Stereoselective Preparation of Enantiomerically Pure Annulated Carbohydrates Using Ring-Closing Metathesis

Article abstract of DOI:10.1021/jo991392z

Ring-closing metathesis has been applied to a series of glucose derivatives to produce cyclopentene derivatives 5a and 5b, cyclohexene derivatives 8 and 9, cycloheptene 12, and cyclooctene 14. Spirocyclic dihydrofurans 19, 26a, and 26b, along with dihydropyran 22, were also produced. A range of fused oxepine derivatives 29a-c and one oxo-cyclononene 31 were also prepared. Cyclopentene 5b was subjected to a sequence of hydrogenation, NBS bromination, and treatment with powdered zinc to furnish the ring-expanded product 35. No such ring expansion occurred when the cyclohexaannulated compound 8 was treated with NBS followed by powdered zinc, leading to aldehyde 39. The spiro dihydrofuran derivative 19 was converted to the aldehyde 42 via the same reaction sequence used to fragment cyclopentene derivative 5b.

Full text of DOI:10.1021/jo991392z

482
J . Org. Chem. 2000, 65, 482-493
Ster eoselective P r ep a r a tion of En a n tiom er ica lly P u r e An n u la ted
Ca r boh yd r a tes Usin g Rin g-Closin g Meta th esis
David J . Holt, William D. Barker, and Paul R. J enkins*
Department of Chemistry, Leicester University, Leicester, LE1 7RH, U.K.
J agannath Panda and Subrata Ghosh*
Department of Organic Chemistry, Indian Association for the Cultivation of Science,
J adavpur, Calcutta - 700 032, India
Received September 2, 1999
Ring-closing metathesis has been applied to a series of glucose derivatives to produce cyclopentene
derivatives 5a and 5b, cyclohexene derivatives 8 and 9, cycloheptene 12, and cyclooctene 14.
Spirocyclic dihydrofurans 19, 26a , and 26b, along with dihydropyran 22, were also produced. A
range of fused oxepine derivatives 29a -c and one oxo-cyclononene 31 were also prepared.
Cyclopentene 5b was subjected to a sequence of hydrogenation, NBS bromination, and treatment
with powdered zinc to furnish the ring-expanded product 35. No such ring expansion occurred
when the cyclohexaannulated compound 8 was treated with NBS followed by powdered zinc, leading
to aldehyde 39. The spiro dihydrofuran derivative 19 was converted to the aldehyde 42 via the
same reaction sequence used to fragment cyclopentene derivative 5b.
In tr od u ction
“The Chiron Approach” to the synthesis of chiral target
molecules involves the use of sugars as starting materi-
als.10 A key element in this strategy is the ability to form
ring systems from carbohydrate molecules.11 Our previ-
ous results in this area have involved carbohydrate
annulation using the Robinson Annulation,12 aldol con-
densation,13 radical cyclization,14 and the application of
these methods to the synthesis of a C-ring synthon of
taxol.15 As part of this continuing program of research
on carbohydrate annulation along with its application to
the synthesis of chiral taxoids16 and other structures, we
have studied the application of RCM in this area. We
report here full details17 of the use of RCM in the
formation of five-, six-, seven-, eight-, and nine-membered
carbocyclic and oxygen-containing annulated ring fused
sugars. Potentially useful examples of the formation of
spiro fused oxygen rings are also reported.
Ring-closing metathesis (RCM), in which two unsub-
stituted olefins undergo ring closure with formal loss of
ethylene, is one of the most popular synthetic methods
at the present time. A very wide range of structures have
been studied in the reaction, which is remarkably toler-
ant of other fuctional groups in the substrate.1 The most
widely used catalyst is the commercially available Grubbs
catalyst 1.2 Oxygen and nitrogen heterocyclic derivatives
of sugars have been prepared by the RCM reaction of
sugars with appropriate side chains.3 Macrocyclic lac-
tones have also been prepared from sugar substrates
using a tungsten catalyst in RCM,4 and lactonization with
the Grubbs catalyst 1 has also been reported.5 Syntheses
of tricolorin A6 and of (+)-cyclitophellitol7 from carbohy-
drate precursors have also been achieved. Recent con-
tributions to this area have included the synthesis of
racemic large and medium ring oxacycles8 and the
synthesis of (+)-valienamine from D-glucose.9
(5) Sukkari, H. E.; Gesson, J .-P.; Renoux, B. Tetrahedron Lett. 1998,
39, 4043.
(6) Fu¨rstner, A.; Muller, T. J . Org. Chem. 1998, 63, 424.
(7) Ziegler, F. E.; Wang, Y. J . Org. Chem. 1998, 63, 426.
(8) Delgado, M.; Mart´ın, J . D. J . Org. Chem. 1999, 64, 4798.
(9) Kapferer, P.; Sarabia, F., Vasella, A. Helv. Chim. Acta 1999, 82,
645.
(10) Hanessian, S. Total Synthesis of Natural Products; The Chiron
Approach; Pergamon: Oxford, 1993.
(11) Ferrier, R. J .; Middleton, S. Chem. Rev. 1993, 93, 2779; Lopez,
J . C. B.; Fraser-Reid, B. J . Chem. Soc., Chem. Commun. 1997, 2251.
(12) (a) Bonnert, R. V.; J enkins, P. R. J . Chem. Soc., Chem.
Commun. 1987, 6. (b) Bonnert, R. V.; Howarth, J .; J enkins, P. R.;
Lawrence, N. J . J . Chem. Soc., Perkin Trans. 1 1991, 1225.
(13) (a) Wood, A. J .; J enkins, P. R.; Fawcett, J .; Russell, D. R. J .
Chem. Soc., Chem. Commun. 1995, 1567. (b) Wood, A. J .; Holt, D. J .;
Dominguez, M.-C.; J enkins, P. R. J . Org. Chem. 1998, 63, 8522.
(14) (a) Bonnert, R. V.; Davies, M. J .; Howarth, J .; J enkins, P. R. J .
Chem. Soc., Chem. Commun. 1987, 148. (b) Bonnert, R. V.; Davies,
M. J .; Howarth, J .; J enkins, P. R.; Lawrence, N. J . J . Chem. Soc.,
Perkin Trans. 1 1992, 27. (c) Wood, A. J .; J enkins, P. R. Tetrahedron
Lett. 1997, 38, 1853.
(15) Boa, A. N.; Clark, J .; J enkins, P. R.; Lawrence, N. J . J . Chem.
Soc., Chem. Commun. 1993, 151.
(16) J enkins, P. R. Pure Appl. Chem., 1996, 68, 771.
(17) For a preliminary report of some of these results see Holt, D.
J .; Barker, W. D.; J enkins, P. R.; Davies, D. L.; Garratt, S.; Fawcett,
J .; Russell, D. R.; Ghosh, S. Angew. Chem., Int. Ed. 1998, 37, 3298.
(1) (a) Fu¨rstner, A. Top. Catal. 1997, 4, 285. (b) Blechert, S.;
Schuster, M. Angew. Chem., Int. Ed. Engl. 1997, 36, 2036. (c) Grubbs,
R. H.; Chang, S. Tetrahedron 1998, 54, 4413. (d) Armstrong, S. K. J .
Chem. Soc., Perkin Trans. 1 1998, 371. (e) Fu¨rstner, A. Alkene
Metathesis in Organic Synthesis; Springer-Verlag: Berlin, 1998.
(2) (a) Schwab, P.; France, M. B.; Ziller, J . W.; Grubbs, R. H. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2039. (b) P. Schwab, P.; Grubbs, R. H.;
Ziller, J . W J . Am. Chem. Soc. 1996, 118, 100.
(3) (a) Overkleeft, H. S.; Pandit, U.K. Tetrahedron Lett. 1996, 37,
547. (b) Leeuwenburgh, M. A.; Overkleeft, H. S.; van der Marel, G. A.;
van Boom, J . H. Synlett 1997, 1263. (c) Ovaa, H.; Leeuwenburgh, M.
A.; Overkleeft, H. S.; van der Marel, G. A.; van Boom, J . H. Tetrahedron
Lett. 1998, 39, 3025. (d) Overkleeft, H. S.; Bruggeman, P.; Pandit, U.K.
Tetrahedron Lett. 1998, 39, 3869.
(4) Descotes, G.; Ramza, J .; Basset, J .-M.; Pagano, S.; Gentil, E.;
Banoub, J . Tetrahedron 1996, 52, 10903.
10.1021/jo991392z CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/30/1999

Preparation of Annulated Carbohydrates
J . Org. Chem., Vol. 65, No. 2, 2000 483
Sch em e 1a
a
Reagents and conditions: i, H2CdCH(CH2)nMgCl, THF, reflux 2 h (for n ) 0, 1); H2CdCH(CH2)nMgBr‚CeCl3, diethyl ether, -40 °C,
1.5-2 h (for n ) 2-4); ii, Cl2((C6H11)3P)2RuCHPh (3-6 mol %), benzene, 60 °C, 17-65 h.
Resu lts a n d Discu ssion
yield of alcohol 10 along with 7% of its isomer 11. The
major product from this reaction, alcohol 27a (50%),
arises from hydride reduction from the Grignard reagent.
Cycloheptaannulation of 10 by RCM occurred readily to
give the cis-fused alcohol 12 in 87% yield.
The preparation of a chiral cyclooctenone from D-
glucose has been reported by Thiem and Werschkun,20
and the synthesis of carbocyclic and heterocyclic eight-
membered rings using RCM has been reported by
Grubbs.21 An efficient reaction occurred in the addition
of 4-pentenylmagnesium bromide to ketone 2a , in the
presence of cerium(III) chloride, to produce the alcohol
13 in 76% yield. We reported a much lower yield of this
product using the Grignard reagent alone in the prelimi-
nary communication of this work.17 RCM of 13 furnished
the cis-fused cyclooctenyl alcohol 14 in 52% yield, along
with 30% recovered starting material.
Addition of 5-hexenylmagnesium bromide to ketone 2a
in the presence of cerium(III) chloride gave alcohol 15 in
55% yield. When this compound was subjected to the
standard RCM conditions no evidence of ring closure was
obtained. However, a peak consistent with an intermo-
lecular metathesis product was observed in the mass
spectrum. When the reaction was carried out under more
dilute conditions with a larger amount of catalyst, only
starting material was obtained.
Spiro-fused tetrahydrofuran and pyran ring systems
have been prepared by spiroether formation,22a-d in-
tramolecular radical addition,22e and intramolecular reac-
tion of an oxonium ion onto an allyl silane.22f Enantio-
Initial studies into the potential use of RCM in
carbohydrate annulation are summarized in Scheme 1.
The ketone 2a 17 was reacted with vinylmagnesium
chloride to produce alcohols 3a and 4a in 33 and 53%
yield, respectively. RCM only occurred with the cis isomer
3a which was converted into the cyclopentene 5a in a
modest 15% yield, with 75% starting material recovered.
The assignment of 5a was confirmed by an X-ray crystal
structure.19 A much improved yield of 98% was obtained
from the methylated compound 3b. We have observed
this kind of phenomenon in our previous work on the
intramolecular aldol condensation, where cyclizaton was
only possible when the side chain was attached to the
sugar at a quaternary center.13 We believe this result
may be explained by a Thorpe-Ingold type of effect, in
which the quaternary center restricts the degrees of
freedom of the carbon chain, making intramolecular
cyclization more efficient. The major product in the
addition of allyl Grignard to ketone 2a is the cis diene 6
as opposed to the trans diene 4a , the major product with
vinyl Grignard. This may be explained by coordination
of the magnesium to the ketone and reaction via allylic
rearrangement in the case of allyl Grignard, which is not
possible with the equivalent vinyl reagent. Both diene
isomers 6 and 7 underwent RCM to produce cyclohexene
derivatives 8 and 9 in 89 and 80% yield, respectively. The
structure of the cis product 8 was confirmed by an X-ray
crystal structure.19
The addition of butenylmagnesium chloride to ketone
2a in the presence of cerium(III) chloride gave a 20%
(20) Werschkun, B.; Thiem, J . Angew. Chem., Int. Ed. Engl. 1997,
36, 2793.
(18) Ferrier, R. J .; Lee, C.-K.; Wood, T. A. J . Chem. Soc., Chem.
Commun. 1991, 690.
(21) (a) Miller, S. J .; Kim, S.-H.; Chen, Z.-R.; Grubbs, R. H. J . Am.
Chem. Soc. 1995, 117, 2108. (b) Visser, M. S.; Heron, N. M.; Didiuk,
M. T.; Sagal, J . F. Hoveyda, A. H. J . Am. Chem. Soc. 1996, 118, 4291.
(c) Fu¨rstner, A.; Langemann, K. J . Org. Chem. 1996, 61, 8746. (d)
Clark, J . S.; Kettle, J . G. Tetrahedron Lett. 1997, 38, 123 and 127. (e)
Nicolaou, K. C.; Postema M. H. D.; Claiborne, C. F. J . Am. Chem. Soc.
1996, 118, 1565.
(19) Crystallographic data for compounds 5a , 8, 14, 19, and 22 in
this paper have been deposited with the Cambridge Crystallographic
Data Center as deposition numbers CCDC-101536; 101537; 101538;
101539; and 1015340, respectively. Copies of the data can be obtained
free of charge on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK (fax: (+44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).

484 J . Org. Chem., Vol. 65, No. 2, 2000
Holt et al.
Sch em e 2a
a
Reagents and conditions: i, H2CdCHMgCl, THF, reflux, 2h; ii, NaH, CH2dCHCH2Br, THF; iii, Cl2((C6H11)3P)2RuCHPh, benzene, 60
°C, 36 h; iv, CH2dCHMgCl, THF, reflux, 2 h.
Sch em e 3a
merically pure spiro products have been prepared from
an enantiomerically pure ketone by addition of an orga-
nometallic and acid-catalyzed ether formation.22g In
seeking applications for our studies on RCM in carbohy-
drate annulation we came upon the idea of trying the
reaction on systems suitable for the formation of spiro
compounds.23 Ketone 1624 was reacted with vinylmagne-
sium chloride to provide the alcohol 17 in 75% yield
(Scheme 2). Deprotonation with sodium hydride and
reaction with allyl bromide produced the ether 18 in 77%
yield, which was readily cyclized to the spiro product 19
in 75% yield, via RCM. A similar sequence involving
addition of allylmagnesium chloride gave alcohol 20 in
65% yield, the ether 21 was obtained in 72% yield and
the RCM reaction gave the spiro dihydropyran 22 in 73%
yield. This sequence seems to have general applicability
as shown by the results described in Scheme 3. Addition
a
Reagents and conditions: i, H2CdCRMgCl, THF, reflux, 2 h;
of vinylmagnesium chloride to ketone 23 gave a 55% yield
of alcohol 24a , which was converted into the ether 25a
in an 80% yield. RCM of the ether 25a produced the spiro
dihydrofuran in 51% yield. The same sequence was
carried out using isopropenyl Grignard to give alcohol
24b (65%), ether 25b (94%), and the spiro compound 26b
in 35% yield.
Studies on the synthesis of medium rings containing
oxygen are shown in Scheme 4. The addition of LiAlH4
or MeLi to ketone 2a produced alcohols 27a and 27b in
90 and 86% yield, respectively. Conversion to the ethers
28a -c was achieved in 78-87% yield and the three RCM
reactions occurred in 87% yield coincidentally. Alcohol
27a was converted into the ether 30 in 83% yield, which
gave the nine-membered ring 31 in 74% yield, as a
product of RCM. The successful formation of the nine-
membered heterocyclic ring 31 is in stark contrast to the
failure of RCM in the case of the carbon-containing
analogue, 15. One difference between the two examples
ii, NaH, CH2dCHCH2Br, DMPU, THF; iii, Cl2((C6H11)3P)2RuCHPh,
benzene, 60 °C, 36 h.
is that in 15 the chains are cis and in 30 they are trans,
another could be due to the oxygen, although a convincing
explanation does not seem possible on the basis of the
available data. The result seems to be in line with
literature precedent as there are far fewer examples of
metathesis leading to nine-membered rather than to
eight-membered rings.1 The three reported examples of
the formation of nine-membered rings all have oxygen
in the ring.25
We will now demonstrate that the methods described
so far can be used to prepare enantiomerically pure
carbocyclic and heterocyclic rings with quaternary cen-
ters. The cyclopentaannulated sugar 5b was reduced to
the saturated derivative 32 in 99% yield (Scheme 5).
Reaction with N-bromosuccinimide according to the
procedure of Hanessian26 gave the bromo ester 33 in good
yield. Treatment of 33 with activated zinc in a Vasella
elimination27 did not produce the expected cyclopentane
product. Instead ring-expansion occurred to produce the
cyclohexanone derivative 35 in 54% yield. The configu-
ration of the new stereogenic center in 35 is in accord
(22) (a) Reynolds, D. D.; Kenyon, W. O. J . Am. Chem. Soc. 1950,
72, 1593. (b) Picard, P.; Leclercq, D.; Moulines, J . Tetrahedron Lett.
1975, 2731. (c) Canonne, P.; Foscolos, G. B.; Belanger, D. J . Org. Chem.
1980, 45, 1828. (d) Piers E.; Ashvinikumar, V. G. J . Org. Chem. 1990,
55, 2380. (e) Middleton, D. S.; Simpkins, N. S. Tetrahedron Lett. 1988,
29, 1315. (f) Paquette, L. A.; Tae, J . J . Org. Chem. 1996, 61, 7860. (g)
Paquette L. A.; Negri, J . T. J . Am. Chem. Soc. 1991, 113, 5072.
(23) After submission of the preliminary communication17 of some
of the results in this paper a publication appeared on the spiroannu-
lation of a different set of sugar derivatives using RCM.; van Hooft, P.
A. V.; Leeuvwenburgh, M. A.; Overkleeft, H. S.; van der Marel, G. A.;
van Boeckel, C. A. A.; van Boom, J . H. Tetrahedron Lett. 1998, 39,
6061.
(25) (a) Barrett, A. G. M.; Baugh, S. P. D.; Gibson, V. C.; Giles, M.
R.; Marshall, E. L.; Procopiou, P. A. J . Chem. Soc., Chem. Commun.
1996, 2231. (b) Crimmins, M. T.; Choy, A. L. J . Org. Chem. 1997, 62,
7548. (c) Delgado, M.; Martin, J . D. Tetrahedron Lett. 1997, 38, 6299.
(26) Hanessian, S.; Plessas, N. R. J . Org. Chem. 1969, 34, 1035.
(27) Vasella, A.; Bernet, B. Helv. Chim. Acta 1979, 62, 1990; Helv.
Chim. Acta 1984, 67, 1328.
(24) Rosenthal, A.; Catsoulacos, P. Can. J . Chem. 1969, 47, 2747.

Preparation of Annulated Carbohydrates
J . Org. Chem., Vol. 65, No. 2, 2000 485
Sch em e 4a
a
Reagents and conditions: i, 27a /LiAlH4, THF, 0 °C, then 3 h reflux; 27b/MeLi, THF, 0 °C, then 6 h rt; ii, NaH, THF, 2 h reflux, then
cool to rt, CH2dCR2CH2Br, HMPA, 2 h, reflux; iii, NaH, THF, 2 h reflux, then cool to rt, CH2dCH(CH2)3Br, HMPA, 2 h reflux; iv,
Cl2((C6H11)3P)2RuCHPh, benzene, 60 °C, 6 h.
Sch em e 5a
In the case of the cyclohexene derivative 8, direct
bromination was possible to furnish the bromo ester 38
in 38% yield (Scheme 6). Treatment with activated zinc
gave the aldehyde 39 in 50% yield, no ring expansion was
observed. The driving force for expanding a five-mem-
bered ring in 34 to a six-membered ring in 35 is clearly
greater than from a six-membered ring in 39 to what
would be a seven-membered ring.
The spiro compound 19 was reduced to the saturated
analogue 40 in 89% yield, reacted with N-bromosuccin-
imide leading to bromo ester 41 in good yield, and
subjected to Vasella elimination to give the aldehyde 42
in 59% yield.
In conclusion we have demonstrated that RCM can be
applied to carbohydrate substrates for the formation of
five- to nine-membered rings, and that the products can
be converted into highly substituted enantiomerically
pure alicylic compounds. Studies on the application of
these compounds in natural product synthesis are un-
derway.
a
Reagents and conditions: i, H2, EtOH, 5% Pd/C; ii, NBS,
Exp er im en ta l Section
BaCO3, CHCl3, reflux; iii, activated Zn, IPC:H2O (10:1), reflux.
All reactions were performed under an atmosphere of
nitrogen (unless otherwise stated in the text) and solvent
extractions dried with anhydrous magnesium sulfate. Tet-
rahydrofuran and diethyl ether were freshly distilled from
sodium benzophenone ketyl. Chloroform was distilled from
phosphorus pentoxide and stored under nitrogen. Dichlo-
romethane was distilled from calcium hydride. Petroleum
ether refers to the 40-60 °C boiling fraction. Flash column
chromatography was performed on Sorbsil C-60 silica gel
(Crosfield Chemicals), 40-60 M. Melting points are uncor-
rected. All chemical shifts were taken directly from the spectra,
and J values are given in hertz.
Meth yl (R)-4,6-O-Ben zylid en e-2-C-eth en yl-3-d eoxy-3-
C-p r op en yl-r-D-glu cop yr a n osid e (3a ) a n d Meth yl (R)-4,6-
O-Ben zyliden e-2-C-eth en yl-3-deoxy-3-C-pr open yl-r-D-m an -
n op yr a n osid e (4a ). Vinylmagnesium chloride (5.70 mL, 9.60
mmol, 15 wt % solution in THF) was added dropwise to an
ice-cooled solution of the ketone 2a (2.00 g, 6.58 mmol) in dry
THF (7.0 mL). The solution was then heated to reflux for 2 h
and allowed to cool to room temperature and then quenched
by portionwise addition to ice/water (300 mL). The resulting
mixture was extracted into diethyl ether (2 × 150 mL), and
the combined organic layers were washed with water (2 × 150
mL), followed by saturated sodium chloride solution (150 mL),
dried, and evaporated to leave a yellow oil. Chromatography
with literature precedent28 where rearrangement occurrs
via the chelated transition state 34. Zinc bromide is
produced in the Vasella reaction which is the Lewis acid
for the rearrangement. We believe the major ring con-
formation of the product 35 is as indicated in structure
36. In the NOESY spectrum of alcohol 35 the major NOE
effects of the methyl group are across the R face of the
ring to the adjacent equatorial proton, and the axial
proton. The NOE effects of the proton on the carbon
bearing the hydroxyl are to the two axial protons on the
â face of the molecule, to the side chain CH and to the
OH. On the assumption that the conformation of the
cyclohexane ring is controlled by the largest substituent
being equatorial, the other possible rearrangement prod-
uct (instead of 35) is shown in structure 37. Here we
would not expect to see an NOE between the equatorial
proton on the carbon bearing the hydroxyl and the other
CH2 protons in the ring.
(28) Schor, L.; Seldes, A. M.; Gros, E. G. J . Chem. Soc., Perkin Trans.
1 1990, 163; J . Chem. Soc., Perkin Trans. 1 1992, 453.

486 J . Org. Chem., Vol. 65, No. 2, 2000
Holt et al.
Sch em e 6a
a
Reagents and conditions: i, H2, MeOH, 5% Pd/C; ii, NBS, BaCO3, CHCl3, reflux; iii, activated Zn, IPC:H2O (10:1), reflux.
on silica gel with petroleum ether-diethyl ether (4:1) as the
eluent yielded 3a as a colorless oil (711 mg, 33%) and 4a as a
colorless oil (1.16 g, 53%). 3a : Rf 0.58, petroleum ether-diethyl
(CH3, OMe), 60.4 (CH, C5), 70.0 (CH2, C6), 76.8 (C, C2), 82.9
(CH, C4), 101.9 (CH, C12), 105.0 (CH, C1), 115.5 (CH2, C11),
116.7 (CH2, C8), 126.6 (CH, Ph), 128.6 (CH, Ph), 129.3 (CH,
Ph), 136.7 (CH, C10), 138.3 (C, Ph), 138.7 (CH, C7); m/z (FAB)
347 (MH+, 20) (found MH+, 347.1858; C20H27O5 requires
347.1859). 4b: Rf 0.38, petroleum ether-diethyl ether (1:1);
δH (250 MHz, CDCl3) 1.26 (3H, s, C3-Me), 2.12-2.48 (3H, 9-H
and OH), 3.36 (3H, s, OMe), 3.72-3.90 (1H, m, 5-H), 3.94-
4.10 (2H, 4-H and 6ax-H), 4.15 (1H, s, 1-H), 4.30 (1H, dd, J
5.0, 10.1, 6eq-H), 4.92-5.10 (2H, m, 11-H), 5.32 (1H, d, J 10.0,
8-Hcis), 5.44 (1H, d, J 17.0, 8-Htrans), 5.58 (1H, s, 12-H), 5.97-
6.19 (1H, m, 10-H), 6.24 (1H, dd, J 10.0, 17.0, 7-H), 7.30-7.56
(5H, Ph); δC (62.9 MHz, CDCl3) 16.3 (CH3, C3-Me), 40.7 (CH2,
C9), 43.3 (C, C3), 56.2 (CH3, OMe), 60.8 (CH, C5), 69.9 (CH2,
C6), 79.0 (C, C2), 80.5 (CH, C4), 101.9 (CH, C12), 106.3 (CH,
C1), 116.0 (CH2, C11), 117.2 (CH2, C8), 126.5 (CH, Ph), 128.6
(CH, Ph), 129.2 (CH, Ph), 137.6 (CH, C10), 138.0 (CH, C7),
138.4 (C, Ph); m/z (FAB) 347 (MH+, 34) (found MH+, 347.1859;
ether (1:1); [R]20 +58.8° (c 5.9, CHCl3); δH (250 MHz, CDCl3)
D
2.09-2.43 (3H, 3-H and 9-H), 2.61 (1H, s, OH), 3.33-3.46 (1H,
m, 4-H), 3.36 (3H, s, overlapping, OMe), 3.68 (1H, t, J 9.8, 6ax-
H), 3.82 (1H, dt, J 4.4, 9.8, 5-H), 4.23 (1H, dd, J 4.4, 9.8, 6eq-
H), 4.29 (1H, s, 1-H), 4.91 (1H, d, J 10.1, 11-Hcis), 5.00 (1H,
dd, J 1.1, 17.2, 11-Htrans), 5.31 (1H, dd, J 1.6, 11.0, 8-Hcis), 5.45
(1H, s, 12-H), 5.56 (1H, dd, J 1.6, 17.2, 8-Htrans), 5.91-6.10
(2H, 7-H and 10-H), 7.27-7.51 (5H, Ph); δC (62.9 MHz, CDCl3)
31.4 (CH2, C9), 46.3 (CH, C3), 55.7 (CH3, OMe), 64.9 (CH, C5),
69.7 (CH2, C6), 75.9 (C, C2), 80.9 (CH, C4), 101.9 (CH, C12),
103.2 (CH, C1), 115.3 (CH2, C11), 117.4 (CH2, C8), 126.5 (CH,
Ph), 128.6 (CH, Ph), 129.3 (CH, Ph), 136.4 (CH, C10), 138.1
(C, Ph), 139.4 (CH, C7); m/z (FAB) 333 (MH+, 39) (found MH+,
333.1703; C19H25O5 requires 333.1702). 4a : Rf 0.46, petroleum
ether-diethyl ether (1:1); [R]20 + 12.9° (c 10.35, CHCl3); δH
D
(250 MHz, CDCl3) 2.08-2.40 (3H, 3-H and 9-H), 2.33 (1H, s,
overlapping, OH), 3.25 (3H, s, OMe), 3.68-3.91 (3H, 4-H, 5-H
and 6ax-H), 4.09 (1H, s, 1-H), 4.18 (1H, dd, J 4.4, 9.8, 6eq-H),
4.85-5.04 (2H, 11-H), 5.18 (1H, d, J 11.0, 8-Hcis), 5.36 (1H, d,
J 17.3, 8-Htrans), 5.45 (1H, s, 12-H), 5.80-6.07 (2H, 7-H and
10-H), 7.22-7.49 (5H, Ph); δC (62.9 MHz, CDCl3) 30.6 (CH2,
C9), 42.7 (CH, C3), 55.6 (CH3, OMe), 65.1 (CH, C5), 69.7 (CH2,
C6), 77.9 (C, C2), 79.0 (CH, C4), 102.1 (CH, C12), 104.5 (CH,
C1), 115.4 (CH2, C11), 116.3 (CH2, C8), 126.6 (CH, Ph), 128.6
(CH, Ph), 129.2 (CH, Ph), 138.4 (C, Ph), 138.8 (CH, C10), 140.7
(CH, C7); m/z (FAB) 333 (MH+, 72) (found MH+, 333.1701;
C
20H27O5 requires 347.1859).
Meth yl (R)-4,6-O-Ben zyliden e-2,3-C-(pr open e-1-yliden e-
3-yl)-3-d eoxy-r-D-glu cop yr a n osid e (5a ). Nitrogen gas was
bubbled through a solution of the diene 3a (106 mg, 0.32 mmol)
in benzene (10 mL) for 2-3 min. The catalyst 1 (8 mg, 0.0097
mmol, 3.0 mol %) was then added and the solution heated at
60 °C for 48 h. The solvent was then removed under reduced
pressure to leave a dark brown oil. Chromatography on silica
gel with petroleum ether-diethyl ether (3:1 to 2:1) as the
eluent yielded starting material 3a as a colorless oil (79 mg,
75%) and 5a as a white solid (15 mg, 15%): mp 148-150 °C;
C
19H25O5 requires 333.1702).
Rf 0.15, petroleum ether-diethyl ether (1:1); [R]20 +28.5° (c
D
Meth yl (R)-4,6-O-Ben zylid en e-2-C-eth en yl-3-d eoxy-3-
0.9, CHCl3); δH (400 MHz, CDCl3) 2.35 (1H, dt, J 5.0, 9.8, 3-H),
2.38-2.45 (1H, m, overlapping, CHH, 9-H), 2.80-2.89 (1H, m,
CHH, 9-H), 2.86 (1H, s, overlapping, OH), 3.12 (1H, t, J 9.8,
4-H), 3.53 (3H, s, OMe), 3.66 (1H, t, J 10.3, 6ax-H), 3.90 (1H,
ddd, J 5.1, 9.8, 10.3, 5-H), 4.31 (1H, dd, J 5.1, 10.3, 6eq-H),
4.76 (1H, s, 1-H), 5.47 (1H, s, 10-H), 5.78-5.83 (1H, m, 7-H),
6.17-6.22 (1H, m, 8-H), 7.33-7.52 (5H, Ph); δC (100.6 MHz,
CDCl3) 35.2 (CH2, C9), 48.0 (CH, C3), 55.8 (CH3, OMe), 61.8
(CH, C5), 69.7 (CH2, C6), 81.5 (CH, C4), 83.5 (C, C2), 100.2
(CH, C10), 102.4 (CH, C1), 126.6 (CH, Ph), 128.7 (CH, Ph),
129.5 (CH, Ph), 133.7 (CH, C8), 138.0 (C, Ph), 138.0 (CH, C7);
m/z (CI) 305 (MH+, 100) (found MH+, 305.1388; C17H21O5
requires 305.1389). Anal. Found: C, 64.36; H, 6.68. C17H20O5
requires C, 67.09; H, 6.62%.
C-m et h yl-3-C-p r op en yl-r-D-glu cop yr a n osid e (3b ) a n d
Meth yl (R)-4,6-O-Ben zylid en e-2-C-eth en yl-3-d eoxy-3-C-
m eth yl-3-C-p r op en yl-r-D-m a n n op yr a n osid e (4b). Vinyl-
magnesium chloride (2.00 mL, 3.37 mmol, 15 wt % solution
in THF) was added dropwise to an ice-cooled solution of the
ketone 2b (729 mg, 2.29 mmol) in dry THF (6.0 mL). The
solution was then heated to reflux for 2 h and allowed to cool
to room temperature and then quenched by dropwise addition
of water (20 mL). The resulting mixture was then diluted with
water (50 mL) and extracted into diethyl ether (2 × 75 mL),
and the combined organic layers were washed with water (50
mL), followed by saturated sodium chloride solution (50 mL),
dried, and evaporated to leave a yellow oil. Chromatography
on silica gel with petroleum ether-diethyl ether (3:1) as the
eluent yielded 3b as a colorless oil (518 mg, 65%) and 4b as a
colorless oil (118 mg, 15%). 3b: Rf 0.62, petroleum ether-
Meth yl (R)-4,6-O-Ben zyliden e-2,3-C-(pr open e-1-yliden e-
3-yl)-3-d eoxy-3-C-m eth yl-r-D-glu cop yr a n osid e (5b). Ni-
trogen gas was bubbled through a solution of the diene 3b (124
mg, 0.36 mmol) in benzene (10 mL) for 2-3 min. The catalyst
1 (10 mg, 0.012 mmol, 3.4 mol %) was then added and the
solution heated at 60 °C for 17 h. The solvent was then
removed under reduced pressure to leave a dark brown oil.
Chromatography on silica gel with petroleum ether-diethyl
ether (2:1) as the eluent yielded 5b as a white solid (112 mg,
98%): mp 107-108 °C; Rf 0.21, petroleum ether-diethyl ether
diethyl ether (1:1); [R]20 +26.6° (c 0.7, CHCl3); δH (250 MHz,
D
CDCl3) 1.23 (3H, s, C3-Me), 2.13-2.32 (2H, m, 9-H), 2.71 (1H,
d, J 1.3, OH), 3.37 (3H, s, OMe), 3.55 (1H, d, J 9.8, 4-H), 3.71
(1H, t, J 10.1, 6ax-H), 3.95 (1H, ddd, J 5.0, 9.8, 10.1, 5-H),
4.27 (1H, s, 1-H), 4.30 (1H, dd, overlapping, J 5.0, 10.1, 6eq-
H), 4.88-5.00 (2H, m, 11-H), 5.25 (1H, dd, J 1.9, 11.0, 8-Hcis),
5.49 (1H, s, 12-H), 5.56 (1H, dd, J 1.9, 17.2, 8-Htrans), 5.90-
6.24 (2H, 7-H and 10-H), 7.28-7.53 (5H, Ph); δC (62.9 MHz,
CDCl3) 14.2 (CH3, C3-Me), 41.9 (CH2, C9), 44.1 (C, C3), 56.3
(1:1); [R]20 +39.5° (c 5.95, CHCl3); δH (250 MHz, CDCl3) 1.31
D
(3H, s, C3-Me), 2.38 (1H, dt, J 2.1, 16.8, CHH, 9-H), 2.52 (1H,

Preparation of Annulated Carbohydrates
J . Org. Chem., Vol. 65, No. 2, 2000 487
dd, J 1.6, 16.8, CHH, 9-H), 2.81 (1H, s, OH), 3.33 (1H, d, J
9.9, 4-H), 3.47 (3H, s, OMe), 3.69 (1H, t, J 10.3, 6ax-H), 3.93
(1H, ddd, J 5.1, 9.9, 10.3, 5-H), 4.31 (1H, dd, J 5.1, 10.3, 6eq-
H), 4.71 (1H, s, 1-H), 5.47 (1H, s, 10-H), 5.74-5.84 (1H, m,
7-H), 6.09-6.19 (1H, m, 8-H), 7.32-7.57 (5H, Ph); δC (62.9
MHz, CDCl3) 13.4 (CH3, C3-Me), 43.1 (CH2, C9), 48.3 (C, C3),
56.0 (CH3, OMe), 58.8 (CH, C5), 69.8 (CH2, C6), 82.6 (CH, C4),
82.9 (C, C2), 101.2 (CH, C10), 102.1 (CH, C1), 126.6 (CH, Ph),
128.6 (CH, Ph), 129.4 (CH, Ph), 134.6 (CH, C8), 137.9 (CH,
C7), 138.3 (C, Ph); m/z (FAB) 319 (MH+, 26) (found MH+,
319.1545; C18H23O5 requires 319.1546). Anal. Found: C, 67.68;
H, 6.92. C18H22O5 requires C, 67.91; H, 6.96%.
(found MH+, 319.1547; C18H23O5 requires 319.1546). Anal.
Found: C, 67.75; H, 7.05. C18H22O5 requires C, 67.91; H, 6.96%.
Meth yl (R)-4,6-O-Ben zyliden e-2,3-C-(bu t-2-en e-1,4-diyl)-
3-deoxy-r-D-m an n opyr an oside (9). Nitrogen gas was bubbled
through a solution of the diene 7 (86 mg, 0.25 mmol) in benzene
(10 mL) for 2-3 min. The catalyst 1 (8 mg, 0.0097 mmol, 3.9
mol %) was then added and the solution heated at 60 °C for
17 h. The solvent was then removed under reduced pressure
to leave a dark brown oil. Chromatography on silica gel with
petroleum ether-diethyl ether (3:1 to 2:1) as the eluent yielded
9 as a colorless oil (63 mg, 80%): Rf 0.13, petroleum ether-
diethyl ether (1:1); [R]18 +8.8° (c 6.0, CHCl3); δH (250 MHz;
D
CDCl3) 1.86 (1Η, dd, J 4.4, 18.2, CHH, 7-H), 1.94-2.10 (1H,
m, CHH, 10-H), 2.04 (1H, s, overlapping, OH), 2.16 (1H, dt, J
5.2, 10.6, 3-H), 2.40-2.55 (1H, m, CHH, 10-H), 2.51-2.67 (1H,
m, overlapping, CHH, 7-H), 3.41 (3H, s, OMe), 3.65 (1H, t, J
10.6, 4-H), 3.76-3.94 (1H, t, J 9.0, 6ax-H; 1H, m, overlapping,
5-H), 4.25 (1H, dd, J 3.6, 9.0, 6eq-H), 4.39 (1H, s, 1-H), 5.53
(1H, s, 11-H), 5.54-5.68 (1H, m, 8-H), 5.70-5.82 (1H, m, 9-H),
7.30-7.53 (5H, Ph); δC (62.9 MHz, CDCl3) 24.4 (CH2, C10),
34.3 (CH2, C7), 37.6 (CH, C3), 55.5 (CH3, OMe), 64.5 (CH, C5),
69.7 (CH2, C6), 71.9 (C, C2), 80.2 (CH, C4), 102.3 (CH, C11),
103.3 (CH, C1), 123.5 (CH, C8), 126.1 (CH, C9), 126.5 (CH,
Ph), 128.6 (CH, Ph), 129.3 (CH, Ph), 138.2 (C, Ph); m/z (FAB)
319 (MH+, 34) (found MH+, 319.1544; C18H23O5 requires
319.1546).
Meth yl (R)-4,6-O-Ben zylid en e-2-C-p r op en yl-3-d eoxy-3-
C-p r op en yl-r-D-glu cop yr a n osid e (6) a n d Meth yl (R)-4,6-
O-Ben zylid en e-2-C-p r op en yl-3-d eoxy-3-C-p r op en yl-r-D-
m a n n op yr a n osid e (7). Allylmagnesium chloride (9.94 mL,
19.88 mmol, 2 M solution in THF) was added dropwise to an
ice-cooled solution of the ketone 2a (2.00 g, 6.58 mmol) in dry
THF (7.0 mL). The solution was then heated to reflux for 2 h,
allowed to cool to room temperature, and then quenched by
portionwise addition to ice/water (300 mL). The resulting
mixture was then treated with saturated ammonium chloride
solution (30 mL) and extracted into diethyl ether (2 × 150 mL),
and the combined organic layers were washed with water (300
mL), followed by saturated sodium chloride solution (300 mL),
dried, and evaporated to leave a yellow oil. Chromatography
on silica gel with petroleum ether-diethyl ether (4:1) as the
eluent yielded 6 as a colorless oil (1.68 g, 74%) and 7 as a
colorless oil (344 mg, 15%). 6: Rf 0.68, petroleum ether-diethyl
Meth yl (R)-4,6-O-Ben zylid en e-2-C-bu t-3-en yl-3-d eoxy-
3-C-p r op en yl-r-D-glu cop yr a n osid e (10) a n d Meth yl (R)-
4,6-O-Ben zylid en e-2-C-bu t-3-en yl-3-d eoxy-3-C-p r op en yl-
r-D-m a n n op yr a n osid e (11). Anhydrous cerium(III) chloride
(2.03 g, 8.23 mmol) in dry diethyl ether (4.0 mL) was stirred
at room temperature for 1.5 h. In another flask, 4-bromo-1-
butene (0.835 mL, 8.23 mmol) in dry diethyl ether (5.0 mL)
was added dropwise to magnesium turnings (220 mg, 9.05
mmol) in dry diethyl ether (4.0 mL) at 0 °C. This mixture was
stirred at 0 °C for 0.25 h and then at room temperature for 1
h. The cerium(III) chloride mixture was then cooled to -78
°C, the freshly prepared Grignard added dropwise via a
cannula, and the resulting mixture stirred at -78 °C for 2 h.
Ketone 2a (500 mg, 1.64 mmol) in dry diethyl ether (6.0 mL)
was added dropwise via a cannula to the cooled (-78 °C)
reaction mixture. The mixture was then stirred at -40 °C for
1.5 h, then added portionwise to ice/water (150 mL) and
saturated ammonium chloride solution (50 mL). The mixture
was then extracted into dichloromethane (2 × 100 mL), and
the combined organic layers were washed with saturated
sodium chloride solution (200 mL), dried, and evaporated to
leave a yellow oil. Chromatography on silica gel with petroleum
ether-diethyl ether (3:1 to 2:1) as the eluent yielded 10 as a
colorless oil (120 mg, 20%), 11 as a colorless oil (39 mg, 7%)
and the reduced product 27a as a white solid (252 mg, 50%):
10 - Rf 0.60, petroleum ether-diethyl ether (1:1); [R]20D +43.1°
(c 2.1, CHCl3); δH (250 MHz, CDCl3) 1.62-1.88 (2H, m, 7-H),
2.00-2.61 (5H, 3-H, 8-H and 11-H), 2.30 (1H, d, overlapping,
J 1.6, OH), 3.40-3.57 (1H, m, 4-H), 3.47 (3H, s, overlapping,
OMe), 3.65-3.90 (2H, 5-H and 6ax-H), 4.28 (1H, dd, J 3.2, 8.7,
6eq-H), 4.55 (1H, s, 1-H), 4.90-5.20 (4H, 10-H and 13-H), 5.53
(1H, s, 14-H), 5.78-6.18 (2H, 9-H and 12-H), 7.32-7.57 (5H,
Ph); δC (62.9 MHz, CDCl3) 27.5 (CH2, C11), 30.9 (CH2, C8),
31.3 (CH2, C7), 46.8 (CH, C3), 55.8 (CH3, OMe), 64.9 (CH, C5),
69.8 (CH2, C6), 74.7 (C, C2), 81.2 (CH, C4), 100.7 (CH, C14),
101.9 (CH, C1), 115.1 (CH2, C10), 115.1 (CH2, C13), 126.5 (CH,
Ph), 128.6 (CH, Ph), 129.2 (CH, Ph), 138.0 (C, Ph), 139.1 (CH,
C12), 139.5 (CH, C9); m/z (FAB) 361 (MH+, 32) (found MH+,
361.2015; C21H29O5 requires 361.2015). 11 - Rf 0.24, petroleum
ether-diethyl ether (1:1); δH (250 MHz, CDCl3) 1.60-2.63 (7H,
3-H, 7-H, 8-H and 11-H), 1.86 (1H, s, overlapping, OH), 3.40
(3H, s, OMe), 3.65-3.96 (3H, 4-H, 5-H and 6ax-H), 4.25 (1H,
dd, J 3.3, 9.3, 6eq-H), 4.38 (1H, s, 1-H), 4.90-5.20 (4H, 10-H
and 13-H), 5.55 (1H, s, 14-H), 5.72-6.16 (2H, 9-H and 12-H),
7.29-7.56 (5H, Ph); δC (62.9 MHz, CDCl3) 27.2 (CH2, C11),
29.2 (CH2, C8), 36.2 (CH2, C7), 43.8 (CH, C3), 55.3 (CH3, OMe),
64.9 (CH, C5), 69.7 (CH2, C6), 76.7 (C, C2), 78.4 (CH, C4), 102.2
(CH, C14), 102.5 (CH, C1), 115.1 (CH2, C10), 116.2 (CH2, C13),
126.5 (CH, Ph), 128.6 (CH, Ph), 129.2 (CH, Ph), 138.2 (C, Ph),
ether (1:1); [R]20 +75.9° (c 4.8, CHCl3); δH (250 MHz, CDCl3)
D
2.32-2.78 (6H, 3-H, 7-H, 10-H and OH), 3.60 (3H, s, OMe),
3.64 (1H, dd, overlapping, J 9.1, 10.7, 4-H), 3.88-4.05 (2H,
5-H and 6ax-H), 4.40-4.49 (1H, m, 6eq-H), 4.68 (1H, s, 1-H),
5.10-5.40 (4H, 9-H and 12-H), 5.70 (1H, s, 13-H), 6.05-6.33
(2H, 8-H and 11-H), 7.53-7.69 (5H, Ph); δC (62.9 MHz, CDCl3)
31.3 (CH2, C10), 36.6 (CH2, C7), 46.6 (CH, C3), 55.7 (CH3,
OMe), 64.8 (CH, C5), 69.8 (CH2, C6), 74.7 (C, C2), 81.1 (CH,
C4), 101.0 (CH, C1), 101.9 (CH, C13), 115.3 (CH2, C9), 119.0
(CH2, C12), 126.5 (CH, Ph), 128.6 (CH, Ph), 129.2 (CH, Ph),
133.6 (CH, C11), 138.1 (C, Ph), 139.3 (CH, C8); m/z (FAB) 347
(MH+, 34) (found MH+, 347.1858; C20H27O5 requires 347.1859).
7: Rf 0.40, petroleum ether-diethyl ether (1:1); [R]20 +9.6°
D
(c 5.8, CHCl3); δH (250 MHz, CDCl3) 2.00-2.16 (2H, 3-H and
OH), 2.26-2.59 (4H, 7-H and 10-H), 3.33 (3H, s, OMe), 3.64-
3.91 (3H, 4-H, 5-H and 6ax-H), 4.22 (1H, dd, J 4.1, 9.8, 6eq-
H), 4.25 (1H, s, overlapping, 1-H), 4.92-5.22 (4H, 9-H and 12-
H), 5.50 (1H, s, 13-H), 5.71-6.10 (2H, 8-H and 11-H), 7.25-
7.52 (5H, Ph); δC (62.9 MHz, CDCl3) 29.4 (CH2, C10), 41.5 (CH2,
C7), 43.6 (CH, C3), 55.3 (CH3, OMe), 65.1 (CH, C5), 69.7 (CH2,
C6), 76.4 (C, C2), 78.7 (CH, C4), 102.1 (CH, C1), 102.9 (CH,
C13), 115.9 (CH2, C9), 119.7 (CH2, C12), 126.5 (CH, Ph), 128.6
(CH, Ph), 129.2 (CH, Ph), 133.1 (CH, C11), 138.3 (C, Ph), 139.1
(CH, C8); m/z (FAB) 347 (MH+, 60) (found MH+, 347.1859;
C
20H27O5 requires 347.1859).
Meth yl (R)-4,6-O-Ben zyliden e-2,3-C-(bu t-2-en e-1,4-diyl)-
3-d eoxy-r-D-glu cop yr a n osid e (8). Nitrogen gas was bubbled
through a solution of the diene 6 (101 mg, 0.29 mmol) in
benzene (10 mL) for 2-3 min. The catalyst 1 (8 mg, 0.0097
mmol, 3.3 mol %) was then added and the solution heated at
60 °C for 17 h. The solvent was then removed under reduced
pressure to leave a dark brown oil. Chromatography on silica
gel with petroleum ether-diethyl ether (3:1 to 2:1) as the
eluent yielded 8 as a white solid (83 mg, 89%): mp 142-143
°C; Rf 0.19, petroleum ether-diethyl ether (1:1); [R]20D +33.6°
(c 8.3, CHCl3); δH (250 MHz, CDCl3) 1.98-2.13 (1Η, m, CHH,
7-H), 2.19-2.58 (5H, 3-H, CHH, 7-H, 10-H and OH), 3.41 (1H,
dd, J 9.1, 10.7, 4-H), 3.50 (3H, s, OMe), 3.68-3.86 (2H, 5-H
and 6ax-H), 4.27 (1H, dd, J 3.5, 9.1, 6eq-H), 4.32 (1H, s, 1-H),
5.51 (1H, s, 11-H), 5.61-5.79 (2H, 8-H and 9-H), 7.34-7.54
(5H, Ph); δC (62.9 MHz, CDCl3) 18.8 (CH2, C10), 30.8 (CH2,
C7), 38.2 (CH, C3), 54.4 (CH3, OMe), 63.7 (CH, C5), 68.3 (CH2,
C6), 69.1 (C, C2), 76.1 (CH, C4), 100.6 (CH, C11), 101.8 (CH,
C1), 121.4 (CH, C8), 123.5 (CH, C9), 125.1 (CH, Ph), 127.2 (CH,
Ph), 127.9 (CH, Ph), 136.6 (C, Ph); m/z (FAB) 319 (MH+, 100)

488 J . Org. Chem., Vol. 65, No. 2, 2000
Holt et al.
138.7 (CH, C12), 139.2 (CH, C9); m/z (FAB) 361 (MH+, 28)
(found MH+, 361.2015; C21H29O5 requires 361.2015).
petroleum ether-diethyl ether (1:1); [R]17 - 79.1° (c 2.4,
D
CHCl3); δH (400 MHz; CDCl3) 1.39 (1Η, dd, J 4.1, 11.0, CHH,
7-H), 1.44-1.56 (1H, m, CHH, 8-H), 1.93-2.11 (3H, CHH, 7-H;
CHH, 8-H and CHH, 9-H), 2.19-2.33 (2H, CHH, 12-H and
3-H), 2.26 (1H, s, overlapping, OH), 2.49-2.61 (1H, m, CHH,
9-H), 2.65 (1H, dd, J 8.4, 12.5, CHH, 12-H), 3.42 (3H, s, OMe),
3.60 (1H, dd, J 9.2, 10.8, 4-H), 3.71 (1H, t, J 9.6, 6ax-H), 3.79
(1H, ddd, J 4.1, 9.2, 9.6, 5-H), 4.17 (1H, s, 1-H), 4.25 (1H, dd,
J 4.1, 9.6, 6eq-H), 5.53 (1H, s, 13-H), 5.68-5.78 (1H, m, 10-
H), 5.80-5.90 (1H, m, 11-H), 7.31-7.54 (5H, Ph); δC (100.6
MHz, CDCl3) 20.9 (CH2, C12), 24.4 (CH2, C8), 26.2 (CH2, C9),
30.8 (CH2, C7), 46.2 (CH, C3), 55.6 (CH3, OMe), 65.3 (CH, C5),
69.9 (CH2, C6), 74.7 (C, C2), 78.1 (CH, C4), 102.0 (CH, C13),
107.3 (CH, C1), 126.5 (CH, Ph), 128.7 (CH, Ph), 129.2 (CH,
C11), 129.3 (CH, Ph), 132.7 (CH, C10), 138.1 (C, Ph); m/z (FAB)
347 (MH+, 10) (found MH+, 347.1858; C20H27O5 requires
347.1859). Anal. Found: C, 69.35; H, 7.35. C20H26O5 requires
C, 69.34; H, 7.56%.
Met h yl (R)-4,6-O-Ben zylid en e-2,3-C-(p en t -3-en e-1,5-
d iyl)-3-d eoxy-r-D-glu cop yr a n osid e (12). Nitrogen gas was
bubbled through a solution of the diene 10 (120 mg, 0.33 mmol)
in benzene (10 mL) for 2-3 min. The catalyst 1 (10 mg, 0.012
mmol, 3.6 mol %) was then added and the solution heated at
60 °C for 17 h. The solvent was then removed under reduced
pressure to leave a dark brown oil. Chromatography on silica
gel with petroleum ether-diethyl ether (3:1) as the eluent
yielded 12 as a white solid (96 mg, 87%): mp 113-114 °C; Rf
0.32, petroleum ether-diethyl ether (1:1); [R]20D - 30.0° (c 3.6,
CHCl3); δH (250 MHz, CDCl3) 1.40-1.59 (1Η, m, CHH, 7-H),
1.77-2.09 (2H, CHH, 7-H and CHH, 8-H), 2.09-2.22 (1H, m,
3-H), 2.24-2.43 (1Η, m, CHH, 11-H), 2.49 (1H, d, J 2.1, OH),
2.54-2.83 (2H, CHH, 8-H and CHH, 11-H), 3.45 (3H, s, OMe),
3.62-3.90 (3H, 4-H, 5-H and 6ax-H), 4.13 (1H, s, 1-H), 4.27
(1H, dd, J 3.8, 9.3, 6eq-H), 5.48 (1H, s, 12-H), 5.68-5.85 (1H,
m, 10-H), 5.93-6.10 (1H, m, 9-H), 7.31-7.57 (5H, Ph); δC (62.9
MHz, CDCl3) 21.2 (CH2, C11), 21.5 (CH2, C8), 31.9 (CH2, C7),
42.8 (CH, C3), 55.7 (CH3, OMe), 65.3 (CH, C5), 69.8 (CH2, C6),
75.1 (C, C2), 76.7 (CH, C4), 101.9 (CH, C12), 105.6 (CH, C1),
126.5 (CH, Ph), 128.6 (CH, Ph), 129.3 (CH, Ph), 129.8 (CH,
C10), 133.7 (CH, C9), 138.2 (C, Ph); m/z (FAB) 333 (MH+, 41)
(found MH+, 333.1703; C19H25O5 requires 333.1702). Anal.
Found: C, 68.65; H, 7.26. C19H24O5 requires C, 68.66; H, 7.28%.
Meth yl (R)-4,6-O-Ben zylid en e-2-C-p en t-4-en yl-3-d eoxy-
3-C-p r op en yl-r-D-glu cop yr a n osid e (13). Anhydrous ceri-
um(III) chloride (2.03 g, 8.23 mmol) in dry diethyl ether (4.0
mL) was stirred at room temperature for 1.5 h. In another
flask, 5-bromo-1-pentene (0.975 mL, 8.23 mmol) in dry diethyl
ether (5.0 mL) was added dropwise to magnesium turnings
(220 mg, 9.05 mmol) in dry diethyl ether (4.0 mL) at 0 °C.
This mixture was stirred at 0 °C for 0.25 h and then at room
temperature for 1 h. The cerium(III) chloride mixture was then
cooled to -78 °C, the freshly prepared Grignard added
dropwise via a cannula, and the resulting mixture stirred at
-78 °C for 2 h. Ketone 2a (500 mg, 1.64 mmol) in dry diethyl
ether (6.0 mL) was added dropwise via a cannula to the cooled
(-78 °C) reaction mixture. The mixture was then stirred at
-40 °C for 2 h and then added portionwise to ice/water (150
mL) and saturated ammonium chloride solution (50 mL). The
mixture was then extracted into dichloromethane (2 × 100
mL), and the combined organic layers were washed with
saturated sodium chloride solution (200 mL), dried, and
evaporated to leave a yellow oil. Chromatography on silica gel
with petroleum ether-diethyl ether (3:1 to 1:1) as the eluent
yielded 13 as a colorless oil (465 mg, 76%) and the reduced
product 27a as a white solid (83 mg, 16%). 13: Rf 0.56,
Meth yl (R)-4,6-O-Ben zylid en e-2-C-h ex-5-en yl-3-d eoxy-
3-C-p r op en yl-r-D-glu cop yr a n osid e (15). Anhydrous ceri-
um(III) chloride (2.03 g, 8.23 mmol) in dry diethyl ether (4.0
mL) was stirred at room temperature for 1.5 h. In another
flask, 6-bromo-1-hexene (1.00 g, 6.13 mmol) in dry diethyl
ether (5.0 mL) was added dropwise to magnesium turnings
(220 mg, 9.05 mmol) in dry diethyl ether (4.0 mL) at 0 °C.
This mixture was stirred at 0 °C for 0.25 h and then at room
temperature for 1 h. The cerium(III) chloride mixture was then
cooled to -78 °C, the freshly prepared Grignard added
dropwise via a cannula, and the resulting mixture stirred at
-78 °C for 2 h. Ketone 2a (500 mg, 1.64 mmol) in dry diethyl
ether (6.0 mL) was added dropwise via a cannula to the cooled
(-78 °C) reaction mixture. The mixture was then stirred at
-40 °C for 2 h and then added portionwise to ice/water (150
mL) and saturated ammonium chloride solution (50 mL). The
mixture was then extracted into dichloromethane (2 × 100
mL), and the combined organic layers were washed with
saturated sodium chloride solution (200 mL), dried, and
evaporated to leave a yellow oil. Chromatography on silica gel
with petroleum ether-diethyl ether (3:1) as the eluent yielded
15 as a colorless oil (350 mg, 55%) and the reduced product
27a as a white solid (139 mg, 28%). 15: Rf 0.65, petroleum
ether-diethyl ether (1:1); [R]20D +35.5° (c 3.1, CHCl3); δH (250
MHz, CDCl3) 1.20-1.78 (6H, 8-H, 9-H and 10-H), 2.00-2.58
(5H, 3-H, 7-H and 13-H), 2.22 (1H, s, overlapping, OH), 3.46
(3H, s, OMe), 3.46 (1H, t, overlapping, J 9.5, 4-H), 3.68-3.88
(2H, 5-H and 6ax-H), 4.20-4.32 (1H, m, 6eq-H), 4.53 (1H, s,
1-H), 4.90-5.13 (4H, 12-H and 15-H), 5.53 (1H, s, 16-H), 5.73-
6.16 (2H, 11-H and 14-H), 7.30-7.57 (5H, Ph); δC (62.9 MHz,
CDCl3) 22.7 (CH2, C8), 30.1 (CH2, C9), 31.3 (CH2, C10), 31.6
(CH2, C13), 34.2 (CH2, C7), 46.8 (CH, C3), 55.7 (CH3, OMe),
64.9 (CH, C5), 69.8 (CH2, C6), 74.9 (C, C2), 81.3 (CH, C4), 100.9
(CH, C1), 101.9 (CH, C16), 114.9 (CH2, C15), 115.0 (CH2, C12),
126.5 (CH, Ph), 128.6 (CH, Ph), 129.2 (CH, Ph), 138.1 (C, Ph),
139.2 (CH, C14), 139.6 (CH, C11); m/z (FAB) 389 (MH+, 33)
(found MH+, 389.2328; C23H33O5 requires 389.2328).
petroleum ether-diethyl ether (1:1); [R]20 +47.3° (c 4.3,
D
CHCl3); δH (250 MHz, CDCl3) 1.22-1.78 (4H, 7-H and 8-H),
2.00-2.58 (5H, 3-H, 9-H and 12-H), 2.22 (1H, s, overlapping,
OH), 3.46 (3H, s, OMe), 3.46 (1H, t, J 9.9, 4-H), 3.68-3.88 (2H,
5-H and 6ax-H), 4.26 (1H, dd, J 3.1, 8.6, 6eq-H), 4.54 (1H, s,
1-H), 4.89-5.13 (4H, 11-H and 14-H), 5.53 (1H, s, 15-H), 5.73-
6.17 (2H, 10-H and 13-H), 7.30-7.56 (5H, Ph); δC (62.9 MHz,
CDCl3) 22.4 (CH2, C8), 31.1 (CH2, C9), 31.3 (CH2, C12), 34.7
(CH2, C7), 46.9 (CH, C3), 55.7 (CH3, OMe), 64.9 (CH, C5), 69.8
(CH2, C6), 74.9 (C, C2), 81.2 (CH, C4), 100.9 (CH, C1), 101.9
(CH, C15), 115.1 (CH2, C14), 115.2 (CH2, C11), 126.4 (CH, Ph),
128.6 (CH, Ph), 129.2 (CH, Ph), 138.0 (C, Ph), 138.9 (CH, C13),
139.5 (CH, C10); m/z (FAB) 375 (MH+, 19) (found MH+,
375.2172; C22H31O5 requires 375.2172).
Meth yl (R)-4,6-O-Ben zylid en e-2-C-eth en yl-3-d eoxy-r-
D-glu cop yr a n osid e (17). Vinylmagnesium chloride (20.60
mL, 34.70 mmol, 15 wt % solution in THF) was added dropwise
to an ice-cooled solution of the ketone 16 (1.85 g, 7.00 mmol)
in dry THF (10.0 mL). The solution was then heated to reflux
for 4 h, allowed to cool to room temperature, and then
quenched by dropwise addition of saturated ammonium chlo-
ride solution (30 mL). The resulting mixture was extracted
into diethyl ether (2 × 100 mL), and the combined organic
layers were washed with saturated sodium chloride solution
(100 mL), dried, and evaporated to leave a brown oil. Chro-
matography on silica gel with petroleum ether-diethyl ether
(4:1) as the eluent yielded 17 as a colorless oil (1.35 g, 75%):
Meth yl (R)-4,6-O-Ben zyliden e-2,3-C-(h ex-4-en e-1,6-diyl)-
3-deoxy-r-D-glu copyr an oside (14). Nitrogen gas was bubbled
through a solution of the diene 13 (144 mg, 0.39 mmol) in
benzene (10 mL) for 2-3 min. The catalyst 1 (10 mg, 0.012
mmol, 3.2 mol %) was then added and the solution heated at
60 °C for 17 h. More catalyst 1 (10 mg, 0.012 mmol, 3.2 mol
%) was then added and the solution heated at 60 °C for a
further 48 h. The solvent was then removed under reduced
pressure to leave a dark brown oil. Chromatography on silica
gel with petroleum ether-diethyl ether (4:1) as the eluent
yielded starting material 13 as a colorless oil (43 mg, 30%)
and 14 as a white solid (69 mg, 52%): mp 109-110 °C; Rf 0.40,
Rf 0.13, petroleum ether-diethyl ether (1:1); [R]20 +76.5° (c
D
3.45, CHCl3); δH (300 MHz, CDCl3) 1.95 (1H, t, J 11.5, 3ax-
H), 2.09 (1H, dd, J 4.2, 11.5, 3eq-H), 2.63 (1H, d, J 0.6, OH),
3.39 (3H, s, OMe), 3.52-3.62 (1H, m, overlapping, 4-H), 3.68
(1H, t, overlapping, 6ax-H), 3.68-3.76 (1H, m, overlapping,
5-H), 4.20 (1H, ddd, J 3.5, 9.1, 6eq-H), 4.35 (1H, s, 1-H), 5.23
(1H, dd, J 1.3, 10.9, 8-Hcis), 5.43 (1H, s, 9-H), 5.47 (1H, dd, J

Preparation of Annulated Carbohydrates
J . Org. Chem., Vol. 65, No. 2, 2000 489
1.3, 17.4, 8-Htrans), 6.03 (1H, ddd, J 0.6, 10.9, 17.4, 7-H), 7.32-
7.52 (5H, Ph); δC (75.8 MHz, CDCl3) 39.1 (CH2, C3), 55.8 (CH3,
OMe), 64.7 (CH, C5), 69.8 (CH2, C6), 72.6 (C, C2), 76.0 (CH,
C4), 102.2 (CH, C9), 102.3 (CH, C1), 116.5 (CH2, C8), 126.6
(CH, Ph), 128.8 (CH, Ph), 129.6 (CH, Ph), 137.8 (C, Ph), 139.1
(CH, C7); m/z (FAB) 293 (MH+, 52), found MH+, 293.1389;
C16H20O5 requires 293.1389.
with petroleum ether-diethyl ether (3:1) as the eluent yielded
20 as a colorless oil (70 mg, 65%): Rf 0.16, petroleum ether-
diethyl ether (1:1); [R]20D +51.6° (c 3.64, CHCl3); δH (250 MHz,
CDCl3) 1.85 (1H, t, J 11.8, 3ax-H), 2.17 (1H, dd, J 4.3, 11.8,
3eq-H), 2.35-2.48 (2H, m, 7-H), 2.51 (1H, br s, OH) 3.46 (3H,
s, OMe), 3.51-3.62 (1H, m, 4-H), 3.68-3.82 (2H, overlapping,
5-H and 6eq-H), 4.62 (1H, dd, J 10.7, 16.1, 6ax-H), 4.34 (1H,
s, 1-H), 5.12-5.18 (1H, m, 9-Htrans), 5.21 (1H, br s, 9-Hcis), 5.52
(1H, s, 10-H), 5.87-6.05 (1H, m, 8-H), 7.30-7.56 (5H, Ph); δC
(75.8 MHz, CDCl3) 37.0 (CH2, C3), 40.9 (CH2, C7), 55.4 (CH3,
OMe), 64.3 (CH, C5), 69.4 (CH2, C6), 72.0 (C, C2), 75.5 (CH,
C4), 101.9 (CH, C1), 102.0 (CH, C9), 118.8 (CH2, C9), 126.2
(CH, Ph), 128.3 (CH, Ph), 129.1 (CH, Ph), 132.5 (CH, C8), 137.4
(C, Ph); m/z (FAB) 347 (MH+, 52) (found MH+, 347.1858,
C17H22O5 requires 347.1859).
Meth yl (R)-4,6-O-Ben zylid en e-2-C-p r op en yl-2-O-p r o-
p en yl-3-d eoxy-r-D-glu cop yr a n osid e (21). Sodium hydride
(65 mg, 60% dispersion in mineral oil, 1.63 mmol) was added
portionwise to an ice-cooled solution of alcohol 20 (312 mg,
0.97 mmol) in dry THF (15.0 mL). The resulting mixture was
heated to reflux for 2 h and allowed to cool to room temper-
ature. Allyl bromide (200 µL, 2.30 mmol) and DMPU (200 µL)
were then added, and the mixture was heated to reflux for 4
h, allowed to cool to room temperature, and quenched by
addition of water (5 mL). The resulting mixture was then
extracted into diethyl ether (2 × 25 mL), the combined organic
layers washed with saturated sodium chloride solution (50
mL), dried, and evaporated to leave a yellow oil. Chromatog-
raphy on silica gel with petroleum ether-diethyl ether (3:1)
as the eluent yielded 21 as a colorless oil (250 mg, 72%): Rf
0.46, petroleum ether-diethyl ether (1:1); [R]20D +35.4° (c 4.42,
CHCl3); δH (250 MHz, CDCl3) 2.01-2.18 (2H, m, 3-H), 2.39-
2.62 (2H, m, 7-H), 3.43 (3H, s, OMe), 3.53-3.66 (1H, m, 4-H),
3.73 (1H, t, J 10.4, 6ax-H) 3.78 (1H, dd, J 3.8, 10.4, 5-H), 3.96
(1H, ddt, J 1.5, 5.4, 12.1 CHH, 10-H), 4.10 (1H, ddt, J 1.5, 5.4,
12.1, CHH 10-H), 4.25 (1H, dd, J 3.8, 10.4, 6eq-H), 4.43 (1H,
s, 1-H), 5.14 (1H, ddd, J 1.6, 3.1 9-Hcis), 5.14-5.22 (2H,
overlapping, 9-Htrans and 12-Hcis), 5.27 (1H, ddd, J 1.7, 3.4, 17.2,
12-Htrans), 5.51 (1H, s, 13-H), 5.77-5.99 (2H, overlapping, 8-H
and 11-H), 7.30-7.56 (5H, Ph); δC (62.9 MHz, CDCl3) 33.2
(CH2, C3), 38.7 (CH2, C7), 55.5 (CH3, OMe), 63.8 (CH2, C10)
64.8 (CH, C5), 69.9 (CH2, C6), 76.1 (CH, C4), 77.0 (C, C2), 102.3
(CH, C13), 102.4 (CH, C1), 116.5 (CH2, C12), 119.8 (CH2, C9),
126.7 (CH, Ph), 128.7 (CH, Ph), 129.1 (CH, Ph), 132.7 (CH,
C8),135.7 (CH, C11) 137.9 (C, Ph); m/z (FAB) 307 (MH+, 28)
(found 307.1545, C20H26O5 requires 307.1546).
Meth yl(R)-4,6-O-Ben zyliden e-2-C-eth en yl-2-O-pr open yl-
3-d eoxy-r-D-glu cop yr a n osid e (18). Sodium hydride (169
mg, 60% dispersion in mineral oil, 4.23 mmol) was added
portionwise to an ice-cooled solution of alcohol 17 (1.18 g, 4.00
mmol) in dry THF (30.0 mL). The resulting mixture was
heated to reflux for 2 h and allowed to cool to room temper-
ature. Allyl bromide (710 µL, 8.20 mmol) and DMPU (400 µL)
were then added, and the mixture was heated to reflux for 4
h, allowed to cool to room temperature, and quenched by
addition of water (10 mL). The resulting mixture was then
extracted into diethyl ether (2 × 50 mL), and the combined
organic layers were washed with saturated sodium chloride
solution (50 mL), dried, and evaporated to leave a yellow solid.
Chromatography on silica gel with petroleum ether-diethyl
ether (3:1) as the eluent yielded 18 as a white solid (1.03 g,
77%): mp 146-147 °C; Rf 0.52, petroleum ether-diethyl ether;
[R]20 +75.1° (c 2.48, CHCl3); δH (300 MHz, CDCl3) 2.16 (1H,
D
dd, J 4.6, 11.5, 3eq-H), 2.25 (1H, t, J 11.5, 3ax-H), 3.52 (3H, s,
OMe), 3.67 (1H, ddd, J 4.4, 4.6, 11.5, 4-H), 3.76 (1H, t, J 9.4,
6ax-H), 3.85 (1H, dd, J 4.4, 9.4, 5-H), 3.91 (1H, ddt, J 1.4, 5.5,
11.5, CHH 9-H), 4.02 (1H, ddt, J 1.4, 5.5, 11.5, CHH 9-H), 4.31
(1H, dd, J 4.4, 9.4, 6eq-H), 4.72 (1H, s, 1-H), 5.18 (1H, ddd, J
1.4, 3.6, 10.5, 11-Hcis), 5.32 (1H, ddd, J 1.4, 3.6, 16.5, 11-Htrans),
5.51 (1H, dd, J 1.7, 7.2, 8-Hcis), 5.53 (1H, s, 12-H), 5.54 (1H,
dd, J 1.7, 13.7, 8-Htrans), 5.95 (1H, dd, overlapping, 7-H), 5.87-
6.02 (1H, m, overlapping, 10-H), 7.32-7.59 (5H, Ph); δC (75.8
MHz, CDCl3) 36.7 (CH2, C3), 55.4 (CH3, OMe), 64.0 (CH2, C9),
64.8 (CH, C5), 69.8 (CH2, C6), 76.2 (CH, C4), 77.5 (C, C2), 100.3
(CH, C1), 102.3 (CH, C12), 116.9 (CH2, C8), 118.8 (CH2, C11),
126.6 (CH, Ph), 128.8 (CH, Ph), 129.5 (CH, Ph), 135.5 (CH,
C10), 137.8 (C, Ph), 139.1 (CH, C7); m/z (FAB) 333 (MH+, 100).
Anal. Found: C, 68.43; H, 7.08. C19H24O5 requires C, 68.66;
H, 7.28%.
Meth yl (R)-4,6-O-Ben zylid en e-2(S)-sp ir o(2,5′-2′,5′-d ih y-
d r ofu r a n )-2,3-d id eoxy-r-D-glu cop yr a n osid e (19). Nitrogen
gas was bubbled through a solution of the diene 18 (279 mg,
0.84 mmol) in benzene (10 mL) for 2-3 min. The catalyst 1
(10 mg, 0.012 mmol, 1.4 mol %) was then added and the
solution heated at 60 °C for 36 h. The solvent was then
removed under reduced pressure to leave a dark brown oil.
Chromatography on silica gel with petroleum ether-diethyl
ether (4:1) as the eluent yielded 19 as a white solid (191 mg,
75%): mp 86-87 °C; Rf 0.12, petroleum ether-diethyl ether
Met h yl (R)-4,6-O-Ben zylid en e-2(R)-sp ir o(2,6′-5′,6′-d i-
h yd r o-2′H-p yr a n )-2,3-d id eoxy-r-D-glu cop yr a n osid e (22).
Nitrogen gas was bubbled through a solution of the diene 21
(250 mg, 0.72 mmol) in benzene (10 mL) for 2-3 min. The
catalyst 1 (10 mg, 0.012 mmol, 1.7 mol %) was then added
and the solution heated at 60 °C for 36 h. The solvent was
then removed under reduced pressure to leave a dark brown
oil. Chromatography on silica gel with petroleum ether-
diethyl ether (3:1) as the eluent yielded 22 as a white solid
(186 mg, 73%): mp 69-70 °C; Rf 0.19, petroleum ether-diethyl
(1:1); [R]14 +47.8° (c 5.8, CHCl3); δH (250 MHz; CDCl3) 2.02
D
(1H, dd, J 4.1, 11.3, 3eq-H), 2.35 (1H, t, J 11.3, 3ax-H), 3.48
(3H, s, OMe), 3.63 (1H, ddd, J 4.1, 9.0, 11.3, 4-H), 3.77 (1H, t,
J 9.4, 6ax-H), 3.86 (1H, ddd, overlapping, J 3.8, 9.0, 9.4, 5-H),
4.31 (1H, dd, J 3.8, 9.4, 6eq-H), 4.39 (1H, s, 1-H), 4.63-4.77
(2H, 7-H and 8-H), 5.54 (1H, s, 10-H), 6.02-6.15 (2H, m, 9-H),
7.30-7.57 (5H, Ph); δC (62.9 MHz, CDCl3) 36.5 (CH2, C3), 55.5
(CH3, OMe), 64.3 (CH, C5), 69.9 (CH2, C6), 75.2 (CH2, C9),
77.2 (CH, C4), 89.5 (C, C2), 102.2 (CH, C10), 102.3 (CH, C1),
126.6 (CH, Ph), 128.7 (CH, Ph), 129.2 (CH, C8), 129.5 (CH,
Ph), 130.4 (CH, C7), 137.9 (C, Ph); m/z (FAB) 305 (MH+, 47)
(found MH+, 305.1389; C17H21O5 requires 305.1389). Anal.
Found: C, 66.97; H, 6.66. C17H20O5 requires C, 67.09; H, 6.62%.
Meth yl (R)-4,6-O-Ben zylid en e-2-C-p r op en yl-3-d eoxy-r-
D-glu cop yr a n osid e (20). Allylmagnesium chloride (0.50 mL,
1.00 mmol, 2 M solution in THF) was added dropwise to an
ice-cooled solution of the ketone 16 (105 mg, 0.40 mmol) in
dry THF (10.0 mL). The solution was then heated to reflux
for 4 h, allowed to cool to room temperature, and then
quenched by dropwise addition of saturated ammonium chlo-
ride solution (2 mL). The resulting mixture was then diluted
with water (50 mL) and extracted into diethyl ether (2 × 50
mL), and the combined organic layers were washed with
saturated sodium chloride solution (100 mL), dried, and
evaporated to leave a brown oil. Chromatography on silica gel
ether (1:1); [R]14 +93.5° (c 9.2, CHCl3); δH (400 MHz; CDCl3)
D
2.09-2.17 (2H, m, 3-H), 2.25-2.33 (1Η, m, CHH, 7-H), 2.37-
2.45 (1H, m, CHH, 7-H), 3.51 (3H, s, OMe), 3.66 (1H, dt, J
6.3, 9.8, 4-H), 3.76 (1H, t, J 9.8, 6ax-H), 3.86 (1H, dt, J 4.4,
9.8, 5-H), 4.15-4.27 (2H, m, 10-H), 4.30 (1H, dd, J 4.4, 9.8,
6eq-H), 4.66 (1H, s, 1-H), 5.56 (1H, s, 11-H), 5.76-5.85 (2H,
8-H and 9-H), 7.32-7.55 (5H, Ph); δC (62.9 MHz, CDCl3) 32.6
(CH2, C7), 36.4 (CH2, C3), 55.6 (CH3, OMe), 61.6 (CH2, C10),
64.8 (CH, C5), 69.8 (CH2, C6), 72.5 (C, C2), 76.0 (CH, C4), 100.1
(CH, C11), 102.3 (CH, C1), 122.1 (CH, C8), 126.2 (CH, C9),
126.6 (CH, Ph), 128.7 (CH, Ph), 129.5 (CH, Ph), 137.8 (C, Ph);
m/z (FAB) 319 (MH+, 88) (found MH+, 319.1545; C18H23O5
requires 319.1546). Anal. Found: C, 67.80; H, 6.73. C18H22O5
requires C, 67.91; H, 6.96%.
Meth yl (R)-4,6-O-Ben zylid en e-2-d eoxy-3-C-(1-m eth yl-
eth en yl)-r-D-a llop yr a n osid e (24b). Isopropenylmagnesium
bromide (25.00 mL, 12.50 mmol, 0.5 M solution in THF) was
added dropwise to a cooled (-78 °C) solution of the ketone 23
(921 mg, 3.50 mmol) in dry THF (40.0 mL). The solution was

490 J . Org. Chem., Vol. 65, No. 2, 2000
Holt et al.
then stirred at -50 °C for 4 h, allowed to warm to room
temperature, and then quenched by dropwise addition of
saturated ammonium chloride solution (40 mL). The resulting
mixture was extracted into diethyl ether (2 × 100 mL), and
the combined organic layers were washed with saturated
sodium chloride solution (100 mL), dried, and evaporated to
leave a yellow solid. Chromatography on silica gel with
petroleum ether-diethyl ether (3:1) as the eluent yielded 24b
as a white solid (694 mg, 65%): Rf 0.24, petroleum ether-
diethyl ether (1:1); [R]20D +117.2° (c 7.23, CHCl3); δH (250 MHz,
CDCl3) 1.83 (3H, d, J 0.7, 9-H), 1.95 (1H, dd, J 1.3, 14.9, 2eq-
H), 2.05 (1H, dd, J 3.9, 14.9, 2ax-H), 3.37 (1H, s, OH), 3.39
(3H, s, OMe), 3.78 (1H, t, J 10.0, 6ax-H), 3.78 (1H, dd,
overlapping, 4-H), 4.21 (1H, dt, J 5.1, 14.8, 5-H), 4.34 (1H, dd,
J 5.1, 10.0, 6eq-H), 4.79 (1H, dd, J 1.3, 3.9, 1-H), 4.97 (1H,
quintet, J 0.7, 8-Htrans), 5.24 (1H, d, J 0.7, 8-Hcis), 5.58 (1H, s,
10-H), 7.32-7.55 (5H, Ph); δC (62.9 MHz, CDCl3) 19.7 (CH3,
C9), 40.2 (CH2, C2), 55.8 (CH3, OMe), 60.0 (CH, C5), 69.8 (CH2,
C6), 73.3 (C, C3), 80.9 (CH, C4), 99.1 (CH, C1), 102.2 (CH,
C10), 113.0 (CH2, C8), 126.6 (CH, Ph), 128.5 (CH, Ph), 129.3
(CH, Ph), 137.9 (C, Ph), 146.9 (C, C7); m/z (EI) 329 (MNa+,
100). Anal. Found: C, 66.82; H, 7.07. C17H22O5 requires C,
66.65; H, 7.24%.
4.31 (1H, dt, J 5.3, 8.9, 5-H), 4.42 (1H, dd, J 5.3, 8.9, 6eq-H),
4.71 (1H, d, J 4.7, 1-H), 5.04-5.11 (2H, overlapping, 8-Hcis and
12-Hcis), 5.13 (1H, br s, 8-Htrans), 5.30 (1H, ddd, J 1.8, 3.7, 17.2,
12-Htrans), 5.49 (1H, s, 13-H), 5.89-6.06 (1H, m, 11-H), 7.35-
7.55 (5H, Ph); δC (62.9 MHz, CDCl3) 19.7 (CH3, C9), 39.4 (CH2,
C2), 55.8 (CH3, OMe), 59.4 (CH, C5), 66.9 (CH2, C9), 70.0 (CH2,
C6), 77.7 (C, C3), 83.3 (CH, C4), 98.6 (CH, C1), 102.3 (CH,
C13), 114.9 (CH2 C8), 115.4 (CH2, C12), 126.5 (CH, Ph), 128.6
(CH, Ph), 129.2 (CH, Ph), 136.6 (CH, C11), 138.3 (C, Ph), 145.3
(C, C7); m/z (FAB) 347 (MH+, 48) (found MH+, 347.18585;
C
20H27O5 requires 347.19592).
Met h yl (R)-4,6-O-Ben zylid en e-3(R)-sp ir o(3,5′-2′,5′-d i-
h yd r ofu r a n )-2,3-d id eoxy-r-D-a llop yr a n osid e (26a ). Nitro-
gen gas was bubbled through a solution of the diene 25a (416
mg, 1.25 mmol) in benzene (20 mL) for 2-3 min. The catalyst
1 (11 mg, 0.013 mmol, 1.1 mol %) was then added and the
solution heated at 60 °C for 36 h. The solvent was then
removed under reduced pressure to leave a dark brown oil.
Chromatography on silica gel with petroleum ether-diethyl
ether (3:1) as the eluent yielded 26a as a white solid (210 mg,
51%): mp 155-157 °C; Rf 0.32, petroleum ether-diethyl ether
(1:1); [R]20D +202.1° (c 2.76, CHCl3); δH (300 MHz, CDCl3) 1.98
(1H, dd, J 1.2, 14.9, 2ax-H), 2.05 (1H, dd, J 4.2, 14.9, 2eq-H),
3.35 (3H, s, OMe), 3.46 (1H, dt, J 2.9, 9.4, 4-H), 3.57-3.69 (1H,
m, 5-H), 4.18-4.30 (2H, m, H-6), 4.62-4.76 (3H, overlapping,
9-H and 1-H), 5.42 (1H, dt, J 2.4, 6.0, 8-H), 5.45 (1H, s, 10-H),
5.95 (1H, dt, J 1.5, 6.0, 7-H), 7.32-7.55 (5H, Ph); δC (62.9 MHz,
CDCl3) 40.3 (CH2, C2), 56.0 (CH3, OMe), 60.0 (CH, C5), 69.8
(CH2, C6), 77.4 (CH2, C9), 81.4 (CH, C4), 87.2 (C, C3), 98.5
(CH, C1), 102.1 (CH, C10), 126.6 (CH, Ph), 128.5 (CH, Ph),
128.9 (CH, C7), 129.2 (CH, Ph), 130.3 (CH, C8), 138.3 (C, Ph);
m/z (EI) 327.5 (MNa+, 100).
Met h yl (R)-4,6-O-Ben zylid en e-3(R)-sp ir o(3,5′-2′,5′-d i-
h yd r o-4′-m et h yl-fu r a n )-2,3-d id eoxy-r-D-a llop yr a n osid e
(26b). Nitrogen gas was bubbled through a solution of the
diene 25b (90 mg, 0.26 mmol) in benzene (8 mL) for 2-3 min.
The catalyst 1 (10 mg, 0.012 mmol, 4.6 mol %) was then added
and the solution heated at 60 °C for 36 h. The solvent was
then removed under reduced pressure to leave a dark brown
oil. Chromatography on silica gel with petroleum ether-
diethyl ether (3:1) as the eluent yielded starting material 25b
as a colorless oil (46 mg, 51%) and 26b as a white solid (29
mg, 35%): mp 143-144 °C; Rf 0.35, petroleum ether-diethyl
ether (1:1); [R]20D +137.9° (c 3.84, CHCl3); δH (250 MHz, CDCl3)
1.71 (3H, dd, J 2.2, 3.8, 10-H), 1.93 (1H, dd, J 0.7, 14.6, 2eq-
H), 2.14 (1H, dd, J 4.7, 14.6, 2ax-H), 3.42 (3H, s, OMe), 3.53-
3.61 (1H, m, 5-H), 4.25-4.40 (2H, m, 6-H), 4.57-4.71 (2H, m,
9-H), 4.78 (1h, d, J 4.7, 1-H), 5.51 (1H, s, 11-H), 5.64 (1H, dd,
J 1.3.1, 8-H), 7.30-7.55 (5H, Ph); δC (100 MHz, CDCl3) 12.3
(CH3, C10), 38.2 (CH2, C2), 56.1 (CH3, OMe), 59.9 (CH, C5),
69.9 (CH2, C6), 75.2 (CH2, C9), 79.2 (CH, C4), 87.9 (C, C3),
98.8 (CH, C1), 102.2 (CH, C11), 124.4 (CH, C8), 126.6 (CH,
Ph), 128.5 (CH, Ph), 129.2 (CH, Ph), 135.1 (C, C7), 138.4 (C,
Ph); m/z (EI) 341 (MNa+, 100). Anal. Found: C, 67.83; H, 7.07.
Meth yl (R)-4,6-O-Ben zylid en e-2-d eoxy-3-C-eth en yl-3-
O-p r op en yl-r-D-a llop yr a n osid e (25a ). Sodium hydride (250
mg, 80% dispersion in mineral oil, 8.33 mmol) was added
portoinwise to an ice-cooled solution of alcohol 24a (1.22 g,
4.18 mmol) in dry THF (25.0 mL). The resulting mixture was
heated to reflux for 2 h and allowed to cool to room temper-
ature. Allyl bromide (680 µL, 7.86 mmol) and DMPU (200 µL)
were then added, and the mixture was heated to reflux for 4
h, allowed to cool to room temperature, and quenched by
addition of water (15 mL). The resulting mixture was then
extracted into diethyl ether (2 × 75 mL), and the combined
organic layers were washed with saturated sodium chloride
solution (150 mL), dried, and evaporated to leave a brown oil.
Chromatography on silica gel with petroleum ether-diethyl
ether (4:1) as the eluent yielded 25a as a colorless oil (1.11 g,
80%): Rf 0.52, petroleum ether-diethyl ether (1:1); [R]20
D
+79.9° (c 5.6, CHCl3); δH (250 MHz, CDCl3) 1.77 (1H, dd, J
4.6, 14.8, 2ax-H), 2.17 (1H, d, J 14.8, 2eq-H), 3.28 (3H, s, OMe),
3.52 (1H, d, J 9.2, 4-H), 3.61 (1H, t, J 10.3, 6ax-H), 3.89-4.05
(2H, m, 9-H), 4.22 (1H, dd, J 5.4, 10.3, 6eq-H), 4.34 (1H, ddd,
J 5.4, 9.2, 10.3, 5-H), 4.64 (1H, d, J 4.6, 1-H), 5.00 (1H, ddd, J
1.9, 3.5, 8.8, 11-Hcis), 5.16 (1H, dd, J 0.9, 3.8, 8-Hcis), 5.21 (1H,
overlapping, 8-Htrans), 5.25 (1H, overlapping, 11-Htrans), 5.41
(1H, s, 12-H), 5.79-5.97 (2H, overlapping, 7-H and 10-H),
7.30-7.57 (5H, Ph); δC (62.9 MHz, CDCl3) 36.9 (CH2, C2), 55.7
(CH3, OMe), 59.3 (CH, C5), 65.7 (CH2, C9), 69.9 (CH2, C6),
75.0 (C, C3), 83.8 (CH, C4), 98.5 (CH, C1), 102.5 (CH, C12),
115.3 (CH2, C8), 117.0 (CH2, C11), 126.7 (CH, Ph), 128.6 (CH,
Ph), 129.3 (CH, Ph), 136.6 (C, C7), 138.3 (C, Ph), 139.0 (CH,
C10); m/z (EI) 333 (MH+, 48) (found 333.17029, C19H24O5
requires 333.17020).
Meth yl (R)-4,6-O-Ben zylid en e-2-d eoxy-3-C-(1-m eth yl-
eth en yl)-3-O-p r op en yl-r-D-a llop yr a n osid e (25b). Sodium
hydride (240 mg, 80% dispersion in mineral oil, 8.00 mmol)
was added portionwise to an ice-cooled solution of alcohol 24b
(610 mg, 2.00 mmol) in dry THF (30.0 mL). The resulting
mixture was heated to reflux for 2 h and allowed to cool to
room temperature. Allyl bromide (344 µL, 4.00 mmol) and
DMPU (200 µL) were then added, and the mixture was heated
to reflux for 4 h, allowed to cool to room temperature, and
quenched by addition of water (10 mL). The resulting mixture
was then extracted into diethyl ether (2 × 50 mL), and the
combined organic layers were washed with saturated sodium
chloride solution (100 mL), dried, and evaporated to leave a
yellow oil. Chromatography on silica gel with petroleum
ether-diethyl ether (3:1) as the eluent yielded 25b as a
colorless oil (650 mg, 94%): Rf 0.45, petroleum ether-diethyl
ether (1:1); [R]20D +77.0° (c 9.64, CHCl3); δH (250 MHz, CDCl3)
1.80 (3H, d, J 0.7, 9-H), 1.86 (1H, dd, J 4.7, 14.8, 2ax-H), 2.23
(1H, dd, J 0.7, 14.8, 2eq-H), 3.37 (3H, s, OMe), 3.71 (1H, t, J
8.9, 6ax-H), 3.87 (1H, d, J 8.5, 4-H), 4.01 (1H, ddt, J 1.6, 5.3,
13.1, CHH 10-H), 4.18 (1H, ddt, J 1.6, 4.9, 13.1, CHH, 10-H),
C
18H22O5 requires C, 67.91; H, 6.96%.
Meth yl (R)-4,6-O-Ben zylid en e-3-d eoxy-3-C-p r op en yl-r-
D-glu cop yr a n osid e (27a ). To a magnetically stirred suspen-
sion of LiAlH4 (8 mg, 0.21 mmol) in THF (8 mL) cooled to 0 °C
was added a solution of the ketone 2a (100 mg, 0.32 mmol) in
THF (2 mL). The reaction mixture was then allowed to warm
to room temperature and refluxed for 3 h. It was then cooled
to 0 ˚C, and to it were added sequentially water (10 µL), 15%
aqueous NaOH (10 µL), and water 30 µL). The resulting
mixture was then stirred for 30 min. The white grannular
precipitate was then filtered off, and the filtrate was dried
(Na2SO4) and evaporated to afford the alcohol 27a (90 mg,
90%): mp 139 °C; [R]20 +71.0° (c 0.52, CHCl3); δH (250 MHz,
D
CDCl3) 1.92 (1H, d, J 11.0, OH), 2.02-2.18 (1H, m, 3-H), 2.42-
2.58 (2H, m, 7-H), 3.32 (1H, dd, J 9.0, 10.8, 4-H), 3.46 (3H, s,
OMe), 3.54 (1H, dt, J 3.8, 11.0, 2-H), 3.67 (1H, t, J 10.0, 6ax-
H), 3.76 (1H, overlapping, ddd, J 4.0, 9.0, 10.0, 5-H), 4.27 (1H,
dd, J 4.0, 10.0, 6eq-H), 4.68 (1H, d, J 3.8, 1-H), 5.05-5.23 (2H,
m, 9-H), 5.48 (1H, s, 10-H), 5.84-6.06 (1H, m, 8-H), 7.29-
7.57 (5H, Ph); δC (62.9 MHz, CDCl3) 30.3 (CH2, C7), 42.5 (CH,
C3), 55.7 (CH3, OMe), 64.1 (CH, C5), 69.7 (CH2, C6), 70.2 (CH,

Preparation of Annulated Carbohydrates
J . Org. Chem., Vol. 65, No. 2, 2000 491
C2), 78.6 (CH, C4), 99.8 (CH, C1), 101.8 (CH, C10), 118.2 (CH2,
C9), 126.5 (CH, Ph), 128.7 (CH, Ph), 129.3 (CH, Ph), 135.1 (CH,
C8), 138.0 (C, Ph); m/z (FAB) 307 (MH+, 54) (found MH+,
307.1546; C17H23O5 requires 307.1546). Anal. Found: C, 65.94;
H, 7.12. C17H22O5 requires C, 66.65; H, 7.24%.
79%: mp 66 °C; [R]21 +40.6° (c 0.80, CHCl3); δH (300 MHz,
D
CDCl3) 1.79 (3H, s, C8-Me), 2.34 (1H, m), 2.48 (2H, m, 10-H),
3.33 (2H, m), 3.44 (3H, s, OMe), 3.66 (1H, t, J 10.1, 6ax-H),
3.80 (1H, m), 3.91 (1H, d, J 12.0, CHH, H-7), 3.96 (1H, d, J
12.0 CHH, H-7), 4.26 (1H, dd, J 4.6, 10.1, 6eq-H), 4.80 (1H, d,
J 3.3, 1-H), 4.91-5.14 (4H, 9-H and 12-H), 5.48 (1H, s, 13-H),
5.89 (1H, m, 11-H), 7.34-7.49 (5H, Ph); δC (75 MHz, CDCl3)
19.9 (CH3, C8-Me), 29.8 (CH2, C10), 40.0 (CH, C3), 55.5 (CH3,
OMe), 63.8 (CH, C5), 69.7 (CH2, C6), 74.9 (CH2, C7), 77.2 (CH,
C2), 78.7 (CH, C4), 97.9 (CH, C1), 101.8 (CH, C13), 113.5 (CH2,
C9), 118.1 (CH2, C12), 126.4 (CH, Ph), 128.6 (CH, Ph), 129.2
(CH, Ph), 134.9 (CH, C8), 138.0 (C, Ph), 142.5 (CH, C11). Anal.
Found: C, 69.84; H, 7.53. C21H28O5 requires C, 69.98; H, 7.83%.
Meth yl (R)-4,6-O-Ben zyliden e-2-O-p en t-4-en yl-3-d eoxy-
3-C-p r op en yl-r-D-glu cop yr a n osid e (30). Prepared by the
Meth yl (R)-4,6-O-Ben zylid en e-2-C-m eth yl-3-d eoxy-3-C-
p r op en yl-r-D-glu cop yr a n osid e (27b). To an ice-cold solu-
tion of the ketone 2a (100 mg, 0.33 mmol) in THF (5 mL) was
added MeLi (500 µL, 0.66 mmol, 1.3 M in diethyl ether) with
stirring. The reaction mixture was then allowed to warm to
room temperature and stirred for 6 h. It was then quenched
by addition of saturated aqueous ammonium chloride solution.
The organic layer was separated, and the aqueous layer was
extracted with diethyl ether (3 × 10 mL). The combined
organic extracts were dried (Na2SO4) and concentrated to yield
the carbinol 27b (90 mg, 86%): mp 143 °C; [R]21 +38.4° (c
procedure described for 28a . Yield: 83%: mp 84 °C; [R]21
D
D
0.29, CHCl3); δH (300 MHz, CDCl3) 1.25 (3H, s, C2-Me), 1.59
(1H, br s, OH), 2.13 (1H, m, 3-H), 2.34-2.50 (2H, m, 7-H), 3.38
(1H, dd, J 9.0, 12.0, 4-H), 3.44 (3H, s, OMe), 3.54-3.85 (2H,
5-H and 6ax-H), 4.25 (1H, dd, J 6.0, 15.0, 6eq-H), 4.29 (1H, s,
1-H), 4.94 (1H, d, J 9.0, 9-Hcis), 5.05 (1H, d, J 18.0, 9-Htrans),
5.49 (1H, s, 10-H), 6.02 (1H, m, 8-H), 7.34-7.49 (5H, Ph); δC
(75 MHz, CDCl3) 20.2 (CH3, C2-Me), 31.5 (CH2, C7), 46.2 (CH,
C3), 55.7 (CH3, OMe), 65.0 (CH, C5), 69.7 (CH2, C6), 73.5 (C,
C2), 81.4 (CH, C4), 101.8 (CH, C1), 104.6 (CH, C10), 115.2
(CH2, C9), 126.4 (CH, Ph), 128.6 (CH, Ph), 129.2 (CH, Ph),
138.0 (C, Ph), 139.3 (CH, C8). Anal. Found: C, 67.68; H, 7.48.
+45.0° (c 0.50, CHCl3); δH (300 MHz, CDCl3) 1.72 (1H, m), 2.16
(2H, m), 2.28 (1H, m), 2.47 (2H, m), 3.21-3.44 (4H, m), 3.45
(3H, s, OMe), 3.66 (2H, m), 3.79 (1H, dt, J 4.6, 10.0, 5-H), 4.26
(1H, dd, J 4.6, 10.0, 6eq-H), 4.81 (1H, d, J 3.3, 1-H), 4.95-
5.13 (4H, 11-H and 14-H), 5.48 (1H, s, 15-H), 5.84 (2H, 10-H
and 13-H), 7.33-7.50 (5H, Ph); δC (75 MHz, CDCl3) 29.2 (CH2,
C8), 29.4 (CH2, C12), 30.2 (CH2, C9), 39.6 (CH, C3), 55.1 (CH3,
OMe), 63.5 (CH, C5), 69.4 (CH2, C7), 69.5 (CH2, C6), 77.2 (CH,
C2), 78.3 (CH, C4), 97.4 (CH, C1), 101.4 (CH, C15), 114.9 (CH2,
C11), 117.7 (CH2, C14), 126.0 (CH, Ph), 128.2 (CH, Ph), 128.9
(CH, Ph), 134.5 (CH, C10), 137.6 (C, Ph), 138.1 (CH, C13).
Anal. Found: C, 70.28; H, 8.91. C22H30O5 requires C, 70.56;
H, 8.07%.
C
18H24O5 requires C, 67.48; H, 7.55%.
Met h yl (R)-4,6-O-Ben zylid en e-2-O-p r op en yl-3-d eoxy-
3-C-p r op en yl-r-D-glu cop yr a n osid e (28a ). To a suspension
of NaH (40 mg, 40% suspension in mineral oil, 0.67 mmol,
prewashed with petroleum ether to free it from mineral oil)
in dry THF (4.0 mL) was added a solution of the alcohol 27a
(80 mg, 0.26 mmol) in dry THF (2.0 mL). The resulting mixture
was refluxed for 2 h and cooled to room temperature, and then
allyl bromide (63 mg, 0.52 mmol) and HMPA (150 µL) were
added. The mixture was again refluxed for 2 h, cooled to room
temperature, and quenched by addition of cold water. The
mixture was then extracted with diethyl ether (3 × 10 mL).
The combined organic extracts were then washed with satu-
rated sodium chloride solution (30 mL), dried (Na2SO4), and
concentrated. Chromatography on silica gel with petroleum
ether-diethyl ether (4:1) as the eluent yielded ether 28a (70
Met h yl (R)-4,6-O-Ben zylid en e-2-O-3-C-(b u t -2-en e-1,4-
d iyl)-3-d eoxy-r-D-glu cop yr a n osid e (29a ). Nitrogen gas was
bubbled through a solution of the diene 28a (50 mg, 0.16 mmol)
in benzene (5 mL) for 2-3 min. The catalyst 1 (5 mg, 0.006
mmol, 3.9 mol %) was then added and the solution heated at
60 °C for 6 h. The solvent was then removed under reduced
pressure to leave a dark brown oil. Chromatography on silica
gel with petroleum ether-diethyl ether (3:1) as the eluent
yielded 29a as a white solid (40 mg, 87%): mp 99 °C; [R]21
D
+50.0° (c 0.35, CHCl3); δH (300 MHz, CDCl3) 2.06 (1H, m,
CHH, 10-H), 2.37 (1H, dq, J 2.7, 10.5, 3-H), 2.83 (1H, dd, J
6.9, 15.0, CHH, 10-H), 3.22 (1H, t, J 9.6, 4-H), 3.46 (3H, s,
OMe), 3.56 (1H, dd, J 3.6, 10.5, 2-H), 3.68 (1H, t, J 10.2, 6ax-
H), 3.84 (1H, dt, J 4.8, 10.2, 5-H), 4.04 (1H, br d, J 14.0, CHH,
7-H), 4.27 (1H, dd, J 4.5, 10.2, 6eq-H), 4.46 (1H, dd, J 4.2,
14.0, CHH, 7-H), 4.73 (1H, d, J 3.6, 1-H), 5.49 (1H, s, 11-H),
5.88 (2H, 8-H and 9-H), 7.36-7.51 (5H, Ph); δC (75 MHz,
CDCl3) 28.9 (CH2, C10), 39.1 (CH, C3), 55.0 (CH3, OMe), 63.2
(CH, C5), 66.9 (CH2, C7), 69.3 (CH2, C6), 80.2 (CH, C2), 83.0
(CH, C4), 99.5 (CH, C1), 101.7 (CH, C11), 126.0 (CH, Ph), 128.2
(CH, Ph), 128.9 (CH, Ph), 130.9 (CH, C8), 131.4 (CH, C9), 137.4
(C, Ph). Anal. Found: C, 67.20; H, 6.90. C18H22O5 requires C,
67.91; H, 6.96%.
mg, 78%): mp 72 °C; [R]21 +31.5° (c 0.10, CHCl3); δH (300
D
MHz, CDCl3) 2.34 (1H, m), 2.48 (2H, m), 3.36 (2H, m), 3.46
(3H, s, OMe), 3.67 (1H, t, J 10.0, 6ax-H), 3.80 (1H, m), 4.09
(2H, m), 4.27 (1H, dd, J 4.5, 10.0, 6eq-H), 4.81 (1H, d, J 3.3,
1-H), 5.09-5.34 (4H, 9-H and 12-H), 5.49 (1H, s, 13-H), 5.91
(2H, 8-H and 11-H), 7.36-7.51 (5H, Ph); δC (75 MHz, CDCl3)
29.5 (CH2, C10), 39.7 (CH, C3), 55.3 (CH3, OMe), 63.5 (CH,
C5), 69.5 (CH2, C6), 71.5 (CH2, C7), 76.6 (CH, C2), 78.4 (CH,
C4), 97.6 (CH, C1), 101.5 (CH, C13), 117.7 (CH2, C9), 117.8
(CH2, C12), 126.1 (CH, Ph), 128.3 (CH, Ph), 129.0 (CH, Ph),
134.6 (CH, C8), 134.8 (CH, C11), 138.0 (C, Ph). Anal. Found:
C, 69.43; H, 7.52. C20H26O5 requires C, 69.34; H, 7.56%.
Meth yl (R)-4,6-O-Ben zylid en e-2-C-m eth yl-2-O-p r op e-
n yl-3-deoxy-3-C-pr open yl-r-D-glu copyr an oside (28b). Pre-
pared by the procedure described for 28a . Yield 87%: mp 125
Met h yl (R)-4,6-O-Ben zylid en e-2-m et h yl-2-O-3-C-(b u t -
2-en e-1,4-d iyl)-3-d eoxy-r-D-glu cop yr a n osid e (29b). Pre-
pared by the procedure described for 29a . Yield 87%: mp 154
°C; [R]21 +60.2° (c 0.40, CHCl3); δH (300 MHz, CDCl3) 1.34
D
(3H, s, C2-Me), 2.24 (1H, m, CHH, 10-H), 2.69 (1H, br d, J
18.0, CHH, 10-H), 2.90 (1H, dt, J 2.4, 11.7, 3-H), 3.40 (1H, t,
J 9.0, 4-H), 3.48 (3H, s, OMe), 3.75 (1H, t, J 10.0, 6ax-H), 3.87
(1H, dt, J 4.5, 10.0, 5-H), 4.05 (1H, br d, J 15.6, CHH, 7-H),
4.29 (1H, dd, J 4.5, 10.0, 6eq-H), 4.39 (1H, s, 1-H), 4.74 (1H,
dd, J 2.4, 15.6, CHH, 7-H), 5.52 (1H, s, 11-H), 5.68 (2H, 8-H
and 9-H), 7.37-7.52 (5H, Ph); δC (75 MHz, CDCl3) 19.6 (CH3,
C2-Me), 25.7 (CH2, C10), 40.7 (CH, C3), 55.1 (CH3, OMe), 62.9
(CH2, C7), 64.5 (CH, C5), 69.4 (CH2, C6), 77.5 (C, C2), 79.5
(CH, C4), 101.7 (CH, C1), 105.3 (CH, C11), 126.0 (CH, Ph),
128.2 (CH, Ph), 128.9 (CH, Ph), 129.1 (CH, C8), 129.8 (CH,
C9), 137.5 (C, Ph). Anal. Found: C, 68.65; H, 7.08. C19H24O5
requires C, 68.66; H, 7.28%.
°C; [R]21 +64.2° (c 0.22, CHCl3); δH (300 MHz, CDCl3) 1.28
D
(3H, s, C2-Me), 2.30 (1H, dd, J 6.4, 13.2), 2.43 (2H, m, 10-H),
3.44 (3H, s, OMe), 3.49 (1H, t, J 10.2, 4-H), 3.69-3.96 (3H,
m), 4.16 (1H, dd, J 5.0, 12.5), 4.25 (1H, dd, J 4.3, 9.8, 6eq-H),
4.44 (1H, s, 1-H), 4.89-5.31 (4H, 9-H and 12-H), 5.52 (1H, s,
13-H), 5.95 (2H, 8-H and 11-H), 7.33-7.50 (5H, Ph); δC (75
MHz, CDCl3) 18.6 (CH3, C2-Me), 31.5 (CH2, C10), 42.5 (CH,
C3), 54.9 (CH3, OMe), 63.5 (CH2, C7), 64.4 (CH, C5), 69.5 (CH2,
C6), 77.0 (C, C2), 81.7 (CH, C4), 101.6 (CH, C1), 103.4 (CH,
C13), 114.7 (CH2, C9), 115.7 (CH2, C12), 126.1 (CH, Ph), 128.3
(CH, Ph), 128.9 (CH, Ph), 135.7 (CH, C8), 138.0 (C, Ph), 138.8
(CH, C11). Anal. Found: C, 69.75; H, 7.64. C21H28O5 requires
C, 69.98; H, 7.83%.
Met h yl (R)-4,6-O-Ben zylid en e-2-O-3-C-(2-m et h yl-b u t -
2-en e-1,4-d iyl)-3-d eoxy-r-D-glu cop yr a n osid e (29c). Pre-
pared by the procedure described for 29a . Yield: 87%: mp 104
Meth yl (R)-4,6-O-Ben zylid en e-2-O-(2-m eth ylp r op en yl)-
3-d eoxy-3-C-p r op en yl-r-D-glu cop yr a n osid e (28c). Pre-
pared by the procedure described for 28a . Ether 28c was
obtained using methallyl chloride as alkylating agent. Yield:
°C; [R]21 +61.5° (c 1.10, CHCl3); δH (300 MHz, CDCl3) 1.69
D
(3H, s, C8-Me), 1.99 (1H, m, CHH, 10-H), 2.39 (1H, dq, J 2.2,
10.5, 3-H), 2.71 (1H, ddd, J 2.0, 8.0, 15.7, CHH, 10-H), 3.18

492 J . Org. Chem., Vol. 65, No. 2, 2000
Holt et al.
(1H, t, J 10.0, 4-H), 3.45 (3H, s, OMe), 3.53 (1H, dd, J 3.5,
10.5, 2-H), 3.66 (1H, t, J 10.5, 6ax-H), 3.82 (1H, dt, J 4.7, 10.5,
5-H), 4.04 (1H, d, J 14.8, CHH, 7-H), 4.23-4.33 (2H, 6eq-H
and CHH, 7-H), 4.71 (1H, d, J 3.5, 1-H), 5.47 (1H, s, 11-H),
5.56-5.60 (1H, m, 9-H), 7.35-7.50 (5H, Ph); δC (75 MHz,
CDCl3) 22.8 (CH3, C8-Me), 28.2 (CH2, C10), 39.3 (CH, C3), 55.0
(CH3, OMe), 63.2 (CH, C5), 69.2 (CH2, C6), 71.6 (CH2, C7),
80.0 (CH, C2), 83.4 (CH, C4), 99.3 (CH, C1), 101.6 (CH, C11),
124.9 (CH, C9), 126.0 (CH, Ph), 128.1 (CH, Ph), 128.9 (CH,
Ph), 137.4 (C, Ph), 138.9 (C, C8). Anal. Found: C, 68.75; H,
7.43. C19H24O5 requires C, 68.66; H, 7.28%.
(1R,1′R,2′S)-1′-Meth yl-2′-h yd r oxy-1-cycloh exa n -3′-on e-
2-p r op en yl-1-ben zoa te (35). Zinc powder (60 g) was acti-
vated by washing with 2 M hydrochloric acid (6 × 30 mL),
water (5 × 35 mL), 10% w/v aqueous potassium carbonate
solution (30 mL), water (4 × 40 mL), 2-propanol (2 × 35 mL),
and diethyl ether (3 × 35 mL). The bromo compound 33 (214
mg, 0.54 mmol) was heated to reflux with the activated zinc
(4.56 g, 0.070 mol) in 2-propanol:water (16:1.6 mL) for 48 h.
The zinc was removed by filtration and washed with diethyl
ether (2 × 50 mL), and the combined organic layers were
washed with water (100 mL) and saturated sodium chloride
solution (100 mL), dried, and evaporated to leave a colorless
oil. Chromatography on silica gel with petroleum ether-
diethyl ether (3:1) as the eluent yielded 35 as a colorless oil
(83 mg, 54%): Rf 0.28, petroleum ether-diethyl ether (1:1);
Meth yl (R)-4,6-O-Ben zylid en e-2-O-3-C-(h ex-4-en e-1,6-
d iyl)-3-d eoxy-r-D-glu cop yr a n osid e (31). Prepared by the
procedure described for 29a . Ether 31 was obtained in 74%
yield with recovery of the diene 30 (17%) after 14 h at 60 °C:
mp 93 °C; [R]21 +49.3° (c 0.20, CHCl3); δH (300 MHz, CDCl3)
[R]20 +57.3° (c 1.8, CHCl3); δH (400 MHz, CDCl3) 0.86 (3H, s,
D
D
1.62 (1H, m), 1.84 (1H, m), 2.03 (1H, m), 2.35 (2H, m), 2.55
(1H, m), 2.68 (1H, m), 3.28 (2H, m), 3.43 (1H, m), 3.46 (3H, s,
overlapping, OMe), 3.72 (2H, m), 4.01 (1H, quin, J 5.4), 4.24
(1H, dd, J 3.8, 9.2, 6eq-H), 4.72 (1H, d, J 3.0, 1-H), 5.51 (1H,
s, 13-H), 5.63 (2H, 10-H and 11-H), 7.35-7.52 (5H, Ph); δC
(75 MHz, CDCl3) 21.6 (CH2, C8), 21.9 (CH2, C12), 27.5
(CH2, C9), 38.9 (CH, C3), 55.2 (CH3, OMe), 64.3 (CH, C5), 69.4
(CH2, C7), 69.5 (CH2, C6), 78.9 (CH, C2), 80.5 (CH, C4), 98.4
(CH, C1), 101.6 (CH, C13), 126.1 (CH, C10), 126.2 (CH, Ph),
128.2 (CH, Ph), 129.0 (CH, Ph), 132.5 (CH, C11), 137.6 (C, Ph).
Anal. Found: C, 69.14; H, 7.64. C20H26O5 requires C, 69.34;
H, 7.56%.
Meth yl (R)-4,6-O-Ben zylid en e-2,3-C-(p r op a n e-1,3-d iyl)-
3-d eoxy-3-C-m eth yl-r-D-glu cop yr a n osid e (32). A solution
of the olefin 5b (100 mg, 0.31 mmol) in dry ethanol (5.0 mL)
was degassed several times with nitrogen. The catalyst (pal-
ladium, 5% on carbon, 10 mg) was then added, and the mixture
was degassed several times with hydrogen and then allowed
to stir under a positive pressure of hydrogen (balloon) for 17
h. At this point the mixture was filtered through a plug of
Celite under reduced pressure, and the residue was washed
with ethanol (3 × 5 mL). The filtrate was then concentrated
under reduced pressure to yield 32 as a pale yellow oil (100
mg, 99%): δH (250 MHz, CDCl3) 1.20 (3H, s, C3-Me), 1.60-
2.24 (6H, 7-H, 8-H and 9-H), 2.70 (1H, br s, OH), 3.37 (1H, d,
J 9.7, 4-H), 3.43 (3H, s, OMe), 3.69 (1H, t, J 10.2, 6ax-H), 3.92
(1H, ddd, J 5.0, 9.7, 10.2, 5-H), 4.31 (1H, dd, J 5.0, 10.2, 6eq-
H), 4.51 (1H, s, 1-H), 5.52 (1H, s, 10-H), 7.31-7.57 (5H, Ph);
δC (62.9 MHz, CDCl3) 14.3 (CH3, C3-Me), 19.9 (CH2, C9), 35.0
(CH2, C8), 35.9 (CH2, C7), 49.4 (C, C3), 56.1 (CH3, OMe), 59.6
(CH, C5), 70.0 (CH2, C6), 80.4 (CH, C4), 81.3 (C, C2), 101.9
(CH, C10), 102.1 (CH, C1), 126.6 (CH, Ph), 128.6 (CH, Ph),
129.3 (CH, Ph), 138.3 (C, Ph); m/z (FAB) 321 (MH+, 6) (found
MH+, 321.1702; C18H25O5 requires 321.1702).
Meth yl (R)-4-O-Ben zoyl-6-C-br om o-2,3-C-(p r op a n e-1,3-
d iyl)-3,6-d id eoxy-r-D-glu cop yr a n osid e (33). Barium car-
bonate (247 mg, 1.25 mmol) and N-bromosuccininmide (61 mg,
0.34 mmol) were added sequentially to a solution of 32 (100
mg, 0.31 mmol) in dry chloroform (10 mL). The mixture was
then heated to reflux for 17 h. The mixture was allowed to
cool to room temperature, barium carbonate removed by
filtration, and the residue washed with dichloromethane (2 ×
10 mL). The filtrate was then washed with water (2 × 30 mL),
dried, and concentrated under reduced pressure to leave a
yellow oil. Chromatography on silica gel with petroleum
ether-diethyl ether (3:1) as the eluent yielded 33 as a colorless
oil (93 mg, 75%): Rf 0.32, petroleum ether-diethyl ether (1:
1); [R]20D +78.6° (c 4.3, CHCl3); δH (250 MHz, CDCl3) 1.26 (3H,
s, C3-Me), 1.53-1.97 (5H, CHH, 7-H, 8-H and 9-H), 2.15-2.38
(1H, m, CHH, 7-H), 2.64 (1H, d, J 2.3, OH), 3.33-3.49 (2H,
m, 6-H), 3.52 (3H, s, OMe), 4.16 (1H, ddd, J 2.9, 7.8, 10.3, 5-H),
4.61 (1H, s, 1-H), 5.04 (1H, d, J 10.3, 4-H), 7.47 (2H, m-Ph),
7.61 (1H, p-Ph), 8.05 (2H, o-Ph); δC (62.9 MHz, CDCl3) 14.6
(CH3, C3-Me), 19.7 (CH2, C9), 33.2 (CH2, C6), 35.5 (CH2, C8),
35.9 (CH2, C7), 51.0 (C, C3), 56.3 (CH3, OMe), 67.4 (CH, C5),
72.6 (CH, C4), 81.1 (C, C2), 101.4 (CH, C1), 129.0 (CH, Ph),
129.8 (C, Ph), 130.2 (CH, Ph), 133.9 (CH, Ph), 166.3 (CO, OBz);
m/z (FAB) 398/400 (M+, 1), 105 (PhCO+, 96) (found M+,
398.0729; C18H23O5Br requires 398.0729).
C3-Me), 1.76-1.91 (2H, 4R-H and 5R-H), 2.03-2.15 (1H, m,
5â-H), 2.15-2.23 (1H, m, 4â-H), 2.35-2.47 (1H, m, 6â-H),
2.52-2.60 (1H, m, 6R-H), 3.56 (1H, d, J 4.1, OH), 4.25 (1H,
dd, J 1.2, 4.1, 2-H), 5.34 (1H, dt, J 1.3, 10.6, H-9cis), 5.41 (1H,
dt, J 1.4, 17.1, H-9trans), 5.67 (1H, d, J 6.7, 7-H), 5.94 (1H, ddd,
J 6.7, 10.6, 17.1, 8-H), 7.39 (2H, m-Ph), 7.61 (1H, p-Ph), 8.13
(2H, o-Ph); δC (100.6 MHz, CDCl3) 15.3 (CH3, C3-Me), 21.7
(CH2, C5), 29.1 (CH2, C4), 39.1 (CH2, C6), 48.0 (C, C3), 77.9
(CH, C2), 78.1 (CH, C7), 119.7 (CH2, C9), 128.9 (CH, Ph), 130.0
(CH, Ph), 130.7 (C, Ph), 132.6 (CH, C8), 133.4 (CH, Ph), 165.5
(CO, OBz), 211.6 (C, C1); m/z (FAB) 289 (MH+, 56), 311 (MNa+,
45) (found MH+, 289.1440; C17H21O4 requires 289.1440).
Met h yl (R)-4-O-Ben zoyl-6-C-b r om o-2,3-C-(b u t -2-en e-
1,4-d iyl)-3,6-d id eoxy-r-D-glu cop yr a n osid e (38). Barium
carbonate (248 mg, 1.26 mmol) and N-bromosuccininmide (61
mg, 0.34 mmol) were added sequentially to a solution of 8 (100
mg, 0.31 mmol) in dry chloroform (10 mL). The mixture was
then heated to reflux for 16 h. The mixture was allowed to
cool to room temperature, barium carbonate removed by
filtration, and the residue washed with diethyl ether (2 × 25
mL). The filtrate was concentrated under reduced pressure to
leave a yellow oil. Chromatography on silica gel with dichlo-
romethane-diethyl ether (97.5:2.5) as the eluent yielded start-
ing material 8 as a white solid (21 mg, 21%) and 38 as a
colorless oil (48 mg, 38%): Rf 0.50, dichloromethane-diethyl
ether (9:1); [R]20 +66.7° (c 2.8, CHCl3); δH (250 MHz, CDCl3)
D
1.83-2.68 (6H, 3-H, 7-H, 10-H and OH), 3.39-3.52 (2H, m,
6-H), 3.57 (3H, s, OMe), 4.02 (1H, ddd, J 2.5, 7.9, 10.2, 5-H),
4.43 (1H, s, 1-H), 5.04 (1H, t, J 10.2, 4-H), 5.57-5.76 (2H, 8-H
and 9-H), 7.48 (2H, m-Ph), 7.62 (1H, p-Ph), 8.05 (2H, o-Ph);
δC (62.9 MHz, CDCl3) 20.3 (CH2, C10), 30.4 (CH2, C7), 31.5
(CH2, C6), 38.4 (CH, C3), 54.6 (CH3, OMe), 69.0 (C, C2), 69.3
(CH, C5), 69.8 (CH, C4), 100.9 (CH, C1), 122.0 (CH, C8), 122.6
(CH, C9), 127.5 (CH, Ph), 128.2 (C, Ph), 128.8 (CH, Ph), 132.5
(CH, Ph), 164.6 (CO, OBz); m/z (EI) 396/398 (M+, 2), 105
(PhCO+, 100) (found M+, 396.0572; C18H21O5Br requires
396.0572).
(1R,1′S,2′R)-2′-F or m yl-2′-h yd r oxy-1-cycloh ex-4′-en e-2-
p r op en yl-1-ben zoa te (39). Zinc powder (60 g) was activated
by washing with 2 M hydrochloric acid (6 × 30 mL), water (5
× 35 mL), 10% w/v aqueous potassium carbonate solution (30
mL), water (4 × 40 mL), 2-propanol (2 × 35 mL), and diethyl
ether (3 × 35 mL). The bromo compound 38 (155 mg, 0.39
mmol) was heated to reflux with the activated zinc (3.32 g,
0.051 mol) in 2-propanol:water (10:1 mL) for 5 h. The zinc was
removed by filtration and washed with diethyl ether (2 × 50
mL), and the combined organic layers were washed with water
(100 mL), saturated sodium chloride solution (100 mL), dried,
and evaporated to leave a colorless oil. Chromatography on
silica gel with petroleum ether-diethyl ether (3:1) as the
eluent yielded 39 as a colorless oil (56 mg, 50%): Rf 0.54,
diethyl ether-petroleum ether (2:1); δH (250 MHz, CDCl3) 2.18
(1H, dd, J 5.0, 17.6, CHH, 7-H), 2.40-2.80 (4H, 3-H, CHH,
7-H and 10-H), 3.95 (1H, s, OH), 5.19-5.33 (2H, m, 6-H), 5.66-
5.97 (3H, 4-H, 5-H, 8-H) 6.06-6.16 (1H, m, 9-H), 7.43 (2H,
m-Ph), 7.56 (1H, p-Ph), 7.95 (2H, o-Ph), 9.81 (1H, s, CHO); δC
(62.9 MHz, CDCl3) 24.8 (CH2, C10), 36.7 (CH2, C7), 47.2 (CH,
C3), 71.3 (CH, C4), 76.2 (C, C2), 117.0 (CH2, C6), 123.8 (CH,
C8), 126.8 (CH, C9), 128.9 (CH, Ph), 129.9 (CH, Ph), 130.0 (C,

Preparation of Annulated Carbohydrates
J . Org. Chem., Vol. 65, No. 2, 2000 493
Ph), 133.6 (CH, Ph), 134.9 (CH, C5), 165.2 (CO, OBz), 202.2
(CH, CHO); m/z (FAB) 287 (MH+, 9), 309 (MNa+, 21) (found
MH+, 287.1281; C17H19O4 requires 287.1283).
3.95 (2H, m, 9-H), 4.07 (1H, ddd, J 2.4, 7.1, 9.6, 5-H), 4.37
(1H, s, 1-H), 4.95 (1H, ddd, J 5.3, 9.6, 11.3, 4-H), 7.42-7.63
(3H, Ph), 8.00 (2H, o-Ph); δC (62.9 MHz, CDCl3) 26.1 (CH2,
C7), 32.9 (CH2, C8), 35.1 (CH2, C3), 35.8 (CH2, C6), 55.8 (CH3,
OMe), 68.5 (CH2, C9), 69.6 (CH, C5), 70.4 (CH, C4), 81.7 (C,
C2), 101.8 (CH, C1), 128.9 (CH, Ph), 129.9 (CH, Ph), 130.1 (CH,
Ph), 133.8 (C, Ph), 165.7 (C, C10); m/z (EI) 407/409 (MNa+,
100). Anal. Found: C, 52.91; H, 5.42. C17H21O5Br requires C,
53.00; H, 5.49%.
Meth yl (R)-4,6-O-Ben zylid en e-2(R)-sp ir o(2,5′-2′,3′,4′,5′-
tetr a h yd r ofu r a n )-2,3-d id eoxy-r-D-glu cop yr a n osid e (40).
A solution of the olefin 19 (363 mg, 1.19 mmol) in dry methanol
(25.0 mL) was degassed several times with nitrogen. The
catalyst (palladium, 5% on carbon, 30 mg) was then added,
and the mixture was degassed several times with hydrogen
and then allowed to stir under a positive pressure of hydrogen
(balloon) for 48 h. At this point the mixture was filtered
through a plug of Celite under reduced pressure, and the
residue was washed with methanol (3 × 5 mL). The filtrate
was then concentrated under reduced pressure to yield a pale
yellow oil. Chromatography on silica gel with petroleum
ether-diethyl ether (2:1) as the eluent yielded 40 as a colorless
oil (323 mg, 89%): Rf 0.22, petroleum ether-diethyl ether (1:
(2R,2′S)-2-(3′-Bu ten yl-2′-ben zoa te)tetr a h yd r ofu r a n -2-
ca r ba ld eh yd e (42). Zinc powder (60 g) was activated by
washing with 2 M hydrochloric acid (6 × 30 mL), water (5 ×
35 mL), 10% w/v aqueous potassium carbonate solution (30
mL), water (4 × 40 mL), 2-propanol (2 × 35 mL), and diethyl
ether (3 × 35 mL). The bromo compound 41 (233 mg, 0.59
mmol) was heated to reflux with the activated zinc (5.08 g,
0.078 mol) in 2-propanol:water (15:1.5 mL) for 3.5 h. The zinc
was removed by filtration and washed with diethyl ether (2 ×
50 mL), and the combined organic layers were washed with
water (150 mL), saturated sodium chloride solution (150 mL),
dried, and evaporated to leave a colorless oil. Chromatography
on silica gel with petroleum ether-diethyl ether (3:1) as the
eluent yielded 42 as a colorless oil (96 mg, 59%): Rf 0.36,
1); [R]20 +67.8° (c 8.64, CHCl3); δH (250 MHz, CDCl3) 1.77-
D
2.14 (5H, overlapping, 3eq-H, 8-H and 7-H), 2.26 (1H, t, J 11.7,
3ax-H), 3.43 (3H, s, OMe), 3.51 (1H, ddd, J 4.3, 8.8, 16.3, 4-H),
3.70 (1H, t, J 8.7, 6ax-H), 3.68-3.94 (3H, overlapping, 5-H and
9-H), 4.25 (1H, dd, J 4.1, 8.7, 6eq-H), 4.26 (1H, s, 1-H), 5.51
(1H, s, 10-H), 7.31-7.53 (5H, Ph); δC (62.9 MHz, CDCl3) 26.1
(CH2, C7), 35.8 (CH2, C8), 36.5 (CH2, C3), 55.5 (CH3, OMe),
64.3 (CH, C5), 68.2 (CH2, C9), 69.9 (CH2, C6), 77.7 (CH, C4),
82.3 (C, C2), 102.2 (CH, C1), 102.2 (CH, C10), 126.6 (CH, Ph),
128.6 (CH, Ph), 129.5 (CH, Ph), 137.9 (C, Ph); m/z (FAB) 307
(MH+, 11) (found MH+ 307.15449, C17H23O5 requires 307.15455).
petroleum ether-diethyl ether (1:1); [R]20 -52.9° (c 3.99,
D
CHCl3); δH (250 MHz, CDCl3) 1.76-2.18 (4H, overlapping, 7-H
and 8-H), 1.94 (1H, overlapping, dd, J 6.3, 14.5, CHH, 3-H)
2.50 (1H, dd, J 10.6, 14.5, CHH, 3-H), 3.83-4.06 (2H, m, 9-H),
5.18 (1H, dt, J 1.0, 10.4, 6-Hcis) 5.32 (1H, dt, J 1.0, 17.1, 6-Htrans
)
Met h yl
(R)-4-O-Ben zoyl-6-C-b r om o-2(R)-sp ir o(2,5′-
5.66-5.77 (1H, m, 5-H), 5.87 (1H, ddd, J 6.3, 10.6, 16.7, 4-H),
7.34-7.68 (3H, Ph), 8.01 (2H, d, 0-Ph), 9.58 (1H, s, 1-H); δC
(62.9 MHz, CDCl3) 25.8 (CH2, C7), 34.5 (CH2, C8), 42.1 (CH2,
C3), 69.6 (CH2, C9), 71.8 (CH, C4), 87.7 (C, C2), 117.3 (CH2,
C6), 128.8 (CH, Ph), 130.1 (CH, Ph), 130.4 (C, Ph), 133.4 (CH,
Ph), 136.4 (CH, C5), 165.5 (C, C10), 205.2 (CH, C1); m/z (EI)
297 (MNa+, 82) (found MH+ 275.1283, C16H19O4 requires
275.1283).
2′,3′,4′,5′-tetr a h yd r ofu r a n )-2,3,6-tr id eoxy-r-D-glu cop yr a -
n osid e (41). Barium carbonate (835 mg, 4.24 mmol) and
N-bromosuccininmide (207 mg, 1.16 mmol) were added se-
quentially to a solution of 40 (323 mg, 1.06 mmol) in dry
chloroform (40 mL). The mixture was then heated to reflux
for 4 h. The mixture was allowed to cool to room temperature,
barium carbonate removed by filtration, and the residue
washed with diethyl ether (2 × 50 mL). The filtrate was
concentrated under reduced pressure to leave a yellow oil.
Chromatography on silica gel with toluene-diethyl ether (3:
1) as the eluent yielded 41 as a white solid (285 mg, 70%): Rf
0.48, petroleum ether-diethyl ether (1:1); [R]20D +89.6° (c 2.87,
CHCl3); δH (250 MHz, CDCl3) 1.84-2.13 (4H, overlapping, 7-H
and 8-H), 2.13 (1H, dd, overlapping, J 5.3, 11.3, 3eq-H), 2.24
(1H, t, J 11.3, 3ax-H), 3.44 (1H, dd, J 7.1, 11.0, CHH, 6-H),
3.54 (3H, s, OMe), 3.59 (1H, dd, J 2.4, 11.0, CHH 6-H), 3.78-
Ack n ow led gm en t. We are grateful to the Engineer-
ing and Physical Sciences Research Council, Pharma-
chemie BV, Haarlem, Holland, to the Indian National
Science Academy - Royal Society (study visit grant to
S.Ghosh), and to CSIR, New Delhi (fellowship to J .
Panda), for their support of this work.
J O991392Z