Synthesis, conformation and chiroptical properties of diaryl esters of tartaric acid

Article abstract of DOI:10.1021/jo900206c

(Chemical Equation Presented) Previously unknown diaryl esters of L-tartaric acid have been synthesized. Their conformations have been studied by DFT calculations, NMR and circular dichroism spectroscopy in solution, as well as by X-ray diffraction in the

Full text of DOI:10.1021/jo900206c

Synthesis, Conformation and Chiroptical Properties of Diaryl Esters
of Tartaric Acid†
Robert Cysewski, Marcin Kwit, Beata Warz˙ajtis, Urszula Rychlewska, and
Jacek Gawron´ski*
Department of Chemistry, Adam Mickiewicz UniVersity, 60-780 Poznan´, Poland
gawronsk@amu.edu.pl
ReceiVed February 5, 2009
Previously unknown diaryl esters of L-tartaric acid have been synthesized. Their conformations have
been studied by DFT calculations, NMR and circular dichroism spectroscopy in solution, as well as by
X-ray diffraction in the crystalline state. The four-carbon tartrate chain of diaryl esters was found to be
extended in all cases, with a higher degree of nonplanarity in the crystals. Dinaphthyl tartrates show
unusually strong exciton Cotton effects (A ) -228 for di-1-naphthyl L-tartrate) due to the coupling of
allowed 1Bb transitions in naphthyl chromophores, despite the acyclic structure and significant distance
(over 10 Å) between the two chromophores.
Introduction
tartaric acid derivatives but also in asymmetric catalysis, for
example, as chiral ligands in the Sharpless-Katsuki asym-
metric epoxidation,4 kinetic resolution of racemic allyl
alcohols,5 asymmetric synthesis of sulfoxides by the
Kagan-Modena method,6 asymmetric Simmons-Smith
reaction,7,8 asymmetric allylation,9,10 asymmetric allylbora-
Tartaric acid belongs to a narrow group of very important
optically active compounds. The study of its stereoisomeric
molecules led Pasteur over 160 years ago to the discovery of
enantiomerism.1 A hundred years later, Bijvoet for the first time
experimentally determined the absolute configuration of an
organic molecule, analyzing the anomalous scattering of zir-
conium KR X-rays by crystals of sodium rubidium tartrate.2
The importance of tartaric acid in the development of organic
stereochemistry has been strengthened by the role of its
derivatives in life sciences and chemistry, especially by the wide
applications of its derivatives in the synthesis of numerous chiral
organic compounds. In synthetic applications, tartaric acid has
served not only as the source of chiral building blocks but also
as the precursor of chiral ligands, auxiliaries, and resolving
agents.3 Among derivatives of tartaric acid, its dialkyl esters
are most frequently used, not only for the preparation of other
(3) (a) Gawronski, J.; Gawronska, K. Tartaric and Malic Acids in Synthe-
sis - A Source Book of Building Blocks, Ligands, Auxiliaries, and ResolVing
Agents; J. Wiley and Sons: New York, 1999. (b) Coppola, G. M.; Schuster,
H. F. R-Hydroxy Acids in EnantioselectiVe Synthesis; Wiley-VCH: Weinheim,
1997. (c) Ghosh, A. K.; Koltun, E. S.; Bilcer, G. Synthesis 2001, 1281.
(4) (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974. (b)
Finn, M. G.; Sharpless, K. B. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic Press: New York, 1985; Vol. 5, pp 247-308.
(5) (a) Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada, Y.; Ikeda, M.;
Sharpless, K. B. J. Am. Chem. Soc. 1981, 103, 6237. (b) Sharpless, K. B.;
Behrens, C. H.; Katsuki, T.; Lee, A. W. M.; Martin, V. S.; Takatani, M.; Viti,
S. M.; Walker, F. J.; Woodard, S. S. Pure. Appl. Chem. 1983, 55, 589.
(6) (a) Pitchen, P.; Kagan, H. B. Tetrahedron Lett. 1984, 25, 1049. (b) Pitchen,
P.; Dunach, E.; Deshmukh, M. N.; Kagan, H. B. J. Am. Chem. Soc. 1984, 106,
8188. (c) Kagan, H. B.; Dunach, E.; Nemecek, C.; Pitchen, P.; Samuel, O.; Zhao,
S. H. Pure Appl. Chem. 1985, 57, 1911. (d) Zhao, S. H.; Samuel, O.; Kagan,
H. B. Tetrahedron 1987, 43, 5135.
* To whom correspondence should be addressed. Tel: (+48) 61 8291291.
Fax: (+48) 61 8291505.
† Dedicated to Professor D. A. Lightner on the occasion of his 70th birthday.
(1) Pasteur, L. C. R. Seances Acad. Sci. 1848, 26, 535.
(2) Bijvoet, J. M.; Peerdeman, A. F.; van Bommel, A. J. Nature 1951, 168,
271.
(7) (a) Ukaji, Y.; Nishimura, M.; Fujisawa, T. Chem. Lett. 1992, 21, 61. (b)
Ukaji, Y.; Sada, K.; Inomata, K. Chem. Lett. 1993, 22, 1227.
(8) (a) Charette, A. B.; Juteau, H. J. Am. Chem. Soc. 1994, 116, 2651. (b)
Charette, A. B.; Prescott, S.; Brochu, C. J. Org. Chem. 1995, 60, 1081.
10.1021/jo900206c CCC: $40.75
Published on Web 05/19/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 4573–4583 4573

Cysewski et al.
SCHEME 1. Synthesis of Diaryl Esters 4a-p of L-Tartaric Acid
tion developed by Roush,11 and homoallenylboration of
aldehydes developed by Brown.12
salt 2 by ester saponification with ethanolic NaOH (yield 98%).
Dry disodium salt 2 was converted to unstable dichloride by
the reaction with oxalyl chloride in dry toluene containing a
catalytic amount of DMF. The dichloride was immediately
subjected to the reaction with phenol or a naphthol in the
presence of pyridine to yield diesters 3a-p (30-67%). Low
yields of diesters 3d,h,m,l can be ascribed to their lower stability
toward workup conditions, due to the presence of electron-
withdrawing substituents in the phenol ring. The hydrolysis of
the dioxolane protecting group in 3 could be selectively achieved
with the aid of TFA-H2O in dichloromethane solution (yield
51-92%). Diaryl L-tartrates 4a-p were characterized by
spectroscopic methods. In particular, the 1H NMR spectra
showed the absence of the dioxolane CHPh proton signal which
is present in 3a-p (δ 6.2-6.5). Signals of the protons attached
to the chiral carbon atoms in diaryl L-tartrates 4a-p were found
in the range δ 5.0-5.5, apparently shifted downfield by ca. 1
ppm in comparison to the corresponding signals of dialkyl
tartrates. It is of interest to note that deacetalization of diaryl
ester 5, a derivative of 3,5-dibromosalicylic acid obtained by a
route similar to that reported here, is described to yield a product
characterized by a signal of the protons at the chiral carbon
atoms shifted to δ 5.92-5.95.16 This may suggest that the
structure of the product is more likely a dilactone 6 or an O,O′-
diacylated diacid 7 (Scheme 2).
Conformational Preferences of Diaryl L-Tartrates. The
conformational preferences of L-tartaric acid and its alkyl ester,
amide, and nitrile derivatives have been a subject of extensive
studies in the past.17-21 Central to the conformational charac-
teristic of these acyclic, highly functionalized molecules is the
extended (trans) or bent (gauche) conformation of the four-
carbon chain. This can be visualized in Newman projections of
the three possible conformers, T, G-, G+ (Scheme 3).
According to accumulated evidence, tartaric acid, its salts,
alkyl esters, and NH-amides exist in an extended (T) conforma-
tion. Bent (G-) conformers are dominant in N,N,N′,N′-tetraalkyl-
tartramides,17 whereas G+ conformers are the most populated
In contrast to the wide availability (including commercial)
of dialkyl tartrates, diaryl tartrates have remained until now
virtually unknown. This is quite obvious considering the
difficulties encountered in chemoselective esterification of
hydroxy acids with phenols. Whereas dialkyl tartrates are readily
available by Fischer esterification of tartaric acid or transes-
terification of a tartrate with the use of excess alcohol, such a
procedure is not applicable to phenols. In fact, we tried many
general procedures for acid activation toward the synthesis of
aryl esters, as described in the literature; however, they did not
afford any aryl ester on reaction with tartaric acid, the difficulty
apparently arising from the competitive reaction of hydroxy
group present in the acid. While seeking a procedure for
preparation of diaryl tartrates directly from tartaric acid, we came
across a method for direct formation of dinaphthyl esters of
malic acid with the use of N,N-bis(2-oxo-3-oxazolidinyl)phos-
phorodiamidic chloride for the activation of carboxylic group.13
In our hands, when applied to tartaric acid, this method failed
to give any ester on reaction with 2-naphthol.
Results and Discussion
Synthesis of Diaryl L-Tartrates. It was obvious that the
synthesis of diaryl L-tartrates would require protection of the
tartrate hydroxy groups. Since the esters of phenols are prone
to hydrolysis under basic conditions (to generate resonance-
stabilized phenolate ion), the protecting group would require
removal conditions orthogonal to those for the ester group.
Benzylidene protecting group for the diols is known to be
selectively removed under mildly acidic (trifluoroacetic acid in
dichloromethane) or neutral (hydrogenolysis with Pd catalysis)
conditions. We therefore adopted this indirect method for the
synthesis of diaryl L-tartrates (Scheme 1).
Starting from the known dimethyl 2,3-O-benzylidene-L-
tartrate (1),14 which can be obtained easily and in high yield
from dimethyl L-tartrate,15 we were able to obtain the disodium
(16) Delaney, E. J.; Massil, S. E.; Shi, G. Y.; Klotz, I. M. Arch. Biochem.
Biophys. 1984, 228, 627.
(17) (a) Gawronski, J.; Gawronska, K.; Rychlewska, U. Tetrahedron Lett.
1989, 30, 6071. (b) Gawronski, J.; Gawronska, K.; Skowronek, P.; Rychlewska,
U.; Warzajtis, B.; Rychlewski, J.; Hoffmann, M.; Szarecka, A. Tetrahedron 1997,
53, 6113.
(18) Gawronski, J.; Dlugokinska, A.; Grajewski, J.; Plutecka, A.; Rychlewska,
U. Chirality 2005, 17, 388.
(19) Gawronski, J.; Gawronska, K.; Wascinska, N.; Plutecka, A.; Rychlewska,
U. Pol. J. Chem. 2007, 81, 1917.
(20) (a) Keiderling, T. A.; Stephens, P. J. J. Am. Chem. Soc. 1997, 99, 8061.
(b) Su, C. N.; Keiderling, T. A. J. Am. Chem. Soc. 1980, 102, 511.
(21) (a) Polavarapu, P. L.; Ewing, C. S.; Chandramouly, T. J. Am. Chem.
Soc. 1987, 109, 7382. (b) Barron, L. D.; Gargano, A. R.; Hecht, L.; Polavarapu,
P. L.; Sugeta, H. Spectrochim. Acta 1992, 48A, 1051. (c) Zhang, P.; Polavarapu,
P. L. J. Phys. Chem. A 2007, 111, 858.
(9) (a) Boldrini, G. P.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A.
J. Chem. Soc., Chem. Commun. 1986, 685. (b) Boldrini, G. P.; Lodi, L.;
Tagliavini, E.; Tarasco, C.; Trombini, C.; Umani-Ronchi, A. J. Org. Chem. 1987,
52, 5447.
(10) Nishida, M.; Tozawa, T.; Yamada, K.; Mukaiyama, T. Chem. Lett. 1996,
25, 1125.
(11) (a) Roush, W. R.; Banfi, L. J. Am. Chem. Soc. 1988, 110, 3979. (b)
Roush, W. R.; Grover, P. T. J. Org. Chem. 1995, 60, 3806.
(12) Soundararajan, R.; Li, G.; Brown, H. C. J. Org. Chem. 1996, 61, 100.
(13) (a) Hartl, M.; Humpf, H. U. Tetrahedron: Asymmetry 2000, 11, 1741.
(b) Fischbeck, A.; Bartke, N.; Humpf, H. U. Chem. Month. 2005, 136, 397.
(14) Sanchez-Sancho, F.; Valverde, S.; Herradon, B. Tetrahedron: Asymmetry
1996, 7, 3209.
(15) For a convenient procedure for synthesis of dimethyl tartrate see: (a)
Houston, T. A.; Wilkinson, B. L.; Blanchfield, J. T. Org. Lett. 2004, 6, 679.
4574 J. Org. Chem. Vol. 74, No. 12, 2009

Diaryl Esters of Tartaric Acid.
SCHEME 2. Possible Products of Hydrolysis of Acetal 5
SCHEME 3. Conformational Preferences of L-Tartaric Acid
Derivatives and Definition of Torsion Angles
linking two chiral centers is staggered and such that two
carboxylate groups are trans (T), two adjacent C-OH bonds
are gauche (G-) and two adjacent C-H bonds are gauche (G+)
(Table 2). However, deviations from the ideal staggered
conformation are significant, the largest being in diphenyl
L-tartrate (angle R ) 147.1(4)°). In this compound, the hydroxy
groups are positioned mutually perpendicular (torsion angle
-93.4(4)°), instead of the expected G- orientation. Conse-
TABLE 1. Diagnostic Coupling Constants from the NMR Spectra
of Diaryl L-Tartrates in Acetone-d6 Solution
compd
3JH,H (Hz)
2JC,H (Hz)
4a
4o
4p
2.5
2.3
2.6
<1
<1
<1
species in the case of tartarodinitriles.19 In all cases, the
conformational equilibrium results from contributions of steric
and stereoelectronic effects, the latter mainly due to antiparallel
1,3-dipole/dipole interactions of the CH and CO bonds.18
3
2
NMR Study. JH,H and JC,H coupling constants of the
protons at chiral carbon atoms of the tartrate molecule are
listed in Table 1.
These coupling constants characterize the conformation of
the four-atom carbon chain in solution.17 Low values of the
coupling constants are characteristic of preferential extended
(T) conformation of the tartrate carbon chain. This conformation
is therefore postulated for diaryl L-tartrates such as 4a, 4o, and
4p, regardless the substitution pattern of the aryl group.
X-ray Diffraction Study. The investigated diphenyl (4a) and
di-2-naphthyl (4p) L-tartrate molecules constitute the first
example of tartaric acid diaryl esters for which the crystal
structure has been determined.22 Figure 1 illustrates the con-
formation in the crystal and numbering scheme of the investi-
gated molecules. Di-2-naphthyl tartrate crystallizes with two
symmetry-independent molecules (labeled with and without
primes) which differ in their molecular conformation.
Potentially C2 symmetrical, the molecules do not attain C2
symmetry in their crystals, and departures from this symmetry
are substantial (Table 2). As in the vast majority of optically
active tartaric acid dialkyl esters so far investigated by X-ray
diffraction,17b,23-26 the conformation around the C*-C* bond
FIGURE 1. Illustration of conformers of the investigated molecules
with atom numbering scheme for (4a) T(sp,sp), (4p), T(sp,sp), and (4p′)
T(ap,ap). Thermal ellipsoids are drawn at 40% probability level. Dashed
lines illustrate intramolecular hydrogen bonds; sp and ap refer to relative
orientation of the vicinal CdO and C-O(H) bonds.
TABLE 2. Selected Torsion Angles (deg) Describing the Molecular
Conformation
torsion angle
4a
4p
4p′
C1-C2-C3-C4 (R)
147.1(4)
71.5(4)
69.2(5)
162.1(2) -154.5(2)
64.1(2) -84.2(2)
66.6(2) -102.1(2)
C3-C2-C1-O10 (ꢀ)
C2-C3-C4-O40 (ꢀ′)
C2-C1-O10-C11 (C12) (γ)
C3-C4-O40-C41 (C42) (γ′)
C1-O10-C11(C12)-C12(C11) (δ)
C1-O10-C11(C12)-C16(C13) (δ)
-178.1(3) -172.0(2)
-173.9(4) -177.2(2)
-66.1(6) -51.5(3)
167.7(2)
178.0(2)
115.3(2)
117.4(5)
133.2(2) -70.5(3)
C4-O40-C41(C42)-C42(C41) (δ′) -76.4(6)
101.7(2) 77.2(3)
C4-O40-C41(C42)-C46(C43) (δ′)
O2-C2-C3-O3
107.5(5) -80.5(3) -106.6(2)
-93.4(4) -75.6(2) -44.0(2)
H2-C2-C3-H3
25.1
43.2
80.5
O1dC1-C2-O2
O4dC4-C3-O3
11.3(6)
13.3(7)
5.1(3) -144.0(2)
5.2(3) -164.2(2)
(22) Allen, F. H. Acta Crystallogr. B 2000, 58, 380.
J. Org. Chem. Vol. 74, No. 12, 2009 4575

Cysewski et al.
quently, the torsion angle between the C*-H bonds situated at
the chiral centers is only 25°. In the two independent molecules
of di-2-naphthyl L-tartrate, these deviations are realized in a
supplementary fashion, i.e., the values of the O2-C2*-C3*-O3
torsion angles are in one molecule bigger and in the other
smaller by 16° than the ideal value of -60° (Table 2).
The usually observed coplanarity of ester and proximal
hydroxy functionalities is retained in two of the three molecules
(i.e., 4a and 4p), although to a different extent. In these two
molecules, the R-hydroxy oxygen eclipses the carbonyl oxygen
(sp conformation), while the molecule 4p′ shows significant
nonplanarity of both R-hydroxyester moieties, the R-hydroxy
oxygen lying closer to the naphtol oxygen (an approximate ap
conformation).PronouncednonplanarityoftheO1′dC1′-C2′-O2′
fragment allows formation of two intramolecular hydrogen
bonds with the same O2′-H donor but two different acceptors
(O3′ and O10′) (Table A, Supporting Information), a situation
not possible within a planar R-hydroxy carboxylate fragment,
where either none or only one intramolecular hydrogen bond
can be formed. The O2′ hydroxyl is additionally involved in
one intermolecular hydrogen bond, thus taking part in the
formation of a rarely observed four-center hydrogen bond.
Clearly, this is a result of an apparent lack of the hydrogen-
bond donors: in all three molecules, the ratio of potential
hydrogen bond donors to hydrogen bond acceptors is 2:6. In
the crystal structure of diphenyl ester, this shortage of hydrogen-
bond donors is compensated by engaging each of the two
hydroxy groups as donors in two intermolecular hydrogen bonds.
One can envisage that realization of such a hydrogen-bond
pattern is sterically demanding, and this is probably the reason
why the diphenyl ester molecule adopts in the solid state a nearly
ac conformation of its four-carbon chain and, moreover, the
hydrogen bonds formed in this crystal are far from being linear
(Table A, Supporting Information).
Only in structure 4p′ is one stabilizing 1,3-CdO/C-H
dipole-dipole interaction realized. Worthy of note is the mutual
orientation of the aryl substituents, which are aligned nearly
parallel in all three molecules. In the diphenyl ester molecule,
the two phenyl rings are inclined at an angle of 11.3(4)°, while
in both crystallographically independent molecules of dinaphthyl
ester the average interplanar angle is only 3.2(2)°.
In both investigated crystal structures, molecules connected
by hydrogen bonds form layers parallel to the (001) lattice plane.
Phenyl or naphthyl groups are concentrated on both sides of
these layers, and one unit cell contains two such layers, as
illustrated in Figure 2.
Compared to optically active tartaric acid and NH-tartramides,
tartrates display much higher conformational flexibility mani-
fested in the ease with which they adjust to packing requirements
in their crystals. Diaryl tartrates seem to outweigh dialkyltartrates
in this respect by not only being able to switch the conformation
around the C(sp3)-C(sp2) bonds (angle ꢀ) from sp to ap but
also in displaying a significant deviation from the extended (T)
four-carbon chain conformation, a phenomenon so far unprec-
edented in tartrates.
FIGURE 2. van der Waals representation of bimolecular hydrophobic
layers characteristic for both investigated diaryl L-tartrates and exempli-
fied by diphenyl L-tartrate (4a).
diaryl tartrates, we selected diphenyl (4a), di-1-naphthyl (4o),
and di-2-naphthyl (4p) L-tartrates, representing various patterns
of aryl ring substitution in relation to the ester C-O bond, for
computational modeling, with the use of Gaussian0327 software
(for computational details, see the Supporting Information).
At the B3LYP/6-311++G(2D,2P) level of calculation, we
found, within the 2.0 kcal ·mol-1 free energy window, two stable
conformers for 4a, four in the case of 4o and three for 4p. Their
relative free energies, populations, symmetries, and consecutive
torsion angles along the molecule chain are listed in Table 3.
Figure 3 shows the structures of these conformers, including
the available intramolecular hydrogen bonds.
In general, all calculated structures belong to the extended
(T) family, with torsion angle R in the range 171-174°. This
is in contrast to the data from the X-ray study (see Table 2)
where angle R is found to be significantly smaller (147-162°).
All calculated structures shown in Figure 3 are stabilized by at
least one intramolecular hydrogen bond of the length 2.05-2.11
Å, involving OH donor and vicinal ester carbonyl group. For
this reason, angle ꢀ is sc in all cases, except in structures not
stabilized by such a hydrogen bond. In these structures (4a,
conformer 2; 4o, conformers 3 and 4), one hydroxy group is
engaged in weak hydrogen bonding with two vicinal oxygens
atoms, i.e., the ester and the other hydroxy group (Figure 3), to
yield angle ꢀ ca. -110°. Only these conformers are stabilized
by one 1,3-CdO/C-H dipole interaction. Furthermore, an
extended conformation is found for the tartrate structure
involving the C*-C-O-CAr bonds (angle γ). In all cases, the
calculated angles γ are close to ideal ap (180°). Incidentally,
in the crystal structures of 4a and 4p angle γ shows a higher
degree of deviation from the ideal value for the ap conformation
(see Table 2). Finally, angle δ describing nonplanarity of the
aryl ring and the ester C-O bond is found in the range 68°-91°,
described as sc. This degree of nonplanarity is expected for the
derivatives of phenols, such as ethers and esters. The corre-
sponding values of angle δ obtained from the crystal structures
of 4a and 4p are negative.
(27) Gaussian 03, ReVision C.02: Frisch, M. J.; Trucks, G. W.; Schlegel,
H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.;
Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi,
J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson,
G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa,
J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo,
J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli,
C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.;
Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.;
Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.;
Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.;
Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople,
J. A. Gaussian, Inc., Wallingford, CT, 2004.
DFT Calculations. In order to obtain a more quantitative
insight into the conformer population of isolated molecules of
(23) Egli, M.; Dobler, M. HelV. Chim. Acta 1989, 72, 1136.
(24) Szarecka, A.; Hoffmann, M.; Rychlewski, J.; Rychlewska, U. J. Mol.
Struct. 1996, 374, 363.
(25) Rychlewska, U.; Warzajtis, B.; Hoffmann, M.; Rychlewski, J. Molecules
1997, 2, 106.
(26) Rychlewska, U.; Warzajtis, B. Acta Crystallogr. B 2000, 56, 833.
4576 J. Org. Chem. Vol. 74, No. 12, 2009

Diaryl Esters of Tartaric Acid.
TABLE 3. Calculated at the B3LYP/6-311++G(2D,2P) Level Relative Free Energies (∆G), Populations, Symmetries, And Torsion Angles r,
ꢀ, γ, δ for Low Energy Conformers of 4a, 4o, and 4p.
torsion anglesa (deg)
ester
conformer
∆G (kcal·mol-1
)
population (%)
symmetry
R
ꢀ; ꢀ′
61.9
59.1; -112.2
58.0;61.9
58.2
55.1; -111.8
55.8; -107.9
62.2;61.3
61.3
γ; γ′
-176.3
177.4; -178.8
178.9; -176.8
178.7
δ; δ′b
73.4
74.4; -78.2
74.5; -91.1
91.4
89.7; -78.7
91.3; -91.3
68.9; 83.7
78.2
4a
conf 1
conf 2
conf 1
conf 2
conf 3
conf 4
conf 1
conf 2
conf 3
0.00
1.02
0.00
0.21
0.88
1.35
0.00
0.40
0.85
85
15
50
35
11
4
58
29
13
C2
C1
C1
C2
C1
C1
C1
C2
C2
171.7
-173.1
171.3
4o
4p
171.4
-174.2
-174.4
171.4
170.8
171.3
178.6; 177.4
179.0; 179.6
-174.7; -176.3
-175.9
62.3
-174.3
67.9
a For definition of torsion angles, see Scheme 2. b The smaller of the two torsion angles is shown.
formations, it is not clear if similar conformational restrictions
apply to the tartrates in solution. Significant Cotton effects, if
observed within electronic transitions of the aryl chromophores,
would attest to limited conformational freedom of diaryl
L-tartrates in solution. The CD/UV spectra of diaryl L-tartrates
in acetonitrile solution are shown in Figures 4-6.
The esters of phenol and its derivatives 4a-n (Figure 4) are
characterized by a weak long-wavelength absorption due to 1Lb-
type transition (not observed in the CD spectra) and a stronger
1La band, located at ca. 220 nm in diphenyl L-tartrate (4a). This
band is shifted to a longer wavelength and becomes more
intensive in substituted phenyl L-tartrates 4b-m. It is associated
with a negative Cotton effect of moderate intensity (∆ε -4 to
-12) in the CD spectra. The origin of this Cotton effect is not
1
fully understood at present. In addition to La transition which
is observed in the UV spectrum there is a possibility of
contribution from the carboxylate n-π* transition. This transi-
tion is of weak oscillator strength but in the case of dialkyl
L-tartrates it can be observed as a distinct negative Cotton effect
at ca. 220 nm.17,18 Nevertheless, the long-wavelength (220-240
nm) negative Cotton effect appears to be characteristic of
absolute configuration and conformation of both dialkyl and
diaryl L-tartrates, and its presence has been confirmed by our
TDDFT calculation of the CD spectrum for the most stable
conformer of 4a. Note that the 4-nitrophenyl derivative 4h
displays an additional negative Cotton effect in the CD spectrum
at ca. 280 nm, apparently due to a transition involving the
π-electron system of the nitro group.
The UV spectrum of diester 4n is remarkable due to the
presence of a strong biphenyl band at 252 nm (ε 37700). In the
CD spectrum, a bisignate Cotton effect is seen within the 252
nm band (∆ε -9.5 at 262 nm, + 3 at 239 nm). This suggests
that the bisignate Cotton effect is of exciton type due to the
interaction of the electronic transition moments of the conjuga-
tion band in the two biphenyl chromophores. A similar exciton
Cotton effect can be seen in the CD spectrum of 4-methoxy-
carbonyl diester 4m. In this case, the bisignate Cotton effect
(∆ε -9 at 240 nm, +3 at 221 nm) is due to exciton interaction
of the two substituted benzoate chromophores.
FIGURE 3. Calculated at B3LYP/6-311++G(2D,2P) level structures
of low energy conformers of 4a, 4o, and 4p with intramolecular
hydrogen bonds shown.
In general, calculated typical structures of diaryl L-tartrates
stabilized by intramolecular OH· · ·OdC hydrogen bond(s) can
be shortly characterized by a sequence of torsion angles: R (ap),
ꢀ (sc), γ (ap), δ (sc). On the other hand, higher energy structures
of C1 symmetry with one bifurcated hydrogen bond can be
described as R (ap), ꢀ (ac), γ (ap), δ (sc). One should bear in
mind, however, that free energy differences between conformers
of diaryl esters are in general not high and in solution
interactions with the solvent molecules may bring about
significant shifts in conformer populations.
An even more pronounced exciton coupling mechanism is
observed in the CD spectra of dinaphthyl L-tartrates 4o and 4p.
1
The intense Bb transition in naphthalene chromophores of 4o
and 4p is located at ca. 220 nm (ε ∼70000) and generates very
strong negative exciton-coupled Cotton effects, i.e., ∆ε -153
at 223 nm, + 75 at 215 nm for 4o and ∆ε -35 at 226 nm, +
23 at 215 nm for 4p (Figures 5 and 6).
Large magnitudes of the Cotton effects may appear surprising
given the number of low energy conformers contributing to the
Circular Dichroism and Optical Rotation of Diaryl
L-Tartrates. Diaryl esters of L-tartaric acid represent rare
examples of molecules bearing an aromatic chromophore
attached to a chiral carboxylic acid through an ester bond.
Although these molecules are acyclic and, according to DFT
calculations on isolated molecules, possess well-defined con-
J. Org. Chem. Vol. 74, No. 12, 2009 4577

Cysewski et al.
FIGURE 4. CD (solid lines) and UV (dashed lines) spectra of esters 4a-n measured in acetonitrile solutions.
4578 J. Org. Chem. Vol. 74, No. 12, 2009

Diaryl Esters of Tartaric Acid.
FIGURE 5. Calculated at TDDFT/B2LYP/6-311++G(2D,2P) level UV (left panels) and CD (right panels) spectra for individual conformers of
4o, Boltzmann-averaged calculated UV and CD spectra (dashed lines) and experimental UV and CD spectra (solid lines, bottom panels) of 4o.
Vertical bars represent oscillator (f) or rotatory strengths (R), respectively. The rotatory strengths R were calculated in velocity representations. All
calculated spectra were wavelength corrected to match the experimental short wavelength λmax value in the UV spectrum.
J. Org. Chem. Vol. 74, No. 12, 2009 4579

Cysewski et al.
FIGURE 6. Calculated at TDDFT/B2LYP/6-311++G(2D,2P) level UV (left panels) and CD (right panels) spectra for individual conformers of
4p, Boltzmann-averaged calculated UV and CD spectra (dashed lines), and experimental UV and CD spectra (solid lines, bottom panels) of 4p.
Vertical bars represent oscillator (f) or rotatory strengths (R), respectively. The rotatory strengths R were calculated in velocity representations. All
calculated spectra were wavelength corrected to match the experimental short wavelength λmax value in the UV spectrum.
population (four in the case of 4o, three in the case of 4p, Table
3). TDDFT calculations of the CD spectra of individual
conformers of 4o and 4p (Figures 4 and 5) provide rationaliza-
tion of the observed high intensity Cotton effects (A ) -228
for 4o, -58 for 4p). All four conformers of 4o are characterized
by a negative helicity of the 1Bb transition electric dipole
moments (the dihedral angle between the electric dipole
transition moments is -45° to -72°); hence, all four conformers
generate negative exciton Cotton effects. This results in a very
strong experimental negative Cotton effect, despite a rather large
spatial separation of the two naphthalene chromophores (ca. 10.5
Å). Conversely, smaller amplitude of the exciton Cotton effect
of 4p is the result of opposite sign contributions of conformers
1 (negative) and 2 (positive), while triple-sign exciton Cotton
effect (-/+/-) was calculated for conformer 3 of 4p. The
population-averaged CD spectrum of 4p is still of negative
amplitude (A ) -58) due to a dominant contribution (58%
population) of conformer 1. We note that the sign and magnitude
4580 J. Org. Chem. Vol. 74, No. 12, 2009

Diaryl Esters of Tartaric Acid.
75%; mp 73-74 °C; 1H NMR (300 MHz, CDCl3) δ 7.6-7.55 (m,
2H), 7.43-7.38 (m, 3H), 6.14 (s, 1H), 4.99 (d, 1H, J ) 4.1 Hz),
4.88 (d, 1H, J ) 4.1 Hz), 3.88 (s, 3H), 3.83 (s, 3H).
TABLE 4. Calculated (at the B3LYP/6-311++G(2D,2P) Level)
and Measured (in Various Solvents) Optical Rotations for Esters 4a,
4o, and 4p
[R]D
Disodium 2,3-O-Benzylidene-L-tartrate (2). The disodium salt
was prepared by hydrolysis of compound 1 (3 g, 0.011 mol) by
the addition of hot ethanol solution of NaOH (0.9 g in 20 mL) and
stirring the mixture overnight at room temperature followed by
concentration in vacuum. The oily white residue was then triturated
with dry diethyl ether and stirred in an ice bath. The crystalline
product 2 was filtered, washed with dry diethyl ether, and dried in
vacuum (yield 3.06 g, 98%): 1H NMR (300 MHz, D2O) δ
7.68-7.64 (m, 2H), 7.54-7.48 (m, 3H), 6.05 (s, 1H), 4.70 (d, 1H,
J ) 4.7 Hz), 4.62 (d, 1H, J ) 4.7 Hz).
Diaryl 2,3-O-Benzylidene-L-tartrates (3a-p). To a suspension
of 2 (0.3 g, 1.1 mmol) in 2 mL of dry toluene containing one drop
of DMF was added dropwise oxalyl chloride (1.2 mL) at 2-3 °C.
After the reaction subsided, the mixture was refluxed at 65 °C for
2 h and then stirred overnight at room temperature. After evapora-
tion of excess oxalyl chloride and the solvent under reduced
pressure, dichloride 3 was obtained and immediately used for diester
preparation without further purification.
To a solution of dichloride 3 in dry dichloromethane (5 mL)
was added 2 equiv of phenol or naphthol, followed by dropwise
addition of pyridine (0.4 mL) in dry dichloromethane (2 mL). After
overnight stirring, the reaction mixture was extracted with 2 N HCl,
and the organic layer was separated and washed twice with distilled
water and then dried over Na2SO4. After filtration, the solvent was
evaporated and the residue purified by radial chromatography on
silica gel plates (2 mm thickness).
[R]D exp (deg)
calcd
ester
4a
conformer (deg) CHCl3 THF Me2CO i-PrOH EtOH MeCN
conf 1
conf 2
-65
+85
∆G Boltzmann averaged -42 -4 -8 -3
4o
-5
-2
+5
conf 1
conf 2
conf 3
conf 4
-75
-29
-40
-64
∆G Boltzmann averaged -55 -27 -44 -13 -36 -24 -21
4p
conf 1
conf 2
conf 3
-141
-45
-45
∆G Boltzmann averaged -101 -35 -35 -24 -34 -27 -12
of the exciton Cotton effect of 4p contrasts with the reported
data for malic acid di-2-naphthyl ester of the same (R)
configuration (A ) +12.9).13 Interestingly, calculations show
nearly canceling contributions of the rotatory strengths to the
long-wavelength Cotton effect of 4o and 4p. This is in
accordance with the experimentally observed small Cotton effect
1
for naphthalene La transition in these esters.
Finally, we calculated the optical rotations of individual
conformers of aryl esters 4a, 4o, and 4p (Table 4).
The two conformers of 4a contribute rotations of opposite
sign. Experimental small negative [R]D values measured in
various solvents (except in acetonitrile) agree qualitatively with
the dominant contribution of conformer 1, characterized by a
negative calculated [R]D. In the case of dinaphthyl esters 4o
and 4p all calculated conformers are characterized by negative
rotation; hence, the population-averaged calculated [R]D agrees
quite well with the negative [R]D values for 4o and 4p measured
experimentally in solvents ranging from chloroform to aceto-
nitrile (Table 4).
Diphenyl 2,3-O-benzylidene-L-tartrate (3a): yield 243 mg
1
(57%); mp 77-79 °C; H NMR (300 MHz, CDCl3) δ 7.68-7.64
(m, 2H), 7.47-7.11(m, 13H), 6.35 (s, 1H), 5.39 (d, 1H, J ) 3.6
Hz), 5.27 (d, 1H, J ) 3.6 Hz); 13C NMR (100 MHz, CDCl3) δ
167.9, 167.4, 150.1, 150.0, 135.2, 130.1, 129.6, 129.5, 128.4, 127.2,
126.5, 126.4, 121.3, 107.2, 77.6, 77.3; HRMS (m/z) 391.1218 [M
+ H] (C23H19O6H, calcd 391.1182).
Bis(4-methylphenyl) 2,3-O-benzylidene-L-tartrate (3b): yield
1
265 mg (58%); mp 97-99 °C; H NMR (300 MHz, CDCl3) δ
7.67-7.63 (m, 2H), 7.44-7.39 (m, 3H), 7.23-7.17 (m, 4H)
7.09-7.06 (m, 2H) 7.02-6.98 (m, 2H) 6.33 (s, 1H), 5.36 (d, 1H,
J ) 3.8 Hz), 5.24 (d, 1H, J ) 3.8 Hz), 2.36 (s, 3H), 2.35 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 168.1, 167.6, 147.9, 147.8, 136.2,
136.1, 135.3, 130.15, 130.11, 130.0, 128.4, 127.2, 120.8, 120.7,
107.2, 77.7, 77.4, 20.89, 20.87; HRMS (m/z): 441.1316 [M + Na]
(C25H22O6Na, calcd 441.1314).
In conclusion, the CD and [R]D data for diaryl L-tartrate
provide additional support for postulated preferred structures
of these esters.
Conclusions
A series of diaryl L-tartrates have been synthesized and
characterized for the first time. Despite their acyclic character,
diaryl esters of L-tartaric acid have a rather rigid, extended
structure as the result of conformational restrictions, mainly due
to intramolecular vicinal hydrogen bonding between the O-H
and CdO groups. Structure stabilizing 1,3-CdO/C-H dipole-
dipole interactions seem to play additional role in determination
of conformer population of diaryl L-tartrates. As a result,
dinaphthyl L-tartrates display large exciton Cotton effects due
to coupling of 1Bb transitions, despite the distance between the
two chromophores which exceeds 10.5 Å. It appears that
1-naphthyl chromophore until now remaining obscure is par-
ticularly well-suited for stereochemical studies with the use of
CD spectroscopy, as it gives rise to much larger Cotton effects,
compared to the commonly used 2-naphthyl chromophore. This
consequently leads to the enhancement of sensitivity of CD
measurements over large interchromophoric distances.
Bis(4-tert-butylphenyl) 2,3-O-benzylidene-L-tartrate (3c): yield
370 mg (67%); oil; 1H NMR (300 MHz, CDCl3) δ 7.67-7.63 (m,
2H), 7.45-7.38 (m, 7H), 7.14-7.02 (m, 4H), 6.34 (s, 1H), 5.37
(d, 1H, J ) 4.1 Hz), 5.25 (d, 1H, J ) 4.0 Hz), 1.33 (s, 9H), 1.32
(s, 9H); 13C NMR (100 MHz, CDCl3) δ 168.0, 167.6, 149.4, 149.3,
147.8, 147.7, 135.3, 130.1, 128.4, 127.2, 126.5, 126.4, 120.43,
120.42, 107.2, 77.7, 77.4, 34.55, 34.52, 31.3; HRMS (m/z) 525.2302
[M + Na] (C31H34O6Na, calcd 525.2253).
Bis(4-formylphenyl) 2,3-O-benzylidene-L-tartrate (3d): yield
1
146 mg (30%); mp 116-118 °C; H NMR (300 MHz, CDCl3) δ
10.03 (s, 1H), 10.01 (s, 1H), 8.02-7.26 (m, 13H), 6.37 (s, 1H),
5.44 (d, 1H, J ) 3.8 Hz), 5.31 (d, 1H, J ) 3.8 Hz); 13C NMR (100
MHz, CDCl3) δ 190.6, 167.2, 166.7, 154.5, 154.4, 134.9, 134.6,
134.5, 131.4, 131.3, 130.3, 128.6, 127.0, 122.0, 121.9, 107.4, 77.5,
77.2; HRMS (m/z) 447.1915 [M + H] (C25H18O8H, calcd 447.1948).
Bis(2-bromophenyl) 2,3-O-benzylidene-L-tartrate (3e): yield
1
378 mg (60%); oil; H NMR (300 MHz, CDCl3) δ 7.70-7.61
(m, 4H), 7.44-7.32 (m, 5H), 7.26-7.13 (m, 4H), 6.39 (s, 1H),
5.66 (d, 1H, J ) 3.8 Hz), 5.52 (d, 1H, J ) 3.6 Hz); 13C NMR
(100 MHz, CDCl3) δ 167.1, 166.7, 147.5, 147.4, 134.9, 133.6,
133.5, 130.2, 128.8, 128.7, 128.4, 128.1, 128.0, 127.4, 123.4, 115.8,
115.7, 107.6, 77.7, 77.3; HRMS (m/z) 570.8700 [M + Na]
(C23H16Br2O6Na, calcd 570.9211).
Experimental Section
Dimethyl 2,3-O-Benzylidene-L-tartrate (1). Compound 1 was
prepared from dimethyl L-tartrate by a literature procedure:14 yield
J. Org. Chem. Vol. 74, No. 12, 2009 4581

Cysewski et al.
Bis(3-bromophenyl) 2,3-O-benzylidene-L-tartrate (3f): yield
315 mg (50%); mp 68-71 °C; H NMR (300 MHz, CDCl3) δ
Bisi(4-biphenyl) 2,3-O-benzylidene-L-tartrate (3n): yield 211
mg (43%); mp 201-203 °C; 1H NMR (300 MHz, CDCl3) δ
7.70-7.18 (m, 23H), 6.38 (s, 1H), 5.44 (d, 1H, J ) 3.8 Hz), 5.31
(d, 1H, J ) 3.8 Hz); 13C NMR (100 MHz, CDCl3) δ 168.0, 167.5,
149.5, 149.4, 140.1, 140.0, 139.8, 139.7, 135.2, 130.1, 128.88,
128.86, 128.7, 128.5, 128.4, 128.3, 127.59, 127.55, 127.2, 127.1,
121.43, 121.40, 107.3, 77.7, 77.4; HRMS (m/z): 565.1848 [M +
Na] (C35H26O6Na, calcd 565.1627).
1
7.65-7.62 (m, 2H), 7.47-7.05 (m, 11H), 6.34 (s, 1H), 5.37 (d,
1H, J ) 3.8 Hz), 5.22 (d, 1H, J ) 3.7 Hz); 13C NMR (100 MHz,
CDCl3) δ 167.4, 166.9, 150.4, 150.3, 135.0, 130.7, 130.6, 130.2,
129.8, 129.7, 128.5, 127.1, 124.66, 124.62, 122.6, 122.5, 120.0,
119.9, 107.3, 77.4, 77.1; HRMS (m/z) 570.8700 [M + Na]
(C23H16Br2O6Na, calcd 570.9211).
Bis(4-bromophenyl) 2,3-O-benzylidene-L-tartrate (3g): yield
320 mg (53%); mp 118-120 °C; H NMR (300 MHz, CDCl3) δ
Bis(1-naphthyl) 2,3-O-benzylidene-L-tartrate (3o): yield 250
mg (47%); mp 124-126 °C; 1H NMR (300 MHz, CDCl3) δ
8.00-7.72 (m, 8H), 7.57-7.34 (m, 11H), 6.49 (s, 1H), 5.70 (d,
1H, J ) 4.1 Hz), 5.59 (d, 1H, J ) 4.1 Hz); 13C NMR (100 MHz,
CDCl3) δ 168.1, 167.4, 145.9, 145.8, 135.1, 134.7, 134.6, 130.2,
128.5, 128.1, 128.0, 127.3, 126.9, 126.8, 126.7, 126.6, 126.5, 126.3,
126.2, 125.3, 125.2, 120.8, 120.7, 117.8, 117.7, 107.5, 77.9, 77.7;
HRMS (m/z) 513.1382 [M + Na] (C31H22O6Na, calcd 513.1314).
Bis(2-naphthyl) 2,3-O-benzylidene-L-tartrate (3p): yield 280
mg (57%); mp 141-143 °C; 1H NMR (300 MHz, CDCl3) δ
7.93-7.24 (m, 19H), 6.42 (s, 1H), 5.51 (d, 1H, J ) 3.8 Hz), 5.39
(d, 1H, J ) 3.8 Hz); 13C NMR (100 MHz, CDCl3) δ 168.1, 167.6,
147.7, 147.6, 135.2, 133.63, 133.61, 131.7, 131.6, 130.1, 129.8,
129.7, 128.5, 127.85, 127.81, 127.75, 127.73, 127.2, 126.9, 126.8,
126.1, 126.0, 120.3, 118.4, 118.3, 107.3, 77.7, 77.5; HRMS (m/z)
513.1225 [M + Na] (C27H22O10Na, calcd 513.1314).
Diaryl L-Tartrates (4a-p). A sample of acetal 3a-p (50 mg)
was dissolved in 2 mL of dry dichloromethane and stirred with a
TFA/H2O mixture (8:2, 0.2 mL) for 30-90 min depending on the
compound used (TLC control). The solution was then washed three
times with distilled water, and the organic layer was dried over
anhydrous Na2SO4. After evaporation, the residue was purified by
radial chromatography. The esters 4a-p were further purified by
crystallization from a minimum amount of hot hexane/ethyl acetate
or dichloromethane/methanol.
1
7.64-7.40 (m, 9H), 7.12-6.96 (m, 4H), 6.33 (s, 1H), 5.36 (d, 1H,
J ) 3.8 Hz), 5.23 (d, 1H, J ) 3.8 Hz); 13C NMR (100 MHz, CDCl3)
δ 167.5, 167.0, 149.0, 148.9, 135.0, 132.7, 132.6, 130.2, 128.5,
127.1, 122.9, 122.8, 119.8, 119.6, 107.3, 77.5, 77.2; HRMS (m/z)
570.8611 [M + Na] (C23H16Br2O6Na, calcd 570.9211).
Bis(4-nitrophenyl) 2,3-O-benzylidene-L-tartrate (3h): yield
1
36% (190 mg); mp 157-159 °C; H NMR (300 MHz, CDCl3) δ
8.37-8.27 (m, 4H), 7.64-7.61 (m, 2H), 7.48-7.40 (m, 5H),
7.29-7.25 (m, 2H), 6.37 (s, 1H), 5.45 (d, 1H, J ) 3.6 Hz), 5.31
(d, 1H, J ) 3.6 Hz); 13C NMR (100 MHz, CDCl3 + CD3COCD3)
δ 167.0, 166.6, 154.6, 154.5, 145.99, 145.90, 134.9, 130.3, 128.6,
127.1, 125.5, 125.4, 122.3, 122.2, 107.4, 77.4, 77.1; HRMS (m/z)
481.1044 [M + H] (C23H16N2O10H, calcd 481.0883).
Bis(2,4-di-tert-butylphenyl) 2,3-O-benzylidene-L-tartrate (3i):
yield 347 mg (52%); mp 49-52 °C; 1H NMR (300 MHz, CDCl3)
δ 7.68-7.64 (m, 2H), 7.44-7.39 (m, 5H), 7.29 (d, 1H, J ) 2.4
Hz), 7.22 (d, 1H, J ) 2.4 Hz), 7.01 (d, 1H, J ) 8.3 Hz), 6.92 (d,
1H, J ) 8.3 Hz), 6.35 (s, 1H), 1.38 (s, 9H), 1.34 (s, 9H), 1.33 (s,
9H), 1.31 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 168.4, 167.7,
148.9, 148.8, 146.4, 146.3, 140.0, 135.0, 130.0, 128.4, 127.2, 124.4,
124.3, 124.0, 123.9, 122.6, 107.2, 77.8, 77.5, 34.73, 34.71, 31.6,
31.4, 30.34, 30.31; HRMS (m/z) 637.3516 [M + Na] (C39H50O6Na,
calcd 637.3505).
Bis(2,4-dichlorophenyl) 2,3-O-benzylidene-L-tartrate (3j):
yield 220 mg (38%); mp 109-111 °C; 1H NMR (300 MHz, CDCl3)
δ 7.66-7.08 (m, 11H), 6.35 (s, 1H), 5.54 (d, 1H, J ) 3.6 Hz),
5.41 (d, 1H, J ) 3.6 Hz); 13C NMR (100 MHz, CDCl3) δ 166.8,
166.3, 144.9, 144.8, 134.7, 132.8, 132.7, 130.39, 130.33, 130.31,
128.5, 128.3, 128.2, 127.56, 127.50, 127.3, 124.24, 124.22, 107.6,
77.5, 76.9; HRMS (m/z) 550.8944 [M + Na] (C23H14Cl4O6Na, calcd
550.9442).
Diphenyl L-tartrate (4a): yield 35 mg (90%); mp 159-162 °C;
[R]2D0 -2.8 (c ) 0.5, acetone); 1H NMR (300 MHz, CD3COCD3) δ
7.49-7.42 (m, 4H), 7.32-7.27 (m, 2H), 7.23-7.19 (m, 4H), 5.10
(s, 2H), 4.98 (s, 2H); 13C NMR (75 MHz, CD3COCD3) δ 170.5,
151.5, 130.1, 126.6, 122.2, 73.8; EI-MS (m/z) 302.1 [M+], 274.0,
181.1, 135.0, 94.0; HRMS (m/z) 325.0670 [M + Na] (C16H14O6Na,
calcd 325.0688). Crystals suitable for X-ray crystallography were
grown from saturated dichloromethane/methanol solution.
Bis(4-methylphenyl) L-tartrate (4b): yield 34 mg (79%); mp
Bis(2,4-dibromo-6-tert-butoxycarbonylphenyl) 2,3-O-ben-
zylidene-L-tartrate (3k): yield 540 mg (54%); mp 84-86 °C; 1H
NMR (300 MHz, CDCl3) δ 8.00-7.90 (m, 4H), 7.71-7.68 (m,
2H), 7.42-7.37 (m, 3H), 6.37 (s, 1H), 5.92 (d, 1H, J ) 3.3 Hz),
5.72 (d, 1H, J ) 3.3 Hz), 1.56 (s, 9H), 1.54 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ 166.7, 166.4, 161.3, 146.4, 146.3, 139.7,
138.96, 138.91, 135.1, 133.5, 133.4, 130.0, 129.8, 128.3, 127.6,
119.8, 119.6, 119.1, 119.0, 107.5, 77.0, 76.4, 33.6, 28.03, 28.01;
HRMS (m/z) 928.8531 [M + Na] (C33H30Br4O10Na, calcd 928.8470).
Bis[2-(phenoxycarbonyl)phenyl] 2,3-O-benzylidene-L-tartrate
1
154-156 °C; [R]2D0 -8.8 (c ) 0.5, acetone); H NMR (300 MHz,
CD3COCD3) δ 7.25-7.22 (m, 4H), 7.08-7.05 (m, 4H), 5.06 (s,
2H), 4.87 (s, 2H), 2.33 (s, 6H); 13C NMR (75 MHz, CD3COCD3)
δ 170.6, 149.3, 136.1, 130.5, 121.9, 73.7, 20.7; FAB-MS (NBA
matrix) (m/z) 330.9 [M + H]; HRMS (m/z) 353.0993 [M + Na]
(C18H18O6Na, calcd 353.1001).
Bis(4-tert-butylphenyl) L-tartrate (4c): yield 38 mg (92%); mp
1
127-130 °C; [R]2D0 -8.4 (c ) 0.5, acetone); H NMR (300 MHz,
CD3COCD3) δ 7.50-7.45 (m, 4H), 7.15-7.10 (m, 4H), 5.08 (s,
2H), 4.93 (s, 2H), 1.33 (s, 18H); 13C NMR (75 MHz, CD3COCD3)
δ 170.6, 149.3, 149.2, 126.9, 121.6, 73.7, 34.9, 31.6; FAB-MS (m/
z) 437.2 [M + Na], 415.2 [M + H]; HRMS (m/z) 437.1823 [M +
Na] (C24H30O6Na, calcd 437.1940).
1
(3l): yield 400 mg (43%); mp 43-45 °C; H NMR (300 MHz,
CDCl3) δ 8.27-8.21 (m, 2H), 7.67-7.09 (m, 21H), 6.20 (s, 1H),
5.66 (d, 1H, J ) 3.7 Hz), 5.52 (d, 1H, J ) 3.7 Hz); 13C NMR (100
MHz, CDCl3) δ 168.1, 167.7, 162.65, 162.62, 150.4, 150.36, 150.30,
135.3, 134.7, 134.6, 132.2, 132.1, 129.9, 129.5, 129.4, 128.2, 127.4,
126.7, 126.6, 126.08, 126.02, 123.73, 123.71, 122.49, 122.44,
121.66, 121.62, 106.9, 77.2, 76.6; HRMS (m/z) 653.0815 [M +
Na] (C37H26O10Na, calcd 653.1424).
Bis(4-formylphenyl) L-Tartrate (4d). In this reaction, aceto-
nitrile was used as solvent instead of dichloromethane: yield 32
1
mg (80%); mp 126-129 °C; [R]2D0 -20.6 (c ) 0.5, acetone); H
NMR (300 MHz, CD3COCD3) δ 10.06 (s, 2H), 8.07-8.02 (m, 4H),
7.48-7.43 (m, 4H), 5.20 (s, 4H); 1H NMR (300 MHz, CD3COCD3
+ D2O) δ 10.06 (s, 2H), 8.07-8.03 (m, 4H), 7.49-7.46 (m, 4H),
5.19 (s, 2H); 13C NMR (75 MHz, CD3COCD3) δ 191.4, 170.0,
155.8, 135.3, 131.6, 123.1, 73.8; ESI-MS (m/z) 359 [M + H];
HRMS (m/z) 381.0377 [M + Na] (C18H14O8Na, calcd 381.0586).
Bis(2-bromophenyl) L-tartrate (4e): yield 33 mg (78%); mp
109-111 °C; [R]2D0 -29.2 (c ) 0.5, acetone); 1H NMR (400 MHz,
CD3COCD3) δ 7.74 (dd, 2H, J ) 1.4, 8.6 Hz), 7.51-7.45 (m, 2H),
7.36-7.25 (m, 4H), 5.26 (s, 2H); 13C NMR (100 MHz, CD3COCD3)
δ 169.8, 148.9, 134.2, 129.7, 128.7, 124.9, 116.3, 73.6; ESI-MS
Bis[4-(methoxycarbonyl)phenyl] 2,3-O-benzylidene-L-tartrate
(3m): yield 322 mg (58%); mp 104-106 °C; 1H NMR (300 MHz,
CDCl3) δ 8.15-8.07 (m, 4H), 7.66-7.63 (m, 2H), 7.45-7.42 (m,
3H), 7.30 (dd, 2H, J ) 2.0, 6.8 Hz), 7.19 (dd, 2H, J ) 2.0, 6.8
Hz), 6.35 (s, 1H), 5.41 (d, 1H, J ) 3.8 Hz), 5.28 (d, 1H, J ) 3.8
Hz), 3.93 (s, 3H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3 +
CD3COCD3) δ 167.4, 166.9, 166.09, 166.08, 153.6, 153.5, 135.1
131.8, 131.4, 131.3, 130.2, 128.5, 128.4, 127.1, 121.29, 121.23,
107.3, 77.5, 77.2, 52.34, 52.31; HRMS (m/z) 529.1226 [M + Na]
(C27H22O10Na, calcd 529.1111).
4582 J. Org. Chem. Vol. 74, No. 12, 2009

Diaryl Esters of Tartaric Acid.
(m/z) 483 [Na+]; HRMS (m/z) 482.8963 [M + Na] (C16H12Br2O6Na,
calcd 482.8898).
yield 27 mg (65%); mp 199-201 °C; [R]2D0 -46.8 (c ) 0.5, DMSO);
1H NMR (300 MHz, DMSO) δ 8.09-8.04 (m, 4H), 7.34-7.30
(m, 4H), 6.28 (d, 2H, J ) 8.0 Hz), 5.03 (d, 2H, J ) 7.8 Hz), 3.87
Bis(3-bromophenyl) L-tartrate (4f): yield 34 mg (81%); mp
1
140-142 °C; [R]2D0 -5.4 (c ) 0.5, acetone); H NMR (400 MHz,
1
(s, 6H); H NMR (300 MHz, DMSO + D2O) δ 8.01-8.05 (m,
CD3COCD3) δ 7.53 (m, 6H), 7.27 (m, 2H), 5.14 (s, 2H); 13C NMR
(100 MHz, CD3COCD3) δ 170.4, 152.3, 131.9, 129.9, 125.7, 122.5,
121.6, 73.8; ESI-MS (m/z) 483 [M + Na+]; HRMS (m/z) 482.9044
[M + Na] (C16H12Br2O6Na, calcd 482.8898).
4H), 7.36-7.31 (m, 4H), 5.03 (s, 2H), 3.87 (s, 6H); 13C NMR (75
MHz, DMSO) δ 169.3, 165.2, 153.8, 130.7, 127.2, 121.9, 72.5,
52.2; EI-MS (m/z) 418.9 [M+], 390.0, 327.1, 239.0, 152.0, 121.0,
93.0; HRMS (m/z) 441.0798 [M + Na] (C20H18O10Na, calcd
441.0827).
Di(4-biphenyl) L-Tartrate (4n). The reaction was carried out
without dichloromethane as cosolvent: yield 30 mg (72%); mp
262-265 °C; [R]2D0 -23.4 (c ) 0.5, DMSO); 1H NMR (300 MHz,
DMSO) δ 7.76 (d, 4H, J ) 7.6 Hz), 7.70 (d, 4H, J ) 7.6 Hz), 7.51
(t, 4H, J ) 7.2 Hz), 7.40 (t, 2H, J ) 7.2 Hz) 7.27 (d, 4H, J ) 7.6
Hz), 6.21 (d, 2H, J ) 7.0 Hz), 5.02 (d, 2H, J ) 6.8 Hz); 13C NMR
(75 MHz, DMSO) δ 169.8, 149.6, 139.0, 137.7, 128.7, 127.6, 127.3,
126.5, 121.8, 72.6; EI-MS (m/z) 454.0 [M+], 420.0, 284.0, 250.9,
170.0, 141.0; HRMS (m/z) 477.1676 [M + Na] (C28H22O6Na, calcd
477.1314).
Di(1-naphthyl) L-tartrate (4o): yield 33 mg (80%); mp 42-47
°C; [R]D20 -12.7 (c ) 0.5, acetone); 1H NMR (300 MHz,
CD3COCD3) δ 8.27-8.23 (m, 2H), 8.02-7.94 (m, 2H), 7.90 (d,
2H, J ) 8.2 Hz) 7.62-7.54 (m, 6H), 7.42 (dd, 2H, J ) 1.0, 7.5
Hz), 5.57 (d, 2H, J ) 7.0 Hz), 5.34 (d, 2H, J ) 7.0 Hz); 1H NMR
(300 MHz, CD3COCD3 + D2O) δ 8.25-8.22 (m, 2H), 8.02-7.99
(m, 2H), 7.92 (d, 2H, J ) 8.2 Hz) 7.62-7.56 (m, 6H), 7.44 (d,
2H, J ) 7.4 Hz) 5.52 (s, 2H); 13C NMR (75 MHz, CD3COCD3) δ
170.7, 147.5, 135.4, 128.5, 127.6, 127.29, 127.22, 126.9, 126.2,
122.4, 118.9, 74.1; EI-MS (m/z) 402.1 [M+], 374.1, 268.9, 185.1,
144.0, 115.1; HRMS (m/z) 425.1126 [M + Na] (C24H18O6Na, calcd
425.1001).
Bi(4-bromophenyl) L-tartrate (4g): yield 32 mg (76%); mp
1
196-199 °C; [R]2D0 -4.2 (c ) 0.5, DMSO); H NMR (300 MHz,
DMSO) δ 7.67 (d, 4H, J ) 8.6 Hz), 7.15 (d, 4H, J ) 8.6 Hz), 6.21
(d, 2H, J ) 7.8 Hz), 4.97 (d, 2H, J ) 7.7 Hz); 13C NMR (75 MHz,
DMSO) δ 169.5, 149.3, 132.3, 123.7, 118.1, 72.5; EI-MS (m/z):
459.9 [M+], 431.9, 382.9, 251.8, 174, 171.9; HRMS (m/z) 482.9044
[M + Na] (C16H12Br2O6Na, calcd 482.8898).
Bis(4-nitrophenyl) L-tartrate (4h): yield 34 mg (83%); mp
144-146 °C; [R]2D0 -24.4 (c ) 0.5, acetone); 1H NMR (300 MHz,
CD3COCD3) δ 8.40-8.34 (m, 4H), 7.56-7.48 (m, 4H), 5.36 (d,
2H, J ) 7.9 Hz), 5.27 (d, 2H, J ) 6.8 Hz); 13C NMR (75 MHz,
CD3COCD3) δ 169.7, 156.1, 146.4, 125.9, 123.4, 73.8; EI-MS (m/
z) 392.9 [M+], 363.9, 277.9, 226.0, 139.1; HRMS (m/z) 415.0533
[M + Na] (C16H12N2O10Na, calcd 415.0390).
Bis(2,4-di-tert-butylphenyl) L-tartrate (4i): yield 34 mg (80%);
mp 72-74 °C; [R]2D0 -12.5 (c ) 0.5, acetone); 1H NMR (300 MHz,
CD3COCD3) δ 7.49 (d, 2H, J ) 2.4 Hz), 7.32 (dd, 2H, J ) 2.4,
8.4 Hz), 7.05 (d, 2H, J ) 8.4 Hz), 5.17 (dd, 2H, J ) 1.4, 7.0 Hz),
5.07 (dd, 2H, J ) 1.4, 7.0 Hz), 1.39 (s, 18H), 1.33 (s, 18H); 13C
NMR (75 MHz, CD3COCD3) δ 170.8, 148.8, 147.9, 140.7, 124.5,
124.4, 123.9, 74.0, 35.25, 35.20, 31.7, 30.6; EI-MS (m/z) 526.2
[M+], 498.2, 305.0, 219.0, 206.1, 191.1, 57.1; HRMS (m/z)
549.3257 [M + Na] (C32H46O6Na, calcd 549.3192).
Bis(2,4-dichlorophenyl) L-tartrate (4j): yield 34 mg (82%); mp
Di(2-naphthyl) L-tartrate (4p): yield 35 mg (85%); mp
196-198 °C; [R]2D0 -23.8 (c ) 0.5, acetone); 1H NMR (300 MHz,
CDCl3) δ 7.93-7.83 (m, 6H), 7.68 (d, 2H, J ) 2.3 Hz), 7.54-7.50
1
87-89 °C; [R]2D0 -23.6 (c ) 0.5, acetone); H NMR (300 MHz,
CD3COCD3) δ 7.67 (d, 2H, J ) 2.6 Hz), 7.51 (dd, 2H, J ) 2.4,
8.7 Hz), 7.39 (d, 2H, J ) 8.6 Hz) 5.25 (s, 4H);13C NMR (75 MHz,
CD3COCD3) δ 169.3, 146.4, 132.4, 130.4, 129.0, 128.2, 125.9, 73.5;
ESI-MS (m/z) 441.0 [M + H]; FAB-MS (m/z) 440.9 [M + H];
HRMS (m/z) 462.9129 [M + Na] (C16H10Cl4O6Na, calcd 463.1546).
bis(2,4-dibromo-6-tert-butoxycarbonylphenyl) L-tartrate (4k):
yield 40 mg (89%); mp 173-175 °C; 1H NMR (300 MHz,
CD3COCD3) δ 8.16 (d, 2H, J ) 2.5 Hz), 8.08 (d, 2H, J ) 2.5 Hz),
5.38 (d, 2H, J ) 8.6 Hz), 5.14 (d, 2H, J ) 8.6 Hz), 1.59 (s, 18H);
13C NMR (75 MHz, CD3COCD3) δ 169.2, 162.38, 147.2, 139.6,
134.1, 129.5, 120.0, 119.8, 84.0, 73.2, 28.0; FAB-MS (m/z) 841.0
[M + Na]+; HRMS (m/z) 840.8405 [M + Na] (C26H26Br4O10Na,
calcd 840.8157).
1
(m, 4H) 7.34 (dd, 2H, J ) 2.4, 8.8 Hz), 5.16 (s, 2H); H NMR
(300 MHz, CD3COCD3 + D2O) δ 8.04-7.93 (m, 6H), 7.76 (d,
2H, J ) 2.2 Hz), 7.61-7.52 (m, 4H) 7.43 (dd, 2H, J ) 2.2, 8.8
Hz), 5.23 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 170.3, 147.8,
133.6, 131.7, 129.8, 127.8, 127.7, 126.8, 126.1, 120.3, 118.4, 72.5;
EI-MS (m/z) 402.2 [M+], 374.0, 269.0, 185.1, 144.0, 115.0; HRMS
(m/z) 425.1203 [M + Na] (C24H18O6Na, calcd 425.1001).
Acknowledgment. This work was supported Grant No. R05
042 02 from the Ministry of Science and Higher Education.
All calculations were performed at the Poznan Supercomputing
Center.
Bis(2-phenoxycarbonylphenyl) L-tartrate (4l): yield 22 mg
1
(51%); mp 39-41 °C; [R]2D0 -84.4 (c ) 0.5, acetone); H NMR
Supporting Information Available: Crystallographic data
(CIF), computational details, Cartesian coordinates for all
calculated structures, CD and UV spectra calculated at the
(300 MHz, CDCl3) δ 8.28 (dd, 2H, J ) 1.4, 7.6 Hz), 7.69-7.63
(m, 2H), 7.45-7.35 (m, 6H), 7.27-7.14 (m, 8H) 5.20 (s, 2H), 3.51
(s, 2H); 13C NMR (75 MHz, CDCl3) δ 169.5, 162.6, 150.4, 150.1,
134.8, 132.1, 129.4, 126.6, 126.0, 123.9, 121.9, 121.5, 72.4; FAB-
MS (m/z) 542.9 [M + H]; HRMS (m/z) 565.0963 [M + Na]
(C30H22O10Na, calcd 565.1111).
1
B3LYP/6-311++G(2D,2P) level, and copies of H and 13C
NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
Bis(4-methoxycarbonylphenyl) L-Tartrate (4m). In this reac-
tion, acetonitrile was used as solvent instead of dichloromethane:
JO900206C
J. Org. Chem. Vol. 74, No. 12, 2009 4583