On the origin of changes in topicity observed in Diels-Alder reactions catalyzed by Ti-TADDOLates

Article abstract of DOI:10.1016/S0957-4166(00)00464-X

New C₂ symmetric TADDOLs containing different groups at the 2-position of the dioxolane ring have been prepared. The Ti catalysts derived from these have been studied in the Diels-Alder reaction of cyclopentadiene and (E)-2-butenoyl-1,3-oxazolidin-2-one. Substituents at the C-2 position of the dioxolane ring can play an important role in determining the selectivity as well as the nature of the major isomer. This effect is more important for TADDOLs containing bulky aromatic groups such as 3,5-dimethylphenyl- or 1-naphthyl at the α-positions. Experimental evidence supports the hypothesis that π-π interactions between aromatic groups at the C-2 and the ones at the α-positions are critical in this respect.

Full text of DOI:10.1016/S0957-4166(00)00464-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 4885–4893
On the origin of changes in topicity observed in Diels–Alder
reactions catalyzed by Ti–TADDOLates
Bele´n Altava, M. Isabel Burguete, Eduardo Garc´ıa-Verdugo, Santiago V. Luis,*
Juan F. Miravet and Mar´ıa J. Vicent
Department of Inorganic and Organic Chemistry, ESTCE, University Jaume I, E-12080 Castello´n, Spain
Received 19 October 2000; accepted 17 November 2000
Abstract
New C2 symmetric TADDOLs containing different groups at the 2-position of the dioxolane ring have
been prepared. The Ti catalysts derived from these have been studied in the Diels–Alder reaction of
cyclopentadiene and (E)-2-butenoyl-1,3-oxazolidin-2-one. Substituents at the C-2 position of the diox-
olane ring can play an important role in determining the selectivity as well as the nature of the major
isomer. This effect is more important for TADDOLs containing bulky aromatic groups such as
3,5-dimethylphenyl- or 1-naphthyl at the a-positions. Experimental evidence supports the hypothesis that
p–p interactions between aromatic groups at the C-2 and the ones at the a-positions are critical in this
respect. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
TADDOLs (a,a%-tetraaryl-1,3-dioxolane-4,5-dimethanols) represent a very useful class of
chiral ligands that have been widely used for the preparation of enantioselective catalysts and
reagents and for other applications.1 They can be easily prepared in both enantiomeric forms
from simple materials and, moreover, their general structure 2 presents a high potential for
molecular diversity through changes in the nature of R, R%, Ar, M, X and Y groups, and this
allows for a better tuning of the desired properties (Scheme 1).
Most efforts have been dedicated, in general, to understand the role played by changes in the
nature of the Ar groups on the final properties of metal TADDOLates such as 3.2 Nevertheless,
much less is known about the exact role played by the R and R% substituents at the 2-position
of the dioxolane ring. In most instances, their role has been mainly associated with the presence
or absence of a C2 symmetry, which is usually considered as an advantageous feature for
enantioselective catalysts.3 However, experimental evidence has been gathered that shows that
* Corresponding author. Tel: +34 964 728239; fax: +34 964 788214; e-mail: luiss@mail.uji.es
0957-4166/00/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00464-X

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Scheme 1.
this is an oversimplification. In recent years we have been involved in the preparation and study
of supported TADDOL derivatives that could be useful for practical applications.4–6 In this
respect, the 2-position of the dioxolane ring is always key for linking to the heterogeneous
support. Accordingly, a better knowledge of the implications that structural modifications in this
position have on their efficiency is required for a better design of the supported systems.
Here we present experimental evidence that aids rationalizing how, in some instances,
substituents at the C-2 position can have a decisive influence on the extent and direction of the
asymmetric induction in the benchmark Diels–Alder reaction of cyclopentadiene and (E)-2-
butenoyl-1,3-oxazolidin-2-one (Scheme 2).
Scheme 2.
2. Results and discussion
Results gathered in Table 1 clearly reveal that the presence of C2 symmetry in the structure
of TADDOLs 2 (R=R%) is not always reflected in higher enantioselectivities. Very large ee
values have been obtained for the simple dialkyl derivative 2a (R=R%=CH3) (see entry 1), but
a complete lack of enantioselectivity was observed for the diphenyl derivative 2c (R=R%=Ph)
(see entry 3).2a
On the other hand, results from different groups have shown that the presence of very bulky
aryl groups at the a positions, like 3,5-dimethylphenyl or 1-naphthyl, but not 2-naphthyl, is
usually accompanied by a reversal in the topicity of the major isomer.1,2 In those cases, the
(2R,3S)-endo-isomer 7 is obtained instead of the normal (2S,3R)-endo-isomer 6 (compare, for
instance, entries 2 and 6). Preliminary Molecular Mechanics calculations suggest that p–p
stacking interactions between one aromatic ring at the 2-position of the dioxolane ring and one
3,5-dimethylphenyl group could be the origin of this phenomenon. The presence of such p–p
interactions seems to decrease the relative energy of the intermediates leading to the formation
of the abnormal (2R,3S)-endo-isomer.2a
The result shown in entry 1 is in good agreement with this hypothesis. In this case, the
absence of aromatic groups at the 2-position leads to the formation of the normal (2S,3R)-iso-

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4887
Table 1
Results obtained in the Diels–Alder reaction of 4 and 5 catalyzed by Ti–TADDOLates 3 in toluene at 0°C in
24 h
Entry
Catalyst
R
R%
Ar
Yield (%)a
endo/exoa
Ee (%)b
1
2
3
4
5
6
7
8
9
10
3a
3b
3c
3d
3e
3f
3g
3h
3i
CH3
Ph
Ph
CH2Ph
(CH2)2Ph
Ph
CH2Ph
(CH2)2Ph
(CH2)2Ph
(CH2)2Ph
CH3
H
Ph
CH2Ph
(CH2)2Ph
H
CH2Ph
(CH2)2Ph
(CH2)2Ph
(CH2)2Ph
3,5-(CH3)2C6H3
3,5-(CH3)2C6H3
3,5-(CH3)2C6H3
3,5-(CH3)2C6H3
3,5-(CH3)2C6H3
2-Naphthyl
2-Naphthyl
2-Naphthyl
Ph
95
100
22
96
100
96
99
97
100
91
89:11
70:30
80:20
75:25
79:21
74:26
83:17
87:13
83:17
87:13
82 (2S,3R)c
24 (2R,3S)d
0d
61 (2R,3S)
33 (2S,3R)
61 (2S,3R)d
65 (2S,3R)
79 (2S,3R)
30 (2S,3R)
41 (2S,3R)
3j
4-MeOC6H4
1
a Determined by H NMR.
1
b Determined by H NMR in the presence of Eu(hfc)3.
c Data from Ref. 1d.
d Data from Ref. 2a.
mer as the major product. The substitution of alkyl groups by phenyl groups at C-2 seems to
be always accompanied by an increase in the amount of the (2R,3S)-isomer formed (entries 2
and 3) that leads to a lack of selectivity for catalyst 3c and to a reversal of topicity when 3b is
used.
In order to obtain additional experimental evidence regarding this general hypothesis, a series
of new TADDOL derivatives was prepared as shown in Scheme 3. Those compounds (2c–2e,
2g–2j) were designed to maintain a C2 symmetry and to have aromatic rings separated from the
ketalic carbon atom by a variable number of methylene groups (n=0–2). As the aryl groups at
the a and a% positions we initially selected the 2-naphthyl 2g–2h and 3,5-dimethylphenyl groups
2c–2e. Ti–TADDOLates containing the first one are described to give always the normal
(2R,3S)-isomer with high enantioselectivities, whereas with the second group the abnormal
(2S,3R)-isomer is often obtained.
Scheme 3.

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The desired TADDOLs were prepared in the usual way starting from ketones 10–12 as shown
in Scheme 3. Compounds 10 and 11 are commercially available, and ketone 12 was obtained, in
good yields, by catalytic hydrogenation of dibenzylideneacetone. Ketalization of 10 and 11 to
afford compounds 13 and 14 was difficult to be accomplished efficiently (60 and 29% yields,
respectively). This might be expected from electronic considerations for 10, but it is more
difficult to rationalize for ketone 11. Initial Molecular Mechanics and Molecular Dynamics
calculations suggest that the preferred conformations both for 11 and for its hemiketal result
from close p–p intramolecular interactions. This is reflected in the existence of a strong steric
hindrance for the attack to the carbonylic or hemiketalic carbon, making ketal formation
difficult.
The corresponding Ti–TADDOLates were obtained by treatment of TADDOLs 2 with
Ti(OPri)2Cl2 in toluene and were used as catalysts for the Diels–Alder reaction between
cyclopentadiene and (E)-2-butenoyl-1,3-oxazolidin-2-one (Scheme 2).2,4 If p–p interactions
between one phenyl group bound to C-2 and one 3,5-dimethylphenyl group at the a position
play a key role to explain the abnormal enantioselectivity behavior of catalysts such as 3b, it was
to be expected that increasing the separation between the ketalic carbon and the phenyl group
(catalysts 3c–3e) would have a large influence on the selectivity observed. This influence was
expected to be much lower for catalysts such as 3g and 3h containing 2-naphthyl groups at the
a and a% positions. This situation was clearly observed in the experimental results, as shown in
Table 1.
If the TADDOLs containing 3,5-dimethylphenyl groups (catalysts 3a–3e) are considered, it
can be seen that the normal (2S,3R)-isomer is obtained with very good enantioselectivity (82%
ee) when the C2 symmetric TADDOL 2a having alkyl groups at C-2 is used. However, a
complete lack of enantioselectivity is observed for catalyst 3c for which phenyl groups have
substituted both methyl groups at C-2. This indicates that the formation of the otherwise minor
isomer (2R,3S) is now as favorable as that of the (2S,3R)-isomer as a result of the presence of
those phenyl groups. The change in topicity is even more dramatic when the catalyst derived
from TADDOL 2d (n=1) is used. In this case a 61% ee is observed, (2R,3S) being the preferred
isomer. A further increase in the length of the aliphatic spacer linking the ketalic carbon and the
phenyl group seems to hinder the p–p interactions of the phenyl group and one of the
3,5-dimethylphenyl substituents, as could be expected. As a consequence, the formation of the
isomer with the reversal topicity is much less favorable and the normal (2S,3R)-isomer is again
obtained as the major product, with 33% ee.
As it was predicted, TADDOLs having 2-naphthyl substituents at the a and a% positions are
not very much affected by the changes in the length of the methylenic spacer between C-2 and
the phenyl group. The normal (2S,3R)-isomer is always obtained as the major product with
good enantioselectivities. For TADDOL 2h (R=R%=Ph(CH2)2, Ar=2-naphthyl) the enantio-
selectivity found was almost as good (79% ee) as that reported for 2a (82% ee). When other aryl
groups such as phenyl or 4-methoxyphenyl were introduced at the a and a% positions, instead of
3,5-dimethylphenyl or 2-naphthyl, results were similar to those found for the latter, but
selectivities were lower as has been usually described for this kind of structural changes (see
entries 9 and 10 in Table 1).
The crucial role played by the aromatic rings in the TADDOL-derived catalysts can also be
exemplified by the results obtained with TADDOL 2k containing aliphatic substituents at a and
a% positions. This compound was synthesized in good yield by reaction of the Grignard reagent
prepared from 1,4-dibromobutane with the ketal 15. When the corresponding Ti–TADDOLate
was assayed for the Diels–Alder reaction in Scheme 2 (catalyst:crotonate ratio 1:10, 0°C, 24 h)

B. Alta6a et al. / Tetrahedron: Asymmetry 11 (2000) 4885–4893
4889
much lower activities (63% after 24 hours) and selectivities [endo/exo: 3.53, ee: 13%, major endo
isomer: (2S,3R)] were observed when compared to those obtained with catalysts obtained from
TADDOLs containing aryl groups at the a positions (Scheme 4).7,8
Scheme 4.
In conclusion, the present results support the hypothesis, suggested by previous Molecular
Mechanic calculations, that p–p interactions play an important role in determining the topicity
changes observed in Diels–Alder reactions catalyzed by Ti–TADDOLates. The occurrence of
such interactions favor the formation of the unusual (2R,3S)-isomer. Those changes are only
observed for very rigid TADDOL derivatives containing very bulky aryl groups (3,5-
dimethylphenyl or 1-naphthyl) at the a positions. For those systems, the introduction of
aliphatic spacers between the ketalic carbon atom and the phenyl group provide a way for
regulating the above-mentioned p–p interactions. For a given length of the linker (n=2), the
interaction between the aromatic group in the substituent at C-2 and the aryl group at the a
position starts to be hindered and the normal topicity is again observed. More work is needed
to fully understand the exact mechanisms for this kind of Ti–TADDOLate catalyzed reactions,
but results in this work allow to rationalize previous observations on this subject with
homogeneous and supported TADDOL derivatives.
3. Experimental
3.1. Synthesis of 1,5-diphenyl-3-pentanone 12
Benzylideneacetone (6.94 g, 0.03 mol) was dissolved in EtOH (100 mL) in a 600 mL Parr
reactor and 5% Pd/C (0.2 g) was added. Hydrogenation was carried out at 8.3 bar (initial
pressure). When the pressure dropped to 4.2 bar, the reactor was opened, the mixture of
reaction was filtered through Celite and the resulting solution was vacuum evaporated to give 12
as colorless oil of high purity (6.72 g, 96.8%). IR (KBr, cm−1): 3085, 3062, 2927, 2860, 1712,
1
1603, 1495, 1459, 1179, 1092, 747, 698. H NMR (CDCl3, l): 2.75 (m, 4H), 2.96 (m, 4H), 7.3
(m, 10H). 13C NMR (CDCl3, l): 29.8, 44.6, 125.9, 128.4, 128.5, 141.0, 209.2. Anal. calc. for
C17H18O: C, 85.7; H, 7.6%. Found: C, 85.7; H, 7.4%.
3.2. Synthesis of (4R,5R)-2,2-diphenyl-1,3-dioxolane-4,5-dicarboxylic acid dimethyl ester 13
Benzophenone 10 (4 g, 23 mmol) was dissolved in MeOH (12 mL) and trimethyl orthoformate
(5 mL, 48.6 mmol) and a catalytic amount of p-toluenesulfonic acid (PTSA) were added. The
mixture was heated under reflux until a white solid was formed. After cooling, a solution of 1N
NaOH (20 mL) was added. The resulting solution was extracted with diethyl ether (30 mL, 3×),
and the organic phase was washed with brine and water, dried over MgSO4 and evaporated

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under vacuum to obtain a white solid. This solid (4.05 g, 18.2 mmol) was dissolved in dry
benzene (100 mL) (CAUTION: the reaction must be carried out in a well-ventilated hood) and
then (R,R)-dimethyl tartrate (3.8 g, 21 mmol) and a catalytic amount of PTSA were added.
Distillation of the benzene/methanol azeotrope was carried out at 60°C, and, after cooling, Et3N
was added to neutralize the acid. The solvent was evaporated under vacuum to give a red oil.
The crude product was purified by crystallization from hexane to give a white solid (3.74 g, 60%
yield). Mp 80–81°C; [h]20=+54.2 (c 0.964, CHCl3). IR (KBr, cm−1): 3060, 2945, 1750, 1590,
1
1250, 1120, 760, 705. H NMR (CDCl3, l): 3.62 (s, 6H), 4.39 (s, 2H), 7.13–7.50 (m, 10H). 13C
NMR (CDCl3, l): 52.8, 76.9, 126.2, 127.9, 128.1, 128.8, 130.1, 132.6, 137.9, 140.0, 169.4, 196.5.
Anal. calc. for C19H18O6: C, 66.6; H, 5.3%. Found: C, 66.7 H, 5.2%.
3.3. Synthesis of (4R,5R)-2,2-Dibenzyl-1,3-dioxolane-4,5-dicarboxylic acid dimethyl ester 14
1,3-Diphenylacetone 11 (4 g, 19 mmol) was dissolved in dry benzene (100 mL) (CAUTION)
and trimethyl orthoformate (4.2 mL, 38 mmol) and a catalytic amount of p-toluenesulfonic acid
(PTSA) were added. The reaction was heated at 70°C during 2 h and then (R,R)-dimethyl
tartrate (4 g, 22 mmol) was added. Distillation of the benzene/methanol azeotrope was carried
out at 60°C, and, after cooling, Et3N was added to neutralize the acid. The solvent was
evaporated under vacuum to give a yellow oil. The crude product was purified by column
chromatography (SiO2) using hexanes/EtOAc 4:1 as the eluent to give a yellow oil (2.05 g, 29%
1
yield). IR (KBr, cm−1): 3062, 2945, 1750, 1590, 1250, 1120, 760, 705. H NMR (CDCl3, l): 3.0
(s, 4H), 3.7 (s, 6H), 4.2 (s, 2H), 7.3 (m, 10H). 13C NMR (CDCl3, l): 45.0, 53.2, 77.8, 116.1,
127.1, 128.4, 131.4, 135.6, 168.9. Anal. calc. for C21H22O6: C, 68.1; H, 6.0%. Found: C, 68.2 H,
5.9%.
3.4. Synthesis of (4R,5R)-2,2-bis(2-phenylethyl)-1,3-dioxolane-4,5-dicarboxylic acid dimethyl
ester 15
1,5-Diphenyl-3-pentanone 12 (5 g, 22 mmol) was dissolved in dry benzene (100 mL)
(CAUTION) and trimethyl orthoformate (3.27 ml, 29 mmol) and a catalytic amount of
p-toluenesulfonic acid (PTSA) were added. The reaction was stirred for 2 h and then (R,R)-
dimethyl tartrate (3.8 g, 22 mmol) was added. Distillation of the benzene/methanol azeotrope
was carried out at 60°C, and, after cooling, Et3N was added to neutralize the acid. The solvent
was evaporated under vacuum to give a yellow oil. The crude product was purified by column
chromatography (SiO2) using as eluent mixtures of hexanes/EtOAc 1:0, 10:0.5, 10:1 to give a
yellow oil (6.7 g, 76% yield). [h]20=+12.4 (c 0.04, THF). IR (KBr, cm−1): 3085, 3062, 1715, 1603,
1
1210, 989, 749, 700. H NMR (CDCl3, l): 2.15 (m, 4H), 2.81 (m, 4H), 3.87 (s, 6H), 4.88 (s, 2H),
7.24–7.40 (m, 10H). 13C NMR (CDCl3, l): 29.8, 39.1, 52.78, 77.19, 116.1, 125.8, 128.2, 128.3,
141.5, 169.6. Anal. calc. for C23H26O6: C, 69.3; H, 6.5%. Found: C, 69.1 H, 6.4%.
3.5. General procedure for the preparation of C2 substituted TADDOL derivatives. Synthesis of
2d
A solution of (3,5-dimethylphenyl)magnesium bromide, obtained from 3,5-dimethylbromo-
benzene (4.1 mL, 34 mmol) and Mg (0.80 g, 34 mmol) in dry THF (40 mL), was carefully added
to compound 14 (0.45 g, 1.3 mmol) in dry THF (20 mL). When the addition was complete,

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the mixture was refluxed for 20 h. After cooling, a saturated solution of NH4Cl was added and,
after filtering, the resulting solution was extracted with EtOAc. The organic phase was dried
(MgSO4) and the solvent evaporated under vacuum. The oil obtained was purified by column
chromatography (SiO2) using hexane/EtOAc mixtures as the eluent to give a white solid (0.57 g,
60% yield). Mp: 115°C; [h]25=−47.5 (c 0.05, CHCl3). IR (KBr, cm−1) 3365, 3028, 3010, 2855,
1
1612, 1495, 1454, 1114, 1031, 812, 758, 699. H NMR (CDCl3, l): 1.8 (s, br, 8H), 2.2 (s, br,
24H), 5.2 (s, br, 2H), 6.8–7.6 (m, 22H). 13C NMR (CDCl3, l): 21.1, 45.8, 81.4, 112.5, 125.5,
126.1, 127.3, 128.0, 129.3 130.5, 133.2, 136.8, 138.6. Anal. calc. for C51H54O4: C, 83.8; H, 7.4%.
Found: C, 84.0%; H, 7.5%.
3.6. Synthesis of TADDOL 2e
This compound was obtained as before starting from 15. Yellow solid (1.64 g, 86% yield). Mp:
97–99°C; [h]20=+9.3 (c 0.046, THF). IR (KBr, cm−1) 3558, 3226, 2920, 1612, 1454, 1378, 1234,
1
1047, 812, 698. H NMR (CDCl3, T=50°C, l): 2.09 (s, 6H), 2.47–2.79 (s+s+m, 18H), 5.33 (s,
broad, 2H), 5.82 (s, br, 1H), 7.08–7.96 (m, 22H).13C NMR (CDCl3, T=50°C, l): 20.6, 20.7,
21.2, 22.5, 30.0, 30.3, 38.7, 43.5, 78.7, 81.2, 111.9, 125.5, 125.6, 126.1, 126.4, 126.6, 127.2, 128.0,
128.1, 129.2, 133.0, 136.6, 136.7, 137.5, 138.1, 141.9. Anal. calc. for C53H58O4·H2O: C, 87.8; H,
7.7%. Found: C, 81.9; H, 7.6%.
3.7. Synthesis of TADDOL 2g
This compound was obtained as described above starting from 14 and a Grignard reagent
prepared from 2-bromonaphthalene. Brown solid (0.68 g, 64% yield). Mp: 103°C; [h]20=−44.0
(c 0.007, CHCl3). IR (KBr, cm−1) 3550, 3055, 1650, 1629, 1600, 1505, 1453, 1272, 1121, 858, 817,
1
795, 746, 699. H NMR (CDCl3, l): 2.81 (dd, 4H, J=14 Hz), 4.44 (s, br, 2H) 7–8.5 (m, 38H).
13C NMR (CDCl3, l): 43.7, 78.3, 81.4, 109.3, 117.7, 123.2, 124.7, 127.9, 130.3, 136.1, 140.7,
141.5, 142.2. Anal. calc. for C59H46O6: C, 86.5; H, 5.6%. Found: C, 86.6; H, 5.6%.
3.8. Synthesis of TADDOL 2h
This compound was obtained as described above starting from 15 and a Grignard reagent
prepared from 2-bromonaphthalene. Yellow solid (0.84 g, 38% yield). Mp: 118°C; [h]20=−33.9
(c 0.009, THF). IR (KBr, cm−1) 3531, 3314, 3057, 3023, 2927, 1600, 1505, 1453, 1273, 1050, 925,
1
857, 819, 754, 699. H NMR (CDCl3, T=50°C, l): 1.75 (m, 4H), 2.52 (m, 4H), 4.93 (s, 1H),
6.81–8.22 (m, 13C NMR (CDCl3, l): 30.3, 39.2, 78.9, 81.4, 111.4, 124.9, 125.5, 125.7, 125.9,
126.0, 126.2, 126.3, 126.35 126.4, 126.9, 127.2, 127.4, 127.5, 127.7, 127.9, 128.0, 128.27, 128.33,
128.5, 128.6, 128.65, 129.0, 132.77, 132.8, 132.9, 140.1, 141.6, 142.9. Anal. calc. for
C61H50O4·H2O: C, 84.6; H, 6.0%. Found: C, 84.3; H, 6.1%.
3.9. Synthesis of TADDOL 2I
This compound was obtained as described above from 15 and phenyl magnesium chloride.
Yellow solid (0.8 g, 50% yield). Mp: 68–70°C; [h]20=+23.15 (c 0.007, THF). IR (KBr, cm−1)
3550, 3027, 2931, 1602, 1449, 1127, 1045, 916, 812, 743. 1H NMR (CDCl3, T=50°C, l): 1.70 (m,
4H), 2.49 (m, 4H), 4.18 (s, 1H), 4.61 (s, 1H), 4.65 (s, 1H), 7.02–7.67 (m, 30H). 13C NMR

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(CDCl3, T=50°C, l): 30.0, 39.1, 78.3, 80.6, 111.7, 125.8, 125.9, 125.95, 127.3, 127.4, 127.45,
127.5, 128.0, 128.3, 128.7, 129.0, 129.1, 141.8, 142.3, 146.0. Anal. calc. for C45H42O4·2H2O: C,
79.2; H, 6.7%. Found: C, 79.6; H, 6.9%.
3.10. Synthesis of TADDOL 2j
This compound was obtained as described above starting from 15 and a Grignard reagent
prepared from bromoanisole. Yellow solid (1.2 g, 42% yield). Mp: 169°C; [h]20=+19.2 (c 0.009,
1
THF). IR (KBr, cm−1) 3529, 3350, 2932, 1608, 1511, 1455, 1298, 1250, 1175, 1033, 831, 694. H
NMR (CDCl3, T=50°C, l): 1.70 (m, 4H), 2.5 (m, 4H), 3.75 (s, 6H), 3.83 (s, 6H), 4.5 (s, 2H),
6.8–7.5 (m, 26H). 13C NMR (CDCl3, T=50°C, l): 30.9, 39.0, 55.1, 55.2, 77.7, 80.7, 110.7, 112.6,
113.5, 125.8, 128.2, 128.4, 129.0, 129.2, 129.8, 130.0, 134.7, 138.6, 158.7, 158.8. Anal. calc. for
C49H52O4·H2O: C, 75; H, 6.6%. Found: C, 75.7; H, 6.7%.
3.11. Synthesis of TADDOL 2k
This compound was obtained as described above, starting from 15 and a Grignard reagent
prepared from 1,4-dibromobutane. White solid (1.2 g, 42% yield). Mp: 140°C; [h]20=+7.15 (c
0.021, CHCl3). IR (KBr, cm−1) 3529, 3350, 2932, 1608, 1511, 1455, 1298, 1250, 1175, 1033, 831,
1
694. H NMR (CDCl3, l): 1.7 (m, 16H), 1.9 (dd, 4H, J=6 Hz, J=9 Hz), 2.7 (dd, 4H, J=6 Hz,
J=9 Hz), 3.9 (s, 2H), 7.2 (m, 10H). 13C NMR (CDCl3, l): 23.8, 24.0, 30.4, 34.7, 38.6, 40.1, 81.6,
81.8, 108.8, 125.7, 125.7, 125.7, 128.2, 128.3, 141.9. Anal. calc. for C29H38O4: C, 77.3; H, 8.5%.
Found: C, 77.4: H, 8.5%.
3.12. General procedure for the Diels–Alder reactions
Under argon, a solution of TiCl2(OiPr)2 (1 M solution in toluene) was added to a solution of
1 mmol of the corresponding TADDOL 2a–k in 20 mL of dry toluene and 3.56 g of molecular
,
sieves (4 A). The mixture was stirred at 0°C for 60 min. After this time, a solution of
(E)-3-butenoyl-1,3-oxazolidin-2-one (10 mmol) in 30 mL of dry toluene and freshly distilled
cyclopentadiene (120 mmol) were added. The mixture was stirred at 0°C for 24 h. After this
period 200 mL of 1N HCl were added and the mixture was stirred for 15 min. The organic phase
was separated, filtered through Celite, and the Celite washed with 200 mL of diethyl ether. The
organic phase was dried (MgSO4) and the solvent evaporated under vacuum. The conversion
1
and the endo/exo selectivity determined by means of H NMR spectroscopy by integration of
the signals of the methyl groups (8+9: 0.81 ppm, 6+7: 1.10 ppm, 5: 1.94 ppm). The endo
cycloadducts were purified by column chromatography on silica gel using hexanes/EtOAc (2:1)
1
as the eluent, and the enantiomeric excess in the endo cycloadducts was determined by H NMR
in presence of Eu(hfc)3 (L/S molar ratio=0.3) and confirmed by polarimetry. The absolute
configuration was assigned taking into account the specific rotation of the pure enantiomer.1c
Acknowledgements
Financial support has been provided by the CICYT (project MAT99-1176) and the Fundacio´
Caixa Castello´-Bancaixa (project P1B97-10).

B. Alta6a et al. / Tetrahedron: Asymmetry 11 (2000) 4885–4893
4893
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