Anionic versus photochemical diastereoselective deconjugation of diacetone D-glucose α,β-unsaturated esters

Article abstract of DOI:10.1016/S0957-4166(03)00365-3

Deconjugation of diacetone D-glucose α,β-unsaturated esters has been conducted by deprotonation using NaHMDS with HMPA as co-solvent followed by stereoselective protonation at low temperature. High selectivities (>95%) were obtained with α-methyl linear compounds.

Full text of DOI:10.1016/S0957-4166(03)00365-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 1819–1827
Anionic versus photochemical diastereoselective deconjugation of
diacetone -glucose a,b-unsaturated esters
D
Fre´de´ric Bargiggia and Olivier Piva*
Laboratoire de Chimie Organique, Photochimie et Synthe`se, UMR CNRS 5622, Universite´ Claude Bernard, Lyon I,
43, Boulevard du 11 novembre 1918, 69622 Villeurbanne, France
Received 11 March 2003; accepted 2 May 2003
Abstract—Deconjugation of diacetone
with HMPA as co-solvent followed by stereoselective protonation at low temperature. High selectivities (>95%) were obtained
with a-methyl linear compounds. © 2003 Elsevier Science Ltd. All rights reserved.
D
-glucose a,b-unsaturated esters has been conducted by deprotonation using NaHMDS
1. Introduction
hydrogen shift leading to a prochiral photodienol P,
which was in situ protonated by an achiral aminoalco-
hol, such as N,N-dimethylaminoethanol. This reaction
has been successfully applied to the synthesis of natural
products, for example (R)-lavandulol2a and more
recently, for related terpenes by Bach et al.2b We also
found that pantolactone, available in both enantiomeric
Some years ago, we reported an efficient diastereoselec-
tive photodeconjugation procedure (de >95%) of a,b-
unsaturated esters using diacetone D-glucose as a chiral
auxiliary1 (Scheme 1, pathway a). Under UV irradia-
tion, conjugated esters underwent a 1,5-sigmatropic
Scheme 1.
* Corresponding author. E-mail: piva@univ-lyon1.fr
0957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00365-3

1820
F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 14 (2003) 1819–1827
forms, could be an alternative candidate to achieve high
selectivities during the protonation step,2c while He´nin
and Muzart have reported the reaction performed with
chiral ammonium carboxylates.3
large scale and enantiomerically pure. Photodeconjuga-
tion of ester 4a appeared therefore as a convenient way
to this end. The starting material and other related
substrates 4b–g were prepared according to a three-step
sequence depicted in Scheme 2 and Table 1.
We devised also an alternative, anionic, procedure in
which the isomerisation of the CꢀC bond was combined
with an a-alkylation process (Scheme 1, pathway b).
Under irradiation at −40°C, ester 4a was smoothly
converted into b,g-unsaturated isomer 5a (Scheme 3,
pathway a). The diastereoselectivity measured on 6a,
obtained after reduction of the CꢀC bond was >95% as
previously observed with similar substrates. Reduction
with LiAlH4 afforded the corresponding alcohol for
which the absolute configuration is known. By com-
parison of the sign of rotation, the (R) configuration
was unambiguously attributed to the new stereogenic
centre and this configuration was similar to those
already obtained for related substrates.1 However, due
to the high dilution conditions (10−2 M), the photo-
chemical procedure was difficult to scale up, and there-
fore we decided to study the deconjugation by action of
a base on 4a (Scheme 3, pathway b). It should be noted
that isomerisation of a,b-unsaturated carboxylic deriva-
Starting from diacetone
D
-glucose a-unsubstituted con-
jugated esters (R1=H), we were able to obtain b,g-
unsaturated isomers in good yields but with lower
diastereoselectivities (de <75%) compared to the photo-
chemical reaction.4 It should be noted that curiously,
the sense of the induction was the same for both
methods using the same chiral alkoxy group.
2. Results and discussion
As part of a program devoted to the synthesis of
amphidinolide R, a complex natural product,5 we
needed to prepare (R)-2-methyl-3-hepten-1-ol on a
Scheme 2.
Table 1. Preparation of unsaturated esters 4a–e
Ester 2
R1
R2
R3
E/Z
Yield
Acid 3
Ester 4
2a
2b
2c
2d
2e
Me
Me
i-Pr
F
H
H
H
H
H
n-Propyl
n-Hexyl
n-Propyl
i-Pr
90/10
85/15
87/13
98/2
73%
95%
60%
87%
81%
3a 85%
3b 72%
3c 95%
3d 71%
3e 91%
4a 85%
4b 73%
4c 73%
4d 72%
4e 84%
n-Bu
Me
60/40
Scheme 3.

F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 14 (2003) 1819–1827
1821
tives has been scarcely described under anionic
conditions6 and to our knowledge, no powerful method
using readily available chiral entities has been reported.
4f, ester 5f already prepared by the photochemical
process in high de (95%)1 was submitted to the same
anionic conditions (NaHMDS) at low temperature. In
this case, the compound was recovered intact with still
the same diastereoselectivity and no traces of ester 4f
were detected in the crude mixture. Consequently, we
have attributed the lack of reactivity to steric difficulties
in abstracting the g-proton.
First attempts performed at low temperature on 4a
using LDA were disappointing. Fortunately, the
replacement of the lithium base by NaHMDS was
highly beneficial and b,g-unsaturated ester 5a was iso-
lated in good yield as a mixture of E/Z isomers.
However, the selectivity determined from the reduced
compound 6a was moderate. This low value could be
relayed apparently to a low control of the E/Z selectiv-
ity of the enolate. In order to modify this ratio, we
decided to add as a co-solvent HMPA, which is well
known to favour the Z-enolate.7 The diastereoselectiv-
ity obtained in this case for 6a was >95%, which shows
unambiguously the importance of the configuration of
the pre-formed enolate. Other additives like DMPU
were not so efficient and only partial deconjugation was
observed. By using the most efficient conditions, the
reaction was next generalised to other a-substituted
a,b-unsaturated esters 4b–g bearing the same diacetone
Under basic conditions, a-fluoroester 4d led to consid-
erable degradation and diacetone
D-glucose was the
sole compound isolated. This could be explained by the
formation of a ketene as already pointed out by Kunz
et al. during alkylation of related saturated diacetone
D
-glucose esters.8,9 For tiglate ester 4g, the formation of
1
isomer 5g was partially observed by H NMR on the
crude mixture; unfortunately, attempts to purify this
compound from the basic reaction mixture was unsuc-
cessful and the starting material 4g was mainly
recovered.
The absolute configuration of the new stereogenic cen-
tres for 5a and 5b were determined by comparison with
data already obtained from the photochemical process.
The major diastereomer isolated was the same in both
cases. This indicates that asymmetric protonation
occurs on the same face probably due to very similar
transition states.
D
-glucose moiety (Scheme 4 and Table 2).
While a similar selectivity was observed with parent
ester 4b (de >95%), results with other substrates were
disappointing. The presence of a bulkier group (R=i-
Pr for 4c or n-butyl for 4e) on carbon 2 affected
considerably the level of induction and only poor de
values were measured for saturated esters 6c and 6e.
Ester 4f, which is usually a substrate of choice to
deliver under UV activation the b,g-unsaturated isomer
was totally recovered unchanged under the anionic
conditions. This lack of reactivity could be due either to
an unfavourable formation of the dienolate because of
steric hindrance, either to its rapid protonation at the
g-position to avoid 1,3-allylic interactions. To deter-
mine the exact reason of this surprising unreactivity of
One of the major drawbacks of the photochemical
process is the impossibility to carry out the reaction
with esters connected to small or medium rings; there-
fore the isomerisation procedure under basic conditions
appears very attractive because of the relative impor-
tance of such compounds in total synthesis. Recently,
Trost et al. reported an effective isomerisation of
cycloalkene carboxylates bearing various chiral auxil-
iaries and selectivities up to 66% were recorded with a
Scheme 4.
Table 2. Asymmetric deconjugation of diacetone
D-glucose esters 4a–g
4
R1
R2
R3
Conversion
5 Yield
E/Z
6 (de)a
6 Yield
a
b
c
d
Me
Me
i-Pr
F
n-Bu
Me
Me
H
H
H
H
H
Me
H
n-Propyl
n-Hexyl
n-Propyl
i-Pr
Me
Me
>99%
>99%
>99%
>99%
52%
77%
80%
60/40
65/35
60/40
–
60/40
–
>95%
>95%
20%
–
25%
–
93%
73%
95%
–
85%
–
83%
b
e
48%
0%
fc
gc
0%
>99%
H
0%d
–
–
–
a De measured using 1H or 13C NMR spectra.
b Diacetone
-glucose was the sole product isolated.
c Previously synthesised (Ref. 1).
d Reconjugation apparently occurred during the purification on silica.
D

1822
F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 14 (2003) 1819–1827
Scheme 5.
+
menthyl derivative.10 Similarly, diacetone
D
-glucose
MS: m/z 281 (M +1, 100), 230 (51), 152 (28), 151 (29),
’
esters 8a and 8b were prepared from 2-cyclopentenoic
and 2-cyclohexenoic acid and submitted to the same
anionic conditions, as reported for compounds 4a–g.
Isomerisation occurred and furnished esters 9a or 9b in
acceptable yields but with low diastereoselectivities of
35 and only 9%, respectively (Scheme 5).
111 (35).
4.2. General procedure for the synthesis of unsaturated
ethyl esters 2
To a suspension of sodium hydride (22 mmol) in anhy-
drous THF (60 ml) was added dropwise a solution of
phosphonoacetate 1 (22 mmol) in THF (20 ml). After
90 min at rt, a solution of aldehyde (20 mmol) in the
same solvent was slowly added. The resulting mixture
was stirred overnight, hydrolysed carefully with wet
ether; the organic layer was washed with brine, dried on
MgSO4 and concentrated under vacuo. The crude mix-
ture was purified by flash-chromatography on silica
(eluent: AcOEt/hexanes: 3/97).
3. Conclusion
The efficiency of both photochemical and anionic reac-
tions can finally be compared. While the photochemical
process was observed with a large number of substrates,
the anionic version described therein is much easier to
carry out onto a large scale but is efficient in only a few
cases. The selectivities and the configuration of the new
stereogenic centre are similar, which indicates that the
dienol and dienolate intermediates are selectively proto-
nated on the same diastereotopic face. According to
previous diastereoselective protonations of enolates,11 it
could be assumed that the selectivities observed resulted
from a kinetic C-protonation by ammonium chloride.
While diacetone glucose is a readily available reagent,
this non-photochemical approach could be attractive
for direct applications in total synthesis.
4.2.1. Ethyl 2-methyl-2-heptenoate, 2a.12 Yield 73% (E/
Z=90/10). 1H NMR (CDCl3): E-isomer: l 6.75 (tq,
J=7.3 and 1.1 Hz, 1H), 4.14 (q, J=7.3 Hz, 2H), 2.17
(dt, J=7.0 and 7.0 Hz, 2H), 1.82 (s, 3H), 1.5–1.2 (m,
2H), 0.93 (t, J=7.3 Hz, 3H). Z-isomer: l 5.91 (tq,
J=7.7 and 1.1 Hz, 1H), 4.18 (q, J=7.35 Hz, 2H), 2.43
(m, 2H), 1.82 (s, 3H), 1.5–1.2 (m, 2H), 0.93 (t, J=7.30
Hz, 3H).
4.2.2. Ethyl 2-methyl-2-decenoate, 2b.13 Yield 95% (E/
Z=85/15). 1H NMR (CDCl3): E-isomer: l 6.76 (tq,
J=7.35 and 1.4 Hz, 1H), 4.19 (q, J=7.35 Hz, 2H), 2.16
(dt, J=7.35 and 7.35 Hz, 2H), 1.82 (s, 3H), 1.5–1.2 (m,
13H), 0.88 (t, J=7.35 Hz, 3H). Z-isomer: l 5.92 (tq,
J=7.35 and 1.6 Hz, 1H), 4.19 (q, J=7.35 Hz, 2H), 2.38
(dt, J=7.35 and 7.35 Hz, 2H), 1.89 (s, 3H), 1.5–1.2 (m,
13H), 0.88 (t, J=7.35 Hz, 3H). 13C NMR (CDCl3):
E-isomer: l 168.3, 142.4, 127.6, 60.3, 31.7, 29.3, 29.1,
28.6, 22.6, 20.6, 14.2, 14.0, 12.2. Z-isomer: l 168.3,
142.9, 127.4, 59.9, 31.7, 29.6, 29.1, 28.5, 22.6, 20.6, 14.2,
14.0, 12.2. IR: w=2960, 2920, 2860, 1720, 1650, 1470,
4. Experimental
The H, 13C and 19F NMR spectra were recorded in
1
CDCl3 using a Bruker AM 300 or a DRX 500 instru-
ment. FT-IR were recorded on a Perkin–Elmer Spec-
trum One instrument. Optical rotations were measured
on a Perkin–Elmer 343 spectrometer. Mass spectra
were obtained on a Finigan-MAT 95XL instrument.
Flash-chromatographies were performed on silica gel
60 (40–63 mesh).
−1
+
’
1270 cm . MS: m/z 213 (M +1), 113, 100, 74. Anal.
calcd for C13H24O2: C, 73.54; H, 11.39. Found: C,
73.85; H, 11.68.
4.1. Triethyl 2-phosphonohexanoate, 1e
Ethyl 2-bromohexanoate (12.21 g, 54.72 mmol) and
triethylphosphite (18.8 ml (109.44 mmol) were heated
under reflux overnight. After removal of ethyl bromide
by distillation under atmospheric pressure, compound
1e (12.17 g, 43.46 mmol) was obtained pure by distilla-
tion under vacuum. Yield 80%. Bp0.05=76–78°C. 1H
NMR (CDCl3): l 4.00–4.30 (m, 6H), 2.18 (dddd,, J=
0.7, 3.9, 10.8 and 22.5 Hz, 1H), 1.70–2.05 (m, 3H),
1.20–1.45 (m, 12H), 0.89 (t, J=6.8 Hz, 3H). 13C NMR
(CDCl3): l 13.7, 14.1, 16.3, 22.1, 26.6, 30.4 (d, J=15.2
Hz), 45.8 (d, J=131.3 Hz), 61.9 (d, J=89.4 Hz), 169.2.
4.2.3. Ethyl 2-isopropyl-2-heptenoate, 2c. Yield 60% (E/
Z=13/87). 1H NMR (CDCl3): E-isomer: l 6.56 (t,
J=7.35 Hz, 1H), 4.19 (q, J=7.4 Hz, 2H), 2.90 (hept,
J=6.6 Hz, 1H), 2.19 (dt, J=7.4 and 7.35 Hz, 2H),
1.20–1.50 (m, 7H), 1.17 (d, J=6.6 Hz, 6H), 0.90 (t,
J=6.6 Hz, 3H). Z-isomer: l 5.68 (t, J=6.6 Hz, 1H),
4.22 (q, J=7.35 Hz, 2H), 2.68 (hept, J=6.6 Hz, 1H),
2.28 (dt, J=7.4 and 7.35 Hz, 2H), 1.20–1.50 (m, 7H),
1.05 (d, J=6.6 Hz, 6H), 0.90 (t, J=6.6 Hz, 3H). 13C
NMR (CDCl3): E-isomer: l 167.7, 140.8, 137.8, 59.9,

F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 14 (2003) 1819–1827
1823
31.2, 29.7, 27.7, 27.3, 20.9, 14.2, 13.8. Z-isomer: l
168.1, 139.0, 135.1, 59.9, 31.9, 31.4, 29.3, 22.7, 22.2,
14.2, 13.8. IR: 2960, 2930, 2870, 1715, 1640, 1465, 1380,
14.1, 11.9. IR: 3060, 2960, 2920, 2860, 2660, 2550, 1690,
1640, 1430, 1380, 1290 cm−1. MS: m/z 185 (M+1), 100.
−1
+
’
1255 cm . MS: m/z 198 (M ), 183, 169, 155, 153, 109.
4.3.3. 2-Isopropyl-2-heptenoic acid, 3c. Yield 95% (E/
1
Z=18/82). H NMR (CDCl3): E-isomer: l 11.5–12.5
4.2.4. (E)-Ethyl 2-fluoro-5-methyl-2-hexenoate, 2d.14
(m, 1H), 6.78 (t, J=7.35 Hz, 1H), 2.29 (hept, J=7.35
Hz, 1H), 1.20–1.55 (m, 6H), 1.04 (d, J=7.35 Hz, 6H),
0.89 (t, J=7.4 Hz, 3H). Z-isomer: l 11.5–12.5 (m, 1H),
5.91 (t, J=7.35 Hz, 1H), 2.42 (hept, J=7.35 Hz, 1H),
1.20–1.50 (m, 6H), 1.04 (d, J=7.35 Hz, 6H), 0.89 (t,
J=7.4 Hz, 3H).
1
Yield 87%. H NMR (CDCl3): l 5.92 (dt, J=22.1 Hz,
J=8.2 Hz, 1H), 4.29 (q, J=7.1 Hz, 2H), 2.42 (ddd,
J=8.4 Hz, J=6.9 Hz, J=1.8 Hz, 2H), 1.72 (m, 1H),
1.33 (t, J=7.1 Hz, 3H), 0.90 (d, J=6.9 Hz, 6H). 13C
NMR (CDCl3): l 161.0 (d, J=35.7 Hz), 144.2 (d,
J=250.3 Hz), 122.3 (d, J=17.8 Hz), 61.1, 34.6, 28.6,
22.1, 14.0. 19F NMR (CDCl3): −122.0 (d, J=22.3 Hz).
IR: 2960, 2870, 1730, 1666, 1465, 1380, 1215 cm−1.
4.3.4. (E)-2-Fluoro-5-methyl-2-hexenoic acid, 3d. Yield
1
71%. H NMR (CDCl3): 6.11 (dt, J=21.3 Hz, J=8.0
Hz, 1H), 2.45 (ddd, J=8.8 Hz, J=6.6 Hz, J=2.2 Hz,
2H), 1.74 (m, 1H), 0.92 (d, J=6.6 Hz, 6H). 13C NMR
(CDCl3): l 166.0 (d, J=37.1 Hz), 146.6 (d, J=247.6
Hz), 125.4 (d, J=17.6 Hz), 61.1, 34.4, 28.7, 22.1. 19F
NMR (CDCl3): −122.1 (d, J=21.9 Hz). IR: 3090, 2960,
2870, 2660, 2550, 1705, 1665, 1440, 1240, 1115 cm−1.
4.2.5. Ethyl 2-butyl-2-pentenoate, 2e. Yield 81% (E/Z=
1
60/40). H NMR (CDCl3): E-isomer: l 6.70 (t, J=7.4
Hz, 1H), 4.17 (q, J=7.2 Hz, 2H), 2.27 (t, J=7.4 Hz,
2H), 2.17 (quint, J=7.5 Hz, 2H), 1.20–1.48 (m, 4H),
1.28 (t, J=7.1 Hz, 3H), 1.04 (t, J=7.4 Hz, 3H), 0.89 (t,
J=7.1 Hz, 3H). Z-isomer: l 5.81 (t, J=7.3 Hz, 1H),
4.20 (q, J=7.2 Hz, 2H), 2.39 (quint, J=7.5 Hz, 2H),
2.23 (t, J=6.6 Hz, 2H), 1.20–1.48 (m, 4H), 1.29 (t,
J=7.1 Hz, 3H), 1.01 (t, J=7.5 Hz, 3H), 0.89 (t, J=7.0
Hz, 3H). 13C NMR (CDCl3): E-isomer: l 168.1, 143.6,
132.1, 60.2, 31.6, 26.38, 22.6, 21.8, 14.2, 13.9, 13.4.
4.3.5. (E)-2-Butyl-2-pentenoic acid, 3e. Yield 91% (E/
1
Z=60/40). H NMR (CDCl3): E-isomer: l 11.50–11.85
(m, 1H), 6.89 (t, J=7.4 Hz, 1H), 2.51 (dq, J=7.50 and
7.66 Hz, 1H), 2.10–2.35 (m, 3H), 1.15–1.55 (m, 4H),
1.06 (t, J=7.5 Hz, 3H), 0.91 (t, J=7.2 Hz, 3H). Z-iso-
mer: l 11.50–11.90 (m, 1H), 6.00 (t, J=7.4 Hz, 1H),
2.16–2.51 (m, 4H), 1.15–1.55 (m, 4H), 1.10 (t, J=7.5
Hz, 3H), 0.89 (t, J=7.2 Hz, 3H). 13C NMR (CDCl3):
E-isomer: l 173.9, 146.8, 131.4, 34.0, 31.5, 26.1, 22.6,
22.1, 13.9. Z-isomer: l 173.9, 146.9, 130.7, 34.0, 31.4,
26.1, 23.2, 22.3, 13.2. Anal. calcd for C9H16O2: C,
69.19; H, 10.32. Found: C, 69.43; H, 10.56.
Z-isomer: l 168.1, 142.4, 131.9, 59.9, 34.2, 31.3, 22.9,
+
’
22.2, 14.2, 13.9, 13.6. MS: m/z 184 (M , 22), 167, 149,
127, 113, 69. Anal. calcd for C11H20O2: C, 71.69; H,
10.94. Found: C, 71.76; H, 11.24.
4.3. Cleavage of ethyl esters 2
Ethyl ester 2 (15 mmol) diluted in ethanol (5 ml) was
added to a solution of potassium hydroxide (1.23 g,
22.05 mmol) in ethanol (95 ml) and water (5 ml). The
mixture was heated for 3 h under reflux, cooled to rt,
half-concentrated under vacuum and acidified with a
2N H2SO4 solution. After extraction with petroleum
ether, the organic phase was dried over MgSO4, filtered
and concentrated. The resulting oil was purified by
flash-chromatography or used directly without further
purification.
4.4. Conversion of acids 3 and 7 into diacetone
cose esters 4 and 8
D-glu-
Typical procedure: To a solution of acid 3 (or 7) (10
mmol) in methylene chloride (10 ml) were successively
added DMAP (0.366 g, 3 mmol) and diacetone
D-glu-
cose (2.60 g, 10 mmol). The reaction was next cooled to
0°C and a solution of dicyclohexylcarbodiimide (2.06 g,
10 mmol) in the same solvent (3 ml) was dropwise
added. After stirring for 10 min at 0°C, the ice–water
bath was removed and the mixture was stirred
overnight at rt. Urea was filtered off and the solvent
removed by concentration under vacuo. Ester 4 (or 8)
was obtained pure by flash-chromatography (eluent:
AcOEt/hexanes: 10/90).
4.3.1. 2-Methyl-2-heptenoic acid, 3a.15 Yield 85% (E/
1
Z=97/3). H NMR (CDCl3): E-isomer: l 10.5–12.5 (s,
1H), 6.92 (tq, J=7.35 and 1.5 Hz, 1H), 2.20 (dt,
J=7.36 and 6.61 Hz, 2H), 1.83 (d, J=1.5 Hz, 3H),
1.20–1.50 (m, 4H), 0.91 (t, J=7.4 Hz, 3H). Z-isomer: l
10.5–12.5 (s, 1H), 6.09 (qt, J=7.35 and 1.4 Hz, 1H),
2.51 (m, 2H), 1.91 (s, 3H), 1.21–1.50 (m, 4H), 0.91 (t,
J=7.4 Hz, 3H).
4.4.1. (E)-(1,2;5,6-Di-O-isopropylidene-D-glucofuranose-
3-O-yl) 2-methyl-2-heptenoate, 4a. Yield 85% (E/Z=90/
10). 1H NMR (CDCl3): l 6.77 (tq, J=7.36 and 1.47 Hz,
1H), 5.87 (d, J=3.67 Hz, 1H), 5.26 (d, J=1.47 Hz,
1H), 4.51 (d, J=3.67 Hz, 1H), 4.26 (d, J=2.2 Hz, 1H),
4.2–4.3 (m, 1H), 4.2–3.9 (m, 2H), 2.16 (q, J=7.35 Hz,
2H), 1.82 (d, J=1.47 Hz, 3H), 1.51 (s, 3H), 1.39 (s,
3H), 1.28 (s, 6H), 1.45–1.2 (m, 4H), 0.89 (t, J=7.35 Hz,
3H). 13C NMR (CDCl3): l 167.0, 142.6, 127.4, 112.5,
109.5, 105.4, 83.7, 80.3, 76.2, 73.0, 67.5, 28.8, 27.1, 27.1,
26.9, 26.5, 22.8, 14.2, 12.6. IR: 2990, 2960, 2930, 2870,
4.3.2. 2-Methyl-2-decenoic acid, 3b.16 Yield 72% (E/Z=
93/7). 1H NMR (CDCl3): E-isomer: l 10.5–11.5 (sl,
1H), 6.92 (tq, J=7.4 and 1.5 Hz, 1H), 2.20 (dt, J=7.4
and 5.15 Hz, 2H), 1.83 (s, 3H), 1.20–1.50 (m, 10H),
0.88 (t, J=6.6 Hz, 3H). Z-isomer: l 10.5–11.5 (sl, 1H),
6.09 (tq, J=7.35 and 1.47 Hz, 1H), 2.51 (m, 2H), 1.83
(s, 3H), 1.20–1.50 (m, 10H), 0.88 (t, J=6.6 Hz, 3H). 13
C
NMR (CDCl3): E-isomer: l 173.6, 145.7, 127.0, 31.8,
29.3, 29.1, 28.9, 28.5, 22.6, 14.1, 11.9. Z-isomer: l
173.6, 146.9, 126.1, 31.8, 29.8, 29.1, 28.9, 28.5, 20.4,
−1
+
’
1720, 1650, 1460, 1370 cm . MS: m/z 385 (M +1),
327. UV (CH2Cl2): m238=2570. [h]2D1=−28 (c 1.0,

1824
F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 14 (2003) 1819–1827
CH2Cl2). HRMS calcd for C20H33O7: 385.2227. Found:
385.2226.
4.4.6. (1,2;5,6-Di-O-isopropylidene- -glucofuranose-3-O-
D
yl) cyclopent-1-ene carboxylate, 8a. Yield 52%. 1H
NMR (CDCl3): l 6.82 (tt, J=2.5 and 1.9 Hz, 1H), 5.88
(d, J=3.6 Hz, 1H), 5.28 (d, J=2.3 Hz, 1H), 4.53 (d,
J=3.8 Hz, 1H), 4.20–4.31 (m, 2H), 4.00–4.20 (m, 2H),
2.46–2.62 (m, 4H), 1.96 (tt J=7.9 and 7.5 Hz, 2H), 1.52
(s, 3H), 1.41 (s, 3H), 1.31 (s, 3H), 1.30 (s, 3H). 13C
NMR (CDCl3): l 163.6, 145.0, 135.9, 112.1, 109.1,
105.0, 83.3, 79.8, 75.8, 72.6, 66.9, 33.3, 31.2, 29.3, 26.6,
26.1, 25.1, 22.9. IR: 2990, 2940, 2900, 1720, 1630, 1460,
1370, 1080 cm−1. MS: m/z 355 (M+1), 313, 297, 225.
[h]2D1=−36 (c 0.1, CH2Cl2). HRMS calcd for C18H26O7+
H: 355.1756. Found: 355.1753.
4.4.2. (E)-(1,2;5,6-Di-O-isopropylidene-D-glucofuranose-
1
3-O-yl) 2-methyl-2-decenoate, 4b. Yield 73%. H NMR
(CDCl3): l 6.78 (tq, J=7.4 and 1.4 Hz, 1H), 5.88 (d,
J=3.7 Hz, 1H), 5.28 (d, J=2.2 Hz, 1H), 4.53 (d, J=3.7
Hz, 1H), 4.2–4.3 (m, 2H), 4.0–4.2 (m, 2H), 2.07 (dt,
J=7.4 and 7.3 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 3H), 1.82
(s, 3H), 1.52 (s, 3H), 1.30 (s, 3H), 1.36–1.22 (m, 10H),
0.88 (t, J=6.6 Hz, 3H). 13C NMR (CDCl3): l 166.7,
144.1, 127.1, 112.2, 109.2, 105.9, 83.4, 80.0, 76.3, 72.7,
67.2, 31.7, 29.3, 29.0, 28.8, 28.5, 26.7, 26.7, 26.2, 25.2,
22.6, 14.0, 12.3. IR: 2990, 2930, 2850, 1720, 1650, 1460,
−1
+
21
’
1370 cm . MS: m/z 443 (M +1), 100. [h]D =−33 (c
1.0, CH2Cl2). Anal. calcd for C23H38O7: C, 64.76; H,
8.98. Found: C 64.69; H, 9.43.
4.4.7. (1,2;5,6-Di-O-isopropylidene- -glucofuranose-3-O-
D
1
yl) cyclohex-1-ene carboxylate, 8b. Yield 80%. H NMR
(CDCl3): l 7.01 (tt, J=1.9 and 1.7 Hz, 1H), 5.88 (d,
J=3.6 Hz, 1H), 5.27 (d, J=1.5 Hz, 1H), 4.52 (d, J=3.8
Hz, 1H), 4.29–4.31 (m, 2H), 4.00–4.12 (m, 2H), 2.15–
2.30 (m, 4H), 1.55–1.71 (m, 4H), 1.52 (s, 3H), 1.41 (s,
3H), 1.31 (s, 3H), 1.30 (s, 3H). 13C NMR (CDCl3): l
166.2, 141.1, 130.3, 112.4, 109.4, 105.4, 83.7, 80.2, 76.3,
72.9, 67.4, 27.0, 26.9, 26.5, 26.1, 25.5, 24.4, 22.2, 21.6.
IR: 2990, 2940, 2900, 1720, 1650, 1460, 1380, 1230,
1080 cm−1. MS: m/z 369 (M+1), 311. [h]2D1=−36 (c 0.1,
CH2Cl2). HRMS calcd for C19H28O7+H: 369.1913.
Found: 369.1911.
4.4.3. (1,2;5,6-Di-O-isopropylidene- -glucofuranose-3-O-
D
yl) 2-isopropyl-2-heptenoate, 4c. Yield 73% (E/Z=90/
1
10). H NMR (CDCl3): E-isomer: l 6.58 (t, J=7.4 Hz,
1H), 5.86 (d, J=3.7 Hz, 1H), 5.30 (d, J=1.4 Hz, 1H),
4.52 (d, J=3.7 Hz, 1H), 3.90–4.20 (m, 4H), 2.68 (hept,
J=7.4 Hz, 1H), 1.90–2.10 (m, 4H), 1.53 (s, 3H), 1.40 (s,
3H), 1.29 (s, 6H), 1.20–1.45 (m, 2H), 0.89–0.95 (m, 9H).
13C NMR (CDCl3): E-isomer: l 167.1, 142.1, 126.3,
112.1, 109.2, 105.1, 83.4, 80.1, 75.8, 73.0, 67.5, 57.2,
28.8, 27.2, 27.1, 26.9, 26.5, 22.8, 13.8, 13.4. IR: 2960,
2930, 2870, 1740, 1630, 1450, 1370, 1220 cm−1. MS: m/z
4.5. General procedure for anionic deconjugations
+
’
+
21
413 (M +H ), 397, 355, 153. [h]D =−21 (c 1.0,
CH2Cl2). HRMS calcd for C22H37O7: 413.2539. Found:
413.2534.
To a solution of conjugated ester 4/8 (2 mmol) and
HMPA (3 equiv.) in THF (10 ml) was added at −78°C
a 1 M THF solution of NaHMDS (3 mmol). After
stirring for 90 min, saturated aqueous NH4Cl solution
(3 ml) was added at once. The organic layer was
washed with water (5 ml) and with brine (5 ml). After
drying on MgSO4, filtration and concentration under
vacuo, the pale yellow viscous oil was purified by
flash-chromatography on silica (eluent: AcOEt/hexanes:
5/95).
4.4.4. (1,2;5,6-Di-O-isopropylidene- -glucofuranose-3-O-
D
1
yl) 2-fluoro-5-methyl-2-hexenoate, 4d.2d Yield 72%. H
NMR (CDCl3): l 5.97 (dt, J=21.3 Hz, J=8.1 Hz, 1H),
5.91 (d, J=3.7 Hz, 1H), 5.36 (s, 1H), 4.55 (d, J=3.7
Hz, 1H), 4.26–4.21 (m, 2H), 4.13–4.00 (m, 2H), 2.43
(ddd, J=8.1, 6.6 Hz and 1.5 Hz, 1H), 1.71 (m, 1H),
1.53 (s, 3H), 1.41 (s, 3H), 1.31 (s, 6H), 0.94 (d, J=6.6
Hz, 6H). 13C NMR (CDCl3): l 159.6 (d, J=37.1 Hz),
146.4 (d, J=224.2 Hz), 124.0 (d, J=17.1 Hz), 112.4,
109.3, 105.0, 83.2, 79.8, 72.5, 67.2, 34.1, 28.6, 26.8, 26.2,
25.1, 22.1. 19F NMR (CDCl3): −122.6 (d, J=21.1 Hz).
IR: 3090, 2960, 2870, 2660, 2550, 1705, 1665, 1440,
4.5.1.
(2R)-(1,2;5,6-Di-O-isopropylidene-D-glucofura-
nose-3-O-yl) 2-methyl-3-heptenoate, 5a. Yield 77% (E/
1
Z=60/40). H NMR (CDCl3): E+Z isomers: l 5.87 (d,
−1
+
J=3.7 Hz, 0.4H) and 5.85 (d, J=3.6 Hz, 0.6H), 5.65–
5.40 (m, 2H), 5.26 (s, 1H), 4.45 (d, J=3.7 Hz, 0.6H),
4.43 (d, J=3.6 Hz, 0.4H), 4.20 (sl, 2H), 4.15–3.95 (m,
2H), 3.13 (dq, J=2.2 and 7.3 Hz, 1H), 1.99 (ddt,
J=7.3, 7.3 and 2.9 Hz, 2H), 1.52 (s, 3H), 1.40 (s, 3H),
1.30 (s, 6H), 1.40–1.25 (m, 2H), 1.26 (d, J=6.9 Hz,
3H), 0.88 (t, J=7.3 Hz, 3H). 13C NMR (CDCl3):
E-isomer: l 172.9, 132.2, 131.7, 128.2, 127.9, 111.9,
111.8, 108.8, 104.8, 83.1, 79.8, 75.6, 75.5, 72.0, 72.0,
67.1, 67.0, 42.6, 37.9, 34.1, 29.1, 26.4, 25.9, 24.9, 22.2,
21.9, 17.5, 16.8, 13.4, 13.2. IR: 2990, 2940, 2870, 1750,
1720, 1460, 1370, 1070 cm−1. UV (CH2Cl2): m231=1530.
’
1240, 1115 cm . MS: m/z 389 (M +1), 331, 291, 245,
119, 103, 101, 85. [h]2D1=−33 (c 1.0, CH2Cl2). Anal.
calcd for C19H29O7F: C, 58.75; H, 7.52. Found: C,
58.87; H, 7.97.
4.4.5. (E)-(1,2;5,6-Di-O-isopropylidene-D-glucofuranose-
1
3-O-yl) 2-butyl-2-pentenoate, 4e. Yield 84%. H NMR
(CDCl3): l 6.71 (t, J=7.5 Hz, 1H), 5.86 (d, J=3.7 Hz,
1H), 5.27 (d, J=2.0 Hz, 1H), 4.50 (d, J=3.7 Hz, 1H),
4.10–4.25 (m, 2H), 3.95–4.06 (m, 2H), 2.27 (t, J=7.1
Hz, 2H), 2.18 (quint, J=7.5 Hz, 2H), 1.51 (s, 3H), 1.39
(s, 3H), 1.29 (s, 6H), 1.25–1.45 (m, 4H), 1.03 (t, J=7.5
Hz, 3H), 0.89 (t, J=3.9 Hz, 3H). 13C NMR (CDCl3): l
166.6, 145.2, 131.5, 112.1, 109.2, 105.0, 83.3, 80.1, 76.1,
72.5, 67.2, 31.4, 26.7, 26.5, 26.4, 25.1, 22.6, 21.8, 13.9,
13.2. IR: 2960, 2920, 2860, 1720, 1650, 1470, 1270 cm−1.
MS: m/z 398 (M), 384, 383, 341, 238, 139, 113, 101, 69..
[h]2D1=−32 (c 0.1, CH2Cl2). Anal. calcd for C21H34O7:
C, 63.29; H 8.60. Found: C, 63.12; H, 7.97.
MS: m/z 385.3 (M+H+), 327.3 (M−OC(CH3)2 ). HRMS
+
calcd for C20H33O7: 385.2227. Found: 385.2226.
4.5.2. (2R)-(1,2;5,6-Di-O-isopropyliden-D-glucofuranose-
3-O-yl) 2-methyl-3-decenoate, 5b. Yield 80% (E/Z=65/
1
35). H NMR (CDCl3): E+Z isomers: l 5.86 (d, J=3.7
Hz, 1H), 5.65–5.40 (m, 2H), 5.26 (sl, 1H), 4.45 (d,

F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 14 (2003) 1819–1827
1825
J=3.7 Hz, 0.6H, E-isomer) and 4.43 (d, J=3.7 Hz,
0.4H, Z-isomer), 3.95–4.25 (m, 4H), 3.49 (quint, J=7.4
Hz, 0.4 H), 3.12 (quint, J=7.3 Hz, 0.6 H), 1.95–2.15
(m, 2H), 1.52 (s, 3H), 1.40 (s, 3H), 1.30 (s, 6H),
1.20–1.40 (m, 11H), 0.88 (t, J=6.5 Hz, 3H). 13C NMR
(CDCl3): E-isomer: l 173.4, 132.9, 128.0, 112.3, 109.2,
105.1, 83.4, 80.1, 75.8, 72.3, 67.4, 42.9, 32.4, 31.7, 29.3,
29.0, 28.8, 28.5, 26.7, 26.2, 25.2, 22.6, 17.2. IR: 2990,
2960, 2930, 2860, 1750, 1460, 1380, 1080 cm−1. MS: m/z
427 (M+1), 369. HRMS calcd for C23H39O7: M+1=
427.2695. Found: M+H+=427.2696.
4.5.6. (1,2;5,6-Di-O-isopropylidene-
D
-glucofuranose-3-O-
yl) cyclohex-2-ene carboxylate, 9b. Yield 45% (de=9%).
1
Major diastereoisomer: H NMR (300 MHz, CDCl3): l
6.17–6.25 (m, 1H), 5.92 (d, J=3.6 Hz, 1H), 5.58 (d,
J=10.0 Hz, 1H), 5.18 (d, J=3.6 Hz, 1H), 4.57 (d,
J=3.6 Hz, 1H), 4.45–4.54 (m, 1H), 4.04–4.34 (m, 4H),
1.81–2.33 (m, 4H), 1.72–1.83 (m, 2H), 1.53 (s, 3H), 1.40
(s, 3H), 1.35 (s, 3H), 1.31 (s, 3H). Minor diastereoiso-
mer: 1H NMR (300 MHz, CDCl3): l 6.17–6.25 (m, 1H),
6.01 (d, J=10.0 Hz, 1H), 5.92 (d, J=3.6 Hz, 1H), 5.22
(d, J=3.4 Hz, 1H), 4.54 (d, J=3.6 Hz, 1H), 4.35–4.44
(m, 1H), 4.04–4.34 (m, 4H), 1.80–2.33 (m, 4H), 1.71–
1.83 (m, 2H), 4.53 (s, 3H), 1.40 (s, 3H), 1.35 (s, 3H),
1.31 (s, 3H). IR: 2990, 2940, 2900, 1750, 1460, 1380,
1250, 1220, 1080, 1020 cm−1. MS.: m/z 367 (M+1), 343,
325, 309, 97. HRMS calcd for C19H28O7+H: 367.1756.
Found: 367.1755.
4.5.3.
(2R)-(1,2;5,6-Di-O-isopropylidene-D-glucofura-
nose-3-O-yl) 2-isopropyl-3-heptenoate, 5c. Yield 83% (E/
1
Z=60/40). H NMR (CDCl3): E+Z isomers: l 5.87 (d,
J=3.7 Hz, 0.4H) and 5.86 (d, J=3.7 Hz, 0.6H), 5.28–
5.80 (m, 3H), 4.52 (d, J=3.7 Hz, 0.4H) and 4.42 (d,
J=3.7 Hz, 0.6H), 4.15–4.30 (m, 2H), 3.95–4.15 (m,
2H), 2.60–2.85 (m, 1.2H) and 2.40 (m, 0.8H), 1.90–2.10
(m, 2H), 1.52 (s, 3H), 1.40 (s, 3H), 1.30 (s, 3H), 1.29 (s,
3H), 1.20–1.40 (m, 2H), 0.85–1.05 (m, 9H). IR: 2960,
2930, 2870, 1740, 1460, 1370, 1215, 1080 cm−1. MS: m/z
413 (M+1), 397, 355.
4.6. Hydrogenation procedure for esters
A solution of b,g-unsaturated ester 5 (10 mmol) in
diethylether (10 ml) containing catalytic amounts of
PtO2 was hydrogenated for 12 h under a hydrogen
atmosphere. After filtration over a pad of silica, the
solvent was removed by concentration. The colourless
and viscous liquid was purified by flash-chromatogra-
phy or used without further purification.
4.5.4.
(2R)-(1,2;5,6-Di-O-isopropylidene-D-glucofura-
nose-3-O-yl) 2-butyl-3-pentenoate, 5e. Yield 48% (E/
1
Z=60/40). H NMR (CDCl3): E+Z isomers: 5.86 (d,
J=3.6 Hz, 1H), 5.20–5.70 (m, 2H), 5.26 (d, J=1.7 Hz,
1H), 4.42 (d, J=5.3 Hz, 1H), 4.17 (sl, 2H), 3.90–4.15
(m, 2H), 3.33 (q, J=7.3 Hz, 0.4 H) and 2.95 (q, J=7.3
Hz, 0.6H), 1.67 (sl, 3H), 1.51 (s, 3H), 1.39 s, 3H), 1.30
(s, 6H), 1.10–1.40 (m, 6H), 0.87 (t, J=6.8 Hz, 3H). 13C
NMR (CDCl3): E-isomer: l 173.0, 128.3, 127.8, 112.3,
109.2, 105.1, 83.4, 80.1, 75.8, 72.3, 67.4, 49.3, 32.0, 29.2,
26.7, 26.2, 25.1, 22.4, 17.9, 13.9. Z-isomer: l 172.9,
128.3, 127.1, 112.3, 109.2, 105.1, 83.4, 80.1, 75.8, 72.3,
67.4, 49.3, 32.2, 29.2, 26.7, 26.2, 25.1, 22.4, 17.9, 13.9.
IR: 2960, 2930, 2860, 1740, 1455, 1380, 1215, 1155,
1080 cm−1.
4.6.1.
(2R)-(1,2;5,6-Di-O-isopropylidene-D-glucofura-
nose-3-O-yl) 2-methyl heptanoate, 6a. Yield 93% (de
1
>95%). H NMR (CDCl3): major diastereoisomer (2R):
l 5.89 (d, J=3.6 Hz, 1H), 5.29 (d, J=2.5 Hz, 1H), 4.46
(dd, J=3.6 and 1.6 Hz, 1H), 4.28–4.20 (m, 2H), 4.12
(ddd, J=12.0, 8.7 and 3.0 Hz, 1H), 4.02 (dd, J=8.7
and 4.7 Hz, 1H), 2.48 (tq, J=6.9 and 7.0 Hz, 1H),
1.80–1.60 (m, 2H), 1.54 (s, 3H), 1.42 (s, 3H), 1.33 (s,
3H), 1.32 (s, 3H), 1.40–1.20 (m, 6H), 1.18 (d, J=7.0
1
Hz, 3H), 0.90 (t, J=7.1 Hz, 3H). H NMR (CDCl3):
minor diastereoisomer (2S): l 5.94 (d, J=3.6 Hz, 1H),
5.24 (d, J=2.5 Hz, 1H), 4.44 (dd, J=3.7 Hz, 1H),
4.40–3.90 (m, 4H), 2.49 (tq, J=7.0 and 7.0 Hz, 1H),
1.80–1.60 (m, 2H), 1.50 (s, 3H), 1.44 (s, 3H), 1.36 (s,
3H), 1.32 (s, 3H), 1.40–1.20 (m, 6H), 1.18 (d, J=6.95
Hz, 3H), 0.90 (t, J=7.1 Hz, 3H). 13C NMR (CDCl3):
major diastereoisomer: l 175.5, 112.5, 109.6, 105.5,
83.7, 80.4, 75.9, 72.7, 72.0, 67.8, 37.9, 33.9, 32.0, 27.0,
26.0, 26.5, 25.5, 22.8, 17.3, 14.3. IR: 2990, 2960, 2930,
2860, 1750, 1460, 1370, 1080 cm−1. MS: m/z 387 (M+
H+), 329. [h]D21=−13 (c 1.0, CH2Cl2). HRMS calcd for
C20H35O7=387.2382. Found: (M+H+)=387.2380.
4.5.5. (1,2;5,6-Di-O-isopropylidene- -glucofuranose-3-O-
D
yl) cyclopent-2-ene carboxylate, 9a. Yield 67% (de=
35%). Major diastereoisomer: 1H NMR (300 MHz,
CDCl3): l 5.90–5.95 (m, 1H), 5.88 (d, J=3.8 Hz, 1H),
5.67–5.74 (m, 1H), 5.27 (s, 1H), 4.48 (d, J=3.8 Hz,
1H), 3.75–4.25 (m, 4H), 2.46–2.62 (m, 4H), 3.54–3.64
(m, 1H), 2.33–2.57 (m, 2H), 2.10–2.20 (m, 2H), 1.51 (s,
3H), 1.40 (s, 3H), 1.31 (s, 3H), 1.30 (s, 3H). 13C NMR
(CDCl3): l 173.6, 134.6, 128.2, 112.3, 109.3, 105.1, 83.4,
80.1, 76.1, 72.5, 67.4, 50.7, 32.1, 26.7, 26.3, 26.1, 25.1,
23.8. Minor diastereoisomer: 1H NMR (300 MHz,
CDCl3): l 5.90–5.95 (m, 1H), 5.88 (d, J=3.8 Hz, 1H),
5.67–5.74 (m, 1H), 5.27 (s, 1H), 4.46 (d, J=3.8 Hz,
1H), 3.75–4.25 (m, 4H), 2.46–2.62 (m, 4H), 3.54–3.64
(m, 1H), 2.33–2.57 (m, 2H), 2.10–2.20 (m, 2H), 1.51 (s,
3H), 1.40 (s, 3H), 1.31 (s, 3H), 1.30 (s, 3H). 13C NMR
(CDCl3): l 171.5, 134.8, 126.4, 112.3, 109.3, 105.1, 83.3,
80.0, 76.0, 72.5, 67.3, 50.5, 33.8, 26.6, 26.4, 26.1, 25.1,
23.8. IR (neat): 2980, 2930, 2900, 1730, 1460, 1370,
1070, 850 cm−1. MS.: m/z 353 (M+1), 295, 261, 154, 81,
69. HRMS calcd for C18H26O7−H: 353.1600. Found:
353.1627.
4.6.2.
(2R)-(1,2;5,6-Di-O-isopropylidene-D-glucofura-
nose-3-O-yl) 2-methyl decanoate, 6b. Yield 73% (de
1
>95%). H NMR (300 MHz, CDCl3): l 5.86 (d, J=3.6
Hz, 1H), 5.27 (d, J=2.0 Hz, 1H), 4.43 (d, J=3.7 Hz,
1H), 3.95–4.25 (m, 4H), 2.46 (dq, J=7.0 and 6.9 Hz,
1H), 1.58–1.72 (m, 1H), 1.51 (s, 3H), 1.40 (s, 3H), 1.30
(s, 3H), 1.29 (s, 3H), 1.20–1.35 (m, 13H), 1.15 (d,
J=6.9 Hz, 3H), 0.87 (t, J=6.4 Hz, 3H). 13C NMR
(CDCl3): l 175.3, 112.3, 109.3, 105.1, 83.5, 80.2, 75.7,
72.4, 67.5, 39.6, 33.7, 31.8, 29.5, 29.4, 29.2, 27.0, 26.9,
26.8, 26.2, 25.2, 22.6, 16.8, 14.0. IR: 2990, 2930, 2860,
1750, 1710, 1460, 1370, 1080 cm−1. MS: m/z 429 (M+

1826
F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 14 (2003) 1819–1827
H+), 371 (M−OC(CH3)2 ). [h]D21=−11 (c 1.0, CH2Cl2).
HRMS calcd for C23H41O7: (M+1H)=429.2852.
Found: (M+1H)=429.2857.
cm−1. [h]2D1=+3.4 (c 1.0, CH2Cl2). Lit. (2S) [h]2D1=−7.8
(c 4.0, CHCl3).
+
4.6.3. (1,2;5,6-Di-O-isopropylidene-
D
-glucofuranose-3-O-
Acknowledgements
1
yl) 2-isopropyl heptanoate, 6c. Yield 95% (de=20%) H
NMR (CDCl3): major diastereoisomer (2R): l 5.84 (d,
J=3.7 Hz, 1H), 5.29 (dd, J=2.5 and 2.2 Hz, 1H), 4.44
(dd, J=3.6 and 1.6 Hz, 1H), 4.30–3.90 (m, 4H), 2.20–
2.10 (m, 1H), 1.80–1.60 (m, 2H), 1.52 (s, 3H), 1.40 (s,
3H), 1.29 (s, 3H), 1.28 (s, 3H), 1.4–1.2 (m, 7H), 1.00–
0.80 (m, 9H). 13C NMR (CDCl3): major diastereoiso-
mer: l 174.5, 112.4, 109.4, 105.1, 83.5, 80.3, 75.7, 72.3,
72.2, 67.7, 53.0, 31.8, 30.8, 39.8, 27.3, 26.8, 26.2, 22.5,
20.6, 20.2, 14.1. IR: 2960, 2930, 2870, 1740, 1460, 1370,
F.B. thanks MENSER for financial support. O.P.
acknowledges CNRS and Re´gion Rhoˆne-Alpes for sub-
stantial funding, ‘AIP Jeune Equipe’ and ‘Programme
Emergence’, respectively.
References
−1
+
21
’
1080 cm . MS: m/z 415 (M +1), 399, 357. [h]D =−25
(c 1.0, CH2Cl2). HRMS calcd for M+1H=415.2695.
Found: M+H+=415.2697.
1. Piva, O.; Pete, J.-P. Tetrahedron: Asymmetry 1992, 3,
759–768.
2. (a) Piva, O. J. Org. Chem. 1995, 60, 7879–7883; (b) Bach,
T.; Ho¨fer, F. J. Org. Chem. 2001, 66, 3427–3434; (c)
Bargiggia, F.; Piva, O. Tetrahedron: Asymmetry 2001, 12,
1389–1394 and references cited therein; (d) Bargiggia, F.;
Dos Santos, S.; Piva, O. Synthesis 2002, 427–437.
3. He´nin, F.; Le´tinois, S.; Muzart, J. Tetrahedron: Asymme-
try 2000, 11, 2037–2044.
4. (a) Faure, S.; Piva, O. Synlett 1998, 1414–1416. For a
similar strategy using other chiral alkoxy groups, see: (b)
Fuji, K.; Tanaka, F.; Node, M. Tetrahedron Lett. 1991,
32, 7281–7282; (c) Tomooka, K.; Nagasawa, A.; Nakai,
T. Chem. Lett. 1998, 1049–1050.
4.6.4. (1,2;5,6-Di-O-isopropylidene- -glucofuranose-3-O-
D
yl) 2-propyl hexanoate, 6e. Yield 85% (de=25%) 1H
NMR (CDCl3): l 5.85 (d, J=3.7 Hz, 1H), 5.29 (d,
J=2.4 Hz, 1H), 4.41 (d, J=3.7 Hz, 1H), 4.10–4.25 (m,
2H), 3.95–4.12 (m, 2H), 2.37 (hept, J=5.2 Hz, 1H),
1.41–1.75 (m, 4H), 1.51 (s, 3H), 1.39 (s, 3H), 1.31 (s,
3H), 1.29 (s, 3H), 1.20–1.35 (m, 9H), 0.89 (t, J=7.1 Hz,
3H). 13C NMR (CDCl3): Major diasteroisomer: l
175.0, 112.3, 109.3, 105.1, 83.5, 80.2, 75.6, 72.2, 67.6,
45.6, 34.6, 32.1, 29.6, 26.8, 26.7, 26.2, 25.1, 22.6, 20.4,
13.9, 13.8. Minor diastereoisomer: l 174.9, 112.3, 109.3,
105.1, 83.5, 80.0, 75.6, 72.1, 67.4, 45.6, 34.6, 32.1, 29.4,
26.8, 26.7, 26.2, 25.1, 22.6, 20.5, 13.9, 13.8. IR: 2990,
2960, 2880, 1730, 1460, 1380, 1370, 1260, 1220, 1080
5. (a) Ishibashi, M.; Takahashi, M.; Kobayashi, J. Tetra-
hedron 1997, 53, 7827–7832; (b) Ishibashi, M.;
Kobayashi, J. Heterocycles 1997, 44, 543–572.
6. (a) Kende, A. S.; Toder, B. H. J. Org. Chem. 1982, 47,
167–169; (b) Harris, F. L.; Weiler, L. Tetrahedron Lett.
1984, 25, 1333–1336; (c) Ikeda, Y.; Yamamoto, H. Tetra-
hedron Lett. 1984, 25, 5181–5182; (d) Alcock, S. G.;
Baldwin, J. E.; Bohlmann, R.; Harwood, L. M.; Seeman,
J. L. J. Org. Chem. 1985, 50, 3526–3535; (e) Ikeda, Y.;
Ukai, J.; Ikeda, N.; Yamamoto, H. Tetrahedron 1987, 43,
743–753; (f) Hudlicky, T.; Radesca, C.; Rigby, H. J. Org.
Chem. 1987, 52, 4397–4399; (g) Najafi, M. R.; Wang,
M.-L.; Zweifel, G. J. Org. Chem. 1991, 56, 2468–2476; (h)
Ihara, M.; Suzuki, S.; Taniguchi, N.; Fukumoto, K. J.
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7. (a) Ireland, R. E.; Mu¨ller, R. H.; Willard, A. K. J. Am.
Chem. Soc. 1976, 98, 2868–2877; (b) Heathcock, C. H. In
Topics in Carbanions Chemistry: Modern Enolate Chem-
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VCH-HCA: Basel, 1992; pp. 1–102.
8. Kunz, H.; Mohr, J. J. Chem. Soc., Chem. Commun. 1988,
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32, 336–358.
10. Trost, B. M.; Doherty, G. A. J. Am. Chem. Soc. 2000,
122, 3801–3810. In this report, the diastereoselectivity can
be enhanced to 75% after one single recrystallisation.
11. (a) Takano, S.; Yamada, S.-i.; Numata, H.; Ogasawara,
K. J. Chem. Soc., Chem. Commun. 1983, 760–761; (b)
−1
+
’
cm . MS: m/z 401 (M +1), 3999, 381, 343. HRMS
calcd for C21H36O7 M+1H=401.2539. Found:
401.2548.
4.7. Reduction by LiAlH4 of esters 6a and 6b
To a suspension of LiAlH4 (15 mmol) in ether (20 ml),
was dropwise added at 0°C an ethereal solution of ester
6 (10 mmol). After 30 min at 0°C, hydrolysis was
performed with aqueous ether. After acidification with
a 1N HCl solution, the aqueous layer was extracted
with ether (3×10 ml). The combined organic layers were
washed with brine and dried over MgSO4. After filtra-
tion and concentration under vacuo, the pale yellow oil
was purified by flash-chromatography on silica (eluent:
AcOEt/hexanes: 20/80).
1
4.7.1. (2R)-2-Methylheptan-1-ol.17 Yield 75%. H NMR
(CDCl3): l 3.51 (dd, J=10.3 and 5.88 Hz, 1H), 3.42
(dd, J=10.3 and 6.6 Hz 1H), 1.70–1.50 (m, 1H), 1.50–
1.20 (m, 10H), 1.20–1.00 (m, 1H), 0.92 (d, J=6.6 Hz,
3H), 0.89 (t, J=7.3 Hz, 3H). 13C NMR (CDCl3): l
68.3, 35.7, 33.1, 32.1, 26.6, 22.6, 16.5, 14.0. IR: 3340,
2960, 2930, 2870, 2860, 1470, 1050 cm−1.
1
4.7.2. (2R)-2-Methyldecan-1-ol.18 Yield 80%. H NMR
(CDCl3): l 3.50 (dd, J=10.3 and 5.8 Hz, 1H), 3.41 (dd,
J=10.3 and 6.6 Hz, 1H), 1.70–1.50 (m, 1H), 1.50–1.00
(m, 14H), 0.91 (d, J=6.6 Hz, 3H), 0.88 (t, J=7.3 Hz,
3H). IR: 3360, 2960, 2920, 2850, 1630, 1470, 1380, 1040

F. Bargiggia, O. Pi6a / Tetrahedron: Asymmetry 14 (2003) 1827–1827
1827
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