Synthesis and solvent sorption characteristics of new types of tartaric acid, lactic acid and TADDOL derived receptor compounds

Article abstract of DOI:10.1016/j.tet.2015.07.061

Based on a modular design strategy, three new types of tartaric acid, lactic acid and TADDOL derived compounds featuring a linear shaped central backbone and terminally attached functional units corresponding to the above substance classes have been developed. This has led to the synthesis of the compounds 1a-6a (tartaric acid derivatives), 7a-11a (lactic acid derivatives) and 1c-6c (TADDOL derivatives). Preparation of the tartaric acid derivatives involved Pd-catalysed cross-coupling reactions followed by transacetalisation and hydrolysis of the corresponding esters in the final step of the synthetic routes. The derivatives of lactic acid have been prepared on a similar reaction sequence but with the use of lactic esters. The TADDOL derivatives were obtained by Grignard reaction between phenylmagnesium bromide and tartaric esters. Optical rotation data are specified for each compound including intermediates. Organic vapour sorption behaviour of selected compounds coated as solid films on the quartz crystal of a QCM device has been studied. Significant differences in the affinities towards organic solvent vapours are observed. They both depend on structural properties of the respective receptor solvent molecules and solvent polarity as well, showing developmental possibility in the application of vapour sensing.

Full text of DOI:10.1016/j.tet.2015.07.061

Tetrahedron 71 (2015) 7695e7705
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and solvent sorption characteristics of new types of
tartaric acid, lactic acid and TADDOL derived receptor compounds
*
Diana Eißmann, Felix Katzsch, Edwin Weber
€
€
Institut fur Organische Chemie, Technische Universitat Bergakademie Freiberg, Leipziger Straße 29, D-09599 Freiberg, Sachsen, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Based on a modular design strategy, three new types of tartaric acid, lactic acid and TADDOL derived
compounds featuring a linear shaped central backbone and terminally attached functional units corre-
sponding to the above substance classes have been developed. This has led to the synthesis of the
compounds 1ae6a (tartaric acid derivatives), 7ae11a (lactic acid derivatives) and 1ce6c (TADDOL de-
rivatives). Preparation of the tartaric acid derivatives involved Pd-catalysed cross-coupling reactions
followed by transacetalisation and hydrolysis of the corresponding esters in the final step of the synthetic
routes. The derivatives of lactic acid have been prepared on a similar reaction sequence but with the use
of lactic esters. The TADDOL derivatives were obtained by Grignard reaction between phenylmagnesium
bromide and tartaric esters. Optical rotation data are specified for each compound including in-
termediates. Organic vapour sorption behaviour of selected compounds coated as solid films on the
quartz crystal of a QCM device has been studied. Significant differences in the affinities towards organic
solvent vapours are observed. They both depend on structural properties of the respective receptor
solvent molecules and solvent polarity as well, showing developmental possibility in the application of
vapour sensing.
Received 31 March 2015
Received in revised form 20 July 2015
Accepted 22 July 2015
Available online 29 July 2015
Keywords:
Carboxylic receptor compounds
TADDOL derivatives
Receptor layer formation
Organic vapour sorption
QCM sensing
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
a related group of spacer type bisisophthalic acids.7 All such com-
pounds in the solid state feature more or less a largely rigid, porous
Solid materials capable of selectively absorbing organic and in-
organic vapours thus providing an opportunity for chemical sen-
soring, filtering, separation, compound storage or topochemical
catalysis are currently a field of high interest.1,2 The so-called metal-
organic frameworks (MOFs), being organiceinorganic hybrid
compounds derived from metal coordination to particular ligand
type linker molecules, are perhaps the most prominent exponents
of this substance class at present.3 A further family of compounds
gaining interest are distinguished by vapour absorption and are
completely organic solid materials featuring a framework of or-
ganic molecules linked via covalent bonds (COFs) or non-covalent
supramolecular interactions.4 Polymeric frameworks of the co-
valent type often use boronic ester, Schiff’s base, or acetylenic bond
formation, while the supramolecularly generated vapour absorbing
materials are mostly based on a hydrogen bonded framework
structure.5 For the purposes of the hydrogen bond stabilized net-
works (HBNs), oligofunctional carboxylic acids as the constituent
molecules play a major role such as trimesic acid and analogues6 or
framework structure, classing them as organic zeolites.8
Organic zeolites forming sorptive host-guest inclusion com-
pound are also known,9 aside from more flexible structures, the
lattices of which are prone to open in contact with a guest vapour.
Respective host structures are often related to clathrate forming
compounds, i.e., they possess a bulky molecular constitution,
mostly endowed with polar functions (carboxyl or hydroxyl
groups), being difficult to access.10 Thus, unlike the hydrogen bond
stabilised networks with the molecules showing outward func-
tional groups, the molecular structures of this specific clathrate
host feature endo-oriented functional groups; being in a rather
difficult situation of forming a stable crystal lattice that promotes
the uptake of solvent as a correction.11 Prototype compounds
having this attribute, which can be used for sensor application,
involve particular dihydroxy substituted biphenyls12,13 and roof-
shaped molecules,14 bulkily modified structures of lactic acid,15,16
or specific derivatives of tartaric acid,17,18 the latter being called
TADDOLs.19
Here we report on a series of new tartaric acids (1ae6a) and
lactic acid derived compounds (7ae11a) including, aside from
specific TADDOLs (3ce6c), a particular new type of bis-TADDOLs
(1c, 2c). This shows the remarkable property of vapour sorption
* Corresponding author. E-mail address: edwin.weber@chemie.tu-freiberg.de
(E. Weber).
http://dx.doi.org/10.1016/j.tet.2015.07.061
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

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D. Eißmann et al. / Tetrahedron 71 (2015) 7695e7705
as solid materials as well as the prospective linker molecules for
coordinative framework construction.2,3 We describe preparation
of these compounds and demonstrate their behaviour as sorptive
materials towards a variety of organic solvent vapours based on
investigation by quartz micro balance with regards to a potential
sensor aspect.
units of linear shape are involved in structural formation. These
consist of p-phenylene and ethynylene moieties, as pointed out in
Figs. 1 and 2.
The new tartaric acid derivatives 1ae6a (Fig. 1) were obtained
by basic (LiOH) hydrolysis of the corresponding esters 1be6b in
yields ranging between 66 and 87 percent. The respective tartaric
ester derivatives 1be6b were prepared from L(þ)-diethyl tartrate
and corresponding arylaldehyde diethylacetals [12a (1b), 12b (2b),
13a (3b), 13b (4b), 14a (5b), 14c (6b)] (Fig. 3), following a trans-
acetalisation.21 The respective diethylacetals 12b, 13a and 13b were
synthesized via Pd-catalysed cross-coupling reaction22 between 4-
ethynylbenzaldehyde diethylacetal (14b) and 4-bromobenzal
dehyde diethylacetal, dimethyl 5-iodoisophthalate or ethyl 4-
bromobenzoate, respectively. The diethylacetals 14a23 and 14b24
were prepared according to the literature procedures while 12a is
a purchasable compound. The diethylacetal 14c was obtained via
reaction between 14b and methyl chloroformiate in the presence of
n-BuLi.25
2. Results and discussion
2.1. Design and synthesis of compounds
In order to obtain solid materials featuring the desired property
of vapour sorption based on tartaric acid, lactic acid and TADDOLs,
host compounds that will make use of the solvent inclusion prin-
ciple in virtue of their bulky constitution paired with the capability
of hydrogen bond formation as well as the terminal attachment of
the characteristic groups to shape a defined backbone unit should
be a promising working plan.20 This has led to the design of mol-
ecules as specified with 1ae11a and 1ce6c in Figs.1 and 2, of which
1ae6a refer to the compounds derived from tartaric acid, 7ae11a
from lactic acid, and 1ce6c being typical of a TADDOL structure.19
Aside from the characteristic polar terminal groups, rigid spacer
The new lactic acid derivatives 7ae11a (Fig. 2) were prepared
from the corresponding ester hydrolysis (LiOH) of 7be11b, similar
to the tartaric acid derivatives. The esters 7b and 11b result
from substitution reactions between L(þ)-ethyl lactate and 1,4-
Fig. 1. Chemical structures of tartaric acid derivatives 1ae6a including ester intermediates 1be6b and corresponding TADDOLs 1ce6c, studied in this paper.

D. Eißmann et al. / Tetrahedron 71 (2015) 7695e7705
7697
Fig. 3. Chemical structures of acetals and lactate intermediates involved in the syn-
theses of the target compounds.
derivatives, the methine carbons of the asymmetric centres, the
respective carboxylic carbons, and also the carbons of the ethyl
groups of the esters appear as two different signals.
Fig. 2. Chemical structures of lactic acid derivatives 7ae11a including ester in-
termediates 7be11b, studied in this paper.
A rather complex behaviour regarding the resonances of the
aromatic protons is observed for the TADDOLs 1ce6c showing such
multiplets in the 1H and a large number of signals in the 13C NMR
spectra being difficult to assign. This, however, is in line with
a previous finding obtained for closely related TADDOLs27 pro-
viding evidence that a seven-membered ring is formed by an
intramolecular hydrogen bond between the two neighbouring OH
groups leading to a complex stereochemical environment. The IR
spectra of 3c and 4c show some unexpected behaviour in that ab-
sorption of the ethyne bond cannot be observed, though the mol-
ecules are unsymmetrical, with reference to the substitution of the
ethynylene unit.
bis(bromomethyl) benzene or ethyl 4-(bromomethyl)benzoate; the
esters 8be10b from Pd-catalysed cross coupling reaction22 be-
tween 15b and 15a, dimethyl 5-iodoisophthalate or ethyl 4-
bromobenzoate, respectively. The lactic ester intermediate 15a
(Fig. 3) was prepared from the substitution reaction of 4-
bromobenzyl bromide with L(þ)-ethyl lactate under basic condi-
tions (NaH), while the ester 15b (Fig. 3) via Pd-catalysed cross-
coupling between 15a and trimethylsilylacetylene followed by
fluoride assisted deprotection of the TMS-protected intermediate
compound.
Another point perhaps calling for an explanation is the isolation
of the TADDOLs 1ce6c co-crystallized as solvates with acetone.
However, TADDOLs and related derivatives are well-known for
their specific behaviour to form highly stable and stoichiometric
crystalline inclusion compounds with organic solvents17e19 this
being the case also with the aforementioned TADDOLs. A similar
argumentation holds for the hydrates of the tartaric acid de-
rivatives 1ae6a considering the distinct enclathration property
found for other rigid framework substituted carboxylic acids.28,29
The TADDOLs 1ce6c (Fig. 1) were synthesized in moderate to
high yields using common Grignard reactions26 between phenyl-
magnesium bromide and corresponding tartaric esters 1be6b.
All new synthesised compounds are proven in their structures
by NMR and IR spectroscopic as well as elemental analytic data.
Noteworthy remarks about this are given in the following: Re-
garding the 1H NMR data of the tartaric acid 1ae6a and ester de-
rivatives 1be6b, the methine protons located at the asymmetric
carbon atoms are split into doublets. Moreover, in the case of these
esters, the ethyl groups occur as separate triplets and quartets at-
tributed to the chirality of the compounds. For a similar reason, in
the 1H NMR spectra of the lactic acid 7ae11a and ester derivatives
7be11b, the benzylic methylene protons are represented by two
doublets and in the case of the lactic esters, the ethyl groups are
split into a triplet and a symmetric multiplet resulting from
a CHAHB spin system. Also the acetals 12e14 (aec) show this
splitting of the ethyl groups due to the diastereotopic property of
the methylene protons. In the 13C NMR of the tartaric acid and ester
2.2. Organic vapour sorption
In demonstration of the expected absorption/desorption be-
haviour of the newly developed solid compounds towards organic
vapour molecules, a quartz crystal microbalance (QCM)30 as the
gravimetric device was used. Here, the corresponding gas-sensing
process is shown via the incorporation of the analyte into the
chemical layer deposited on the quartz crystal, leading to a mass

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D. Eißmann et al. / Tetrahedron 71 (2015) 7695e7705
increase. As a result, the resonance frequency of the quartz crystal is
shifted. The theoretical correlation is given by the Sauerbrey’s
equation:31
D
f ¼ C
D
m;
where
D
f stands for the frequency shift and C for a calibration
constant (including the resonance frequency of the non-loaded
quartz, the frequency constant of the quartz, its density, and the
electrode surface).
In practice, this measurement involves controlled dipping of the
gold plated quartz into a 0.01N solution of the respective com-
pound dissolved in ethanol and subsequent evaporation of the
solvent to form the receptor layer. Compounds that have been in-
vestigated in this respect include the tartaric acids 1ae6a, lactic
acid derivatives 7ae11a as well as the TADDOLs 1ce6c. The organic
vapours that have been selected for the sorption study are n-hex-
ane, tetrahydrofuran (THF), dichloromethane (DCM), acetone and
ethanol, these being exemplary solvents of low and high polarity as
well as of aprotic and protic nature. Taking into account the molar
masses of both the solvent and the absorbent, a factor x0 can be
deduced indicating the number of solvent molecules being absor-
bed per molecule of the receptor:
Fig. 5. Comparison of the ratios of absorption involving solid TADDOL derivatives
1ce6c as QCM coating materials for vapours of various solvents.
D
nðsolventÞ
x0 ¼
:
D
nðreceptorÞ
This means an absorption ratio of 100% equals an inclusion
stoichiometry of 1:1. The results for the ratio of absorption (x0 in
mol%) obtained for the different receptor molecules are illustrated
in Figs. 4e6.
Fig. 6. Comparison of the ratios of absorption involving solid lactic acid derivatives
7ae11a as QCM coating materials for vapours of various solvents.
behaviour of 2ae4a and 6a, having ethynylene units, as opposed to
1a and 5a lacking this particular type of bond. Whereas the ethy-
nylene containing receptor compounds absorb ethanol in higher
amounts than acetone, it is the reverse for the receptors free of
ethynylene. Moreover, a comparison indicates that in the series of
tartaric acid derived receptors, the compounds with a symmetric
structure (1a and 2a), tend to show the highest absorption ratios.
Conversion of the tartaric acid functionality of 1ae6a to TADDOL
units such as in 1ce6c has a decisive effect on the absorption
property of the substance. That is, compared to the acid analogues
1ae6a, the TADDOLs 1ce6c are much more effective and demon-
strate distinctly higher ratios of the absorbed vapours, particularly
in the case of THF, which is taken up by 3c in a nearly 1:4 inclusion
stoichiometry (Fig. 5). On the other hand, relative to the rest of the
solvents, the apolar n-hexane is much less preferred by the TAD-
DOLS, as was the case for the tartaric acid derivatives. The polar
solvent vapours dichloromethane, acetone and ethanol are roughly
equally absorbed in generally moderate amounts, with some vari-
ation in the ratio of solvent uptake depending on the respective
TADDOL.
Fig. 4. Comparison of the ratios of absorption involving solid tartaric acid derivatives
1ae6a as QCM coating materials for vapours of various solvents.
With reference to the tartaric acid derivatives 1ae6a (Fig. 4), it is
shown that all these compounds absorb n-hexane and dichloro-
methane (DCM) in only small amounts, while THF, acetone and
ethanol are absorbed much more efficiently. This can easily be
explained by the fact that the molecular structures of the latter
solvents behave as efficient hydrogen bond acceptors and form
strong hydrogen bonds with the carboxylic acid groups of the re-
ceptor molecules. Derivatives 2ae4a, containing a diphenylethyne
spacer unit, favour ethanol while compounds 1a, 5a and 6a, fea-
turing a benzene spacer, are most efficient in the absorption of THF.
Aside from this structural relation, the presence of an ethynylene
unit in the spacer moiety is also important in other respects of the
absorption property. This is shown with the different receptor

D. Eißmann et al. / Tetrahedron 71 (2015) 7695e7705
7699
Among the molecular solids of the series studied, the lactic acid
derivatives 7ae11a are generally the least effective of all in vapour
uptake (Fig. 6). Nevertheless, there are preferences for such de-
rivatives. As before, absorption of the apolar n-hexane is of no
significance, while the more polar solvents ranging from THF to
ethanol provide higher degrees of absorption. In more detail, the
bis-lactic acid derivative 7a has high affinity for THF, acetone and
EtOH. The tricarboxylic acid derivative 9a behaves similarly, al-
though in this range of solvents 9a is slightly less efficient for THF.
Forming a sharp contrast to 7a, the ethynylene spacered analogue
8a is distinctly inferior in the sorption of the same solvent vapours.
Moreover, 10a features the basic structural framework as contained
in 9a bearing only one acid group in p-position, which shows,
however, distinct inferiority in solvent sorption to 9a.
For the potential use of a solid compound as sensor material, not
only the quantity of solvent absorption in general but also the
relative amounts of absorbed vapours, i.e., the degree of selectivity
is of great importance. Considering the data in this respect, there is
no compound indicating a respective preference to only one of the
examined solvent vapours. However, as derivable from Fig. 4, the
tartaric acid receptors could perhaps be used for detection of THF in
the presence of n-hexane or dichloromethane, just as in selected
compounds of this substance class for the detection of acetone or
ethanol when n-hexane or dichloromethane are present. Never-
theless, as long as the results of the corresponding solvent com-
petition experiments are not in hand, conclusions in this
connection invariably suffer to a rather great extent due to
uncertainty.
Another precondition for the application of a solid receptor
compound in vapour sensing is the reversibility of the absorption
and desorption process. In order to allow a short measuring time,
this process should be completed as fast as possible. Data of an
exemplary study involving the tartaric acid derivative 1a as the
receptor compound and n-hexane, dichloromethane, ethanol and
acetone as the solvent vapours in this sequence is illustrated in
Fig. 7. The diagram shows that at the beginning of the respective
analyte gas flow, a very strong decrease of the resonance frequency
occurs, which can be explained by overloading due to the high
concentration of the saturated gas atmosphere at the beginning of
the influx of air. In the respective sensor experiment, all the sol-
vents studied are desorbed by the outflow of synthetic air, which
requires a longer time before the initial frequency value is reached.
The better the analyte is absorbed, the longer the time is for com-
plete desorption of the solvent from the receptor layer. For com-
parison, frequency changes of an untreated reference quartz are
also given in Fig. 7 ascertaining the effectiveness of the receptor
coating without doubt.
Owing to the chirality of the receptor molecules being ensured
by the presence of the enantiomerical pure tartaric and lactic acid
derived building units, enantioselective vapour sorption could have
been expected.15,16 However, corresponding QCM experiments us-
ing solvent vapours as racemates or separate enantiomers were
found to show only unsatisfactory results.
3. Conclusions
Sequences of reaction steps involving transacetalisation, Pd-
catalysed cross-coupling, hydrolysis and Grignard reactions are
demonstrated to be successful in the synthesis of new types of
tartaric acid, lactic acid and TADDOL derived receptors yielding the
compounds in high quantity and purity. As solid coatings of
a quartz crystal microbalance (QCM), the compounds prove effec-
tive in the sorption of organic solvent vapours leading, however, to
different results, depending both on the structural properties of
receptor, solvent molecules as well as on solvent polarity. On the
part of receptors, a general conclusion with reference to the effi-
ciency of solvent absorption is roughly as follows: TAD-
DOLS>tartaric acid derivatives>lactic acid derivatives. Regarding
the variety of solvent vapours, this basically becomes noticeable in
the fact that n-hexane and dichloromethane are absorbed in only
small amounts as compared with THF, acetone and ethanol being in
conformity in polarity and hydrogen bonding lines of reasoning.
More profound conclusions regarding the sorption behaviour of the
different receptors based on the structural interdependence of re-
ceptors and analytes are difficult to substantiate. However, deduced
from an exemplary study showing reversibility of the absorption/
desorption processes, we conclude that the present series of com-
pounds easily provide for the formation of solid receptor layers,
which are potentially useful in practical vapour sensing by in-
strumental means of QCM measurement. In addition to the ex-
amples given in this paper, this is an indication to the number of
other common solvent vapours but in a qualified sense of enan-
tiospecification. Nevertheless, the present compounds, due to their
functional behaviour and chirality, also appear promising as spacer
units in the design of the metal coordinated framework struc-
tures2,3 that may meet the requirements of enantioselection in this
field of application.
4. Experimental
4.1. General
€
Melting points were measured on a BUCHI Melting Point B-450
(BUCHI Labortechnik AG, Flawil, Switzerland). 1H NMR and 13C
€
NMR spectra (ppm) were recorded on a Bruker DPX 400 (400.1 and
100.6 MHz, respectively) and a Bruker Avance III 500 (500.1 and
125.8 MHz, respectively) using TMS as reference. IR spectra were
obtained from a Nicolet FT-IR 510 spectrometer as liquid films in
a NaCl cell or in KBr pellets. Optical rotation measurements were
performed on a Perkin-Elmer 241 polarimeter at 20 ꢀC and
20
with
l
¼589.3 nm (NaD line). The [
a
]
values are given in
D
[deg ml dmꢁ1
Starting
g
ꢁ1].
compounds
including
bromobenzene, 1,4-
bis(bromomethyl)benzene, 4-bromobenzaldehyde diethylacetal,
4-bromobenzoic acid, L(þ)-diethyl tartrate, dimethyl 5-amino
isophthalate, ethyl 4-(bromomethyl)benzoate, L(þ)-ethyl lactate,
4-formylbenzoic acid, terephthalaldehyde bis(diethylacetal) (12a)
and other reagents were purchased from commercial sources. Di-
methyl 5-iodoisophthalate32 and ethyl 4-bromobenzoate33 were
prepared as described in the literature. Solvents were purified and
dried using standard laboratory procedures.
Fig. 7. Absorption and desorption vs time of solid tartaric acid derivative 1a as QCM
coating material for various solvent vapours by response monitoring of frequency
change. Sequence of the solvent vapours used in the experiment refers to their rates of
absorption.

7700
D. Eißmann et al. / Tetrahedron 71 (2015) 7695e7705
4.2. Synthesis of acetals and lactate intermediates
BuLi (34.4 ml, 55 mmol, 1.6M in n-hexane) at ꢁ60 ꢀC under argon.
Stirring was continued at the same temperature for 30 min. This
mixture was then added to ꢁ60 ꢀC cooled methyl chloroformiate
(5.67 g, 60 mmol). After warming up to room temperature, the
mixture was quenched with water. The aqueous layer was
extracted with diethyl ether. The combined organic phases were
washed with aqueous Na2CO3 and NaCl solutions, then dried
(Na2SO4) and evaporated under reduced pressure to give a brown
oil. Column chromatography (SiO2, EtOAc/n-hexane 1:10, Rf¼0.35)
4.2.1. 4,40-Ethynylenedibenzaldehyde bis(diethylacetal) (12b). 4-
Bromobenzaldehyde diethylacetal and 4-ethynylbenzaldehyd
diethylacetal (14b) were reacted using cross-coupling conditions
and working up as described in the literature34 to yield the com-
pound (35%, white solid, mp 72e74 ꢀC) showing the reported an-
alytical data.34
4.2.2. 4-[3,5-Di(methoxycarbonyl)phenylethynyl]benzaldehyde di-
ethylacetal (13a). Dimethyl 5-iodoisophthalate (16.00 g, 50 mmol)
and 4-ethynylbenzaldehyde diethylacetal (14b) (11.20 g, 55 mmol)
were dissolved in degassed triethylamine (250 ml). To the solution,
the catalyst [composed of Pd(PPh3)2Cl2 (364 mg, 0.5 mmol), CuI
(188 mg, 1.0 mmol), PPh3 (392 mg, 1.5 mmol)] was added and the
mixture was stirred under argon at 110 ꢀC until completion of the
reaction (DC-analysis). The suspension was diluted with diethyl
ether and washed with aqueous NH4Cl and NaCl solutions. After
drying over Na2SO4, the solvent was removed under reduced
pressure to yield 12.80 g (65%) of a yellow oil after column chro-
matography (SiO2, EtOAc/n-hexane 1:6, Rf¼0.40). MS (GCeMS): m/
yielded 10.75 g (82%) of a yellow oil. MS (GCeMS): m/z¼262 [M]þ.
3
1H NMR (CDCl3, 500 MHz):
d
¼1.24 (t, 6H, CH3, JHH¼7.05);
3.50e3.62 (m, sym., 4H, OCHAHB); 3.84 (s, 3H, OCH3); 5.51 (s, 1H,
3
CH, acetal); 7.49 (d, 2H, aryl-H, JHH¼8.25); 7.58 (d, 2H, aryl-H,
3JHH¼8.25); 13C NMR (CDCl3, 125 MHz):
d
¼15.10 (CH3); 52.72
(OCH3), 61.05 (CH2); 80.41, 86.30 (C^C); 100.64 (CH, acetal);
119.29, 126.91, 132.83, 141.86 (aryl-C); 154.38 (COOMe). IR (NaCl
cell): 2224 (C^C); 1714 (C]O); 1606, 1565 (C]C, Ar); 1169, 1116,
1052 (acetal). Elemental analysis calculated for C15H18O4: C, 68.68;
H, 6.92. Found: C, 68.66; H, 6.82.
4.2.7. Ethyl
O-[(4-bromophenyl)methyl]-(S)-lactate
(15a). To
z¼396 [M]þ. 1H NMR (CDCl3, 500 MHz):
d
¼1.25 (t, 6H, CH3,
a cooled (0 ꢀC) suspension of sodium hydride (5.00 g, 125 mmol,
60% suspended in oil) in dichloromethane (60 ml) was added
dropwise L(þ)-ethyl lactate (5.95 g, 50 mmol) dissolved in
dichloromethane (25 ml). After having stirred for 30 min, a solu-
tion of 4-bromobenzyl bromide in dichloromethane (60 ml) was
added dropwise and the mixture was stirred for 5 h at room
temperature. Water was added and the mixture was extracted
with dichloromethane. The combined organic phases were dried
(Na2SO4) and evaporated under reduced pressure to yield 7.86 g
3JHH¼7.10); 3.50e3.65 (m, sym., 4H, CHAHB); 3.96 (s, 6H, OCH3);
5.52 (s, 1H, CH, acetal); 7.49 (d, 2H, aryl-H; 3JHH¼8.25); 7.55 (d, 2H,
aryl-H, 3JHH¼8.25) 8.36 (s, 2H, aryl-H); 8.60 (s, 1H, aryl-H); 13C NMR
(CDCl3, 125 MHz):
d¼15.09 (CH3), 52.40 (OCH3); 60.92 (CH2); 87.41,
91.05 (C^C); 100.83 (CH); 122.23, 124.24, 126.72, 129.90, 130.83,
131.48, 136.35, 139.77 (aryl-C); 165.44 (COOMe). IR (NaCl cell): 2217
(C^C); 1733 (C]O); 1611, 1596, 1505 (C]C, Ar); 1193, 1156, 1059
(acetal). Elemental analysis calculated for C23H24O6: C, 69.68; H,
6.10. Found: C, 69.57; H, 6.25.
(55%) of a light-yellow liquid after column chromatography (SiO2,
20
Et2O/n-hexane 1:9, Rf¼0.39). [
a
]
¼ꢁ50.6 (c¼0.57, CHCl3). MS
D
4.2.3. 4-[4-(Ethoxycarbonyl)phenylethynyl]benzaldehyde
diethyl-
(GCeMS): m/z¼286 [M]þ. 1H NMR (CDCl3, 500 MHz):
¼1.29 (t,
d
3
3
acetal (13b). Ethyl 4-bromobenzoate (11.44 g, 50 mmol) and 4-
ethynylbenzaldehyde diethylacetal (14b) (11.20 g, 55 mmol) were
reacted using the cross-coupling conditions described for the
synthesis of (13a). Column chromatography (SiO2, EtOAc/n-hexane
1:4, Rf¼0.65) yielded 45% of a light yellow solid. mp 37e39 ꢀC. MS
3H, CH2CH3, JHH¼7.15); 1.43 (d, 3H, CHCH3, JHH¼6.85); 4.03 (q,
1H, CH, JHH¼6.85); 4.18e4.24 (m, sym., 2H, CHAHBCH3); 4.40 (d,
3
1H, aryl-CH2, 2JHH¼11.75); 4.63 (d, 1H, aryl-CH2, 2JHH¼11.75); 7.24
(d, 2H, aryl-H, JHH¼8.45); 7.46 (d, 2H, aryl-H, JHH¼8.45); 13C
3
3
NMR (CDCl3, 125 MHz):
d
¼14.13 (CH2CH3); 18.55 (CHCH3); 60.77
(GCeMS): m/z¼352 [M]þ. 1H NMR (CDCl3, 500 MHz):
d
¼1.23 (t, 6H,
(CH2CH3); 71.06 (aryl-CH2); 74.14 (CH); 121.56, 129.42, 131.38,
136.62 (aryl-C); 172.89 (COOEt). IR (NaCl cell): 1746 (C]O); 1591
(C]C, Ar); 1071 (CeO); 1027 (CeBr). Elemental analysis calcu-
lated for C12H15O3Br: C, 50.19; H, 5.27. Found: C, 50.21; H, 5.33.
CH3, 3JHH¼7.10); 1.40 (t, 3H, CH3, 3JHH¼7.15); 3.51e3.65 (m, sym., 4H,
CHAHB); 4.38 (q, 2H, CH2, 3JHH¼7.15); 5.52 (s, 1H, CH, acetal); 7.48 (d,
2H, aryl-H, 3JHH¼8.25); 7.55 (d, 2H, aryl-H, 3JHH¼8.25); 7.58 (d, 2H,
aryl-H, 3JHH¼8.30); 8.03 (d, 2H, aryl-H, 3JHH¼8.30); 13C NMR (CDCl3,
125 MHz):
d
¼14.31, 15.17 (CH3); 60.91, 61.13 (CH2); 88.84, 92.11
4.2.8. Ethyl O-[(4-ethynylphenyl)methyl]-(S)-lactate (15b). Aryl
bromide 15a (14.36 g, 50 mmol), trimethylsilylacetylene (6.18 g,
63 mmol), Pd(PPh3)2Cl2 (0.35 g, 0.5 mmol), CuI (0.19 g, 1.0 mmol)
and PPh3 (0.39 g, 1.5 mmol) in triethylamine (150 ml) were reacted
for 5 h at 70 ꢀC using the procedure described for 13a to yield
13.80 g (91%) of the TMS-protected intermediate compound as
a yellow-orange liquid. Rf¼0.46 (Et2O/n-hexane 1:6). MS (GCeMS):
m/z¼304 [M]þ. For deprotection, to this intermediate compound
(12.00 g, 40 mmol) dissolved in THF (65 ml) was added a solution of
tetrabutylammonium fluoride (1.17 g, 3.5 mmol) in THF (6.5 ml).
The mixture was stirred for 2 h at room temperature and the sol-
(C^C); 100.95 (CH); 122.58, 126.73, 127.81, 129.40, 129.81, 131.45,
131.56, 139.71 (aryl-C); 166.06 (COOEt). IR (cmꢁ1, KBr): 2214 (C^C);
1717 (C]O); 1606, 1562, 1515 (C]C, Ar); 1173, 1128, 1059 (acetal).
Elemental analysis calculated for C22H24O4: C, 62.04; H, 10.41.
Found: C, 61.93; H, 10.18.
4.2.4. 4-(Ethoxycarbonyl)benzaldehyde diethylacetal(14a). 4-Formyl-
benzoic acid was reacted with thionyl chloride and triethyl ortho-
formiate in ethanol according to the literature procedure.23,34 to
yield the compound (90%, yellow liquid) showing analytical data,
which correspond to the literature specifications.23
vent evaporated to yield 8.17 g (88%) of a yellow liquid after column
20
chromatography (SiO2, Et2O/n-hexane 1:6, Rf¼0.28). [
a
]
¼ꢁ48.6
D
4.2.5. 4-Ethynylbenzaldehyde diethylacetal (14b). 4-Bromobenz-
aldehyde diethylacetal and MEBINOL were reacted using the cross-
coupling conditions and deprotection procedure as described in
the literature24,34 to yield the compound (95%, brownish-red liquid)
showing the reported analytical data.34
(c¼0.23, CHCl3). MS (GCeMS): m/z¼232 [M]þ. 1H NMR (CDCl3,
3
500 MHz):
d
¼1.29 (t, 3H, CH2CH3, JHH¼7.15); 1.43 (d, 3H, CHCH3,
3JHH¼6.85); 3.08 (s, 1H, hCH); 4.03 (q, 1H, CH, JHH¼6.85);
4.18e4.24 (m, sym., 2H, CHAHBCH3); 4.43 (d, 1H, aryl-CH2,
2JHH¼12.00); 4.68 (d, 1H, aryl-CH2, 2JHH¼12.00); 7.32 (d, 2H, aryl-H;
3
3JHH¼8.20); 7.47 (d, 2H, aryl-H, JHH¼8.20); 13C NMR (CDCl3,
3
4.2.6. 4-[2-(Methoxycarbonyl)ethynyl]benzaldehyde
(14c). To a stirred solution of 4-ethynylbenzaldehyde diethylacetal
(14b) (10.21 g, 50 mmol) in THF (150 ml) was added dropwise n-
diethylacetal
125 MHz):
d
¼14.10 (CH2CH3); 18.52 (CHCH3); 60.75 (CH2CH3);
71.32 (aryl-CH2); 74.16 (CH); 77.18, 83.36 (C^C); 121.38, 127.54,
132.02, 138.39 (aryl-C); 172.91 (COOEt). IR (NaCl cell): 2108 (C^C);

D. Eißmann et al. / Tetrahedron 71 (2015) 7695e7705
7701
1749 (C]O); 1511 (C]C, Ar); 1068 (CeO). Elemental analysis cal-
culated for C14H16O3: C, 72.39; H, 6.94. Found: C, 72.11; H, 6.83.
136.06, 136.33 (aryl-C); 165.34 (COOMe); 168.84, 169.32 (COOEt). IR
(cmꢁ1, KBr): 2217 (C^C); 1742 (C]O); 1616, 1591, 1515 (C]C, Ar);
1217,1198,1106 (acetal). Elemental analysis calculated for C27H26O10
:
4.3. Tartaric ester derivatives 1be6b (general procedure)
C, 63.53; H, 5.13. Found: C, 63.37; H, 5.24.
To a solution of the corresponding diethyl acetal and L(þ)-
diethyl tartrate in toluene (p.a.), a catalytic amount of pyridinium
tosylate was added. In order to remove the by-product ethanol from
the mixture, the solvent was distilled off during the reaction. The
residue was diluted with diethyl ether and washed with borax and
water to remove unreacted L(þ)-diethyl tartrate. The organic phase
was dried over Na2SO4 and evaporated under reduced pressure.
Specific details for each compound including procedure of purifi-
cation are given below.
4.3.4. Diethyl 2-{4-[4-(ethoxycarbonyl)phenylethynyl]phenyl}-(4R,5R)-
1,3-dioxolane-4,5-dicarboxylate (4b). Ethyl 4-[4-(diethoxymethyl)-
phenylethynyl]benzoate (13b) (8.80 g, 25 mmol), L(þ)-diethyl tar-
trate (5.66 g, 27.5 mmol), pyridinium tosylate (0.25 g, 1 mmol) in
toluene (250 ml) were used to yield 3.85 g (33%) of a pale yellow solid
after column chromatography (SiO2, EtOAc/n-hexane 1:4, Rf¼0.35).
20
mp. 70e73 ꢀC. [
a]
D
¼þ19.3 (c¼0.46, CHCl3). MS (ESI): m/z¼489.0
3
[MþNa]þ. 1H NMR (CDCl3, 500 MHz):
d
¼1.34 (t, 3H, CH3, JHH¼7.15);
3
3
1.39 (t, 3H, CH3, JHH¼7.15); 1.43 (t, 3H, CH3, JHH¼7.15); 4.31 (q, 2H,
3
3
CH2, JHH¼7.15); 4.37 (q, 2H, CH2, JHH¼7.15); 4.42 (q, 2H, CH2,
3JHH¼7.15); 4.87 (d, 1H, CH, 3JHH¼4.00); 4.98 (d, 1H, CH, 3JHH¼4.00);
6.20 (s,1H, CH, acetal); 7.61e7.63 (m, 6H, aryl-H); 8.05 (d, 2H, aryl-H,
4.3.1. Tetraethyl 2,20-(benzene-1,4-diyl)bis[(4R,5R)-1,3-dioxolane-4,
5-dicarboxylate]
(1b). 1,4-Bis(diethoxymethyl)benzene
(12a)
(7.06 g, 25 mmol), L(þ)-diethyl tartrate (11.31 g, 55 mmol), pyr-
idinium tosylate (0.50 g, 2 mmol) in toluene (300 ml) were used.
The crude product was crystallized from toluene to yield 9.18 g
(72%) of a white solid. mp. 68e70 ꢀC (lit.35 mp 69e71 ꢀC).
3JHH¼8.10); 13C NMR (CDCl3, 125 MHz):
¼14.07, 14.15, 14.30 (CH3);
d
61.12, 62.09, 62.10 (CH2); 77.41, 77.70 (CH); 89.47, 91.79 (C^C); 106.17
(CH, acetal); 124.33, 127.28, 127.64, 129.47, 130.02, 131.51, 131.70,
136.05 (aryl-C); 166.02, 168.95, 169.48 (COOEt). IR (cmꢁ1, KBr): 2214
(C^C); 1761 (C]O); 1606, 1562; 1521 (C]C, Ar); 1220, 1116, 1100
(acetal). Elemental analysis calculated for C26H26O8: C, 66.94; H, 5.62.
Found: C, 67.19; H, 5.77.
20
20
[
a]
¼ꢁ16.5 (c¼0.51, CHCl3) [lit.35
[
a
]
¼ꢁ34.0 (c¼1.0, MeOH)].1H
D
D
NMR (CDCl3, 500 MHz):
d
¼1.30 (t, 6H, CH3, 3JHH¼7.10); 1.35 (t, 6H,
3
3
CH3, JHH¼7.10); 4.26 (q, 4H, CH2, JHH¼7.15); 4.32 (q, 4H, CH2,
3JHH¼7.15); 4.84 (d, 2H, CH, 3JHH¼4.05); 4.95 (d, 2H, CH, 3JHH¼4.05);
6.18 (s, 2H, CH, acetal); 7.62 (s, 4H, aryl-H); 13C NMR (CDCl3,
4.3.5. Diethyl 2-[4-(ethoxycarbonyl)phenyl]-(4R,5R)-1,3-dioxolane-
4,5-dicarboxylate (5b). Ethyl 4-(diethoxymethyl)benzoate (14a)
(6.30 g, 25 mmol), L(þ)-diethyl tartrate (5.66 g, 27.5 mmol), pyr-
idinium tosylate (0.25 g, 1 mmol) in toluene (225 ml) were used to
125 MHz):
d
¼14.03, 14.12 (CH3); 62.02, 62.04 (CH2); 77.38, 77.59
(CH); 106.24 (CH, acetal); 127.16, 137.27 (aryl-C); 168.94, 169.55
(COOEt). IR (cmꢁ1, KBr): 1752 (C]O); 1619 (C]C, Ar); 1217, 1103,
1071 (acetal). Elemental analysis calculated for C24H30O12: C, 56.47;
H, 5.92. Found. C, 56.21; H, 6.08.
yield 6.49 g (71%) of a yellow oil after column chromatography (SiO2,
20
EtOAc/n-hexane 1:4, Rf¼0.36). [
a
]
¼ꢁ10.1 (c¼0.36, CHCl3). MS
D
(GCeMS): m/z¼365 [MꢁH]þ.1H NMR (CDCl3, 500 MHz):
¼1.30 (t,
d
3
3
4.3.2. Tetraethyl 2,20-(ethynylene-dibenzene-4,1-diyl)bis[(4R,5R)-1,3-
dioxolane-4,5-dicarboxylate] (2b). Bis[4-(diethoxymethyl)phenyl]-
acetylene (12b) (9.56 g, 25 mmol), L(þ)-diethyl tartrate (11.31 g,
55 mmol), pyridinium tosylate (0.50 g, 2 mmol) in toluene (500 ml)
were used to yield 6.10 g (42%) of a white solid after column
chromatography (SiO2, EtOAc/n-hexane 1:2, Rf¼0.31). mp. 74e77 ꢀC
3H, CH3, JHH¼7.15); 1.36 (t, 3H, CH3, JHH¼7.15); 1.40 (t, 3H, CH3,
3JHH¼7.15); 4.26 (q, 2H, CH2, 3JHH¼7.15); 4.33 (q, 2H, CH2, 3JHH¼7.15);
4.38 (q, 2H, CH2, 3JHH¼7.15); 4.85 (d, 1H, CH, 3JHH¼3.90); 4.97 (d, 1H,
CH, 3JHH¼3.90); 6.21 (s,1H, CH, acetal); 7.67 (d, 2H, aryl-H, 3JHH¼8.20);
8.07 (d, 2H, aryl-H, 3JHH¼8.20); 13C NMR (CDCl3, 125 MHz):
¼13.96,
d
14.06,14.19 (CH3); 60.99, 62.00, 62.04 (CH2); 77.34, 77.63 (CH); 105.83
(CH, acetal); 127.03, 129.47, 131.69, 140.14 (aryl-C); 166.05, 168.80,
169.32 (COOEt). IR (NaCl cell): 1756 (C]O); 1617, 1580, 1513 (C]C,
Ar); 1214, 1174, 1103 (acetal). Elemental analysis calculated for
20
20
(lit.34 mp 74e77 ꢀC). [
a]
¼þ19.0 (c¼0.61, CHCl3) [lit.34
[
a
]
¼þ19.0
D
D
(c¼0.01 mol/l, CHCl3). 1H NMR (CDCl3, 400 MHz):
d
¼1.31 (t, 6H, CH3,
3
3
3JHH¼7.15); 1.36 (t, 6H, CH3, JHH¼7.15); 4.28 (q, 4H, CH2, JHH¼7.15);
3
4.33 (q, 4H, CH2, JHH¼7.15); 4.83 (d, 2H, CH, 3JHH¼4.00); 4.95 (d, 2H,
C18H22O8: C, 59.01; H, 6.05. Found: C, 59.00; H, 5.96.
3
CH, JHH¼4.00); 6.17 (s, 2H, CH, acetal); 7.54e7.59 (m, 8H, aryl-H,
AA0BB0system); 13C NMR (CDCl3, 100 MHz):
d
¼14.08, 14.16 (CH3);
4.3.6. Diethyl 2-{4-[2-(methoxycarbonyl)ethynyl]phenyl}-(4R,5R)-1,
3-dioxolane-4,5-dicarboxylate (6b). Methyl 3-[4-(diethoxymethyl)-
phenyl]propynoate (14c) (6.55 g, 25 mmol), L(þ)-diethyl tartrate
(5.66 g, 27.5 mmol), pyridinium tosylate (0.25 g, 1 mmol) in toluene
62.09, 62.14 (CH2); 77.42, 77.69 (CH); 89.84 (C^C); 106.25 (CH,
acetal); 124.69, 127.23, 131.64, 135.71 (aryl-C); 168.82, 169.25
(COOEt). IR (cmꢁ1, KBr): 1742 (C]O); 1613, 1562, 1521 (C]C, Ar);
1220, 1195, 1100 (acetal). Elemental analysis calculated for
(350 ml) were used to yield 5.83 g (62%) of a yellow oil after column
20
C
32H34O12: C, 62.94; H, 5.61. Found: C, 62.80; H, 5.70.
chromatography (SiO2, EtOAc/n-hexane 1:3, Rf¼0.38). [
a
]
¼þ5.3
D
(c¼0.37, CHCl3). MS (GCeMS): m/z¼375 [MꢁH]þ. 1H NMR (CDCl3,
3
4.3.3. Diethyl 2-{4-[3,5-(dimethoxycarbonyl)phenylethynyl]phenyl}-
(4R,5R)-1,3-dioxolane-4,5-dicarboxylate (3b). Dimethyl 5-[4-(dieth-
oxymethyl)phenylethynyl]-1,3-benzene dicarboxylate (13a) (9.90 g,
25 mmol), L(þ)-diethyl tartrate (5.66 g, 27.5 mmol), pyridinium
tosylate (0.25 g,1 mmol)in toluene (300 ml) were used toyield 9.82 g
(62%) of a yellow oil after column chromatography (SiO2, EtOAc/n-
500 MHz):
d
¼1.29 (t, 3H, CH3, JHH¼7.20); 1.35 (t, 3H, CH3,
3JHH¼7.20); 3.84 (s, 3H, CH3); 4.26 (q, 2H, CH2, JHH¼7.15); 4.33 (q,
3
3
3
2H, CH2, JHH¼7.15); 4.84 (d, 1H, CH, JHH¼3.90); 4.95 (d, 1H, CH,
3JHH¼3.90); 6.17 (s, 1H, CH, acetal); 7.52 (d, 2H, aryl-H, JHH¼8.20);
3
7.56 (d, 2H, aryl-H, 3JHH¼8.20); 13C NMR (CDCl3, 125 MHz):
¼13.94,
d
14.03 (CH3); 52.72 (CH3); 62.02, 62.04 (CH2); 77.25, 77.63 (CH);
80.77, 85.67 (C^C); 105.67 (CH, acetal); 120.85, 127.31, 132.83,
138.12 (aryl-C); 154.17 (COOMe); 168.79, 169.22 (COOEt). IR (NaCl
cell): 2230 (C^C); 1761 (C]O); 1615, 1571, 1515 (C]C, Ar); 1209,
1171, 1103 (acetal). Elemental analysis calculated for C19H20O8: C,
60.63; H, 5.36. Found: C, 60.34; H, 5.56.
hexane 1:3, Rf¼0.27), which crystallized to give a white solid. mp.
20
66e68 ꢀC. [
a]
D
¼þ14.1 (c¼0.51, CHCl3). MS (ESI): m/z¼533.0
[MþNa]þ. 1H NMR (CDCl3, 500 MHz):
d
¼1.31 (t, 3H, CH3, 3JHH¼7.15);
3
1.36 (t, 3H, CH3, JHH¼7.15); 3.95 (s, 6H, OCH3); 4.28 (q, 2H, CH2,
3JHH¼7.15); 4.33 (q, 2H, CH2, 3JHH¼7.15); 4.85 (d, 1H, CH, 3JHH¼3.95);
4.97 (d,1H, CH, 3JHH¼3.95); 6.18 (s,1H, CH, acetal); 7.58 (d, 2H, aryl-H,
3JHH¼8.45); 7.61 (d, 2H, aryl-H, 3JHH¼8.45); 8.35 (s, 2H, aryl-H); 8.61
4.4. Tartaric acid derivatives 1ae6a (general procedure)
(s,1H, aryl-H); 13C NMR (CDCl3,125MHz):
d¼13.93,14.01 (CH3), 52.37
(OCH3); 61.95, 61.96 (CH2); 77.22, 77.56 (CH); 87.98, 90.67 (C^C);
105.98 (CH, acetal); 123.89, 123.99, 127.21, 129.99, 130.82, 131.57,
A solution of the corresponding ester and LiOH in THF and water
was stirred at room temperature for 5 h. The reaction mixture was

7702
D. Eißmann et al. / Tetrahedron 71 (2015) 7695e7705
diluted with water, acidified with 1M HCl and repeatedly extracted
with diethyl ether. After washing the combined organic extracts
with water and drying it over Na2SO4, the solvent was removed
under reduced pressure. The obtained crude product was purified
by stirring it in cold dichloromethane. Specific details for each
compound are given below.
analysis calculated for C20H14O8ꢂ2H2O: C, 57.42; H, 4.34. Found: C,
57.65; H, 4.17.
4.4.5. 2-(4-Carboxyphenyl)-(4R,5R)-1,3-dioxolane-4,5-dicarboxylic
acid (5a). Triester 5b (1.83 g, 5.0 mmol) and LiOH (0.75 g,
31.3 mmol) in THF (95 ml) and water (9þ28 ml) were used to yield
20
0.93 g (66%) of a white solid. mp. 203e206 ꢀC (dec). [
a
]
¼ꢁ20.6
D
4.4.1. 2,20-(Benzene-1,4-diyl)bis[(4R,5R)-1,3-dioxolane-4,5-
dicarboxylic acid] (1a). Tetraester 1b (2.55 g, 5.0 mmol) and LiOH
(1.0 g, 41.8 mmol) in THF (125 ml) and water (7.5þ35 ml) were
(c¼0.28, EtOH). MS (ESI): m/z¼281.03 [MꢁH]ꢁ. 1H NMR (DMSO-d6,
3
500 MHz):
d
¼4.79 (d, 1H, CH, JHH¼3.90); 4.94 (d, 1H, CH,
3JHH¼3.90); 6.08 (s, 1H, CH, acetal); 7.69 (d, 2H, aryl-H, 3JHH¼8.15);
3
used to yield 1.47 g (74%) of a white solid. mp. 108e110 ꢀC (dec).
7.99 (d, 2H, aryl-H, JHH¼8.15); 13.63 (br, s, 3H, COOH); 13C NMR
20
[
a
]
¼ꢁ30.1 (c¼0.40, EtOH). MS (ESI): m/z¼397.04 [MꢁH]ꢁ. 1H
(DMSO-d6, 125 MHz):
d
¼76.86, 77.28 (CH); 104.47 (CH, acetal);
D
3
NMR (DMSO-d6, 500 MHz):
d
¼4.78 (d, 2H, CH, JHH¼3.85); 4.94
127.51, 129.34, 132.07, 140.70 (aryl-C); 167.02 (ArCOOH); 170.54,
171.04 (CHCOOH). IR (cmꢁ1, KBr): 3120 (OH); 1755 (C]O); 1619,
1581, 1515 (C]C, Ar); 1223, 1100 (acetal). Elemental analysis cal-
culated for C12H10O8ꢂH2O: C, 48.01; H, 4.03. Found: C, 48.21; H, 4.14.
3
(d, 2H, CH, JHH¼3.85); 6.04 (s, 2H, CH, acetal); 7.63 (s, 4H, aryl-
H); 13.40 (br, s, 4H, COOH); 13C NMR (DMSO-d6, 125 MHz):
d
¼76.82, 77.33 (CH), 104.92 (CH, acetal); 127.35, 137.78 (aryl-C);
170.72, 171.19 (COOH); IR (cmꢁ1, KBr): 3212 (OH); 1755 (C]O);
1596 (C]C, Ar); 1192, 1122, 1100 (acetal). Elemental analysis
calculated for C16H14O12ꢂ2H2O: C, 44.25; H, 4.18. Found: C, 44.29;
4.29.
4.4.6. 2-[4-(2-Carboxyethynyl)phenyl]-(4R,5R)-1,3-dioxolane-4,5-
dicarboxylic acid (6a). Triester 6b (1.88 g, 5.0 mmol) and LiOH
(0.75 g, 31.3 mmol) in THF (50 ml) and water (10þ30 ml) were used
to yield 1.18 g (77%) of a white solid. mp. 153e155 ꢀC (dec).
20
4.4.2. 2,20-(Ethynylene-dibenzene-4,1-diyl)bis[(4R,5R)-1,3-
dioxolane-4,5-dicarboxylic acid] (2a). Tetraester 2b (3.05 g,
5.0 mmol) and LiOH (1.0 g, 41.8 mmol) in THF (110 ml) and water
[a
]
¼ꢁ2.9 (c¼0.30, EtOH). MS (ESI): m/z¼305.03 [MꢁH]ꢁ. 1H NMR
D
3
(CDCl3, 500 MHz):
d
¼4.80 (d, 1H, CH, JHH¼3.80); 4.96 (d, 1H, CH,
3JHH¼3.80); 6.07 (s, 1H, CH, acetal); 7.66e7.71 (m, 4H, aryl-H,
(11þ33 ml) were used to yield 1.72 g (69%) of a white solid. mp.
AA0BB0-system); 13.48 (br, s, 3H, COOH); 13C NMR (CDCl3,125 MHz):
20
183e186 ꢀC (dec). [
a
]
¼þ11.8 (c¼0.50, EtOH). MS (MALDI/CCA):
d
¼76.85, 77.45 (CH); 82.36, 83.96 (C^C); 104.50 (CH, acetal);
D
m/z¼685.4 [MþCCA]þ. 1H NMR (DMSO-d6, 500 MHz):
d
¼4.80 (d,
120.42, 128.00, 132.69, 138.79 (aryl-C); 154.29 (hCCOOH); 170.70,
171.07 (CHCOOH). IR (cmꢁ1, KBr): 3110 (OH); 2214 (C^C); 1730 (C]
O); 1625, 1508 (C]C, Ar); 1212, 1116, 1100 (acetal). Elemental
analysis calculated for C14H10O8ꢂH2O: C, 51.86; H, 3.73. Found: C,
51.80; H, 3.88.
3
3
2H, CH, JHH¼3.90); 4.85 (d, 2H, CH, JHH¼3.85); 6.05 (s, 2H, CH,
acetal); 7.64 (s, 8H, aryl-H); 13.46 (br, s, 4H, COOH); 13C NMR
(DMSO-d6, 125 MHz):
d
¼76.80, 77.33 (CH); 89.80 (C^C); 104.73
(CH, acetal); 123.55, 127.84, 131.49, 136.76 (aryl-C); 170.69, 171.13
(COOH). IR (cmꢁ1, KBr): 3177 (OH); 1749 (C]O); 1600, 1559, 1521
(C]C, Ar); 1217, 1122, 1103 (acetal). Elemental analysis calcu-
lated for C24H18O12ꢂ2H2O: C, 53.94; H, 4.15. Found: C, 54.09; H,
4.32.
4.5. Lactic ester derivatives 7b and 11b
A general procedure as described for the synthesis of 15a
applies.
4.4.3. 2-[4-(3,5-Dicarboxyphenylethynyl)phenyl]-(4R,5R)-1,3-
dioxolane-4,5-dicarboxylic acid (3a). Tetraester 3b (2.67 g,
5.0 mmol) and LiOH (1.0 g, 41.8 mmol) in THF (125 ml) and water
4.5.1. DiethylO,O0-[(benzene-1,4-diyl)dimethylene]di-(S)-lactate(7b). 1,
4-Bis(bromomethyl)benzene (6.58 g, 25 mmol) in dichloromethane
(25 ml), L(þ)-ethyl lactate (5.91 g, 50 mmol) in dichloromethane
(25 ml) and sodium hydride (5.00 g, 125 mmol, 60% suspended in oil)
in dichloromethane (60 ml) were used to yield 1.59 g (19%) of a col-
(12þ35 ml) were used to yield 1.85 g (87%) of a white solid. mp.
20
225e230 ꢀC (dec). [
a
]
¼þ15.5 (c¼0.42, EtOH). MS (ESI): m/
D
z¼425.05 [MꢁH]ꢁ. 1H NMR (DMSO-d6, 500 MHz):
¼4.81 (d, 1H,
d
CH, 3JHH¼3.85); 4.97 (d, 1H, CH, 3JHH¼3.85); 6.05 (s, 1H, CH, acetal);
ourless liquid after column chromatography (SiO2, EtOAc/n-hexane
3
3
20
7.66 (d, 2H, aryl-H; JHH¼8.20); 7.71 (d, 2H, aryl-H; JHH¼8.20);
1:6, Rf¼0.21). [
a
]
¼ꢁ74.7 (c¼0.67, CHCl3). MS (GCeMS): m/z¼338
D
8.28 (s, 2H, aryl-H); 8.47 (s, 1H, aryl-H); 13.48 (br, s, 4H, COOH); 13
NMR (DMSO-d6, 125 MHz):
C
[M]þ. 1H NMR (CDCl3, 500 MHz):
d
¼1.29 (t, 6H, CH2CH3, JHH¼7.15);
3
d
¼76.84, 77.38 (CH); 88.25, 90.64
1.43 (d, 6H, CHCH3, 3JHH¼6.85); 4.04 (q, 2H, CH, 3JHH¼6.85); 4.20e4.23
(m, sym., 4H, CHAHBCH3), 4.44 (d, 2H, aryl-CH2, 2JHH¼11.70); 4.69 (d,
(C^C); 104.73 (CH, acetal); 123.15, 123.28, 127.84, 129.97, 131.71,
132.17, 135.73, 137.13 (aryl-C); 165.92 (ArCOOH); 170.70, 171.12
(CHCOOH). IR (cmꢁ1, KBr): 3082 (OH); 2214 (C^C); 1720 (C]O);
1600, 1515 (C]C, Ar); 1119; 1100 (acetal). Elemental analysis cal-
culated for C21H14O10ꢂ2H2O: C, 56.76; H, 3.63: Found. C, 56.79; H,
3.91.
2H, aryl-CH2, JHH¼11.70); 7.34 (s, 4H, aryl-H); 13C NMR (CDCl3,
2
125 MHz):
d
¼14.08 (CH2CH3); 18.52 (CHCH3); 60.68 (CH2CH3); 71.50
(aryl-CH2); 73.78 (CH); 127.91, 137.09 (aryl-C); 173.08 (COOEt). IR
(NaCl cell): 1749 (C]O); 1518 (C]C, Ar); 1068 (CeO). Elemental
analysis calculated for C18H26O6: C, 63.89; H, 7.74. Found: C, 63.67; H,
7.48.
4.4.4. 2-[4-(4-Carboxyphenylethynyl)phenyl]-(4R,5R)-1,3-dioxolane-
4,5-dicarboxylic acid (4a). Triester 4b (2.33 g, 5.0 mmol) and LiOH
4.5.2. Ethyl
O-[4-(ethoxycarbonyl)phenylmethyl]-(S)-lactate
(0.75 g, 31.3 mmol) in THF (115 ml) and water (11þ34 ml) were used
(11b). Ethyl 4-(bromomethyl)benzoate (6.05 g, 25 mmol) in
dichloromethane (20 ml), L(þ)-ethyl lactate (2.94 g, 25 mmol) in
dichloromethane (20 ml) and sodium hydride (1.55 g, 65 mmol, 60%
suspended in oil) in dichloromethane (30 ml) were used to yield
2.52 g (36%) of a colourless oil after column chromatography (SiO2,
20
to yield 1.51 g (79%) of a white solid. mp.>300 ꢀC (dec). [
a
]
¼þ9.4
D
(c¼0.38, EtOH). MS (ESI): m/z¼381.06 [MꢁH]ꢁ. 1H NMR (DMSO-d6,
3
500 MHz):
d
¼4.79 (d, 1H, CH, JHH¼3.80); 4.95 (d, 1H, CH,
3JHH¼3.80); 6.05 (s, 1H, CH, acetal); 7.66 (s, 4H, aryl-H); 7.69 (d, 2H,
aryl-H, 3JHH¼8.20); 7.98 (d, 2H, aryl-H, 3JHH¼8.20); 13.35 (br, s, 3H,
EtOAc/n-hexane 1:2, Rf¼0.36). [
a
]
20ꢁ49.6 (c¼0.56, CHCl3). MS
D
COOH); 13C NMR (DMSO-d6, 125 MHz):
d¼76.81, 77.34 (CH); 89.43,
(GCeMS): m/z¼338 [M]þ. 1H NMR (CDCl3, 500 MHz):
d¼1.29 (t, 3H,
3
3
91.63 (C^C); 104.69 (CH, acetal); 123.25, 126.48, 127.89, 129.69,
130.80, 131.61, 131.73, 137.07 (aryl-C); 166.78 (ArCOOH), 170.71,
171.13 (CHCOOH). IR (cmꢁ1, KBr): 3072 (OH); 2214 (C^C); 1733 (C]
O); 1609, 1562, 1518 (C]C, Ar); 1220, 1125, 1103 (acetal). Elemental
CH2CH3, JHH¼7.10); 1.39 (t, 3H, CH2CH3, JHH¼7.10); 1.46 (d, 3H,
CHCH3, 3JHH¼6.85); 4.05 (q, 1H, CH, 3JHH¼6.85); 4.20e4.24 (m, sym.,
2H, CHAHBCH3); 4.37 (q, 2H, CH2CH3, 3JHH¼7.10) 4.51 (d, 1H, aryl-CH2,
2
2JHH¼12.00); 4.75 (d, 1H, aryl-CH2, JHH¼12.00); 7.42e7.45 (m, 2H,

D. Eißmann et al. / Tetrahedron 71 (2015) 7695e7705
7703
aryl-H); 8.00e8.05 (m, 2H, aryl-H); 13C NMR (CDCl3, 125 MHz):
125 MHz):
d
¼14.16, 14.24 (CH2CH3); 18.61 (CHCH3); 60.84
d¼14.07, 14.15 (CH2CH3); 18.48 (CHCH3); 60.76 (CH2CH3); 71.17 (aryl-
(CH2CH3); 71.44 (aryl-CH2); 74.25 (CH); 88.68, 92.08 (C^C); 122.03,
127.72,127.76,129.39,129.74,131.42,131.70,138.39 (aryl-C); 165.96,
173.00 (COOEt). IR (NaCl cell): 2223 (C^C); 1749 (C]O); 1607,
1560, 1520 (C]C, Ar); 1071 (CeO). Elemental analysis calculated for
CH2); 74.30 (CH); 127.22, 129.51, 129.72, 142.70 (aryl-C); 166.25,
172.83 (COOEt). IR (NaCl cell): 1746 (C]O); 1580 (C]C, Ar); 1073
(CeO). Elemental analysis calculated for C15H20O5: C, 64.27; H, 7.19.
Found: C, 63.94; H, 7.03.
C23H24O5: C, 72.61; H, 6.36. Found: C, 72.28; H, 6.57.
4.6. Lactic ester derivatives 8be10b
4.7. Lactic acid derivatives 7ae11a
A general procedure following the synthesis of compound 13a is
The general procedure as described for the tartaric acid de-
used.
rivatives 1ae6a via hydrolysis of the corresponding esters applies.
4.6.1. Diethyl O,O0-[ethynylene-bis(benzene-4,1-diyl-methylene)]di-
(S)-lactate (8b). Ethyl O-[(4-bromophenyl)methyl]-(S)-lactate
(15a) (7.15 g, 25 mmol), Ethyl O-[(4-ethynylphenyl)methyl]-(S)-
lactate (15b) (5.80 g, 25 mmol), Pd(PPh3)2Cl2 (182 mg, 0.25 mmol),
CuI (94 mg, 0.50 mmol), PPh3 (196 mg, 0.75 mmol) in triethylamine
(110 ml) were reacted at 90 ꢀC for 3 h to yield 5.92 g (54%) of
4.7.1. O,O0-(Benzene-1,4-diyl-dimethylene)di-(S)-lactic acid (7a). Di
ester 7b (1.69 g, 5.0 mmol) and LiOH (0.5 g, 20.9 mmol) in THF
(150 ml) and water (15þ50 ml) were used to yield 1.37 g (97%) of
20
a white solid. mp. 98e102 ꢀC. [
a
]
¼ꢁ74.75 (c¼0.28, EtOH). MS
D
(ESI): m/z¼280.6 [MꢁH]ꢁ. 1H NMR (DMSO-d6, 500 MHz):
¼1.48 (d,
d
3
3
6H, CH3, JHH¼6.90); 4.10 (q, 2H, CH, JHH¼6.90); 4.51(d, 2H, CH2,
2
a yellow liquid after column chromatography (SiO2, EtOAc/n-hex-
2JHH¼11.70); 4.70 (d, 2H, CH2, JHH¼11.70); 7.36 (s, 4H, aryl-H);
20
ane 1:4, Rf¼0.39). [
a
]
D
¼ꢁ64.3 (c¼0.44, CHCl3). MS (GCeMS): m/
10.27 (br, s, 2H, COOH); 13C NMR (DMSO-d6, 125 MHz):
d
¼18.35
z¼438 [M]þ. 1H NMR (CDCl3, 500 MHz):
d
¼1.30 (t, 6H, CH2CH3,
(CH3); 71.73 (CH2); 73.42 (CH); 128.14, 136.93 (aryl-C); 178.60
(COOH). IR (cmꢁ1, KBr): 3129 (OH); 1720 (C]O); 1515 (C]C, Ar);
1074 (CeO). Elemental analysis calculated for C14H18O6: C, 59.57; H,
6.43. Found: C, 59.33; H, 6.60.
3JHH¼7.15); 1.45 (d, 6H, CHCH3, JHH¼6.85); 4.05 (q, 2H, CH,
3
3JHH¼6.85); 4.19e4.26 (m, sym., 4H, CHAHBCH3); 4.46 (d, 2H, aryl-
2
2
CH2, JHH¼11.95); 4.70 (d, 2H, aryl-CH2, JHH¼11.95); 7.37 (d, 4H,
aryl-H, 3JHH¼8.20); 7.51 (d, 4H, aryl-H, 3JHH¼8.20); 13C NMR (CDCl3,
125 MHz):
d
¼14.19 (CH2CH3); 18.62 (CHCH3); 60.84 (CH2CH3);
4.7.2. O,O0-[Ethynylene-bis(benzene-4,1-diyl-methylene)]di-(S)-lac-
tic acid (8a). Diester 8b (2.19 g, 5.0 mmol) and LiOH (0.5 g,
71.52 (aryl-CH2); 74.20 (CH); 89.28 (C^C); 122.62, 127.72, 131.59,
137.84 (aryl-C); 173.06 (COOEt). IR (NaCl cell): 1746 (C]O); 1613,
1564, 1517 (C]C, Ar); (CeO) 1068. Elemental analysis calculated for
20.9 mmol) in THF (200 ml) and water (20þ65 ml) were used to
20
yield 1.51 g (79%) of a white solid. mp. 182e186 ꢀC. [
a
]
D
¼ꢁ59.05
C
26H30O6: C, 71.21; H, 6.90. Found: C, 70.93; H, 6.79.
(c¼0.38, EtOH). MS (ESI): m/z¼381.0 [MꢁH]ꢁ. 1H NMR (DMSO-d6,
3
500 MHz):
d
¼1.34 (d, 6H, CH3, JHH¼6.85); 4.03 (q, 2H, CH,
2
4.6.2. Ethyl O-{4-[3,5-di(methoxycarbonyl)phenylethynyl]phenyl-
3JHH¼6.85); 4.46 (d, 2H, CH2, JHH¼12.25); 4.62 (d, 2H, CH2,
3
methyl}-(S)-lactate (9b). Dimethyl 5-iodoisophthalate (8.00 g,
25 mmol), ethyl O-[(4-ethynylphenyl)methyl]-(S)-lactate (15b)
(5.80 g, 25 mmol), Pd(PPh3)2Cl2 (182 mg, 0.25 mmol), CuI (94 mg,
0.50 mmol) and PPh3 (196 mg, 0.75 mmol) in triethylamine (75 ml)
were reacted at 90 ꢀC for 10 h to yield 6.08 g (64%) of a yellow liquid
2JHH¼12.25); 7.39 (d, 4H, aryl-H, JHH¼8.15); 7.54 (d, 4H, aryl-H,
3JHH¼8.15); 12.75 (br, s, 2H, COOH); 13C NMR (DMSO-d6, 125 MHz):
d
¼18.52 (CH3); 70.37 (CH2); 73.76 (CH); 89.28 (C^C); 121.33,
127.75, 131.33, 139.09 (aryl-C); 174.19 (COOH). IR (cmꢁ1, KBr): 3072
(OH); 1711 (C]O); 1609, 1562, 1518 (C]C, Ar); 1065 (CeO). Ele-
mental analysis calculated for C22H22O6: C, 69.10; H, 5.80. Found: C,
68.84; H, 5.73.
after column chromatography (SiO2, EtOAc/n-hexane 1:4, Rf¼0.35).
20
[
a]
¼þ14.1 (c¼0.42, CHCl3). MS (GCeMS): m/z¼424 [M]þ. 1H NMR
D
3
(CDCl3, 500 MHz):
d
¼1.29 (t, 3H, CH2CH3, JHH¼7.15); 1.44 (d, 3H,
CHCH3, 3JHH¼7.15); 3.96 (s, 6H, OCH3); 4.04 (q, 1H, CH, 3JHH¼6.85);
4.21e4.25 (m, sym., 2H, CHAHBCH3); 4.41 (d, 1H, aryl-CH2,
2JHH¼12.00); 4.64 (d, 1H, aryl-CH2, 2JHH¼12.00); 7.38 (d, 2H, aryl-H,
3JHH¼8.50); 7.53 (d, 2H, aryl-H, 3JHH¼8.50); 8.36 (s, 2H, aryl-H); 8.62
4.7.3. O-[4-(3,5-Dicarboxyphenylethynyl)phenylmethyl]-(S)-lactic
acid (9a). Triester 9b (2.12 g, 5.0 mmol) and LiOH (0.75 g,
31.3 mmol) in THF (200 ml) and water (20þ65 ml) were used to
20
yield 1.23 g (67%) of a white solid. mp. 212e215 ꢀC. [
a
]
¼þ15.48
D
(s, 1H, aryl-H); 13C NMR (CDCl3, 125 MHz):
d
¼14.21 (CH2CH3); 18.66
(c¼0.37, EtOH). MS (ESI): m/z¼367.0 [MꢁH]ꢁ. 1H NMR (DMSO-d6,
3
(CHCH3); 52.50 (OCH3); 60.90 (CH2CH3); 71.49 (aryl-CH2); 74.32
(CH); 87.38, 91.13 (C^C); 121.84, 124.36, 127.79, 129.99, 130.92,
131.77, 136.46, 138.55 (aryl-C); 165.59 (COOMe), 173.07 (COOEt). IR
(NaCl cell): 2216 (C^C); 1733 (C]O); 1593, 1509 (C]C, Ar); 1067
(CeO). Elemental analysis calculated for C24H24O7: C, 67.91; H, 5.70.
Found: C, 67.63; H, 5.84.
500 MHz):
d
¼1.37 (d, 3H, CHCH3, JHH¼6.85); 4.05 (q, 1H, CH,
3JHH¼6.85); 4.49 (d, 1H, aryl-CH2, JHH¼12.30); 4.65 (d, 1H, aryl-
2
CH2, 2JHH¼12.30); 7.44 (d, 2H, aryl-H, 3JHH¼8.15); 7.63 (d, 2H, aryl-
3
4
H, JHH¼8.15); 8.26 (d, 2H, aryl-H, JHH¼1.45); 8.45 (t, 1H, aryl-H,
4JHH¼1.30); 12.84 (br, s, 3H, COOH); 13C NMR (DMSO-d6, 125 MHz):
d
¼18.55 (CH3); 70.42 (CH2); 73.82 (CH); 87.46, 91.03 (C^C);
120.77, 123.47, 127.78, 129.80, 131.66, 132.11, 135.64, 139.66 (aryl-
C); 165.98 (ArCOOH), 174.26 (COOH). IR (cmꢁ1, KBr): 3075 (OH);
2214 (C^C); 1708 (C]O); 1597, 1511 (C]C, Ar); 1071 (CeO). Ele-
mental analysis calculated for C20H16O7: C, 65.22; H, 4.38. Found:
C, 65.03; H, 4.47.
4.6.3. Ethyl O-{4-[4-(ethoxycarbonyl)phenylethynyl]phenylmethyl}-
(S)-lactate (10b). Ethyl 4-bromobenzoate (5.72 g, 25 mmol), ethyl
O-[(4-ethynylphenyl)methyl]-(S)-lactate (15b) (5.80 g, 25 mmol),
Pd(PPh3)2Cl2 (182 mg, 0.25 mmol), CuI (94 mg, 0.50 mmol) and
PPh3 (196 mg, 0.75 mmol) in triethylamine (75 ml) were reacted at
90 ꢀC for 10 h to yield 3.04 g (32%) of a yellow liquid after column
4.7.4. O-[4-(4-Carboxyphenylethynyl)phenylmethyl]-(S)-lactic acid
(10a). Diester 10b (1.90 g, 5.0 mmol) and LiOH (0.5 g, 20.9 mmol) in
20
chromatography (SiO2, EtOAc/n-hexane 1:6, Rf¼0.30). [
a]
¼27.4
D
(c¼0.38, CHCl3). MS (GCeMS): m/z¼380 [M]þ. 1H NMR (CDCl3,
THF (200 ml) and water (20þ55 ml) were used to yield 1.10 g (68%)
3
20
500 MHz):
d
¼1.30 (t, 3H, CH2CH3, JHH¼7.15); 1.43 (t, 3H, CH2CH3,
of a white solid. mp. 224e227 ꢀC. [
a
]
D
¼ꢁ27.1 (c¼0.32, EtOH). MS
3JHH¼7.15); 1.46 (d, 3H, CHCH3, JHH¼6.85); 4.06 (q, 1H, CH,
(ESI): m/z¼323.2 [MꢁH]ꢁ. 1H NMR (DMSO-d6, 500 MHz):
¼1.35 (d,
d
3
3JHH¼6.85); 4.21e4.26 (m, sym., 2H, CHAHBCH3); 4.47 (d, 1H, aryl-
3H, CH3, JHH¼6.85); 4.05 (q, 1H, CH, JHH¼6.85); 4.48 (d, 1H, aryl-
3
3
2
2
2
2
CH2, JHH¼12.00); 4.70 (d, 1H, aryl-CH2, JHH¼12.00); 7.37 (d, 2H,
aryl-H, 3JHH¼8.15); 7.53 (d, 2H, aryl-H, 3JHH¼8.15); 7.58 (d, 2H, aryl-
CH2, JHH¼12.35); 4.64 (d, 1H, aryl-CH2, JHH¼12.35); 7.42 (d, 2H,
aryl-H, 3JHH¼8.15); 7.59 (d, 2H, aryl-H, 3JHH¼8.15); 7.68 (d, 2H, aryl-
H, JHH¼8.40); 8.02 (d, 2H, aryl-H, JHH¼8.40); 13C NMR (CDCl3,
H, JHH¼8.35); 7.98 (d, 2H, aryl-H, JHH¼8.35); 12.96 (br, s, 2H,
3
3
3
3

7704
D. Eißmann et al. / Tetrahedron 71 (2015) 7695e7705
COOH); 13C NMR (DMSO-d6, 125 MHz):
d
¼18.54 (CH3); 70.35 (CH2);
calculated for C72H58O8ꢂacetone: C, 81.20; H, 5.82. Found: C, 80.91;
H, 5.98.
73.81 (CH); 88.63, 92.03 (C^C); 120.82, 126.67, 127.79, 129.65,
130.72, 131.55, 131.59, 139.66 (aryl-C); 166.80 (ArCOOH), 174.21
(COOH). IR (cmꢁ1, KBr): 3072 (OH); 2217 (C^C); 1711 (C]O); 1606,
1559, 1518 (C]C, Ar); 1062 (CeO). Elemental analysis calculated for
4.8.3. (4R,5R)-a,a, ,a
a0 0-Tetraphenyl-2-{[3,5-bis(diphenylhydroxy-
methyl)phenyl]ethynylbenzene-4-yl}-1,3-dioxolane-4,5-dimethanol
(3c). Tetraester 3b (1.28 g, 2.5 mmol), Mg (0.73 g, 30.0 mmol) and
bromobenzene (4.71 g, 30.0 mmol) in THF (25 ml) were used to
yield 2.15 g (88%) of a white solid after column chromatography
(SiO2, EtOAc/n-hexane 1:3, Rf¼0.29) of the oily crude product and
C
19H16O5: C, 70.36; H, 4.97: Found: C, 70.09; H, 4.83.
4.7.5. O-(4-Carboxyphenylmethyl)-(S)-lactic acid (11a). Diester 11b
(1.40 g, 5.0 mmol) and LiOH (0.5 g, 20.9 mmol) in THF (150 ml) and
water (15þ45 ml) were used to yield 0.95 g (85%) of a white solid.
subsequent treatment by stirring with n-hexane. mp. 124e127 ꢀC.
20
20
mp. 139e142 ꢀC. [
a]
¼ꢁ54.5 (c¼0.22, EtOH). MS (ESI): m/z¼223.0
[a
]
¼þ69.7 (c¼0.98, CHCl3). MS (ESI): m/z¼978.5 [M]ꢁ. 1H NMR
D
D
[MꢁH]ꢁ. 1H NMR (DMSO-d6, 500 MHz):
d
¼1.35 (d, 3H, CH3,
(CDCl3, 500 MHz):
d
¼2.31 (s, 1H, OH); 3.25 (s, 1H, OH); 2.79 (s, 2H,
3JHH¼6.85); 4.04 (q, 1H, CH, JHH¼6.85); 4.51 (d, 1H, CH2,
OH); 5.12 (d, 1H, CH, 3JHH¼5.00); 5.29 (d, 1H, CH, 3JHH¼5.00); 5.15 (s,
3
2JHH¼12.60); 4.68 (d, 1H, CH2, JHH¼12.60); 7.47 (d, 2H, aryl-H,
1H, CH, acetal); 7.06e7.48 (m, 47H, aryl-H); 13C NMR (CDCl3,
2
3JHH¼8.10); 7.93 (d, 2H, aryl-H, 3JHH¼8.10); 12.90 (br, s, 2H, COOH);
125 MHz):
d
¼78.43, 78.62 (CeOH); 80.86, 81.56 (CH); 81.77
13C NMR (DMSO-d6, 125 MHz):
d¼18.53 (CH3); 70.29 (CH2); 73.85
(CeOH); 89.00, 90.16 (C^C); 104.51 (CH, acetal); 126.70, 126.86,
127.02, 127.28, 127.35, 127.39, 127.53, 127.70, 127.79, 127.87, 127.90,
127.98, 128.12, 128.16, 128.24, 129.64, 131.39, 136.91, 142.97, 144.01,
144.26, 145.96, 146.30, 146.71 (aryl-C). IR (cmꢁ1, KBr): 3560 (OH);
1594, 1492 (C]C, Ar); 1163, 1116, 1084 (acetal). Elemental analysis
calculated for C69H54O6ꢂacetone: C, 83.37; H, 5.83. Found: C, 83.22;
H, 6.09.
(CH); 127.30, 129.38, 129.91, 143.42 (aryl-C); 167.26 (ArCOOH),
174.17 (COOH). IR (cmꢁ1, KBr): 3079 (OH); 1685 (C]O); 1613, 1575,
1511 (C]C, Ar); 1065 (CeO). Elemental analysis calculated for
C
11H12O5: C, 58.93; H, 5.39. Found: C, 59.40; H, 5.52.
4.8. TADDOLs 1ce6c (general procedure)
4.8.4. (4R,5R)-a,a, ,a
a0 0-Tetraphenyl-2-{[4-diphenylhydroxymethyl)
To a solution of phenylmagnesium bromide (prepared from
magnesium and bromobenzene in dry THF following the usual
procedure)26 was slowly added the corresponding ester dissolved
in dry THF. The mixture was heated under reflux for 6 h, then
quenched with ice and diluted with diethyl ether. The organic layer
was separated and washed with aqueous NH4Cl solution. The
aqueous layer was extracted several times with diethyl ether. The
combined organic phases were washed with water, dried (Na2SO4)
and evaporated. Specific details for each compound including
procedure of purification are given below.
phenyl]ethynylbenzene-4-yl}-1,3-dioxolane-4,5-dimethanol
(4c). Triester 4b (1.14 g, 2.5 mmol), Mg (0.55 g, 22.2 mmol) and
bromobenzene (3.53 g, 22.2 mmol) in THF (25 ml) were used to
yield 0.89 g (45%) of a white solid after column chromatography
(SiO2, EtOAc/n-hexane 1:3, Rf¼0.43) of the oily crude product and
subsequent treatment by stirring with n-hexane. mp. 95e97 ꢀC.
20
[
a
]
¼þ83.1 (c¼0.79, CHCl3). MS (ESI): m/z¼795.5 [MꢁH]ꢁ. 1H NMR
D
(CDCl3, 500 MHz):
d
¼2.80 (s, 1H, OH); 3.19 (s, 1H, OH); 3.50 (s, 1H,
OH); 5.14 (d, 1H, CH, 3JHH¼4.95); 5.31 (d, 1H, CH, 3JHH¼4.95); 5.19 (s,
1H, CH, acetal); 7.10e7.58 (m, 38H, aryl-H); (CDCl3þD2O, 500 MHz):
d
d
¼2.80, 3.19 and 3.50 signals disappear; 13C NMR (CDCl3, 125 MHz):
¼78.34, 78.58 (CeOH); 80.86, 81.60 (CH); 81.81 (CeOH); 89.21,
4.8.1. (4R,40R,5R,50R)- a0 a0 a00 a00 a000 000-Octaphenyl-2,20-(ben-
a,a, , , , , ,a
zene-1,4-diyl)bis(1,3-dioxolane-4,5-dimethanol) (1c). Tetraester 1b
(1.27 g, 2.5 mmol), Mg (0.73 g, 30.0 mmol) and bromobenzene
(4.71 g, 30.0 mmol) in THF (50 ml) were used to yield 1.57 g (66%) of
89.73 (C^C); 104.45 (CH, acetal); 126.75, 126.88, 127.03, 127.24,
127.34, 127.36, 127.48, 127.63, 127.84, 127.91, 127.97, 128.11, 128.13,
128.20, 128.69, 129.49, 131.12, 131.38, 136.89, 143.00, 144.33, 145.95,
146.45, 147.05 (aryl-C). IR (cmꢁ1, KBr): 3563 (OH); 1600, 1521, 1499
(C]C, Ar); 1179, 1112, 1090 (acetal). Elemental analysis calculated
for C56H44O5ꢂacetone: C, 82.88; H, 5.89. Found: C, 82.51; H, 5.97.
a white solid after crystallization from acetone. mp. 282e283 ꢀC.
20
[
a]
¼þ48.4 (c¼0.95, CHCl3). MS (ESI): m/z¼949.3 [MꢁH]ꢁ. 1H
D
NMR (CDCl3, 500 MHz):
d
¼2.36 (s, 2H, OH); 3.36 (s, 2H, OH); 5.08
(d, 2H, CH, 3JHH¼5.00); 5.25 (d, 2H, CH, 3JHH¼5.00); 5.10 (s, 2H, CH,
acetal); 7.07e7.35 (m, 44H, aryl-H); 13C NMR (CDCl3, 125 MHz):
4.8.5. (4R,5R)-a,a, ,a
a0 0-Tetraphenyl-2-[4-(diphenylhydroxymethyl)-
d
¼78.37, 78.53 (CeOH); 80.76, 81.60 (CH), 104.46 (CH, acetal);
phenyl]-1,3-dioxolane-4,5-dimethanol (5c). Triester 5b (0.91 g,
2.5 mmol), Mg (0.55 g, 22.2 mmol) and bromobenzene (3.53 g,
22.2 mmol) in THF (25 ml) were used to yield 0.99 g (57%) of a white
solid after column chromatography (SiO2, EtOAc/n-hexane 1:4,
126.65, 126.82, 126.99, 127.15, 127.21, 127.33, 127.45, 127.65, 127.82,
128.11, 128.19, 138.10, 142.92, 144.06, 144.18, 146.03 (aryl-C). IR
(cmꢁ1, KBr): 3370 (OH); 1597, 1496 (C]C, Ar); 1169, 1119, 1100
(acetal). Elemental analysis calculated for C64H54O8ꢂ acetone: C,
79.74; H, 5.99. Found: C, 79.65; 6.09.
Rf¼0.32) of the oily crude product and subsequent treatment by
20
stirring with n-hexane. mp. 93e96 ꢀC. [
a
]
D
¼þ38.6 (c¼0.69, CHCl3).
MS(ESI): m/z¼696.6 [M]ꢁ. 1H NMR (CDCl3, 500 MHz):
¼1.59 (s, 1H,
d
4.8.2. (4R,40R,5R,50R)-
a,
a
,
a0
,
a0
,
a00
,
a00
,
a000
,
a
000-Octaphenyl-2,20-(ethyny-
OH); 2.78 (s, 1H, OH); 3.38 (s, 1H, OH); 5.11 (d, 1H, CH, 3JHH¼5.05);
3
lene-dibenzene-4,1-diyl)bis(1,3-dioxolane-4,5-dimethanol)
(2c). Tetraester 2b (1.52 g, 2.5 mmol), Mg (0.73 g, 30.0 mmol) and
bromobenzene (4.71 g, 30.0 mmol) in THF (25 ml) were used to
yield 2.57 g (98%) of a white solid after crystallization of the oily
5.30 (d, 1H, CH, JHH¼5.05); 5.12 (s, 1H, CH, acetal); 7.11e7.53 (m,
34H, aryl-H); 13C NMR (CDCl3, 125 MHz):
d
¼78.46, 78.52 (CeOH);
80.72, 81.45 (CH); 81.81 (CeOH); 104.68 (CH, acetal); 127.30,127.85,
127.87, 127.89, 127.93, 128.17, 135.78, 141.62, 143.02, 144.22, 145.88,
146.13, 146.59, 148.04 (aryl-C). IR (cmꢁ1, KBr): 3557 (OH); 1597,
1496 (C]C, Ar); 1182, 1125, 1087 (acetal). Elemental analysis cal-
culated for C48H40O5ꢂ2 acetone: C, 79.78; H, 6.45. Found: C, 79.82;
H, 6.28.
crude product from acetone/ethanol. mp. 203e206 ꢀC.
20
[
a
]
¼þ136.3 (c¼1.05, CHCl3). MS (ESI): m/z¼1049.3 [MꢁH]ꢁ. 1H
D
NMR (CDCl3, 500 MHz):
d
¼2.44 (s, 2H, OH); 3.33 (s, 2H, OH); 5.12 (d,
3
3
2H, CH, JHH¼5.00); 5.29 (d, 2H, CH, JHH¼5.00); 5.18 (s, 2H, CH,
acetal); 7.10e7.50 (m, 48H, aryl-H); 13C NMR (CDCl3, 125 MHz):
d
¼78.42, 78.63 (CeOH); 80.89, 81.60 (CH); 89.59 (C^C); 104.50
4.8.6. (4R,5R)-a,a, ,a
a0 0-Tetraphenyl-2-{4-[2-(diphenylhydroxy-
(CH, acetal); 124.07, 126.74, 126.86, 127.02, 127.22, 127.27, 127.38,
127.52, 127,68, 127.88, 128.13, 128.15, 128.24, 131.43, 137.03, 142.99,
143.99, 144.28, 145.95 (aryl-C). IR (cmꢁ1, KBr): 3560 (OH); 1597,
1518, 1496 (C]C, Ar); 1173, 1119, 1087 (acetal). Elemental analysis
methyl)ethynyl]phenyl}-1,3-dioxolane-4,5-dimethanol (6c). Triester
6b (0.94 g, 2.5 mmol), Mg (0.55 g, 22.2 mmol) and bromobenzene
(3.53 g, 22.2 mmol) in THF (25 ml) were used to yield 1.47 g (82%)
of a white solid after column chromatography (SiO2, EtOAc/n-

D. Eißmann et al. / Tetrahedron 71 (2015) 7695e7705
7705
hexane 1:3, Rf¼0.43) of the oily crude product and subsequent
References and notes
20
treatment by stirring with n-hexane. mp. 80e83 ꢀC. [
a
]
¼þ41.3
D
(c¼0.72, CHCl3). MS (ESI): m/z¼720.4 [MꢁH]ꢁ. 1H NMR (CDCl3,
1. Xu, R.; Pang, W.; Yu, J.; Huo, Q.; Chen, J. Chemistry of Zeolites and Related Porous
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500 MHz):
d
¼3.24 (s, 1H, OH); 3.65 (s, 1H, OH); 3.82 (s, 1H, OH);
5.09 (d, 1H, CH, 3JHH¼5.20); 5.23 (d, 1H, CH, 3JHH¼5.20); 5.16 (s, 1H,
CH, acetal); 7.04e7.63 (m, 34H, aryl-H); 13C NMR (CDCl3,
125 MHz):
d
¼74.49, 78.17, 78.49 (CeOH); 80.80, 81.57 (CH); 86.49,
92.49 (C^C); 104.21 (CH, acetal); 125.92, 126.72, 126.89, 127.46,
127.49, 127.94, 127.99, 128.09, 131.40, 137.17, 142.97, 143.51, 143.97,
144.44, 144.98, 145.85 (aryl-C). IR (cmꢁ1, KBr): 3554 (OH); 2227
(C^C); 1603, 1492 (C]C, Ar); 1179; 1116; 1087 (acetal). Elemental
analysis calculated for C50H40O5ꢂacetone: C, 81.72; H, 5.95. Found:
C, 81.98; H, 6.18.
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4.9. Vapour sorption experiments
For the sorption experiments, a quartz crystal microbalance
consisting of two electronic quartzes (10 MHz) with gold electrodes
(FOQ Piezo Technik, Germany) was used. The reference quartz is
uncoated while the other quartz is coated with the solid receptor
compound (1ae6a, 1ce6c and 7ae11a, respectively). The mea-
surements were carried out at constant temperature (25 ꢀC) and
with a constant flow of synthetic air (10 L/h). A multichannel fre-
quency counter (HKR sensor systems Munich, Germany) with
a resolution of 1 Hz was used to measure the resonance frequencies
of the quartzes, which can be read by a computer using a serial
interface. The coating of the quartz was realized by dipping in
a 0.01M solution of the respective receptor compound in CHCl3. The
change of the frequency is proportional to the increase of the quartz
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relation results from the Sauerbrey equation.31 In consideration of
the molar mass of the used solvents, the percentage of the adsorbed
solvent can be obtained:
€
13. Meinhold, D.; Seichter, W.; Kohnke, K.; Seidel, J.; Weber, E. Adv. Mater. 1997, 9,
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16. Ehlen, A.; Wimmer, C.; Weber, E.; Bargon, J. Angew. Chem., Int. Ed. 1993, 32,
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€
17. Goldberg, I.; Stein, Z.; Weber, E.; Dorpinghaus, N.; Franken, S. J. Chem. Soc.,
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€
18. Weber, E.; Dorpinghaus, N.; Wimmer, C.; Stein, Z.; Krupitsky, H.; Goldberg, I. J.
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19. Seebach, D.; Beck, A. K.; Heckel, A. Angew. Chem., Int. Ed. 2001, 40, 92e138.
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D
D
nðsÞ
nðrÞ
MðsÞ
MðrÞ
D
D
f ðsÞ
f ðrÞ
D
D
mðsÞ
mðrÞ
D
D
nðsÞ MðsÞ
nðrÞ MðrÞ
x0
¼
¼ x
¼
¼ x ¼
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28. Weber, E.; Csoregh, I.; Stensland, B.; Czugler, M. J. Am. Chem. Soc. 1984, 106,
D
f(s).frequency shift solvent;
D
f(r).frequency shift receptor;
€
Dm(s).mass of solvent absorbed;
Dm(r).mass of receptor layer;
3297e3306.
M(s).molar mass solvent; M(r).molar mass receptor.
€
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Financial support by the Deutsche Forschungsgemeinschaft
(Priority Program 1362 ‘Porous Metal-Organic Frameworks’) is
gratefully acknowledged.