Use of 1,3-dibenzyl-dihydrouracil in the chain extension of 2,3-O-isopropylidene-D-glyceraldehyde

Article abstract of DOI:10.1016/S0040-4039(02)02701-6

The aldol-type addition of 1,3-dibenzyl-dihydrouracil 2 to 2,3-O-isopropylidene-D-glyceraldehyde 3 was examined in different solvents and under Lewis acid catalysis in order to establish the stereochemical preferences. A stereodivergent synthesis of 5-trihydroxypropyl-dihydrouracil derivatives 4 and its C-5 epimer 5 was realized. The synthesis of ureido polyols 8 and 10 was obtained via the reductive ring opening of the templates 4 and 5.

Full text of DOI:10.1016/S0040-4039(02)02701-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 671–675
Use of 1,3-dibenzyl-dihydrouracil in the chain extension of
2,3-O-isopropylidene- -glyceraldehyde
D
Fausta Ulgheri,a John Bacsa,b Luigi Nassimbenib and Pietro Spanua,*
aIstituto di Chimica Biomolecolare CNR, Sezione di Sassari Trav. La Crucca 3, Baldinca, 07040 Li Punti Sassari, Italy
bDepartment of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
Received 19 September 2002; revised 22 November 2002; accepted 24 November 2002
Abstract—The aldol-type addition of 1,3-dibenzyl-dihydrouracil 2 to 2,3-O-isopropylidene-D-glyceraldehyde 3 was examined in
different solvents and under Lewis acid catalysis in order to establish the stereochemical preferences. A stereodivergent synthesis
of 5-trihydroxypropyl-dihydrouracil derivatives 4 and its C-5 epimer 5 was realized. The synthesis of ureido polyols 8 and 10 was
obtained via the reductive ring opening of the templates 4 and 5. © 2003 Elsevier Science Ltd. All rights reserved.
In the synthesis of enantiomerically pure bioactive
molecules, the synthetic strategy involving as a key
operation the diastereoselective carbonꢀcarbon bond
formation between heterocyclic compounds and
homochiral aldehydo or imino sugars has been widely
used. Numerous five- or six-membered heterocycles
such as 2-substituted-furans, -pyrroles, -thiophenes,1
and -thiazoles,2 3-substituted-isoxazolines3 and -2,5-
diketopiperazines4 have shown their utility for the syn-
thesis of multichiral molecules with biological interest.
reductive ring opening of dihydrouracil adducts 4 and 5
was also investigated.10 At first, the starting material
DBDHU 2 was prepared by simple N-protection of
commercially available DHU (dihydrouracil) 1 in a
92% yield (Scheme 1).11
To achieve the goal of a good stereochemical control at
the newly formed C-5 and C-1% stereocenters we have
investigated a number of protocols in different anhy-
drous solvents. The effect of a binary reagent system
composed of a lithium enolate and a Lewis-acid (SnCl4
or BF3·Et2O) was also examined as reported in Table
1.12 At first, the influence of the solvent without any
Lewis acid added was examined using aldehyde 3
For this purpose, we decided to explore the potentiali-
ties of dihydrouracil 1 as a new homologating reagent
both because of the biological importance of dihy-
dropyrimidinone derivatives5 or because of the interest
that C-glycosylated dihydropyrimidinones have shown
as C-linked glycoside analogues of N-linked natural
products.6 Furthermore reductive or hydrolytic DHU
ring opening has been used for the synthesis of biologi-
cally important compounds as b-ureido-alcohols and
-acids7 or a-substituted-b-aminoacids.8
Herein we report a simple and stereodivergent homolo-
gating approach to 5-trihydroxypropyl-dihydrouracil
derivatives based on the aldol-type addition of
DBDHU (1,3-dibenzyl-dihydrouracil) 2 to 2,3-O-iso-
propylidene-
-glyceraldehyde 3 (Scheme 1).9 In order
D
to evaluate the synthetic potentialities of this procedure
in the stereoselective synthesis of b-ureido polyols, the
Keywords: dihydrouracil; dihydropyrimidin-2,4-dione; glyceralde-
hyde.
* Corresponding author. Tel.: +39-079-3961033; fax: +39-079-
3961036; e-mail: p.spanu@iatcapa.ss.cnr.it
Scheme 1. Reagents and conditions: (i) NaH, BnBr, DMF; (ii)
LDA, THF, 4 h, −78°C; (iii) LDA, SnCl4, Et2O, 4 h, −78°C;
(iv) LDA 2 equiv., THF, −20°C, 2 h.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02701-6

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F. Ulgheri et al. / Tetrahedron Letters 44 (2003) 671–675
Table 1. Diastereoselective synthesis of 5-trihydroxy-
propyl-DHU derivatives, effect of solvent and Lewis acid
additiona
of the reaction partners in the addition step. It should
be noted that in both cases the Si-face of aldehyde 3
reacts selectively according to the Felkin–Anh
model.12,14 The preferential addition of the Re-face of
the enolate to the Si-face of the aldehyde to give the
aldol 4 can be explained considering an ‘open’ transi-
tion state TS1 preferred rather than TS2 (Fig. 1).
Entry Solvent
Lewis
acid
Isomer ratiob Yield (%)c
1
2
3
4
5
6
7
8
THFd
–
–
–
–
81/16/3/0
40/34/20/6
42/42/8/8
43/30/15/12
–
77/23/0/0
26/69/2/3
34/34/16/16
–
88
66
28
79
Et2Od
DMEe
Moreover, the effect of BF3·Et2O or SnCl4 addition to
the aldehyde before adding the enolate was examined in
different solvents. When anhydrous Et2O along with
SnCl4 was used, reversal of the stereochemistry with
respect to the uncatalyzed reaction occurred, resulting
in the preferential formation of compound 5 over 4 and
only a marginal amount of the other two diastereomers
(entry 7).
THF/TMEDAd
n-Hexaned
THFd
–
SnCl4
SnCl4
SnCl4
SnCl4
BF3·Et2O 51/34/13/2
BF3·Et2O 45/35/12/8
38
78
28
Et2Od
DMEe
9
n-Hexaned
THFd
10
11
12
13
22
32
Et2Od
DMEe
BF3·Et2O
BF3·Et2O
–
–
The preferential 5,1%-anti-1%,2%-anti selectivity comes
from a ‘like’ approach and may be attributed to a cyclic
transition state because of the tin(IV) coordination.15 In
this case a Zimmerman–Traxler model can be consid-
ered so the transition state TS3 leading to the aldol 5
results preferred rather than TS4 (Fig. 2).16
n-Hexaned
a All reactions were carried out on a 1 mmol scale under argon.
b Determined by NMR analysis, (5S,1%S,2%R) (4)/(5R,1%S,2%R) (5)/
(5S,1%R,2%R)/(5R,1%R,2%R).
c Isolated yield of mixtures of diastereomers. When the reactions were
incomplete the starting material DBDHU was recovered.
d Reaction temperature −78°C.
As described in entry 6, the addition of SnCl4 to the
THF solution reduces yield and diastereoselectivity
with respect to entry 1 but no prevalence of compound
5 was observed. Unsatisfactory yields and diastereose-
lectivity were obtained when BF3·Et2O was added in
different solvents (entries 10–13). Starting from the
e Reaction temperature −50°C.
(entries 1–5). Low diastereoselectivity, modest yields
and even no reactivity were observed when anhydrous
DME, Et2O, THF/TMEDA (1/1) and n-hexane were
used (entries 2–5). Whereas using anhydrous THF in
the same reaction conditions compound 4 (5S,1%S,2%R)
was obtained in high yield and good diastereoselectivity
with a small amount of its C-5 epimer 5 (5R,1%S,2%R)
(entry 1).13
readily available isopropylidene-protected L-glyceralde-
hyde, we have synthesized ent-4 and ent-5 by using the
same reaction protocols described for their
enantiomers.
A clean C-5 epimerization was also obtained when
compound 5 was treated with 2 equiv. of LDA at
−20°C for 2 h resulting in the formation of compound
4 (54/46 isomer ratio 4/5)17 or when compound 5 was
allowed to react in a thermostated (50°C) Tris–HCl
buffer/THF 1/1 solution pH 8.3 for 7 days (9/91 isomer
ratio 4/5) (Scheme 1). On the other hand no epimeriza-
tion at the C-5 stereocenter was observed when a THF
solution of the adduct 5 or 4 was allowed to react with
2 equiv. of LDA at −78°C for 3 h.
Formation of isomers 4 (5,1%-syn-1%,2%-anti ) and 5 (5,1%-
anti-1%,2%-anti ) results by an unlike (Re enolate, Si
aldehyde) and like (Si enolate, Si aldehyde) approach
Extending the scope of this procedure we have investi-
gated the reductive ring cleavage of DHU templates 4
and 5. At first the free hydroxyl group within 5 was
protected as TBS–ether by exposure to TBSTf in
CH2Cl2 in the presence of 2,6-lutidine. Then the addi-
tion of a large excess of NaBH4 to an EtOH/H2O (3/1)
solution of compound 6 effected the cleavage of DHU
ring. Ureido polyol 8 was synthesized in a 68% yield for
the two steps with a small amount (ꢀ3%) of partially
reduced compound 9.18 The same procedure was
applied to compound 4 to give the ureido polyol 10 in
a 61% yield for the two steps (Scheme 2).19
Figure 1.
The (5R,1%S) configuration of the two new stereocenters
in the pyrimidindione 5 was unambiguously determined
by a single-crystal X-ray analysis of compound 9 (Fig.
3).20 The absolute configuration of compound 5 con-
firms the (5S,1%S) configuration for its C-5 epimer 4.
Figure 2.

F. Ulgheri et al. / Tetrahedron Letters 44 (2003) 671–675
673
gress for the synthesis of enantiopure, C-glycosyl-b-
amino acids and iminosugars.
Acknowledgements
We are grateful to Regione Autonoma della Sardegna
for the generous financial support. We thank Professor
L. Colombo (University of Pavia) and Professor G.
Casiraghi (University of Parma) for helpful discussions
and Mr. R. Dallocchio (CNR ICB-Sassari) for com-
puter assistance.
References
1. For a review, see: (a) Casiraghi, G.; Zanardi, F.; Rassu,
G.; Spanu, P. Chem. Rev. 1995, 1677–1716; (b) Casiraghi,
G.; Rassu, G. Synthesis 1995, 607–629; (c) Casiraghi, G.;
Zanardi, F.; Appendino, G.; Rassu, G. Chem. Rev. 2000,
1929–1972; (d) Battistini, L.; Casiraghi, G.; Rassu, G.;
Zanardi, F. Chem. Soc. Rev. 2000, 29, 109–118. For same
references: (a) Casiraghi, G.; Colombo, L.; Rassu, G.;
Spanu, P.; Gasparri Fava, G.; Ferrari Belicchi, M. Tetra-
hedron 1990, 46, 5807–5824; (b) Casiraghi, G.; Rassu, G.;
Spanu, P.; Pinna, L. J. Org. Chem. 1992, 57, 3760–3763;
(c) Spanu, P.; Rassu, G.; Pinna, L.; Battistini, L.; Casir-
aghi, G. Tetrahedron: Asymmetry 1997, 8, 3237–3243; (d)
Spanu, P.; Rassu, G.; Ulgheri, F.; Zanardi, F.; Battistini,
L.; Casiraghi, G. Tetrahedron 1996, 52, 4829–4838; (e)
Rassu, G.; Pinna, L.; Spanu, P.; Zanardi, F.; Battistini,
L.; Casiraghi, G. J. Org. Chem. 1997, 62, 4513–4517.
2. For a review on the synthetic application of thiazole see:
(a) Dondoni, A. Synthesis 1998, 1681–1706. (b) Applica-
tion in carbohydrate chemistry: Dondoni, A.; Marra, A.
In Preparative Carbohydrate Chemistry; Hanessian, S.,
Ed.; Marcel Dekker: New York; 1997; p. 173; (c) Don-
doni, A.; Marra, A. Chem. Rev. 2000, 100, 4395–4421.
3. (a) Lopez-Sastre, J. A.; Martin-Ramos, J. D.; Rodriguez-
Amo, J. F.; Santos-Garcia, M.; Sanz-Tejedor, M. A.
Tetrahedron: Asymmetry 2000, 11, 4791–4803; (b) Santos,
M.; Sanz-Tejedor, M. A.; Rodriguez-Amo, J. F.; Arroyo,
Y.; Lopez-Sastre, J. A. Tetrahedron: Asymmetry 2001, 12,
3447–3456.
Scheme 2. Reagents and conditions: (i) TBSCl, DMF, imida-
zole or TBSTf, CH2Cl2, 2,6-lutidine; (ii) NaBH4, EtOH/H2O
(3/1), rt.
4. (a) Schollkopf, U. Tetrahedron 1983, 39, 2085–2091; (b)
Grauert, M.; Schollkopf, U. Liebigs Ann. Chem. 1985,
1817–1824; (c) Kobayashi, S.; Furuta, T.; Hayashi, T.;
Nishijima, M.; Hanada, K. J. Am. Chem. Soc. 1998, 120,
908–919; (d) Kobayashi, S.; Furuta, T. Tetrahedron 1998,
54, 10275–10294; (e) Ruiz, M.; Ojea, V.; Ruanova, T. M.;
Quintela, J. M. Tetrahedron: Asymmetry 2002, 13, 795–
799; (f) Ruiz, M.; Ojea, V.; Quintela, J. M. Synlett 1999,
204–206; (g) Ruiz, M.; Ruanova, T. M.; Ojea, V.; Quin-
tela, J. M. Tetrahedron Lett. 1999, 40, 2021–2024.
5. (a) Holley, R. W.; Apgar, J.; Everett, G. A.; Madison, J.
T.; Marquisee, M.; Merril, S. H.; Penswick, J. R.; Zamir,
A. Science 1965, 147, 1462–1465; (b) Wu, S.; Janusz, J.
M.; Sheffer, J. B. Tetrahedron Lett. 2000, 41, 1159–1163
and references cited therein; (c) Wu, S.; Janusz, J. M.
Tetrahedron Lett. 2000, 41, 1165–1169; (d) Steinberg, S.;
Misch, A.; Sprinzl, M. Nucl. Acids Res. 1993, 21, 3011–
3015; (e) Stuart, J. W.; Basti, M. M.; Smith, W. S.;
Figure 3. X-Ray structure of compound 9.
In summary we have shown the first use of dihydro-
uracil as a new homologating reagent for the chain
extension of isopropylidene protected glyceraldehyde.
Enantiomerically
pure
5-trihydroxypropyl-DHU
derivatives have been synthesized in high yields and
good diastereoselectivity in a stereodivergent way.
Starting from compounds 4 and 5 the synthesis of
ureido polyols 8 and 10 was realized via the reductive
heterocycle ring cleavage. Studies are currently in pro-

674
F. Ulgheri et al. / Tetrahedron Letters 44 (2003) 671–675
Forrest, B.; Guenther, R.; Sierzputowska-Gracz, H.; 2,3-O-isopropylidene-
D
- or -L-glyceraldehyde (1.1 equiv.).
Nawrot, B.; Malkiewicz, A.; Agris, P. F. Nucleosides
Nucleotides 1996, 15, 1009–1028 and references cited
therein; (f) Temperilli, A.; Ruggieri, D.; Salvati, P. Eur. J.
Med. Chem. Chim. Ther. 1988, 23, 77–82; (g) Skaric, V.;
Matulic-Adamic, J. Helv. Chim. Acta 1983, 66, 687–693.
When Lewis acid assisted couplings were examined the Li
enolate was transferred via cannula to the solution con-
taining glyceraldehyde (1.1 equiv.) and Lewis acid (1.2
equiv.). After quenching the reaction mixture with
aqueous citric acid solution, the crude material was
purified by flash chromatography. The ratio of the four
diastereomers was determined on the crude product by
NMR.
6. (a) Dondoni, A.; Massi, A.; Sabbatini, S. Tetrahedron
Lett. 2001, 42, 4495–4497; (b) Sano, H.; Mio, S.; Kita-
gawa, J.; Sugai, S. Tetrahedron: Asymmetry 1994, 5,
2233–2240.
Compound 4: 1H NMR (300 MHz, CDCl3) l 1.23 (s,
3H), 1.27 (s, 3H), 2.55 (d, J=4.5, 1H), 2.95 (ddd, J=3.9,
6.3 and 11.2, 1H), 3.10 (dd, J=6.3 and 12.0, 1H), 3.52 (t,
J=12.0, 1H), 3.83–3.91 (m, 2H), 4.08 (td, J=3.0 and 7.8,
1H), 4.15-4.19 (m, 1H), 4.56 (d, J=15.0, 1H), 4.71 (d,
J=15.0, 1H), 5.01 (s, 2H), 7.22–7.31 (m, 10H). 13C NMR
(75.4 MHz, CDCl3) l 170.5, 153.0, 137.4, 136.0, 128.5,
128.1, 128.0, 127.8, 127.5, 127.0, 109.3, 74.6, 68.9, 67.1,
51.7, 44.1, 43.1, 40.4, 26.5, 24.8. Colorless oil, [h]2D0=+9
(c 1.7, CHCl3). Compound 5: 1H NMR (300 MHz,
CDCl3) l 1.28 (s, 3H), 1.29 (s, 3H), 2.95 (ddd, J=4.8, 9.3
and 9.3, 1H), 3.35 (d, J=9.3, 2H), 3.51–3.59 (m, 1H),
3.91 (dd, J=5.1 and 8.4, 1H), 4.01–4.17 (m, 3H), 4.65 (s,
2H), 5.51 (s, 2H), 7.22–7.41 (m, 10H). 13C NMR (75.4
MHz, CDCl3) l 171.7, 152.9, 137.2, 135.9, 128.8, 128.4,
128.1, 127.4, 109.6, 76.9, 72.4, 67.6, 51.7, 44.3, 44.0, 43.3,
26.6, 25.2. Colorless oil [h]2D0=−22 (c 1.3, CHCl3).
14. Nucleophilic addition of organometals to acetonide-pro-
tected glyceraldehyde generally exhibits anti diastereose-
lectivity rationalized by a Felkin–Anh or a Felkin–Anh
b-chelate transition state: (a) Jurczak, J.; Pikul, S.; Bauer,
T. Tetrahedron 1986, 42, 447–488; (b) Devant, R. M.;
Radunz, H.-E. Formation of CꢀC Bonds by Addition to
Carbonyl Groups; Houben-Weyl, Georg Thieme: Stutt-
gart/New York, 1995; E-21, pp. 1220–1235 and references
cited therein.
7. (a) Kondo, Y.; Witkop, B. J. Am. Chem. Soc. 1968, 90,
764–770; (b) Kunieda, T.; Witkop, B. J. Am. Chem. Soc.
1971, 93, 3478–3487; (c) Cerutti, P.; Kondo, Y.; Landis,
W. R.; Witkop, B. J. Am. Chem. Soc. 1968, 90, 771–775;
(d) Kautz, J.; Schnackerz, K. D. Eur. J. Biochem. 1989,
181, 431–435; (e) Jahnke, K.; Podschun, B.; Schnackerz,
K. D.; Kautz, J.; Cook, P. F. Biochemistry 1993, 32,
5160–5166; (f) Sander, E. G. J. Am. Chem. Soc. 1969, 91,
3629–3634.
8. (a) Dietrich, R. F.; Sakurai, T.; Kenyon, G. L. J. Org.
Chem. 1979, 44, 1894–1896; (b) Rachina, V.; Blagoeva, I.
Synthesis 1982, 967–968.
9. A lithiated DHU derivative has been used as an ‘amide
a-anion’ for the synthesis of 5-acyl-uridines nucleoside
analogues. Hiroyuki, H.; Hiromichi, T.; Tadashi, M.
Chem. Pharm. Bull. 1982, 30, 4589–4592. 5-C-Glycosyl
uracil derivatives have been synthesized as nucleoside
analogues via addition of 5-lithio uracil to aldehydo
sugars. (a) Lerch, U.; Burdon, M. G.; Moffatt, J. G. J.
Org. Chem. 1971, 36, 1507–1513; (b) Asbun, W.; Binkley,
S. B. J. Org. Chem. 1966, 31, 2215–2219.
10. For some examples of bioactive glycosyl ureido deriva-
tives, see: (a) Velazquez, S.; Chamorro, C.; Perez-Perez,
M.-J.; Alvarez, R.; Jimeno, M.-L.; Martin-Domenech,
A.; Perez, C.; Gago, F.; De Clercq, E.; Balzarini, J.;
San-Felix, A.; Camarasa, M.-J. J. Med. Chem. 1998, 41,
4636–4647; (b) Diaz Perez, V. M.; Ortiz Mellet, C.;
Fuentes, J.; Garcia Fernandez, J. M. Carbohydr. Res.
2000, 326, 161–175. For some examples of the use of
glycosyl ureido derivatives for the synthesis of bioactive
molecules see: (a) Garcia-Moreno, M. I.; Benito, J. M.;
Ortiz Mellet, C.; Garcia Fernandez, J. M. J. Org. Chem.
2001, 66, 7604–7614; (b) Piekarska-Bartoszewicz, B.;
Temeriusz, A. Carbohydr. Res. 1990, 203, 302–307; (c)
Avalos Gonzalez M.; Cintas Moreno, P.; Gomez Monter-
rey, I. M.; Jimenez Requejo, J. L.; Palacios Albarran, J.
C.; Rebolledo Vicente, F. Carbohydr. Res. 1990, 197,
310–317.
15. The formation of an ate complex or the transmetallation
of the lithium enolate to Sn(IV) enolate can be
considered.
16. Aldol reactions between a-chiral aldehydes and E(O)-
enolates preferentially give the Felkin-type adduct by
abiding both Felkin–Anh rule and the Zimmerman–
Traxler model: (a) Mengel, A.; Reiser, O. Chem. Rev.
1999, 99, 1191–1223; (b) Roush, W. R. J. Org. Chem.
1991, 56, 4151–4157; (c) Gennari, C.; Vieth, S.; Comotti,
A.; Vulpetti, A.; Goodman, J. M.; Paterson, I. Tetra-
hedron 1992, 48, 4439–4458.
17. Only 3% of epimerization was observed for the com-
pound 4 in the same reaction condition.
11. Compound 2: 1H NMR (300 MHz, CDCl3) l 4.08 (t,
J=6.6, 2H), 4.67 (t, J=6.6, 2H), 6.04 (s, 2H), 6.43 (s,
2H), 7.22–7.44 (m, 10H). 13C NMR (75.4 MHz, CDCl3)
l 168.9, 153.8, 137.8, 136.3, 128.8, 128.6, 128.3, 127.9,
127.8, 127.3, 51.6, 43.9, 41.8, 31.7. White solid, mp
81–83°C.
12. Yamaguchi, M. In Comprehensive Organic Synthesis;
Trost, B. M.; Fleming, I., Eds. Lewis Acid Promoted
Addition Reactions of Organometallic Compounds; Perg-
amon Press: Oxford/New York, 1991; Vol. 1, pp. 325–
352.
18. By changing the reaction conditions (EtOH/H2O ratio
and NaBH4 equiv.) we obtained a larger amount of the
compound 9 up to 35%. Whereas using LiBH4 (6 equiv.)
in THF we obtained only the product 9.
19. Compound 8: 1H NMR (300 MHz, CDCl3) l 0.28 (s,
3H), 0.32 (s, 3H), 0.81 (s, 9H), 1.31 (s, 3H), 1.39 (s, 3H),
1.94–1.99 (m, 1H), 3.14 (dd, J=3.3 and 15.0, 1H), 3.66–
3.82 (m, 6H), 3.96–4.06 (m, 2H), 4.21 (d, J=16.2, 1H)
4.33–4.15 (m, 2H), 4.80 (d, J=16.2, 1H), 6.19 (bs, 1H),
7.19–7.37 (m, 10H). 13C NMR (75.4 MHz, CDCl3) l
159.6, 140.0, 138.0, 128.6, 128.4, 127.5, 127.2, 126.8,
109.5, 76.1, 75.7, 67.6, 60.0, 50.0, 45.0, 44.0, 29.7, 26.4,
25.7, 25.3, 17.9, −3.9, −4.6. Colorless oil [h]2D0=−12 (c 0.8,
CHCl3). Compound 9: 1H NMR (300 MHz, CDCl3) l
0.02 (s, 3H), 0.10 (s, 3H), 0.86 (s, 9H), 1.31 (s, 3H), 1.39
13. Typical procedure: DBDHU lithium enolate obtained by
adding LDA (1.2 equiv.) to a solution of DBDHU 2 (1.0
equiv.) in anhydrous solvent at −78°C under argon, was
allowed to react at a same temperature for 4 h with

F. Ulgheri et al. / Tetrahedron Letters 44 (2003) 671–675
675
(s, 3H), 2.34 (m, 1H), 3.08 (dd, J=5.4 and 10.5, 1H),
3.56–3.66 (m, 1H), 3.72–3.76 (m, 1H), 3.81–3.84 (m, 1H),
3.94 (s, 1H), 3.95–4.03 (m, 2H), 4.43 (d, J=10.6, 1H),
4.75 (s, 2H), 5.11 (bs, 1H), 5.28 (d, J=15.3, 1H), 7.23–
7.65 (m, 10H). 13C NMR (75.4 MHz, CDCl3) l 155.5,
138.8, 137.9, 128.5, 127.8, 127.7, 127.1, 127.0, 109.4, 77.8,
76.2, 72.5, 67.1, 51.6, 49.4, 42.2, 41.3, 26.3, 25.6, 25.1,
17.9, −4.4, −4.6. Colorless crystals, mp 152–154°C,
3.97 (dd, J=6.3 and 7.5 1H), 4.06–4.14 (m, 2H), 4.36–
4.42 (m, 2H), 4.5 (s, 1H), 5.48 (bs, 1H), 7.14–7.38 (m,
10H). 13C NMR (75.4 MHz, CDCl3) l 159.0, 139.4,
137.1, 128.8, 128.4, 127.5, 127.1, 126.7, 108.8, 76.6, 72.8,
67.1, 59.4, 50.6, 45.5, 44.6, 29.1, 26.4, 25.7, 25.0, 17.9,
−4.4. Colorless oil [h]2D0=+15 (c 1.5, CHCl3).
20. Crystallographic data for this structure have been
deposited with the Cambridge Crystallographic Data cen-
tre as supplementary publication no. CCDC 193684.
Copies of the data can be obtained free of charge on
application to CCDC 12 Union Road, Cambridge
CB21EZ (Fax: (+44) 1223-336-036. E-mail: deposit@
ccdc.cam.ac.uk).
1
[h]2D0=+21 (c 0.9, CHCl3). Compound 10: H NMR (300
MHz, CDCl3) l 0.20 (s, 3H), 0.28 (s, 3H), 0.82 (s, 9H),
1.24 (s, 3H), 1.31 (s, 3H), 1.90–1.98 (s, 1H), 3.13 (dd,
J=3.6 and 15.3, 1H), 3.56–3.64 (m, 1H), 3.67–3.76 (m,
3H), 3.79 (dd, J=3.9 and 6.0, 1H), 3.81–3.86 (m, 1H),