Synthesis of 4-octuloses. Part 7: Highly stereoselective synthesis of 2,3-anhydrosugar derivatives as key intermediates in the preparation of sugar β-lactams

Article abstract of DOI:10.1016/S0957-4166(00)00421-3

Reaction of either 1 or 4 with (N,N-dibenzylcarbamoylmethylene)dimethylsulfurane 2 in DMSO afforded 2,3-anhydro-4,5-O-isopropylidene-D-arabino-pentonamide 3 or N,N-dibenzyl 2,3-anhydro-4,5:6,7-di-O-isopropylidene-β-D-glycero-D-galacto-oct-4-u lo-4,8-pyranosonamide 5, respectively. The configurations of 3 and 5 were determined on the basis of their spectroscopic data, in the first case, and by chemical transformation into the known 2,3-anhydro-4,5:6,7-di-O-isopropylidene-β-D-glycero-D-galacto-oct-4-u lo-4,8-pyranose 11. Treatment of 3 and 5 with lithium hexamethyldisilazide in THF provided the corresponding sugar β-lactams 12, 13 and 14, respectively.

Full text of DOI:10.1016/S0957-4166(00)00421-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 4509–4519
Synthesis of 4-octuloses. Part 7: Highly stereoselective
synthesis of 2,3-anhydrosugar derivatives as key
intermediates in the preparation of sugar b-lactams†
Isidoro Izquierdo,* Maria T. Plaza, Rafael Robles and Antonio J. Mota
Department of Organic Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
Received 12 September 2000; accepted 17 October 2000
Abstract
Reaction of either 1 or 4 with (N,N-dibenzylcarbamoylmethylene)dimethylsulfurane 2 in DMSO
afforded 2,3-anhydro-4,5-O-isopropylidene- -arabino-pentonamide or N,N-dibenzyl 2,3-anhydro-
4,5:6,7-di-O-isopropylidene-b- -glycero- -galacto-oct-4-ulo-4,8-pyranosonamide 5, respectively. The
configurations of 3 and 5 were determined on the basis of their spectroscopic data, in the first case, and
by chemical transformation into the known 2,3-anhydro-4,5:6,7-di-O-isopropylidene-b- -glycero-D-
D
3
D
D
D
galacto-oct-4-ulo-4,8-pyranose 11. Treatment of 3 and 5 with lithium hexamethyldisilazide in THF
provided the corresponding sugar b-lactams 12, 13 and 14, respectively. © 2000 Elsevier Science Ltd. All
rights reserved.
1. Introduction
b-Lactams (azetidin-2-ones) have attracted the attention of researchers from all over the world
for many years, since the discovery of the important role played by such cyclic systems in the
inhibition of bacterial cell wall synthesis produced by the b-lactam antibiotics,2 but the increase
in the resistance3 shown by microorganisms to some of the most used antimicrobial agents, have
encouraged the search for new molecules bearing such a moiety that overcome this important
problem.
Our group has recently reported on the highly stereoselective synthesis, starting from common
hexuloses (
D
-fructose and
-sorbose), of several derivatives of 4-octulose,4,5a 2-deoxy-4-octulose5
L
and 2,3-dideoxy-4-octulosononitriles6 used as chiral intermediates in the synthesis of poly-
hydroxyindolizidine analogues1,6,7 of castanospermine, a potent glycosidase inhibitor. Continu-
ing with our efforts in preparing molecules that could show important biological activities, we
* Corresponding author. E-mail: isidoro@platon.ugr.es
†
Part VI: see Ref. 1.
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00421-3

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I. Izquierdo et al. / Tetrahedron: Asymmetry 11 (2000) 4509–4519
planned the synthesis and use of 4-octulosono-a,b-epoxiamide derivatives, such as A shown in
Scheme 1, as a key intermediate in the stereoselective synthesis of the already mentioned
polyhydroxyindolizidines as well as sugar b-lactams, according to previous results.8 We describe
herein the application of this methodology to the synthesis of the latter compounds by an
intramolecular cyclization of A (see Scheme 1) with the simultaneous transfer of the chiral
information located in the sugar moiety to the target molecule.
Scheme 1.
The synthesis of chiral a,b-epoxyamides in a highly stereoselective manner by reaction of
aldehydo-sugars, such as 2,3-O-isopropylidene- -glyceraldehyde, with stabilized sulfur ylides
D
derived from N,N-dimethyl and diethylamide has been reported by Lo´pez-Herrera et al.9 Herein
we have utilized this process but using (N,N-dibenzylcarbamoylmethylene)dimethyl sulfurane 2
as the sulfur ylide. More recently,10 treatment of aldehydes with a camphor-derived chiral
sulfonium ylide has been also reported. On the other hand, the use of carbohydrates as starting
templates for the preparation of chiral b-lactams has been introduced by different groups,
involving methods using aminosugars,11
L
-ascorbic acid,12 -glyceraldehyde derivatives,13 as well
D
as [2+2] cycloaddition reactions between enosugars and isocyanates.14
2. Results and discussion
Reaction of 2,3-O-isopropylidene- -glyceraldehyde 1 with (N,N-dibenzylcarbamoylmeth-
D
ylene)dimethyl sulfurane 2, prepared in situ from the corresponding sulfonium salt and
NaCH2SOCH3 in anhydrous DMSO, proceeded in a highly stereocontrolled manner providing,
in 67% yield, mainly N,N-dibenzyl 2,3-anhydro-4,5-O-isopropylidene-
D
-arabino-pentonamide 3,
slightly contaminated with the -xylo isomer. The configurations of the two new stereogenic
D
centers (C-2,3) in 3 were determined as follows: the chemical shifts for H-2,3 (l 3.64 and 3.33,
respectively), as well as the J2,3 value (2 Hz), suggest a trans disposition for such protons. On the
other hand, the J3,4 (5.3 Hz) for 3 were relevant in order to establish the stereochemistry of 3,
since these values matched quite well (l 3.58 and 3.20, J2,3 2.1, J3,4 5.4 Hz)‡ with those
previously reported9a for the N,N-dimethyl analogue, and since changing the N,N-substituents
should have little significance, the configuration of 3 can be reasonably assumed (Scheme 2).
In a similar way, compound 4 reacted with 2 to afford N,N-dibenzyl 2,3-anhydro-4,5:6,7-di-
O-isopropylidene-b-
D
-glycero- -galacto-oct-4-ulo-4,8-pyranosonamide 5 (see above), but in this
D
case the configurational assignment of 5 proved to be very troublesome. Thus, in a first
approach we tried to correlate compound 5 with the corresponding ester 6, whose absolute
‡ These values for the
D
-xylo isomer were l 3.63 and 3.22, J2,3 2.1, J3,4 3.5 Hz, respectively.9a

I. Izquierdo et al. / Tetrahedron: Asymmetry 11 (2000) 4509–4519
4511
Scheme 2.
configuration is known,5b after transforming both compounds into the same 2-dibenzylamino-3-
hydroxy derivative 7; treatment with N,N-dibenzylamine was hoped to effect the regioselective15
opening of the oxirane ring concomitant with a transamidation of the ester 6, but unfortunately
the latter process did not take place and instead ester 8 was obtained. Attempts to interchange
functionality between 7 and 8 were unsuccessful and a new strategy had to be envisaged. Thus,
compounds 5 and 6 were treated in a sealed tube with aqueous ammonia in methanol in order
to promote the appropriate transformations (regioselective oxirane ring opening at C-2 and
transamidation) in both molecules leading again to a common compound, namely 2-amino-2-
deoxy-4,5:6,7-di-O-isopropylidene-b-
D
-glycero- -talo-oct-4-ulo-4,8-pyranoson amide 10; this
D
occurred with 6, but transamidation of 5 again did not take place and the related N,N-dibenzyl-
amide 9 was obtained. Steric factors are presumably responsible for the difficulty found in the
displacement of the N,N-dibenzyl group in 5 by other nucleophiles.
An attempt to open regio- and stereoselectively the 2,3-oxirane ring in 5 with NaBH4 in
refluxing methanol, according to the literature,9b was unsuccessful and decomposition of the
molecule occurred, but when 5 was treated with LiBH4 in THF at room temperature, only
reduction of the N,N-dibenzylcarbamoyl to a hydroxymethyl group took place and the known5b
2,3-anhydro-4,5:6,7-di-O-isopropylidene-b-
D
-glycero- -galacto-oct-4-ulo-4,8-pyranose 11 was
D
isolated, thus confirming the stereochemistry of the new created stereogenic centers (C-2,3)
(Scheme 3).
Scheme 3.

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I. Izquierdo et al. / Tetrahedron: Asymmetry 11 (2000) 4509–4519
Formation of 11 could be attributed (Scheme 4) to a nucleophilic displacement of the
N,N-dibenzyl by hydride to afford an intermediate aldehyde, followed by its reduction.
Scheme 4.
Finally, reaction of a,b-epoxyamides 3 and 5 with lithium hexamethyldisilazide (LHMDS) in
THF at low temperature (−10°C) gave (Scheme 5) the related b-lactams 12, 13, in :1:1 ratio,
and 14. The low and high stereoselectivity, respectively, found in the intramolecular cyclizations
of 3 and 5 could be rationalized in terms of steric interactions of the small and large substituent
at C-3 with the phenyl group at C-4. Thus, molecular modeling calculations (AM1) on
compounds 12, 13, and 14 and on the unisolated cis-isomer of the latter indicated a small (:3
kcal/mol) difference in ground-state stability between 12 and 13, and :8 kcal/mol in the case
of 14 and its cis-isomer.
Scheme 5.
3. Experimental
3.1. General
Melting points were determined with a Gallenkamp apparatus and are uncorrected. Solutions
1
were dried over MgSO4 before concentration under reduced pressure. The H and 13C NMR
spectra were recorded with Bruker AMX-300, AM-300, ARX-400, and AMX-500 spectrometers
for solutions in CDCl3 (internal Me4Si). IR spectra were recorded with a Perkin–Elmer 782
instrument and mass spectra with a Hewlett–Packard HP-5988-A and Fisons mod. Platform II
and VG Autospec-Q mass spectrometers. Optical rotations were measured for solutions in
CHCl3 (1 dm tube) with a Jasco DIP-370 polarimeter. TLC was performed on precoated silica
gel 60 F254 aluminum sheets and detection by charring with H2SO4. Column chromatography

I. Izquierdo et al. / Tetrahedron: Asymmetry 11 (2000) 4509–4519
4513
was performed on silica gel (Merck, 7734). The noncrystalline compounds, for which elemental
analyses were not obtained, were shown to be homogeneous by chromatography and character-
ized by NMR and HRMS.
3.2. N,N-Dibenzyl-h-bromoacetamide
To an ice-water cooled and well stirred solution of commercial dibenzylamine (Aldrich, 15 g,
76 mmol) in dichloromethane (70 mL), aqueous 40% sodium hydroxide solution (30 mL) was
added and then a solution of bromoacetyl bromide (Aldrich, 6.6 mL, 76 mmol) in
dichloromethane (15 mL) was added dropwise. The mixture was left to reach room temperature
(1 h). The organic phase was separated and the aqueous extracted with dichloromethane (2×25
mL). The combined organic phase and extracts were washed with water and concentrated.
Column chromatography (ether/hexane, 1:3“2:1) afforded the title compound (23.5 g, 97%)
with data identical to those found in the literature.16
3.3. (N,N-Dibenzylcarbamoylmethylene)dimethylsulfonium bromide
A mixture of N,N-dibenzyl-a-bromoacetamide (23.4 g, 73.5 mmol) and dimethyl sulfide (20
mL) was stirred at room temperature in a sealed tube for 24 h. The reaction mixture was then
diluted with ether (30 mL) and the crystalline sulfonium salt filtered off and thoroughly washed
1
with ether to yield 25.7 g, 92%: mp: 134–135°C. NMR data (MeOH-d4): H, l 7.44–7.23 (m,
10H, 2 PhCH2), 4.84 (s, 2H, CH2CO), 5.59 (s, 4H, 2 PhCH2), and 3.02 (s, 6H, SMe2); 13C, l
165.50 (OꢀCNꢁ), 137.24, 136.42, 130.19, 129.80, 129.35, 129.21, 128.86, and 128.41 (PhCH2),
51.91 and 49.77 (SCH2 and PhCH2), and 25.83 (SMe2). Anal. calcd for C18H22BrNOS: C, 56.84;
H, 5.83; N, 3.68. Found: C, 56.43; H, 6.28; N, 3.81.
3.4. Reaction of 2,3-O-isopropylidene-
D
-glyceraldehyde 1 with (N,N-dibenzylcarbamoyl-
methylene)dimethyl sulfurane 2
To a stirred solution of NaCH2SOCH3 from sodium hydride (80% oil dispersion, 500 mg, 16.7
mmol) and imidazole (100 mg, 1.47 mmol) in dry DMSO (25 mL) was added (N,N-dibenzylcar-
bamoylmethylene)dimethylsulfonium bromide (5.76 g, 18 mmol) and the mixture kept at room
temperature for 10 min. A solution of compound 1 (1.3 g, 10 mmol) in dry THF (15 mL) was
added dropwise. After 1 h, the mixture was partitioned into ether/water (50 mL), the organic
phase separated and the aqueous extracted with ether (3×50 mL), the combined organic phase
and extracts were washed with water and concentrated to a residue that was chromatographed
(ether/hexane, 1:2“1:1) to afford syrupy N,N-dibenzyl 2,3-anhydro-4,5-O-isopropylidene-
arabino-pentonamide (3, 2.47 g, 67%) slightly contaminated with the
-xylo isomer, [h]2D3 −6,
1669 (OꢀCNꢁ), 1382 and 1372 (CMe2) cm−1. NMR data: 1H, l 7.40–7.12
D
-
D
24
film
max
[h] −20 (c 1.4); w
405
(m, 10H, 2 PhCH2), 4.63 and 4.57 (2 d, 2H, J=14.8 Hz, PhCH2), 4.59 (s, 2H, PhCH2), 4.09 (dd,
1H, J4,5=5.4, J5,5%=7.6 Hz, H-5), 3.91 (q, 1H, H-4), 3.86 (dd, 1H, J4,5%=5.3 Hz, H-5%), 3.64 (d,
1H, J2,3=2 Hz, H-2), 3.33 (dd, 1H, J3,4=5.3 Hz, H-3), 1.32 and 1.29 (2 s, 6H, CMe2); 13C, l
167.24 (C-1), 136.48, 135.84, 129.12, 128.77, 128.58, 128.01, 127.78, and 126.74 (PhCH2), 110.13
(CMe2), 74.81 (C-4), 66.87 (C-5), 58.09 (C-3), 52.05 (C-2), 49.21 and 48.56 (PhCH2), 26.43 and
25.10 (CMe2). Mass spectrum (EI): m/z 368 (0.6%, M++1), 367 (0.4, M+), 353 (2.0, M++1−Me),
352 (8.7, M+−Me), 277 (1.1, M++1−C7H7), 276 (6.7, M+−C7H7), 267 (8.6, M++1−C5H9O2), 266
(37.7, M+−C5H9O2), 196 (85.1, Bn2N+), 91 (100, C7H+7), and 43 (69.8, Ac+).

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3.5. Reaction of 2,3:4,5-di-O-isopropylidene-i- -arabino-hexos-2-ulopyranose 4 with sulfurane
D
2
Reaction of 4 (1.95 g, 7.55 mmol) in dry THF (20 mL) with sulfurane 2, prepared from
(N,N-dibenzyl carbamoylmethylene)dimethylsulfonium bromide (4.20 g, 13.2 mmol), sodium
hydride (80% oil dispersion, 400 mg, 13.3 mmol) and imidazole (100 mg, 1.47 mmol) in dry
DMSO (15 mL) as above, gave, after column chromatography (ether/hexane, 1:3“1:1), N,N-
dibenzyl 2,3-anhydro-4,5:6,7-di-O-isopropylidene-b-
D
-glycero- -galacto-oct-4-ulo-4,8-pyranoson-
D
amide (5, 3.14 g, 84%) as a colorless solid foam: [h]2D7 +12 (c 1.1); w
1664 (OꢀCNꢁ), 1383 and
film
max
1373 (CMe2) cm−1. NMR data, see Tables 1 and 2. Anal. calcd for C28H33NO7: C, 67.86; H,
6.71; N, 2.83. Found: C, 67.42; H, 6.65; N, 2.87.
3.6. Synthesis of methyl 2,3-anhydro-4,5:6,7-di-O-isopropylidene-i-
D
-glycero- -galacto-oct-4-
D
ulo-4,8-pyranosonate 6
Reaction of 4 (4.7 g, 19.4 mmol) in dry THF (35 mL) with (methoxycarbonyl-
methylene)dimethylsulfurane, prepared from (methoxycarbonylmethylene)dimethyl sulfonium
bromide (8.75 g, 60 mmol), sodium hydride (80% oil dispersion, 1.25 g, 42 mmol) and imidazole
(200 mg, 2.94 mmol) in dry DMSO (30 mL) as above, gave, after column chromatography
(ether/hexane, 1:3), 6 (4.2 g, 70%), which had the same physical and spectroscopic data as those
previously reported.5b
3.7. N,N-Dibenzyl 2-dibenzylamino-2-deoxy-4,5:6,7-di-O-isopropylidene-i-
D
-glycero- -talo-
D
oct-4-ulo-4,8-pyranosonamide 7
A stirred solution of 5 (70 mg, 0.14 mmol) and dibenzylamine (60 mL, 0.31 mmol) in dry
methanol (2 mL) was heated in a sealed tube at 80°C for 48 h. TLC (ether/hexane, 2:3) then
revealed the presence of a faster-running compound. The mixture was concentrated and the
residue supported on silica gel and chromatographed (ether/hexane, 1:4) to afford 7 (85 mg,
23
film
87%) as a colorless syrup: [h]2D2 +3, [h] +14 (c 1.2); w
3264 (OH), 1623 (OꢀCNꢁ), 1382 and
405
max
1372 (CMe2) cm−1. NMR data, see Tables 1 and 2. Anal. calcd for C42H48N2O7: C, 72.81; H,
6.98; N, 4.04. Found: C, 72.51; H, 7.30; N, 4.21.
3.8. Methyl 2-dibenzylamino-2-deoxy-4,5:6,7-di-O-isopropylidene-i-
D
-glycero- -talo-oct-
D
4-ulo-4,8-pyranosonate 8
A stirred solution of 6 (210 mg, 0.64 mmol) and dibenzylamine (190 mg, 0.96 mmol) in dry
methanol (2 mL) was heated in a sealed tube at 60°C for 16 h. TLC (ether/hexane, 1:1) then
showed the presence of a faster-running compound. The mixture was concentrated and the
residue supported on silica gel and chromatographed (ether/hexane, 1:4) to afford 8 (275 mg,
82%) that crystallized on standing, mp: 127–128°C; [h]2D2 −61 (c 1.3); w
3456 (OH), 1712
film
max
(CO2Me), 1382 and 1373 (CMe2) cm−1. NMR data, see Tables 1 and 2. Anal. calcd for C29H37
NO8: C, 66.01; H, 7.07; N, 2.66. Found: C, 66.18; H, 7.21; N, 2.70.

Table 1
1H NMR data for compounds 5 and 7–10
Compound
1H Chemical shifts (l) with multiplicities and coupling constants (Hz)
H-2
H-3
H-5
H-6
H-7
H-8a
H-8e
PhCH2
PhCH2
CMe2
5
3.94d
3.45d
4.33d
4.61dd
4.21bdd
3.81dd
3.68d
7.40–7.15m
4.71d & 4.37d
J=14.7
4.60d & 4.46d
J=16.5
1.46s, 1.44s
1.35s, 1.30s
J
2,3=2
J
5,6=2.6
J6,7=7.9
J7,8a=1.9
8a,8e=13
J
7a
4.21s
4.46d
4.85d
5,6=2.6
4.70dd
6,7=7.9
4.25dd
3.83dd
3.50d
7.35–6.91m
5.18d & 3.67d
J=14.8
1.57s, 1.47s
1.38s
/
J
3,OH=9.1
J
J
J7,8a=1.7
J
8a,8e=12.8
4.16d & 3.64d
J=13.6
4.01d & 3.59d
J=17.3
8b
9c
4.02bs
3.78bd
4.14dd
4.66d
5,6=2.7
4.62dd
6,7=7.8
4.18dd
4.19dd
3.73dd
3.54d
3.60d
7.37–7.19m
7.30m
4.00d & 3.73d
J=14.6
1.58s, 1.40s
1.37s, 1.34s
J
2,3=0.8
J
J
J7,8a=1.4
J3,OH=10.5
J
8a,8e=12.9
4.62s
4.24d
5,6=2.4
4.60dd
6,7=7.6
3.85dd
4.94d & 4.16d
J=14.7
1.41s, 1.39s
1.31s
(
J
2,NH=9.6
J
J
J7,8a=1.9
J
8a,8e=12.7
4.79d & 4.37d
J=16.2
4
10d
3.61bs
3.80bd
4.69d
5,6=2.8
4.59dd
6,7=7.9
4.20dd
3.88dd
3.69d
–
–
1.50s, 1.47s
1.42s, 1.32s
J2,3=3.8
J
J
J7,8a=1.8
J
8a,8e=12.9
a OH-3 at l 7.83.
b OH-3 and OMe at l 4.92 and 3.74, respectively.
c NH2 and OH at l 5.43 and 1.80, respectively.
d NH2 and OH at l 7.26s, 5.96 and 2.00, respectively.

Table 2
13C NMR data for compounds 5 and 7–10
/
Compound
C-1
C-2
C-3
C-4
C-5
C-6
C-7
C-8
CMe2
CMe2
CH2Ph
5
7
167.21
174.76
173.73
177.22
178.63
50.88
50.91
57.16
47.08
55.22
57.91
69.23
73.37
77.64
74.42
100.76
104.77
103.82
103.69
104.63
70.11
69.61
69.67
70.25
70.04
70.77
70.65
70.95
70.34
70.29
71.97
71.01
70.43
70.84
70.77
61.52
61.07
61.61
61.15
61.26
109.40
109.27
108.78
108.74
109.01
108.74
109.07
108.95
109.07
108.99
26.35, 26.05
24.85, 24.26
26.67, 26.46
25.76, 23.97
26.56, 26.15
25.52, 24.27
26.56, 25.99
25.54, 23.93
26.63, 25.96
25.66, 24.02
49.16, 47.79
54.82, 48.99
47.48
55.68
8a
9
49.82, 48.19
–
10
)
a OMe at 51.64 ppm.
9

I. Izquierdo et al. / Tetrahedron: Asymmetry 11 (2000) 4509–4519
4517
3.9. N,N-Dibenzyl 2-amino-2-deoxy-4,5:6,7-di-O-isopropylidene-i-
D
-glycero- -talo-oct-4-ulo-
D
4,8-pyranosonamide 9
A stirred solution of 5 (2.1 g, 4.24 mmol) and aqueous 30% ammonia solution (15 mL) in
methanol (15 mL) was heated in a sealed tube at 100°C, for 3 h. TLC (ether/triethylamine,
10:0.1) then revealed the presence of a slower-running compound. The mixture was concentrated
and the residue supported on silica gel and chromatographed (ether/methanol/triethylamine,
15:1:0.1) to afford 9 (1.95 g, 90%) as a colorless syrup: [h]2D7 −22 (c 1); w
3382 (OH, NH2),
film
max
1623 (OꢀCNꢁ), 1382 and 1373 cm−1 (CMe2). NMR data, see Tables 1 and 2. Anal. calcd for
C42H48N2O7: C, 72.81; H, 6.98; N, 4.04. Found: C, 72.51; H, 7.30; N, 4.21. Mass spectrum
(LSIMS): m/z: 535.24202 (M++Na) for C42H48N2NaO7 535.24226 (deviation −0.4 ppm).
3.10. 2-Amino-2-deoxy-4,5:6,7-di-O-isopropylidene-i-
D
-glycero- -talo-oct-4-ulo-4,8-pyranoson-
D
amide 10
A stirred solution of 6 (200 mg, 0.6 mmol) and aqueous 30% ammonia solution (5 mL) in
methanol (5 mL) was heated in a sealed tube at 100°C for 3 h. TLC (ether/methanol/triethyl-
amine, 10:2:0.1) then showed the presence of a slower-running compound. The mixture was
concentrated and the residue supported on silica gel and chromatographed (ether/methanol/tri-
ethylamine, 10:1:0.2) to afford crystalline 10 (95 mg, 47%): mp: 159–160°C; [h]2D2 −23 (c 0.8);
KBr
w
3436 and 3312 (OH and NH2), 1675 (OꢀCNꢁ), 1384 and 1372 (CMe2) cm−1. NMR data,
max
see Tables 1 and 2. Anal. calcd for C14H24N2O7: C, 50.59; H, 7.28; N, 8.43. Found: C, 50.29; H,
7.14; N, 8.20.
3.11. 2,3-Anhydro-4,5:6,7-di-O-isopropylidene-i-
D
-glycero- -galacto-oct-4-ulo-4,8-pyranose 11
D
To a stirred solution of 5 (130 mg, 0.26 mmol) in dry THF (8 mL) lithium borohydride (100
mg) was added portionwise. After 3 days, TLC (ether/hexane, 2:1) then showed a slower-run-
ning compound. The mixture was diluted with methanol, neutralized with acetic acid, and finally
concentrated. The residue was partitioned into dichloromethane/water, the organic phase
separated and concentrated. Column chromatography (ether/hexane, 1:2) gave 11 (50 mg, 73%),
which showed the same physical and spectroscopic data as those previously reported.5b
3.12. (3R,4R)-1-Benzyl-3-(2%,3%-O-isopropylidene-
2-one 12 and its (3R,4S)-isomer 13
D
-erythro-propanetriol-1%-yl)-4-phenylazetidin-
To a stirred and cooled (−10°C) solution of 3 (1.6 g, 4.35 mmol) in dry THF (30 mL) was
added dropwise an M solution of LHMDS in the same solvent (4 mL), and the mixture was
allowed to reach room temperature. After 2 h, TLC (ether) then revealed the presence of two
slower-running compounds. The mixture was neutralized with acetic acid, concentrated and the
residue dissolved in ether, washed with brine, then concentrated. Column chromatography
25
(ether/hexane, 1:1“2:1) afforded first crystalline 12 (320 mg): mp: 119–120°C; [h]2D3 +7, [h]
405
KBr
1
+27 (c 1); w
3456 (OH), 1733 (OꢀCNꢁ), 1380 and 1370 (CMe2) cm−1. NMR data: H, l
max

4518
I. Izquierdo et al. / Tetrahedron: Asymmetry 11 (2000) 4509–4519
7.40–7.15 (m, 10H, Ph and PhCH2), 4.85 and 3.79 (2d, 2H, J=15 Hz, PhCH2), 4.41 (d, 1H,
J3,4=1.9 Hz, H-4), 4.07–4.03 (m, 3H, H-2%,3%a,3%b), 3.93–3.90 (m, 1H, H-1%), 3.21 (dd, 1H,
J
1%,3=6.2 Hz, H-3), 1.35 and 1.30 (2s, 6H, CMe2); 13C, l 168.13 (C-2), 137.19, 135.35, 129.00,
128.81, 128.59, 128.39, 127.79, and 126.78 (PhCH2), 109.43 (CMe2), 77.70 (C-2%), 70.96 (C-1%),
66.55 (C-3%), 62.78 (C-3), 57.12 (C-4), 44.63 (PhCH2), 26.73 and 25.22 (CMe2). Anal. calcd for
C22H25NO4: C, 71.91; H, 6.86; N, 3.81. Found: C, 71.42; H, 6.85; N, 4.04.
Eluted second (530 mg) was a mixture of 12 and 13, in a 2:3 ratio. Finally pure 13 (320 mg)
26
KBr
was obtained as a colorless solid: mp: 170–171°C; [h]2D6 −59, [h] −163 (c 0.8); w
3413 (OH),
405
max
1744 (OꢀCNꢁ), 1387 and 1372 (CMe2) cm−1. NMR data: H, l 7.41–7.14 (m, 10H, Ph and
PhCH2), 4.95 and 3.95 (2 d, 2H, J=15 Hz, PhCH2), 4.60 (d, 1H, J3,4=5.7 Hz, H-4), 3.99–3.95
(m, 2H, 3%a,3%b), 3.85 (m, 1H, H-2%), 3.69 (dd, 1H, J1%,3=3.8 Hz, H-3), 3.50 (dd, 1H, J1%,2%=5.4
Hz, H-1%), 1.26 and 1.23 (2s, 6H, CMe2); 13C, l 167.45 (C-2), 135.36, 135.15, 128.94, 128.85,
128.68, 128.56, 127.86, and 127.42 (PhCH2), 109.30 (CMe2), 77.35 (C-2%), 68.02 (C-1%), 65.97
(C-3%), 57.63 and 57.04 (C-3,4), 44.84 (PhCH2), 26.44 and 25.25 (CMe2). Anal. calcd for
C22H25NO4: C, 71.91; H, 6.86; N, 3.81. Found: C, 71.89; H, 7.15; N, 3.90.
1
3.13. (3S,4S)-1-Benzyl-3-(2%,3%:4%,5%-di-O-isopropylidene-i-
D
-manno-hex-2%-ulo-2%,6%-pyranos-
1%-yl)-4-phenylazetidin-2-one 14
To a stirred and cooled (−10°C) solution of 5 (305 mg, 0.6 mmol) in dry THF (10 mL) was
added dropwise an M solution of LHMDS in the same solvent (2 mL), and the mixture was
allowed to reach room temperature. After 1 h, TLC (ether/hexane, 3:1) then revealed the
presence of a slower-running compound. Work-up of the mixture as above, gave, after column
chromatography (ether/hexane, 1:1) crystalline 14 (255 mg, 84%): mp: 135–136°C; [h]2D1 −19 (c
KBr
max
1
1); w
3406 (OH), 1748 (OꢀCNꢁ), 1382 and 1373 (CMe2) cm−1. NMR data: H, l 7.35–7.05
(m, 10H, Ph and PhCH2), 4.87 and 3.71 (2d, 2H, J=14.9 Hz, PhCH2), 4.62 (d, 1H, J3%,4%=2.7
Hz, H-3%), 4.58 (dd, 1H, J4%,5%=7.8 Hz, H-4%), 4.31 (d, 1H, J3,4=1.8 Hz, H-4), 4.17 (dd, 1H, H-5%),
4.03 (dd, 1H, J1%,3=8.6, J1%,OH=5.5 Hz, H-1%), 3.74 (dd, 1H, J5%,6%a=1.7 Hz, H-6%a), 3.57 (d, 1H,
J
6%a,6%e=12.9 Hz, H-6%e), 3.38 (dd, 1H, H-3), 3.00 (d, 1H, OH-1%), 1.42, 1.39, 1.31, and 1.24 (4s,
12H, 2CMe2); 13C, l 168.94 (C-2), 137.47, 135.42, 128.83, 128.77, 128.70, 128.43, 128.22, 127.67,
and 127.04 (Ph and PhCH2), 109.27 and 108.97 (2CMe2), 103.63 (C-2%), 71.99 (C-1%), 70.97
(C-5%), 70.22 (C-4%), 70.04 (C-3%), 61.10 (C-6%), 60.46 (C-3), 58.84 (C-4), 44.38 (PhCH2), 26.67,
25.87, 25.59 and 23.97 (2CMe2). Anal. calcd for C28H33NO7: C, 67.86; H, 6.71; N, 2.83. Found
C, 67.59; H, 7.02; N, 3.09.
Acknowledgements
This work was supported by Ministerio de Educacio´n y Cultura (Spain) (Project PB98-1357)
and by a grant (A. J. Mota) from the University of Granada (Spain).
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