Steric course of some cyclopropanation reactions of L-threo-hex-4- enopyranosides

Article abstract of DOI:10.1016/j.tet.2004.03.018

Completely protected 4-deoxy-α-L-threo-hex-4-enopyranosides 1c,d undergo the dichlorocarbene addition affording exclusively diastereomeric adducts 5c,d with the cyclopropane ring anti to the C-3 alkyloxy substituent, while the reaction with 3-unprotected derivatives 1a,b affords a mixture of syn and anti derivatives. Under the Simmons-Smith cyclopropanation adducts 2a-d with a syn stereochemistry are obtained. Starting from 5b, the cyclopropanated sugar 3b is obtained by reduction with LiAlH₄, thus the two diastereomers 2b and 3b can be stereoselectively obtained through the two different pathways. For a useful comparison, 4-deoxy-β-L-threo-hex-4- enopyranoside 1e was also subjected to the above two cyclopropanation methods affording the expected cycloadduct 2e and a diastereomeric mixture of dichlorocycloadducts 4e and 5e (4e/5e=2.8:1).

Full text of DOI:10.1016/j.tet.2004.03.018

Tetrahedron 60 (2004) 3787–3795
Steric course of some cyclopropanation reactions
of L-threo-hex-4-enopyranosidesq
a
a
a
a
Antonino Corsaro,a Ugo Chiacchio, Roberto Adamo, Venerando Pistara, Antonio Rescifina,
,
*
`
Roberto Romeo,b Giorgio Catelani,c Felicia D’Andrea,c Manuela Marianic
and Emanuele Attolinoc
a
`
Dipartimento di Scienze Chimiche, Universita di Catania, viale A. Doria 6, 95125 Catania, Italy
Dipartimento Farmaco Chimico, Universita di Messina, viale Annunziata, 98100 Messina, Italy
b
`
c
`
Dipartimento di Chimica Bioorganica e Biofarmacia, Universita di Pisa, via Bonanno 33, 56126 Pisa, Italy
Received 12 December 2003; revised 12 February 2004; accepted 4 March 2004
Abstract—Completely protected 4-deoxy-a-L-threo-hex-4-enopyranosides 1c,d undergo the dichlorocarbene addition affording exclusively
diastereomeric adducts 5c,d with the cyclopropane ring anti to the C-3 alkyloxy substituent, while the reaction with 3-unprotected derivatives
1a,b affords a mixture of syn and anti derivatives. Under the Simmons–Smith cyclopropanation adducts 2a-d with a syn stereochemistry are
obtained. Starting from 5b, the cyclopropanated sugar 3b is obtained by reduction with LiAlH4, thus the two diastereomers 2b and 3b can be
stereoselectively obtained through the two different pathways. For a useful comparison, 4-deoxy-b-L-threo-hex-4-enopyranoside 1e was also
subjected to the above two cyclopropanation methods affording the expected cycloadduct 2e and a diastereomeric mixture of
dichlorocycloadducts 4e and 5e (4e/5e¼2.8:1).
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
and by the addition of sulfur ylides.12,13 2,3-Cyclopropa-
nated carbohydrates were also obtained by benzophenone
sensitized addition of methanol and subsequent treatment
with toluene-p-sulfonyl chloride in the presence of pyri-
dine.14,15
Among several methods for the synthesis of cyclopropanes
starting from unsaturated carbohydrates,2 the most com-
monly used are the additions of the methylene–zinc–iodide
complex, generated from diethyl zinc and diiodomethane
(the Furukawa modification3 of the Simmons–Smith
reaction4,5), and additions of carbenes generated by the
formal elimination of hydrogen halide from haloform with a
strong base6 or by transition metal-catalyzed decomposition
of diazo compounds.7 Other routes such as the additions of
sulfur ylides8 are used rather sparingly.
To our best knowledge, there are no reports in literature on
the cyclopropanation of 3,4-unsatutared sugars and only a
single example is reported on the cyclopropanation of a
4,5-unsaturated a-D-pyranoside with a modified Simmons–
Smith reaction.16
As a part of a research project on the exploitation in sugar
chemistry of hex-4-enopyranosides derived from lactose,17
we here report the results of our investigations on
cyclopropanation reactions of a-L-threo-hex-4-enopyrano-
sides 1a-d and, for a useful comparison, on those of
protected methyl anomer 1e by means of the two classical
methods, which uses the methylene–zinc–iodide complex
and dichlorocarbene.
While cyclopropanation reactions of 1,2-glycals have been
extensively studied because of their easy accessibility,2,9 on
the contrary, those of the other unsaturated sugars have
attracted very little attention. The cyclopropanation of
2,3-unsaturated sugars was accomplished by using the
classic Simmons–Smith reaction with diiodomethane and
the Zn/Cu couple,10 and by addition of the dichlorocarbene
with chloroform and 50% aqueous sodium hydroxide in the
presence of benzyltriethylammonium chloride (TEBAC)11
2. Results and discussion
q See Ref. 1.
The Simmons–Smith cyclopropanation with diethyl zinc
reagent and diiodomethane in dry diethyl ether of hex-4-
enopyranosides 1a,17c 1b18 gave a nearly quantitative yield
of diastereomerically pure cycloadducts 2a,b, as judged by
Keywords: Cyclopropanations; Dichlorocarbene; Simmons–Smith; Hex-4-
enopyranosides; Lactose; Dehalogenations.
*
Corresponding author. Tel.: þ39-095-7385017; fax: þ39-095-580138;
e-mail address: acorsaro@unict.it
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.03.018

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A. Corsaro et al. / Tetrahedron 60 (2004) 3787–3795
Scheme 1. i) CH2l2, Et2Zn, Et2O; ii) CHCl3, NaOH 50%, Et3NþPhCl2; iii) LiAlH4 6 eq., dry THF; iv) LiAlH4 12 eq., dry THF.
1
TLC and inspection of the H NMR spectra19 of the crude
reaction mixtures (Scheme 1).
with the hydroxyl directed cyclopropanation of the allylic
C-3 oxygen by coordination with zinc under Simmons–
Smith conditions.21 Moreover, diagnostic enhancements
were the positive ones of H-7a [3.7% (glucosyl, 2a) and
4.0% (methyl, 2b)] and H-7b [3.9% (glucosyl, 2a) and 3.4%
(methyl, 2b)] protons upon irradiation of H-2 and H-4
protons, respectively (Fig. 1). Besides the signals of the
pyranoside ring, the 13C NMR spectra of 2a and 2b show
diagnostic 0cyclopropane ca0rbons patterns at 14.51 (C-70),
22.10 (C-4 ) and 65.43 (C-5 ), and 14.63 (C-7), 22.25 (C-4)
and 59.63 (C-5) ppm, respectively.
The structures of 2a,b deriving from the formation of the
cyclopropane ring on the upper face of the double bond
bearing the C-3 hydroxyl group, was assigned on the basis
of the values of coupling constants between H-3 and H-4
protons and the NOE enhancements upon their irradiation.
The high value of J3,4 (7.5 Hz) is consistent with a cis-
relationship between the two H-3 and H-4 protons20 and
Figure 1. NOE effect in cyclopropanated sugars 2b-5b.

A. Corsaro et al. / Tetrahedron 60 (2004) 3787–3795
3789
Figure 2. NOE effect in cyclopropanated sugars 2e-5e.
The treatment of 1a,b with chloroform and 50% aqueous
sodium hydroxide in the presence of catalytic amount of
triethylbenzyl ammonium chloride afforded mixtures of
two dichloromethylene adducts 4a,b and 5a,b, which were
separated by flash chromatography and then stereo-
the involvement of the zinc coordination, while by means
of the dichlorocyclopropanation reaction these afforded
exclusively adducts 5c,d indicating the influence of an effect
of steric hindrance exerted by C-3 and C-1 substituents, both
shielding the upper face.
1
chemically defined on the basis of their H NMR spectra.
Global yields of 64% (diastereomeric ratio 4a/5a¼60:40)22
and 65% (diastereomeric ratio 4b/5b¼90:10)22 were
obtained starting from 1a and 1b, respectively. Stereo-
isomers 4a,b were characterized by a high value of J3,4 (8.0
and 8.3 Hz, respectively) and NOE enhancements of vicinal
protons almost the same of those observed for 2a,b, and then
to these a stereochemistry with the cyclopropane ring in cis
to the coordinating C-3 oxygenated substituent was assigned
and it was confirmed23 by the conversion of 4a,b into 2a,b
by treatment with a large excess (12 equiv.) of lithium
aluminium hydride (LiAlH4).
Finally, with the aim of determining the role of the
orientation of the anomeric substituent on the stereo-
chemical course of the cyclopropanations, the reactions of
the fully protected 4-deoxy-b-L-threo-hex-4-enopyranoside
1e25 were studied. Owing to previous observations26 on the
regioselective formation of 1e as a by-product during the
preparation of methyl 2,3,6-tri-O-benzyl-4-imidazylsulfo-
nyl-a-D-galactopyranoside (7), we studied some base-
promoted elimination reactions of 7, in order to improve
the somewhat unsatisfactory yield reported25 for the
preparation of 1e by treatment of the triflate analogous
of 7 with methyl lithium. We found, however, a series of
unexpected results giving a complex picture of the leaving
group properties of this type of sulfonate, that we will be
present in a forthcoming paper.27 A low yield (24%)
preparation of 1e was, however, achieved by treatment of 7
with potassium t-butoxide (t-BuOK) in DMF, giving also
the hex-3-enopyranoside 8 (20%), previously reported only
as 4-deuterated derivative.28
Stereoisomers 5a,b, in which the cyclopropane ring was on
the opposite side to that of C-3 oxygenated group, instead,
showed a J3,4 of 4.5 and 5.0 Hz, respectively, and
characteristic NOE enhancements (3.8 and 3.0%, respec-
tively) of H-2 proton upon irradiation of H-4 proton,
confirmed by the corresponding enhancement of H-4
proton (4.0 and 3.4%, respectively) upon irradiation of
H-2 proton.
The addition reaction of 1e with methylene–zinc–iodide
complex gave nearly quantitative yield of the expected
adduct 2e, while the dichlorocarbene addition afforded a
diastereomeric mixture of both adducts 4e and 5e in the
2.8:1 ratio indicating a balance between the steric effects of
the C-1 and C-3 substituents. The structures of 2e, 4e and 5e
were assigned on the basis of their spectroscopic analyses
(Fig. 2), as well as the structure of 3e obtained by reduction
of 5e with LiAlH4.
As expected, the dechlorination of 5b by reduction with an
excess of LiAlH4, as above described, to give 3b with the
stereochemistry opposite to that one of 2b, was apparent
from the value of J3,4 of 5.5 Hz and NOE enhancement of
their H-2 proton (5.7%) upon irradiation of H-4 proton,
respectively.
In order to improve the face-selectivity of the cyclopropa-
nation, the pyranoside 1b was converted into the sterically
more demanding 3-O-methyl (1c) and 3-O-benzyl (1d)24
derivatives. These compounds, subjected to the Simmons–
Smith cyclopropanation gave exclusively 2c,d confirming
The results of our investigations on the dichlorocyclo-
propanation of sugars 1a-e were not completely in line with
those of 1,2-glycals, which are known to undergo the

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A. Corsaro et al. / Tetrahedron 60 (2004) 3787–3795
carbene addition to the opposite side to that of 3-alkyloxy
substituent because of steric effects.2,20 While sterically
demanding derivatives 1c,d react with dichlorocarbene
giving 5c,d like 1,2-glycals, hexenopyranosides 1a,b gave
exclusively or predominantly the cyclopropanated sugars
4a,b arising from the syn addition to the C-3 substituent and
furthermore 1e afforded a mixture of 2.8:1 adducts 4e and
5e.
mations (Fig. 3) was then selected for the optimization at
PM3 level of their transition states (TS). For each case the
attachment of dichlorocarbene was considered on both faces
of C-4–C-5 double bond: the up one (U) and the down one
(D) referred to the sugar moiety in the Haworth projection,
respectively. The obtained results are reported in Table 1.
From these data it is evident that the E conformation is the
preferred one for 1d, which exists in a E/A ratio of 1.8:1,
whereas there is an inversion for compound 1e (E/A
ratio¼1:17.8). For the cyclopropanation of 1d, the most
favored approaches take place clearly at the down face of
the double bond in both E and A conformations, even if the
lowest energy value corresponds to 1dAD-TS. Therefore,
the less stable conformer 1dA reacts more quickly than the
most stable 1dE, in completely accord with the Curtin–
Hammett principle.30 These results are in very good
agreement with the exclusive formation of 5d, as exper-
imentally observed. Furthermore, the geometries 1dED-TS
and 1dAD-TS, which lead to compound 5d, are the only
ones in which both benzyl groups at C-3 and C-5 positions
lie in the upper rim of the pyranoside moiety, so facilitating
the attack of dichlorocarbene at the pyranoside bottom
(Fig. 4).
For this reason, the steric course of dichlorocyclopropa-
nation reactions of the two fully benzylated a- and
b-hexenopyranosides 1d and 1e was rationalized on the
basis of molecular mechanics and semiempirical calcu-
lations. (The ab initio methods are to be discarded because
of the complexity of substrates.)
At first, a conformational analysis at the molecular
mechanics level was performed and thereafter the lower
energy conformers, located within 2.0 kcal/mol from the
lowest one, were subjected to full minimization at
semiempirical PM3 level29 of calculation. The lowest
energy conformer of 1e and 1d with the anomeric
substituent in both equatorial (E) and axial (A) confor-
Figure 4. 1dED-TS and 1dAD-TS, where hydrogen atoms have been
omitted for better clarity.
For the cyclopropanation of b-hex-4-enopyranoside 1e, the
calculated TS energies predict the formation of both
products 4e and 5e in a 3.2:1 ratio, which is not far from
the experimentally observed 2.8:1 ratio.
Interestingly, by using a ratio of 6 equiv. of lithium
aluminium hydride with respect to 4b, the reduction was
partially realized and a single monochlorocyclopropane
derivative 6b was obtained with a 90% yield. Its stereo-
chemistry, characterized by the replacement of chlorine
atom in cis-position with respect to H-4 proton, was
deduced from NOE experiments which show a positive
enhancement (4.3%) of the signal of the unique H-7b proton
on irradiation of H-4 proton, confirmed by the enhancement
(7.8%) of H-4 proton on irradiation of H-7b proton. The
interest in this reaction derives just from its stereochemistry
due to the attack of the hydride to the exo-halogen atom,
which is the most reactive because of the reduced steric
hindrance in line with the literature report.31
Figure 3. Preferred conformations of compounds 1d and 1e.
Table 1. PM3 values for dichlorocyclopropanation reaction of compounds
1d,e
DHf (kcal/mol) DDHf (kcal/mol)a Calculated ratio (%)b
1dE
1dA
1eA
1eE
1dEU-TS
1dED-TS
1dAU-TS
1dAD-TS
1eAU-TS
1eAD-TS
1eEU-TS
1eED-TS
2100.29
299.95
299.58
297.86
225.57
233.74
230.76
234.23
231.32
230.65
230.94
230.21
0.00
0.34
0.00
1.72
8.66
0.49
3.47
0.00
0.00
0.67
0.38
1.11
63.9
36.1
94.7
5.3
0.0
30.5
0.2
69.3
49.8
16.2
26.3
7.7
The incorporation of a cyclopropane ring into a carbo-
hydrate provides an interesting method for obtaining
strained and reactive three-membered systems combined
with the carbohydrate stereochemistry. Now we are
investigating the cyclopropanation of a- and b-hex-4-
enopyranosides with ethyl diazoacetate in the presence
of rhodium acetate as catalyst and the electrophilic
a
Since 1d,e exists in equilibrium between E and A conformers, the
Curtin–Hammett principle30 was applied and their relative energies were
calculated assuming the energy of the most stable TS as point zero.
On the basis of the Boltzmann distribution.
b

A. Corsaro et al. / Tetrahedron 60 (2004) 3787–3795
3791
Scheme 2.
cyclopropane ring opening into a branched sugar or
expansion of carbohydrate moiety to seven-membered
oxacycles.
127.38, 127.43, 127.52, 127.64, 128.12, 128.14 (aromatic
CH), 137.75, 137.81 (aromatic C), 148.99 (C4). Anal. Calcd
for C22H26O5: C, 71.33; H, 7.07%. Found: C, 71.41; H, 7.11.
3.3. Synthesis of methyl-2,3,6-tri-O-benzyl-4-deoxy-b-L-
threo-hex-4-enopyranoside, 1e
3. Experimental
A solution of 726 (1.50, 2.52 mmol) in dry DMF (25 mL)
was treated with solid t-BuOK (850 mg, 7.50 mmol) at 0 8C
under vigorous stirring. The reaction mixture was left to
reach room temperature and further stirred until TLC
analysis (1:1, hexane/AcOEt) showed the complete dis-
appearance of the starting material. Excess t-BuOK was
destroyed by adding solid Et3N·HCl followed by 10 min
stirring. The dark mixture was diluted with water (25 mL),
extracted with Et2O (3£50 mL). Organic phases were
collected, dried (Na2SO4), filtered, concentrated at reduced
pressure to give a crude residue that was directly subjected
to a chromatography over silica gel (7:3, hexane /AcOEt) to
give pure samples of 1e (304 mg, 27% yield) and 8 (225 mg,
20% yield) (Scheme 2).
3.1. General methods
Melting points were determined with a Kofler hot-stage
apparatus and are uncorrected. Optical rotations were
measured on a Perkin–Elmer 241 polarimeter at 20^2 8C.
1H NMR spectra were recorded in the stated solvent with a
Varian Unity Inova (500 MHz for the proton and 125 MHz
for the carbon spectra) and with a Brucker 200 AC
instruments (200 MHz for the proton and 50 MHz for the
carbon spectra). In all cases Me4Si was used as the internal
standard. All reactions were followed by TLC on Kieselgel
60 F254 with detection by UV light and/or with ethanolic
10% phosphomolybdic or sulphuric acid, and heating.
Kieselgel 60 (E. Merck, 70–230 and 230–400 mesh,
respectively) was used for the column and flash chroma-
tography. Solvents were dried by distillation according to
3.3.1. Methyl 2,3,6-tri-O-benzyl-4-deoxy-b-L-threo-hex-
4-enopyranoside, 1e. Syrup, 27% yield, [a]2D5¼þ76 (c 1.2,
CHCl3); lit:25 [a]D25¼þ78 (c 1.0, CHCl3); 1H NMR in
complete accordance with reported data;25 13C NMR
(50 MHz, CDCl3) d 56.6 (OCH3), 69.0 (C-6), 71.3, 72.1
and 73.0 (CH2), 73.2 and 76.1 (C-2, C-3), 99.4 and 99.7
(C-1, C-4), 127.6–128.3 (aromatic CH), 137.9, 138.1 and
138.4 (aromatic C), 148.6 (C-5).
standard procedure,32 and storage over 4 A molecular sieves
˚
activated at least 24 h at 400 8C. MgSO4 was used as the
drying agent for solutions. New starting compounds were
prepared as follows.
3.2. Synthesis of methyl 2,6-di-O-benzyl-3-O-methyl-4-
deoxy-(a-L-threo-hex-4-enopyranoside, 1c
3.3.2. Methyl-2,3,6-tri-O-benzyl-4-deoxy-b-L-threo-hex-
3-enopyranoside, 8. Syrup, 20% yield, [a]2D5¼235 (c 1.0,
CHCl3); lit:28 [a]2D5¼240 for the 4-deuterated analogous;
1H NMR (200 MHz, CDCl3) d 3.45 (dd, 1H, J¼5.1,
To a stirred solution of 1b (290 mg, 0.81 mmol) in dry
acetone (5 mL), potassium hydroxide powder (45 mg,
0.81 mmol) and methyl iodide (0.1 mL, 1.62 mmol) were
added and the solution was then refluxed. After 5 h, the
reaction mixture was evaporated at reduced pressure and
then extracted twice with dichloromethane (10 mL); the
combined organic layers were washed with brine (20 mL),
water (20 mL), and dried (Na2SO4). Flash chromatography
of the crude gave derivative 1c with nearly quantitative yield.
10.0 Hz, H-6a), 3.52 (s, 3H, OCH3), 3.53 (dd, 1H, J5,6b
¼
6.0 Hz, H-6b), 4.17 (ddd, 1H, J¼0.9, 2.8, 3.7 Hz, H-2),
4.53–4.61 (AB system, 2H, JA,B¼12.1 Hz, CH2Ph), 4.54
(m, 1H, J¼1.8, 2.8 Hz, H-5), 4.63–4.81 (AB system, 2H,
JA,B¼11.5 Hz, CH2Ph), 4.76 (dd, 1H, J¼0.9, 1.8 Hz, H-4),
4.81–4.89 (AB system, 2H, JA,B¼11.3 Hz, CH2Ph), 4.86 (d,
1H, J¼3.7 Hz, H-1), 7.25–7.39 (m, 15H, aromatic H); 13C
NMR (50 MHz, CDCl3) d 56.2 (OCH3), 68.2 and 71.4 (C-2,
C-5), 69.1 (C-6), 72.9, 73.3 and 73.4 (CH2), 95.9 (C-4), 98.3
(C-1), 127.4–128.3 (aromatic CH), 136.7, 138.1 and 138.5
(aromatic C), 151.4 (C-3). Anal. Calcd for C28H30O5: C,
75.31; H, 6.77%. Found C, 75.29; H, 6.78.
3.2.1. Methyl 2,6-di-O-benzyl-3-O-methyl-4-deoxy-a-L-
threo-hex-4-enopyranoside, 1c. Clear syrup, 98% yield,
[a]2D5¼þ101.2 (c 0.4, CHCl3); 1H NMR (CDCl3, 200 MHz)
d 3.34 (s, 3H, C1–OCH3), 3.50 (s, 3H, C3–OCH3), 3.66
(dd, 1H, J¼4.2, 5.0 Hz, H-2), 3.82 (dd, 1H, J¼3.6, 4.2 Hz,
H-3), 3.98 (s, 2H, H-6a, H-6b), 4.54 (s, 2H, CH2), 4.65–4.81
(AB system, 2H, JAB¼12 Hz, CH2), 4.88 (d, 1H, J¼5.0 Hz,
H-1), 5.10 (d, 1H, J¼3.6 Hz, H-4) 7.22–7.28 (m, 10H,
aromatic H); 13C NMR (CDCl3, 50 MHz) d 55.35 (C1–
OCH3), 56.67 (C3–OCH3), 68.77 (C-6), 71.94 and 72.73
(CH2), 74.82 (C-3), 75.99 (C-2), 98.45 (C-1), 100.79 (C-5),
3.4. Cyclopropanation under Simmons–Smith
conditions of 1a-e
To a stirred solution of 4,5-unsatured carbohydrate

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A. Corsaro et al. / Tetrahedron 60 (2004) 3787–3795
(0.84 mmol) in dry diethyl ether (3 mL), diethyl zinc
(420 mL of a 1 M solution in hexane, 4.2 mmol) and
diiodomethane (340 mL, 4.2 mmol) were added at room
temperature. The solution was then heated at 40 8C in a
sealed vessel. After 2 h, a saturated solution of NaHCO3
(2 mL) was added to the reaction mixture which was then
neutralized with diluted HCl (2 mL) and extracted twice
with diethyl ether (10 mL); the combined organic layers
were washed with brine (20 mL), water (20 mL), and dried
(Na2SO4). Flash chromatography of the crude gave the
cyclopropanated sugars.
7.5, 10.0 Hz, H-4), 3.09 (dd, 1H, J¼7.0, 8.0 Hz, H-2), 3.25–
3.91 (AB system, 2H, JAB¼10.5 Hz, H-6a, H-6b), 3.45
(s, 3H, C1–OCH3), 3.54 (s, 3H, C3–OCH3), 3.97 (dd, 1H,
J¼7.0, 7.5 Hz, H-3), 4.45 (d, 1H, J¼8.0 Hz, H-1), 4.55–
4.61 (AB system, 2H, JAB¼12.0 Hz, C6–OCH2Ph), 4.64–
4.85 (AB system, 2H, JAB¼11.5 Hz, C2–OCH2Ph), 7.24–
7.37 (m, 10H, aromatic H); 13C NMR (CDCl3, 50 MHz) d
14.52 (C-7), 19.87 (C-4), 56.51 (C1–OCH3), 56.68 (C3–
OCH3), 60.28 (C-5), 73.05, 74.04 and 74.63 (CH2), 79.80
(C-3), 81.90 (C-2), 103.28 (C-1), 127.28, 127.31, 127.50,
127.60, 128.10 and 128.28 (aromatic CH), 138.20 and
139.02 (aromatic C). Anal. Calcd for C23H28O5: C, 71.85;
H, 7.34%. Found: C, 71.92; H, 7.29.
3.4.1. 4-O-[(1R,3R,4R,5S,6R)-4-Benzyloxy-1-benzyloxy-
methyl-2-oxabicyclo[4.1.0]heptan-3-yl]-2,3:5,6-di-O-iso-
propylidene-aldehydo-D-glucose dimethyl acetal, 2a.
3.4.4. (1R,3R,4R,5S,6R)-4,5-Bis-benzyloxy-1-benzyloxy-
methyl-3-methoxy-2-oxabicyclo[4.1.0]heptane, 2d. Syrup,
1
Syrup, 96% yield, [a]2D5¼248.1 (c 0.4, CHCl3); H NMR
(CDCl3, 500 MHz) d 0.77 (dd, 1H, J¼6.0, 10.0 Hz, H-70a),
0.86 (dd, 1H, J¼6.0, 6.5 Hz, H-70b) 1.35, 1.41, 1.42 and
1.43 (s£4, each 3H, CH3), 1.49 (ddd, 1H, J¼6.5, 8.5,
10.0 Hz, H-40), 3.21–3.86 (AB system, 2H, JAB¼10.0 Hz,
H-60a, H-60b), 3.41 and 3.42 (s£2, each 3H, OCH3), 3.62
(dd, 1H, J¼1.0, 6.5 Hz, H-20), 3.99 (dd, 1H, J¼6.0, 6.5 Hz,
H-4), 4.02 (dd, 1H, J¼6.0, 7.5 Hz, H-3), 4.13–4.19 (AB
system, 2H, JAB¼8.0 Hz, H-6a, H-6b), 4.27 (t, 1H, J¼
8.5 Hz, H-30), 4.29 (dd, 1H, J¼6.5, 8.0 Hz, H-5), 4.39 (t, 1H,
J¼6.5 Hz, H-1), 4.49–4.61 (AB system, 2H, JAB¼12.0 Hz,
CH2Ph), 4.54–4.97 (AB system, 2H, JAB¼12.0 Hz,
CH2Ph), 4.63 (dd, 1H, J¼6.5, 7.5 Hz, H-2), 4.84 (d, 1H,
J¼8.0 Hz, H-10), 7.27–7.35 (m, 10H, aromatic 0 H); 13C
NMR (CDCl3, 50 MHz) d 14.51 (C-70), 22.10 (C-4 ), 25.24,
26.71, 26.90 and 27.21 (CH3), 55.46 and 55.52 (OCH3),
65.43 (C-50), 66.65 (C-6), 70.62 (C-30), 73.13 (C-60), 74.15
and 74.16 (CH2Ph), 74.57 (C-2), 75.11 (C-4), 77.55 (C-5),
77.57 (C-3), 81.98 (C-20), 102.35 (C-10), 105.00 (C-1),
108.36 and 109.94 (CMe2), 127.26, 127.41, 127.56, 127.76,
127.88, 128.03, 128.21 and 128.29 (aromatic CH), 138.13
and 138.44 (aromatic C). Anal. Calcd for C35H48O11: C,
65.20; H, 7.50%. Found: C, 65.31; H, 7.59.
97% yield, [a]2D5¼23.6 (c 0.2, CHCl3); H NMR (CDCl3,
1
500 MHz) d 0.82 (dd, 1H, J¼6.0, 10.5 Hz, H-7a), 0.97
(dd, 1H, J¼6.0, 7.0 Hz, H-7b), 1.48 (ddd, 1H, J¼6.0, 7.0,
10.5 Hz, H-4), 3.19 (dd, 1H, J¼7.5, 8.0 Hz, H-2), 3.24–3.90
(AB system, 2H, JAB¼11.0 Hz, H-6a, H-6b), 3.54 (s, 3H,
OCH3), 4.18 (dd, 1H, J¼7.0, 7.5 Hz, H-3), 4.44 (d, 1H,
J¼8.0 Hz, H-1), 4.54–4.60 (AB system, 2H, JAB¼12.0 Hz,
C6–OCH2Ph), 4.59–4.77 (AB system, 2H, JAB¼12.0 Hz,
C2–OCH2Ph), 4.66–4.86 (AB system, 2H, JAB¼11.0 Hz,
C3–OCH2Ph), 7.24–7.36 (m, 15H, aromatic H); 13C NMR
(CDCl3, 50 MHz) d 14.85 (C-7), 20.45 (C-4), 56.77
(OCH3), 60.56 (C-5), 70.68, 74.33 and 74.42 (CH2), 77.87
(C-3), 81.32 (C-2), 103.51 (C-1), 127.43, 127.60, 127.50,
127.72, 127.81, 128.18 and 128.36 (aromatic CH), 138.25,
138.54 and 138.90 (aromatic C). Anal. Calcd for C29H32O5:
C, 75.63; H, 7.00%. Found: C, 75.71; H, 7.09.
3.4.5. (1R,3S,4R,5S,6R)-4,5-Bis-benzyloxy-1-benzyloxy-
methyl-3-methoxy-2-oxabicyclo[4.1.0]heptane, 2e. Clear
syrup, 98% yield, [a]D25¼þ101,9 (c 0.72, CHCl3); 1H NMR
(CDCl3, 500 MHz) d 0.85 (ddd, 2H, J¼6.0, 7.5, 9.5 Hz,
H-7a, H-7b), 1.58 (ddd, 1H, J¼6.0, 7.5, 9.5 Hz, H-4), 3.28
(dd, 1H, J¼2.7, 8.5 Hz, H-2), 3.44–3.62 (AB system, 2H,
JAB¼10.5 Hz, J6a–7b¼0.75 Hz, H-6a, H-6b), 3.36 (s, 3H,
OCH3), 4.24 (dd, 1H, J¼6.5, 8.5 Hz, H-3), 4.44 (d, 1H,
J¼2.7 Hz, H-1), 4.55–4.61 (AB system, 2H, JAB¼12.1 Hz,
C6–OCH2Ph), 4.64–4.81 (AB system, 2H, JAB¼12.2 Hz,
C3–OCH2Ph), 4.65–4.79 (AB system, 2H, JAB¼11.8 Hz,
C2–OCH2Ph), 7.25–7.39 (m, 15H, aromatic H); 13C NMR
(CDCl3, 50 MHz) d 14.90 (C-7), 20.40 (C-4), 56,37
(OCH3), 59.36 (C-5), 70.97 and 72.84 (CH2), 73.19 (C-2),
73.30 (C-6), 78.34 (C-3), 99.69 (C-1), 127.48, 127.66,
127.89 and 128.33, (aromatic CH), 138.15, 138.44 and
138.77 (aromatic C). Anal. Calcd for C29H32O5: C, 75.63;
H, 7.00%. Found: C, 75.71; H, 7.11.
3.4.2. (1R,3R,4R,5S,6R)-4-Benzyloxy-1-benzyloxy-
methyl-3-methoxy-2-oxabicyclo[4.1.0]heptan-5-ol, 2b.
1
Syrup, 97% yield, [a]2D5¼þ21.3 (c 0.1, CHCl3); H NMR
(CDCl3, 500 MHz) d 0.79 (dd, 1H, J¼6.0, 10.0 Hz, H-7a),
0.91 (dd, 1H, J¼6.0, 6.5 Hz, H-7b), 1.50 (ddd, 1H, J¼6.0,
7.5, 10.0 Hz, H-4), 2.31 (bs, 1H, OH), 3.01 (dd, 1H, J¼7.5,
8.0 Hz, H-2), 3.24–3.87 (AB system, 2H, JAB¼10.5 Hz,
H-6a, H-6b), 3.54 (s, 3H, OCH3), 4.29 (bt, 1H, J¼7.5 Hz,
H-3), 4.42 (d, 1H, J¼8.0 Hz, H-1), 4.56–4.61 (AB system,
2H, JAB¼12.0 Hz, C6–OCH2–Ph), 4.57–4.92 (AB system,
2H, JAB¼11.5 Hz, C2–OCH2–Ph), 7.26–7.35 (m, 10H,
aromatic H); 13C NMR (CDCl3, 50 MHz) d 14.63 (C-7),
22.25 (C-4), 56.83 (C-5), 59.63 (OCH3), 70.41 (C-3), 73.03
(C-6), 74.13 (CH2), 74.34 (CH2), 81.50 (C-2), 103.40 (C-1),
127.33, 127.54, 127.69, 127.88, 128.31 and 128.40
(aromatic CH), 138.21 and 138.51 (aromatic C). Anal.
Calcd for C22H26O5: C, 71.33; H, 7.07%. Found: C, 71.39;
H, 7.12.
3.5. Cyclopropanation under the dichlorocarbene
conditions of 1a-e
To a vigorously stirred solution of 4,5-unsaturared carbo-
hydrate 1a-e (1.92 mmol) in chloroform (6 mL), containing
benzyltriethylamonium chloride (10 mg), aqueous sodium
hydroxide (2.5 g in 5 mL) was added. The reaction
mixture was stirred for 2 h at room temperature, diluted
with water (12 mL) and then extracted with dichloro-
methane. The combined extracts were dried (Na2SO4),
concentrated and the residue was purified by flash
3.4.3. (1R,3R,4R,5S,6R)-4-Benzyloxy-1-benzyloxymethyl-
3,5-dimethoxy-2-oxabicyclo[4.1.0]heptane, 2c. Syrup,
96% yield, [a]D25¼þ58.1 (c 1.2, CHCl3); 1H NMR
(CDCl3, 500 MHz) d 0.80 (dd, 1H, J¼10.0, 6.0 Hz, H-7a),
0.89 (dd, 1H, J¼6.0, 7.0 Hz, H-7b), 1.50 (ddd, 1H, J¼7.0,

A. Corsaro et al. / Tetrahedron 60 (2004) 3787–3795
3793
chromatography to give the dichlorocyclopropanated sugars
4a,b,e and 5a-e.
3.5.4. 4-O-[(1R,3R,4R,5S,6S)-4-Benzyloxy-1-benzyloxy-
methyl-7,7-dichloro-2-oxabicyclo-[4.1.0]heptan-3-yl]-
2,3:5,6-di-O-isopropylidene-aldehydo-D-glucose dimethyl
acetal, 5a. Syrup, 7% yield, [a]2D5¼þ7.1 (c 0.2, CHCl3); 1H
NMR (CDCl3, 500 MHz) d 1.32, 1.39, 1.40 and 1.42 (s£4,
each 3H, CH3), 1.44 (bs, 1H, OH), 1.86 (d, 1H, J¼4.5 Hz,
H-40), 3.38 (t, 1H, J¼7.5 Hz, H-20), 3.46 and 3.47 (s£2, each
3H, OCH3), 3.75–3.99 (AB system, 2H, JAB¼11.0 Hz,
H-60a, H-60b), 4.00 (dd, 1H, J¼6.5, 8.5 Hz, H-6a), 4.11
(dd, 1H, J¼1.5, 7.0 Hz, H-4), 4.13 (dd, 1H, J¼6.5, 8.5 Hz,
H-6b), 4.22 (dd, 1H, J¼1.5, 4.5 Hz, H-3), 4.32 (dd, 1H,
J¼6.5, 8.5 Hz, H-5), 4.35 (dd, 1H, J¼4.5, 7.5 Hz, H-30),
4.47 (d, 1H, J¼7.5 Hz, H-1), 4.52–4.73 (AB system, 2H,
JAB¼12.0 Hz, CH2), 4.53 (dd, 1H, J¼4.5, 7.5 Hz, H-2),
4.54–4.98 (AB system, 2H, JAB¼11.0 Hz, CH2), 5.14
(d, 1H, J¼7.5 Hz, H-10), 7.28–7.37 (m, 10H, aromatic H);
13C NMR (CDCl3, 50 MHz) d 25.37, 26.44, 26.84 and
27.32 (CH3), 29.68 (C-7), 32.35 (C-40), 53.08 and 55.81
(OCH3), 62.69 (C-50), 65.40 (C-6), 65.50 (C-70) 69.49
(C-30), 72.01 (C-60), 73.55 and 74.30 (CH2Ph), 74.96 (C-2),
75.38 (C-4), 77.53 and 77.54 (C-3, C-5), 81.47 (C-20),
102.13 (C-10), 105.40 (C-1), 108.47 and 110.17 (CMe2),
127.47, 127.64, 128.00, 128.15, 128.39 and 128.61
(aromatic CH), 138.12 and 138.26 (aromatic C). Anal.
Calcd for C36H48Cl2O11: C, 58.91; H, 6.50%. Found: C,
59.02; H, 6.59.
3.5.1. 4-O-[(1S,3R,4R,5S,6R)-4-Benzyloxy-1-benzyloxy-
methyl-7,7-dichloro-2-oxabicyclo-[4.1.0]heptan-3-yl]-
2,3:5,6-di-O-isopropylidene-aldehydo-D-glucose dimethyl
acetal, 4a. Syrup, 38% yield, [a]2D5¼29.3 (c 0.2, CHCl3);
1H NMR (CDCl3, 500 MHz) d 1.34, 1.39, 1.42 and 1.44
(s£4, each 3H, CH3), 1.60 (bs, 1H, OH), 2.19 (d, 1H, J¼
8.0 Hz, H-40), 3.36 and 3.42 (s£2, each 3H, OCH3), 3.55
(t, 1H, J¼8.5 Hz, H-20), 3.71–4.05 (AB system, 2H, JAB
¼
10.5 Hz, H-60a, H-60b), 4.00 (dd, 1H, J¼6.5, 9.0 Hz, H-6a),
4.04 (dd, 1H, J¼1.0, 7.0 Hz, H-4), 4.10 (dd, 1H, J¼6.5,
8.5 Hz, H-6b), 4.17 (dd, 1H, J¼1.0, 7.5 Hz, H-3), 4.27 (dd,
1H, J¼8.0, 8.5 Hz, H-30), 4.30 (dd, 1H, J¼6.5, 7.0 Hz, H-5),
4.41 (d, 1H, J¼6.5 Hz, H-1), 4.52–4.64 (AB system, 2H,
JAB¼12.0 Hz, CH2), 4.56–4.94 (AB system, 2H, JAB
¼
11.5 Hz, CH2), 4.68 (dd, 1H, J¼6.5, 7.5 Hz, H-2) 4.97 (d,
1H, J¼8.5 Hz, H-10), 7.28–7.37 (m, 10H, aromatic H); 13
C
NMR (CDCl3, 50 MHz) d 25.34, 26.44, 26.55 and 27.33
(CH3), 37.34 (C-40), 55.78 (2£OCH3), 63.97 (C-50), 64.40
(C-70), 65.43 (C-6), 70.93 (C-30), 71.71 (C-60), 73.74, (CH2),
73.96 (C-2), 74.48 (CH2), 74.99 (C-4), 77.51 and 77.53
(C-3, C-5), 80.70 (C-20), 103.27 (C-10), 105.13 (C-1), 108.48
and 110.05 (CMe2), 127.58, 127.86, 127.92, 128.16, 128.50
and 128.46 (aromatic CH), 137.70 and 138.26 (aromatic C).
Anal. Calcd for C36H46Cl2O11: C, 58.91; H, 6.50%. Found:
C, 58.99; H, 6.53.
3.5.5. (1R,3R,4R,5S,6S)-4-Benzyloxy-1-benzyloxymethyl-
7,7-dichloro-3-methoxy-2-oxabicyclo[4.1.0]heptan-5-ol,
1
3.5.2. (1S,3R,4R,5S,6R)-4-Benzyloxy-1-benzyloxymethyl-
7,7-dichloro-3-methoxy-2-oxabicyclo[4.1.0]heptan-5-ol,
5b. Syrup, 61% yield, [a]2D5¼215.0 (c 0.1, CHCl3); H
NMR (CDCl3, 500 MHz) d 1.75, (d, 1H, J¼5.0 Hz, H-4),
2.54 (bd, 1H, J¼2.0 Hz, OH), 3.42 (dd, 1H, J¼5.0, 10.0 Hz,
1
4b. Syrup, 26% yield, [a]2D5¼þ37.6 (c 3.2, CHCl3); H
NMR (CDCl3, 500 MHz) d 2.19 (d, 1H, J¼8.5 Hz, H-4),
2.28 (d, 1H, J¼6 Hz, OH), 3.54 (t, 1H, J¼8.5 Hz, H-2), 3.58
(s, 3H, OCH3), 3.69–4.09 (AB system, 2H, JAB¼10.5 Hz,
H-6a, H-6b), 4.31 (bq, 1H, spl. h 8 Hz, H-3), 4.50 (d, 1H,
J¼8.5 Hz, H-1), 4.57–4.62 (AB system, 2H, JAB¼12.5 Hz,
C6–OCH2Ph), 4.65–4.89 (AB system, 2H, JAB¼11.5 Hz,
C2–OCH2Ph), 7.27–7.39 (m, 10H, aromatic H); 13C NMR
(CDCl3, 50 MHz) d 37.44 (C-4), 57.41 (OCH3), 64.01
(C-5), 64.40 (C-7), 71.10 (C-3), 71.59 (C-6), 73.59 and
74.49 (CH2), 80.41 (C-2), 104.62 (C-1), 127.60, 127.82,
l27.89, 127.94, 128.21 and 128.46 (aromatic CH), 137.64
and 138.22 (aromatic C). Anal. Calcd for C22H24Cl2O5: C,
60.15; H, 5.51%. Found: C, 60.21; H, 5.58.
H-2), 3.46 (s, 3H, OCH3), 3.67–4.01 (AB system, 2H, JAB
¼
11.5 Hz, H-6a, H-6b), 3.77 (ddd, 1H, J¼2.5, 5.0, 10.0 Hz,
H-3), 4.56–4.75 (AB system, 2H, JAB¼11.5 Hz,
C2–OCH2Ph), 4.59–4.65 (AB system, 2H, JAB¼12 Hz,
C6–OCH2Ph), 4.70 (d, 1H, J¼5.0 Hz, H-1), 7.29–7.39
(m, 10H, aromatic H); 13C NMR (CDCl3, 50 MHz) d 36.60
(C-4), 55.51 (OCH3), 62.93 (C-5), 65.80 (C-7), 67.09 (C-3),
70.67 (C-6), 73.02 and 73.30 (CH2), 82.16 (C-2), 107.11
(C-1), 127.71, 127.84, 127.95, 128.06, 128.33 and 128.55
(aromatic CH), 137.55 and 137.86 (aromatic C). Anal.
Calcd for C22H24Cl2O5: C, 60.15; H, 5.51%. Found: C,
60.24; H, 5.57.
3.5.6. (1R,3R,4R,5S,6S)-4-Benzyloxy-1-benzyloxymethyl-
7,7-dichloro-3,5-dimethoxy-2-oxabicyclo[4.1.0]heptane,
5c. Syrup, 68% yield, [d]2D5¼27.3 (c 1.4, CHCl3); 1H NMR
(CDCl3, 500 MHz) d 1.65, (d, 1H, J¼4.5 Hz, H-4), 3.47
(s, 3H, C1–OCH3), 3.53 (dd, 1H, J¼3.5, 4.0 Hz, H-2),
3.54 (s, 3H, C3–OCH3), 3.55 (dd, 1H, J¼3.5, 4.5 Hz,
H-3), 3.66–4.14 (AB system, 2H, JAB¼11.5 Hz, H-6a,
H-6b), 4.63–4.68 (AB system, 2H, JAB¼11.0 Hz, C6–
OCH2Ph), 4.75 (d, 1H, J¼4.0 Hz, H-1),4.69–4.82 (AB
system, 2H, JAB¼11.5 Hz, C2–OCH2Ph), 7.32–7.42 (m,
10H, aromatic H); 13C NMR (CDCl3, 50 MHz) d 35.86
(C-4), 55.68 (C1–OCH3), 57.43 (C3–OCH3), 63.08 (C-5),
65.46 (C-7), 70.63 (C-6), 72.98 and 73.81 (CH2), 77.11
(C-3), 81.09 (C-2), 107.93 (C-1), 127.51, 127.61, 127.66,
127.69, 127.84, 128.27, 128.30 and 128.45 (aromatic
CH), 137.80 and 138.16 (aromatic C). Anal. Calcd for
C23H26Cl2O5: C, 60.93; H, 5.78%. Found: C, 61.02; H,
5.85.
3.5.3. (1S,3S,4R,5S,6R)-4,5-Bis-benzyloxy-1-benzyloxy-
methyl-7,7-dichloro-3-methoxy-2-oxabicyclo[4.1.0]hep-
tane 4e. Yellow oil, 48% yield, [a]2D5¼þ11.9 (c 0.27,
1
CHCl3); H NMR (CDCl3, 500 MHz) d 2.01 (d, 1H, J¼
8.0 Hz, H-4), 3.33 (s, 3H, OCH3), 3.58–3.86 (AB system,
2H, JAB¼11.4 Hz, H-6a, H-6b), 3.85 (dd, 1H, J¼3.3,
8.0 Hz, H-2), 4.19 (t, 1H, J¼8.0 Hz, H-3), 4.57–4.81 (AB
system, 2H, JAB¼11.9 Hz, CH2Ph), 4.59–4.64 (AB system,
2H, JAB¼12.1 Hz, CH2Ph), 4.61 (d, 1H, J¼3.3 Hz, H-1),
4.73–4.81 (AB system, 2H, JAB¼12.0 Hz, C2–OCH2Ph),
7.26–7.43 (m, 15H, aromatic H); 13C NMR (CDCl3,
50 MHz) d 35.10 (C-4), 56,90 (OCH3), 63.34 (C-5), 65.13
(C-7), 71.33 (C-6), 71.90 (CH2), 72.37 (C-3), 72.95 (CH2),
73.59 (CH2) 76.70 (C-2), 100.64 (C-1), 127.76, 127.84,
127.94, 128.22, 128.33, 128.40 and 128.51 (aromatic CH),
137.77, 138.16 and 138.24 (aromatic C). Anal. Calcd for
C29H30Cl2O5: C, 65.79; H, 5.71%. Found: C, 65.71; H, 5.68.

3794
A. Corsaro et al. / Tetrahedron 60 (2004) 3787–3795
3.5.7. (1R,3R,4R,5S,6S)-4,5-Bis-benzyloxy-1-benzyloxy-
methyl-7,7-dichloro-3-methoxy-2-oxabicyclo[4.1.0]hep-
tane, 5d. Syrup, 65%, yield, [a]2D5¼211.8 (c 0.4, CHCl3);
1H NMR (CDCl3, 500 MHz) d 1.68, (d, 1H, J¼5.0 Hz, H-4),
3.44 (s, 3H, OCH3), 3.57 (dd, 1H, J¼4.5, 10.0 Hz, H-2),
3.63–4.10 (AB system, 2H, JAB¼11.5 Hz, H-6a, H-6b),
3.67 (dd, 1H, J¼5.0, 10.0 Hz, H-3), 4.61 (s, 2H,
C6–OCH2Ph), 4.67–4.81 (AB system, 2H, JAB¼11.5 Hz,
C2–OCH2Ph), 4.68–4.75 (AB system, 2H, JAB¼12.0 Hz,
C3–OCH2Ph), 4.71 (d, 1H, J¼4.5 Hz, H-1), 7.27–7.39
(m, 15H, aromatic H); 13C NMR (CDCl3, 50 MHz) d 33.31
(C-4), 55.72 (OCH3), 63.15 (C-5), 65.50 (C-7), 70.66
(C-6), 72.20, 73.01 and 74.98 (CH2), 75.36 (C-3), 81.18
(C-2), 108.01 (C-1), 127.61, 127.67, 127.83, 128.27,
128.29, 128.31, 128.43 and 128.45 (aromatic CH), 137.64,
137.82 and 138.20 (aromatic C). Anal. Calcd for
C29H30Cl2O5: C, 65.79; H, 5.71%. Found: C, 65.72; H, 5.78.
4.59–4.75 (AB system, 2H, JAB¼11.8 Hz, C2–OCH2Ph),
4.71 (d, 1H, J¼4.5 Hz, H-1), 7.29–7.38 (m, 10H, aromatic
H); 13C NMR (CDCl3, 50 MHz) d 14.18 (C-7), 24.98 (C-4),
55.25 (OCH3), 60.37 (C-3), 65.32 (C-3), 71.18 (C-6), 72.99
and 73.05 (CH2), 83.54 (C-2), 107.66 (C-1), 127.59, 127.88,
128.31, 128.39, 128.49 and 128.66 (aromatic CH), 137.80
and 138.01 (aromatic C). Anal. Calcd for C22H26O5: C,
71.33; H, 7.07%. Found: C, 71.42; H, 7.14.
3.6.2. (1R,3S,4R,5S,6S)-4,5-Bis-benzyloxy-1-benzyloxy-
methyl-3-methoxy-2-oxabicyclo[4.1.0]heptane, 3e. Yel-
low oil, 68% yield, [a]2D5¼256.7 (c 0.2, CHCl3); 1H NMR
(CDCl3, 500 MHz) d 0.72 (t, 1H, J¼7.0 Hz, H-7a), 0.86
(dd, 1H, J¼7.0, 7.5 Hz, H-7b), 1.52 (dd, 1H, J¼1.0, 7.5 Hz,
H-4), 3.35–3.70 (AB system, 2H, JAB¼11.0 Hz, H-6a,
H-6b), 3.46 (s, 3H, OCH3), 3.54 (1H, dd, J¼2.0, 7.0, Hz,
H-2), 4.00 (dd, 1H, J¼1.0, 7.0 Hz, H-3), 4.57–4.65 (AB
system, 2H, JAB¼11.0 Hz, CH2Ph), 4.58–4.64 (AB system,
2H, JAB¼11.5 Hz, CH2Ph), 4.68–4.76 (AB system, 2H,
JAB¼12.0 Hz, CH2Ph), 4.72 (d, 1H, J¼2.0 Hz, H-1), 7.28–
7.35 (m, 15H, aromatic H); 13C NMR (CDCl3, 50 MHz) d
13.69 (C-7), 30.93 (C-4), 56.55 (OCH3), 59.37 (C-5), 71.60
(C-6), 72.76, 73.00 and 73.32 (CH2), 75.25 (C-3), 76.74
(C-2), 99.53 (C-1), 127.59, 127.89, 128.03, 128.29, 128.35,
128.49, 128.57 and 128.66 (aromatic CH), 137.87, 138.26
and 138.57 (aromatic C). Anal. Calcd for C29H32O5: C,
75.63; H, 7.00%. Found: C, 75.69; H, 7.07.
3.5.8. (1R,3S,4R,5S,6S)-4,5-Bis-benzyloxy-1-benzyloxy-
methyl-7,7-dichloro-3-methoxy-2-oxabicyclo[4.1.0]hep-
tane, 5e. Yellow oil, 47% yield, [a]2D5¼þ36.7 (c 0.20,
1
CHCl3); H NMR (CDCl3, 500 MHz) d 1.55 (d, 1H, J¼
3.3 Hz, H-4), 3.42 (s, 3H, OCH3), 3.66–3.90 (AB system,
2H, JAB¼11.0 Hz, H-6a, H-6b), 3.67 (1H, dd, J¼3.3,
8.4 Hz, H-2), 3.99 (dd, 1H, J¼3.3, 8.4 Hz, H-3), 4.56 (s, 2H,
C6–OCH2Ph), 4.65–4.71 (AB system, 2H, JAB¼11.6 Hz,
C3–OCH2Ph), 4.67–4.81 (AB system, 2H, JAB¼12.0 Hz,
C2–OCH2Ph), 4.88 (d, 1H, J¼3.3 Hz, H-1), 7.26–7.37
(m, 15H, aromatic H); 13C NMR (CDCl3, 50 MHz) d 38.39
(C-4), 56,18 (OCH3), 63.42 (C-5), 64.02 (C-7), 71.93 (C-6),
72.12 (C-3), 72.62, 73,38 and 73.68 (CH2), 76.12 (C-2),
100.87 (C-1), 127.59, 127.73, 127.88, 127.90, 128.33,
128.40 and 128,49 (aromatic CH), 137.71, 137.86 and
138,22 (aromatic C). Anal. Calcd for C29H30Cl2O5: C,
65.79; H, 5.71%. Found: C, 65.84; H, 5.67.
3.7. Conversion of 4b into 6b by reduction with 6 equiv.
excess of lithium aluminum hydride
Initially, in the case of 4b (350 mg, 0.80 mmol), when an
excess of 4.80 mmol (182 mg) of lithium aluminium
hydride was used, the corresponding monohalogenated
cyclopropane sugar 6b after flash chromatography was
obtained with a 90% yield.
3.6. Conversion of 4a,b into 2a,b and 5b,e into 3b,e by
reduction with 12 equiv. excess lithium aluminium
hydride
3.7.1. (1S,3S,4R,5S,6R,7S)-4-Benzyloxy-1-benzyloxy-
methyl]-7-chloro-3-methoxy-2-oxabicyclo[4.1.0]heptan-
5-ol, 6b. Syrup, 90% yield, [a]2D5¼24.2 (c 0.2, CHCl3); 1H
NMR (CDCl3, 500 MHz) d 1.89 (dd, 1H, J¼8.0, 8.5 Hz,
H-4), 2.19 (bs, 1H, OH), 3.24 (d, 1H, J¼8.5 Hz, H-7), 3.33–
3.90 (AB system, 2H, JAB¼10.0 Hz, H-6a, H-6b), 3.57
(t, 1H, J¼8.5 Hz, H-2), 3.61 (s, 3H, OCH3), 4.40 (dd, 1H,
J¼8.0, 8.5 Hz, H-3), 4.49 (d, 1 h, J¼8.5 Hz, H-1), 4.54–
4.60 (AB system, 2H, JAB¼12.0 Hz, CH2Ph), 4.72–4.95
(AB system, 2H, JAB¼11.5 Hz, CH2Ph), 7.29–7.40
(m, 10H, aromatic H); 13C NMR (CDCl3, 50 MHz) d
25.47 (C-4), 38.51 (C-7), 57.21 (OCH3), 59.39 (C-5), 71.75
(C-3), 72.06 (C-6), 73.32 and 74.40 (CH2Ph), 82.06 (C-2),
104.63 (C-1), 127.48, 127.63, 127.88, 128.35 and 128.45
(aromatic CH), 137.67 and 139.41 (aromatic C). Anal.
Calcd for C22H25ClO5: C, 65.26; H, 6.22%. Found: C,
65.34; H, 6.29. m/z: FAB 404 (M21), 368 (M235).
To a stirred solution of 4a,b or 5b,e (0.80 mmol) in
tetrahydrofuran (10 mL) a solution containing an excess of
lithium aluminium hydride (316 mg, 9.6 mmol) in dry
tetrahydrofuran (4 mL) was added. After being stirred for
4 h at room temperature, the reaction mixture was cooled in
ice and quenched by careful addition of saturated aqueous
sodium sulphate. The salts were filtered and washed several
times with hot ethyl acetate. The filtrate was dried (Na2SO4)
and concentrated. The residue of chromatographic purifi-
cation furnished cyclopropanated sugars in pure form.
Cyclopropanated sugars 2a and 2b were separated in 23 and
75% yield, respectively, and their structures were confirmed
1
by superimposable H and 13C NMR spectra.
3.6.1. (1R,3R,4R,5S,6S)-4-Benzyloxy-1-benzyloxymethyl-
3-methoxy-2-oxabicyclo[4.1.0]heptan-5-ol 3b. Syrup,
76% yield, [a]D25¼213.5 (c 0.3, CHCl3); 1H NMR
(CDCl3, 500 MHz) d 0.92 (t, 1H, J¼7.5 Hz, H-7a), 0.96
(dd, 1H, J¼7.5, 8.0 Hz, H-7b), 1.46 (dd, 1H, J¼5.5, 8.0 Hz,
H-4), 2.30 (bs, 1H, OH), 3.42 (s, 3H, OCH3), 3.47–3.94
(AB system, 2H, JAB¼10.3 Hz, H-6a, H-6b), 3.49 (1H, d,
J¼4.5, 10.0 Hz, H-2), 3.84 (dd, 1H, J¼5.5, 10.0 Hz, H-3),
4.50–4.56 (AB system, 2H, JAB¼12.1 Hz, C6–OCH2Ph),
Acknowledgements
This work was performed with funds provided by Consorzio
Interuniversitario Nazionale ‘La Chimica per l’Ambiente’
within the project ‘Ambiente Terrestre: Chimica per
l’Ambiente’ financed by M.I.U.R. in accordance with Law

A. Corsaro et al. / Tetrahedron 60 (2004) 3787–3795
3795
(d) Catelani, G.; Corsaro, A.; D’Andrea, F.; Mariani, M.;
`
Pistara, V.; Vittorino, E. Carbohydr. Res. 2003, 338, 2349.
n. 488/92. Partial support to G.C. from M.I.U.R. (Rome) in
the frame of COFIN 2002 is also acknowledged.
18. Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F. Gazz. Chim.
Ital. 1992, 122, 135.
19. Although for the correct naming of the cyclopropanated
compounds (see Section 3) the two fused systems were
numbered as in formula A, the classical carbohydrate
numbering, as in Figures 1 and 2, was used for the assignment
of NMR parameters.
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