Synthesis of unsaturated diesters of primary, secondary and tertiary diols derived from dimethyl (+)-tartrate and galactaric acid

Article abstract of DOI:10.1002/ejoc.201300130

The preparation of symmetrical unsaturated diesters of dioe first was the reaction of mixed anhydrides, obtained from α,β-unsaturated acids and benzoyl chloride, with diols 3 (primary), 5 (secondary), and 7 (primary), i.e., Yamaguchi-SantaLucia's method, however only the symmetrical diacrylates of diols 5 and 7 were obtained quantitatively. In the other ten cases studied the reactions led to mixtures of symmetrical and unsymmetrical diesters that were difficult to separate. The mixed anhydrides did not react with the tertiary diols 4 (TADDOL) and 8. The average yield obtained in desired symmetrical diesters in the 12 cases studied was 54 %. The acylation of the diols with the anhydrides of the unsaturated acids, was found to be an excellent method, leading to the symmetrical unsaturated diesters of diols 3, 5, 7 as the only products of reaction, in an average yield of 83 %. Unfortunately, the method could not be applied to diesters derived from the tertiary diols 4 (TADDOL) and 8. The third method studied was the reaction between the alkoxides prepared with solutions of nBuLi in ether with the unsaturated acid chlorides at-50 °C, i.e., the Kaiser-Woodruff protocol. This was found to be the best of the three methods tested. The method was applied with success to the synthesis of the desired unsaturated diesters derived from diols 3-5, 7, and 8. The average yield of the 19 cases studied was 78 %. Copyright

Full text of DOI:10.1002/ejoc.201300130

FULL PAPER
DOI: 10.1002/ejoc.201300130
Synthesis of Unsaturated Diesters of Primary, Secondary and Tertiary Diols
Derived from Dimethyl (+)-Tartrate and Galactaric Acid
Jimena Scoccia,[a,b] Darío C. Gerbino,*[a,b] Victor F. Terraza,[a,b] Adriana E. Zúñiga,[a] and
Julio C. Podestá*[a,b]
Keywords: Synthetic methods / Symmetrical unsaturated diesters / Diols
The preparation of symmetrical unsaturated diesters of dioe
first was the reaction of mixed anhydrides, obtained from α,β-
unsaturated acids and benzoyl chloride, with diols 3 (pri-
acids, was found to be an excellent method, leading to the
symmetrical unsaturated diesters of diols 3, 5, 7 as the only
products of reaction, in an average yield of 83%. Unfortu-
mary), 5 (secondary), and 7 (primary), i.e., Yamaguchi–Santa- nately, the method could not be applied to diesters derived
Lucía’s method, however only the symmetrical diacrylates of
diols 5 and 7 were obtained quantitatively. In the other ten
cases studied the reactions led to mixtures of symmetrical
and unsymmetrical diesters that were difficult to separate.
The mixed anhydrides did not react with the tertiary diols
4 (TADDOL) and 8. The average yield obtained in desired
symmetrical diesters in the 12 cases studied was 54%. The
acylation of the diols with the anhydrides of the unsaturated
from the tertiary diols 4 (TADDOL) and 8. The third method
studied was the reaction between the alkoxides prepared
with solutions of nBuLi in ether with the unsaturated acid
chlorides at –50 °C, i.e., the Kaiser–Woodruff protocol. This
was found to be the best of the three methods tested. The
method was applied with success to the synthesis of the de-
sired unsaturated diesters derived from diols 3–5, 7, and 8.
The average yield of the 19 cases studied was 78%.
nient protocols for the synthesis of unsaturated diesters of
diols derived from dimethyl (R,R)-tartrate (1) and ga-
lactaric acid (2).
Introduction
Unsaturated diesters such as TADDOL dimethacrylate
have been synthesized and successfully employed in stereo-
selective cyclopolymerizations,[1,2] and also in the stereose-
lective synthesis of optically active macrodiolides through
cyclohydrostannation reactions.[3] We have recently reported
the synthesis of unsaturated diesters through esterification
of TADDOL with α,β-unsaturated carboxylic acid chlor-
ides, in the presence of n-butyllithium (nBuLi) in n-hex-
ane.[4] These reactions lead to mixtures of the correspond-
ing mono- and diesters, the latter in higher yields. The
average yields of pure unsaturated diesters using this
method were around 72%. It should be mentioned that al-
though the synthesis of TADDOL dimethacrylate (9) was
reported in 1997,[1] we were not able to find any reference
to other unsaturated diesters in the chemical literature other
than those of TADDOL reported by us.[4]
Results and Discussion
Diols 3,[5] 4,[6] 5,[7] 7,[8] and 8 (Scheme 1) used in the es-
terification reactions were obtained from commercially
available dimethyl (R,R)-tartrate (1) and galactaric acid (2)
following known procedures.
As shown in Scheme 1, diol 8 was obtained in excellent
yield from the previously reported diester 6 through ad-
dition of an excess of phenylmagnesium bromide in tetra-
hydrofuran (THF).
First, we studied the esterification of these diols by
means of Yamaguchi’s method.[9a] The approach involves
two steps: (a) the reaction of an aliphatic acid with 2,4,6-
trichlorobenzoyl chloride (Yamaguchi’s reagent) and isola-
tion of the corresponding mixed anhydride A, and (b) reac-
tion of the anhydride with an alcohol in the presence of the
nucleophilic catalyst 4-(dimethylamino)pyridine (DMAP)
to give ester B regioselectively (Scheme 2).
It has recently been reported that through the use of
benzoyl chloride instead of the highly hindered 2,4,6-tri-
chlorobenzoyl chloride it was also possible to obtain the
mixed esters in excellent yields.[9b] Taking into account the
To determine the scope of the cyclohydrostannation reac-
tions, we needed a new set of unsaturated systems. This
prompted us to carry out a study to establish more conve-
[a] Departmento de Química, Universidad Nacional del Sur,
Av. Alem 1253, 8000 Bahía Blanca, Argentina
Fax: +54-291-4595187
E-mail: jpodesta@criba.edu.ar
dgerbino@uns.edu.ar
Homepage: www.uns.edu.ar
[b] INQUISUR, CONICET Bahía Blanca,
Av. Alem 1253, 8000 Bahía Blanca, Argentina
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300130.
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Synthesis of Unsaturated Diester Diols
at room temperature. Subsequently, Et3N (12 mmol) fol-
lowed by 25% cat. DMAP and diol (1.5 mmol) were added.
As shown in Scheme 3, these reactions lead to the forma-
tion of mixtures of the symmetrical diesters I and the mixed
diesters II. Unfortunately, we were not able to separate
these mixtures either by column chromatography or by
crystallization.
Following the same protocol, mixed anhydrides C were
reacted with primary diol 7. The results obtained in these
reactions are shown in Scheme 4. In this case, using mixed
anhydride C derived from acrylic acid (9), we were able to
obtain quantitatively the desired symmetrical diester 21.
Unfortunately, using the mixed anhydrides C derived from
α,β-unsaturated carboxylic acids 10–12, mixtures of the
symmetrical (III) and mixed (IV) diesters were obtained
that, again, could not be separated.
It should be noted that neither in the reactions involving
diol 3 nor in those carried out with diol 7, did the mass
spectra of the reaction products show the presence of the
diols, indicating that the reactions had reached completion.
Under the same reaction conditions, we also studied the
esterification of the secondary diol 5 with the unsaturated
acids 9–12 following Yamaguchi–SantaLucia’s procedure
(Scheme 5).
As shown in Scheme 5, symmetrical diester 28 was ob-
tained quantitatively. However, the reactions of 5 with the
mixed anhydrides C derived from α,β-unsaturated carbox-
ylic acids 10–12 gave inseparable mixtures of the symmetri-
cal diesters V and the mixed diesters VI.
Scheme 1. Synthesis of diols 3–5, 7 and 8, starting from dimethyl
(R,R)-tartrate (1) or galactaric acid (2).
All attempts at the esterification of tertiary diols 4
(TADDOL) and
8 following Yamaguchi–SantaLucia’s
method failed, probably for steric reasons.
The results described above clearly indicate that Yamagu-
chi’s method is not suitable for the preparation of symmetri-
cal diesters of substituted acrylic acids. Most of the reac-
tions led to inseparable mixtures of symmetrical and mixed
diesters, and only the symmetrical unsaturated diesters 21
and 28 could be obtained in pure form. Furthermore, the
reactions only take place with primary and secondary diols
and not with tertiary alcohols.
Typically, acylation of alcohols is carried out by treat-
ment with acid anhydrides. Therefore, we prepared the sym-
metric anhydrides of acrylic (9) and methacrylic (10) ac-
ids,[10] and reacted them with diol 3 (Scheme 6). We found
that although the only products in both cases were the cor-
responding symmetrical unsaturated diesters 13 and 14,
respectively, they were formed in very low yields (less than
20%). In the case of unsaturated acids 11 and 12, no reac-
tion was observed and only starting material was recovered
(Scheme 6).
Scheme 2. Yamaguchi reaction.
When the same reactions were performed in the presence
of DMAP, a dramatic increase in the yields of the symmet-
previous report, we prepared a series of anhydrides through rical unsaturated diesters 13 and 14 was found. Taking into
the reaction between α,β-unsaturated acids and benzoyl account these results, we carried out the “one pot” esterifi-
chloride and then reaction of these mixed anhydrides with cation of diols 3, 5, and 7 with the symmetrical anhydrides
primary diol 3. The results are summarized in Scheme 3.
The α,β-unsaturated carboxylic acid (3 mmol) and benz-
derived from acids 9–12, according to Scheme 7.
As shown in Scheme 7, in all cases the reactions lead
oyl chloride (3 mmol) were dissolved in anhydrous THF exclusively to the symmetrical unsaturated diesters of both
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Scheme 3. Yamaguchi–SantaLucia esterification of diol 3.
Scheme 4. Yamaguchi–SantaLucía esterification of diol 7.
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Synthesis of Unsaturated Diester Diols
primary and secondary diols 3 and 5, respectively, in high
yields. Similarly, acylation of diol 8 using this method led
to the corresponding symmetrical unsaturated diesters 21–
24 in excellent yield (Scheme 7).
Unfortunately, we could not prepare the unsaturated di-
esters of tertiary alcohols 4 or 8 using this method. How-
ever, acylation of primary diols 3 and 7, and secondary diol
5, with in situ generated symmetric anhydrides in the pres-
ence of DMAP proceeded smoothly to give the correspond-
ing symmetrical unsaturated diesters in very high yields. It
should be noted that esters 21–24, obtained from primary
diol 5, were easily isolated because they precipitated in the
reaction medium.
In a previous paper,[4] we reported the esterification of
TADDOL with α,β-unsaturated carboxylic acid chlorides
in THF, using nBuLi in n-hexane to generate the corre-
sponding alkoxides, following the process developed by
Kaiser and Woodruff.[11a] The method leads, in all cases, to
mixtures of unsaturated di- and mono esters with the for-
mer being generated in higher proportion. These mixtures
were separated by column chromatography. We later found
that by performing the acylation of TADDOL with the
same reagents but working at –50 °C and using diethyl ether
as solvent, it was possible to obtain higher yields and, more
importantly, the desired unsaturated diesters were the only
products.[11b] The results obtained using this method for the
esterification of diols 3–5 are summarized in Scheme 8. The
results obtained in the esterifications of diols 7 and 8 are
summarized in Scheme 9.
Scheme 5. Yamaguchi–SantaLucia esterification of secondary diol
5.
As shown in Scheme 9, we were not able to obtain the
type VIII diester from 2,3-diphenylpropenoic acid (12) pri-
marily due to solubility problems.
It should be noted that, taking into account that the
solutions of nBuLi in diethyl ether decompose fairly rapid,
the alkoxylation reactions were carried out using freshly
prepared solutions of the reagent.
Taking into account the results included in Schemes 8
and 9, this method enables the synthesis of the desired sym-
metrical diesters of the diols derived from (+)-tartaric acid
(diesters of types I, V, and VII) and galactaric acid (type III
and VIII diesters) with very good to excellent yields.
A summary of the yields obtained using the three meth-
ods studied is enclosed in Table 1. For comparison pur-
poses, some results obtained previously in the esterification
with unsaturated acid chlorides of TADDOL (4) in THF at
0 °C using BuLi in n-hexane to generate the alkoxides have
also been included.[4,11b]
As shown in Table 1, Method B, Yamaguchi–Santa Lu-
cía’s protocol, is only useful for the synthesis of diacrylates
21 and 28 derived from diols 7 and 5, respectively, because
the reactions with the other substrates lead, in all cases, to
mixtures of symmetrical and unsymmetrical diesters, from
which we were not able to separate the desired symmetrical
unsaturated diesters in pure form.
Method C (i.e., acylation of the diol with the anhydride
of the unsaturated acid; Table 1) was found to be an excel-
lent method for the synthesis of unsaturated diesters of pri-
mary and secondary diols. Unfortunately, the approach
Scheme 6. Synthesis of symmetrical anhydrides.
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D. C. Gerbino, J. C. Podestá et al.
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Scheme 7. Synthesis of unsaturated diesters of diols 3, 5, and 7.
Scheme 8. Synthesis of symmetrical unsaturated diesters of diols 3–5.
could not be applied to the synthesis of diesters derived lowed by addition of the unsaturated acids chlorides) was
from tertiary diols, probably for steric reasons. The average found to be the best of the three methods tested. Thus, as
yield of the 12 cases studied was of 83%.
shown in Table 1, this method was applied with success to
the synthesis of the saturated diesters derived from primary
(3 and 7), secondary (5), and tertiary diols (4 and 8). The
average yield of the 19 cases studied was 78%.
On the other hand, Method D (Kaiser and Woodruff
protocol; i.e., preparation of the alkoxides at –50 °C using
freshly prepared solutions of nBuLi in diethyl ether fol-
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Synthesis of Unsaturated Diester Diols
SantaLucía’s method (Method B, Table 1), i.e., the reaction
of mixed anhydrides, obtained from α,β-unsaturated acids
and benzoyl chloride, with diols 3, 5, and 7. Although the
symmetrical diacrylates of diols 5 and 7 were obtained
quantitatively, in all the other cases the reactions led to mix-
tures of symmetrical and unsymmetrical diesters, which
were difficult to separate. Furthermore, the mixed anhy-
drides do not react with tertiary diols 4 and 8. Therefore,
from a practical point of view, this method is not conve-
nient in general for the synthesis of unsaturated symmetri-
cal diesters. (2) Acylation of the diol with the anhydride of
the unsaturated acid, Method C, was found to be an excel-
lent method for the synthesis of the desired symmetrical
unsaturated diesters of primary and secondary diols. How-
ever, also in this case, the anhydrides do not react with terti-
ary diols 4 or 8. (3) Finally, the preparation of the alkoxides
with nBuLi in diethyl ether followed by addition of the un-
saturated acid chloride, was found to be the best of the
three methods tested. Using this method, reactions of the
lithium alkoxides of diols 3–5, 7, and 8 with the unsaturated
acid chlorides led, in all cases, to the corresponding unsatu-
rated diesters in very good yields.
Scheme 9. Synthesis of symmetrical unsaturated diesters of diols 7
and 8.
Table 1. Synthesis of di-unsaturated esters of diols 3–5, 7, and 8.[a]
Compd. Method A[b] Method B[d] Method C[e] Method D[f]
Yield [%]
Yield [%]
Yield [%]
Yield [%]
13
14
15
16
21
22
23
24
28
29
30
31
39
40
41
42
43
44
45
62
–
67
–
81
67
31
30
100
83
27
18
100
62
27
24
–
–
–
–
–
–
–
85
81
79
70
73
92
95
91
77
82
86
83
–
–
–
–
–
–
–
62
67
76
73
81
78
76
73
71
77
79
75
87
82
86
88
88
81
79
–
Experimental Section
–
–
58
59
–
General: Reactions were monitored by thin-layer chromatography
on silica gel plates (60F-254) visualized under UV light and/or
using 5% phosphomolybdic acid in ethanol. Column chromatog-
raphy was performed over silica gel 60 (70–230 mesh). NMR spec-
tra were recorded at 25 °C with a Bruker Avance 300 multinuclear
instrument, using CDCl3 as solvent; chemical shifts (δ) are reported
in ppm with respect to TMS, 1H and 13C. IR spectra were recorded
with an FTIR Nicolet Nexus 470/670/870 spectrophotometer. Mass
spectra were obtained with a Finnigan MAT Incos 50 Galaxy Sys-
tem (DIP-MS) (EI) or a Finnigan MAT 900 (ESI) spectrometer;
high-resolution mass spectra were recorded with a Finnigan HSQ-
30 (HR-EIMS) or on a Finnigan MAT 900 (HR-ESI-MS) instru-
ment. The method of ionization is given in parentheses. Specific
rotations were measured with a Polar L-μP, IBZ Messtechnik in-
strument. Elemental analyses (C, H) were performed with a Carlo–
Erba Instrument. The melting points were determined with a
Kofler hot stage apparatus and are not corrected.
–
70[c]
74[c]
57[c]
73[c]
–
–
–
[a] Only the symmetrical unsaturated diesters are included. [b] Re-
action conditions: diol, unsaturated acid chloride, nBuLi (n-hex-
ane), THF. [c] See ref.[4]. [d] Yamaguchi–SantaLucia’s method;
most compounds could not be isolated pure; yields from the mass
spectra. [e] Reaction conditions: anhydride, Et3N, diol, THF. [f] Re-
action conditions: diol in Et2O, nBuLi (Et2O), unsaturated acid
chloride.
All reactions were carried out under an argon atmosphere. Solvents
were dried and distilled in accordance with standard procedure.
All the solvents and reagents were commercially available and of
analytical grade. Diols 3,[5] 4,[6] 5,[7] and 7,[8] were prepared by know
procedures. Compounds 39–42 have been reported previously.[4]
From a preparative point of view, it should be mentioned that sec-
ondary diol 5 was obtained stereoselectively by reduction of the
corresponding diketone with LiAlH4. Purification of the resulting
We have also tested the esterification of the primary and
secondary diols with acids 9–12 using the N,N-dicyclohex-
ylcarbodiimide (DCC)/4-(dimethylamino)pyridine (DMAP)
method.[12] The yields obtained were poor, and with tertiary
diols 4 and 8, no esterification products were obtained.
The same results were obtained when we attempted the
esterification of diols 3–5, 7, and 8 using Staudinger’s reac- diastereomeric mixture of diols afforded pure 5 after column
tion with benzylazide.[13]
chromatography.
{2,2,2Ј,2Ј-Tetramethyl[4,4Ј-bi(1,3-dioxolane)]-5,5Ј-diyl}bis(diphenyl-
methanol) (8): Under an argon atmosphere, magnesium turnings
Conclusions
(8.01 g, 0.33 mol) and some iodine crystals were introduced into a
dry flask, then 31.4 mL of a solution of bromobenzene (46.92 g,
0.30 mol) in anhydrous THF (120 mL) was added. As soon as the
reaction started, the remainder of the THF solution was added at
such a rate that gentle reflux was maintained. After complete ad-
To establish a general and convenient protocol for the
synthesis of unsaturated diesters of diols derived from di-
methyl (R,R)-tartrate (1) and galactaric acid (2), three
methods of esterification were studied. (1) Yamaguchi– dition, the reaction was heated to reflux for 1 h by heating with an
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D. C. Gerbino, J. C. Podestá et al.
FULL PAPER
oil bath. Finally, the reaction mixture was allowed to cool to room
temperature. To the Grignard solution was added with stirring and
cooling by an ice bath, a solution of diethyl (2,3:4,5-di-O-isoprop-
ylidene)galactarate (20.78 g, 0.06 mol) in anhydrous THF
(160 mL). The reaction mixture was heated at reflux for 2 h and
then cooled to room temperature. Aqueous saturated ammonium
chloride solution (500 mL) was carefully added, cooling the mix-
ture with an ice bath, whereupon diol 8 precipitated from the clear
solution. Filtration gave the product (33 g, 0.058 mol, 97%) as a
white solid; m.p. 233–235 °C. 1H NMR (300 MHz, CDCl3): δ =
1.26 (s, 6 H), 1.41 (s, 6 H), 3.86 (d, J = 5.1 Hz, 2 H), 3.90 (s, 2 H),
4.63 (d, J = 5.1 Hz, 2 H), 7.26–7.52 (m, 20 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 26.8, 78.3, 82.7, 110.1, 127.1, 127.2, 127.3,
H), 7.06–7.19 (m, 10 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
27.3, 75.2, 79.4, 110.9, 127.2, 128.0, 128.4, 131.1, 136.4, 164.7 ppm.
FTIR (KBr): ν = 3057 (w), 3030 (w), 2985 (m), 2940 (w), 1715 (s),
˜
1640 (m), 1615 (w), 1490 (w), 1455 (w), 1294 (w), 1155 (m), 760
(w), 701 (m) cm–1. HRMS (ESI): calcd. for C25H26O6Na [M +
Na]+ 445.1627; found 445.1622.
Synthesis of Unsaturated Diesters of Diols 3, 5 and 7 (Method C).
Typical Procedure for [(4S,5S)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl]-
bismethyl Bis(2-methylacrylate) (14): Under argon, methacrylic acid
(0.25 mL, 3 mmol), triethylamine (1.67 mL, 12 mmol), methacry-
loyl chloride (0.29 mL, 3 mmol), DMAP (0.046 g, 25 mol-%) and
diol 3 (0.24 g, 1.5 mmol) were suspended in anhydrous THF
(15 mL). The reaction mixture was stirred at r.t for 1 h (reaction
monitored by TLC). The reaction was quenched by the addition of
10% hydrochloric acid (50 mL). The solution was extracted with
ethyl acetate (2ϫ 60 mL), and the combined organic extracts were
washed with saturated sodium hydrogen carbonate (2ϫ 50 mL),
dried with anhydrous magnesium sulfate, filtered and the solvent
was removed under reduced pressure. The crude product was puri-
fied by column chromatography (silica gel 60; hexane/EtOAc,
127.6, 127.8, 128.0, 144.2, 144.3 ppm. FTIR (film): ν = 3605 (w),
˜
3560 (s), 3081 (w), 3052 (m), 2971 (w), 1885 (w), 1820 (w), 1700
(w), 1598 (m), 1512 (m), 1490 (w), 1453 (m), 1395 (m), 1350 (m),
1160 (m), 1110 (s), 1049 (s), 930 (m), 897 (m), 740 (s), 697 (s) cm–1.
HRMS (ESI): calcd. for C36H38O6Na [M + Na]+ 589.2566; found
589.2561.
Synthesis of Unsaturated Diesters of Diols 3, 4 and 7 (Method A).
Typical Procedure for [(4S,5S)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl]-
bismethanolyl Diacrylate (13): Under argon, a solution of 3 (1.00 g,
6.17 mmol) in anhydrous THF (27 mL) was cooled to 0 °C and
then a solution of nBuLi (1.5 m in n-hexane, 10 mL, 15 mmol) was
added slowly by using a syringe. The mixture was stirred at room
temp. for 30 min and cooled to 0 °C, and acryloyl chloride (1.5 mL,
18.5 mmol) was added slowly. A white precipitate (LiCl) formed
immediately. The mixture was heated to reflux for 1 h and then
stirred at room temp. overnight. The reaction was quenched by the
addition of aqueous saturated sodium hydrogen carbonate (90 mL),
the organic layer was separated and the aqueous layer was ex-
tracted with Et2O (3ϫ 30 mL). The combined organic extracts
were washed with water (20 mL) and brine (20 mL), and then dried
with anhydrous magnesium sulfate. The solvent was removed under
reduced pressure and the crude product was purified by column
chromatography (silica gel 60; hexane/EtOAc, 90:10) to give 13
(1.03 g, 3.81 mmol, 62%) as a colorless oil. [α]2D5 = –9.95 (c = 0.51,
90:10) to give 14 (0.36 g, 1.2 mmol, 81%) as a colorless oil; [α]2D5
=
–9.83 (c = 0.58, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 1.43 (s,
6 H), 1.96 (dd, 6 H), 4.14–4.16 (m, 2 H), 4.26–4.39 (m, 4 H), 5.60
(dd, J = 1.5 Hz, 2 H), 6.15 (dd, J = 1.5 Hz, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 18.2, 26.9, 63.8, 75.9, 110.1, 126.0, 135.8,
166.9 ppm. FTIR (Film): ν = 3025 (m), 2985 (w), 2917 (m), 1718
˜
(s), 1631 (m), 1493 (m), 1410 (m), 1169 (m), 1074 (m), 803 (m), 748
(s), 608 (s) cm–1. HRMS (ESI): calcd. for C15H22O6Na [M + Na]+
321.1314; found 321.1319.
Synthesis of Unsaturated Diesters of Diols 3, 4, 5, 7 and 8 (Method
D). Typical Procedure for [(4R,5R)-2,2-Dimethyl-1,3-dioxolane-4,5-
diyl]bis(diphenylmethanolyl) Diacrylate (39): Under argon, a solu-
tion of 4 (1.50 g, 3.21 mmol) in anhydrous Et2O (10 mL) was co-
oled to –50 °C, then a solution of nBuLi (1.3 m in Et2O, 5.9 mL,
7.70 mmol) was added slowly by using a syringe. The mixture was
kept at –50 °C for 1 h and subsequently acryloyl chloride (0.8 mL,
9.63 mmol) was added slowly. The mixture was warmed to room
temperature and stirred overnight. The reaction was quenched by
the addition of aqueous saturated sodium hydrogen carbonate
(25 mL), the organic layer was separated, and the aqueous layer
was extracted with Et2O (3ϫ 25 mL). The combined organic ex-
tracts were washed with water (15 mL) and brine (20 mL), and then
dried with anhydrous magnesium sulfate. The solvent was removed
under reduced pressure and the crude product was purified by col-
umn chromatography (silica gel 60; hexane/Et2O, 70:30) to give 39
(1.60 g, 2.79 mmol, 87%) as a white solid. The m.p. and spectro-
scopic characteristics were identical to those reported previously
for this compound.[4]
1
CHCl3). H NMR (300 MHz, CDCl3): δ = 1.34 (s, 3 H); 1.35 (s, 3
H); 4.04–4.33 (m, 6 H); 5.76–5.81 (m, J = 10.4, 1.6 Hz, 2 H), 6.02–
6.12 (m, J = 10.4, 17.3 Hz, 2 H), 6.32–6.39 (m, J = 17.3, 1.6 Hz, 2
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 26.6, 63.5, 75.7, 109.9,
127.6, 131.0, 165.2 ppm. FTIR (Film): ν = 1165 (m), 1075 (m), 884
˜
(m), 751 (s), 705 (s) cm–1. HRMS (ESI): calcd. for C13H18O6Na [M
+ Na]+ 293.1001; found 293.1007.
Synthesis of Unsaturated Diesters of Diols 3, 5 and 7 (Method B).
Typical Procedure for (1R,1ЈR)-[(4S,5S)-2,2-Dimethyl-1,3-dioxol-
ane-4,5-diyl]bis(phenylmethanolyl) Bisacrylate (28): Under argon,
acrylic acid (0.21 mL, 3 mmol), benzoyl chloride (0.35 mL,
3 mmol) and diol 5 (0.47 g, 1.5 mmol) were suspended in anhydrous
THF (15 mL). Triethylamine (1.67 mL, 12 mmol) was added slowly
followed by DMAP (0.046 g, 25 mol-%) and the reaction mixture
was stirred at 65 °C for 1 h (reaction monitored by TLC). The reac-
tion was quenched by the addition of 10% hydrochloric acid
(50 mL) and the solution was extracted with ethyl acetate (2ϫ
60 mL). The combined organic extracts were washed with saturated
sodium hydrogen carbonate (2ϫ 50 mL), and dried with anhydrous
magnesium sulfate. The solvent was removed under reduced pres-
sure and the crude product was purified by column chromatog-
raphy (alumina; hexane/EtOAc, 92:8) to give 28 (0.57 g, 1.35 mmol,
(2E,2ЈE)-[(4S,5S)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl]bismethanolyl
Bis(2-Methyl-3-phenylacrylate) (15): White solid; m.p. 45–48 °C;
1
[α]2D5 = –6.0 (c = 0.50, CHCl3). H NMR (300 MHz, CDCl3): δ =
1.50 (s, 6 H), 2.14 (s, 6 H), 4.21–4.32 (m, 2 H), 4.41–4.53 (m, 4 H),
7.31–7.40 (m, 10 H), 7.70–7.83 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 14.0, 27.0, 64.2, 76.2, 110.2, 127.8, 128.3, 128.4, 129.6,
135.7, 139.7, 168.2 ppm. FTIR (KBr): ν = 3092 (w), 3072 (w), 2990
˜
(m), 2945 (w), 1703 (s), 1580 (m), 1454 (m), 1370 (m), 1254 (s),
1111 (s), 771 (m), 698 (m) cm–1. HRMS (ESI): calcd. for
C27H30O6Na [M + Na]+ 450.2042; found 450.2035.
90%) as a white solid; m.p. 88–90 °C; [α]2D5 = –6.8 (c = 0.47,
(2E,2ЈE)-[(4S,5S)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl]bismethanolyl
1
CHCl3). H NMR (300 MHz, CDCl3): δ = 1.33 (s, 3 H), 1.35 (s, 3 Bis(2,3-diphenylacrylate) (16): White solid; m.p. 113–114 °C; [α]2D5
1
H), 4.11–4.14 (m, 2 H), 5.40–5.43 (m, 2 H), 5.67 (dd, J = 10.4 Hz, = 94 (c = 0.17, CHCl3). H NMR (300 MHz, CDCl3): δ = 1.33 (s,
2 H), 6.01 (dd, J = 10.4, 17.3 Hz, 2 H), 6.30 (dd, J = 17.3 Hz, 2
6 H), 4.03 (s, 2 H), 4.21–4.33 (m, 4 H), 7.10–7.42 (m, 20 H), 7.91
4424
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4418–4426

Synthesis of Unsaturated Diester Diols
(s, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 26.7, 63.9, 75.6,
109.8, 127.9, 128.2, 128.7, 129.2, 129.6, 130.7, 132.0, 134.4, 135.6,
(300 MHz, CDCl3): δ = 1.5 (s, 6 H), 2.1 (s, 6 H), 4.2–4.3 (m, 2 H),
4.4–4.5 (m, 4 H), 7.3–7.4 (m, 10 H), 7.7–7.8 (m, 2 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 14.1, 27.6, 75.6, 79.7, 111.1, 127.4,
141.0, 167.3 ppm. FTIR (KBr): ν = 3052 (m), 2921 (w), 2852 (w),
˜
1708 (s), 1642 (m), 1389 (s), 1356 (s), 1245 (m), 1172 (m), 755 (m), 128.2, 128.3, 128.4, 128.5, 128.6, 129.7, 135.78, 137.0, 167.5 ppm.
714 (s), 694 (s) cm–1. HRMS (ESI): calcd. for C37H34O6Na [M + FTIR (KBr): ν = 3092 (w), 3072 (w), 2990 (m), 2945 (w), 1703 (s),
˜
Na]+ 597.2253; found 597.2259.
1580 (m), 1454 (m), 1370 (m), 1254 (s), 1111 (s), 771 (m), 698
(m) cm–1. HRMS (ESI): calcd. for C39H38O6Na [M + Na]+
625.2566; found 625.2570.
{(4R,4ЈS,5S,5ЈR)-2,2,2Ј,2Ј-Tetramethyl-[4,4Ј-bi(1,3-dioxolane)]-5,5Ј-
diyl}bis(methylene) Diacrylate (21): White solid; m.p. 79–81 °C. H
1
(2E,2ЈE)-(1R,1ЈR)-[(4R,5R)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl]-
bis(phenylmethanolyl) Bis(2,3-diphenylacrylate) (31): White solid;
m.p. 112–114 °C. [α]2D5 = +9.5 (c = 0.85, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 1.12 (s, 6 H), 4.05 (s, 2 H), 5.51 (s, 2 H),
7.13–7.31 (m, 30 H), 7.70–7.84 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 27.0, 75.5, 79.1, 110.6, 127.3, 127.8, 128.2, 128.4,
128.7, 129.1, 129.8, 130. 27, 132.3, 134.6, 135.8, 137.0, 141.0,
NMR (300 MHz, CDCl3): δ = 1.31 (s, 6 H), 1.34 (s, 6 H), 3.74–
3.75 (m, 2 H), 4.12–4.17 (m, 4 H), 4.42–4.45 (m,2 H), 5.79 (dd, J
= 10.7, 1.4 Hz, 2 H), 6.06–6.15 (m, J = 10.7 Hz, 2 H), 6.36–6.41
(dd, J = 10.7, 1.4 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
26.9, 64.3, 78.3, 78.7, 110.5, 128.1, 131.2, 165.8 ppm. FTIR (KBr):
ν = 3030 (m), 2990 (w), 2931 (m), 1725 (s), 1628 (m), 1480 (m),
˜
1400 (m), 1162 (m), 1065 (m), 881 (m), 745 (s), 699 (s) cm–1. HRMS
(ESI): calcd. for C18H26O8Na [M + Na]+ 393.1526; found 393.1531.
166.7 ppm. FTIR (KBr): ν = 3060 (w), 3027 (w), 2962 (m), 2921
˜
(m), 1716 (s), 1495 (m), 1450 (m), 1238 (s), 1168 (s), 800 (w), 760
(w) cm–1. HRMS (ESI): calcd. for C49H42O6Na [M + Na]+
749.2879; found 749.2885.
{(4R,4ЈS,5S,5ЈR)-2,2,2Ј,2Ј-Tetramethyl-[4,4Ј-bi(1,3-dioxolane)]-5,5Ј-
diyl}bis(methylene) Bis(2-methylacrylate) (22): White solid; m.p.
142–144 °C. H NMR (300 MHz, CDCl3): δ = 1.35 (s, 6 H), 1.38
1
{(4S,4ЈR,5R,5ЈS)-2,2,2Ј,2Ј-Tetramethyl-[4,4Ј-bi(1,3-dioxolane)]-5,5Ј-
diyl}bis(diphenylmethanolyl) Diacrylate (43): White solid; m.p. 180–
182 °C. H NMR (300 MHz, CDCl3): δ = 1.47 (s, 12 H), 4.08 (d,
(s, 6 H), 1.94 (s, 6 H), 3.83–3.84 (m, 2 H), 4.19–4.24 (m, 4 H), 4.44–
4.49 (m, 2 H), 5.58 (s, 2 H), 6.14 (s, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 18.3, 26.9, 64.2, 78.3, 78.7, 110.4, 125.9, 136.0,
1
2 H), 5.74–5.86 (m, 4 H), 6.11–6.17 (m, 2 H), 6.25–6.35 (m, 2 H),
7.27–7.53 (m, 20 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 26.1,
27.5, 79.1, 86.4, 109.8, 126.8, 127.4, 128.1, 128.4, 129.2, 130.1,
167.1 ppm. FTIR (KBr): ν = 3033 (m), 2984 (w), 2921 (m), 1720
˜
(s), 1630 (m), 1490 (m), 1403 (m), 1168 (m), 1060 (m), 884 (m), 744
(s), 702 (s) cm–1. HRMS (ESI): calcd. for C20H30O8Na [M + Na]+
421.1839; found 421.1844.
130.2, 140.4, 143.5, 163.9 ppm. FTIR (KBr): ν = 3060 (w), 3031
˜
(w), 2974 (m), 2937 (m), 1744 (s), 1634 (m), 1495 (m), 1450 (m),
1266 (m), 1168 (s), 759 (s), 702 (s) cm–1. HRMS (ESI): calcd. for
C42H42O8Na [M + Na]+ 697.2778; found 697.2785.
(2E,2ЈE)-{(4R,4ЈS,5S,5ЈR)-2,2,2Ј,2Ј-Tetramethyl-[4,4Ј-bi(1,3-dioxol-
ane)]-5,5Ј-diyl}bis(methylene) Bis(2-methyl-3-phenylacrylate) (23):
White solid; m.p. 124–126 °C. 1H NMR (300 MHz, CDCl3): δ =
1.33 (s, 6 H), 1.36 (s, 6 H), 2.06 (s, 6 H), 3.83–3.84 (m, 2 H), 4.24–
4.27 (m, 4 H), 4.45–4.48 (m, 2 H), 7.29–7.33 (m, 10 H), 7.67 (s, 2
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.1, 27.1, 64.7, 78.4,
78.9, 110.5, 128.1, 128.4, 129.7, 135.7, 135.8, 139.5, 168.4 ppm.
{(4S,4ЈR,5R,5ЈS)-2,2,2Ј,2Ј-Tetramethyl-[4,4Ј-bi(1,3-dioxolane)]-5,5Ј-
diyl}bis(diphenylmethanolyl) Bis(2-methylacrylate) (44): White so-
1
lid; m.p. 191–193 °C. H NMR (300 MHz, CDCl3): δ = 0.77 (s, 6
H), 1.43 (s, 6 H), 1.98 (s, 6 H), 4.13 (m, 2 H), 5.52 (m, 2 H), 5.75
(m, 2 H), 6.13 (s, 2 H), 7.10–7.60 (m, 20 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 18.8, 26.1, 27.6, 78.9, 79.4, 86.5, 110.0,
125.3, 126.9, 127.4, 127.8, 128.4, 129.4, 138.3, 141.0, 144.0,
FTIR (KBr): ν = 3056 (m), 3027 (m), 2982 (s), 2937 (m), 1703 (s),
˜
1576 (w), 1491 (m), 1450 (m), 1258 (m), 1111 (m), 771 (s), 694
(s) cm–1. HRMS (ESI): calcd. for C32H38O8Na [M + Na]+
573.2465; found 573.2470.
165.4 ppm. FTIR (KBr): ν = 3064 (w), 3027 (w), 2982 (m), 2941
˜
(w), 1728 (s), 1634 (m), 1495 (m), 1450 (m), 1249 (m), 1151 (s), 767
(s), 698 (s) cm–1. HRMS (ESI): calcd. for C44H46O8Na [M + Na]+
725.3091; found 725.3098.
(2E,2ЈE)-{(4R,4ЈS,5S,5ЈR)-2,2,2Ј,2Ј-Tetramethyl-[4,4Ј-bi(1,3-dioxol-
ane)]-5,5Ј-diyl}bis(methylene) Bis(2,3-diphenylacrylate) (24): White
solid; m.p. 194–196 °C. H NMR (300 MHz, CDCl3): δ = 1.28 (s,
1
(2E,2ЈE)-{(4S,4ЈR,5R,5ЈS)-2,2,2Ј,2Ј-Tetramethyl-[4,4Ј-bi(1,3-dioxol-
ane)]-5,5Ј-diyl}bis(diphenylmethanolyl) Bis(2-methyl-3-phenylacry-
late) (45): White solid; m.p. 168–170 °C. 1H NMR (300 MHz,
CDCl3): δ = 1.13 (s, 6 H), 1.28 (s, 6 H), 2.14 (s, 6 H), 3.74 (d, 2
H), 4.49 (d, 2 H), 7.20–7.36 (m, 40 H), 7.75 (s, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.1, 26.8, 78.3, 82.8, 110.0, 127.1, 127.3,
127.6, 127.8, 128.0, 128.6, 129.2, 130.0, 135.1, 142.7, 144.2, 144.3,
6 H), 1.33 (s, 6 H), 3.70–3.72 (m, 2 H), 4.15–4.32 (m, 4 H), 4.51–
4.56 (m, 2 H), 7.08–7.37 (m, 20 H), 7.90 (s, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 26.8, 27.0, 64.3, 77.7, 78.6, 110.2, 127.9,
128.2, 128.6, 129.1, 129.8, 130.6, 132.2, 134.5, 135.8, 140.8,
167.5 ppm. FTIR (KBr): ν = 3064 (w), 3048 (m), 2986 (m), 2904
˜
(m), 1715 (s), 1625 (m), 1597 (w), 1495 (m), 1446 (m), 1245 (s),
1172 (s), 763 (s), 702 (s) cm–1. HRMS (ESI): calcd. for C42H42O8Na
[M + Na]+ 697.2778; found 697.2783.
164.9 ppm. FTIR (KBr): ν = 3051 (w), 3021 (w), 2960 (m), 2932
˜
(w), 1721 (s), 1625 (m), 1491 (m), 1440 (m), 1130 (m), 1055 (s), 751
(s), 698 (s) cm–1. HRMS (ESI): calcd. for C56H54O8Na [M + Na]+
877.3717; found 877.3723.
(1R,1ЈR)-[(4R,5R)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl]bis(phenyl-
methanolyl) Bis(2-methylacrylate) (29): White solid; m.p. 48–50 °C;
[α]2D5 = –6.1 (c = 0.49, CHCl3). H NMR (300 MHz, CDCl3): δ =
1
Supporting Information (see footnote on the first page of this arti-
1.28 (s, 6 H), 1.79 (s, 6 H), 4.04–4.10 (m, 2 H), 5.35–5.45 (m, 4 H),
6.04–6.08 (m, 2 H), 7.02–7.15 (m, 10 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 18.2, 27.4, 75.2, 79.5, 110.8, 125.9, 127.2, 128.4, 128.4,
1
cle): H and 13C NMR spectra of the new compounds.
136.0, 136.8, 166.0 ppm. FTIR (Film): ν = 3068 (w), 3035 (w), 2986
˜
Acknowledgments
(m), 2937 (w), 1719 (s), 1638 (m), 1621 (w), 1499 (w), 1454 (w),
1298 (w), 1160 (m), 763 (w), 702 (m) cm–1. HRMS (ESI): calcd. for
C27H30O6Na [M + Na]+ 473.1940; found 473.1946.
This work was supported by grants from Agencia Nacional de Pro-
moción Científica y Tecnológica (ANPCyT) (Capital Federal, Ar-
gentina/BID, Project No. 1728/OC-AR PICT), Consejo Nacional
de Investigaciones Científicas y Técnicas (CONICET) (Buenos
Aires, Argentina), and Universidad Nacional del Sur (Bahía
(2E,2ЈE)-(1R,1ЈS)-[(4R,5R)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl]bis-
(phenylmethanolyl) Bis(2-methyl-3-phenylacrylate) (30): White so-
lid; m.p. 45–48 °C; [α]2D5 = –6.0 (c = 0.50, CHCl3). 1H NMR
Eur. J. Org. Chem. 2013, 4418–4426
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4425

D. C. Gerbino, J. C. Podestá et al.
FULL PAPER
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knowledged. A postdoctoral fellowship to D. C. G. and a grant for
a short scientific visit to Germany to J. C. P. from the Alexander
von Humboldt Foundation are also gratefully acknowledged.
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Received: January 24, 2013
Published Online: May 23, 2013
4426
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4418–4426