Synthesis of mono- and diunsaturated esters of TADDOL

Article abstract of DOI:10.1055/s-2005-872123

The synthesis of fourteen new mono- and diesters of (4R,5R)-2,2-dimethyl- α,α,α′,α′-tetraphenyl-1,3-dioxolane-4, 5-dimethanol (TADDOL) is reported. This study shows that esterifications of TADDOL (1) with acid chlorides, derived from normal and α,β- unsat

Full text of DOI:10.1055/s-2005-872123

PAPER
2491
Synthesis of Mono- and Diunsaturated Esters of TADDOL
C. Gerbino,a,b Sandra D. Mandolesi,a Liliana C. Koll,*a,c Julio C. Podestá*a,c
S
ynthesis of Mono
a
-
a
nd Diuns
r
aturate
d
í
E
sters
o
of
T
A
D
DO
L
a
b
c
Universidad Nacional del Sur, Departamento de Química, Avenida Alem 1253, 8000 Bahía Blanca, Argentina
Comisión de Investigaciones Científicas (CIC), Provincia de Buenos Aires, Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad de Buenos Aires, Argentina
Fax +54(291)4595187; E-mail: jpodesta@uns.edu.ar
Received 28 February 2005
a 95% overall yield of a mixture of the diester 3 and mo-
noester 4, the former in much higher yield. It is notewor-
thy that Seebach used acetyl chloride under similar
conditions to obtain the corresponding monoester as the
Abstract: The synthesis of fourteen new mono- and diesters of
(4R,5R)-2,2-dimethyl-a,a,a¢,a¢-tetraphenyl-1,3-dioxolane-4,5-di-
methanol (TADDOL) is reported. This study shows that esterifica-
tions of TADDOL (1) with acid chlorides, derived from normal and
a,b-unsaturated carboxylic acids, in the presence of n-butyllithium only product (84%) of the reaction, even when using a
(BuLi) can lead to both mixtures of the corresponding mono- and
large excess of acetyl chloride.3
diesters, the latter in higher yield, and to just the diesters, depending
on the structure of the starting acids. These reactions take place in
most cases in good to excellent overall yields (57–95%). The reac-
tion between a dichloro derivative of TADDOL and the silver salts
of a,b-unsaturated acids also gives the corresponding unsaturated
diesters of TADDOL in good yields.
1. n-BuLi,THF
Ph Ph
–78 °C
O
O
2. n-PrCOCl
OH
OH
O
Ph
O
OH
Ph
Ph
Ph
Ph Ph
1
Key words: TADDOL, a,b-unsaturated esters, butyllithium, unsat-
urated acid silver salts
O
O
1. MeLi, Et2O, –78 °C
2. PhCOCl
2 (70%)
Ph
Ph
Ph
Unsaturated esters of (4R,5R)-2,2-dimethyl-a,a,a¢,a¢-
tetraphenyl-1,3-dioxolane-4,5-dimethanol (TADDOL),1
like TADDOL dimethacrylate (9), have been synthesized
and successfully employed in stereoselective cyclopoly-
merizations.2,3 In the course of our investigations, we con-
sidered it of interest to study some reactions of
unsaturated esters of TADDOL. However, although the
synthesis of diester 9 was reported in 19972 we were not
able to find any reference to other unsaturated esters of
TADDOL in the chemical literature. This prompted us to
carry out a study on the synthesis of this type of TADDOL
esters.
O
Ph
O
O
O
Ph
OH
O
O
O
Ph
Ph
Ph
+
Ph
Ph
Ph
O
O
O
3 (80%)
4 (15%)
Scheme 1
Taking into account these results, we investigated the syn-
thesis of unsaturated esters of TADDOL. Again, using the
DCC/DMAP method we were unable to obtain any prod-
ucts of esterification. However, through the reaction of
TADDOL (1) and BuLi with the chlorides of a,b-unsatur-
ated acids at 0 °C we succeeded in obtaining a series of
new unsaturated mono- and diesters of TADDOL 5–16, as
shown in Scheme 2, in good to excellent overall yields.
The reactions were carried out by mixing diol 1 in tetrahy-
drofuran with BuLi in hexane and then adding the acid
chlorides to the mixture at 0 °C; the reaction mixtures
were then heated at reflux temperature (refluxing times
are included in Table 1) and left at room temperature for
12 hours.
To begin with we studied the esterification of butanoic
and benzoic acids with TADDOL (1). All the attempts we
made to carry out the esterifications of these acids using
the N,N¢-dicyclohexylcarbodiimide (DCC)/4-(dimethyl-
amino)pyridine (DMAP) method failed.
We then used the reaction between TADDOL (1) and the
corresponding acyl chlorides in the presence of n-butyl-
lithium (BuLi) in hexane and methyllithium (MeLi) in di-
ethyl ether, according to Scheme 1. In this scheme, it can
be seen that whereas the reaction of diol 1 with butanoyl
chloride in the presence of BuLi at –78 °C, followed by
warming the reaction mixture to room temperature, leads
to monoester 2 as the only product in 70% yield, the reac-
tion of 1 with benzoyl chloride in the presence of MeLi at
–78 °C followed by warming to room temperature leads to
As shown in Scheme 2, these reactions can lead in some
cases to the diesters, e.g. 5 and 6, as the only products and
in other cases to a mixture of diesters (major product) and
monoesters (minor product), e.g. 7–16. Taking into ac-
count that in all cases a large excess of the corresponding
acid chloride was used, the formation of the mixtures
might be related to structural factors. The average overall
yield for all of the reactions was 78.5%. We found that
complete separation of the mixtures of mono- and di-
esters, as well as their purification, could be performed in
SYNTHESIS 2005, No. 15, pp 2491–2496
x
x.
x
x
.
2
0
0
5
Advanced online publication: 04.08.2005
DOI: 10.1055/s-2005-872123; Art ID: M01005SS
© Georg Thieme Verlag Stuttgart · New York

2492
D. C. Gerbino et al.
PAPER
R
O
R
O
surprise, instead of the expected TADDOL mixed acrylate
methacrylate diester, we obtained in both cases monoun-
saturated diester 17 as the only product in over 50% yield.
The formation of diester 17 could be explained in terms of
the monoester 10 reacting with BuLi in such a fashion that
1,4-addition to the monoester takes precedence over the
competing deprotonation of 10.
Ph Ph
O
1. n-BuLi, THF, 0 °C
OH
OH
O
Ph
O
R
Ph
Ph
O
2.
Ph
Ph Ph
COCl
O
O
1
1. n-BuLi, THF, 0 °C
Unsaturated diesters of TADDOL can also be obtained
from the reaction between silver salts of the unsaturated
acids and (4R,5R)-4,5-bis[chloro(diphenyl)methyl]-2,2-
dimethyl-1,3-dioxolane (18),4 as shown in Scheme 4.
Thus, the reaction between the silver salts of acrylic and
methacrylic acid and the dichloride 18 in toluene under re-
flux led to the corresponding unsaturated diesters 7 and 9,
respectively, as the only products in good yields (70 and
79%, respectively). One point of interest concerned the
synthesis of the starting dichloride 18. Following the tech-
nique given in the literature,4 i.e. the reaction of 1 and
thionyl chloride in the presence of triethylamine, dichlo-
ride 18 is obtained pure with an average yield of 50%. We
were able to improve the yield by halogenation of 1 using
phosphorus pentachloride in chloroform and in the pres-
ence of calcium carbonate. Using this method, the average
yield of 18 rose to 60%.
R2
R1
N°
R
%
2.
5
6
Me 65
Ph 57
COCl
R2
R2
R2
O
R1
O
R1
O
R1
O
O
O
OH
O
Ph
Ph
+
Ph
Ph
Ph
Ph
Ph
Ph
O
O
O
N°
R1
R2
%
N°
R1
H
R2
%
20
15
Me 10
7
H
H
H
70
74
8
H
9
Me
H
10
12
14
16
Me
H
H Ph
Ph Ph
H
11
13
15
Me 75
7
21
H
Ph
Ph
63
73
Ph
Scheme 2
R
R
Ph Ph
R
O
O
all cases by column chromatography using neutral alumi-
na as adsorbent. It should be noted that in several cases we
were not able to achieve good separation using silica gel.
Cl
Cl
COOAg
O
Ph
O
O
O
Ph
Ph
toluene, reflux
Ph
Ph Ph
O
O
18
Interestingly, in the case of methacryloyl chloride, when
we lowered the reaction temperature to –78 °C we exclu-
sively obtained the corresponding TADDOL monoester
10 in 65% yield, even when using an excess of acid chlo-
ride (Scheme 3). It is noteworthy that all attempts we
made to obtain exclusively the monoesters of the other un-
saturated acids under these reaction conditions failed.
N°
R
%
7
9
H
70
79
Me
Scheme 4
In order to obtain mixed unsaturated esters of TADDOL,
we attempted the reaction of monoester 10 in the presence
of BuLi with acryloyl chloride at 0 and –78 °C. To our
In summary, fourteen new mono- and diesters of TAD-
DOL have been synthesized. Esterification of TADDOL
(1) with acid chlorides derived from normal and a,b-un-
saturated carboxylic acids is performed at low tempera-
tures followed by warming to room temperature or reflux
of the reaction mixture, respectively. This reaction leads
both to mixtures of the corresponding mono- and diesters,
with the latter as the major product, and to just the di-
esters, depending on the structure of the starting acids. It
is also shown that by using this method, the esterification
of monounsaturated esters of TADDOL, which should
lead to mixed unsaturated esters, is not possible. This is
because nucleophilic addition of BuLi to the unsaturated
ester group in the starting TADDOL derivative takes
place before the attack of the unsaturated acid chloride, as
demonstrated by the formation of a mixed saturated–un-
saturated diester. The reaction between a dichloro deriva-
tive of TADDOL and the silver salts of a,b-unsaturated
acids gives the corresponding unsaturated diesters of
TADDOL in good yields.
1
1. n-BuLi /
THF / –78 °C
2.
COCl
1. n-BuLi / THF / 0 °C
O
HO
O
O
55%
Ph
Ph
Ph
Ph
O
Ph
2.
O
O
O
COCl
Ph
Ph
O
52%
Ph
1. n-BuLi / THF / –78 °C
O
O
10 (65%)
17
Scheme 3
Synthesis 2005, No. 15, 2491–2496 © Thieme Stuttgart · New York

PAPER
Synthesis of Mono- and Diunsaturated Esters of TADDOL
2493
trometer. Mass spectra were obtained using an ESI-TOF Bruker
BIOTOF II spectrometer at Santiago de Compostela University
(Spain). Melting points were determined on a Kofler hot stage and
are uncorrected. Specific rotations were measured with a Polar
L-mP, IBZ Messtechnik. All the solvents and reagents used were an-
alytical reagent grade.
Reaction conditions, yields, and some selected physical
and spectroscopic data for those compounds synthesized
are summarized in Table 1; 1H and 13C NMR spectroscop-
ic data are given in Table 2.
The NMR spectra were obtained using a Bruker ARX 300 instru-
ment. Infrared spectra were recorded with a Nicolet Nexus FT spec-
Table 1 Reaction Conditions, Yields, and Some Selected Physical and Spectroscopic Data for Compounds 2–17
25
Product Methoda Refluxing Yield Mp (°C)
[a]D
IR (KBr) (cm–1)
ESI-HRMS m/z [M + Na]+
Time (h)
(%)
b
2
3
4
5
6
7
A
70
158–160
135–137
185–187
170–172
181–183
160–162
–75.6
(c 0.48, CHCl3)
3491, 3060, 3055, 2966, 2928,
1739, 1495, 1448, 1172, 1079,
889, 757, 703
calcd for C35H36O5:
559.2460; found: 559.2455
b
b
A*
A*
B
80
15
65
57
70
–78.7
(c 0.40, CHCl3)
3056, 3029, 2978, 2928, 1724,
1600, 1499, 1445, 1102, 1067,
881, 714, 695
calcd for C45H38O6:
697.2566; found: 697.2561
–64.3
(c 0.42, CHCl3)
3584, 3056, 3021, 2978, 2956,
1732, 1596, 1491, 1448, 1106,
1071, 885, 761, 703
calcd for C38H34O5:
593.2307; found: 593.2299
1
–120.5
(c 0.44, CHCl3)
3056, 3029, 2959, 2928, 1720,
1650, 1495, 1448, 1130, 1071,
881, 726, 699
calcd for C41H42O6:
653.2879; found: 653.2874
B
2.5
4
–47.2
(c 0.43, CHCl3)
3056, 3025, 2959, 2932, 1716,
1631, 1495, 1445, 1110, 1072,
881, 761, 695
calcd for C51H46O6:
777.3192; found: 777.3187
C
–129.2
(c 0.42, CHCl3)
3056, 3025, 2986, 2932, 1728,
1631, 1499, 1405, 1172, 1079,
889, 747, 707
calcd for C37H34O6:
597.2256; found: 597.2248
7
8
B
B
1
1
70
20
144–146
166–168
–96.7
(c 0.30, CHCl3)
3584, 3056, 3029, 2932, 2858,
1735, 1634, 1495, 1448, 1176,
1071, 889, 749, 699
calcd for C34H32O5:
543.2147; found: 543.2142
c
c
9
C
4
79
–103.2
(c 1.0, CHCl3)
3055, 3052, 2990, 2928, 1728,
1638, 1495, 1448, 1149, 1071,
885, 753, 697
9
B
B
1
1
74
15
10
187–189
197–199
145–147
175–177
178–180
–97.4
(c 0.42, CHCl3)
3600, 3052, 3051, 2982, 2928,
1732, 1638, 1495, 1448, 1153,
1075, 881, 746, 703
calcd for C35H34O5:
557.2303; found: 557.2299
11
12
13
14
B
B
B
B
2
2
2
2
75
10
63
7
–92.8
(c 0.43, CHCl3)
3052, 3050, 2974, 2897, 1732,
1658, 1491, 1440, 1165, 1075,
893, 757, 691
calcd for C39H38O6:
625.2566; found: 625.2561
–69.2
(c 0.40, CHCl3)
3603, 3056, 3029, 2928, 2854,
1732, 1646, 1499, 1444, 1168,
1075, 893, 757, 699
calcd for C35H34O5:
557.2303; found: 557.2299
–42.0
(c 0.40, CHCl3)
3056, 3021, 2990, 2928, 1716,
1634, 1491, 1448, 1161, 1071,
885, 745, 699
calcd for C49H42O6:
749.2879; found: 749.2874
–48.0
(c 0.40, CHCl3)
3590, 3058, 3032, 2931, 2873,
1725, 1624, 1490, 1445, 1170,
1071, 891, 762, 699
calcd for C40H36O5:
619.2460; found: 619.2455
Synthesis 2005, No. 15, 2491–2496 © Thieme Stuttgart · New York

2494
D. C. Gerbino et al.
PAPER
Table 1 Reaction Conditions, Yields, and Some Selected Physical and Spectroscopic Data for Compounds 2–17 (continued)
Product Methoda Refluxing Yield Mp (°C)
[a]D
IR (KBr) (cm–1)
ESI-HRMS m/z [M + Na]+
25
Time (h)
(%)
15
16
17
B
B
1
73
205–207
214–216
56–58
–91.9
(c 0.41, CHCl3)
3052, 3025, 2988, 2935, 1716,
1623, 1495, 1448, 1168, 1075,
877, 761, 699
calcd for C61H50O6:
901.3504; found: 901.3499
1
21
–52.0
(c 0.40, CHCl3)
3588, 3052, 3025, 2928, 2868,
1724, 1623, 1495, 1448, 1168,
1083, 881, 761, 702
calcd for C46H40O5:
695.2772; found: 695.2768
B
A
2
b
55
52
–60.0
(c 0.36, CHCl3)
3095, 3056, 2959, 2858, 1736,
1631, 1495, 1448, 1367, 1169,
1065, 889, 803, 699
calcd for C42H46O6:
669.3192; found: 669.3187
a Method A: ratio of [TADDOL (1)/BuLi/acid chloride] 1.0:2.2:2.5; –78 °C; A*: ratio of [TADDOL (1)/MeLi/acid chloride] 1.0:2.2:2.5; –78
°C; B: ratio of [TADDOL (1)/BuLi/acid chloride] 1.0:2.4:3.0; 0 °C. C: ratio of (18/silver salt) 1.0:2.2; r.t.
b Conducted at r.t.
c See ref. 2.
Table 2 1H and 13C NMR Spectroscopic Data for Compounds 2–17
Product
1H NMR (CDCl3/TMS) d, J (Hz)
13C NMR (CDCl3/TMS) d
2
0.75 (t, 3 H, 3J = 7.6 Hz), 0.78 (s, 6 H), 1.35–1.52 (m, 2 H),
13.71, 18.21, 27.45, 27.37, 37.66, 77.85, 78.92, 81.32, 86.20,
2.13 (t, 2 H, 3J = 7.6 Hz), 2.74 (s, 1 H), 4.61 (d, 1 H, 3J = 7.2 110.03, 127.01, 127.30, 127.44, 127.67, 128.28, 128.93,
Hz), 5.44 (d, 1 H, 3J = 7.2 Hz), 7.15–7.34 (m, 20 H)
129.07, 129.83, 139.89, 143.17, 143.45, 147.29, 171.29
3
4
0.65 (s, 6 H), 5.94 (s, 2 H), 6.82–7.49 (m, 30 H)
27.65, 78.16, 88.29, 110.35, 127.11, 127.47, 127.55, 127.73,
127.96, 129.06, 129.88, 130.57, 131.09, 131.41, 132.44,
141.48, 144.24, 165.66
0.69 (s, 3 H), 0.78 (s, 3 H), 2.07 (s, 1 H), 4.83 (d, 1 H, 3J = 7.6 27.38, 27.65, 77.26, 78.99, 81.48, 86.97, 110.22, 127.11,
Hz), 5.77 (d, 1 H, 3J = 7.6 Hz), 6.99–7.40 (m, 23 H), 7.90–7.94 127.24, 127.40, 127.43, 127.51, 127.67, 128.23, 128.41,
(m, 2 H)
128.81, 129.21, 129.75, 130.07, 132.33, 132.64, 141.46,
143.16, 147.42, 164.76
5
6
7
8
0.57 (s, 6 H), 1.52 (s, 6 H), 1.61 (d, 6 H, 3J = 7.0 Hz), 5.76 (s, 11.21, 13.68, 26.41, 78.12, 86.40, 108.93, 125.73, 126.14,
2 H), 6.75 (q, 2 H, 3J = 7.0 Hz), 7.09–7.44 (m, 20 H)
126.20, 126.30, 126.88, 127.81, 129.87, 137.04, 140.45,
143.36, 165.78
0.62 (s, 6 H), 1.79 (s, 6 H), 5.88 (s, 2 H), 7.07–7.32 (m, 30 H), 13.44, 26.48, 78.27, 87.11, 109.16, 125.88, 126.33, 126.43,
7.57 (s, 2 H)
126.49, 126.93, 127.22, 127.40, 127.96, 128.95, 129.01,
134.58, 138.91, 140.32, 143.25, 166.70
1.48 (s, 6 H), 5.43 (s, 2 H), 5.68 (dd, 2 H, 3J = 10.1 Hz, 2J =
27.68, 78.50, 87.78, 109.81, 127.22, 127.74, 127.77, 127.99,
1.3 Hz), 5.98 (dd, 2 H, 3J = 17.2 Hz, 3J = 10.1 Hz), 6.24 (dd, 129.43, 130.37, 131.36, 131.40, 140.53, 143.99, 165.03
2 H, 3J = 17.2 Hz, 2J = 1.3 Hz), 7.12–7.36 (m, 20 H)
0.72 (s, 3 H), 0.73 (s, 3 H), 2.42 (s, 1 H), 4.70 (d, 1 H, 3J = 7.1 27.41, 27.54, 79.01, 81.46, 86.55, 110.22, 127.04, 127.29,
Hz), 5.55 (d, 1 H, 3J = 7.1 Hz), 5.62 (dd, 1 H, 3J = 10.3 Hz, 2J 127.46, 127.60, 127.63, 127.68, 128.34, 128.89, 129.16,
= 1.3 Hz), 5.99 (dd, 1 H, 3J = 17.2 Hz, 3J = 10.3 Hz), 6.22 (dd, 129.89, 130.09, 130.21, 140.47, 143.22, 143.66, 147.44,
1 H, 3J = 17.2 Hz, 2J = 1.3 Hz), 7.14–7.38 (m, 20 H)
164.05
9
0.61 (s, 6 H), 1.68 (s, 6 H), 5.45 (d, 2 H, 2J = 1.2 Hz), 5.72 (s, 18.73, 27.83, 78.03, 88.20, 110.43, 127.23, 127.32, 127.76,
2 H), 6.07 (d, 2 H, 2J = 1.2 Hz), 7.13–7.27 (m, 20 H)
127.79, 127.88, 129.31, 130.79, 138.41, 141.57, 144.55,
166.74
10
0.68 (s, 3 H), 0.71(s, 3 H), 1.85 (s, 3 H), 2.06 (bs, 1 H), 4.72 18.78, 27.38, 27.54, 78.97, 81.45, 86.45, 110.29, 124.71,
(d, 1 H, 3J = 7.1 Hz), 5.42 (d, 1 H, 2J = 1.5 Hz), 5.62 (d, 1 H, 127.03, 127.20, 127.26, 127.32, 127.60, 127.62, 127.66,
3J = 7.1 Hz), 6.02 (d, 1 H, 2J = 1.5 Hz), 7.11–7.38 (m, 20 H) 128.30, 128.66, 129.31, 129.91, 138.45, 141.30, 142.81,
144.24, 147.76, 165.41
11
0.75 (s, 6 H), 1.76 (dd, 6 H, 3J = 6.8 Hz, 4J = 1.5 Hz), 5.58 (s, 17.93, 27.31, 78.11, 87.01, 109.34, 125.75, 126.69, 127.16,
2 H), 5.76 (dd, 2 H, 3J = 13.7 Hz, 4J = 1.5 Hz), 6.84 (dq, 2 H, 127.25, 127.44, 128.98, 130.14, 140.56, 143.99, 144.14,
3J = 13.7 Hz, 3J = 6.8 Hz), 7.13–7.45 (m, 20 H)
164.78
Synthesis 2005, No. 15, 2491–2496 © Thieme Stuttgart · New York

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Synthesis of Mono- and Diunsaturated Esters of TADDOL
2495
Table 2 1H and 13C NMR Spectroscopic Data for Compounds 2–17 (continued)
Product
1H NMR (CDCl3/TMS) d, J (Hz)
13C NMR (CDCl3/TMS) d
12
0.81 (s, 6 H), 1.73 (dd, 3 H, 3J = 6.8 Hz, 4J = 1.2 Hz), 2.76 (s, 17.82, 27.28, 27.39, 78.76, 81.48, 86.06, 109.90, 124.17,
1 H), 4.77 (d, 1 H, 3J = 7.2 Hz), 5.65 (d, 1 H, 3J = 7.2 Hz), 5.73 126.85, 127.08, 127.13, 127.22, 127.40, 127.49, 128.07,
(dd, 1 H, 3J = 15.4 Hz, 4J = 1.2 Hz), 6.82 (m, 1 H, 3J = 15.4
Hz, 3J = 6.8 Hz), 7.12–7.46 (m, 20 H)
128.72, 128.92, 129.71, 140.23, 143.27, 143.50, 144.11,
147.19, 164.04
13
14
0.70 (s, 6 H), 5.63 (s, 2 H), 6.23 (d, 2 H, 3J = 16.0 Hz), 6.97– 27.76, 78.48, 87.92, 110.02, 120.87, 127.21, 127.68, 127.77,
7.33 (m, 30 H), 7.43 (d, 2 H, 3J = 16.0 Hz)
127.95, 128.46, 128.99, 129.45, 130.50, 130.67, 134.38,
141.13, 144.45, 145.23, 165.97
0.76 (s, 3 H), 0.81 (s, 3 H), 2.62 (s, 1 H), 4.73 (d, 1 H, 3J = 7.2 27.39, 27.58, 78.96, 81.59, 86.58, 110.02, 119.71, 127.06,
Hz), 5.62 (d, 1 H, 3J = 7.2 Hz), 6.23 (d, 1 H, 3J = 16.2 Hz), 7.18 127.12, 127.37, 127.41, 127.45, 127.59, 127.68, 128.27,
(d, 1 H, 3J = 16.2 Hz), 7.10–7.41 (m, 25 H)
128.28, 128.89, 128.96, 134.58, 140.44, 143.67, 143.78,
144.47, 147.03, 164.83
15
16
0.84 (s, 6 H), 6.31 (s, 2 H), 7.02–7.65 (m, 40 H), 8.16 (s, 2 H) 27.82, 78.54, 89.01, 110.88, 126.80, 127.49, 127.60, 127.64,
127.99, 128.44, 129.37, 129.90, 130.74, 130.95, 134.41,
135.76, 141.29, 141.90, 144.07, 167.33
0.64 (s, 3 H), 0.66 (s, 3 H), 2.25 (s, 1 H), 4.53 (d, 1 H, 3J = 7.2 27.46, 78.98, 81.68, 86.92, 110.45, 126.86, 127.24, 127.33,
Hz), 5.63 (d, 1 H, 3J = 7.2 Hz), 6.89–7.36 (m, 30 H), 7.68 (s, 127.38, 127.51, 127.65, 127.75, 128.24, 128.33, 128.84,
1 H)
129.02, 129.20, 129.43, 129.74, 129.81, 130.87, 134.24,
134.76, 136.83, 140.24, 141.22, 142.62, 144.15, 147.92,
165.55
17
0.72 (s, 3 H), 0.82 (t, 3 H, 3J = 6.9 Hz), 0.88 (s, 3 H), 0.92 (t, 14.22, 16.36, 22.72, 26.73, 27.15, 27.41, 32.18, 33.10, 39.75,
3 H, 3J = 7.1 Hz), 1.04–1.51 (m, 8 H), 2.42 (m, 1 H), 5.05 (d, 78.62, 79.69, 86.81, 87.47, 108.69, 126.88, 126.98, 127.10,
1 H, 3J = 7.7 Hz), 5.06 (d, 1 H, 3J = 7.7 Hz), 5.72 (dd, 1 H, 3J = 127.42, 127.75, 127.83, 129.35, 129.79, 129.88, 130.03,
10.3 Hz, 2J = 1.5 Hz), 6.09 (dd, 1 H, 3J = 17.1 Hz, 3J = 10.3
130.16, 131.28, 138.34, 139.75, 142.13, 143.06, 164.27,
Hz), 6.28 (dd, 1 H, 3J = 17.1 Hz, 2J = 1.5 Hz), 7.11–7.43 (m, 174.56
20 H)
TADDOL Monobutanoate (2); Typical Procedure (Method A):
A solution of TADDOL (1; 0.93 g, 2.0 mmol) in dry THF (8.5 mL)
was treated with a 1 M solution of n-BuLi in hexane (4.4 mL, 4.4
mmol) at –78 °C for 1 h. Butanoyl chloride (0.53 g, 5.0 mmol) was
then added, and the mixture was warmed to r.t. and stirred over-
night. After hydrolysis with sat. NaHCO3 (ca. 45 mL), the organic
layer was separated and the aqueous layer was extracted with Et2O
(3 × 12 mL). The combined organic extracts were washed once with
H2O and sat. NaCl, and then dried (anhyd MgSO4). The solvent was
removed under reduced pressure and the crude product was purified
by column chromatography (silica gel 60, Et2O–hexane 10:90) to
give 2 as white crystals; yield: 0.75 g (70%).
(75%), and 12 as white crystals (Et2O–hexane 7:93); yield: 0.17 g
(10%).
TADDOL Diacrylate (7); Typical Procedure (Method C):
To a solution of 18 (2.02 g, 4.0 mmol) in dry toluene (40 mL) was
added acrylic acid silver salt (1.50 g, 8.80 mmol). The preparation
was carried out at r.t. under a nitrogen atmosphere and with magnet-
ic stirring. The mixture was refluxed for 4 h and in the absence of
light. The resulting AgCl was removed by filtration using a porous
plate and washing the precipitate once with dry toluene. The filtrate
was mixed with activated charcoal and then warmed up briefly in a
rotatory evaporator. The solvent was distilled off under reduced
pressure, and recrystallization (dry hexane) of the resulting solid
gave 7 as white crystals; yield: 1.61 g (70%).
TADDOL Di-(E)-but-2-enoate (11); Typical Procedure (Meth-
od B):
A solution of TADDOL (1; 1.50 g, 3.2 mmol) in dry THF (14 mL)
was cooled to 0 °C. Then, a 1.4 M solution of n-BuLi in hexane (5.5
mL, 7.68 mmol) was added slowly with a syringe. The mixture was
stirred at r.t. for 30 min and cooled to 0 °C, and (E)-but-2-enoyl
chloride (1.0 g, 0.9 mL, 9.6 mmol) was added slowly. A white pre-
cipitate (LiCl) formed immediately. The mixture was refluxed for 2
h and then stirred at r.t. overnight. After cooling to 0 °C, the reaction
was quenched by the addition of sat. aq NaHCO3 (ca. 50 mL). The
organic layer was separated and the aqueous layer was extracted
with Et2O (3 × ca. 15 mL). The combined organic extracts were
washed once with H2O and sat. NaCl, and then dried (anhyd
MgSO4). The solvent was removed under reduced pressure and the
crude product was purified by column chromatography (silica gel
60, Et2O–hexane 5:95) to give 11 as white crystals; yield: 1.45 g
(4R,5R)-4,5-Bis[chloro(diphenyl)methyl]-2,2-dimethyl-1,3-di-
oxolane (18)
A solution of TADDOL (1; 6.0 g, 12.9 mmol), dry CHCl3 (66 mL),
and CaCO3 (2.63 g, 26 mmol) was cooled to 0 °C under a nitrogen
atmosphere and with magnetic stirring. Then, PCl5 (7.14 g, 34
mmol) was added and the mixture stirred at r.t. overnight. A solu-
tion of sat. NaHCO3 (ca. 100 mL) previously cooled to 0 °C was
added to the mixture, which was then stirred vigorously until CO2
evolution had ceased. The organic layer was separated, washed with
H2O and sat. NaCl, and then dried (MgSO4). The filtrate was mixed
with activated charcoal and then warmed up briefly in a rotatory
evaporator. The solvent was distilled off under reduced pressure,
and recrystallization (dry hexane) of the resulting solid gave 18 as
white crystals; yield: 3.84 g (60%).
Synthesis 2005, No. 15, 2491–2496 © Thieme Stuttgart · New York

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D. C. Gerbino et al.
PAPER
Acknowledgment
References
This work was supported by CONICET (Capital Federal, Argenti-
na) and Universidad Nacional del Sur (Bahía Blanca, Argentina).
We acknowledge a fellowship awarded to D.C.G. from CIC
(Buenos Aires Province, Argentina). We are thankful to Prof A.
Mouriño, Santiago de Compostela University (Spain), for his help
in connection with the mass spectra. A travel grant given to J.C.P.
from the Alexander von Humboldt Foundation is also gratefully
acknowledged.
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Synthesis 2005, No. 15, 2491–2496 © Thieme Stuttgart · New York