Synthesis and Reactions of 1,2-Cyclopropanated Sugars

Article abstract of DOI:10.1021/jo970948k

Diastereospecific cyclopropanation of glycals 1, 2, 3, 4, and 41 was carried out using either dihalocarbene addition or zinc-carbenoid addition to yield 1,2-cyclopropanated sugars. Dichloroand dibromocarbenes added stereoselectively anti to the C₃

Full text of DOI:10.1021/jo970948k

7694
J . Org. Chem. 1997, 62, 7694-7703
Syn th esis a n d Rea ction s of 1,2-Cyclop r op a n a ted Su ga r s
C. V. Ramana, R. Murali, and M. Nagarajan*
School of Chemistry, University of Hyderabad, Hyderabad-500 046, India
Received May 29, 1997X
Diastereospecific cyclopropanation of glycals 1, 2, 3, 4, and 41 was carried out using either
dihalocarbene addition or zinc-carbenoid addition to yield 1,2-cyclopropanated sugars. Dichloro-
and dibromocarbenes added stereoselectively anti to the C3 benzyloxy group, whereas (under
Simmons-Smith conditions) the cyclopropanes were formed syn to the same substituent. The
reactions of these 1,2-cyclopropanated sugars to provide either ring expanded glycosides or C2-
branched chain glycosides were explored. Solvolytic ring expansion of 1,2-dibromocyclopropanated
sugars with K2CO3 in refluxing methanol yielded the corresponding chiral oxepins 20-22.
Electrophilic ring openings of parent cyclopropanes (14 and 17 derived from glucal 1) were carried
out with different electrophiles to give functionalized 2-deoxy-2-C-branched chain glycosides. The
ring openings of 14 in different solvents resulted in both R- and â-anomers, whereas 17 gave
exclusively the R-anomer.
In tr od u ction
ated sugars and Heathcock reported a facile synthesis
of 3,4,6-tri-O-benzyl-2-C-methyl-D-glucal from 17.7
The unusual bonding and strain present in cyclopro-
panes as well as their ability to interact with adjacent
π-electron systems and p-electron centers, enables them
to undergo selective transformations. The chemical
resemblance of cyclopropanes to that of double bonds8
makes possible hydrogenation, halogenation, and acid
and electrophilic additions accompanied by concomitant
ring cleavage. In fact, the utility of such building blocks
for organic synthesis has been well recognized.9 Among
the many applications of cyclopropane derivatives in
organic synthesis are solvolytic one-carbon homologation,
synthesis of allenes from double bonds via dihalocyclo-
propanes, solvolytic ring opening of cyclopropyl carbinols,
ring enlargement (to five-membered rings) of vinyl cy-
clopropanes, and Cope rearrangement of cis-divinylic
cyclopropanes for either synthesis or annelation of seven-
membered rings.
1,2-Anhydrosugars are important synthetic intermedi-
ates for the synthesis of a variety of C-1 substituted
sugars. A well-known example of this class of compounds
is Brigl’s anhydride, prepared more than 70 years ago.1
Their high reactivity is attributed to the strained epoxide
ring which is also part of an acetal. Recently, a straight-
forward route to 1,2-anhydrosugars was developed by
Danishefsky, via expoxidation of glycals with dimethyl-
dioxirane.2a He has also made extensive use of them in
oligosaccharide synthesis.2 However, comparatively little
attention has been bestowed on 1,2-aziridino and 1,2-
cyclopropanated sugars. Descotes3 showed that a 1,2-
aziridino sugar is the intermediate in the conversion of
a glycosylamine derivative to a 2-aminoglycoside. Later
Danishefsky exploited this concept by employing sul-
fonamidoglycosylation of glycals for rapid assembly of
modified 2-amino-2-deoxy oligosaccharides.4 In 1967,
Brimacombe and co-workers described the synthesis of
3,4,6-tri-O-methyl-1,5-anhydro-2-deoxy-1,2-C-methylene-
D-glycero-D-gulo-hexitol by addition of dichlorocarbene to
trimethylglucal followed by dechlorination of the adduct
with LiAlH4.5 The high reactivity of cyclopropanes and
the absence of further work in this area prompted us to
study the synthesis and reactions of 1,2-cyclopropanated
sugars. A preliminary communication has appeared.6 In
this paper, we present a detailed account of our results.
In the interim period, Fraser-Reid and Hoberg published
preliminary accounts of their work on 1,2-cyclopropan-
Our interest in 1,2-cyclopropanated sugars, as shown
in path A, Scheme 1, arose from the possibility that the
solvolytic ring enlargement of dihalocyclopropanes would
yield chiral oxepins, which, either alone or fused with
other rings, are found in several complex natural prod-
ucts. However, there is a paucity of general methods for
(7) (a) Hoberg, J . O.; Bozell, J . J . Tetrahedron Lett. 1995, 36, 6831.
(b) Hoberg, J . O.; Claffey, D. J . Tetrahedron Lett. 1996, 37, 2533. (c)
Henry, K. J ., J r.; Fraser-Reid, B. Tetrahedron Lett. 1995, 36, 8901. (d)
Timmers, C. M.; Leeuwenburgh, M. A.; Verheijen, J . C; van der Marel,
G. A.; van Boom, J . H. Tetrahedron: Asymmetry 1996, 7, 49. (e) Scott,
R. W.; Heathcock, C. H. Carbohydr. Res. 1996, 291, 205. (f) Recently
Danishefsky has used the glycal cyclopropane solvolysis strategy for
the introduction of the gem-dimethyl group. Bertinato, P.; Sorensen,
E. J .; Meng, D.; Danishefsky, S. J . J . Org. Chem. 1996, 61, 8000.
* Fax: 0091-40-3010120/3010145. E-mail: mnsc@uohyd.ernet.in.
X Abstract published in Advance ACS Abstracts, September 15, 1997.
(1) Brigl, P. Z. Physiol. Chem. 1922, 122, 257.
(2) (a) Halcomb, R. L.; Danishefsky, S. J . J . Am. Chem. Soc. 1989,
111, 6661. (b) Gordon, D. M.; Danishefsky, S. J . Carbohydr. Res. 1990,
206, 361. (c) Liu, K. K.-C.; Danishefsky, S. J . J . Org. Chem. 1994, 59,
1892. (d) Liu, K. K.-C.; Danishefsky, S. J . J . Org. Chem. 1994, 59, 1895.
(3) (a) Lafont, D.; Descotes, G. Carbohydr. Res. 1987, 166, 195. (b)
Lafont, D.; Descotes, G. Carbohydr. Res. 1988, 175, 35.
(4) (a) Griffith, D. A.; Danishefsky, S. J . J . Am. Chem. Soc. 1990,
112, 5811. (b) Park, T. K.; Kim, I. J .; Danishefsky, S. J . Tetrahedron
Lett. 1995, 36, 9089. (c) Kim, I. J .; Park, T. K.; Hu, S.; Abrampah, K.;
Zhang, S.; Livingston, P. O.; Danishefsky, S. J . J . Org. Chem. 1995,
60, 7716 (and references cited therein).
(8) de Meijere, A. Angew. Chem., Int. Ed. Engl. 1979, 18, 809 and
references cited therein.
(9) For recent reviews covering this area, see: (a) Rappoport, Z. The
Chemistry of the Cyclopropyl Group; Wiley-Interscience, New York,
1987. (b) de Meijere, A.; Wessjohann, L. Synlett 1990, 20. (c) Wong,
H. N. C. In Rodds Chemistry of Carbon Compounds Vol IIa/ IIb, Chapter
2; Sainsbury, M., Ed.; Elsevier Science Publishers B.V.: Amsterdam,
1992, and references cited therein. (d) Nair, V. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Semmelhack, M. E., Eds.;
Pergamon Press: Oxford, 1991; Vol. 4, Chapter 4.7, p 999.
(5) Brimacombe, J . S.; Evans, M. E.; Forbes, E. J .; Foster, A. B.;
Webber, J . M. Carbohydr. Res. 1967, 4, 239.
(6) Murali, R.; Ramana, C. V.; Nagarajan, M. J . Chem. Soc., Chem.
Commun. 1995, 217.
S0022-3263(97)00948-1 CCC: $14.00 © 1997 American Chemical Society

Synthesis and Reactions of 1,2-Cyclopropanated Sugars
J . Org. Chem., Vol. 62, No. 22, 1997 7695
Ta ble 1
Sch em e 1
Sch em e 2
the synthesis of functionalized oxepanes/oxepins10 and
there are very few reports on the synthesis of chiral
oxepins.11 Another aspect of our interest in 1,2-cyclo-
propanated sugars is their potential ability to undergo,
in presence of a protic solvent, an electrophilic ring
opening12 assisted by the pyranose oxygen to furnish a
2-deoxy-2-C-branched chain glycoside with defined C-2
stereochemistry, inherently present in the cyclopropane
(Scheme 1, path B). A similar strategy is known with
3,4-dihydro-2H-pyran;13 with glycals the products not
only reveal the stereo- and regioselectivtiy aspects but
also yield synthetically important intermediates.
In this context, we envisioned that a convenient face
selective cyclopropanation of appropriately protected 1,2-
unsaturated sugars or glycals is possible on the basis of
the directing effect of the C-3 substituent. As shown in
Scheme 2, the steric hindrance associated with the C-3
benzyloxy group is expected to direct a bulky dihalocar-
bene to the less hindered R-face of 3,4,6-tri-O-benzyl-D-
glucal as reported earlier, by Brimacombe,5 whereas the
same C-3 benzyloxy group, by coordinating with zinc
would result in a â-cyclopropanation under Simmons-
Smith14 conditions.
in the presence of a catalytic amount of triethylbenzyl-
ammonium chloride, afforded the corresponding dichloro
adduct 5 in 84% yield. This procedure was extended to
3,4,6-tri-O-benzyl-D-galactal (2), 3,4-di-O-benzyl-L-rham-
nal (3), and 3,4-di-O-benzyl-D-xylal (4). All the glycal
derivatives 1-4 gave single adducts with dichlorocar-
bene. The individual results are tabulated in Table 1.
When the reaction was performed replacing chloroform
by bromoform under otherwise identical conditions, no
product could be isolated. The reaction mixture turned
black within a few minutes and also became very viscous.
Decreasing the concentration of sodium hydroxide solu-
tion did not offer any useful results. This problem was
overcome by employing a large excess of potassium
fluoride and smaller amounts of alkali.16 Under these
conditions, the addition of dibromocarbene took place
cleanly and the dibromocyclopropanes were obtained in
good yields. Barring 3,4-di-O-benzyl-L-rhamnal (3) which
gave two adducts 11 and 12 in a 7:1 ratio, the other
glycals gave only single adducts. These results are
presented in Table 2.
Resu lts a n d Discu ssion
Gross and co-workers added dihalocarbenes generated
by a phase transfer catalyzed procedure to unsaturated
sugars.15 We adopted a similar methodology with glycals.
Thus, treatment of 3,4,6-tri-O-benzyl-D-glucal (1) dis-
solved in chloroform, with 50% aqueous sodium hydroxide
(10) (a) Nakata, T.; Nomura, S.; Matsukura, H. Tetrahedron Lett.
1996, 37, 213. (b) Palazo´n, J . M.; Mart´ın, V. S. Tetrahedron Lett. 1995,
36, 3549. (c) Nicolaou, K. C.; Theodorakis, E. A.; Rutges, F. P. J . T.;
Tiebes, J .; Sato, M.; Untersteller, D.; Xiao, X.-Y. J . Am. Chem. Soc.
1995, 117, 1171. (d) Hishiyama, O. H.; Hirama, S. O. T. Synlett 1995,
1252. (e) Kadota, I.; Matsukawa, Y.; Yamamoto, Y. J . Chem. Soc.,
Chem. Commun. 1993, 1638. (f) Ravelo, J . L.; Regueiro, A.; Mart´ın, J .
D. Tetrahedron Lett. 1992, 33, 3389. (g) Molander G. A.; Andrews, S.
W. J . Org. Chem. 1989, 54, 3114.
(11) (a) Nicolaou, K. C.; Prasad, C. V. C.; Somers P. K.; Hwang, C.
K. J . Am. Chem. Soc. 1989, 111, 5330 and 5335. (b) Moody, C. J .; Sie,
E.-R. H. B.; Kulagowski, J . J . J . Chem. Soc., Perkin Trans. 1 1994,
501. (c) Kadata, I.; Gevorgyan, V.; Yamada V.; Yamamoto, Y. Synlett
1991, 823. (d) Soler, M. A.; Palazo´n J . M.; Mart´ın, V. S. Tetrahedron
Lett. 1993, 34, 5471. (e) Datta, S.; Chattopadhyay, P.; Mukhopadhyay,
R.; Bhattacharjya, A. Tetrahedron Lett. 1993, 34, 3585. (f) Berger, D.;
Overman, L. E.; Renhowe, P. A. J . Am. Chem. Soc. 1993, 115, 9305.
(12) Reissig, H. U. In Topics in Current Chemistry 144 (Small Ring
Compounds in Organic Synthesis); deMeijere, A., Ed.; Springer-
Verlag: Berlin 1988; p 73 and references cited therein.
We established the stereochemistry of the products of
1
addition of dihalocarbenes to glycals 1, 2, 3, and 4 by H
NMR spectroscopy. The C-2 hydrogen, in all the adducts,
resonated around 2.0 ppm and appeared as a doublet of
doublets with the sole of exception of 12 in which it was
an apparent triplet. The four-line pattern of the C-2
hydrogen had coupling constants around 8 and 4 Hz. The
larger value was assigned to J 1,2 coupling as evidenced
from the H-1 signal (a doublet with 8 Hz coupling
constant). The smaller value of the coupling between C-2
and C-3 protons suggests a quasi axial-equatorial ar-
rangement. In adduct 12, the H-2 proton appeared as
an apparent triplet with a coupling constant of 8 Hz. This
is possible only if the concerned protons H-1, H-2, and
H-3 are all on the same face of the molecule. Therefore,
(13) Skattebøl, L. J . Org. Chem. 1970, 35, 3200.
(14) (a) Chan, J . H.; Rickborn, B. J . Am. Chem. Soc. 1968, 90, 6406.
(b) Poulter, C. D.; Friedrich, E. C.; Winstein, S. J . Am. Chem. Soc.
1969, 91, 6892.
(16) Fedorynski M.; Makosza, M. J . Organomet. Chem. 1973, 51,
(15) Duchaussoy, P.; Cesare, P. D.; Gross, B. Synthesis 1979, 198.
6406.

7696 J . Org. Chem., Vol. 62, No. 22, 1997
Ramana et al.
Ta ble 2
Ta ble 4
to both dichloro- and dibromocyclopropanes and lay
centered at 0.9 ppm. The additional multiplets at 0.7
ppm integrating for two protons were assigned to the
protons attached to C-7, thus confirming the complete
reduction of dichloro adducts.
In order to examine the validity of our assumption
regarding the synthesis of the other diastereomeric
cyclopropanes, we attempted to cyclopropanate glycals
under Simmons-Smith conditions, where the reaction
is known to proceed via an oxygen-directed pathway with
allylic alcohols and ethers to yield products with the
cyclopropane ring syn to the coordinating oxygen. The
Friedrich-modified version of the Simmons-Smith reac-
tion,18 using acetyl chloride as an activator, was found
to be convenient, and single diastereomers were obtained
with glycals 1-3. These results are summarized in Table
4.
Ta ble 3
1
It was immediately obvious from their H NMR spectra
that these cyclopropanes were different from the ones
obtained by LAH reduction of the corresponding dichloro
adducts 5-7. The C-3 hydrogen, in all cases, appeared
as an apparent triplet, suggesting that J 2,3 and J 3,4 are
nearly equal. It is known in the case of glucose and
rhamnose that the C-3 and C-4 hydrogens, which are
trans diaxial to one another, have large couplings. This,
taken together with the larger value of cis J 2,3 makes it
clear that the products obtained have the stereochemistry
as shown above (Table 4). Similar results have also been
reported by Hoberg et al.7a
After identification of simple procedures for both
diastereomers of 1,2-cyclopropanated sugars, efforts to-
ward their utility in the synthesis of chiral oxepin
derivatives through solvolytic ring expansion and func-
tionalized 2-deoxy 2-branched chain sugars by electro-
philic ring openings were initiated.
it is reasonable to assume that J 2,3 is around 4 Hz when
H-2 and H-3 are trans to one another and is around 8
Hz when they are cis to one another. This is in keeping
with the report that in cyclopropanes17 the 1,2-cis cou-
plings are larger than the 1,2-trans couplings. Thus, the
products of dihalocyclopropanation are either exclusively
or predominantly formed on the face of the double bond
away from the C-3 substituent, as expected on steric
grounds.
As shown in Scheme 3, we anticipated that the cyclo-
propyl cation resulting from the loss of endo halogen19
would rearrange in such a way that the positive charge
of the resultant allyl cation is placed at C-1, due to its
stabilization by the adjacent oxygen atom. Capture by
a nucleophilic solvent like methanol would then provide
a seven-membered glycoside.
Dehalogenation of these adducts with LAH in THF was
next attempted. Our studies showed that the reductions
of dichlorocyclopropanes were clean and economical
compared to their dibromo counterparts. Table 3 sum-
marizes the yields of these dehalogenation reactions.
1
In the H NMR spectrum, the multicipity of the H-2
signal increased and also moved further upfield compared
(17) (a) Graham, J . D.; Rogers, M. T. J . Am. Chem. Soc. 1962, 84,
2249. (b) Williamson, K. L.; Lanford, C. A.; Nicholson, C. R. J . Am.
Chem. Soc. 1964, 86, 762. (c) Wiberg, K. B.; Barth, D. E.; Schertler, P.
H. J . Org. Chem. 1973, 38, 378.
(18) Friedrich, E. C.; Lewis, E. J . J . Org. Chem. 1990, 55, 6892.
(19) (a) Skell, P. S; Sandler, S. R. J . Am. Chem. Soc. 1958, 80, 2024.
(b) Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl. 1969,
8, 781.

Synthesis and Reactions of 1,2-Cyclopropanated Sugars
J . Org. Chem., Vol. 62, No. 22, 1997 7697
Sch em e 3
Sch em e 4
Ta ble 5
were carried with 1.5 equiv of acid in MeOH at rt). Later
when the reaction was performed in refluxing methanol
containing 1.5 equiv of HCl for 15 days, we were able to
obtain about 40% conversion (70% yield) in case of the
R-cyclopropane 14 giving methyl 3,4,6-tri-O-benzyl-2-
deoxy-2-C-methyl-â-D-glucopyranoside (23) exclusively.
Under similar conditions â-cyclopropane 17 was unreac-
tive and increasing the amount of HCl caused its decom-
position.
When R-cyclopropane 14 was treated with N-bromo-
succinimide in methanol (8 h), it gave rise to two ring-
opened products 24 and 25 (R- and â-anomers) in a 20:
80 ratio (72%). Under similar conditions, the â-cyclo-
propane 17 reacted at a much slower rate (24 h) but with
higher selectivity giving only the R-anomer 26 (62%).
When N-iodosuccinimide was used as a source of I+ (in
MeOH) R-cyclopropane 14 reacted within 12 h giving both
R- and â-anomers (27 and 28) in a 20:80 ratio, whereas
the reaction with â-cyclopropane 17 gave only 10%
conversion. When N-iodosuccinimide was replaced by
iodonium di(s-collidine) perchlorate, the reaction with
R-cyclopropane 14 was over within 6 h giving both R- and
â-anomers (27 and 28, 15:85) in 86% yield. Again, the
reaction was incomplete with â-cyclopropane 17 (36 h,
45% conversion) giving only the R-anomer (29) in about
70% yield.
All the above products were readily characterized from
their spectral and analytical data. The 13C NMR spectra
of all three diastereomeric bromo and iodo derivatives
showed only 11 lines in addition to the aromatic signals.
The high-field signals around 31 and 47 ppm in 24 and
25 were assigned to C7 and C2, respectively. The DEPT-
135 spectra of these substrates showed that the carbon
attached to bromine or iodine was a methylene and not
a methine, thus establishing the preference for ring
opening over ring expansion. The larger coupling con-
stant (J ) 8.5 Hz) for the anomeric proton of 25, when
compared to 24 (J ) 2.6 Hz) and also that of 28 (J ) 8.6
Hz) to 27 (J ) 3 Hz), shows that 25 and 28 are
â-anomers.21 In the 13C NMR spectra, C1 of 24 resonates
at 102.3 ppm and that of 25 at 99.23 ppm, once again
confirming the anomeric assignment.21 Finally, the
optical rotations of these anomers were also found to be
in accord with Hudson’s rule.22
Solvolysis of the dichloro- and dibromocyclopropanes
was attempted initially with silver ion and Lewis acid
catalysis. No reaction was observed under mild condi-
tions (stirring at room temperature in AcOH). Under
more vigorous conditions (AcOH or 1,4-dioxane, reflux
temperatures) the starting material was completely
destroyed. However, when boiled with excess K2CO3 in
methanol,20 adducts 9, 10, and 11 underwent smooth
solvolysis providing ring-expanded oxepins 20-22 as
anomeric mixtures in good yields (Table 5). The anomers
of 20 could be separated by column chromatography
while those of 21 and 22 were inseparable. The product
identities were established by extensive NMR studies as
well as by analytical methods. The presence of narrow
1
doublets at δ 5.17 and 6.80 in the H NMR spectrum of
20 (major) confirmed that ring expansion had indeed
taken place. These signals correspond to anomeric and
olefinic protons (H-1 and H-3), respectively, as estab-
lished by 2D NMR studies (COSY and HETCOR). The
minor anomer of 20 also showed similar spectral features.
Although the anomers of 21 and 22 were inseparable,
their 1H and 13C NMR spectra indicated that they also
have an oxepin skeleton.
As shown in Scheme 4, in the electrophilic ring opening
of a 1,2-cyclopropanated sugar, although the competitive
formation of a septanoside is possible, it is less likely due
to preferential edge selection of the C1-C7 bond by the
incoming electrophile on the basis of steric consider-
ations.
In this context, the R- and â-cyclopropanes 14 and 17,
respectively, derived from 3,4,6-tri-O-benzyl-D-glucal (1)
were chosen to investigate the ring opening. Our initial
attempts using a proton as an electrophile to carry out
the ring opening of cyclopropanes 14 and 17 were
unsuccessful with hydrochloric acid, acetic acid, and
perchloric acid as the proton source (all the reactions
Encouraged by this, and to further examine the
generality of this method, the ring-opening reactions of
14 and 17 were carried out in different alcohols and the
results are summarized in the Tables 6 and 7. As can
be seen from the alcohols chosen, the glycosides formed
from them can be hydrolyzed to the free sugars under
acidic or neutral conditions, imparting flexibility to the
method, if needed.
The reaction of cyclopropane 14 in 2-chloroethanol with
NBS as an activator was complete in 4 h, giving 30 (R-
anomer) and 31 (â-anomer) in a 35:65 ratio, whereas
cyclopropane 17 took 12 h to go to completion yielding
only the R-anomer 32. In 2,2,2-trichloroethanol, the
(21) Bundle, D. R.; Lemieux, R. U. Methods Carbohydr. Chem. 1976,
7, 79.
(22) Hudson, C. S. J . Am. Chem. Soc. 1909, 31, 66.
(20) Banwell, M. G.; Corbett, M.; Gulbis, J .; Mackay, M. F.; Reum,
M. E. J . Chem. Soc., Perkin Trans. 1 1993, 945.

7698 J . Org. Chem., Vol. 62, No. 22, 1997
Ramana et al.
Ta ble 6
Ta ble 7
reaction was fast with R-cyclopropane 14 (1 h, 33 and
34 were obtained in 1:1 ratio) and took nearly 8 h with
â-cyclopropane 17, yielding only R-anomer 35. Surpris-
ingly, the opening of 14 with benzyl alcohol was sluggish,
taking 36 h. The corresponding R- and â-anomers 36 and
37 were obtained in a 35:65 ratio. Under similar condi-
tions, even after 4 days, only 20% conversion (40% yield)
was observed with 17. This clearly indicates the higher
reactivity of R-cyclopropane 14 over â-cyclopropane 17.
The openings of R- and â-cyclopropanes with water as
nucleophile were carried out in a 1:2 mixture of water
and 1,4-dioxane. These reactions did not show much
difference in reactivity. In all the above cases, the R- and
â-anomers of the glucopyranoside products from 14 were
easily separable by chromatography and the ratios
determined from 1H NMR spectra matched with those
obtained from the separated products.
These experiments clearly reveal that the reactions
with â-cyclopropane 17 are slower and display higher
anomeric selectivity when compared to those of R-cyclo-
propane 14. This is interesting because the ring openings
of R-cyclopropane 14, with all nucleophiles, give both

Synthesis and Reactions of 1,2-Cyclopropanated Sugars
J . Org. Chem., Vol. 62, No. 22, 1997 7699
Sch em e 5a
the other hand, under similar conditions, the reaction
with â-cyclopropane 45 was incomplete and yielded the
levomannosan 47 derivative in 35% yield after 36 h.
These results clearly indicate that the lower reactivity
of the â-cyclopropane 45, when compared to 44, is due to
steric hindrance to the approach of the electrophile.
While R-cyclopropane 44 reacts clearly and rapidly by an
SN2 type process to give the levoglucosan derivative 46
in 71% yield, the â-cyclopropane 45, with no such option
available, forms the levomannosan derivative 47 in a
much lower yield, probably through an SN1 mechanism.
In conclusion, we have developed convenient proce-
dures for the synthesis of 1,2-cyclopropanted sugars in
both diastereomeric forms. These cyclopropanated sug-
ars can be readily converted to chiral oxepin derivatives
as well as to 2-C-branched sugars of defined stereochem-
istry. Applications of these results to the synthesis of
oxepane-containing compounds and branched disaccha-
rides are in progress.
a
Reagents and Conditions: (a) CHCl3, 50% aqueous NaOH, 24
Exp er im en ta l Section
h; (b) HCO2H:ether (1:2), 1 h; (c) LAH, THF, 24 h; (d) NBS,
CH3CN, 4 Å molecular sieves, 5 or 36 h; (e) Zn-CuCl, AcCl, CH2I2,
ether, reflux, 2 h.
Ma t er ia ls. Unless specified otherwise, reagent grade
reactants and solvents were used as received from chemical
suppliers. Solvents were dried by appropriate methods wher-
ever needed. Glycals 1-4 and 41 were prepared according to
available literature methods.23a,b All organic extracts were
dried over anhydrous magnesium sulfate. Acme silica gel
100-200 mesh was used for column chromatography.
3,4,6-Tr i-O-ben zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-(d ich lo-
r om eth ylen e)-D-glycer o-D-gu lo-h exitol (5). Aqueous so-
dium hydroxide (5.0 g in 10 mL) was added to a vigorously
stirred solution of tribenzyl-D-glucal (1) (1.60 g, 3.84 mmol) in
chloroform (10 mL) containing benzyltriethylammonium chlo-
ride (20 mg). The reaction mixture was stirred at 35 °C for 4
h and then diluted with water (25 mL) and extracted with
dichloromethane. The combined extracts were dried and
concentrated, and the residue was purified by chromatography
to furnish 5 (1.60 g, 84%) as a colorless solid (hexane): mp )
62-63 °C; [R]25D ) +78 (c 1, CHCl3); 1H NMR δ 7.40-7.25 (m,
15H), 4.92-4.40 (m, 6H), 3.91-3.87 (d, J ) 7.9 Hz, 1H), 3.81-
3.74 (m, 3H), 3.55-3.53 (m, 2H), 1.81-1.75 (dd, J ) 4.4, 7.9
Hz, 1H); 13C NMR δ 138.34, 138.09, 128.51, 128.43, 128.20,
127.81, 127.18, 127.73, 80.01, 77.53, 75.33, 74.63, 73.44, 71.96,
70.30, 61.62, 59.05, 34.41. Anal. Calcd for C28H28Cl2O4: C,
67.33; H, 5.65. Found: C, 67.13; H, 5.66.
inversion and retention, but those of â-cyclopropane 17
proceed with complete inversion. The greater reactivity
of cyclopropane 14 when compared to cyclopropane 17
can be accounted for by the increased steric hindrance
to the approach of the electrophile to the three-membered
ring in the latter compound. Exclusive formation of the
R-glycoside from cyclopropane 17 is then a consequence
of an elctrophile-activated SN2 type ring opening of the
cyclopropane by the external nucleophile. With the
R-cyclopropane 14, the â-glycoside is formed predomi-
nantly by the same route, while simultaneous formation
of the R-anomer in this case points to the possible
involvement of an SN1 pathway. It may be noted in both
instances that the R-glycoside is the one favored by the
anomeric effect.
To better understand the processes taking place, we
prepared the R- and â-cyclopropanes 44 and 45 with a
free 6-OH group as outlined below. 3,4-Di-O-benzyl-6-
O-trityl-D-glucal (41)23b on dichlorocarbene addition fol-
lowed by detritylation using 2:1 ether/formic acid23c gave
43, which on dehalogenation with LAH in THF yielded
the corresponding R-cyclopropane 44 in 45% overall yield.
Suprisingly, under Simmon-Smith cyclopropanation
conditions, 41 directly yielded the required 6-OH â-cy-
clopropane 45 in 70% yield (Scheme 5).
The ring opening of these cyclopropanes with an
electrophile in an aprotic solvent will result in the
intramolecular attack of 6-OH at C-1, giving a levogly-
cosan derivative. This should be particularly favorable
for the cyclopropane 44, where the 6-OH group and
cyclopropane are well set to react in an SN2 type process.
In cyclopropane 45 the SN2 type process can be ruled out,
but formation of a levoglycosan derivative is possible by
an SN1 pathway.
The intramolecular ring opening of R-cyclopropane 44
in acetonitrile with NBS as an activator in the presence
of 4 Å molecular sieves took place smoothly within 5 h
giving the levoglucosan derivative 46 in 71% yield. On
3,4,6-Tr i-O-ben zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-(d ich lo-
r om eth ylen e)-D-glycer o-L-m a n n o-h exitol (6). Reaction of
3,4,6-tri-O-benzyl-D-galactal (2) under the same conditions as
1 for 24 h gave 6 in 92% yield: syrup; [R]25 ) +13.5 (c 1.2,
D
CHCl3); 1H NMR δ 7.38-7.25 (m, 15H) 4.96-4.39 (m, 6H),
3.91-3.79 (m, 3H), 3.64-3.52 (m, 3H), 1.99-1.93 (dd, J ) 8.9,
4.2 Hz, 1H); 13C NMR δ 138.68, 138.0, 137.65, 128.63, 128.50,
128.38, 127.98, 127.86, 127.72, 78.05, 75.32, 74.58, 73.55,
71.70, 71.21, 69.16, 61.81, 58.69, 31.09. Anal. Calcd for
C28H28Cl2O4: C, 67.33; H, 5.65. Found: C, 67.06; H, 5.67.
3,4-Di-O-ben zyl-1,5-a n h yd r o-2,6-d id eoxy-1,2-C-(d ich lo-
r om eth ylen e)-L-glycer o-L-gu lo-h exitol (7). Under identical
conditions 3,4-di-O-benzyl-L-rhamnal (3) gave 7 in 95% yield
after a reaction time of 18 h: colorless syrup, [R]25 ) -40 (c
D
1.2, CHCl3); 1H NMR δ 7.32-7.25 (m, 10H), 4.94-4.57 (m, 4H),
3.95-3.72 (m, 3H), 3.29 (t, J ) 7.4 Hz, 1H), 1.84-1.78 (dd, J
) 8.2, 4.2 Hz, 1H), 1.30-1.27 (d, J ) 6.4 Hz, 3H); 13C NMR δ
138.33, 137.73, 128.52, 128.36, 127.99, 127.92, 127.75, 81.07,
77.04, 76.06, 74.49, 71.99, 61.42, 57.86, 33.92, 19.84. Anal.
Calcd for C21H22Cl2O3: C, 64.13; H, 5.64. Found: C, 63.92;
H, 5.62.
3,4-Di-O-b en zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-(d ich lor o-
m eth ylen e)-D-gu lo-p en titol (8). Aqueous sodium hydroxide
(500 mg in 1 mL) was added to a vigorously stirred solution of
3,4-di-O-benzyl-D-xylal (4) (45 mg, 0.15 mmol) in chloroform
(1 mL) containing benzyltriethylammonium chloride (5 mg).
The biphasic reaction mixture was stirred at room temperature
(23) (a) Chmielewski, M.; Fokt, I.; Grodner, J .; Grynkiewicz, G.;
Szeja, W. J . Carbohydr. Chem. 1989, 8, 735. (b) Esswein, A.; Rembold,
H.; Schmidt, R. R. Carbohydr. Res. 1990, 200, 287. (c) Bessodes, M.;
Komiotis, D.; Antonakis, K. Tetrahedron Lett. 1986, 27, 579.

7700 J . Org. Chem., Vol. 62, No. 22, 1997
Ramana et al.
for 18 h, diluted with water (10 mL), and worked up. 8 was
filtrate was dried and concentrated. The residue on chromato-
obtained as a syrup after chromatographic purification (31 mg,
graphic purification furnished 14 as a colorless syrup (270 mg,
55%): [R]25 ) +17.3 (c 1.1, CHCl3); 1H NMR δ 7.36-7.20 (m,
78%): [R]25 ) +62 (c 1, CHCl3); 1H NMR δ 7.37-7.25 (m,
D
D
10H), 4.91-4.59 (m, 4H), 3.99-3.64 (m, 5H), 1.88-1.77 (dd, J
) 7.9, 3.8 Hz, 1H); 13C NMR δ 138.20, 137.64, 128.60, 128.46,
128.01, 127.78, 76.04, 75.39, 72.83, 72.02, 68.98, 60.87, 59.86,
33.08. Anal. Calcd for C20H20Cl2O3: C, 63.33; H, 5.32.
Found: C, 63.25; H, 5.29.
15H), 4.82-4.53 (m, 6H), 3.72-3.55 (m, 6H), 1.0-0.80 (m, 1H),
0.75-0.67 (m, 2H); 13C NMR δ 138.71, 138.55, 138.41, 128.45,
128.0, 127.76, 127.66, 80.17, 77.17, 76.90, 73.51, 73.36, 71.20,
70.21, 49.73, 14.93, 11.60. Anal. Calcd for C28H30O4: C, 78.11;
H, 7.02. Found: C, 78.0; H, 7.05.
3,4,6-Tr i-O-b en zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-(d ib r o-
m om eth ylen e)-D-glycer o-D-gu lo-h exitol (9). A solution of
sodium hydroxide (2.0 g) and potassium fluoride (15.0 g) in
water (15 mL) was added to a vigorously stirred solution of 1
(2.50 g, 6 mmol) in bromoform (10 mL) containing benzyltri-
ethylammonium chloride (20 mg). The biphasic mixture was
stirred for 2 days at room temperature and then diluted with
water (40 mL) and extracted with ether. The combined ether
extracts were washed with brine, dried, and concentrated. The
residue was purified by chromatography followed by crystal-
lization from methanol-ethyl acetate to give 2.80 g (79%) of
9: mp ) 58-60 °C; [R]25D ) +72 (c 1, CHCl3); 1H NMR δ 7.40-
7.25 (m, 15H), 4.85-4.40 (m, 6H), 3.98-3.94 (d, J ) 7.8 Hz,
1H), 3.91-3.68 (m, 3H), 3.56-3.53 (m, 2H), 1.91-1.85 (dd, J
) 4.56, 7.8 Hz, 1H); 13C NMR δ 138.18, 137.89, 137.71, 128.36,
128.24, 128.07, 127.77, 127.59, 80.06, 79.71, 74.83, 74.30,
3,4,6-Tr i-O-ben zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-m eth yl-
en e-D-glycer o-L-m a n n o-h exitol (15). This was obtained in
71% yield from the LAH reduction of dichloro adduct 10 for 8
1
h: [R]25 ) +13.6 (c 1.15, CHCl3); H-NMR δ 7.35-7.28 (m,
D
15H), 4.88-4.52 (m, 6H), 3.81-3.52 (m, 6H), 1.28-1.10 (m,
1H), 0.80-0.68 (m 1H), 0.40-0.31 (m, 1H); 13C NMR δ 138.96,
138.71, 138.49, 128.65, 128.42, 128.34, 127.89, 127.58, 127.53,
77.17, 74.98, 73.70, 73.42, 73.35, 71.37, 69.35, 48.93, 14.47,
11.04. Anal. Calcd for C28H30O4: C, 78.11; H, 7.02. Found:
C, 78.20; H, 7.06.
3,4-Di-O-ben zyl-1,5-a n h yd r o-2,6-d id eoxy-1,2-C-m eth yl-
en e-L-glycer o -L-gu lo-h exitol (16). On carrying out the LAH
reduction on dichlorocyclopropane 7 as mentioned above for 4
h, 16 was obtained as a colorless syrup after chromatography
(67%): [R]25 ) -11 (c 1, CHCl3); 1H-NMR δ 7.36-7.15 (m,
D
10H), 4.82-4.74 (d, 2H), 4.55-4.48 (m, 2H), 3.69-3.59 (m, 2H),
3.57-3.49 (m, 1H), 3.36-3.17 (t, J ) 6.6 Hz, 1H), 1.29-1.26
(d, J ) 6.5 Hz, 3H), 1.05-0.92 (m, 1H), 0.76-0.65 (m, 2H);
13C NMR δ 138.74, 138.57, 128.42, 128.29, 127.96, 127.79,
127.68, 81.83, 79.93, 73.63, 71.99, 71.21, 49.34, 18.91, 14.33,
10.15. Anal. Calcd for C21H24O3: C, 77.75; H, 7.46. Found:
C, 77.56; H, 7.50.
73.06, 71.53, 70.0, 59.06, 35.0, 34.06. Anal. Calcd for C28H28
Br2O4: C, 57.16; H, 4.80. Found: C, 57.0; H, 4.73.
-
3,4,6-Tr i-O-b en zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-(d ib r o-
m om eth ylen e)-D-glycer o-L-m a n n o-h exitol (10). Reaction
of 3,4,6-tri-O-benzyl-D-galactal (2) under the same conditions
as 1 for 48 h gave 6 in 71% yield: pale yellow syrup; [R]25
)
D
1
+20 (c 1, CHCl3); H NMR δ 7.38-7.25 (m, 15H), 4.97-4.44
(m, 6H), 3.99-3.95 (d, J ) 8.8 Hz, 1H), 3.90-3.87 (m, 2H),
3.61-3.51 (m, 3H), 2.10-2.04 (dd, J ) 8.8, 4.0 Hz, 1H); 13C
NMR δ 138.62, 137.93, 137.63, 129.23, 128.61, 128.47, 128.35,
127.85, 127.69, 78.50, 77.70, 74.61, 73.52, 71.89, 71.13, 69.08,
59.13, 35.15, 32.16; HRMS calcd for C28H28Br2O4 (M - H)+
589.0415, found 589.0414.
3,4,6-Tr i-O-ben zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-m eth yl-
en e-D-glycer o-D-ta lo-h exitol (17). To a stirred suspension
of zinc dust (765 mg, 11.7 mmol) and cuprous chloride (250
mg, 2.5 mmol) in dry ether (1 mL) at room temperature was
added 1 equiv of diiodomethane. After 5 min, acetyl chloride
(20 µL) was added and the mixture was heated for 5 min at
40 °C. A solution of tribenzylglucal 1 (1.10 g, 2.65 mmol) in
ether (4 mL) was then added. Five minutes later, an ad-
ditional 2 equiv of diiodomethane was added and the heating
was continued for 90 min. The reaction mixture was diluted
with ether and washed with 5% sodium hydroxide solution,
brine, and dried. The residue, after solvent evaporation, was
purified by chromatography to furnish 17 as a low-melting
solid, 1.0 g (89%).
Under identical conditions, 3,4-di-O-benzyl-L-rhamnal (3)
gave 11 and 12 in 81% yield.
3,4-Di-O-b en zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-(d ib r om o-
m eth ylen e)-L-glycer o-L-gu lo-h exitol (11): 69%, syrup; [R]25
D
) -49 (c 1, CHCl3); 1H NMR δ 7.43-7.26 (m, 10H), 4.95-4.60
(m, 4H), 3.98-3.82 (m, 2H), 3.74-3.66 (dd, J ) 9.1, 4.3 Hz,
1H), 3.30 (dd, J ) 9.1, 7.3 Hz, 1H), 1.93-1.87 (dd, J ) 7.9, 4.2
Hz, 1H), 1.31-1.27 (d, J ) 6.4 Hz, 3H); 13C NMR δ 138.34,
137.86, 128.60, 128.43, 128.08, 127.97, 127.83, 81.13, 79.66,
76.66, 74.58, 72.02, 58.33, 35.11, 33.73, 20.06; HRMS calcd
for C21H22Br2O3 (M - H)+ 480.9838, found 480.9842.
3,4,6-Tr i-O-ben zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-m eth yl-
en e-D-glycer o-L-a llo-h exitol (18). The procedure described
for 17 was followed. 18 was obtained from 2 as a colorless
syrup (80%): [R]25 ) -73.3 (c 0.9, CHCl3); 1H NMR δ 7.31
D
3,4-Di-O-b en zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-(d ib r om o-
m eth ylen e)-L-glycer o-L-ta lo-h exitol (12): 12%, white solid;
mp ) 104-106 °C (MeOH); [R]25D ) +48 (c 1, CHCl3); 1H NMR
δ 7.36-7.26 (m, 10H), 4.96-4.85 (dd, J ) 9.8, 11.7 Hz, 2H),
4.73-4.59 (dd, J ) 11.7, 17.7 Hz, 2H), 4.20-4.12 (dd, J ) 8.2,
7.2, 1H), 4.02-3.99 (d, J ) 7.9 Hz, 1H), 3.62-3.52 (dd, J )
7.2, 9.9 Hz, 1H), 3.49 3.36 (m, 1H), 2.55-2.45 (t, J ) 8 Hz,
1H), 1.32-1.29 (d, J ) 6 Hz, 3H); 13C NMR δ 138.38, 137.95,
128.65, 128.42, 128.13, 128.01, 127.79, 81.43, 78.46, 74.95,
74.86, 71.03, 62.68, 33.92, 31.19, 17.61. Anal. Calcd for
C21H22Br2O3: C, 52.30; H, 4.60. Found: C, 52.30; H, 4.59.
3,4-Di-O-ben zyl-2-d eoxy-1,2-C-(d ibr om om eth ylen e)-D-
(m, 15H), 4.99-4.41 (m, 6H), 4.07-4.01 (t, J ) 5.5 Hz, 1H),
3.90-3.82 (m, 2H), 3.51-3.45 (m, 3H), 1.60-1.40 (m, 1H),
1.30-1.20 (m, 1H), 0.80-0.60 (m, 1H); 13C NMR δ 138.83,
138.66, 137.91, 128.25, 127.99, 127.93, 127.77, 127.55, 127.28,
76.01, 74.59, 74.24, 73.76, 73.31, 69.54, 69.26, 53.90, 14.13,
12.09. Anal. Calcd for C28H30O4: C, 78.11; H, 7.02. Found:
C, 77.97; H, 7.10.
3,4-Di-O-ben zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-m eth ylen e-
L-glycer o-L-ta lo-h exitol (19). Using the procedure described
for 17, 19 was obtained from 3 as a colorless syrup (87%):
1
[R]25 ) +89 (c 1.1, CHCl3); H NMR δ 7.32-7.18 (m, 10H),
D
4.89-4.81 (dd, J ) 11.6, 5.5 Hz, 2H), 4.65-4.57 (dd, J ) 11.2,
3.3 Hz, 2H), 4.17-4.11 (t, J ) 6.9 Hz, 1H), 3.82-3.73 (m, 1H),
3.45-3.30 (m, 1H), 3.08-2.98 (dd, J ) 9.7, 7.0 Hz, 1H), 1.40-
1.27 (m, 1H), 1.23-1.20 (d, J ) 6.6 Hz, 3H), 0.80-0.75 (m,
2H); 13C NMR δ 138.41, 127.95, 127.86, 127.41, 127.11, 83.06,
78.24, 73.82, 73.63, 69.26, 54.42, 17.51, 15.30, 11.61. Anal.
Calcd for C21H24O3: C, 77.75; H, 7.46. Found: C, 77.79; H,
7.48.
gu lo-p en titol (13): 64%, pale yellow syrup; [R]25 ) +13.7
D
1
(c 0.7, CHCl3); H NMR δ 7.42-7.26 (m, 10H), 4.90-4.60 (m,
4H), 4.0-3.70 (m, 5H), 1.92-1.86 (dd, J ) 7.8, 3.8 Hz, 1H);
13C NMR δ 138.24, 137.72, 128.58, 128.46, 128.22, 128.04,
127.78, 78.71, 75.40, 72.91, 71.97, 69.47, 60.37, 34.06, 32.81;
mass spectral data m/ z 467 (M - 1), 377, 325, 263, 182, 101,
91.
3,4,6-Tr i-O-ben zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-m eth yl-
en e-D-glycer o-D-gu lo-h exitol (14). To a stirred suspension
of lithium aluminum hydride (277 mg, 7.29 mmol) in dry
tetrahydrofuran (4 mL) was added a solution of the dichloro-
cyclopropane 5 (400 mg, 0.80 mmol) in tetrahydrofuran (10
mL). After being stirred for 2 h at room temperature, the
reaction mixture was cooled in ice and quenched by careful
addition of saturated aqueous sodium sulfate. The salts were
filtered and washed several times with hot ethyl acetate. The
Solvolysis Exp er im en ts w ith Dibr om ocyclop r op a n es
9, 10, a n d 11 u n d er Ba sic Con d ition s. The reaction
mixture containing the dibromocyclopropane (1 equiv) and
anhydrous potassium carbonate (6 equiv) in methanol (10 mL/
mmol of substrate) was refluxed for 12 h under a nitrogen
atmosphere. The reaction mixture was cooled to room tem-
perature, diluted with water, and extracted with dichlo-
romethane. The combined organic extracts were dried and
concentrated under reduced pressure, and the products were

Synthesis and Reactions of 1,2-Cyclopropanated Sugars
J . Org. Chem., Vol. 62, No. 22, 1997 7701
separated by chromatography. The dibromocyclopropane 9
Meth yl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-(br om om eth yl)-
gave the following products:
r-D-glu cop yr a n osid e (24): colorless syrup, [R]25 ) +87.3
D
(c 1, CHCl3); 1H NMR δ 7.36-7.16 (m, 15H), 5.0-4.99 (d, J )
2.6 Hz, 1H), 4.92-4.53 (m, 6H), 3.85-3.57 (m, 6H), 3.40 (s,
3H), 3.35-3.25 (t, 1H), 2.17-2.34 (m, 1H); 13C NMR δ 138.22,
138.09, 128.52, 128.40, 127.86, 127.72, 99.23, 80.35, 79.48,
75.27, 74.79, 73.61, 70.96, 68.79, 55.26, 48.51, 30.60. Anal.
Calcd for C29H33O5Br: C, 64.32; H, 6.14. Found: C, 64.30; H,
6.35.
Ma jor p r od u ct of 20: yield 38.4%; [R]25 ) +69 (c 2,
D
CHCl3); 1H NMR δ 7.34-7.14 (m, 15H, ArH), 6.79 (s, 1H, H-3),
5.17 (s, 1H, H-1), 4.73 (s, 1H, H-4), 4.66-4.25 (m, 6H,
OCH2Ph), 3.72-3.59 (m, 4H, H-5, H-6, H-7, H-7'), 3.45 (s, 3H,
OCH3); 13C NMR δ 138.44, 138.20, 137.78, 137.64 (C-2), 128.37,
128.06, 127.91, 127.73, 127.53, 112.56 (C-3), 98.98 (C-1), 79.42
(C-5), 76.30 (C-4), 73.21 (OCH2Ph), 71.60 (OCH2Ph, C-6), 70.86
(OCH2Ph), 69.73 (C-7) 55.19 (OCH3). Anal. Calcd for C29H31
BrO5: C, 64.56; H, 5.79. Found: C, 64.75; H, 5.84.
-
Meth yl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-(br om om eth yl)-
â-D-glu cop yr a n osid e (25): colorless syrup, [R]25 ) +22 (c
D
1
Min or p r od u ct of 20: yield 29.3%; [R]25 ) +26.7 (c 1,
1, CHCl3); H NMR δ 7.34-7.19 (m, 15H), 5.0-4.58 (m, 6H),
D
CHCl3); 1H NMR δ 7.34-7.27 (m, 15H, ArH), 6.80 (s, 1H, H-3),
5.09 (s, 1H, H-1), 4.80-4.50 (m, 7H, OCH2Ph, H-4), 4.0-3.85
(m, 4H, H-5, H-6, H-7, H-7'), 3.52 (s, 3H, OCH3); 13C NMR δ
138.46, 138.37, 137.87, 137.10 (C-2), 128.48, 128.41, 128.32,
128.0, 127.79, 127.63, 114.70 (C-3), 101.20 (C-1), 76.11 (C-5),
74.97 (C-6), 74.73 (C-4), 73.35, 72.25, 70.95, 70.65 (C-7), 55.80
(OCH3). Anal. Calcd for C29H31BrO5: C, 64.56; H, 5.79.
Found: C, 64.45; H, 5.75.
Solvolysis of the dibromocyclopropane 10 gave an insepa-
rable mixture of products 21 in 55% yield: 1H NMR δ 7.41-
7.32 (m, 15H), 6.67 (s, 1H, H-3), 4.86 (s, 1H, H-1), 4.90-4.70
(m, 8H), 3.79-3.70 (m, 3H), 3.49 (s, 3H, OCH3), 3.46 (s, 3H,
OCH3); 13C NMR δ 138.69, 138.35, 138.27, 138.19, 137.96,
137.16, 137.03, 128.32, 128.17, 128.06, 127.77, 127.63, 127.31,
112.65, 107.53, 101.52, 100.26, 75.95, 74.67, 73.47, 73.39,
73.28, 72.66, 72.23, 71.39, 70.76, 70.69, 68.46, 55.70, 55.56.
Anal. Calcd for C29H31BrO5: C, 64.56; H, 5.79. Found: C,
64.52; H, 5.78.
Solvolysis of the dibromocyclopropane 11 gave the corre-
sponding products 22: 60% yield; 1H NMR δ 7.43-7.30 (m,
10H, ArH), 6.81 (s, 1H, H-3), 5.06 (s, 1H, H-1), 4.80-4.50 (m,
4H, OCH2Ph), 3.80-3.52 (m, 3H), 3.50 (s, 3H, OCH3), 1.43 (d,
J ) 6.3 Hz, 3H, H-7); 13C NMR δ 138.46, 137.88, 137.68,
128.77, 128.40, 128.25, 127.92, 127.79, 127.54, 127.18, 114.02,
101.49, 81.66, 76.04, 72.43, 71.33, 70.97, 55.57, 19.35. Anal.
Calcd for C22H25BrO4: C, 60.97; H, 5.81. Found: C, 61.05; H,
5.82.
4.45-4.40 (d, J ) 8.5 Hz, 1H), 3.87-3.46 (m, 10H), 2.20-1.81
(m, 1H); 13C NMR δ 138.44, 138.30, 138.11, 128.52, 128.42,
127.86, 102.29, 80.01, 79.85, 75.58, 75.14, 74.84, 73.62, 69.04,
57.25, 47.70, 31.60. Anal. Calcd for C29H33O5Br: C, 64.32;
H, 6.14. Found: C, 64.25; H, 6.18.
Meth yl 3,4,6-Tr i-O-ben zyl-2-d eoxy-2-C-(br om om eth yl)-
r-D-m a n n op yr a n osid e (26). Stirring cyclopropane 17 (215
mg, 0.5 mmol) with NBS (108 mg, 0.6 mmol) in MeOH (5 mL)
for 24 h and purification yielded the ring-opened product 26
(170 mg, 62%) as a colorless syrup: [R]25D ) +36 (c 0.8, CHCl3);
1H NMR δ 7.39-7.22 (m, 15H), 5.03 (s, 1H), 4.83-4.40 (m,
6H), 4.07-4.0 (dd, J ) 9.4 Hz, 1H), 3.85-3.40 (m, 6H), 3.38
(s, 3H), 2.69-2.58 (m, 1H); 13C NMR δ 138.34, 138.26, 138.15,
128.51, 128.39, 127.91, 127.79, 99.71, 79.57, 74.88, 74.33,
73.53, 71.92, 71.11, 68.99, 55.03, 46.24, 29.57. Anal. Calcd
for C29H33O5Br: C, 64.32; H, 6.14. Found: C, 64.25; H, 6.0.
Rin g Op en in g of Cyclop r op a n e 14 w ith NIS/MeOH. As
mentioned above for NBS, after cyclopropane 14 was stirred
for 12 h with NIS (1.2 equiv) in MeOH and purification of the
reaction mixture, the anomers 27and 28 were obtained in a
20:80 ratio (86%).
Rin g Op en in g of Cyclop r op a n e 14 w ith BCIP /MeOH.
To a stirred solution of cyclopropane 14 (207 mg, 0.48 mmol)
in methanol (5 mL) was added BCIP (325 mg, 0.69 mmol).
After 6 h, the reaction mixture was concentrated in vacuo and
the crude product was dissolved in 15 mL of dichloromethane,
washed with 15 mL of saturated sodium bisulfite and 15 mL
of brine, and purified by column chromatography. The ano-
mers 27 and 28 were obtained in a 15:85 ratio (245 mg, 86%).
Meth yl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-(iod om eth yl)-r-
Meth yl 3,4,6-Tr i-O-ben zyl-2-d eoxy-2-C-m eth yl-â-D-glu -
cop yr a n osid e (23). A solution of cyclopropane 14 (165 mg,
0.38 mmol) and acetyl chloride (0.38 mL) in methanol (5 mL)
was heated at 80 °C for 15 days. The reaction mixture was
diluted with dichloromethane, treated with solid sodium
bicarbonate, and concentrated. On purification by column
chromatography unreacted 14 eluted first (98 mg) followed by
23 (49 mg, 70% with respect the recovered cyclopropane) which
was obtained as a colorless solid: mp ) 104 -105 °C (ether/
D-glu cop yr a n osid e (27): colorless syrup, [R]25 ) +69.2 (c
D
0.4, CHCl3); 1H NMR δ 7.36-7.15 (m, 15H), 4.96-4.94 (d, J )
3.0 Hz, 1H), 4.93-4.51 (m, 6H), 3.82-2.97 (m, 10H), 2.24-
2.08 (m, 1H); 13C NMR δ 138.40, 128.57, 128.47, 127.89, 127.77,
101.07, 81.29, 79.16, 75.45, 74.84, 73.66, 71.09, 68.79, 55.38,
48.46, 3.05. Anal. Calcd for C29H33O5I: C, 59.19; H, 5.65.
Found: C, 59.22; H, 5.68.
hexane); [R]25 ) +4.5 (c 0.2, CHCl3); 1H NMR δ 7.35-7.26
D
(m, 15H), 5.0-4.50 (m, 6H), 4.04-3.99 (d, J ) 8.0 Hz, 1H),
3.80-3.40 (m, 7H), 3.27-3.24 (t, 1H), 1.85-1.75 (m, 1H); 1.06-
1.03 (d, J ) 6.4 Hz, 3H); 13C NMR δ 138.42, 128.49, 128.20,
127.96, 127.87, 127.71, 105.68, 85.37, 79.55, 75.32, 75.23,
74.83, 73.62, 70.75, 56.85, 42.79, 12.62. Anal. Calcd for
C29H34O5: C, 75.29; H, 7.41. Found: C, 75.31; H, 7.45.
Gen er a l P r oced u r e for NBS-Activa ted Rin g-Op en in g
Rea ction s of Cyclop r op a n e 14 a n d Cyclop r op a n e 17
w ith Differ en t Solven ts. To a stirred solution of the
cyclopropane (215 mg, 0.5 mmol) in 5 mL of solvent at 0 °C,
under nitrogen, was added 107 mg (0.6 mmol) of NBS, and
the stirring was continued until the reaction mixture showed
the absence of starting material on TLC. Except with benzyl
alcohol, where the reaction mixture was concentrated by
distilling out the benzyl alcohol under reduced pressure, in
general, the reaction mixture was coevaporated with toluene
in vacuo. An aqueous workup in all the above reactions was
found to be less efficient. Chromatographic purifications were
carried out using 5% ethyl acetate in hexane. Yields are based
on the amount of pure material obtained. The anomeric ratios
were calculated by 1H NMR (for crude reaction mixture) as
well as using chromatographically separated products.
Rin g Op en in g of Cyclop r op a n e 14 w ith NBS/MeOH.
As described above, stirring cyclopropane 14 (290 mg, 0.67
mmol) with NBS (145 mg, 0.81 mmol) in MeOH (6 mL) for 8
h and purification of the reaction mixture gave the anomers
24 and 25 in a 20:80 ratio (263 mg, 72%).
Meth yl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-(iod om eth yl)-â-
D-glu cop yr a n osid e (28): low-melting solid, [R]25 ) +53.2
D
1
(c 0.5, CHCl3); H NMR δ 7.36-7.19 (m, 15H), 4.97-4.58 (m,
6H), 4.32-4.27 (d, J ) 8.6 Hz, 1H), 3.78-3.49 (m, 10H), 1.35-
1.21 (m, 1H); 13C NMR δ 138.45, 138.24, 138.08, 129.79, 128.59,
128.54, 128.44, 127.89, 127.70, 104.39, 81.65, 79.75, 75.63,
75.13, 74.80, 73.61, 68.96, 57.34, 46.32, 6.97. Anal. Calcd for
C29H33O5I: C, 59.19; H, 5.65. Found: C, 59.45; H, 5.72.
Meth yl 3,4,6-Tr i-O-ben zyl-2-d eoxy-2-C-(iod om eth yl)-r-
D-m a n n op yr a n osid e (29). As described above, after cyclo-
propane 17 (310 mg, 072 mmol) was stirred for 36 h with BCIP
(405 mg, 0.87 mmol) in MeOH (6 mL), followed by the usual
workup and chromatographic purification of the reaction
mixture, 134 mg (70%, based on recovered 17) of the corre-
sponding ring-opened product 29 was obtained as a colorless
syrup: [R]25 ) +32.3 (c 0.3, CHCl3); 1H NMR δ 7.35-7.14
D
(m, 15H), 4.96 (s, 1H), 4.85-4.43 (m, 6H), 3.98-3.91 (m, 1H),
3.81-3.65 (m, 5H), 3.42 (s, 3H), 3.22-3.11 (t, 1H), 2.69-2.58
(m, 1H); 13C-NMR δ 138.41, 138.30, 138.21, 128.51, 128.38,
127.90, 127.76, 127.66, 100.92, 80.16, 74.81, 74.11, 73.53,
71.90, 71.38, 69.07, 55.0, 46.77, 2.0. Anal. Calcd for C29H33
-
O5
I: C, 59.19; H, 5.65. Found: C, 59.29; H, 5.70.
On further elution, unreacted 17 was obtained (173 mg).
Rin g Op en in g of Cyclop r op a n e 14 w ith NBS/ClCH2-
CH2OH. After cyclopropane 14 (110 mg, 0.25 mmol) was
stirred with NBS (50 mg, 0.28 mmol) in 2-chloroethanol (3 mL)
for 4 h, TLC showed clearly the disappearance of starting

7702 J . Org. Chem., Vol. 62, No. 22, 1997
Ramana et al.
compound and the formation of two close spots, which were
separated and identified as 30 and 31 (35:65 ratio, 137 mg,
91% yield).
was purified. Products 36 and 37 were obtained in a 35:65 ratio
(383 mg, 91% yield).
Ben zyl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-(br om om eth yl)-
r-D-glu cop yr a n osid e (36): colorless syrup, [R]25 ) +85.5
2′-Ch lor oeth yl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-(br om o-
D
1
m eth yl)-r-D-glu cop yr a n osid e (30): colorless syrup, [R]25
(c 1, CHCl3); H NMR δ 7.38-7.14 (m, 20H), 5.25-5.23 (d, J
D
) +78.9 (c 0.9, CHCl3); 1H NMR δ 7.34-7.12 (m, 15H), 5.16-
5.14 (d, J ) 3.4 Hz, 1H), 4.94-4.49 (m, 6H), 3.93-3.60 (m,
10H), 3.41-3.30 (t, 1H), 2.36-2.19 (m, 1H); 13C NMR δ 138.0,
128.56, 128.45, 127.94, 127.82, 98.48, 80.22, 79.29, 75.40,
74.91, 73.59, 71.38, 68.57, 68.33, 48.44, 42.83, 30.53. Anal.
Calcd for C30H34O5BrCl: C, 61.08; H, 5.83. Found: C, 61.0;
H, 5.85.
) 3.2 Hz, 1H), 4.92-4.49 (m, 8H), 3.83-3.64 (m, 6H), 3.42-
3.32 (t, 1H), 2.38-2.22 (m, 1H); 13C-NMR δ 138.23, 137.66,
128.61, 128.52, 127.90, 98.03, 80.57, 79.63, 75.41, 74.99, 73.71,
71.48, 70.06, 68.85, 48.73, 30.66. Anal. Calcd for C35H37
O5Br: C, 68.07; H, 6.04. Found: C, 68.10; H, 6.10.
-
Ben zyl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-(br om om eth yl)-
â-D-glu cop yr a n osid e (37): colorless solid, mp ) 91-93 °C
1
(ether/hexane); [R]25 ) -7.5 (c 1, CHCl3); H NMR δ 7.38-
D
2′-Ch lor oeth yl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-(br om o-
m eth yl)-â-D-glu cop yr a n osid e (31): low-melting solid, [R]25
7.12 (m, 20H), 4.99-4.59 (m, 9H), 3.92-3.69 (m, 6H), 3.54-
3.45 (m, 1H), 2.02-1.89 (m, 1H); 13C NMR δ 138.48, 138.38,
138.24, 128.49, 128.35, 127.88, 100.47, 80.09, 79.87, 75.57,
75.23, 74.85, 73.64, 71.44, 69.07, 47.73, 31.61. Anal. Calcd
for C35H37O5Br: C, 68.07; H, 6.04. Found: C, 67.98; H, 6.11.
Rin g Open in g of Cyclopr opan e 17 with NBS/P h CH2OH.
The reaction was incomplete even after 4 days. Distillation
followed by purification afforded 38 in 40% yield (with respect
to the cyclopropane recovered) as colorless syrup.
D
) +22.5 (c 0.8, CHCl3); 1H NMR δ 7.34-7.18 (m, 15H), 4.94-
4.53 (m, 7H), 4.21-4.07 (m, 1H), 3.86-3.66 (m, 9H), 3.51-
3.41 (m, 1H), 1.97-1.84 (m, 1H); 13C NMR δ 138.34, 138.14,
138.04, 128.49, 128.43, 127.84, 101.35, 79.86, 79.59, 75.54,
75.10, 74.83, 73.56, 69.84, 68.89, 47.54, 42.62, 31.49. Anal.
Calcd for C30H34O5BrCl: C, 61.08; H, 5.83. Found: C, 61.22;
H, 5.82.
Rin g Op en in g of Cyclop r op a n e 17 w ith NBS/ClCH2-
CH2OH. The reaction took 12 h for completion and yielded
the corresponding ring-opened product 32 in 71% yield (as a
colorless syrup).
Ben zyl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-(br om om eth yl)-
r-D-m a n n o p yr a n osid e (38): [R]25 ) +59.8 (c 0.5, CHCl3);
D
1H NMR δ 7.35-7.18 (m, 20H), 5.21 (s, 1H), 4.82-4.41 (m,
8H), 4.14-4.07 (dd, J ) 5.4, 9.2 Hz, 1H), 3.86-3.58 (m, 5H),
3.49-3.33 (t, 1H), 2.77-2.64 (m, 1H); 13C NMR δ 138.27,
137.52, 128.38, 127.94, 127.75, 126.98, 98.33, 79.50, 74.86,
74.43, 73.52, 71.99, 71.51, 69.55, 68.97, 46.39, 29.55. Anal.
Calcd for C35H37O5Br: C, 68.07; H, 6.04. Found: C, 67.96; H,
6.08.
2′-Ch lor oeth yl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-(br om o-
m eth yl)-r-D-m a n n op yr a n osid e (32): [R]25 ) +38.4 (c 0.9,
D
CHCl3); 1H NMR δ 7.36-7.17 (m, 15H), 5.13 (s, 1H), 4.82-
4.41 (m, 6H), 4.11-4.04 (dd, J ) 5.2, 9.3 Hz, 1H), 3.95-3.50
(m, 9H), 3.48-3.38 (t, J ) 11 Hz, 1H), 2.71-2.65 (m, 1H); 13
C
NMR δ 138.09, 128.25, 127.80, 127.59, 98.89, 79.09, 74.61,
74.09, 73.33, 71.83, 71.45, 68.80, 67.92, 46.06, 42.62, 29.40.
Anal. Calcd for C30H34O5BrCl: C, 61.08; H, 5.83. Found: C,
61.25; H, 5.91.
Rin g Op en in g of Cyclop r op a n e 14 w ith NBS/H 2O. To
a solution of cyclopropane 14 (250 mg, 0.58 mmol) in dioxane/
water (6 mL, 2:1) was added NBS (125 mg, 0.70 mmol), and
the stirring was continued for 8 h. The reaction mixture was
then concentrated to half its volume in vacuo and extracted
with dichloromethane. The combined extracts were dried and
concentrated. Purification by chromatography and recrystal-
lization from ether/hexane yielded 39 (198 mg, 66% yield) as
a colorless solid.
R in g Op en in g of Cyclop r op a n e 14 w it h NBS/Cl3C-
CH2OH. The ring opening of 14 (85 mg, 0.197 mmol) with
NBS (44 mg) in 2,2,2-trichloroethanol was complete within 1
h and yielded both R- and â-anomers in equal amounts (116
mg, 89% yield).
2′,2′,2′-Tr ich lor oeth yl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-
3,4,6-Tr i-O-b en zyl-2-d eoxy-2-C-(b r om om et h yl)-D-glu -
(br om om eth yl)-r-D-glu cop yr a n osid e (33): colorless syrup,
cop yr a n ose (39): mp ) 110-112 °C; [R]25 ) +61.2 (c 1,
D
1
[R]25 ) +70 (c 0.5, CHCl3); H NMR δ 7.38-7.21 (m, 15H),
D
CHCl3); 1H NMR δ 7.34-7.18 (m, 15H), 5.54-5.51 (bs) and
4.92-4.56 (m, together 7H), 4.14-3.26 (m, 8H), 2.33-2.17 and
1.89-1.72 (2m’s, together 1H); 13C NMR δ 138.07, 137.92,
128.49, 128.08, 127.93, 95.46, 92.43, 79.83, 79.67, 75.54, 75.39,
74.91, 74.73, 73.59, 70.91, 68.98, 48.71, 48.62, 30.92. Anal.
Calcd for C28H31O5Br: C, 63.75; H, 5.93. Found: C, 64.09; H,
6.07.
5.35-5.34 (d, J ) 2.9 Hz, 1H), 4.96-4.51 (m, 6H), 4.29-4.07
(m, 2H), 3.86-3.66 (m, 6H), 3.47-3.35 (t, 1H), 2.42-2.24 (m,
1H); 13C NMR δ 137.92, 128.49, 127.91, 98.83, 96.01, 79.91,
79.57, 79.16, 75.49, 75.07, 73.65, 72.42, 68.02, 48.72, 29.94.
Anal. Calcd for C30H32O5BrCl3: C, 54.69; H, 4.89. Found: C,
54.75; H, 4.91.
2′,2′,2′-Tr ich lor oeth yl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-
Rin g Op en in g of Cyclop r op a n e 17 w ith NBS/H2O.
When the reaction was carreid out under conditions similar
to those described above, cyclopropane 17 (294 mg, 0.68 mmol)
provided the corresponding ring-opened product 40 (210 mg,
61%) as a colorless solid.
(br om om eth yl)-â-D-glu cop yr a n osid e (34): colorless syrup,
1
[R]25 ) +24 (c 0.2, CHCl3); H NMR δ 7.38-7.21 (m, 15H),
D
5.01-4.54 (m, 6H), 4.52-4.46 (d, J ) 12.6 Hz, 1H), 4.20-4.11
(d, J ) 11.7, 1H), 3.97-3.45 (m, 8H), 2.10-1.97 (m, 1H); 13C
NMR δ 138.35, 137.99, 128.50, 127.85, 101.40, 96.03, 80.73,
79.78, 79.41, 75.54, 75.26, 74.86, 73.61, 68.74, 48.57, 31.15.
Anal. Calcd for C30H32O5BrCl3: C, 54.69; H, 4.89. Found: C,
54.65; H, 4.91.
3,4,6-Tr i-O-ben zyl-2-d eoxy-2-C-(br om om eth yl)-D-m a n -
n op yr a n ose (40): mp ) 90-91 °C (ether/hexane); [R]25
)
D
+23.9 (c 1, CHCl3); 1H NMR δ 7.34-7.14 (m, 15H), 5.5 (s, 1H),
4.82-4.41 (m, 6H), 4.16-4.02 (m, 2H), 3.84-3.35 (m, 5H), 3.12
(b, 1H), 2.69-2.57 (m, 1H); 13C-NMR δ 138.27, 138.16, 137.95,
128.53, 128.49, 128.01, 127.80, 93.16, 78.98, 74.72, 74.63,
73.45, 71.98, 71.03, 69.35, 46.39, 29.74. Anal. Calcd for
C28H31O5Br: C, 63.75; H, 5.93. Found: C, 63.84; H, 6.09.
3,4-Di-O-ben zyl-6-O-(tr ip h en ylca r bin yl)-1,5-a n h yd r o-
2-d eoxy-1,2-C-(d ich lor om eth ylen e)-D-glycer o-D-gu lo-h ex-
itol (42). Aqueous sodium hydroxide (4.0 g in 8 mL) was
added to a vigorously stirred solution of the glucal 41 (1.88 g,
3.31 mmol) in chloroform (8 mL) containing benzyltriethylam-
monium chloride (20 mg). The reaction mixture was stirred
at rt for 36 h and then diluted with water (25 mL) and
extracted with dichloromethane. The combined extracts were
dried and concentrated, and the residue was purified by
R in g Op en in g of Cyclop r op a n e 17 w it h NBS/Cl3C-
CH2OH. The ring opening of 17 (375 mg, 0.87 mmol) with
NBS (186 mg, 1.05 mmol) in 2,2,2-trichloroethanol took 8 h
for completion and yielded the corresponding ring-opened
product 35 (350 mg, 89% yield) as a pale yellow syrup.
2′,2′,2′-Tr ich lor oeth yl 3,4,6-tr i-O-ben zyl-2-d eoxy-2-C-
(br om om eth yl)-r-D-m a n n op yr a n osid e (35): [R]25D ) +51.3
(c 1, CHCl3); 1H NMR δ 7.35-7.13 (m, 15H), 5.33 (s, 1H), 4.81-
4.41 (m, 6H), 4.26-4.08 (m, 3H), 3.86-3.61 (m, 5H), 3.48-
3.37 (t, 1H), 2.79-2.68 (m, 1H); 13C NMR δ 138.27, 138.0,
128.57, 128.47, 127.97, 127.79, 100.03, 96.64, 79.44, 78.79,
74.75, 74.14, 73.60, 72.50, 72.27, 68.97,46.09, 29.21. Anal.
Calcd for C30H32O5BrCl3: C, 54.69; H, 4.89. Found: C, 54.32;
H, 4.88.
chromatography to furnish 42 (1.58 g, 73%) as a colorless
1
Rin g Open in g of Cyclopr opan e 14 with NBS/P h CH2OH.
Cyclopropane 14 (295 mg, 0.69 mmol) was treated with benzyl
alcohol and NBS (193 mg, mmol). After 36 h benzyl alcohol
was distilled from the reaction mixture and the crude product
syrup: [R]25 ) +42.3 (c 1, CHCl3); H NMR δ 7.50-7.0 (m,
D
25H), 4.84-4.68 (m, 4H), 4.29-4.24 (d, J ) 10.7 Hz, 1H), 4.08-
4.05 (d, J ) 7.8 Hz, 1H), 3.90 (m, 3H) 3.52-3.47 (d, J ) 10
Hz, 1H), 1.93 (dd, J ) 4.1, 7.8 Hz, 1H); 13C NMR δ 143.90,

Synthesis and Reactions of 1,2-Cyclopropanated Sugars
J . Org. Chem., Vol. 62, No. 22, 1997 7703
1
138.28, 137.81, 128.85, 128.61, 128.30, 128.01, 127.67, 127.25,
86.99, 80.54, 77.61, 76.09, 74.79, 72.18, 63.95, 61.82, 59.26,
34.77. Anal. Calcd for C40H36Cl2O4: C, 73.73; H, 5.57.
Found: C, 73.65; H, 5.55.
70%): [R]25 ) -70.1 (c 1, CHCl3); H-NMR δ 7.39-7.21 (m,
D
10H), 4.89-4.58 (m, 4H), 4.24-4.16 (m, 1H), 3.85-3.74 (m,
2H), 3.69-3.54 (m, 1H), 3.38-3.32 (m, 2H), 1.98 (b, 1H), 1.50-
1.25 (m, 1H), 0.88-0.73 (m, 2H); 13C NMR δ 138.54, 138.42,
128.43, 128.03, 127.87, 127.74, 127.57, 78.74, 78.55, 77.92,
74.21,70.0, 62.52, 55.10, 15.69, 11.98. Anal. Calcd for
21H24O4: C, 74.09; H, 7.11. Found: C, 73.98; H, 7.09.
3,4-Di-O-ben zyl-2-d eoxy-2-C-(br om om eth yl)-1,6-a n h y-
3,4-Di-O-b en zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-(d ich lor o-
m eth ylen e)-D-glycer o-D-gu lo-h exitol (43).23c To a solution
of 42 (1.41 g, 2.164 mmol) in ether (6 mL) was added 5 mL of
formic acid, and the solution was stirred at rt for 1 h. The
reaction mixture was concentrated in vacuo and the residue
diluted with dichloromethane. The dichloromethane layer was
washed with saturated bicarbonate solution and brine, dried,
and concentrated. Purification of the crude product by column
chromatography using initially 5% ethyl acetate in hexane to
elute triphenylcarbinol and then with 25% ethyl acetate
C
d r o-â-D-glu cop yr a n ose (46). To a solution of the substrate
44 (70 mg, 0.21 mmol) in acetonitrile (5 mL) was added 140
mg of 4 Å molecular sieves, and the contents were stirred for
30 min. To this NBS (44 mg, 0.25 mmol) was added, and the
stirring was continued for 5 h. The reaction mixture was
diluted with toluene, filtered, and concentrated in vacuo, and
the crude product was purified chromatographically without
any aqueous workup to yield the levoglucosan derivative 46
yielded the detritylated product (43) as a colorless solid (650
1
mg, 74%): mp ) 83-84 °C; [R]25 ) +74.2 (c 1.5, CHCl3); H
D
(61 mg, 70%) as a colorless syrup: [R]25 ) -70.8 (c 0.75,
NMR δ 7.42-7.31 (m, 10H), 5.00-4.66 (m, 4H), 3.91- 3.87 (d,
J ) 8.7 Hz, 1H), 3.85-3.80 (dd, J ) 9.8, 3.9 Hz, 1H), 3.78-
3.60 (m, 4H), 1.98 (bs, 1H), 1.89-1.80 (dd, J ) 3.9, 8.7 Hz,
1H); 13C NMR δ 138.11, 137.58, 128.59, 128.17, 128.06, 79.77,
77.14, 74.97, 74.79, 72.11, 62.76, 61.04, 58.81, 33.90. Anal.
Calcd for C21H22Cl2O4: C, 61.62; H, 5.42. Found: C, 61.68;
H, 5.42.
D
CHCl3); 1H-NMR δ 7.38-7.26 (m, 10H), 5.58 (s, 1H), 4.64-
4.51 (m, 5H), 4.17-4.14 (d, J ) 6.9 Hz, 1H), 3.77-3.68 (m,
2H), 3.54-3.40 (m, 3H), 2.31-2.23 (t, 1H); 13C NMR δ 137.99,
137.67, 128.56, 128.49, 127.97, 127.78, 101.55, 76.46, 74.80,
74.56, 71.49, 71.32, 64.92, 45.56, 31.70. Anal. Calcd for
C
21H23BrO4: C, 60.15; H, 5.53. Found: C, 60.07; H, 5.61.
3,4-Di-O-ben zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-m eth ylen e-
D-glycer o-D-gu lo-h exitol (44). To a stirred suspension of
lithium aluminum hydride (455 mg, 12 mmol) in dry tetrahy-
drofuran (4 mL) was added a solution of the dichlorocyclopro-
pane 43 (330 mg, 0.80 mmol) in tetrahydrofuran (10 mL). After
24 h of stirring at rt, the reaction mixture was cooled in ice
and quenched with a saturated aqueous sodium sulfate. The
3,4-Di-O-ben zyl-2-d eoxy-2-C-(br om om eth yl)-1,6-a n h y-
d r o-â-D-m a n n op yr a n ose (47). To a solution of 45 (110 mg,
0.32 mmol) in acetonitrile (7 mL) was added 220 mg of 4 Å
molecular sieves, and it was stirred for 30 min. NBS (70 mg,
0.39 mmol) was added and the stirring continued. The
reaction was found to be incomplete even after 36 h. It was
diluted with toluene and filtered. It was then concentrated
in vacuo, and the crude product was purified as described
above to yield the levomannosan derivative 47 (47 mg, 35%)
usual workup and purification yielded 44 (228 mg, 84%) as a
1
colorless low-melting solid: [R]25 ) +24.5 (c 0.9, CHCl3); H
D
NMR δ 7.35-7.29 (m, 10H), 4.89-4.62 (m, 4H), 3.87- 3.40 (m,
6H), 2.11 (b, 1H), 1.08-0.93 (m, 1H), 0.81-0.69 (m, 2H); 13C
NMR δ 138.49, 138.35, 128.51, 128.0, 127.79, 126.98, 79.61,
76.91, 76.53, 73.61, 71.25, 62.58, 49.98, 14.43, 10.29; HRMS
calcd for (M - Bn)+ C14H17O4 249.1127, found 249.1128.
3,4-Di-O-ben zyl-1,5-a n h yd r o-2-d eoxy-1,2-C-m eth ylen e-
D-glycer o-D-ta lo-h exitol (45). To a stirred suspension of zinc
dust (330 mg, 5.03 mmol) and cuprous chloride (108 mg, 1.08
mmol) in dry ether (1 mL) was added diiodomethane (327 mg,
1.12 mmol). After 5 min, acetyl chloride (20 µL) was added
and the mixture was heated for 5 min at 40 °C. A solution of
glucal 41 (670 mg, 1.12 mmol) in ether (3 mL) was then added.
Five minutes after the addition of the glucal, an additional
amount (2 equiv) of diiodomethane was added and the heating
was continued for 2 h. Usual workup and purification by
chromatography furnished 45 as a pale yellow syrup (282 mg,
as a colorless syrup: [R]25 ) -12.4 (c 0.5, CHCl3); 1H NMR δ
D
7.38-7.25 (m, 10H), 5.50 (s, 1H), 4.64 (s, 2H), 4.59-4.57 (m,
1H), 4.46-4.45 (d, J ) 1.65 Hz, 2H), 4.14-4.11 (d, J ) 6.9
Hz, 1H), 3.77-3.66 (m, 2H), 3.52-3.44 (m, 3H), 2.43-3.32 (m,
1H); 13C NMR δ 137.69, 128.63, 128.51, 128.10, 127.87, 101.12,
75.0, 73.91, 73.74, 73.17, 71.35, 64.74, 44.41, 30.38; calcd for
(M - Br)+ C21H23O4 339.1596, found 339.1615.
Ack n ow led gm en t. C.V.R. and R.M. thank UGC
(New Delhi), CSIR (New Delhi), and DST (New Delhi)
for financial support. We acknowledge the COSIST
programme in Organic Chemistry for instrumental
facilities.
J O970948K