Steric constraints against [3,3]-sigmatropic rearrangement of allylic azides. A convenient approach to β-L-4-aminopent-2-enoglyceropyranosides

Article abstract of DOI:10.1016/S0957-4166(01)00450-5

Starting from alkyl α-D-4-0-methanesulphonylpent-2-enoglyceropyranosides 13a-c, nucleophilic substitution carried out with polymer-supported azide ion led to regioisomeric mixtures of the azides 14a-c and 15a-c. An analogous result, due to a [3,3]-sigmatr

Full text of DOI:10.1016/S0957-4166(01)00450-5

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 2731–2741
Steric constraints against [3,3]-sigmatropic rearrangement of
allylic azides. A convenient approach to
b- -4-aminopent-2-enoglyceropyranosides
L
Cristiana Fava, Roberta Galeazzi, Giovanna Mobbili and Mario Orena*
Dipartimento di Scienze dei Materiali e della Terra, Universita` di Ancona, Via Brecce Bianche, I-60131 Ancona, Italy
Received 4 October 2001; accepted 15 October 2001
Abstract—Starting from alkyl a-
out with polymer-supported azide ion led to regioisomeric mixtures of the azides 14a–c and 15a–c. An analogous result, due to
a [3,3]-sigmatropic rearrangement, was observed starting from methyl a- -hex-2-enoerythropyranoside derivatives 6a and 6b. On
the contrary, starting from alkyl b- -4-O-methanesulphonylpent-2-enoglyceropyranosides 21a–c, azides 22a–c were exclusively
D-4-O-methanesulphonylpent-2-enoglyceropyranosides 13a–c, nucleophilic substitution carried
D
D
obtained, and subsequently converted into the corresponding amino derivatives 23a–c. The behaviour of b-anomers 21a–c was
ascribed to steric interactions in the cyclic transition state, as supported by ab initio calculations. © 2001 Elsevier Science Ltd.
All rights reserved.
1. Introduction
of the amino group, we were particularly interested in
evaluating the use of polymeric reagents such as solid
supported azide ion, in order to avoid aqueous work-up
of the reactions.5
In connection with a project directed to preparing
non-proteinogenic amino acids and peptide mimetics in
enantiomerically pure form,1 we have devised carbohy-
drates containing an allylic amine moiety such as 1a
and 1b which could be the starting material of our
synthetic approach proceeding via either CꢀC2 or
Cꢀheteroatom bond formation,3 leading to either 2 or
3, respectively4 (Scheme 1). Moreover, for introduction
2. Results and discussion
As a first attempt, we focused on the nucleophilic
displacement of the mesyl group in 2-hexenopyran-
osides 6a and 6b6–8 carried out by using Amberlite
IRA-900-supported azide ion9 (Scheme 2). However,
the reaction proceeded only in refluxing benzene,10 and
thermal [3,3]-sigmatropic rearrangement of the azido
group occurred,11–13 to give an inseparable mixture of
regioisomeric azides 7 and 8.10,14,15
Owing to this result, hex-2-enopyranosides 5a and 5b
were unsuitable for our aims. In our opinion, however,
the [3,3]-sigmatropic rearrangement could be prevented
by a sterically demanding b-substituent at C(1), but
testing this hypothesis was discarded, due to the
difficulty in preparing significant amount of methyl
b-D
-hex-2-enopyranosides.8 Thus, we turned our atten-
tion to pent-2-enopyranosides 10 and 11,16,17 which can
be obtained in good yield and high stereoselection
Scheme 1.
starting from 3,4-di-O-acetyl-
-xylal, 9,18 the b-anomer
D
11 being the major component of the reaction
* Corresponding author. Tel.: +39 71 2204720; fax: +39 71 2204714;
e-mail: orena@popcsi.unian.it
mixture16,19 (Scheme 3).
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00450-5

2732
C. Fa6a et al. / Tetrahedron: Asymmetry 12 (2001) 2731–2741
with polymer-supported azide ion, a single azido
derivative (22a–c, respectively) was exclusively obtained
in good yield, whose structure was assigned by 1H
NMR data. In this case the product arising from [3,3]-
sigmatropic rearrangement was not observed, even after
protracted heating of the pure isolated azides 22a–c
(Scheme 6).
Therefore, by reduction of the allylic azides 22 with
LiAlH4, the amines 23 were obtained, which were even-
tually converted into the corresponding amides 24,
useful intermediates to obtain stereoselectively both
CꢀC1,2 and Cꢀheteroatom3 bonds (Scheme 7).
The outcome of the reaction starting from the b-
anomer was ascribed to the steric interaction at the
transition state between the rearranging azido group
and the substituent at C(1). In fact, when this interac-
tion is lacking, as in the a-anomers 14, the azido group
can easily undergo rearrangement to give a mixture of
regioisomeric azides 14 and 15.
Scheme 2. (a) TBDPSCl or TBDMSCl, Et3N, DMAP, DCM
(for 5a, 76%; for 5b, 69%); (b) MsCl, Et3N, DMAP, AcOEt
(for 6a, 86%; for 6b, 88%); (c) IRA 900 in the azide form,
refluxing benzene (for 7a+8a, 85%, d.r. 50:50; for 7b+8b, 83%,
d.r. 50:50).
Scheme 3. (a) I2, ROH, Et2O (79% for 10a+11a, a:b 15:85;
90% for 10b+11b, a:b 15:85; 88% for 10c+11c, a:b 15:85).
Scheme 4. (a) Amberlite IRA-900 in the methoxide form,
MeOH (for 12a–c, 100%); (b) MsCl, Et3N, DMAP, AcOEt
(for 13a, 89%; for 13b, 93%; for 13c, 90%); (c) Amberlite
IRA-900 in the azide form, refluxing benzene (for 14a+15a,
85%, d.r. 70:30; for 14b+15b, 91%, d.r. 40:60; for 14c+15c,
89%, d.r. 30:70).
When methanesulphonyl derivatives 13a–c, having a-
configuration at the anomeric centre, were treated in
refluxing benzene with azide ion on Amberlite IRA-900,
nucleophilic displacement of the methanesulphonyl
group occurred, followed by [3,3]-sigmatropic rear-
rangement, in agreement with the results observed
starting from a- -hex-2-enopyranosides 6a and 6b.
D
Therefore, the regioisomeric allylic azides 14 and 15
were obtained and, after chromatographic separation,
their structures were assigned by 1H NMR spectral
analysis (Scheme 4).
In order to unambiguously confirm the assigned
configurations, the corresponding amines 16 and 18
were prepared by reduction of both 14a and 15a with
LiAlH4. These compounds were directly converted into
the corresponding p-iodobenzamides 17 and 19, whose
1
structures were assigned on the basis of their H NMR
spectral data (Scheme 5).
In contrast to the above results, when the methane-
sulphonyl derivatives 21a–c, having b-configuration at
the anomeric centre, were treated in refluxing benzene
Scheme 5. (a) LiAlH4, THF; (b) p-IC6H4COCl, Et3N,
DMAP, AcOEt (90% for 17; 92% for 19).

C. Fa6a et al. / Tetrahedron: Asymmetry 12 (2001) 2731–2741
2733
involved in the rearrangement reactions.20 The transi-
tion structures of the two possible [3,3]-sigmatropic
rearrangements, whose geometries are reported in Figs.
1 and 2, were located at B3LYP/6-31G* level of
theory21 together with the structures of the starting
reagents and final products.22
From the calculations, for pathway 1 (14a—TS-1) the
activation energy (DE‡) was found to be 18.57 kcal/mol
lower than for pathway 2 (22a—TS-2) (Scheme 8 and
Tables 1 and 2). This large difference could be due to
the steric hindrance between the rearranging azido and
the isopropyl groups leading to A, as it appears from
the geometry of TS-2 (Fig. 2). Moreover, this highly
destabilising steric interaction redirects the attack of the
azido group so that the correct orientation for the
reaction is not reached. This result is in agreement with
Scheme 6. (a) IRA 900 in the methoxide form, MeOH (for
20a–c, 100%); (b) MsCl, Et3N, DMAP, AcOEt (for 21a, 95%;
for 21b, 91%; for 21c, 90%); (c) IRA 900 in the azide form,
refluxing benzene (for 22a, 81%; for 22b, 89%; for 22c, 86%).
Scheme 7. (a) LiAlH4, THF (87% for 23a; 88% for 23b; 76%
for 23c); (b) R¦COCl, Et3N, DMAP, AcOEt (71% for 24a;
76% for 24b; 91% for 24c).
Figure 2. Optimised geometry of TS-2.
Scheme 8. Pathways involved in [3,3]-sigmatropic rearrange-
ments.
Table 1. Activation energies (DE‡) for pathways 1 and 2
Level of theory
DE‡ (298 K)
Figure 1. Optimised geometry of TS-1.
Pathway 1
Pathway 2
HF/631G*
B3LYP/6.31G*
HF/6.31G*
75.43
56.99
97.94
75.56
In order to confirm this suggestion, a quantum mechan-
ical ab initio investigation was performed, with the aim
to find out and characterise all the stationary points
B3LYP/6.31G*

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C. Fa6a et al. / Tetrahedron: Asymmetry 12 (2001) 2731–2741
Table 2. Total energies (au) of reagents, transition struc-
tures and products for pathways 1 and 2
4.2. Methyl a- -6-O-t-butyldiphenylsilyl-2,3-dideoxy-
D
hex-2-enoerythropyranoside 5a
HF/6-31G* (au)a
B3LYP/6-31G* (au)b
To a solution containing methyl a-D-2,3-dideoxyhex-2-
enoerythropyranoside 48 (2.4 g, 15 mmol), triethyl-
amine (1.5 g, 15 mmol) and DMAP (0.3 g) in
dichloromethane (25 mL) t-butyldiphenylsilyl chloride
(4.1 g, 15 mmol) dissolved in dichloromethane (10 mL)
was added at 0°C and the mixture was stirred for 2 h.
Water (50 mL) was added and the mixture was
extracted with ethyl acetate (3×100 mL). After drying
(Na2SO4), the solvent was removed under reduced pres-
sure and the residue was purified by silica-gel chro-
matography (cyclohexane:ethyl acetate 90:10) to give
the title compound in 76% yield; colourless viscous oil;
14a
TS-1
22a
TS-2
15a
A
−623.474617255
−623.354400735
−623.470863991
−623.314791416
−623.46633935910
−623.474634447
−627.275060282
−627.184239474
−627.270789852
−627.150378038
−627.268018548
−627.274399962
a Optimised at the same level of theory.
b Single point on the RHF/6-31G* geometry.
1
IR (CHCl3): 3350 cm−1; H NMR: l 1.08 (s, 9H), 2.58
experimental data, since the azide A was never observed
(d, 1H, J=4.6, OH), 3.39 (s, 3H), 3.72–3.83 (m, 1H),
3.86–3.94 (m, 2H), 4.19–4.30 (m, 1H), 4.85 (br s, 1H),
5.71–5.80 (m, 1H), 5.92–5.99 (m, 1H), 7.37–7.51 (m, 6
ArH), 7.65–7.78 (m, 4 ArH); 13C NMR: l 19.7, 27.3,
56.2, 66.2, 67.0, 71.0, 95.6, 126.4, 128.3, 130.4, 133.3,
133.5, 136.1; [h]D +106.4 (c 0.5, CHCl3). Anal. calcd for
C23H30O4Si: C, 69.31; H, 7.59. Found: C, 69.24; H,
7.52%.
in the reaction mixture.23
3. Conclusions
From the observed results, supported by quantum-
mechanical calculations, we can conclude that [3,3]-sig-
matropic rearrangement of the azido group in
b-pentenopyranosides 22 is strongly influenced by steric
interaction of the anomeric substituent in the transition
state. Thus, the easy access to either 4-amino-, 23, or
4-amido pent-2-enopyranosides, 24, makes these com-
pounds attractive as key intermediates for the prepara-
tion of homochiral bioactive compounds. Applications
directed to the synthesis of enantiomerically pure non-
proteinogenic amino acids are currently underway in
our laboratory.
4.3. Methyl a- -6-O-t-butyldimethylsilyl-2,3-dideoxy-
D
hex-2-enoerythropyranoside 5b
Following the procedure described for compound 5a,
but using t-butyldimethylsilyl chloride, the title com-
pound was obtained in 69% yield; colourless oil; IR
1
(CHCl3): 3345 cm−1; H NMR: l 0.09 (s, 6H), 0.89 (s,
9H), 2.87 (d, 1H, J=3.7, OH), 3.40 (s, 3H), 3.59–3.77
(m, 1H), 3.79 (dd, 1H, J=6.0, J=9.6), 3.89 (dd, 1H,
J=4.9, J=9.6), 4.16 (m, 1H), 4.84 (s, 1H), 5.67–5.74
(m, 1H), 5.88–5.97 (m, 1H); 13C NMR: l −4.6, 18.7,
26.3, 56.1, 65.6, 67.1, 70.9, 95.6, 126.1, 133.6; [h]D +99.6
(c 0.5, CHCl3). Anal. calcd for C13H26O4Si: C, 56.90; H,
9.55. Found: C, 56.84; H, 9.59%.
4. Experimental
4.1. General procedures
4.4. Methyl a- -6-O-t-butyldiphenylsilyl-4-O-methane-
D
Melting points were measured on an Electrothermal IA
9000 apparatus and are uncorrected. IR spectra were
recorded in CHCl3 on a Nicolet Fourier-transform
infrared 20-SX spectrophotometer. Diastereomeric
ratios (d.r.) were determined by GC analysis using a
sulphonyl-2,3-dideoxyhex-2-enoerythropyranoside 6a
To a solution containing compound 5a (4.8 g, 12
mmol), triethylamine (1.2 g, 12 mmol) and N,N-
dimethylaminopyridine (DMAP) (0.3 g) in ethyl acetate
(70 mL), methanesulphonyl chloride (1.4 g, 12 mmol)
dissolved in ethyl acetate (10 mL) was added at 0°C.
After stirring for 3 h at 0°C, the suspension was poured
into water–ice and extracted with ethyl acetate (3×100
mL). After drying (Na2SO4), the solvent was removed
at reduced pressure and the residue was purified by
silica-gel chromatography (cyclohexane:ethyl acetate
1:1) to give the title compound in 86% yield; colourless
Chrompack 9001 instrument equipped with
a
Chrompack 7720 capillary column (50 m×0.25 mm i.d.;
1
stationary phase CP-Sil-5 CB). H and 13C NMR spec-
tra were recorded at 200 and 50 MHz, respectively, on
a Varian Gemini 200 spectrometer, using CDCl3 as a
solvent. Chemical shifts (l) are reported in ppm relative
to TMS and coupling constants (J) in Hz. The assign-
1
ment of all separate signals in the H NMR spectra was
made on the basis of coupling constants, selective pro-
ton–proton homonuclear decoupling experiments, pro-
ton–proton COSY experiments and proton–carbon
HETCOR experiments. Optical rotations were mea-
sured on a Perkin–Elmer 241 polarimeter. Mass spectra
(MS) were obtained by electron impact (EI) on a
Hewlett–Packard 5989B mass spectrometer. Column
chromatography was performed using silica gel 60
(230–400 mesh).
1
oil; H NMR: l 1.09 (s, 9H), 2.93 (s, 3H), 3.67 (s, 3H),
3.85–3.91 (m, 2H), 3.91–4.02 (m, 1H), 4.94 (d, 1H,
J=2.6), 5.30 (br d, 1H, J=9.0), 6.85–6.94 (m, 1H),
6.07–6.15 (m, 1H), 7.34–7.48 (m, 6 ArH), 7.66–7.78 (m,
4 ArH); 13C NMR: l 19.8, 27.3, 56.5, 62.9, 69.6, 71.7,
95.7, 128.1, 128.2, 128.3, 128.4, 129.4, 129.6, 130.1,
130.3, 135.3, 135.7, 136.0, 136.1, 136.2, 136.4; [h]D
+105.6 (c 0.5, CHCl3). Anal. calcd for C24H32O6SSi: C,
60.48; H, 6.77. Found: C, 60.41; H, 6.83%.

C. Fa6a et al. / Tetrahedron: Asymmetry 12 (2001) 2731–2741
2735
4.5. Methyl a-
D
-6-O-t-butyldimethylsilyl-4-O-methane-
NMR spectra. Colourless oil; IR (CHCl3): 2093 cm−1.
Anal. calcd for C13H25N3O3Si: C, 52.14; H, 8.42; N,
14.03. Found: C, 52.08; H, 6.81; N, 14.07%.
sulphonyl-2,3-dideoxyhex-2-enoerythropyranoside 6b
Following the procedure described for compound 6a,
but starting from 5b, the title compound was obtained
4.10. Methyl a- -4-azido-6-O-t-butyldimethylsilyl-2,3,4-
D
1
in 88% yield; colourless oil; H NMR: l 0.10 (s, 6H),
trideoxyhex-2-enothreopyranoside 7b
0.91 (s, 9H), 3.08 (s, 3H), 3.44 (s, 3H), 3.74–3.95 (m,
3H), 4.89 (s, 1H), 5.19 (d, 1H, J=10.3), 5.81–5.92 (m,
1H), 6.05–6.14 (m, 1H); 13C NMR: l −4.9, 18.8, 26.4,
39.5, 56.4, 62.3, 69.4, 71.9, 95.7, 129.3, 129.6; [h]D
+114.3 (c 0.5, CHCl3). Anal. calcd for C14H28O6SSi: C,
47.70; H, 8.01. Found: C, 47.64; H, 7.97%.
1H NMR: l 1.11 (s, 9H), 3.32–3.41 (m, 1H), 3.44 (s,
3H), 3.81 (d, 2H, J=7.0), 4.07–4.25 (m, 1H), 4.90 (d,
1H, J=1.4), 6.03–6.16 (m, 2H); 13C NMR: l −4.8, 18.6,
26.3, 52.7, 56.0, 63.0, 71.1, 95.6, 125.2, 131.0.
4.11. Methyl a- -2-azido-6-O-t-butyldimethylsilyl-2,3,4-
D
4.6. Methyl a-
D
-4-azido-6-O-t-butyldiphenylsilyl-2,3,4-
-2-
trideoxyhex-3-enoglyceropyranoside 8b
trideoxyhex-2-enothreopyranoside 7a and methyl a-
D
azido-6-O-t-butyldiphenylsilyl-2,3,4-trideoxyhex-3-eno-
glyceropyranoside 8a
1H NMR: l 1.09 (s, 9H), 3.39–3.40 (m, 1H), 3.61 (dd,
1H, J=6.1, J=10.2), 3.47 (s, 3H), 3.79 (dd, 1H, J=4.9,
J=10.2), 4.15–4.26 (m, 1H), 4.83 (s, 1H), 5.75–5.87 (m,
1H), 6.20–6.28 (m, 1H); 13C NMR: l −4.9, 18.4, 26.3,
55.5, 56.5, 66.2, 69.3, 100.4, 119.2, 133.1.
To a solution containing the methanesulphonate 6a (1.8
g, 4.0 mmol) in benzene (40 mL), Amberlite IRA-900 in
the azide form9 (5.0 g, 3.0 mequiv./g) was added and
the suspension was stirred under reflux for 2 h. The
resin was then filtered off and the solvent removed
under reduced pressure. The residue was purified by
silica-gel chromatography (cyclohexane:ethyl acetate
80:20), to give as a 1:1 inseparable mixture the regioiso-
meric azides 7a and 8a in 85% overall yield which gave
however distinct signal patterns in the 1H and 13C
NMR spectra. Colourless oil; IR (CHCl3): 2098 cm−1.
Anal. calcd for C23H29N3O3Si: C, 65.22; H, 6.90; N,
9.92. Found: C, 65.16; H, 6.85; N, 9.86%.
4.12. Isopropyl a-
glyceropyranoside 10a and isopropyl b-
2,3-dideoxypent-2-enoglyceropyranoside 11a
D
-4-O-acetyl-2,3-dideoxypent-2-eno-
D
-4-O-acetyl-
A solution containing di-O-acetyl-
-xylal 918 (4.0 g, 20
D
mmol) and isopropyl alcohol (3.0 mL) in diethyl ether
(40 mL) was added at rt to a solution containing iodine
(1.5 g, 6 mmol) in diethyl ether (40 mL) and the
mixture was stirred for 3 h. An aqueous saturated
solution of Na2S2O4 (30 mL) was then added, the
mixture was extracted with ethyl acetate (3×100 mL)
and the organic layer was subsequently washed with
10% aqueous NaHCO3 (50 mL) and brine (150 mL).
After drying (Na2SO4), the solvent was removed under
reduced pressure to give a residue which was purified
by silica-gel column chromatography (cyclohex-
ane:ethyl acetate 4:1) to give compounds 10a and 11a
(15:85 d.r.) in 79% overall yield.
4.7. Methyl a- -4-azido-6-O-t-butyldiphenylsilyl-2,3,4-
D
trideoxyhex-2-enothreopyranoside 7a
1H NMR: l 1.10 (s, 9H), 3.35–3.42 (m, 1H), 3.43 (s,
3H), 3.90 (d, 2H, J=7.1), 4.21–4.34 (m, 1H), 4.94 (d,
1H, J=1.5), 6.07–6.21 (m, 2H), 7.36–7.52 (m, 6 ArH),
7.65–7.79 (m, 4 ArH); 13C NMR: l 19.7, 27.3, 52.8,
56.1, 63.9, 71.1, 90.5, 125.3, 128.2, 130.3, 131.0, 133.8,
136.1, 136.2.
4.12.1. Isopropyl a- -4-O-acetyl-2,3-dideoxypent-2-eno-
D
glyceropyranoside 10a. Colourless oil; IR (CHCl3): 1741
4.8. Methyl a- -2-azido-6-O-t-butyldiphenylsilyl-2,3,4-
D
1
cm−1; H NMR: l 1.17 (d, 6H, 50%, J=6.2), 1.24 (d,
trideoxyhex-3-enoglyceropyranoside 8a
6H, 50%, J=6.2), 2.06 (s, 3H), 3.82 (d, 2H, J=7.0),
3.97 (m, 1H, J=6.2), 5.03 (s, 1H), 5.28 (m, 1H),
5.77–5.98 (m, 2H); 13C NMR: l 21.4, 22.3, 24.0, 60.2,
65.5, 70.6, 92.7, 129.0, 130.2, 170.8; [h]D +97.1 (c 0.5,
CHCl3); MS m/z: 200 (M+), 185, 141, 82, 60. Anal.
calcd for C10H16O4: C, 59.98; H, 8.05. Found: C, 60.04;
H, 7.99%.
1H NMR: l 1.11 (s, 9H), 3.35–3.41 (m, 1H), 3.45 (s,
3H), 3.72 (dd, 1H, J=7.0, J=10.0), 3.91 (dd, 1H,
J=6.1, J=10.0), 4.41–4.35 (m, 1H), 4.84 (s, 1H), 5.78–
5.89 (m, 1H), 6.29–6.38 (m, 1H), 7.36–7.52 (m, 6 ArH),
7.65–7.79 (m, 4 ArH); 13C NMR: l 19.8, 27.3, 55.5,
56.4, 66.7, 69.2, 100.4, 119.5, 128.2, 130.3, 131.1, 133.1,
136.1, 136.2.
4.12.2. Isopropyl b- -4-O-acetyl-2,3-dideoxypent-2-eno-
D
4.9. Methyl a-
D
-4-azido-6-O-t-butyldimethylsilyl-2,3,4-
-2-
glyceropyranoside 11a. Colourless oil; IR (CHCl3): 1738
1
trideoxyhex-2-enothreopyranoside 7b and methyl a-
D
cm−1; H NMR: l 1.17 (d, 6H, 50%, J=6.2), 1.22 (d,
azido-6-O-t-butyldimethylsilyl-2,3,4-trideoxyhex-3-eno-
glyceropyranoside 8b
6H, 50%, J=6.2), 2.08 (s, 3H), 3.80 (d, 1H, J=13.1),
3.97 (m, 1H, J=6.2), 4.18 (dd, 1H, J=2.9, J=13.1),
4.91–4.97 (m, 1H), 5.10 (d, 1H, J=2.4), 5.95–6.09 (m,
2H); 13C NMR: l 21.4, 22.2, 23.9, 61.4, 63.9, 70.3, 91.5,
125.1, 131.9, 170.8; [h]D +120.4 (c 0.5, CHCl3); MS
m/z: 200 (M+), 185, 141, 82, 60. Anal. calcd for
C10H16O4: C, 59.98; H, 8.05. Found: C, 59.94; H,
8.00%.
Following the same procedure as for compounds 4a
and 5a, but starting from the methanesulphonate 6b, an
inseparable 1:1 mixture of the regioisomeric azides 7b
and 8b was obtained in 83% overall yield which gave
however distinct signal patterns in the 1H and 13C

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C. Fa6a et al. / Tetrahedron: Asymmetry 12 (2001) 2731–2741
4.13. Benzyl a-
D
-4-O-acetyl-2,3-dideoxypent-2-eno-
-4-O-acetyl-2,3-
4.15. Preparation of alcohols 12a–c and 20a–c. General
procedure
glyceropyranoside 10b and benzyl b-
D
dideoxypent-2-enoglyceropyranoside 11b
A solution containing 10a–c or 11a–c (20 mmol) in
methanol (30 mL) was added to the resin IRA 900 (5.0
g) in the methoxide form prepared in methanol (30
mL).24 The mixture was stirred at rt for 1 h, then the
resin was filtered off and washed with methanol (10
mL). The solvent was removed under reduced pressure
and the residue was purified by silica-gel chromatogra-
phy (cyclohexane:ethyl acetate 7:3) to give 12a–c or
20a–c.
Following the same procedure described for com-
pounds 10a and 11a, but starting from di-O-acetyl-D-
xylal 9 and benzyl alcohol, compounds 10b and 11b
were obtained in 90% overall yield (d.r. 15:85).
4.13.1. Benzyl a- -4-O-acetyl-2,3-dideoxypent-2-eno-
D
glyceropyranoside 10b. Colourless oil; IR (CHCl3): 1738
1
cm−1; H NMR: l 2.08 (s, 3H), 3.83–3.94 (m, 2H), 4.58
(d, 1H, J=11.7), 4.83 (d, 1H, J=11.7), 5.04 (m, 1H),
5.25–5.36 (m, 1H), 5.82–5.93 (m, 1H), 5.94–6.01 (m,
1H), 7.23–7.41 (m, 5 ArH); 13C NMR: l 21.4, 60.6,
65.5, 70.5, 93.8, 128.2, 128.5, 128.9, 129.5, 129.6, 138.3,
170.8; [h]D +77.1 (c 0.5, CHCl3); MS m/z: 248 (M+),
189, 141, 107, 91, 82. Anal. calcd for C14H16O4: C,
67.73; H, 6.50. Found: C, 67.68; H, 6.44%.
4.15.1. Isopropyl a-
D
-2,3-dideoxypent-2-enoglycero-
pyranoside 12a. The title compound was prepared in
quantitative yield starting from isopropyl a-
tyl-2,3-dideoxypent-2-enoglyceropyranoside
D
-4-O-ace-
10a.
Colourless oil; IR (CHCl3): 3411 cm−1; 1H NMR: l
1.17 (d, 6H, 50%, J=6.2), 1.24 (d, 6H, 50%, J=6.2),
1.81 (br d, 1H, J=6.5, OH), 3.71 (dd, 1H, J=7.8,
J=11.0), 3.79 (dd, 1H, J=5.5, J=11.0), 3.97 (m, 1H,
J=6.2), 4.11–4.32 (m, 1H), 5.04 (s, 1H), 5.69–5.77 (m,
1H), 5.96–6.05 (m, 1H); 13C NMR: l 22.4, 24.1, 63.6,
64.0, 70.8, 93.1, 128.5, 133.4; [h]D +37.9 (c 0.5, CHCl3);
MS m/z: 158 (M+), 140, 99, 82, 81. Anal. calcd for
C8H14O3: C, 60.74; H, 8.92. Found: C, 60.69; H, 8.86%.
4.13.2. Benzyl b- -4-O-acetyl-2,3-dideoxypent-2-eno-
D
glyceropyranoside 11b. Colourless oil; IR (CHCl3): 1732
1
cm−1; H NMR: l 2.09 (s, 3H), 3.86 (d, 1H, J=13.0),
4.21 (dd, 1H, J=2.8, J=13.0), 4.58 (d, 1H, J=11.7),
4.80 (d, 1H, J=11.7), 4.93–4.99 (m, 1H), 5.10 (d, 1H,
J=2.0), 5.95–6.15 (m, 2H), 7.25–7.39 (m, 5 ArH); 13C
NMR: l 21.6, 61.8, 63.8, 70.3, 92.5, 125.6, 128.3, 128.8,
129.0, 131.4, 138.1, 171.0; [h]D +137.7 (c 0.5, CHCl3);
MS m/z: 248 (M+), 189, 141, 107, 91, 82. Anal. calcd
for C14H16O4: C, 67.73; H, 6.50. Found: C, 67.67; H,
6.53%.
4.15.2. Benzyl a-
oside 12b. The title compound was prepared in quanti-
-4-O-acetyl-2,3-
D
-2,3-dideoxypent-2-enoglyceropyran-
tative yield starting from benzyl a-
D
dideoxypent-2-enoglyceropyranoside 10b. Low melting
1
solid; IR (CHCl3): 3401 cm−1; H NMR: l 2.48 (br s,
4.14. p-Methoxybenzyl a- -4-O-acetyl-2,3-dideoxypent-
D
1H, OH), 3.70 (dd, 1H, J=8.3, J=11.0), 3.79 (dd, 1H,
J=5.6, J=11.0), 4.12–4.28 (m, 1H), 4.56 (d, 1H, J=
11.7), 4.80 (d, 1H, J=11.7), 5.01 (br s, 1H), 5.76 (ddd,
1H, J=1.7, J=2.5, J=10.3), 5.95–6.06 (m, 1H), 7.35
(m, 5 ArH); 13C NMR: l 63.5, 64.0, 70.5, 93.9, 127.6,
128.3, 129.0, 134.0, 138.0; [h]D +73.3 (c 0.5, CHCl3);
MS m/z: 206 (M+), 188, 115, 91, 81, 77. Anal. calcd for
C12H14O3: C, 69.89; H, 6.84. Found: C, 69.84; H,
6.79%.
2-enoglyceropyranoside 10c and p-methoxybenzyl b-D-
4-O-acetyl-2,3-dideoxypent-2-enoglyceropyranoside 11c
The title compounds were prepared in 88% overall yield
(d.r. 15:85) as described for 10a and 11a, starting from
di-O-acetyl-
D
-xylal, 9, and p-methoxybenzyl alcohol.
4.14.1. p-Methoxybenzyl a-
D
-4-O-acetyl-2,3-dideoxy-
pent-2-enoglyceropyranoside 10c. Colourless oil; IR
1
(CHCl3): 1743 cm−1; H NMR: l 2.07 (s, 3H), 3.80 (s,
4.15.3. p-Methoxybenzyl a-D-2,3-dideoxypent-2-eno-
glyceropyranoside 12c. The title compound was pre-
pared in a quantitative yield starting from p-methoxy-
3H), 3.83–3.87 (m, 2H), 4.63 (ABq, 2H, J=11.4), 5.02
(br s, 1H), 5.25–5.36 (m, 1H), 5.81–5.97 (m, 2H), 6.87
(d, 2 ArH, J=8.6), 7.28 (d, 2 ArH, J=8.6); 13C NMR:
l 21.2, 55.5, 60.4, 65.5, 70.0, 93.4, 114.2, 129.3, 129.8,
130.1, 130.2, 130.3, 159.7, 170.6; [h]D +63.4 (c 0.5,
CHCl3); MS m/z: 278 (M+), 263, 219, 189, 141, 122,
121, 81, 60. Anal. calcd for C15H18O5: C, 64.74; H, 6.52.
Found: C, 64.69; H, 6.56%.
benzyl
a-D-4-O-acetyl-2,3-dideoxypent-2-enoglycero-
pyranoside 10c. Colourless oil; IR (CHCl3): 3347 cm−1;
1H NMR: l 2.05 (br s, 1H, OH), 3.71 (dd, 1H, J=8.1,
J=11.0), 3.79 (dd, 1H, J=5.6, J=11.), 3.80 (s, 3H),
4.15–4.28 (m, 1H), 4.62 (ABq, 2H, J=11.3), 4.98 (br s,
1H), 5.69–5.79 (m, 1H), 5.94–6.04 (m, 1H), 6.86 (d, 2
ArH, J=8.6), 7.27 (d, 2 ArH, J=8.6); 13C NMR: l
55.7, 63.4, 63.8, 70.1, 93.5, 114.3, 127.6, 130.1, 130.3,
134.0, 146.9, 159.8; [h]D +31.0 (c 0.5, CHCl3); MS m/z:
236 (M+), 221, 218, 206, 189, 121, 103, 81, 77. Anal.
calcd for C13H16O4: C, 66.09; H, 6.83. Found: 66.12; H,
6.79%.
4.14.2. p-Methoxybenzyl b- -4-O-acetyl-2,3-dideoxy-
D
pent-2-enoglyceropyranoside 11c. Colourless oil; IR
1
(CHCl3): 1743 cm−1; H NMR: l 2.09 (s, 3H), 3.80 (s,
3H), 3.85 (d, 1H, J=13.0), 4.19 (dd, 1H, J=2.8, J=
13.0), 4.61 (ABq, 2H, J=11.4), 4.91–4.98 (m, 1H), 5.07
(d, 1H, J=2.4), 5.96–6.11 (m, 2H), 6.85 (d, 2 ArH,
J=8.6), 7.37 (d, 2 ArH, J=8.6); 13C NMR: l 21.5,
55.6, 61.7, 63.8, 69.9, 92.2, 114.3, 125.4, 130.1, 130.2,
131.5, 159.8, 170.9; [h]D +58.3 (c 0.5, CHCl3); MS m/z:
278 (M+), 263, 219, 189, 141, 122, 121, 81, 60. Anal.
calcd for C15H18O5: C, 64.74; H, 6.52. Found: C, 64.69;
H, 6.56%.
4.15.4. Isopropyl b-
D
-2,3-dideoxypent-2-enoglycero-
pyranoside 20a. The title compound was prepared in a
quantitative yield starting from isopropyl b-
D
-4-O-ace-
11a.
tyl-2,3-dideoxypent-2-enoglyceropyranoside
Colourless oil; IR (CHCl3): 3410 cm−1; 1H NMR: l

C. Fa6a et al. / Tetrahedron: Asymmetry 12 (2001) 2731–2741
2737
1.17 (d, 6H, 50%, J=6.1), 1.22 (d, 6H, 50%, J=6.1),
2.15 (br d, 1H, J=7.2, OH), 3.75 (d, 1H, J=12.4),
3.76–3.87 (m, 1H), 3.97 (m, 1H, J=6.1), 4.14 (dd, 1H,
J=2.6, J=12.4), 5.03 (d, 1H, J=3.4), 5.84 (dd, 1H,
J=3.4, J=9.9), 6.12 (dd, 1H, J=5.3, J=9.9); 13C
NMR: l 22.3, 24.0, 61.9, 64.6, 91.7, 129.3, 129.5; [h]D
+101.4 (c 0.5, CHCl3); MS m/z: 158 (M+), 140, 99, 82,
81. Anal. calcd for C8H14O3: C, 60.74; H, 8.92. Found:
C, 60.69; H, 8.97%.
1H, J=9.0, J=15.1), 5.03 (br s, 1H), 5.14–5.26 (m,
1H), 5.84–5.95 (m, 1H), 5.96–6.05 (m, 1H); 13C NMR:
l 22.3, 24.0, 39.1, 60.6, 61.8, 71.1, 92.6, 127.7, 131.9;
[h]D +98.2 (c 0.5, CHCl3). Anal. calcd for C9H16O5S: C,
45.75; H, 6.83. Found: C, 45.69; H, 6.77%.
4.16.2. Benzyl a-
pent-2-enoglyceropyranoside 13b. The title compound
-2,3-
D
-4-O-methanesulphonyl-2,3-dideoxy-
was prepared in 93% yield starting from benzyl a-
D
dideoxypent-2-enoglyceropyranoside 12b. White solid;
4.15.5. Benzyl b-
side 20b. The title compound was prepared in a quanti-
-4-O-acetyl-2,3-
D
-2,3-dideoxypent-2-enoglyceropyrano-
1
mp 53–55°C; H NMR: l 3.06 (s, 3H), 3.95 (dd, 1H,
J=6.0, J=11.2), 4.03 (dd, 1H, J=7.8, J=11.2), 4.58
(d, 1H, J=11.7), 4.82 (d, 1H, J=11.7), 5.04 (br s, 1H),
5.19–5.28 (m, 1H), 5.95 (ddd, 1H, J=1.5, J=3.5, J=
10.3), 5.99–6.81 (m, 1H), 7.35 (m, 5 ArH); 13C NMR: l
39.1, 60.9, 70.7, 71.0, 93.5, 128.2, 128.6, 129.0, 129.3,
129.4, 129.9, 131.2 [h]D +84.2 (c 0.5, CHCl3). Anal.
calcd for C13H16O5S: C, 54.92; H, 5.67. Found: C,
54.86; H, 5.72%.
tative yield starting from benzyl b-
D
dideoxypent-2-enoglyceropyranoside 11b. Low melting
1
solid; IR (CHCl3): 3411 cm−1; H NMR: l 3.81 (d, 1H,
J=8.8, OH), 3.81 (d, 1H, J=12.7), 4.16 (dd, 1H,
J=2.3, J=12.7), 4.57 (d, 1H, J=11.8), 4.79 (d, 1H,
J=11.8), 5.01 (d, 1H, J=3.1), 5.87 (dd, 1H, J=3.1,
J=10.0), 6.11 (dd, 1H, J=5.3, J=10.0), 7.36 (m, 5
ArH); 13C NMR: l 61.8, 65.0, 70.2, 92.6, 128.3, 128.6,
129.0, 129.9, 138.1; [h]D +99.2 (c 0.5, CHCl3); MS m/z:
206 (M+), 188, 115, 91, 82, 77. Anal. calcd for
C12H14O3: C, 69.89; H, 6.84. Found: C, 69.95; H,
6.78%.
4.16.3. p-Methoxybenzyl a- -4-O-methanesulphonyl-2,3-
D
dideoxypent-2-enoglyceropyranoside 13c. The title com-
pound was prepared in 90% yield starting from
p-methoxybenzyl a-D-2,3-dideoxypent-2-enoglyceropy-
4.15.6. p-Methoxybenzyl b-D-2,3-dideoxypent-2-eno-
glyceropyranoside 20c. The title compound was pre-
pared in a quantitative yield starting from p-methoxy-
1
ranoside 12c. White solid; mp 74–76°C; H NMR: l
3.06 (s, 3H), 3.81 (s, 3H), 3.94 (dd, 1H, J=5.9, J=
11.2), 4.02 (dd, 1H, J=7.9, J=11.2), 4.63 (ABq, 2H,
J=11.4), 5.02 (br s, 1H), 5.15–5.35 (m, 1H), 5.87–5.96
(m, 1H), 5.98–6.07 (m, 1H), 6.89 (d, 2 ArH, J=8.7),
7.29 (d, 2 ArH, J=8.7); 13C NMR: l 39.1, 55.8, 60.9,
70.4, 70.9, 93.2, 114.4, 128.1, 129.9, 130.3, 130.4, 131.4,
159.9; [h]D +61.2 (c 0.5, CHCl3). Anal. calcd for
C14H18O6S: C, 53.49; H, 5.77. Found: C, 53.54; H,
5.73%.
benzyl
b-D-4-O-acetyl-2,3-dideoxypent-2-enoglycero-
pyranoside 11c. White solid; mp 59–60°C; IR (CHCl3):
3351 cm−1; 1H NMR: l 1.86 (d, 1H, OH, J=8.5),
3.75–3.92 (m, 1H), 3.81 (s, 3H), 3.82 (d, 1H, J=12.1),
4.16 (dd, 1H, J=2.8, J=12.1), 4.62 (ABq, 2H, J=
11.4), 5.14 (d, 1H, J=3.1), 5.87 (dd, 1H, J=3.1, J=
9.9), 6.13 (dd, 1H, J=5.2, J=9.9), 6.99 (d, 2 ArH,
J=8.7), 7.27 (d, 2 ArH, J=8.7); 13C NMR: l 55.7,
61.8, 65.0, 69.7, 92.3, 114.3, 128.7, 129.8, 130.2, 130.3,
159.8; [h]D +68.4 (c 0.5, CHCl3); MS m/z: 236 (M+),
221, 218, 206, 189, 121, 103, 81, 77. Anal. calcd for
C13H16O4: C, 66.09; H, 6.83. Found: C, 66.03; H,
6.87%.
4.16.4.
Isopropyl
b-D-4-O-methanesulphonyl-2,3-di-
deoxypent-2-enoglyceropyranoside 21a. Compound 21a
was prepared in 95% yield starting from isopropyl
b-D
-2,3-dideoxypent-2-enoglyceropyranoside
20a.
1
Colourless oil; H NMR: l 1.08 (d, 6H, 50%, J=6.2),
1.13 (d, 6H, 50%, J=6.2), 3.04 (s, 3H), 3.82 (dd, 1H,
J=1.2, J=13.5), 3.88 (m, 1H, J=6.2), 4.13 (dd, 1H,
J=2.3, J=13.5), 4.75 (br s, 1H), 5.01–5.12 (m, 1H),
5.96–6.02 (m, 2H); 13C NMR: l 22.2, 23.9, 39.3, 61.5,
70.1, 70.6, 91.3, 123.9, 133.6; [h]D +102.0 (c 0.5,
CHCl3); MS m/z: 236 (M+). Anal. calcd for C9H16O5S:
C, 45.75; H, 6.83. Found: C, 45.69; H, 6.77%.
4.16. Preparation of methanesulphonates 13a–c and
21a–c. General procedure
To a solution containing the alcohols 12a–c or 20a–c
(6.4 mmol), triethylamine (0.64 g, 6.4 mmol) and
DMAP (0.3 g) in ethyl acetate (70 mL), methane-
sulphonyl chloride (0.7 g, 6.4 mmol) dissolved in ethyl
acetate (10 mL) was added at 0°C. After 3 h the
suspension was poured in ice–water and extracted with
ethyl acetate (3×100 mL). After drying (Na2SO4), the
residue was purified by chromatography on silica gel
(cyclohexane:ethyl acetate 1:1) to give the methane-
sulphonates 13a–c or 21a–c.
4.16.5. Benzyl b- -4-O-methanesulphonyl-2,3-dideoxy-
D
pent-2-enoglyceropyranoside 21b. Compound 21b was
prepared in 91% yield as reported for 6a, but starting
from benzyl b-D-2,3-dideoxypent-2-enoglyceropyran-
1
oside 20b. Colourless oil; H NMR: l 3.06 (s, 3H), 4.06
(d, 1H, J=13.3), 4.25 (dd, 1H, J=2.6, J=13.5), 4.59
(d, 1H, J=11.7), 4.79 (d, 1H, J=11.7), 4.85–4.92 (m,
1H), 5.11 (d, 1H, J=1.6), 6.04–6.19 (m, 2H), 7.36 (m, 5
ArH); 13C NMR: l 39.5, 61.9, 69.8, 70.6, 92.3, 124.4,
128.6, 128.9, 129.0, 133.0, 137.8; [h]D +81.4 (c 0.5,
CHCl3); MS m/z: 284 (M+). Anal. calcd for C13H16O5S:
C, 54.92; H, 5.67. Found: C, 54.85; H, 5.71%.
4.16.1. Isopropyl a- -4-O-methanesulphonyl-2,3-di-
D
deoxypent-2-enoglyceropyranoside 13a. The title com-
pound was obtained in 89% yield starting from isopro-
pyl a- -2,3-dideoxypent-2-enoglyceropyranoside 12a.
D
1
Colourless oil; H NMR: l 1.05 (d, 6H, 50%, J=6.2),
1.21 (d, 6H, 50%, J=6.2), 3.07 (s, 3H), 3.87–4.06 (m,
1H, J=6.2), 3.90 (dd, 1H, J=5.9, J=15.1), 3.99 (dd,

2738
C. Fa6a et al. / Tetrahedron: Asymmetry 12 (2001) 2731–2741
4.16.6. p-Methoxybenzyl b-
D
-4-O-methanesulphonyl-2,3-
4.17.2.1. Benzyl a-L-4-azido-2,3,4-trideoxypent-2-
dideoxypent-2-enoglyceropyranoside 21c. Compound
21c was prepared in 90% yield starting from p-
enoglyceropyranoside 14b. Colourless oil; IR (CHCl3):
1
2099 cm−1; H NMR: l 3.31–3.41 (m, 1H), 3.94 (d, 1H,
methoxybenzyl
b-D
-2,3-dideoxypent-2-enoglyceropy-
J=12.1), 4.23 (dd, 1H, J=2.3, J=12.1), 4.59 (d, 1H,
J=11.8), 4.80 (d, 1H, J=11.8), 5.08 (d, 1H, J=2.6),
6.06 (dd, 1H, J=5.1, J=10.0), 6.15 (dd, 1H, J=2.6,
J=10.0), 7.36 (m, 5 ArH); 13C NMR: l 53.8, 61.5, 70.4,
93.5, 123.4, 128.5, 128.7, 128.8, 129.0, 130.0, 138.7; [h]D
−66.8 (c 0.5, CHCl3); MS m/z: 231 (M+), 203, 107, 96,
91, 77. Anal. calcd for C12H13N3O2: C, 62.33; H, 5.67;
N, 18.17. Found: C, 62.37; H, 5.62; N, 18.24%.
1
ranoside 20c. White solid; mp 67–69°C; H NMR: l
3.07 (s, 3H), 3.81 (s, 3H), 4.05 (d, 1H, J=13.5), 4.24
(dd, 1H, J=2.5, J=13.5), 4.62 (ABq, 2H, J=11.3),
4.85–4.91 (m, 1H), 5.09 (d, 1H, J=1.6), 6.04–6.16 (m,
2H), 6.89 (d, 2 ArH, J=8.8), 7.28 (d, 2 ArH, J=8.8);
13C NMR: l 39.4, 55.7, 61.8, 69.7, 70.1, 91.9, 114.3,
124.3, 129.8, 130.3, 133.1, 159.9; [h]D +77.6 (c 0.5,
CHCl3); MS: 314 (M+). Anal. calcd for C14H18O6S: C,
53.49; H, 5.77. Found: C, 53.44; H, 5.72%.
4.17.2.2. Benzyl a-2-azido-2,3,4-trideoxypent-3-eno-
pyranoside 15b. Colourless oil; IR (CHCl3): 2100 cm−1;
1H NMR: l 3.47–3.54 (m, 1H), 4.09–4.34 (m, 2H), 4.63
(d, 1H, J=11.9), 4.84 (d, 1H, J=11.9), 4.93 (d, 1H,
J=1.4), 5.74–5.87 (m, 1H), 6.12–6.22 (m, 1H), 7.37 (m,
5 ArH); 13C NMR: l 55.9, 60.9, 70.5, 98.3, 119.4, 128.5,
128.7, 128.9, 131.5, 138.7; [h]D +68.8 (c 0.5, CHCl3);
MS m/z: 231 (M+), 203, 107, 96, 91, 81, 77. Anal. calcd
for C12H13N3O2: C, 62.33; H, 5.67; N, 18.17. Found: C,
62.26; H, 5.73; N, 18.22%.
4.17. Preparation of azides 14a–c, 15a–c and 22a–c.
General procedure
To a solution containing the methanesulphonates 13a–c
and 21a–c (4.0 mmol) in benzene (40 mL), Amberlite
IRA-900 in the azide form9 (5.0 g, 3.0 mequiv./g) was
added and the suspension was refluxed for 2 h. The
resin was then filtered off and the solvent removed
under reduced pressure. The residue was purified by
silica-gel chromatography (cyclohexane:ethyl acetate
4:1), to give pure isolated azides 14a–c, 15a–c and
22a–c.
4.17.3. p-Methoxybenzyl a-L-4-azido-2,3,4-trideoxypent-
2-enoglyceropyranoside 14c and p-methoxybenzyl a-2-
azido-2,3,4-trideoxypent-3-enopyranoside 15c. Starting
from the methanesulphonyl derivative 13c, the title
compounds were obtained in 89% overall yield and 3:7
d.r.
4.17.1.
Isopropyl
a-L-4-azido-2,3,4-trideoxypent-2-
enoglyceropyranoside 14a and isopropyl a-2-azido-2,3,4-
trideoxypent-3-enopyranoside 15a. Starting from
methanesulphonyl derivative 13a, the title compounds
were obtained in 85% overall yield and 7:3 d.r.
4.17.3.1. p-Methoxybenzyl a-L-4-azido-2,3,4-trideoxy-
pent-2-enoglyceropyranoside 14c. Colourless oil; IR
1
(CHCl3): 2098 cm−1; H NMR: l 3.28–3.35 (m, 1H),
3.80 (s, 3H), 3.93 (dd, 1H, J=1.0, J=12.2), 4.21 (dd,
1H, J=2.7, J=12.2), 4.62 (ABq, 2H, J=11.4), 5.05 (d,
1H, J=2.6), 6.02 (dd, 1H, J=5.0, J=10.9), 6.09 (dd,
1H, J=2.6, J=10.9), 6.89 (d, 2 ArH, J=8.6), 7.29 (d,
2 ArH, J=8.6); 13C NMR: l 52.2, 55.7, 62.9, 70.0, 92.2,
114.4, 124.6, 130.1, 130.3, 131.4, 159.9; [h]D −136.1 (c
0.5, CHCl3); MS m/z: 261 (M+), 246, 233, 124, 121, 96,
81, 77. Anal. calcd for C13H15N3O3: C, 59.76; H, 5.79;
N, 16.08. Found: C, 59.71; H, 5.74; N, 16.13%.
4.17.1.1. Isopropyl a-L-4-azido-2,3,4-trideoxypent-2-
enoglyceropyranoside 14a. Colourless oil; IR (CHCl3):
1
2097 cm−1; H NMR: l 1.18 (d, 6H, 50%, J=6.2), 1.23
(d, 6H, 50%, J=6.2), 3.28–3.37 (m, 1H), 3.90 (d, 1H,
J=12.2), 3.89–4.09 (m, 1H, J=6.2), 4.21 (dd, 1H,
J=2.9, J=12.2), 5.08 (d, 1H, J=2.2), 5.98–6.13 (m,
2H); 13C NMR: l 24.0, 22.3, 52.3, 62.7, 70.6, 91.6,
124.4, 131.8; [h]D −53.6 (c 0.5, CHCl3); MS m/z: 182
(M+), 154, 123, 107, 95. Anal. calcd for C8H13N3O2: C,
52.74; H, 6.64. Found: C, 52.78; H, 6.59%.
4.17.3.2. p-Methoxybenzyl a-2-azido-2,3,4-trideoxy-
pent-3-enopyranoside 15c. Colourless oil; IR (CHCl3):
1
2098 cm−1; H NMR: l 3.44–3.51 (m, 1H), 3.81 (s, 3H),
4.17.1.2. Isopropyl a-2-azido-2,3,4-trideoxypent-3-
enopyranoside 15a. Colourless oil; IR (CHCl3): 2097
4.15 (ddd, 1H, J=2.4, J=3.8, J=17.1), 4.27 (ddd, 1H,
J=2.3, J=4.7, J=17.1), 4.66 (ABq, 2H, J=11.4),
5.71–5.83 (m, 1H), 6.08–6.19 (m, 1H), 6.89 (d, 2 ArH,
J=8.7), 7.29 (d, 2 ArH, J=8.7); 13C NMR: l 55.7,
55.9, 60.8, 70.1, 98.0, 114.4, 124.6, 130.1, 130.3, 131.4,
159.9; [h]D +181.3 (c 0.5, CHCl3); MS m/z: 261 (M+),
246, 233, 124, 121, 96. Anal. calcd for C13H15N3O3: C,
59.76; H, 5.79; N, 16.08. Found: C, 59.74; H, 5.75; N,
16.12%.
1
cm−1; H NMR: l 1.19 (d, 6H, 50%, J=6.2), 1.24 (d,
6H, 50%, J=6.2), 3.41–3.53 (m, 1H), 3.87–4.08 (m, 1H,
J=6.2), 4.12 (ddd, 1H, J=2.1, J=4.0, J=17.2), 4.25
(ddd, 1H, J=2.4, J=4.6, J=17.2), 4.88 (d, 1H, J=2.6),
5.69–5.81 (m, 1H), 6.06–6.16 (m, 1H); 13C NMR: l
22.1, 23.8, 56.6, 61.2, 70.8, 97.7, 119.9, 131.4; [h]D −71.4
(c 0.5, CHCl3); MS m/z: 182 (M+), 154, 123, 107, 95.
Anal. calcd for C8H13N3O2: C, 52.74; H, 6.64. Found:
C, 52.68; H, 6.70%.
4.17.4. Isopropyl b-L-4-azido-2,3,4-trideoxypent-2-eno-
glyceropyranoside 22a. Starting from the methane-
sulphonyl derivative 21a, the title compound was
obtained in 81% yield; colourless oil; IR (CHCl3): 2101
4.17.2. Benzyl a-L-4-azido-2,3,4-trideoxypent-2-eno-
glyceropyranoside 14b and benzyl a-2-azido-2,3,4-
trideoxypent-3-enopyranoside 15b. Starting from
methanesulphonyl derivative 13b, the title compounds
were obtained in 91% overall yield and 40:60 d.r.
1
cm−1; H NMR: l 1.17 (d, 6H, 50%, J=6.1), 1.24 (d,
6H, 50%, J=6.1), 3.71–3.83 (m, 2H), 3.87–4.06 (m, 1H,
J=6.1), 3.88–3.93 (m, 1H), 5.04 (s, 1H), 5.82–6.03 (m,

C. Fa6a et al. / Tetrahedron: Asymmetry 12 (2001) 2731–2741
2739
2H); 13C NMR: l 22.4, 24.1, 53.6, 61.1, 70.7, 92.6,
128.4, 130.5; [h]D −132.2 (c 0.5, CHCl3); MS m/z: 183
(M+), 182, 107, 154, 123, 95. Anal. calcd for
C8H13N3O2: C, 52.45; H, 7.15; N, 22.94. Found: C,
52.39; H, 7.19; N, 22.89%.
5.00 (d, 1H, J=2.9), 5.85 (dd, 1H, J=2.9, J=10.0),
6.01 (dd, 1H, J=5.3, J=10.0), 7.05 (d, 1H, J=7.9,
NH), 7.45 (d, 2 ArH, J=8.6), 7.76 (d, 2 ArH, J=8.6);
13C NMR: l 22.1, 23.8, 42.8, 62.6, 70.6, 91.9, 99.1,
127.4, 129.1, 129.9, 131.7, 138.1, 167.2; [h]D −48.2 (c
0.5, CHCl3); MS m/z: 387 (M+), 357, 328, 303, 302,
299, 248, 231, 203, 161, 127, 101, 87, 81. Anal. calcd for
C15H18NO3I: C, 46.53; H, 4.69; N, 3.62. Found: C,
46.47; H, 4.64; N, 3.67%.
4.17.5. Benzyl b-L-4-azido-2,3,4-trideoxypent-2-eno-
glyceropyranoside 22b. Starting from the methane-
sulphonyl derivative 21b, the title compound was
obtained in 89% yield; colourless oil; IR (CHCl3): 2101
cm−1; 1H NMR: l 3.82–3.89 (m, 2H), 3.90–4.03 (m,
1H), 4.59 (d, 1H, J=11.8), 4.83 (d, 1H, J=11.8), 5.05
(s, 1H), 5.89–5.98 (m, 1H), 5.99–6.07 (m, 1H), 7.36 (m,
5 ArH); 13C NMR: l 53.8, 61.6, 70.4, 93.6, 128.5, 128.7,
129.0, 129.1, 130.1, 138.2; [h]D −140.4 (c 0.5, CHCl3);
MS m/z: 231 (M+), 203, 107, 96, 91, 77. Anal. calcd for
C12H13N3O2: C, 62.33; H, 5.67; N, 18.17. Found: C,
62.27; H, 5.64; N, 18.21%.
4.18.2. Isopropyl a-2-(p-iodobenzamido)-2,3,4-trideoxy-
pent-3-enopyranoside 19. Starting from 15a, the title
compound was obtained in 92% yield; white solid; mp
1
71–73°C; IR (CHCl3): 3340, 1648 cm−1; H NMR: l
1.23 (d, 6H, 50%, J=6.1), 1.26 (d, 6H, 50%, J=6.1),
3.87–4.05 (m, 1H, J=6.1), 4.06 (ddd, 1H, J=2.3, J=
2.3, J=16.8), 4.28 (ddd, 1H, J=2.2, J=4.4, J=16.8),
4.38–4.49 (m, 1H), 4.95 (s, 1H), 5.79–5.92 (m, 1H),
5.98–6.09 (m, 1H), 6.16 (d, 1H, J=8.1), 7.51 (d, 2 ArH,
J=8.5), 7.79 (2 ArH, J=8.5); 13C NMR: l 22.2, 23.7,
46.9, 97.1, 99.1, 121.9, 129.1, 130.5, 138.3, 166.4; [h]D
−61.6 (c 0.5, CHCl3); MS m/z: 387 (M+), 357, 328, 300,
299, 248, 232, 231, 203, 177, 149, 127, 81. Anal. calcd
for C15H18NO3I: C, 46.53; H, 4.69; N, 3.62. Found: C,
46.49; H, 4.75; N, 3.66%.
4.17.6. p-Methoxybenzyl b-L-4-azido-2,3,4-trideoxypent-
2-enoglyceropyranoside 22c. Starting from the methane-
sulphonyl derivative 21c, the title compound was
obtained in 86% yield; colourless oil; IR (CHCl3): 2097
1
cm−1; H NMR: l 3.80 (s, 3H), 3.78–4.01 (m, 3H), 4.64
(ABq, 2H, J=11.5), 5.03 (br s, 1H), 5.87–5.96 (m, 1H),
5.96–6.04 (m, 1H), 6.90 (d, 2 ArH, J=8.7), 7.30 (d, 2
ArH, J=8.7); 13C NMR: l 53.8, 54.8, 55.7, 70.0, 93.3,
114.4, 114.7, 128.5, 130.2, 130.3, 159.9; [h]D −137.5 (c
0.5, CHCl3); MS m/z: 261 (M+), 246, 233, 166, 122,
121, 96, 81, 77. Anal. calcd for C13H15N3O3: C, 59.76;
H, 5.79; N, 16.08. Found: C, 59.72; H, 5.75; N, 16.13%.
4.19. Preparation of amines 23a–c. General procedure
To a solution containing the azides 22a–c (11 mmol) in
dry THF (40 mL), LiAlH4 (0.4 g, 10 mmol) was added
at 0°C under an argon atmosphere and the mixture was
stirred for 2 h. Then, methanol (1 mL) was added,
followed by a 4 M NaOH solution (30 mL), and the
mixture was extracted with ethyl acetate (3×150 mL).
After drying (Na2SO4), the solvent was removed under
reduced pressure and the residue was purified by silica-
gel chromatography (cyclohexane:ethyl acetate 1:4).
4.18. Preparation of amides 17 and 19. General
procedure
To a solution of the azides 14a or 15a (1.5 g, 8.0 mmol)
in dry THF (30 mL), LiAlH4 (0.31 g, 8.0 mmol) was
added at 0°C under an argon atmosphere and the
mixture was stirred for 2 h. Then, methanol (1 mL) was
added, followed by a 4 M NaOH solution (30 mL), and
the mixture was extracted with ethyl acetate (3×150
mL). After drying (Na2SO4), the solvent was removed
under reduced pressure to give the corresponding
amines which were directly acylated: A solution con-
taining the amines 16 or 18 (1.1 g, 3.6 mmol), triethyl-
amine (0.4 g, 4 mmol) and DMAP (0.3 g) in ethyl
acetate (70 mL) was treated by slow addition of a
solution of 4-iodobenzoyl chloride (1.0 g, 3.7 mmol) in
ethyl acetate (20 mL) at 0°C. After stirring for 1 h,
water (40 mL) was added and the mixture was
extracted with ethyl acetate. After drying (Na2SO4), the
solvent was removed under reduced pressure and the
residue was purified by silica-gel chromatography
(cyclohexane:ethyl acetate 7:3), to give pure isolated 9
or 10.
4.19.1.
Isopropyl
b-L-4-amino-2,3,4-trideoxypent-2-
enoglyceropyranoside 23a. Starting from 22a, the title
compound was obtained in 87% yield; colourless oil; IR
(CHCl3): 3346 cm−1; H NMR: l 1.17 (d, 6H, 50%,
1
J=6.2), 1.22 (d, 6H, 50%, J=6.2), 1.45 (br s, 2H, NH),
3.42–3.51 (m, 1H), 3.48–3.75 (m, 2H), 3.84–4.08 (m,
1H, J=6.2), 5.01 (s, 1H), 5.65–5.68 (m, 1H), 5.86–5.98
(m, 1H); 13C NMR: l 22.3, 24.1, 45.8, 64.9, 70.2, 92.4,
127.0, 135.7; [h]D −83.2 (c 0.5, CHCl3); MS m/z: 158
(M++1), 157, 114, 98, 69. Anal. calcd for C8H15NO2: C,
61.62; H, 9.62; N, 8.91. Found: C, 61.58; H, 9.67; N,
8.94%.
4.19.2. Benzyl b-L-4-amino-2,3,4-trideoxypent-2-eno-
glyceropyranoside 23b. Starting from 22b, the title com-
pound was obtained in 88% yield; colourless oil; IR
1
(CHCl3): 3348 cm−1; H NMR: l 1.16 (br s, 2H, NH),
3.46 (dd, 1H, J=9.5, J=9.5), 3.78 (dd, 1H, J=4.4,
J=9.5), 4.05–4.25 (m, 1H), 4.56 (d, 1H, J=11.8), 4.81
(d, 1H, J=11.8), 5.01 (br s, 1H), 5.70–5.81 (m, 1H),
5.89–6.01 (m, 1H), 7.35 (m, 5 ArH); 13C NMR: l 45.7,
62.2, 65.1, 70.2, 93.4, 126.4, 128.3, 128.4, 128.8, 136.0,
138.4; [h]D −63.6 (c 0.5, CHCl3); MS m/z: 206 (M++1),
205, 115, 107, 98, 99, 77. Anal. calcd for C12H15NO2: C,
70.22; H, 7.37; N, 6.82. Found: C, 70.17; H, 7.33; N,
6.86%.
4.18.1. Isopropyl a- -4-(p-iodobenzamido)-2,3,4-tride-
L
oxypent-2-enoglyceropyranoside 17. Starting from 14a,
the title compound was obtained in 90% yield; white
1
solid; mp 66–68°C; IR (CHCl3): 3338, 1651 cm−1; H
NMR: l 1.12 (d, 6H, 50%, J=6.1), 1.17 (d, 6H, 50%,
J=6.1), 3.69 (d, 1H, J=12.1), 3.84–3.98 (m, 1H, J=
6.1), 4.17 (dd, 1H, J=3.2, J=12.1), 4.31–4.22 (m, 1H),

2740
C. Fa6a et al. / Tetrahedron: Asymmetry 12 (2001) 2731–2741
4.19.3.
p-Methoxybenzyl
b-
L
-4-amino-2,3,4-tri-
J=11.0), 4.59 (ABq, 2H, J=11.3), 4.77–4.91 (m, 1H),
5.01 (s, 1H), 5.79 (m, 1H,), 5.90 (m, 1H), 6.73 (d, 1H,
NH), 6.83 (d, 2 ArH, J=8.7), 7.24 (d, 2 ArH, J=8.7),
7.25–7.53 (m, 3 ArH), 7.68–7.78 (m, 2 ArH); 13C NMR:
l 44.2, 55.7, 62.1, 70.1, 93.6, 114.3, 127.7, 128.8, 128.9,
129.8, 129.9, 130.2, 130.3, 130.5, 131.2, 132.1, 134.5,
159.8, 167.9; [h]D −80.0 (c 0.5, CHCl3) MS m/z: 339
(M+), 204, 203, 166, 112, 107, 105, 99, 77. Anal. calcd
for C20H21NO4: C, 70.78; H, 6.24; N, 4.13. Found: C,
70.74; H, 6.20; N, 4.17%.
deoxypent-2-enoglyceropyranoside 23c. Starting from
22c, the title compound was obtained in 76% yield;
colourless oil; IR (CHCl3): 3345 cm−1; H NMR: l 1.89
1
(br s, 2H, NH2), 3.41–3.56 (m, 2H), 3.69–3.83 (m, 1H),
3.78 (s, 3H), 4.59 (ABq, 2H, J=11.4), 4.97 (br s, 1H),
5.64–5.76 (m, 1H), 5.86–5.96 (m, 1H), 6.86 (d, 2 ArH,
J=8.6), 7.27 (d, 2 ArH, J=8.6); 13C NMR: l 45.7,
55.7, 65.0, 69.8, 93.1, 114.3, 126.6, 130.1, 130.2, 135.7,
159.7; [h]D +77.4 (c 0.5, CHCl3); MS m/z: 236 (M++1),
235, 221, 220, 166, 112, 107, 99, 77. Anal. calcd for
C13H17NO3: C, 66.36; H, 7.28; N, 5.95. Found: C,
66.31; H, 7.24; N, 5.89%.
4.21. Computational methods
Ab initio molecular orbitals and DFT calculations were
carried out using the GAUSSIAN 94 program pack-
age.20 For DFT calculations the hybrid functional
B3LYP which contains gradient corrections for both
exchange and correlation was chosen. The geometry of
the reactants, products and transition structures were
fully optimised at RHF/6-31G* theory level. The calcu-
lated stationary points (local minima and saddle points)
were characterised by harmonic vibrational frequency
calculations at both HF/6-31G* and B3LYP/6-31G*
levels.21,22,25 Transition structures were characterised by
a single imaginary frequency whereas reactant and
products had none. The Becke3LYP method is found
to predict activation barriers for closed- and open-shell
pathways of pericyclic reactions in excellent agreement
with the available experimental data.26
4.20. Preparation of amides 24a–c. General procedure
To a solution containing the amine 23a–c (10 mmol),
triethylamine (1.1 g, 11 mmol) and DMAP (0.3 g) in
ethyl acetate (70 mL) at 0°C, a solution containing the
appropriate acyl chloride (11 mmol) in ethyl acetate (20
mL) was slowly added. After 1 h, water (40 mL) was
added and the mixture was extracted with ethyl acetate
(3×150 mL). After drying (Na2SO4), the solvent was
removed under reduced pressure and the residue was
purified by silica-gel chromatography (cyclohex-
ane:ethyl acetate 7:3) to give the amides 24a–c.
4.20.1. Isopropyl b-
L
-4-iodoacetamido-2,3,4-trideoxy-
24a. Starting from
pent-2-enoglyceropyranoside
iodoacetyl chloride and 23a, the title compound was
obtained in 71% yield; colourless oil; IR (CHCl3): 1674
Acknowledgements
1
cm−1; H NMR: l 1.17 (d, 6H, 50%, J=6.2), 1.23 (d,
6H, 50%, J=6.2), 3.65 (dd, 1H, J=8.1, J=11.0), 3.88
(s, 2H), 3.82 (dd, 1H, J=5.4, J=11.0), 3.88–4.06 (m,
1H, J=6.2), 4.49–4.64 (m, 1H), 5.05 (s, 1H), 5.72–5.94
(m, 2H), 6.12 br d, 1H, J=8.1, NH); 13C NMR: l 22.4,
24.1, 44.4, 61.9, 71.0, 93.1, 129.8, 130.3, 167.5; [h]D
−81.3 (c 0.5, CHCl3); MS m/z: 325 (M+), 267, 132, 120,
114, 69. Anal. calcd for C10H16NO3I: C, 36.94; H, 4.96;
N, 4.31. Found: C, 36.87; H, 4.92; N, 4.25%.
We thank M.I.U.R. (Roma, Italy) for a grant (PRIN
2000) and Dr. Luca Santini for valuable technical
support.
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methylmalonyl chloride and 23b, the title compound
was obtained in 76% yield; colourless oil; IR (CHCl3):
1
3346, 1743, 1685 cm−1; H NMR: l 3.31 (s, 2H), 3.67
(dd, 1H, J=9.3, J=11.0), 3.71 (s, 3H), 3.87 (dd, 1H,
J=5.5, J=11.0), 4.56 (d, 1H, J=11.7), 4.57–4.80 (m,
1H), 4.80 (d, 1H, J=11.7), 5.04 (br s, 1H), 5.75–6.02
(m, 2H), 7.10 (d, 1H, NH, J=8.1), 7.21–7.39 (m, 5
ArH); 13C NMR: l 41.7, 43.8, 52.9, 61.7, 70.4, 93.7,
128.2, 128.3, 128.5, 128.9, 131.0, 138.1, 165.7, 169.8;
[h]D −38.8 (c 0.5, CHCl3); MS m/z: 306 (M++1), 305,
290, 275, 198, 184, 169, 118, 101, 98, 91, 77. Anal. calcd
for C16H19NO5: C, 62.94; H, 6.27; N, 4.59. Found: C,
62.89; H, 6.32; N, 4.63%.
4.20.3. p-Methoxybenzyl b-L-4-benzamido-2,3,4-tri-
4. A similar product, prepared in low yield starting from
deoxypent-2-enoglyceropyranoside 24c. Starting from
benzoyl chloride and 23c, the title compound was
obtained in 91% yield; white crystals; mp 72–74°C; IR
D
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1
(CHCl3): 3344, 1658 cm−1; H NMR: l 3.74 (s, 3H),
3.76 (dd, 1H, J=8.1, J=11.0), 3.95 (dd, 1H, J=5.5,

C. Fa6a et al. / Tetrahedron: Asymmetry 12 (2001) 2731–2741
2741
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1907–1913.
15. The structural assignment was confirmed by conversion
of both 7b and 8b into the corresponding p-iodobenza-
mides I and II (R=TBDMS, R%=p-IC6H4CO), which
were easily separated and characterised.
21. (a) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37,
785–789; (b) Becke, A. D. Phys. Rev. A 1988, 38, 3098–
3100; (c) Miehlich, B.; Savin, A.; Stoll, H.; Preuss, H.
Chem. Phys. Lett. 1989, 157, 200–206; (d) Becke, A. D. J.
Chem. Phys. 1993, 98, 5648–5652.
22. Imaginary frequency corresponding to the expected reac-
tion coordinate for TS-1: 188.31i cm−1. Imaginary fre-
quency corresponding to the expected reaction coordinate
for TS-2: 402.49i cm−1
23. The same behaviour was observed by us for [3,3]-sigmat-
ropic thermal rearrangement of 4-O-imidoyl derivatives
IIIa,b and IVa,b. In fact, IIIa,b, where steric constraints
are missing, gave the corresponding trichloroacetamides
Va,b in moderate yield. On the contrary, only traces of
decomposition products, together with unchanged start-
ing material, were observed after protracted heating of
IVa,b (Scheme 9). A similar effect was already observed
for 1-trichloroacetimidoylpent-2-enopyranosides. See:
Dyong, I.; Weygand, J.; Thiem, J. Liebigs Ann. Chem.
1986, 577–599.
Compound I: white solid; mp 66–68°C; IR (CHCl3):
1
3345, 1654 cm−1; H NMR: l 0.06 (s, 3H), 0.07 (s, 3H),
0.90 (s, 9H), 3.49 (s, 3H), 3.78 (d, 2H, J=4.5), 4.19–4.28
(m, 1H), 4.47–4.61 (m, 1H), 4.80 (s, 1H), 5.86–6.08 (m,
2H), 6.16 (d, 1H, J=8.7, NH), 7.48 (d, 2 ArH, J=8.4),
7.77 (d, 2 ArH, J=8.4); 13C NMR: l −4.75, 18.9, 26.4,
46.0, 56.4, 65.5, 69.2, 99.1, 100.5, 123.0, 129.2, 131.5,
134.0, 138.1, 166.5; [h]D −58.2 (c 0.5, CHCl3).
Compound II: white solid; mp 58–60°C; IR (CHCl3):
1
3345, 1654 cm−1; H NMR: l 0.05 (s, 6H), 0.88 (s, 9H),
3.47 (s, 3H), 3.74 (dd, 1H, J=6.6, J=11.1), 3.86 (dd, 1H,
J=4.4, J=11.1), 4.08–4.26 (m, 1H), 4.52–4.62 (m, 1H),
3.94 (d, 1H, J=2.9), 5.92 (dd, 1H, J=2.9, J=9.9), 6.16
(dd, 1H, J=5.7, J=9.9), 6.39 (d, 1H, J=8.8, NH), 7.48
(d, 2 ArH, J=8.5), 7.78 (d, 2 ArH, J=8.5); 13C NMR: l
−4.8, 18.8, 26.3, 43.7, 55.9, 63.6, 70.5, 94.6, 96.0, 128.6,
129.0, 129.1, 138.3, 166.6; [h]D −78.4 (c 0.5, CHCl3).
16. Fraser-Reid, B.; McLean, A.; Usherwood, E. W.;
Yunker, M. Can. J. Chem. 1970, 48, 2877–2884.
Scheme 9. (a) Refluxing toluene, 36 h (40% for IIa; 38% for
IIb).
24. Reed, III, I. A.; Risbood, P. A.; Goodman, L. J. Chem.
Soc., Chem. Commun. 1981, 760–761.
17. Fraser-Reid, B.; Carthy, B. J.; Holder, N. L.; Yunker, M.
Can. J. Chem. 1971, 49, 3038–3044.
25. (a) Roothan, C. C. Rev. Mod. Phys. 1951, 23, 69–88; (b)
For a description of the basis set, see: Hehre, W.;
Radom, L.; Schleyer, P.v. R.; Pople, J. A. Ab initio
Molecular Orbital Theory; Wiley: New York, 1986.
26. (a) Jursic, B. S. J. Mol. Struct. (THEOCHEM) 1995, 358,
139–143; (b) Houk, K. N.; Beno, B. R.; Nendel, M.;
Black, K.; Yoo, H. Y.; Wilsey, S.; Lee, J. K. J. Mol.
Struct. (THEOCHEM) 1997, 398–399, 169–179.
18. Weygand, F. Methods Carbohydr. Chem. 1962, 1, 182.
19. Koreeda, M.; Houston, T. A.; Shull, B. K.; Klemke, E.;
Tuinman, R. J. Synlett 1995, 90–91. Diethyl ether was
used instead of THF since significant amounts of 4-
iodobutanol were observed among the reaction products,
due to ring opening of THF under the described reaction
conditions.
20. Gaussian 94; Frish, M. J.; Trucks, G. W.; Schlegel, H. B.;