even more ﬂexible 15, no speciﬁc range of values can be

distinguished. In contrast, there are rigid 10 and 11, where the

ζ torsion angle adapts only a −sc or +sc conformation,

respectively. Conformation of the backbone aﬀects energy of

the whole molecule and, to a lesser extent, the chiroptical

properties.

the blade appears at the more crowded side of the molecule

and the plane of the phenyl group is facing the bulkier

substituent at the stereogenic center.

In the particular cases of the lowest-energy conformers No. 1

of 6 and No. 1 of 14, the CO···H−C_orthointeractions

involving the second ketone or carbomethoxy carbonyl group

compete and prevail over the attractive (O)C−O···H−C_ortho

interactions. The possibility for the double CO···H−C_ortho

structure-stabilizing interactions limits the number of thermally

available conformers. Hence, not only the steric hindrance

(gem-dimethyl group) but, most of all, the strong electrostatic

interactions determine the structure and properties. This is the

reason why these compound show the unexpectedly high

degree of induction of optical activity among all items under

study.

As an eﬀect of the cascade process, a nonequal population of

optically active conformational diasteroisomers is formed. Such

a residual diasteroisomerism cannot be directly observed

experimentally; however, a nearly perfect similarity between

the calculated and the experimental ECD spectra strongly

supports this conclusion (Figures 2 and SI_79 −SI_130).

The performed theoretical analysis led to the conclusion that

even for the conformationally labile esters discussed here the

dominant impact on the overall ECD spectrum can be

attributed to the lowest-energy conformer of the given

compound. At this point of the discussion, we took the liberty

to make a digression. “The lowest-energy conformer of a given

compound is considered to dominate over the overall ECD

spectrum.” However, this is a kind of generalization that is not

supported by any strict rule. The relation ‘the more the

abundant conformer, the more eﬀect on the chiroptical

response’ is rather an expectation that has now become the

prevailing rule. One should bear in mind that the overall ECD

spectrum is a function of population of conformers as well as

rotatory strengths generated by them. Moreover, for a given

structure, there is no direct correlation between rotatory

strengths and conformer population.

Conformation of the trityl group, described by the sets of

β₁−β₃and γ₁−γ₃angles, are of the key importance for the

observed induced ECD. The β₁−β₃torsion angles (β = O

C−C−C_ipso) determine the spatial orientation of each phenyl

blade relative to the carbonyl group. In the majority of cases,

one of the phenyl groups lies parallel to the (O)C−

C(−C_ipso) bond (the associated β angle is in an ac

conformation), whereas the second phenyl is almost parallel

to the CO bond (the β angle adapts an ac conformation, but

of the opposite sign to the previously mentioned one). The sp

conformation of the third β angle resulted from possible C

O···H−C_orthointeractions (the calculated CO···H−C_ortho

distance ranging from 2.11 to 2.60 Å). These interactions

constitute the main factor aﬀecting the structure (helicity) of

the trityl group. Furthermore, the conformation of this

particular ring, as deﬁned precisely by the γ angle (γ =

(O)C−C−C_ipso−C_ortho, of the two possibilities the absolute

values ≤90° has been chosen) is sc. The orientation of the

second phenyl, parallel to the (O)C−C(−C_ipso) bond, is sp

and is controlled by the attractive (O)C−O···H−C_ortho

interactions. The remaining phenyl ring, whose protons are

not involved in any CH···O interactions, adjusted the

conformation to other phenyl rings present in the chromo-

phore and to the substituents ﬂanking chirality element. This

particular phenyl ring orientates itself in such a way as to

maximize the probability of both intratrityl CH···π and π···

C_sp3H interactions with the protons from the chiral backbone

(if possible). In other words, this particular conformation of

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One can expect that for the compounds having more than

one noninteracting ester groups, the CEs magnitude should be

the linear combination of the contributions from individual

chromophores. However, the presence of an additional trityl

group in the proximity does not automatically increase the

observed CEs amplitudes. This is particularly seen for

symmetrical derivative 21. Signiﬁcantly, the separation of the

two stereogenic centers by one −CH₂− group results in a

reduction in the intensity of the CEs. In compounds 18, 20,

and 21 the trityl−trityl matching interrupts the cascade

chirality induction from stereogenic center to the chromo-

phore (see Figure 4). Thus, the chiroptical response is much

Figure 4. (a) Direct chirality transfer from stereogenic center to the

trityl chromophore. (b) Trityl−trityl matching interrupting the

chirality transfer from stereogenic centers to the chromophores.

smaller than that observed for 19 and 22, where the TrCOO

fragments are separated by two methylene groups. In 19 and

22, again the stereogenic center(s) play the key role in chirality

induction, which in these cases takes place accordingly to the

above-described mechanism.

Control over the Solid-State Molecular Organization

in the Crystals of Esters. As the intentionally designed ester

molecules do not contain functional groups commonly

regarded as hydrogen bond donors, the classical hydrogen

bonds cannot be observed in the crystal structure. However,

the presence of the trityl group in the molecules favors the

occurrence of π-electron system interactions. We have decided

to use such a nonclassical supramolecular tool (the trityl

group) allowing to predict the organization of molecules in the

crystal. In the particular cases, we have expected to observe a

characteristic supramolecular motif, which is the 6-fold phenyl

embrace (Figure 5a,b).²⁹In the great majority, the analyzed

compounds were chiral, and we expected to observe the oﬀset

6-fold phenyl embrace formation (Figure 5d). However, our

previous experience with trityl-containing derivatives has

shown that they can crystallize with an increased number of

molecules in an asymmetric unit (Z′ > 1). Thereby, in an

asymmetric unit we often have observed two (or more)

molecules of the opposite helicity, where the trityl groups

formed pseudocentrosymmetric dimers.²⁷The beneﬁts of

creating this supramolecular synthon are comparable to those

of the formation of a classical hydrogen bond. The percentage

share of individual intermolecular interactions in the Hishfeld

surface for molecules in the crystal structure was calculated and

is shown in the Figure SI_131. The summary of crystallo-

graphic data for analyzed compounds is presented in Table

SI_55.

Figure 3. (a) Deﬁnition of torsion angles α, β₁-β₃, γ₁-γ₃, δ, and ζ.

Example structures of calculated, ΔΔG-based, lowest-energy con-

formers of esters (b) 1; (c) 6; (d) 14; and (e) 15 and the (f) C₂-

symmetrical conformer no. 3 of 22. Dashed lines indicate possible

attractive interactions. Distances are in Angstroms.

However, in the cases discussed here, the expected

correlations between the abundance of the given lowest energy

conformer and its impact on the overall ECD spectrum has

been fulﬁlled. To be as strict as possible, for each of

compounds 1, 4, 6, 10, 11, 14, 15, 18, and 20−22, we have

estimated the similarity factors (∑) between the experimental

ECD spectrum and the one calculated for the lowest energy

conformer of a given ester (see Table 2).⁴¹With the exception

of 21, the similarity factors ∑ have ranged from 0.91 to 0.98,

which quantitatively indicated a very good match between the

experimental and theoretical results. The lower ∑ value

estimated for 21 (0.85) resulted from deﬁciencies of

experimental data rather than poor reproduction of material

reality by theoretical methods.⁴²

Referring again to the lowest energy conformers as the

representative examples, we have correlated the helicity of the

trityl chromophore, deﬁned either as M (−90° < γ < 0°), P (0°

< γ < 90°), or 0 (−5° ≤ γ ≤ 5°) to the sequence of the CE

appearing in the spectral region of the trityl UV absorption.

The negative/positive/negative (∓/−) sequence of CEs

correlates with PPP or PPM chromophore helicity, whereas

in a MMM or MM0-helical chromophore, CEs of the opposite

sequence, namely, /+ are generated.

We have chosen compound 1 as a model molecule in the

structural study. The bulky trityl part of the molecule is

expected to dominate the crystal packing mode in 1. In the

crystal of 1, the asymmetric unit consists of two symmetrically

independent molecules A and B, which diﬀer in the

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the speciﬁc protective eﬀect of the trityl group on the

stereogenic center. In other words, the packing of the mode of

the molecules in the crystal is indiﬀerent to both the absolute

conﬁguration at the stereogenic center and conformation of

the aliphatic chain.²⁷

Replacing the aliphatic substituent with the 2-phenylethyl

group resulted in the emergence of competition for the

interactions of trityl systems. Compound 5 crystallizes in two

polymorphic forms, designated here as 5-α and 5-β.

Interestingly, both forms are monoclinic, belonging to the

P2₁symmetry group, and the crystals of both forms were

obtained in one crystallization. Surprisingly, the X-ray powder

pattern, measured for the ground sample, shows no diﬀraction

picks that would indicate the presence of a detectable amount

of 5-α (Figure SI_135). It can be assumed that under the

conditions of crystallization, 5-α is formed in a very small

amount, while 5-β is more preferred. However, the trans-

formation of 5-α formed during the primary crystallization into

the 5-β polymorph, by grinding the sample in a mortar, cannot

be excluded.

For both polymorphs of 5, the asymmetric unit contains of

two molecules, A and B, that diﬀer in geometry. In the case of

the 5-α polymorph, the trityl groups of A and B molecules

form propellers characterized by opposite helicities and

arranged in the 6-fold phenyl embrace supramolecular synthon

stabilized by edge-to-face interactions. In the crystal, molecules

A and B form alternately arranged layers which penetrate each

other (see Figure 6b,d). In the crystal of 5-β, the trityl groups

also form propellers, but of the same MMM helicity, so it is

impossible to create expected supramolecular motif. In this

particular case, the trityl groups from A and B interact with

each other, but the acceptor of the C−H···π interaction is the

outer side of the trityl group (Figure 5c). As predicted, the

phenylethyl substituent of molecule A interacts with the inner

side of the trityl system of B through both edge-to-face and C−

H···π interactions (the CH₃group is the donor). Similar to the

α form, one can note the formation of alternating layers of

molecules A and B in the crystal structure of 5-β (see Figure

6e).

In principle, introducing centrosymmetry into the system

should result in increased possibilities of forming the desired

(centrosymmetric) supramolecular synthon. In the crystal

structure of (rac)-5, the trityl groups interact with each other;

however, the 6-fold phenyl embrace motif is not observed. The

acceptor for the edge-to-face interactions is the outer side of

the trityl group (see Figure 6f). Also the structure of the

molecule itself diﬀers from that found in the crystals of the α

and β polymorphs, which proves high conformational liability

of this compound.

The introduction of a relatively large menthol (or neo-

menthol) substituent to the ester molecule resulted in a

reduction of the trityl groups interactions. In the crystal

structures of 10 and 11, the interactions of trityl groups are

very limited and are replaced by interaction with a menthyl

substituent. In both cases, the crystals are made from layers of

molecules. The mutual alignment of molecules, the structure of

layers, and intermolecular interactions are closely related to the

geometry of the substituent (see Figure SI_136).

A separate group is formed by derivatives containing two

trityl substituents at the opposite ends of the aliphatic chain. In

terms of the geometry of the molecule and the arrangement of

the molecules in the crystal, compounds 18, 19, and 21 turned

out to be very similar. It is worth noting that for all these

Figure 5. Examples of the 6-fold phenyl embrace supramolecular

synthons (shown as space-ﬁll models) found in the crystal structures

of (a) 1 and (b) 5-α. (c) Interaction of trityl groups without

formation of phenyl embrace synthon in 5-β, and (d) oﬀset 6-fold

phenyl embrace in (rac)-5.

conformation of the 2-butyl chain. In molecule A the aliphatic

part adapts bent conformation, while in molecule B it is is

extended. In the crystal structure, the trityl groups arrange

themselves as propellers of opposite helicities and mutually

interact to form the supramolecular six-ring motif, stabilized by

edge-to-face interactions. The three-dimensional crystal

structure is stabilized by numerous C−H···π interactions

involving also aliphatic 2-butyl substituents as donors (Figure

6a,c).

The 6-fold phenyl embrace supramolecular synthon is

almost centrosymmetric, so we have decided to check the

eﬀect of the stereogenic center and enantiomeric purity on the

molecular packing in the crystals of (R)-1 and (rac)-1.

Comparison of the lattice parameters and analysis of the

packing mode of molecules in crystals of (rac)-1 and (R)-1

have shown that the crystals are isostructural. Furthermore,

(rac)-1 crystallizes as a solid solution of the enantiomers (the

reﬁned ratio of the occupancy factors is 77.5:22.5). The

disorder in the crystal concerns not only the conﬁguration on

the stereogenic center but also the conformation of the 2-butyl

chain of the molecule: the alkyl group adapts either an

extended or bent conformation. The (rac)-1 is an example of

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Figure 6. (a) Molecular structure of asymmetric unit of 1. (b) Molecular structure of asymmetric unit of compound 5. (c) Molecular packing in the

crystal of 1 (mol A, green and mol B, orange) and comparing of molecular packing in the crystal structures of (d) 5-α (mol A, green and mol B,

violet), (e) 5-β (mol A, orange and mol B, black), and (f) (rac)-5. Hydrogen atoms are omitted for clarity. The oxygen atoms are shown as balls.

compounds the helicity of all trityl groups is MMM. This could

lead us to a simple supposition that formation of the desired 6-

fold supramolecular motif would not be possible. In the crystal

of 18, the molecule lies on the 2-fold axis passing through the

C_sp2−C_sp2bond. Such an arrangement of the molecule causes

substitutional disorder: The position of the methyl group in

the molecule cannot be determined unambiguously, and in the

adopted model, it is equally likely attached to the C2 or C2′

atom (the atom numbering scheme is shown in Figure

SI_137). The molecule is folded in such a way that a kind of

cavity is formed between the trityl groups, into which another

molecule ﬁts, and the whole system is stabilized by the C−

H···π interactions (Figure 7a). This type of association of the

molecules is observed in the crystals of compounds 18, 19, and

21. The crystal structure of 19 is disordered in a manner

similar to that found for crystal of 18. The methyl group in the

crystal structure of 19 cannot be located; therefore, in the

adopted model it is equally likely to be attached to the C2 and

C4 atom (the atom numbering scheme is shown in Figure

SI_138). This is, however, not the only disorder. As

mentioned, the molecules are arranged in columns; however,

in the crystal of 19 some of them are shifted by half the length

of the molecule relative to the adjacent columns. This is the

case for about 15% of the columns in the crystal (disorder

model is presented in Figure SI_138). In general, in the crystal

structures of 18, 19, and 21, the molecules are arranged in

columns stabilized as a whole by compensation of C−H···π

interactions.

The structure of the column is stabilized by the mutual

interactions of the trityl groups, but the 6-fold phenyl embrace

synthon has not been found in the crystals of 18, 19, and 21.

The characteristic motifs of the arrangement of molecules are

shown in Figure 7b,c. Is worth emphasizing that in the case of

the structure of compound 19, in order to maintain the

characteristic arrangement of the molecules, it should be

assumed that the shifting of the columns by half the length of

the molecules occurs much more often (it concerns half of

them). Due to the fact that the molecular arrangement motif

seems to be repetitive in this group of compounds, it can be

assumed that this is the reason for the column disorder (as a

tendency toward a more favorable arrangement of the

molecules).

The crystal structure of 20 is an exception. The compound

crystallizes with four molecules in the asymmetric unit, and the

geometry of the molecules (in pairs A and C as well as B and

D) remains very similar. Similar to compounds 18, 19, and 21,

the helicity of both trityl groups in one molecule is always the

same: PPP for molecules A and C and MMM for molecules B

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have control over the conformation of the molecule and the

trityl fragment in particular. In the ﬁrst approximation, the

ability to generate nonzero Cotton eﬀects depends on the

structure of the inducer. A greater structural diﬀerentiation is

expected to reﬂect in higher power in dynamic chirality

induction. However, the situation is not as simple as it might

seem at ﬁrst glance, and there are some additional factors that

should be taken into account. Deﬁnitely, more eﬀective

chirogenesis is observed for derivatives in which the TrCOO

group is attached directly to the stereogenic center. For esters

8 and 9, having the stereogenic center spaced from the oxygen

atom and thus, from the “hub” of the propeller, the observed

amplitudes of Cotton eﬀects are the weakest within the whole

series. However, the contingency to additional CO···H−

C_orthointeractions with substituent’s carbonyl group seems to

be an equally important or even more important structural

factor than steric hindrances.

Looking more broadly, the transmission of information from

the chiral inducer to the structurally adaptable chromophoric

probes is not only an interesting phenomenon but also has

found practical applications in stereochemical assignments.¹²A

simple model of the optical activity of chiral esters of

triphenylacetic acid, as proposed by us (shown in Figure 8),

allows the sequence of CEs to be correlated within the

substitution pattern at the stereogenic center (not necessarily

with the absolute conﬁguration).

Figure 7. (a) Intermolecular C−H···π interaction in crystal structure

of 18. (b) Molecular columns in crystal of 21 (view along c-axis). (c)

Molecular packing in crystal of 21 (view along b-axis). (d)

Comparison of the geometry of symmetrically independent molecules

in crystal structure of 20. (e) Molecular packing in the crystal of 20

(alternating layers of A + B and C + D molecules). Hydrogen atoms

are omitted for clarity. The oxygen atoms are shown as balls.

and D. Speciﬁc sorting of the molecules in the crystal structure

is observed. Molecules A and B as well as C and D form

alternating layers (001), as shown in the Figure 7d,e. In the

crystal structure, the interacting trityl groups (in the pairs A−B

and C−D) led to the formation of a pseudocentrosymmetric 6-

fold phenyl embrace supramolecular synthon.

Figure 8. Correlation model of ECD spectrum with the dominant

conformation for chiral esters of triphenylacetic acid (projection

down the O−C(O) bond).

Comparison of triphenylacetic acid esters with previously

studied triphenylacetamides leads to the conclusion that in

both cases the mechanism of generating optical activity is

slightly diﬀerent. For both types of compounds, the CO···

H−C_orthointeractions most aﬀect the structure. However, for

secondary amides, the amide group acts as a speciﬁc hydrogen

bond donor that additionally stabilizes the conformation

through attractive (N)H···C_ipsointeraction.¹⁹In the case of

esters, the linking oxygen atom serves as hydrogen bond

acceptor. The tertiary amides have no counterpart among

esters and control their conformation by sterical repulsions

between trityl group and substituent at the nitrogen atom. The

direct comparison of ECD data found for 1 with that of the

respective triphenylacetamide having 2-butane substituent at

the nitrogen atom clearly indicates the greater eﬃciency of the

chirality transmission process in the ester.

CONCLUSIONS

■

In this work, some attempts have been made at a

comprehensive approach to triphenylacetic acid esters, and

the compounds are characterized by high structural diversity.

The usability and versatility of such speciﬁc trityl derivatives as

chirality-sensing stereodynamical probes has been proven. At

the molecular level, the mechanism of action of these

compounds is based on some fundamental processes, namely,

chirality induction and chirality transfer through a set of weak

but complementary noncovalent interactions. Thus, the

formation of sets of conformational diasteroisomers, charac-

terized by a speciﬁc propeller’s twist, is responsible for the

generation of optical activity.

The electronic circular dichroism spectroscopy in con-

junction with theoretical calculations enables the determi-

nation of such a residual stereoisomerism in the chiral

triphenylacetic acid ester. The tendency to maximize the

attractive CH···O and CH···π interactions is considered to

The bent structure of chiral O-trityl ethers, possibly by

directing sterical interactions between the inducer and the

chromophore, led to the generation of strong chiroptical

response.⁹For example, the consequence of the bevel gear

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polarimeter was used for optical rotation ([α]_D) measurements

(carried out at ca. 20 °C). Column chromatography was performed

on J. T. Baker Silica Gel 40 μm (chromatography grade). Merck

Kieselgel type 60F₂₅₄analytical plates were used for TLC analyses.

mechanism of chirality transmission taking place in the trityl

ether of menthol was the appearance of intense CEs in the

higher-energy region of ECD spectrum (Δε = +25.6 at 208 nm

and Δε = −80.4 at 194 nm). On the contrary, CEs measured

for the trityl ether of (S)-2-butanol (Δε = −3.8 at 208 nm, Δε

= 16.7 at 194 nm) are comparable to those measured for 1.⁹

However, the chirogenesis eﬃciency in the dynamically chiral

trityl derivatives rises as follows: triphenylacetamides <

triphenylacetic acid esters < O-trityl ethers.

Melting points were measured on Buchi Melting Point B-545 and

̈

uncorrected. All reagents were used as purchased from commercial

suppliers. All solvents were provided by local suppliers and were

puriﬁed by conventional methods prior to use.

(R)-Methyl 2-cyclohexyl-2-hydroxyacetate was prepared according

to the literature procedure.^22h

General Procedure for Synthesis of the Esters of Triphenyl-

acetic Acid. To a suspension of triphenylacetic acid (1.24 g, 4.3

mmol) in 15 mL of dry toluene containing three drops of DMF was

added dropwise thionyl chloride (1.5 mL). The mixture was gently

reﬂuxed at 80 °C for 3 h using the heating mantle as the heat source.

After cooling and evaporation of all volatiles under reduced pressure,

the crude triphenylacetic acid chloride was used without further

puriﬁcation.

The esters were prepared by fusing triphenylacetic acid chloride (1

equiv) with an excess of an anhydrous alcohol (x equiv) at 125 °C

(oil bath) by 18 h. The mixture was cooled and dissolved in CH₂Cl₂.

To the mixture was added silica gel (ca. 100 mg), and all volatiles

were removed by evaporation under reduced pressure. The crude

products were puriﬁed by column chromatography on silica gel

(eluent n-hexane/CH₂Cl₂).

In general, the process of dynamic induction of an optical

activity in any probe is easily observed for inducers of

signiﬁcant structural variability. The inducers, characterized by

small or even negligible diﬀerences in substituents ﬂanking

stereogenic center, are studied rather unwillingly. The

unprecedently high sensitivity of the triphenylacetic acid to

molecular chirality is clearly illustrated with the derivative of

tetrahydrofuran 15. The probe can distinguish the diﬀerence

between oxygen atom and methylene group.

Unexpectedly, the process of optical activity generation is

interrupted by the presence of the second trityl group in close

proximity. In these compounds, the trityl−trityl interactions

could be more important for chirogenesis that the direct

chirality induction from the permanent stereogenic center to

the chromophore.

During all experimental work, no unexpected or unusually high

safety hazards were encountered.

The ﬁeld of supramolecular chemistry needs new synthons

that will allowed predictable interactions, which will make it

possible to control or at least predict the distribution of

molecules in the crystal.⁴³The trityl group is a substituent with

great potential to participate in intermolecular interactions, and

our intention was to use this group as a supramolecular tool. In

the studied materials, phenyl rings take part in interactions,

acting as the donor and acceptor of edge-to-face interactions. It

should be emphasized that both the inner and outer side of the

trityl group take part in the interactions. Unfortunately, the

expected (and desired) 6-fold phenyl embrace is a supra-

molecular synthon with high unreliability and low predict-

ability. The conclusion from the research conducted by us and

others seems not very optimistic, namely, the prediction of a

material structure that is based on the structure of the trityl-

containing molecule seems to be largely random. This is

obviously due to the various alternative possibilities to phenyl

groups interactions and, therefore, to formation of diverse

aggregates that remain similar in energy.

Our study can be presented in a broader context. Despite

some recent experimental ﬁndings, the cascade chirality

induction, understood as a sequential induction of helicity in

molecular propeller and then in a prochiral substrate, has never

been a subject of in-depth studies.⁵Demonstrating the

relationship between asymmetric synthesis and dynamic

induction of optical activity will conﬁrm the universal nature

of the observed phenomena.

(R)-sec-Butyl 2,2,2-triphenylacetate (1). Scale 0.82 mmol, x = 3;

eluent n-hexane/CH₂Cl₂4:1 to 2:1. Yield 168 mg (59%), white

crystalline solid. Mp 96−97 °C. [α]²_D⁰−2 (c 1.01, CHCl₃). H NMR

1

(300 MHz, CDCl₃) δ 7.35−7.20 (m, 15H), 4.97 (h, J = 6.2 Hz, 1H),

1.53−1.43 (m, 2H), 1.17 (d, J = 6.3 Hz, 3H), 0.71 (t, J = 7.5 Hz, 3H).

¹³C{¹H} NMR (75 MHz, CDCl3) δ 173.1, 143.1, 130.3, 127.6, 126.7,

74.1, 67.6, 28.5, 18.9, 9.5. ATR-IR 3055, 3028, 2968, 2928, 2879,

1716, 1489, 1443, 1211, 1186, 761, 741, 699 cm⁻¹. HRMS (ESI) m/z:

[M + Na]⁺Calcd for C₂₄H₂₄O₂Na 367.1669. Found 367.1675.

(rac)-sec-Butyl-2,2,2-triphenylacetate ((rac)-1).^22bThe title com-

pound was obtained from (rac)-2-butanol and triphenylacetyl chloride

under the above-mentioned reaction conditions. Scale 1.6 mmol.

Yield 372 mg (70%), white crystalline solid. The NMR spectra of

product (rac)-1 were the same as those described for (R)-1. HRMS

(ESI) m/z: [M + K]⁺Calcd for C₂₄H₂₄O₂K 383.1408. Found

383.1416.

(S)-Pentan-2-yl 2,2,2-triphenylacetate (2). Scale 0.62 mmol, x =

2; eluent n-hexane/CH₂Cl₂4:1 to 2:1. Yield 189 mg (85%), colorless

oil. [α]²_D⁰+5 (c 2.32, CHCl₃). ¹H NMR (300 MHz, CDCl₃) δ 7.30−

7.20 (m, 15H), 5.04 (h, J = 6.3 Hz, 1H), 1.51−1.26 (m, 2H), 1.18−

1.04 (m, 2H), 1.17 (d, J = 6.3 Hz, 3H), 0.79 (t, J = 7.3 Hz, 3H).

¹³C{¹H} NMR (75 MHz, CDCl₃) δ 173.1, 143.1, 130.3, 127.6, 126.7,

72.6, 67.6, 37.7, 19.4, 18.3, 13.8. ATR-IR 3059, 3033, 2959, 2932,

2873, 1724, 1493, 1446, 1216, 1118, 741, 727, 695 cm⁻¹. HRMS

(ESI) m/z: [M + Na]⁺Calcd for C₂₅H₂₆O₂Na 381.1825. Found

381.1825.

(S)-Octan-3-yl 2,2,2-triphenylacetate (3). Scale 1.09 mmol, x = 3;

eluent n-hexane/CH₂Cl₂4:1 to 2:1. Yield 390 mg (89%), colorless oil.

[α]²_D⁰+5.5 (c 3.32, CHCl₃). H NMR (300 MHz, CDCl₃) δ 7.29−

1

7.22 (m, 15H), 4.92 (quintet, J = 6.1 Hz, 1H), 1.57−1.41 (m, 4H),

1.20−1.03 (m, 6H), 0.83 (t, J = 6.9 Hz, 3H), 0.71 (t, J = 7.4 Hz,

3H).¹³C{¹H} NMR (75 MHz, CDCl₃) δ 173.2, 143.2, 130.4, 127.6,

126.7, 67.7, 32.8, 31.7, 26.3, 24.7, 22.5, 14.0, 9.4. ATR-IR 3059, 3033,

2955, 2931, 2859, 1723, 1493, 1447, 1217, 1186, 740, 726, 696 cm⁻¹.

HRMS (ESI) m/z: [M + Na]⁺Calcd for C₂₈H₃₂O₂Na 423.2295.

Found 423.2309.

EXPERIMENTAL SECTION

■

1

General Information. H and ¹³C 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

SiMe₄. HR-MS spectra were obtained with a Bruker Impact HD,

QTOF MS spectrometer. UV and ECD spectra were recorded in

spectroscopic grade cyclohexane or acetonitrile using a JASCO J-810

instrument. The UV and ECD measurements were performed in

quartz cell (0.5 mm path length), at a scanning speed of −50 nm

min⁻¹and a resolution of 0.5 nm. The concentrations of the samples

are collected in Table SI_1. FT-IR spectra were measured on a

Nicolet iS 50 spectrometer using ATR module. A JASCO P-2000

(R)-3-Methylbutan-2-yl-2,2,2-triphenylacetate (4). Scale 0.57

mmol, x = 3.3; eluent n-hexane/CH₂Cl₂4:1 to 2:1. Yield 144 mg

(71%), white amorphous solid. Mp 92−95 °C. [α]²_D⁰+3.6 (c 0.84,

CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ 7.29−7.21 (m, 15H), 4.90−

4.84 (m, 1H), 1.74−1.63 (m, 1H), 1.12 (d, J = 6.4 Hz, 2H), 0.69 (dd,

J = 6.8, 3.3 Hz, 6H). ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 173.0,

143.1, 130.3, 127.6, 126.7, 67.6, 32.4, 18.0, 17.5, 16.0. ATR-IR 3057,

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Article

3020, 2961, 2934, 2873, 1715, 1489, 1443, 1209, 1185, 760, 743, 699

cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for C₂₅H₂₆O₂Na

381.1825. Found 381.1830.

NMR (75 MHz, CDCl₃) δ 172.9, 143.1, 130.3, 127.6, 126.6, 76.1,

67.6, 46.9, 40.3, 34.2, 31.5, 25.1, 22.7, 22.1, 15.6. ATR-IR 3091, 3064,

3036, 2946, 2932, 2869, 2850, 1725, 1494, 1447, 1214, 1194, 743,

698 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for C₃₀H₃₄O₂Na

449.2451. Found 449.2455.

(1S,2S,5R)-2-Isopropyl-5-methylcyclohexyl-2,2,2-triphenylace-

tate (11). Scale 1.1 mmol, x = 1; eluent n-hexane/CH₂Cl₂4:1 to 2:1.

Yield 411 mg (86%), white crystalline solid. Mp 103−105 °C. [α]_D²⁰

+11 (c 1.02, CHCl₃). ¹H NMR (300 MHz, CDCl₃) δ 7.28−7.19 (m,

15H), 5.32 (bs, 1H), 1.97−1.92 (m, 1H), 1.52−1.51 (m, 1H), 1.02−

0.82 (m, 5H), 0.77 (d, J = 5.7 Hz, 3H), 0.71 (t, J = 5.5 Hz, 6H).

¹³C{¹H} NMR (75 MHz, CDCl₃) δ 172.8, 143.1, 130.3, 127.6, 126.6,

(R)-1-Phenylethyl-2,2,2-triphenylacetate (5). Scale 1.0 mmol, x =

3; eluent n-hexane/CH₂Cl₂4:1 to 2:1; crystallized by n-hexane. Yield

168 mg (17%), white crystalline solid. Mp 120−122 °C. [α]²_D⁰+14 (c

1

0.5, CHCl₃). H NMR (400 MHz, CDCl₃) δ 7.28−7.15 (m, 18H),

7.08−7.06 (m, 2H), 6.02 (q, J = 6.6 Hz, 1H), 1.46 (d, J = 6.6 Hz,

3H). ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 172.5, 142.9, 141.0, 130.3,

128.2, 127.7, 127.6, 126.7, 126.2, 73.9, 67.4, 22.0. ATR-IR 3088,

3055, 3032, 2978, 2930, 1723, 1490, 1445, 1216, 1197, 760, 696

cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for C₂₈H₂₄O₂Na

415.1669. Found 415.1679.

72.8, 67.9, 47.2, 38.7, 34.7, 28.5, 26.4, 25.1, 22.1, 21.0, 20.9. ATR-IR

3059, 3023, 2965, 2954, 2914, 2882, 2849, 1714, 1494, 1443, 1226,

1215, 740, 698 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for

C₃₀H₃₄O₂Na 449.2451. Found 449.2467.

(rac)-1-Phenylethyl-2,2,2-triphenylacetate ((rac)-5). The title

compound was obtained from (rac)-1-phenylethanol and triphenyla-

cetyl chloride under above-mentioned reaction conditions. Yield 116

mg (30%), white crystalline solid. The NMR spectra of the product

(rac)-5 were the same as described for (R)-5. HRMS (ESI) m/z: [M

+ K]⁺Calcd for C₂₈H₂₄O₂K 431.1408. Found 431.1422.

(R)-1-Cyclohexyl-2-methoxy-2-oxoethyl-2,2,2-triphenylacetate

(6). Scale 0.97 mmol, x = 1.3; eluent n-hexane/CH₂Cl₂4:1 to 2:1;

separated from triphenylmethanol by column chromatography on

alumina (eluent n-hexane/CH₂Cl₂1:1). Yield 48 mg (16%), colorless

oil. [α]²_D⁰−27 (c 0.95, CHCl₃). ¹H NMR (300 MHz, CDCl₃) δ 7.32−

7.21 (m, 15H), 4.80 (d, J = 4.4 Hz, 1H), 3.73 (s, 3H), 1.80−1.71 (m,

1H), 1.38−0.65 (m, 10H). ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

173.4, 170.0, 142.7, 130.3, 127.7, 126.7, 77.9, 67.4, 52.0, 39.4, 28.7,

27.0, 25.9, 25.7. ATR-IR 3059, 3033, 2928, 2854, 1735, 1493, 1447,

1173, 743, 696 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for

C₂₉H₃₀O₄Na 465.2036. Found 465.2030.

(S)-2-Methoxy-2-oxo-1-phenylethyl 2,2,2-triphenylacetate (7).

Scale 1 mmol, x = 3; eluent n-hexane/CH₂Cl₂4:1 to 2:1; separated

from triphenylmethanol by column chromatography on alumina

(eluent n-hexane/CH₂Cl₂1:1). Yield 66 mg (15%), colorless oil. [α]_D²⁰

+72 (c 1.04, CHCl₃). ¹H NMR (300 MHz, CDCl₃) δ 7.31−7.17 (m,

20H), 6.01 (s, 1H), 3.71 (s, 3H). ¹³C{¹H} NMR (100 MHz, CDCl₃)

δ 173.1, 169.1, 142.5, 133.3, 130.4, 128.9, 128.5, 127.7, 127.2, 126.9,

75.5, 67.4, 52.6. ATR-IR 3057, 3028, 2957, 1752, 1729, 1492, 1449,

1218, 1170, 740, 694 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for

C₂₉H₂₄O₄Na 459.1567. Found 459.1566.

Cholestan-3β-yl triphenylacetate (12). Scale 0.74 mmol, x = 1;

eluent n-hexane/CH₂Cl₂4:1 to 2:1. Yield 364 mg (78%), white

amorphous solid. Mp 125−127 °C (lit. 127−129 °C).^22d[α]_D²⁰+19 (c

1

0.94, CHCl₃). H NMR (300 MHz, CDCl₃) δ 7.35−7.17 (m, 15H),

4.86 (tt, J = 11.1, 5.0 Hz, 1H), 1.96−1.92 (m, 1H), 1.83−1.57 (m,

5H), 1.51−0.95 (m, 25H), 0.89 (d, J = 4.2 Hz, 3H), 0.87 (d, J = 1.3

Hz, 3H), 0.85 (d, J = 1.3 Hz, 3H), 0.74 (s, 3H), 0.63 (s, 3H).

¹³C{¹H} NMR (75 MHz, CDCl₃) δ 173.0, 143.2, 130.4, 127.6, 126.7,

75.4, 67.4, 56.4, 56.3, 54.2, 44.7, 42.6, 40.0, 39.5, 36.7, 36.2, 35.8,

35.5, 35.46, 33.6, 32.0, 28.6, 28.3, 28.0, 27.1, 24.2, 23.9, 22.6, 21.2,

12.0. ATR-IR 3059, 3023, 2930, 2865, 1727, 1493, 1467, 1445, 1214,

741, 697 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for C₄₇H₆₂O₂Na

681.4642. Found 681.4631.

Testosterone triphenylacetate (13). Reaction temp. 165 °C, scale

0.95 mmol, x = 1; eluent n-hexane/CH₂Cl₂4:1 to 0:1. Yield 83 mg

(16%), white amorphous solid. Mp 73−83 °C. [α]²_D⁰+56 (c 1.6,

1

CHCl₃). H NMR (300 MHz, CDCl₃) δ 7.30−7.19 (m, 15H), 5.72

(s, 1H), 4.69 (t, J = 8.9, 7.9 Hz, 1H), 2.41−2.17 (m, 5H), 2.03−1.96

(m, 1H), 1.85−1.38 (m, 9H), 1.14 (s, 3H), 1.07−0.83 (m, 5H), 0.43

(s, 3H). ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 199.6, 173.5, 171.0,

143.0, 142.5, 130.3, 127.6, 126.8, 123.9, 84.0, 67.5, 53.6, 49.9, 42.5,

38.6, 36.5, 35.3, 33.9, 32.8, 31.4, 29.7, 27.0, 23.6, 20.5, 17.3. ATR-IR

3058, 3023, 2923, 2852, 1726, 1672, 1492, 1446, 1215, 1187, 744,

697 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for C₃₉H₄₂O₃Na

581.3026. Found 581.3036.

(S)-2-Methylbutyl-2,2,2-triphenylacetate (8). Scale 1 mmol, x = 3;

eluent n-hexane/CH₂Cl₂4:1 to 2:1. Yield 371 mg (95%), white

(R)-4,4-Dimethyl-2-oxotetrahydrofuran-3-yl-2,2,2-triphenylace-

tate (14). Scale 1.1 mmol, x = 2.2; eluent n-hexane/CH₂Cl₂4:1 to

1:1. Yield 196 mg (46%), white amorphous solid. Mp 133−142 °C.

[α]²_D⁰+11 (c 1.02, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ 7.34−7.22

(m, 15H), 5.51 (s, 1H), 3.94 (q, J = 9.1 Hz, 2H), 0.96 (s, 3H), 0.59

(s, 3H). ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 172.3, 171.9, 142.4,

130.2, 127.9, 127.0, 76.2, 75.9, 67.3, 40.1, 22.6, 19.3. ATR-IR 3049,

2998, 2973, 2959, 2927, 1786, 1742, 1496, 1476, 1464, 1448, 1175,

1149, 750, 701 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for

C₂₆H₂₄O₄Na 423.1567. Found 423.1549.

amorphous solid. Mp 64−66 °C. [α]²_D⁰+3.3 (c 1.12, CHCl₃). H

1

NMR (300 MHz, CDCl₃) δ 7.31−7.17 (m, 15H), 4.04 (dq, J = 12.9,

6.0 Hz, 2H), 1.66−1.55 (m, 1H), 1.23−1.11 (m, 1H), 1.08−0.94 (m,

1H), 0.78 (t, J = 7.4 Hz, 3H), 0.72 (d, J = 6.8 Hz, 3H). ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 173.7, 143.0, 130.3, 127.6, 126.8, 70.1,

67.6, 34.0, 25.8, 16.4, 11.1. ATR-IR 3063, 3034, 2955, 2928, 2875,

1727, 1493, 1444, 1223, 1198, 697 cm⁻¹. HRMS (ESI) m/z: [M +

Na]⁺Calcd for C₂₅H₂₆O₂Na 381.1825. Found 381.1830.

(3S)-3,7-Dimethyloct-6-en-1-yl-2,2,2-triphenylacetate (9). Scale 1

mmol, x = 3; eluent n-hexane/CH₂Cl₂4:1 to 2:1. Yield 286 mg (66%)

as nonseparable mixture of isomers, diﬀering in the position of the

double bond in the skeleton of the molecule; the title compound

consists of the major fraction (over 90%). Colorless oil. [α]²_D⁰−2.3 (c

(S)-Tetrahydrofuran-3-yl-2,2,2-triphenylacetate (15). Scale 1

mmol, x = 3; eluent n-hexane/CH₂Cl₂4:1 to 0:1. Yield 145 mg

(40%), colorless oil. [α]_D²⁰−3.1 (c 1.12, CHCl₃). ¹H NMR (300 MHz,

CDCl₃) δ 7.32−7.18 (m, 15H), 5.45−5.41 (m, 1H), 3.94−3.89 (m,

1H), 3.78−3.70 (m, 2H), 3.61−3.55 (m, 1H), 2.13−2.01 (m, 1H),

1.89−1.81 (m, 1H). ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 173.2,

142.7, 130.2, 127.7, 126.9, 76.1, 72.6, 66.9, 32.5. ATR-IR 3054, 3023,

2924, 2870, 1723, 1489, 1445, 1205, 742, 699 cm⁻¹. HRMS (ESI) m/

z: [M + Na]⁺Calcd for C₂₄H₂₂O₃Na 381.1461. Found 381.1469.

(R)-1-Methylpyrrolidin-3-yl-2,2,2-triphenylacetate (16). Scale 1.1

mmol, x = 2; eluent n-hexane/CH₂Cl₂4:1 to CH₂Cl₂/MeOH 98:2.

1

1.79, CHCl₃). H NMR (300 MHz, CDCl₃) δ 7.31−7.16 (m, 15H),

5.01 (t, J = 6.9, 1H), 1.92−1.81 (m, 1H), 1.66 (s, 3H), 1.57 (s, 3H),

1.38−1.00 (m, 6H), 0.78 (d, J = 6.1 Hz, 3H). ¹³C{¹H} NMR (101

MHz, CDCl₃) δ 173.6, 143.0, 131.2, 130.3, 127.6, 126.8, 109.7, 67.5,

64.0, 36.8, 35.2, 29.2, 25.7, 25.3, 19.1, 17.6. ATR-IR 3059, 3022, 2961,

2925, 1729, 1493, 1446, 1212, 1184, 740, 697 cm⁻¹. HRMS (ESI) m/

z: [M + Na]⁺Calcd for C₃₀H₃₄O₂Na 449.2451. Found 449.2464.

(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl-2,2,2-triphenylace-

tate (10). Scale 1.1 mmol, x = 1; eluent n-hexane/CH₂Cl₂4:1 to 1:1.

Yield 262 mg (55%), white crystalline solid. Mp 101−102 °C (lit.

Yield 95 mg (24%), light brown oil. [α]²_D⁰−6 (c 0.83, CHCl₃). H

1

NMR (300 MHz, CDCl₃) δ 7.31−7.16 (m, 15H), 5.37−5.30 (m,

1H), 2.99−2.93 (m, 1H), 2.51−2.35 (m, 3H), 2.26 (s, 1H), 2.21−

2.12 (m, 1H), 1.77−1.68 (m, 1H). ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 173.2, 142.8, 130.2, 127.7, 126.8, 75.8, 67.3, 61.3, 54.7,

42.0, 32.1. ATR-IR 3058, 3032, 2940, 2839, 2781, 1725, 1493, 1446,

1216, 1177, 742, 696 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for

C₂₅H₂₆NO₂[M + H]⁺: 372.1958. Found 372.1953.

100−101 °C).²⁰[α]_D²⁰−5 (c 1.26, CHCl₃). H NMR (300 MHz,

1

CDCl₃) δ 7.30−7.19 (m, 15H), 4.74 (td, J = 10.9, 4.3 Hz, 1H), 2.18−

2.11 (m, 1H), 1.67−1.56 (m, 2H), 1.52−1.39 (m, 1H), 1.22−1.10

(m, 2H), 1.02−0.95 (m, 2H), 0.90 (d, J = 6.9 Hz, 3H), 0.88−0.74 (m,

1H), 0.62 (d, J = 6.9 Hz, 3H), 0.53 (d, J = 6.9 Hz, 3H). ¹³C{¹H}

6444

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J. Org. Chem. 2021, 86, 6433−6448

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Article

(R)-1-(2,2,2-Triphenylacetyl)pyrrolidin-3-yl-2,2,2-triphenylace-

tate (17). Scale 2 mmol, x = 0.5; eluent n-hexane/CH₂Cl₂4:1 to

CH₂Cl₂/MeOH 99:1. Yield 95 mg (21%), white amorphous solid. Mp

93−103 °C. [α]²_D⁰−81 (c 0.66, CHCl₃). ¹H NMR (400 MHz,

CDCl₃) δ 7.29−7.07 (m, 60H), 5.43−5.41 (m, 1H), 5.09 (t, J = 3.7

Hz, 1H), 3.89 (dd, J = 14.4, 5.0 Hz,H), 3.72−3.67 (m, 1H), 3.22 (dd,

J = 11.8, 4.4 Hz, 1H), 2.93 (d, J = 12.9 Hz, 1H), 2.81−2.78 (m, 1H),

2.22 (dd, J = 12.8, 4.3 Hz, 1H), 1.98 (td, J = 11.1, 6.0 Hz, 1H), 1.82−

1.67 (m, 3H), 1.50−1.48 (m, 1H). ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 172.9, 172.7, 171.4, 171.2, 143.1, 142.52, 142.49, 142.4,

142.2, 130.34, 130.30, 130.2, 130.14, 130.09, 127.9, 127.73, 127.72,

127.69, 127.6, 127.1, 126.9, 126.7, 126.6, 126.5, 76.1, 72.4, 67.5, 53.3,

52.4, 45.9, 45.8, 32.0, 29.0. ATR-IR 3057, 3022, 2928, 1728, 1636,

1491, 1445, 1385, 1212, 1181, 741, 696 cm⁻¹. HRMS (ESI) m/z: [M

+ Na]⁺Calcd for C₄₄H₃₇NO₃Na 650.2666. Found 650.2664.

ASSOCIATED CONTENT

* Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.joc.1c00279.

■

sı

Experimental details, calculation details, X-ray crystallog-

raphy details, total energies, percentage populations and

structures of all calculated low-energy conformers,

calculated UV and ECD spectra, copies of UV and

ECD spectra of 1−22 measured in cyclohexane and

acetonitrile, ¹H and ¹³C{H} NMR spectra of all

synthesized new compounds, and Cartesian coordinates

for all calculated structures (PDF)

FAIR data, including the primary NMR FID ﬁles, for

compounds 1−22 (ZIP)

(R)-Propane-1,2-diyl-bis(2,2,2-triphenylacetate) (18). Scale 2

mmol, x = 1; eluent n-hexane/CH₂Cl₂4:1 to 0:1. Yield 136 mg

(22%), white crystalline solid. Mp 154−156 °C. [α]²_D⁰−5 (c 0.83,

Accession Codes

CCDC 2039790−2039800 contain the supplementary crys-

tallographic data for this paper. These data can be obtained

free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by

emailing data_request@ccdc.cam.ac.uk, or by contacting The

Cambridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

1

CHCl₃). H NMR (400 MHz, CDCl₃) δ 7.27−7.21 (m, 2H), 7.21−

7.07 (m, 28H), 5.24−5.17 (m, 1H), 4.32 (dd, J = 11.9, 3.5 Hz, 1H),

4.10 (dd, J = 11.9, 5.2 Hz, 1H), 0.91 (d, J = 6.5 Hz, 3H). ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 173.3, 172.6, 142.7, 142.6, 130.3, 130.22,

130.20, 127.8, 127.7, 127.6, 127.1, 126.9, 126.8, 69.7, 67.5, 67.4, 66.7,

15.7. ATR-IR 3059, 3022, 2999, 2924, 1735, 1724, 1488, 1444, 1209,

1181, 744, 696 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for

C₄₃H₃₆O₄Na 639.2506. Found 639.2514.

AUTHOR INFORMATION

Corresponding Author

■

Marcin Kwit − Faculty of Chemistry, Adam Mickiewicz

(R)-Butane-1,3-diyl bis(2,2,2-triphenylacetate) (19). Scale 1

mmol, x = 0.5; eluent n-hexane/CH₂Cl₂4:1 to 0:1. Yield 211 mg

(67%), white crystalline solid. Mp 192−197 °C. [α]²_D⁰−14 (c 1.42,

CHCl₃). ¹H NMR (300 MHz, CDCl₃) δ 7.30−7.14 (m, 30H), 4.83−

4.72 (m, 1H), 4.01 (dt, J = 11.0, 5.5 Hz, 1H), 3.76 (dt, J = 11.3, 6.8

Hz, 1H), 1.66 (q, J = 5.9 Hz, 2H), 1.07 (d, J = 6.3 Hz, 3H). ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 173.3, 172.6, 142.9, 130.2, 127.9, 127.72,

127.7, 127.2, 126.84, 126.75, 69.4, 67.4, 61.6, 34.3, 19.4. ATR-IR

3087, 3060, 3024, 2991, 2924, 2854, 1722, 1488, 1443, 1206, 1183,

745, 698 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for C₄₄H₃₈O₄Na

653.2662. Found 653.2657.

(2R,3R)-Butane-2,3-diyl-bis(2,2,2-triphenylacetate) (20). Scale 1

mmol, x = 0.5; eluent n-hexane/CH₂Cl₂4:1 to 0:1. Yield 39 mg

(12%), white crystalline solid. Mp 146−150 °C. [α]²_D⁰+16 (c 1.1,

CHCl₃). ¹H NMR (600 MHz, CDCl₃) δ 7.22−7.13 (m, 15H), 5.01−

4.97 (m, 1H), 0.83 (d, J = 6.4 Hz, 3H). ¹³C{¹H} NMR (150 MHz,

CDCl₃) δ 172.7, 142.7, 130.3, 127.7, 126.8, 72.6, 67.5, 14.9. ATR-IR

3055, 3024, 2991, 2938, 2851, 1732, 1493, 1443, 1209, 1176, 740,

696 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for C₄₄H₃₈O₄Na

653.2662. Found 653.2652.

(2R,4R)-Pentane-2,4-diyl-bis(2,2,2-triphenylacetate) (21). Scale 1

mmol, x = 0.5; eluent n-hexane/CH₂Cl₂4:1 to 0:1. Yield 48 mg

(14%), white crystalline solid. Mp 267−270 °C. [α]²_D⁰+12 (c 0.66,

CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ 7.29−7.19 (m, 15H), 4.81−

4.72 (m, 1H), 1.52−1.49 (dd, J = 7.3, 5.8 Hz, 1H), 1.01 (d, J = 6.2

Hz, 3H). ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 172.7, 142.9, 130.2,

127.7, 126.7, 69.4, 67.5, 42.1, 19.6. ATR-IR 3088, 3059, 3027, 2983,

2924, 2853, 1720, 1492, 1444, 1207, 1185, 758, 744, 698 cm⁻¹.

HRMS (ESI) m/z: [M + Na]⁺Calcd for C₄₅H₄₀O₄Na 667.2819.

Found 667.2819.

́

University, 61 614 Poznan, Poland; Centre for Advanced

́

Technologies, Adam Mickiewicz University, 61 614 Poznan,

Poland; orcid.org/0000-0002-7830-4560;

Email: marcin.kwit@amu.edu.pl

Authors

Natalia Prusinowska − Faculty of Chemistry, Adam

Mickiewicz University, 61 614 Poznan, Poland; Centre for

Advanced Technologies, Adam Mickiewicz University, 61 614

́

Poznan, Poland

Agnieszka Czapik − Faculty of Chemistry, Adam Mickiewicz

́

University, 61 614 Poznan, Poland

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.joc.1c00279

Author Contributions

All authors have given approval to the ﬁnal version of the

manuscript.

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

This work was supported by a research grant from National

Science Center (NCN) Poland, Grant UMO-2016/21/B/

ST5/00100. All calculations were performed at Poznan

Supercomputing and Networking Centre.

DEDICATION

■

(2R,5R)-Hexane-2,5-diyl-bis(2,2,2-triphenylacetate) (22). Scale 1

mmol, x = 0.5; eluent n-hexane/CH₂Cl₂4:1 to 0:1. Yield 96 mg

(31%), white amorphous solid. Mp 147−149 °C. [α]²_D⁰+11 (c 0.86,

Dedicated to Prof. Janusz Jurczak on the occasion of his 80th

birthday anniversary.

1

CHCl₃). H NMR (300 MHz, CDCl₃) δ 7.23−7.16 (m, 15H), 4.84

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(dt, J = 11.4, 5.5 Hz, 1H), 1.06 (d, J = 6.2 Hz, 5H). ¹³C{¹H} NMR

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31.0, 19.5. ATR-IR 3059, 3025, 2969, 2926, 2855, 1720, 1489, 1444,

1212, 1199, 738, 699 cm⁻¹. HRMS (ESI) m/z: [M + Na]⁺Calcd for

C₄₆H₄₂O₄Na 681.2975. Found 681.2972.

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6448

https://doi.org/10.1021/acs.joc.1c00279

J. Org. Chem. 2021, 86, 6433−6448

Article Doi

Chiral Triphenylacetic Acid Esters: Residual Stereoisomerism and Solid-State Variability of Molecular Architectures

DOI: 10.1021/acs.joc.1c00279

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Article abstract of DOI:10.1021/acs.joc.1c00279

Full text of DOI:10.1021/acs.joc.1c00279

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