Intramolecular 1,8-hydrogen atom transfer. Stereoselectivity of the hexopyranos-5′-yl radical reactions in Hexp-(1→4)-Hexp disaccharide systems

Article abstract of DOI:10.1021/jo801499d

(Chemical Equation Presented) The stereoselective reduction of hexopyranos-5′-yl radicals in α-D-Hexp-(1→4)-D-Hexp disaccharide models is described. These radicals are generated from a 6-O-yl radical located in the other monosaccharic unit through a 1,8-hydrogen atom transfer. The reaction, which is strongly influenced by steric and stereoelectronic effects, permits in some cases the transformation of α-D-Hexp-(1→4)-D-Hexp into β-L-Hexp-(1→4)-D-Hexp disaccharides in a single step with high diastereoselectivity.

Full text of DOI:10.1021/jo801499d

Intramolecular 1,8-Hydrogen Atom Transfer. Stereoselectivity of the
Hexopyranos-5′-yl Radical Reactions in Hexp-(1f4)-Hexp
Disaccharide Systems
´
Angeles Mart´ın,* Ine´s Pe´rez-Mart´ın, Lu´ıs M. Quintanal, and Ernesto Sua´rez*
Instituto de Productos Naturales y Agrobiolog´ıa del C.S.I.C., Carretera de La Esperanza 3,
38206 La Laguna, Tenerife, Spain
angelesmartin@ipna.csic.es; esuarez@ipna.csic.es
ReceiVed July 8, 2008
The stereoselective reduction of hexopyranos-5′-yl radicals in R-D-Hexp-(1f4)-D-Hexp disaccharide
models is described. These radicals are generated from a 6-O-yl radical located in the other monosaccharic
unit through a 1,8-hydrogen atom transfer. The reaction, which is strongly influenced by steric and
stereoelectronic effects, permits in some cases the transformation of R-D-Hexp-(1f4)-D-Hexp into ꢀ-L-
Hexp-(1f4)-D-Hexp disaccharides in a single step with high diastereoselectivity.
Introduction
Less is known about the stereoselectivity of hexopyranos-5-
yl radical reactions and detailed studies have not been reported
so far except for a few examples.4 These radicals with a pseudo-
C-glycoside structure appear to be in a similar situation with
regard to the pyranose ring conformation and stereoelectronic
stabilization effects. Indeed, the galactopyranos-5-yl radical (III)
with an axial oxygenated substituent at C-4 remains in the 4C1
chair of its precursor 2, while the glucopyranos-5-yl radical (IV)
adopts a B1,4 boat conformation as determined by ESR
spectroscopy (Scheme 1).5 In consequence, we should expect a
preponderant formation of R-axial substitution products. This
seems to be especially the case for the two examples known
The conformational aspects of hexopyranos-1-yl radicals and
the stereoselectivity of their reactions have been extensively
studied in recent years.1 It was found that the conformation of
these radicals depends critically on the electronegativity and
stereochemistry of the 2-oxygenated substituent.2 Thus, man-
nopyranos-1-yl radicals (I) retain the 4C1 chair of their precursor
1, while glucopyranos-1-yl radicals (II) exist preferentially in
a B2,5 boat conformation (Scheme 1). Both radicals, with the
2-oxygenated substituent axially disposed, show a high pro-
pensity for quenching along the R-axial direction. This stereo-
selectivity is caused by two main stereoelectronic effects that
have been termed the radical anomeric effect and the quasi-
homo-anomeric effect [ꢀ-oxygen effect].3
(3) (a) Beckwith, A. L. J.; Duggan, P. J. Tetrahedron 1998, 54, 4623–4632.
(b) Beckwith, A. L. J.; Duggan, P. J. Tetrahedron 1998, 54, 6919–6928. (c)
Korth, H.-G.; Sustmann, R.; Dupuis, J.; Giese, B. J. Chem. Soc., Perkin Trans.
2 1986, 1453–1459. (d) Barton, D. H. R.; Hartwig, W.; Motherwell, W. B.
J. Chem. Soc., Chem. Commun. 1982, 4397–4410.
(1) (a) Renaud, P. In Radicals in Organic Synthesis; Renaud, P., Sibi, M. P.,
Eds.; Wiley-VCH: Weinheim, 2001; Vol. 1, pp 400-415. (b) Praly, J.-P. AdV.
Carbohydr. Chem. Biochem. 2000, 56, 65–151. (c) Curran, P. C.; Porter, N. A.;
Giese, B. Stereochemistry of Radical Reactions: Concepts, Guidelines, and
Synthetic Applications; VCH: Weinheim, 1996; pp 131-135. (d) Giese, B.
Angew. Chem., Int. Ed. Engl. 1989, 28, 969–980.
(2) (a) Giese, B.; Dupuis, J.; Leising, M.; Nix, M.; Lindner, H. J. Carbohydr.
Res. 1987, 171, 329–341. (b) Dupuis, J.; Giese, B.; Ru¨egge, D.; Fischer, H.;
Korth, H.-G.; Sustmann, R. Angew. Chem., Int. Ed. Engl. 1984, 23, 896–898.
(4) For a recent review on radicals in carbohydrate chemistry, see: (a) Pearce,
A. J.; Mallet, J.-M.; Sinay¨, P. In Radicals in Organic Synthesis; Renaud, P.;
Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 2, pp 538-577. (b) Sowa,
C. E.; Thiem, J. Angew. Chem., Int. Ed. Engl. 1994, 33, 1979–1981. (c) Korth,
H.-G.; Sustmann, R.; Gro¨ninger, K. S.; Leisung, M.; Giese, B. J. Org. Chem.
1988, 53, 4364–4369. (d) Blattner, R.; Ferrier, R. J.; Renner, R. J. Chem. Soc.,
Chem. Commun. 1987, 1007–1008.
(5) Korth, H.-G.; Praly, J.-P.; Somsa´k, L.; Sustmann, R. Chem. Ber. 1990,
123, 1155–1160.
7710 J. Org. Chem. 2008, 73, 7710–7720
10.1021/jo801499d CCC: $40.75 2008 American Chemical Society
Published on Web 09/09/2008

Intramolecular 1,8-Hydrogen Atom Transfer
SCHEME 1. Conformation of Hexopyranos-1-yl and Hexopyranos-5-yl Radicalsa
a R ) protective group; R1 ) see text; X ) Br.
SCHEME 2. Reduction of Hexopyranos-5′-yl Radicals in
r-D-Glcp-(1f4)-ꢀ-D-Glcp Disaccharidesa
where the n-Bu3SnH reduction of (5S)-1,2,3,4-tetra-O-acetyl-
5-bromo-8-cyano-6,7,8-trideoxy-ꢀ-D-xylo-octopyranose (2, R )
Ac; R1 ) (CH2)2CN; X ) Br)4d and (5S)-1,2,3,4,6-penta-O-
acetyl-5-bromo-R-D-xylo-hexopyranose (2, R ) Ac; R1
)
CH2OAc, X ) Br)4c apparently proceed by axial quenching with
total retention of configuration.
The reduction of methyl (5R)-1,2,3,4-tetra-O-acetyl-5-bromo-
D-xylo-hexopyranuronate (2, R ) Ac; R1 ) CO2Me; X ) Br)
has been studied in more detail.6 The stereochemistry of the
reaction seems to be dependent on the temperature and/or
concentration of the tin hydride as well as on the configuration
of the substituent at C-1.6c Surprisingly, the products were
obtained with diastereoselectivities up to 3:1 in favor of the
inverted L-iduronic acid derivative. At first sight, this is probably
attributable to a radical stabilization by the carboxylate group,
which permits ring inversion to a 1C4 chair and stannane
quenching along the ꢀ-axial direction. This apparently anoma-
lous behavior has attracted some preparative interest because
L-iduronic acid is a key constituent of heparin and other related
glycosaminoglycans and is essential for the construction of
heparin-based oligosaccharides.7
a PhtNOH ) N-hydroxyphthalimide; TBTH ) n-Bu3SnH; TBTD )
n-Bu3SnD.
tion, we have now found that this stereoselectivity can be
improved up to a inversion/retention ratio of 2.5:1 by slowing
down the stannane quenching reducing the amount and con-
centration of tin hydride (entry 2).
This last result, which suggests that 1,8-HAT may be a
synthetically useful protocol for the inversion of configuration
at C-5′ and consequent transformation of this ꢀ-maltose deriva-
tive 4 into a ꢀ-L-Idop-(1f4)-ꢀ-D-Glcp system (7) in a single
step, encouraged a further exploratory effort with variously
structured disaccharide substrates.10
Results and Discussion
In a previous paper from this laboratory we have described
an example of 1,8-hydrogen atom transfer (HAT) between the
two glucopyranose units of a heptamethylated R-D-Glcp-(1f4)-
ꢀ-D-Glcp disaccharide (ꢀ-maltose) (3)8 through a nine-
membered transition state (Scheme 2).9 The hydrogen abstrac-
tion from C-5′ is promoted, in a highly efficient and completely
regioselective manner, by the 6-O-yl radical (V) generated in
situ from reaction of the 6-O-phthalimide derivative 4 with
n-Bu3SnH/AIBN. In this case the C-radical (VI) reduction gave
also predominant inversion of the configuration at C-5′ and
consequent transformation of this D-glucose moiety in L-idose
(L-Ido/D-Glc, 1.6:1) (Table 1, entry 1). After some experimenta-
It has been suggested that the quasi-homo-anomeric effect
increases with the increase in electronegativity of the ꢀ-oxygen-
ated substituent2b so we decided to prepare the heptaacetylated
6-O-phthalimide11 derivative 6 from the alcohol 5 and N-
hydroxyphthalimide under Mitsunobu conditions.12 To our
delight, the HAT reaction afforded the inverted product 8 with
excellent diastereoselectivity (8/5, 14:1) (entry 3). In these aldose
systems, as in the uronate system, a mechanism of ꢀ-axial radical
1
(6) For a review on the preparation of L-iduronic synthons, see: (a) Pellissier,
H. Org. Prep. Proced. Int. 2002, 34, 441–465. (b) Yu, H. N.; Furukawa, J.-I.;
Ikeda, T.; Wong, C.-H. Org. Lett. 2004, 6, 723–726. (c) Medakovic, D.
Carbohydr. Res. 1994, 253, 299–300. (d) Chiba, T.; Sinay¨, P. Carbohydr. Res.
1986, 151, 379–389. (e) Blattner, R.; Ferrier, R. J. J. Chem. Soc., Perkin Trans.
1 1980, 1523–1527. (f) Ferrier, R. J.; Tyler, P. C. J. Chem. Soc., Perkin Trans.
1 1980, 1528–1534.
(7) (a) Noti, C.; de Paz, J. L.; Polito, L.; Seeberger, P. H. Chem. Eur. J.
2006, 12, 8664–8686. (b) Zhou, Y.; Lin, F.; Chen, J.; Yu, B. Carbohydr. Res.
2006, 341, 1619–1629. (c) de Paz, J. L.; Mart´ın-Lomas, M. Eur. J. Org. Chem.
2005, 1849–1858. (d) Lubineau, A.; Lortat-Jacob, H.; Gavard, O.; Sarrazin, S.;
Bonnaffe´, D. Chem. Eur. J. 2004, 10, 4265–4282. (e) Lohman, G. J. S.;
Seeberger, P. H. J. Org. Chem. 2004, 69, 4081–4093. (f) Bindscha¨dler, P.; Noti,
C.; Castagnetti, E.; Seeberger, P. H. HelV. Chim. Acta 2003, 89, 2591–2610.
(8) (a) Aspinall, G. O.; Igarashi, O.; Krishnamurthy, T. N.; Mitura, W.;
Funabashi, M. Can. J. Chem. 1976, 54, 1708–1713. (b) Aspinall, G. O.;
Krishnamurthy, T. N.; Mitura, W.; Funabashi, M. Can. J. Chem. 1975, 53, 2182–
2188.
quenching on the inverted C4 chair could also be operating.
In order to calculate correct diastereoselective ratios deuterium
incorporation studies using n-Bu3SnD/AIBN as reagent were
carried out to discriminate between deuterated alcohol 5
produced by abstraction with retention and the undeuterated one
generated by reduction of the alkoxyl radical prior to the
abstraction reaction. As expected, complete incorporation of
(10) This disaccharide model is closely related to R-L-Idop-(1f4)-R-D-Glcp,
a repetitive unit in heparin glycosaminoglycan.
(11) (a) Kim, S.; Lee, T. A.; Song, Y. Synlett 1998, 471–472. (b) Okada,
K.; Okamoto, K.; Oda, M. J. Am. Chem. Soc. 1988, 110, 8736–8738. (c) Okada,
K.; Okamoto, K.; Oda, M. J. Chem. Soc., Chem. Commun. 1989, 1636–1637.
(d) Barton, D. H. R.; Blundell, P.; Jaszberenyi, J. Cs. Tetrahedron Lett. 1989,
30, 2341–2344.
(9) Francisco, C. G.; Herrera, A. J.; Kennedy, A. R.; Melia´n, D.; Sua´rez, E.
Angew. Chem., Int. Ed. 2002, 41, 856–858.
(12) (a) Mitsunobu, O. Synthesis 1981, 1–28. (b) Grochowski, E.; Jurczak,
J. Synthesis 1976, 682–684.
J. Org. Chem. Vol. 73, No. 19, 2008 7711

Mart´ın et al.
TABLE 1. Stereoselective Reduction of Hexopyranos-5′-yl
Radicals
SCHEME 3. Reduction of Hexopyranos-5′-yl Radicals in
r-D-Talp-(1f4)-r-D-Glcp Disaccharidesa
a PhtNOH ) N-hydroxyphthalimide; TBTH ) n-Bu3SnH; TBTD )
n-Bu3SnD.
SCHEME 4. Reduction of Hexopyranos-5′-yl Radicals in
r-D-Manp-(1f4)-r-D-Glcp Disaccharidesa
a Isolated 1,8-abstraction yield. b The yield of retention product was
estimated by n-Bu3SnD/AIBN experiments. c n-Bu3SnH (9 equiv), AIBN
(0.15 equiv), PhH 1.8 M, reflux, 1 h. d n-Bu3SnH (1 equiv), AIBN (0.1
equiv), PhH 0.01 M, reflux, 1 h. e Included retained product 15 (22%).
f Included abstraction product 30 (5%).
a PhtNOH ) N-hydroxyphthalimide; TBTH ) n-Bu3SnH; TBTD )
n-Bu3SnD.
SCHEME 5. Reduction of Hexopyranos-5′-yl Radicals in
r-L-Rhap-(1f4)-r-D-Galp Disaccharidesa
deuterium at C-5′ is detected in the inverted product 8 and there
is no observable deuterium scrambling at other positions of the
molecule within NMR detection limits. The results are sum-
marized in Table 1 and in Supporting Information.
To better understand the scope and stereoselectivity of this
C-5′ radical stannane quenching, we decided to prepare various
disaccharides with the correct relative stereochemistry at the
four chiral centers (C-4, C-5, C-1′, and C-5′) involved in the
1,8-HAT reaction:13 R-D-Talp-(1f4)-R-D-Glcp (9, 11), R-D-
Manp-(1f4)-R-D-Glcp (17, 19), and R-L-Rhap-(1f4)-R-D-Galp
(23, 25) (Schemes 3-5). Compounds 9 and 17 were effectively
synthesized by TMSOTf-mediated glycosylation of methyl 6-O-
tert-butyldiphenylsilyl-2,3-di-O-methyl-R-D-glucopyranoside, us-
ing 2,3,4-tri-O-methyl-6-deoxy-R-D-talopyranosyl and 2,3,4,6-
tetra-O-methyl-R-D-mannopyranosyl trichloroacetimidates, respec-
tively, as glycosyl donors.14 Analogously, compound 23 (Scheme
5) was synthesized by glycosylation of methyl 6-O-tert-
butyldiphenylsilyl-2,3-di-O-methyl-R-D-galactopyranoside with
2,3,4-tri-O-methyl-R-L-rhamnopyranosyl trichloroacetimidate.15
The corresponding acetates 11, 19, and 25 were prepared by a
a PhtNOH ) N-hydroxyphthalimide; TBTH ) n-Bu3SnH; TBTD )
n-Bu3SnD.
completely analogous synthetic protocol as described in Sup-
porting Information.
(13) Mart´ın, A.; Pe´rez-Mart´ın, I.; Quintanal, L. M.; Sua´rez, E. Org. Lett.
2007, 9, 1785–1788.
The R-D-Talp-(1f4)-R-D-Glcp disaccharide 9 with the D-
talose moiety was selected, because the presence of the three
axial substituents was expected to enhance the chair inversion
rate (Scheme 3). Indeed, when methylated 6-O-phthalimide 10
was treated with n-Bu3SnH/AIBN the ꢀ-L-Allp-(1f4)-R-D-Glcp
(14) (a) Matsuo, I.; Isomura, M.; Miyazaki, T.; Sakakibara, T.; Ajisaka, K.
Carbohydr. Res. 1997, 305, 401–413. (b) Kere´kgya´rto´, J.; Kamerling, J. P.;
Bouwstra, J. B.; Vliegenthart, J. F. G.; Lipta´k, A. Carbohydr. Res. 1989, 186,
51–62. For a review on disaccharide synthesis with trichloroacetimidates, see:
(c) Schmidt, R. R.; Jung, K.-H. In PreparatiVe Carbohydrate Chemistry;
Hanessian, S., Ed.; Marcel Dekker: New York, 1997; pp 283-312.
7712 J. Org. Chem. Vol. 73, No. 19, 2008

Intramolecular 1,8-Hydrogen Atom Transfer
disaccharide 13 was obtained in good yield and excellent
inversion-retention ratio (13/9, 13:1) (entry 4). In stark contrast,
the 6-O-phthalimide 12 with the peracetylated D-talose moiety
afforded preferentially retained product 11 with modest dias-
tereoselectivity (14/11, 0.5:1) (entry 5). In this last case the
reaction was accompanied by an unexpected side product 15 in
low yield (22%). The structure and stereochemistry of 15 with
a 4′-deoxygenated carbon and a 1,3,5-trioxocane cycle as
principal features were determined by extensive use of 1H and
13C NMR including DEPT, and 2D-COSY, HMBC, and HSQC
experiments. When the reaction was carried out with n-Bu3SnD,
compound 16 was obtained with approximately 86% deuterium
incorporation at C-4′. The axial disposition of the deuterium
inversion reaction, the pyranose ring undergoes conformational
changes from 1C4 to 4C1 chair and the radical quenching is now
from the R-axial side of the molecule. The formation of two
minor products 29 and 30 from these reactions deserves a brief
comment (Scheme 5). The 4-deoxy-1,3,5-trioxocane 29 was
formed in 5% yield during the reduction of 6-O-phthalimide
24. In principle, this product is analogous to 15, but the absence
of deuterium incorporation at C-4′ when the reaction was carried
out using n-Bu3SnD suggests that only one mechanism operates
in this case and argues in favor of a 5′-radical reductive
elimination and subsequent alcohol addition to the 4′-enol ether.
The isolation of a small amount of undeuterated 4′-enol ether
30 during the reaction of 6-O-phthalimide 26 with n-Bu3SnD/
AIBN supports the proposed mechanism.
1
was determined by H NMR indicating an effective shielding
of the R-pyranose ring by the 1,3,5-trioxocane moiety.16 These
results suggest that the formation of 15 takes place by two
different mechanisms: (a) a 5′-radical reductive elimination to
give a 4′-enol ether and subsequent alcohol addition which is
responsible for the minor undeuterated compound (vide infra)
and (b) an interesting tandem 1,8-HAT-intramolecular cine
substitution mechanism with the 4′-acetate as the leaving group
and the oxygen at C-6 acting with an umpolung reactivity during
the reaction, first as an electrophilic alkoxyl radical and then as
a nucleophile.17 The stereochemistry of 15 suggests that the
nucleophilic attack occurred by the R-axial side on the stabilized
From the study of the results summarized in Table 1 several
general conclusions can be drawn. With the O-methyl-protected
carbohydrates 4, 10, 18, and 24 the steric effects clearly govern
the stereochemical course of the reaction, whereas stereoelec-
tronic factors appear to be less important (entries 2, 4, 6, and
8). The observed inversion/retention ratio is in reasonably good
4
agreement with the expected instability of the C1 chair, and
the number of axial substituents in the starting monosaccharide
R-D-Tal > R-L-Rha g R-D-Man > R-D-Glc, 13, 4.5, 3.5, and
2.5, respectively.18
On the contrary, it is also clear that stereoelectronic factors
are much more important than steric effects in the cases of the
O-acetyl-protected carbohydrates 6 and 12. The reaction of
acetylated R-D-Glc 6 occurs by ꢀ-axial radical quenching to
give the ꢀ-L-Ido derivative 8 where the 4′-acetyl group is axially
disposed, with excellent inversion/retention ratio (entry 3). The
reaction of acetylated R-D-Tal 12 is illustrative of the greater
importance of stereoelectronic over steric effects in these
esterified carbohydrates, an R-axial radical attack now giving
principally retention of configuration at 5′ (entry 5). In striking
contrast the O-methyl-R-D-Tal derivative 10, in a relatively
4
radical in a C1 chair conformation (VII) with retention of
configuration at C-5′ (Scheme 3).
Next, we were interested in studying the influence of the
stereochemistry of substituents other than C-4′. In this context,
disaccharide R-D-Manp-(1f4)-R-D-Glcp (17), which differs
from 3 only in the configuration at C-2′, was selected (Scheme
4). The reaction of permethylated 6-O-phthalimide 18 with
n-Bu3SnH/AIBN afforded, after acetylation, disaccharide ꢀ-L-
Gulp-(1f4)-R-D-Glcp 21 with an inversion-retention ratio of
3.5:1, which is somewhat higher than that of compound 4 (2.5:
1) (compare entries 6 and 2). On the other hand, compound 22
with an inversion-retention ratio of 2:1, substantially lower than
in the case of compound 6 (14:1), is obtained during the reaction
of tetraacetyl 6-O-phthalimide 20 (compare entries 7 and 3).
From the results of these two experiments, it is evident that the
stereochemistry of the reduction of the C-5′ radical is strongly
influenced by both the stereochemistry and nature of the C-2′
substituent.
Our next models, the R-L-Rhap-(1f4)-R-D-Galp derivatives
(23 and 25), may not be so useful from the synthetic point of
view (Scheme 5). Indeed, the C-5′ inversion should transform
the L-rhamnose moiety into a readily accessible 6-deoxy-D-
gulose, but we believe them to be important to shed some light
on the stereochemistry of the reaction mechanism and further
extend the scope of the methodology. In both cases the reaction
predominantly produced inverted D-disaccharides (27 and 28,
respectively) with high diastereoselectivity (entries 8 and 9).
Contrary to the other examples discussed above during the
4
unstable C1 conformation and with the 4′-methoxyl group in
the axial position, almost exclusively gives inversion (entry 4).
In the reaction of the esterified D-Man 20 and L-Rha 26
models, the equatorial-equatorial interaction between the gly-
cosidic bond and the 2′-acetyl substituent seems to be an
important source of instability for the inverted product and a
substantial decrease in the inversion preference is observed
(compare entries 7 and 9 with 3). This effect is not observed in
the case of O-methyl-D-Man 18 and L-Rha 24 models, perhaps
due to the lower steric demand of the methoxyl groups (compare
entries 6 and 8 with 2).19 We are currently engaged in further
studies using more electronegative and more sterically demand-
ing substituents to expand the synthetic utility of this methodology.
Experimental Section
General Methods. Melting points were determined with a hot-
stage apparatus. Optical rotations were measured at the sodium line
at ambient temperature in CHCl3 solutions. IR spectra were recorded
in film unless otherwise stated. NMR spectra were determined at
500 MHz for 1H and 125.7 MHz for 13C in CDCl3 unless otherwise
stated, in the presence of TMS as internal standard. Mass spectra
were determined at 70 eV unless otherwise stated. Merck silica
gel 60 PF (0.063-0.2 mm) was used for column chromatography.
(15) (a) Wang, J.; Li, J.; Tuttle, D.; Takemoto, J. Y.; Chang, C.-W. T. Org.
Lett. 2002, 4, 3997–4000. (b) van Steijn, A. M. P.; Kamerling, J. P.; Vliegenthart,
J. F. G. Carbohydr. Res. 1991, 211, 261–277.
(16) By comparison of the 4-H coupling constant with those of the
undeuterated compound 15. Compound 16: 2.03 (1H, br d, J3′,4′eq ) 5.0 Hz,
4′-Heq). Compound 15: 1.98 (1H, dd, Jgem ) 12.6, J3′,4′ax ) 12.6 Hz, 4′-Hax);
2.06 (1H, dd, Jgem ) 12.6, J3′,4′eq ) 4.8 Hz, 4′-Heq).
(17) For a review, see: (a) Crich, D. In Radicals in Organic Synthesis; Renaud,
P., Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 2, pp 188-206. For a
related 1,5-HAT-intramolecular cine substitution reaction, see: (b) Crich, D.;
Huang, X.; Newcomb, M. J. Org. Chem. 2000, 65, 523–529. (c) Crich, D.; Huang,
X.; Newcomb, M. Org. Lett. 1999, 1, 225–227.
(18) Rao, V. S. R.; Qasba, P. K.; Balaji, P. V.; Chandrasekaran, R.
Conformation of Carbohydrates, Harwood Academic: Australia, 1998; pp 49-
90.
(19) Beckwith, A. L. J.; Page, D. M. J. Org. Chem. 1998, 63, 5144–5153.
J. Org. Chem. Vol. 73, No. 19, 2008 7713

Mart´ın et al.
Circular layers of 1 mm of Merck silica gel 60 PF254 were used on
a Chromatotron for centrifugally assisted chromatography. Com-
mercially available reagents and solvents were analytical grade or
were purified by standard procedures prior to use. All reactions
involving air- or moisture-sensitive materials were carried out under
a nitrogen atmosphere. The spray reagents for TLC analysis were
conducted with 0.5% vanillin in H2SO4-EtOH (4:1) and further
heating until development of color.
Reductive HAT of Methyl 2,3,4,6-Tetra-O-methyl-r-D-glu-
copyranosyl-(1f4)-2,3-di-O-methyl-6-O-phthalimido-r-D-glu-
copyranoside (4). Method A with n-Bu3SnH. A solution of
phthalimide 49 (32 mg, 0.055 mmol) in dry benzene (4.1 mL)
containing n-Bu3SnH (15 µL, 0.055 mmol) and AIBN (1 mg, 0.006
mmol) was heated at reflux temperature for 1 h. After cooling to
room temperature the reaction mixture was concentrated under
reduced pressure. The residue was dissolved in CH3CN, washed
with n-hexane and the combined more polar extracts were
concentrated under reduced pressure. Column chromatography of
the crude residue (hexanes-EtOAc, 10:90 f 0:100) afforded
methyl 2,3,4,6-tetra-O-methyl-R-D-glucopyranosyl-(1f4)-2,3-di-
O-methyl-ꢀ-D-glucopyranoside (3) (7 mg, 0.016 mmol, 29%) and
methyl 2,3,4,6-tetra-O-methyl-ꢀ-L-idopyranosyl-(1f4)-2,3-di-O-
methyl-ꢀ-D-glucopyranoside (7) (13 mg, 0.030 mmol, 54%), both
as colorless oils.
95.5 (CH), 101.0 (CH), 123.5 (2 × CH), 128.8 (2 × C), 134.5 (2
× CH), 163.1 (2 × C), 169.5 (C), 169.6 (C), 169.9 (C), 170.2 (C),
170.4 (C), 170.6 (C); MS m/z (rel int) 722 (M+ - CH3O, <1), 694
(1), 634 (1), 331 (66), 169 (100); HRMS m/z calcd for C32H36NO18
722.1932, found 722.1902. Anal. Calcd for C33H39NO19: C, 52.59;
H, 5.22; N, 1.86. Found: C, 52.70; H, 5.24; N, 1.99.
Reductive HAT of Methyl 2,3,4,6-Tetra-O-acetyl-r-D-glu-
copyranosyl-(1f4)-2,3-di-O-acetyl-6-O-phthalimido-ꢀ-D-glu-
copyranoside (6). Method A with n-Bu3SnH. A solution of
phthalimide 6 (24 mg, 0.032 mmol) in dry benzene (2.4 mL)
containing n-Bu3SnH (9 µL, 0.003 mmol) and AIBN (1 mg, 0.003
mmol) was heated at reflux temperature for 1 h. After cooling to
room temperature the reaction mixture was concentrated under
reduced pressure. The residue was dissolved in CH3CN, washed
with n-hexane and the combined more polar extracts were
concentrated under reduced pressure. Column chromatography of
the crude residue (hexanes-EtOAc, 50:50 f 30:70) afforded
methyl 2,3,4,6-tetra-O-acetyl-R-D-glucopyranosyl-(1f4)-2,3-di-O-
acetyl-ꢀ-D-glucopyranoside (5) (1.5 mg, 0.002 mmol, 8%) and
methyl 2,3,4,6-tetra-O-acetyl-ꢀ-L-idopyranosyl-(1f4)-2,3-di-O-
acetyl-ꢀ-D-glucopyranoside (8) (13.5 mg, 0.022 mmol, 69%), both
as colorless oils. Compound 8: [R]D -2.1 (c, 0.12); IR 3545, 1752
1
cm-1; H NMR (400 MHz) δH 2.03 (3H, s), 2.04 (3H, s), 2.08
(3H, s), 2.108 (6H, s), 2.111 (3H, s), 3.42 (1H, ddd, J ) 9.5, 2.6,
2.6 Hz), 3.49 (3H, s), 3.88 (1H, dd, J ) 12.4, 2.6 Hz), 3.98 (1H,
dd, J ) 9.5, 9.5 Hz), 4.05 (1H, dd, J ) 12.7, 3.2 Hz), 4.14 (1H,
dd, J ) 10.3. 7.9 Hz), 4.19 (1H, ddd, J ) 11.1, 7.9, 1.6 Hz), 4.25
(1H, dd, J ) 10.3, 3.2 Hz), 4.41 (1H, d, J ) 7.7 Hz), 4.79-4.80
(2H, m), 4.84 (1H, dd, J ) 9.8, 7.9 Hz), 4.93 (1H, d, J ) 1.6 Hz),
Method B with n-Bu3SnD. A solution of phthalimide 4 (25 mg,
0.042 mmol) in dry benzene (3.2 mL) containing n-Bu3SnD (12
µL, 0.043 mmol) and AIBN (1 mg, 0.004 mmol) was heated at
reflux temperature for 1 h. After this time another portion of
n-Bu3SnD (12 µL, 0.043 mmol) and AIBN (1 mg, 0.004 mmol)
were added and heating at reflux was continued for an additional
1 h. After cooling to room temperature the reaction mixture was
concentrated under reduced pressure. The residue was dissolved
in CH3CN, washed with n-hexane and the combined more polar
extracts were concentrated under reduced pressure. Column chro-
matography of the crude residue (hexanes-EtOAc, 10:90 f 0:100)
afforded methyl 2,3,4,6-tetra-O-methyl-R-D-[5-2H]glucopyranosyl-
(1f4)-2,3-di-O-methyl-R-D-glucopyranoside (3-[D]) (7.8 mg, 0.018
5.05 (1H, dd, J ) 2.9, 2.9 Hz), 5.17 (1H, dd, J ) 9.8, 9.8 Hz); 13
C
NMR (100.6 MHz) δC 20.57 (2 × CH3), 20.60 (CH3), 20.64 (CH3),
20.68 (CH3), 20.71 (CH3), 57.1 (CH3), 61.3 (CH2), 62.543 (CH2),
65.176 (CH), 66.1 (CH), 67.8 (CH), 71.94 (CH), 71.98 (CH), 74.5
(CH), 74.6 (CH), 76.1 (CH), 98.9 (CH), 101.5 (CH), 167.7 (C),
169.2 (C), 169.3 (C), 169.4 (C), 169.9 (C), 170.6 (C); MS m/z (rel
int) 577 (M+ - CH3O, 4), 549 (1), 517 (1), 331 (52), 169 (100);
HRMS m/z calcd for C24H33O16 577.1769, found 577.1783. Anal.
Calcd for C25H36O17: C, 49.34; H, 5.96. Found: C, 49.58; H, 5.74.
Method B with n-Bu3SnD. A solution of phthalimide 6 (28 mg,
0.037 mmol) in dry benzene (2.8 mL) containing n-Bu3SnD (10
µL, 0.037 mmol) and AIBN (1 mg, 0.004 mmol) was heated at
reflux temperature for 1 h. After this time another portion of
n-Bu3SnD (10 µL, 0.037 mmol) and AIBN (1 mg, 0.004 mmol)
were added and heating at reflux was continued for an additional
1 h. After cooling to room temperature the reaction mixture was
concentrated under reduced pressure. The residue was dissolved
in CH3CN, washed with n-hexane and the combined more polar
extracts were concentrated under reduced pressure. Column chro-
matography of the crude residue (hexanes-EtOAc, 50:50 f 30:
70) afforded methyl 2,3,4,6-tetra-O-acetyl-R-D-[5-2H]glucopyranosyl-
(1f4)-2,3-di-O-methyl-ꢀ-D-glucopyranoside (5-[D]) (4.7 mg, 0.008
mmol, 21%, 1H/2H ratio, 8:2 by 1H NMR) (contaminated with ca.
10% of an inseparable, unidentified product) and methyl 2,3,4,6-
tetra-O-acetyl-ꢀ-L-(5-2H)idopyranosyl-(1f4)-2,3-di-O-acetyl-ꢀ-D-
glucopyranoside [8-(D)] (13.4 mg, 0.022 mmol, 59%), as colorless
oils. Compound (5-[D]): 13C NMR δC 20.5 (CH3), 20.56 (CH3),
20.60 (CH3), 20.63 (CH3), 20.7 (CH3), 20.9 (CH3), 57.2 (CH3),
61.2 (CH2), 61.794 (CH2, C-6′-D), 61.853 (CH2), 68.139 (CH, C-4′-
D), 68.198 (2 × CH), 69.4 (CH), 70.2 (CH), 70.4 (CH), 72.2 (CH),
74.3 (CH), 75.4 (CH), 95.06 (CH), 101.5 (CH), 169.5 (C), 169.6
(C), 170.0 (C), 170.3 (C), 170.5 (C), 170.7 (C); MS m/z (rel int)
578 (M+ - CH3O, <1), 577 (<1), 550 (<1), 549 (<1), 332 (12),
331 (38), 169 (100); HRMS m/z calcd for C24H322HO16 578.1831,
found 578.1829; calcd for C24H33O16 577.1769, found 577.1783.
Compound 8-(D): 1H NMR (400 MHz) δH 2.03 (3H, s), 2.04 (3H,
s), 2.08 (3H, s), 2.109 (6H, s), 2.111 (3H, s), 3.42 (1H, ddd, J )
9.8, 2.9, 2.9 Hz), 3.50 (3H, s), 3.88 (1H, br d, J ) 12.7 Hz), 3.98
(1H, dd, J ) 9.5, 9.5 Hz), 4.05 (1H, br d, J ) 12.7 Hz), 4.14 (1H,
d, J ) 11.7 Hz), 4.25 (1H, d, J ) 11.7 Hz), 4.41 (1H, d, J ) 8.0
1
mmol, 41%, H/2H ratio 7:3) and methyl 2,3,4,6-tetra-O-methyl-
R-L-(5-2H)idopyranosyl-(1f4)-2,3-di-O-methyl-R-D-glucopyrano-
side [7-(D)] (6.3 mg, 0.014 mmol, 33%), both as colorless oils.
Methyl 2,3,4,6-Tetra-O-acetyl-r-D-glucopyranosyl-(1f4)-2,3-
di-O-acetyl-6-O-phthalimido-ꢀ-D-glucopyranoside (6). DEAD (50
µL, 0.306 mmol) was added dropwise to a stirred solution of methyl
2,3,4,6-tetra-O-acetyl-R-D-glucopyranosyl-(1f4)-2,3-di-O-acetyl-
R-D-glucopyranoside (5)20 (74.5 mg, 0.122 mmol), N-hydroxyph-
thalimide (50.5 mg, 0.306 mmol) and PPh3 (79 mg, 0.306 mmol)
in dry THF (1.2 mL) and the resulting solution was stirred at 0 °C
for 1.5 h. Then the solvent was removed and the crude was
quenched with water and extracted with ether. The combined
extracts were dried over Na2SO4 and concentrated under reduced
pressure. The residue obtained was purified by column chroma-
tography (hexanes-EtO2, 30:70) to give compound 6 (70 mg, 0.093
mmol, 76%) as a white foam: [R]D +76.6 (c, 0.325); IR 1746 cm-1
;
1H NMR (400 MHz) δH 1.983 (3H, s), 1.986 (3H, s), 2.00 (3H, s),
2.026 (3H, s), 2.035 (3H, s), 2.08 (3H, s), 3.19 (3H, s), 3.82 (1H,
ddd, J ) 9.8, 4.5, 1.6 Hz), 4.03-4.09 (2H, m), 4.28 (1H, dd, J )
12.7, 4.5 Hz), 4.39 (1H, dd, J ) 7.9, 4.5 Hz), 4.42 (1H, d, J ) 9.0
Hz), 4.46 (1H, dd, J ) 13.0, 4.8 Hz), 4.58 (1H, dd, J ) 13.0, 1.6
Hz), 4.80 (1H, dd, J ) 9.3, 7.7 Hz), 4.87 (1H, dd, J ) 10.6, 4.0
Hz), 5.03 (1H, dd, J ) 9.8, 9.8 Hz), 5.24 (1H, dd, J ) 9.0, 9.0
Hz), 5.35 (1H, dd, J ) 10.6, 9.8 Hz), 5.45 (1H, d, J ) 4.0 Hz),
7.71-7.75 (2H, m), 7.79-7.83 (2H, m); 13C NMR (100.6 MHz)
δC 20.5 (CH3), 20.56 (2 × CH3), 20.62 (2 × CH3), 20.9 (CH3),
56.3 (CH3), 61.9 (CH2), 68.1 (CH), 68.5 (CH), 69.5 (CH), 70.1
(CH), 71.7 (CH), 71.8 (CH), 73.8 (CH), 75.2 (CH), 75.4 (CH2),
(20) (a) Bock, K.; Pedersen, H. Acta Chem. Scand. Ser. B 1988, 42, 75–85.
(b) Cottaz, S.; Apparau, C.; Driguez, H. J. Chem. Soc., Perkin Trans. 1 1991,
2235–2241.
7714 J. Org. Chem. Vol. 73, No. 19, 2008

Intramolecular 1,8-Hydrogen Atom Transfer
Hz), 4.79-4.80 (2H, m), 4.85 (1H, dd, J ) 9.5, 7.7 Hz), 4.93 (1H,
d, J ) 1.6 Hz), 5.06 (1H, dd, J ) 2.9, 2.9 Hz), 5.17 (1H, dd, J )
9.5, 9.5 Hz); 13C NMR (100.6 MHz) δC 20.57 (2 × CH3), 20.61
(CH3), 20.65 (CH3), 20.69 (CH3), 20.72 (CH3), 57.1 (CH3), 61.3
(CH2), 62.487 (CH2), 65.127 (CH), 66.1 (CH), 67.8 (CH), 71.9
(CH), 74.5 (CH), 74.6 (CH), 76.1 (CH), 98.9 (CH), 101.5 (CH),
167.8 (CH), 169.2 (CH), 169.3 (C), 169.4 (C), 169.9 (C), 170.6
(C); MS m/z (rel int) 578 (M+ - CH3O, <1), 532 (<1), 518 (1),
332 (31), 170 (100); HRMS m/z calcd for C24H322HO16 578.1831,
found 578.1818.
m/z calcd for C17H31O9 379.1968, found 379.1975. Anal. Calcd for
C18H34O10: C, 52.67; H, 8.35. Found: C, 52.72; H, 8.32.
Method B with n-Bu3SnD. A solution of phthalimide 10 (33
mg, 0.059 mmol) in dry benzene (4.5 mL) containing n-Bu3SnD
(16 µL, 0.059 mmol) and AIBN (1 mg, 0.006 mmol) was heated
at reflux temperature for 1 h. After this time another portion of
n-Bu3SnD (16 µL, 0.059 mmol) and AIBN (1 mg, 0.006 mmol)
were added and heating at reflux was continued for an additional
1 h. After cooling to room temperature the reaction mixture was
concentrated under reduced pressure. The residue was dissolved
in CH3CN, washed with n-hexane and the combined more polar
extracts were concentrated under reduced pressure. Chromatotron
chromatography (CHCl3-MeOH, 100:0 f 99:1) gave methyl 2,3,4-
tri-O-acetyl-6-deoxy-ꢀ-L-(5-2H)allopyranosyl-(1f4)-2,3-di-O-meth-
yl-R-D-glucopyranoside [13-(D)] (13.6 mg, 0.033 mmol, 56%) and
methyl 2,3,4-tri-O-acetyl-6-deoxy-R-D-[5-2H]talopyranosyl-(1f4)-
2,3-di-O-methyl-R-D-glucopyranoside (9-[D]) (1.5 mg, 0.004 mmol,
Methyl 6-Deoxy-2,3,4-tri-O-methyl-r-D-talopyranosyl-(1f4)-2,3-
di-O-methyl-6-O-phthalimido-r-D-glucopyranoside (10). DEAD
(230 µL, 1.462 mmol) was added dropwise to a stirred solution of
the alcohol 9 (240 mg, 0.585 mmol), N-hydroxyphthalimide (238
mg, 1.462 mmol) and PPh3 (383 mg, 1.462 mmol) in dry THF
(6.4 mL) and the resulting solution was stirred at 0 °C for 1.5 h.
Then the solvent was removed and the crude was quenched with
water and extracted with Et2O. The combined extracts were dried
over Na2SO4 and concentrated under reduced pressure. The residue
obtained was purified by column chromatography (Et2O-AcOEt,
90:10 f 0:100) to give compound 10 (147 mg, 0.265 mmol, 45%)
1
6%, H/2H ratio, 3:7), both as colorless oils. Compound 13-(D):
1H NMR (400 MHz) δH 1.24 (3H, s), 2.81 (1H, d, J ) 2.4 Hz),
2.93 (1H, dd, J ) 7.9, 2.4 Hz), 3.21 (1H, dd, J ) 9.5, 3.7 Hz),
3.39 (3H, s), 3.41 (3H, s), 3.51 (3H, s), 3.52 (3H, s), 3.55 (1H,
ddd, J ) 9.8, 2.6, 2.6 Hz), 3.57 (1H, dd, J ) 9.3, 9.3 Hz), 3.59
(3H, s), 3.64 (3H, s), 3.66 (1H, m), 3.69 (1H, dd, J ) 10.1, 9.0
Hz), 3.94 (1H, dd, J ) 12.7, 2.6 Hz), 3.96 (1H, dd, J ) 2.4, 2.4
Hz), 4.81 (1H, d, J ) 3.7 Hz), 5.09 (1H, d, J ) 8.0 Hz); 13C NMR
(100.6 MHz) δC 17.328 (CH3), 55.1 (CH3), 57.4 (CH3), 59.0 (CH3),
59.3 (CH3), 60.9 (CH3), 61.1 (CH3), 61.7 (CH2), 70.2 (CH), 75.06
(CH), 75.13 (CH), 81.8 (CH), 82.1 (CH), 83.002 (CH), 83.5 (CH),
97.9 (CH), 101.031 (CH); MS m/z (%) 380 (M+ - CH3O, <1),
307 (2), 265 (24), 101 (50), 88 (100); HRMS m/z calcd for
C17H302HO9 380.2031 found 380.2045. Compound 9-[D]: 1H NMR
δH 1.33 (3H, s), 3.24 (1H, dd, J ) 9.0, 3.4 Hz), 3.36 (1H, dd, J )
2.9, 0.8 Hz), 3.42 (3H, s), 3.44-3.47 (2H, m), 3.49 (3H, s), 3.50
(3H, s), 3.51 (3H, s), 3.52 (1H, m), 3.55 (3H, s), 3.56-3.60 (2H,
m), 3.62 (3H, s), 3.73-3.81 (2H, m), 4.83 (1H, d, J ) 3.7 Hz),
5.29 (1H, d, J ) 2.1 Hz); 13C NMR (100.6 MHz) δC 16.370 (CH3),
16.496 (CH3), 55.2 (CH3), 57.1 (CH3), 58.8 (CH3), 59.2 (CH3),
61.0 (CH3), 61.1 (CH3), 62.1 (CH2), 68.5 (CH), 70.3 (CH), 76.8
(CH), 77.5 (CH), 77.6 (CH), 78.011 (CH), 78.074 (CH), 82.4 (CH),
83.2 (CH), 97.4 (CH), 100.051 (CH), 100.079 (CH); MS (FAB)
m/z (%) 434 (M+ + Na, 100), 433 (28); HRMS m/z calcd for
C18H332HNaO10 434.2112, found 434.2133; calcd for C18H34NaO10
433.2050, found 433.2050.
1
as a foam: [R]D +89.6 (c, 0.435); IR 1789, 1734 cm-1; H NMR
δH 1.19 (3H, d, J ) 6.5 Hz), 3.25 (1H, dd, J ) 9.5, 3.5 Hz), 3.35
(1H, m), 3.42 (1H, dd, J ) 3.5, 3.5 Hz), 3.45 (3H, s), 3.460 (1H,
m), 3.463 (3H, s), 3.48 (3H, s), 3.49 (3H, s), 3.52 (3H, s), 3.53
(1H, dd, J ) 9.5, 9.5 Hz), 3.57 (1H, dd, J ) 9.0, 9.0 Hz), 3.60
(3H, s), 3.89 (1H, dddd, J ) 6.5, 6.5, 6.5, 1.5 Hz), 3.93 (1H, ddd,
J ) 9.0, 7.0, 2.0 Hz), 4.36 (1H, dd, J ) 11.5, 6.5 Hz), 4.42 (1H,
dd, J ) 11.0, 2.0 Hz), 4.80 (1H, d, J ) 3.5 Hz), 5.26 (1H, d, J )
1.5 Hz), 7.72-7.76 (2H, m), 7.80-7.83 (2H, m); 13C NMR δC
16.5 (CH3), 55.6 (CH3), 56.6 (CH3), 58.7 (CH3), 59.1 (CH3), 60.9
(CH3), 61.4 (CH3), 67.7 (CH), 69.1 (CH), 76.9 (CH), 77.2 (CH),
77.3 (CH), 77.8 (CH2), 78.0 (CH), 81.9 (CH), 82.8 (CH), 97.2 (CH),
99.7 (CH), 123.5 (2 × CH), 128.8 (2 × C), 134.5 (2 × CH), 163.2
(2 × C); MS m/z (%) 578 (M+ + Na, 100), 556 (M+ + H, 33);
HRMS m/z calcd for C26H37NNaO12 578.2213, found 578.2230.
Anal. Calcd for C26H37NO12: C, 56.21; H, 6.71; N, 2.52. Found:
C, 56.02; H, 6.92; N, 2.35.
Reductive HAT of Methyl 6-Deoxy-2,3,4-tri-O-methyl-r-D-
talopyranosyl-(1f4)-2,3-di-O-methyl-6-O-phthalimido-r-D-glu-
copyranoside (10). Method A with n-Bu3SnH. A solution of
phthalimide 10 (33 mg, 0.059 mmol) in dry benzene (4.5 mL)
containing n-Bu3SnH (16 µL, 0.059 mmol) and AIBN (1 mg, 0.006
mmol) was heated at reflux temperature for 1 h. After this time
another portion of n-Bu3SnH (16 µL, 0.059 mmol) and AIBN (1
mg, 0.006 mmol) were added and heating at reflux was continued
for an additional 1 h. After cooling to room temperature the reaction
mixture was concentrated under reduced pressure. The residue was
dissolved in CH3CN, washed with n-hexane and the combined more
polar extracts were concentrated under reduced pressure. Chroma-
totron chromatography (CHCl3-MeOH, 100:0 f 99:1) gave methyl
6-deoxy-2,3,4-tri-O-methyl-ꢀ-L-allopyranosyl-(1f4)-2,3-di-O-methyl-
R-D-glucopyranoside (13) (16.5 mg, 0.040 mmol, 68%) and methyl
6-deoxy-2,3,4-tri-O-methyl-R-D-talopyranosyl-(1f4)-2,3-di-O-methyl-
R-D-glucopyranoside (9) (2 mg, 0.005 mmol, 8%), both as colorless
oils. Compound 13: [R]D +87.1 (c, 0.56); IR 3498 cm-1; 1H NMR
(400 MHz) δH 1.25 (3H, d, J ) 6.3 Hz), 2.81 (1H, dd, J ) 9.6, 2.5
Hz), 2.93 (1H, dd, J ) 7.8, 2.5 Hz), 3.21 (1H, dd, J ) 9.6, 3.8
Hz), 3.40 (3H, s), 3.42 (3H, s), 3.517 (3H, s), 3.521 (3H, s), 3.55
(1H, ddd, J ) 10.1, 2.5, 2.5 Hz), 3.57 (1H, dd, J ) 9.3, 9.3 Hz),
3.59 (3H, s), 3.64 (3H, s), 3.65 (1H, dd, J ) 12.7, 2.4 Hz), 3.69
(1H, dd, J ) 10.1, 9.1 Hz), 3.85 (1H, dddd, J ) 9.1, 6.1, 6.1, 6.1
Hz), 3.95 (1H, dd, J ) 12.6, 2.5 Hz), 3.96 (1H, dd, J ) 2.5, 2.5
Hz), 4.82 (1H, d, J ) 3.8 Hz), 5.09 (1H, d, J ) 8.1 Hz); 13C NMR
(100.6 MHz) δC 17.467 (CH3), 55.1 (CH3), 57.4 (CH3), 59.0 (CH3),
59.3 (CH3), 61.0 (CH3), 61.1 (CH3), 61.7 (CH2), 68.9 (CH), 70.2
(CH), 75.08 (CH), 75.14 (CH), 81.8 (CH), 82.1 (CH), 83.109 (CH),
Methyl 2,3,4-Tri-O-acetyl-6-deoxy-r-D-talopyranosyl-(1f4)-2,3-
di-O-methyl-6-O-phthalimido-r-D-glucopyranoside (12). DEAD
(120 µL, 0.760 mmol) was added dropwise to a stirred solution of
the alcohol 11 (150 mg, 0.304 mmol), N-hydroxyphthalimide (124
mg, 0.760 mmol) and PPh3 (199 mg, 0.760 mmol) in dry THF
(3.3 mL) and the resulting solution was stirred at 0 °C for 1 h.
Then the solvent was removed and the crude was quenched with
water and extracted with Et2O. The combined extracts were dried
over Na2SO4 and concentrated under reduced pressure. The residue
obtained was purified by column chromatography (hexanes-Et2O,
50:50 f 0:100) to give compound 12 (187 mg, 0.293 mmol, 96%)
1
as a colorless oil: [R]D +99.2 (c, 0.36); IR 1789, 1738 cm-1; H
NMR (400 MHz) δH 1.16 (3H, d, J ) 6.3 Hz), 1.98 (3H, s), 2.12
(3H, s), 2.14 (3H, s), 3.26 (1H, dd, J ) 9.5, 3.4 Hz), 3.46 (3H, s),
3.49 (3H, s), 3.58 (1H, dd, J ) 9.5, 8.7 Hz), 3.59 (3H, s), 3.76
(1H, dd, J ) 10.1, 8.7 Hz), 3.92 (1H, ddd, J ) 10.1, 3.4, 3.4 Hz),
4.26 (1H, dddd, J ) 6.3, 6.3, 6.3, 1.6 Hz), 4.41 (2H, d, J ) 3.4
Hz), 4.78 (1H, d, J ) 3.4 Hz), 5.17 (1H, ddd, J ) 3.4, 1.6, 1.6
Hz), 5.20 (1H, ddd, J ) 3.7, 1.6, 1.6 Hz), 5.25 (1H, d, J ) 1.6
Hz), 5.26 (1H, dd, J ) 3.7, 3.7 Hz), 7.75 (2H, m), 7.83 (2H, m);
13C NMR (100.6 MHz) δC 16.1 (CH3), 20.6 (CH3), 20.7 (CH3),
20.9 (CH3), 55.7 (CH3), 58.8 (CH3), 61.0 (CH3), 65.8 (CH), 65.9
(CH), 67.3 (CH), 68.9 (CH), 69.0 (CH), 76.8 (CH), 77.1 (CH2),
81.9 (CH), 82.7 (CH), 97.4 (CH), 100.4 (CH), 123.6 (2 × CH),
128.9 (2 × C), 134.5 (2 × CH), 163.2 (2 × C), 169.6 (C), 169.8
(C), 170.6 (C); MS m/z (%) 579 (M+ - AcOH, <1), 435 (1), 273
83.5 (CH), 97.9 (CH), 101.063 (CH); MS m/z (%) 379 (M+
CH3O, <1), 346 (<1), 307 (2), 265 (29), 101 (62), 88 (100); HRMS
-
J. Org. Chem. Vol. 73, No. 19, 2008 7715

Mart´ın et al.
(96), 88 (100); HRMS m/z calcd for C27H33NO13 579.1952, found
579.1948. Anal. Calcd for C29H37NO15: C, 54.46; H, 5.83; N, 2.19.
Found: C, 54.13; H, 6.22; N, 2.30.
copyranoside [14-(D)] (4.2 mg, 0.008 mmol, 12%), and methyl
2,3,4-tri-O-acetyl-6-deoxy-R-D-(5-2H)talopyranosyl-(1f4)-2,3-di-
O-methyl-R-D-glucopyranoside [11-(D)] (9.3 mg, 0.019 mmol,
27%), all as colorless oils. Compound 16: 1H NMR (Only the
deuterated compound is described) δH 1.40 (3H, s), 2.01 (3H, s),
2.035 (1H, br d, J ) 5.0 Hz), 2.13 (3H, s), 3.14 (1H, dd, J ) 9.2,
3.6 Hz), 3.40 (3H, s), 3.49 (1H, dd, J ) 9.0, 9.0 Hz), 3.51 (3H, s),
3.55 (1H, dd, J ) 9.0, 9.0 Hz), 3.58 (3H, s), 3.62-3.66 (2H, m),
3.83 (1H, dd, J ) 12.3, 11.2 Hz), 4.75 (1H, d, J ) 3.6 Hz), 4.96
(1H, d, J ) 1.7 Hz), 5.21 (1H, m), 5.51 (1H, dd, J ) 4.8, 3.1 Hz);
13C NMR δC 20.88 (CH3), 20.94 (CH3), 25.4 (CH3), 35.042 (CH,
t, JCD ) 19.6 Hz), 35.372 (CH2), 55.1 (CH3), 59.1 (CH3), 61.4
(CH3), 64.0 (CH2), 64.306 (CH), 64.352 (CH), 66.1 (CH), 67.3
(CH), 79.6 (CH), 81.1 (CH), 81.5 (CH), 97.6 (CH), 98.4 (CH),
100.598 (C), 169.8 (C), 170.0 (C); MS m/z (%) 435 (M+, 1), 404
(1), 375 (1), 274 (13), 101 (46), 88 (100); HRMS m/z calcd for
Reductive HAT of Methyl 2,3,4-Tri-O-acetyl-6-deoxy-r-D-
talopyranosyl-(1f4)-2,3-di-O-methyl-6-O-phthalimido-r-D-glu-
copyranoside (12). Method A with n-Bu3SnH. A solution of
phthalimide 12 (41 mg, 0.064 mmol) in dry benzene (4.8 mL)
containing n-Bu3SnH (17 µL, 0.064 mmol) and AIBN (1 mg, 0.006
mmol) was heated at reflux temperature for 2 h. After this time
another portion of n-Bu3SnH (17 µL, 0.064 mmol) and AIBN (1
mg, 0.006 mmol) were added and heating at reflux was continued
for an additional 1 h. After cooling to room temperature the reaction
mixture was concentrated under reduced pressure. The residue was
dissolved in CH3CN, washed with n-hexane and the combined more
polar extracts were concentrated under reduced pressure. Chroma-
totron chromatography (hexanes-EtOAc, 60:40 f 40:60) gave
methyl (5R)-5,6-anhydro-2,3-di-O-acetyl-4,6-dideoxy-R-L-erythro-
hexos-5-ulopyranosyl-(1f4)-2,3-di-O-methyl-R-D-glucopyrano-
side (15) (6 mg, 0.014 mmol, 22%), methyl 2,3,4-tri-O-acetyl-6-
deoxy-ꢀ-L-allopyranosyl-(1f4)-2,3-di-O-methyl-R-D-
glucopyranoside (14) (5.5 mg, 0.011 mmol, 17%), and methyl 2,3,4-
tri-O-acetyl-6-deoxy-R-D-talopyranosyl-(1f4)-2,3-di-O-methyl-R-
D-glucopyranoside (11) (12 mg, 0.024 mmol, 38%), all as colorless
oils. Compound 15: [R]D +77.7 (c, 0.26); IR 1748 cm-1; 1H NMR
δH 1.40 (3H, s), 1.98 (1H, dd, J ) 12.6, 12.6 Hz), 2.01 (3H, s),
2.06 (1H, dd, J ) 12.6, 4.8 Hz), 2.13 (3H, s), 3.14 (1H, dd, J )
9.2, 3.6 Hz), 3.40 (3H, s), 3.49 (1H, dd, J ) 9.0, 9.0 Hz), 3.51
(3H, s), 3.56 (1H, dd, J ) 9.0, 9.0 Hz), 3.58 (3H, s), 3.61-3.66
(2H, m), 3.83 (1H, dd, J ) 12.3, 11.2 Hz), 4.75 (1H, d, J ) 3.6
Hz), 4.96 (1H, d, J ) 1.7 Hz), 5.21 (1H, m), 5.52 (1H, ddd, J )
12.0, 5.0, 3.1 Hz); 13C NMR δC 20.88 (CH3), 20.94 (CH3), 25.4
(CH3), 35.375 (CH2), 55.1 (CH3), 59.1 (CH3), 61.4 (CH3), 64.0
(CH2), 64.355 (CH), 66.1 (CH), 67.3 (CH), 79.6 (CH), 81.1 (CH),
81.5 (CH), 97.6 (CH), 98.4 (CH), 100.626 (C), 169.8 (C), 170.0
(C); MS m/z (%) 434 (M+, 2), 403 (3), 374 (5), 273 (29), 101 (50),
88 (100); HRMS m/z calcd for C19H30O11 434.1788, found
434.1780. Anal. Calcd for C19H30O11: C, 52.53; H, 6.96. Found:
C, 52.81; H, 6.62. Compound 14: [R]D +60.3 (c, 0.36); IR 3520,
C19H292HO11 435.1851, found 435.1842. Compound 14-(D): H
1
NMR δH 1.22 (3H, s), 2.01 (6H, s), 2.13 (3H, s), 2.71 (1H, br s),
3.22 (1H, dd, J ) 9.5, 3.8 Hz), 3.40 (3H, s), 3.52 (3H, s), 3.54
(1H, dd, J ) 9.5, 9.5 Hz), 3.55 (1H, m), 3.62 (3H, s), 3.68 (1H,
m), 3.72 (1H, dd, J ) 9.2, 9.2 Hz), 3.94 (1H, br d, J ) 12.9 Hz),
4.69 (1H, d, J ) 2.8 Hz), 4.81 (1H, dd, J ) 8.1, 2.8 Hz), 4.84 (1H,
d, J ) 3.6 Hz), 5.22 (1H, d, J ) 8.1 Hz), 5.60 (1H, dd, J ) 2.8,
2.8 Hz); 13C NMR δC 17.022 (CH3), 20.57 (2 × CH3), 20.63 (CH3),
55.2 (CH3), 59.0 (CH3), 61.0 (CH3), 61.3 (CH2), 68.6 (CH), 69.7
(CH), 70.0 (CH), 70.985 (CH), 74.5 (CH), 82.3 (CH), 83.4 (CH),
97.6 (CH), 98.8 (CH), 169.0 (C), 169.3 (C), 169.8 (C); MS m/z
(%) 435 (M+ - AcOH, 7), 274 (98), 101 (24), 88 (100); HRMS
m/z calcd for C19H292HO11 435.1851, found 435.1843. Compound
1
11-(D): H NMR (400 MHz) δH 1.22 (3H, s), 2.00 (3H, s), 2.13
(3H, s), 2.15 (3H, s), 3.21 (1H, dd, J ) 9.3, 3.4 Hz), 3.43 (3H, s),
3.50 (3H, s), 3.56 (1H, dd, J ) 9.3, 9.3 Hz), 3.60 (3H, s), 3.61-3.64
(2H, m, 4-H), 3.75 (1H, br dd, J ) 12.2, 2.9 Hz), 3.81 (1H, dd, J
) 12.2, 1.1 Hz), 4.82 (1H, d, J ) 3.4 Hz), 5.15 (1H, m), 5.19 (1H,
ddd, J ) 4.0, 1.6, 1.1 Hz), 5.25 (1H, dd, J ) 3.7, 3.7 Hz), 5.25
(1H, m); 13C NMR (100.6 MHz) δC 15.996 (CH3), 20.59 (CH3),
20.63 (CH3), 20.8 (CH3), 55.2 (CH3), 58.8 (CH3), 61.2 (CH3), 61.8
(CH2), 65.9 (CH), 67.3 (CH), 68.715 (CH), 70.0 (CH), 76.5 (CH),
82.4 (CH), 83.0 (CH), 97.4 (CH), 100.4 (CH), 169.7 (C), 169.8
(C), 170.5 (C); MS m/z (%) 435 (M+ - AcOH, 2), 274 (61), 101
(22), 88 (100); HRMS m/z calcd for C19H292HO11 435.1851, found
435.1849.
1
1752 cm-1; H NMR (400 MHz) δH 1.23 (3H, d, J ) 6.1 Hz),
2.014 (3H, s), 2.015 (3H, s), 2.13 (3H, s), 3.22 (1H, dd, J ) 9.5,
3.7 Hz), 3.40 (3H, s), 3.52 (3H, s), 3.54 (1H, dd, J ) 9.5, 9.5 Hz),
3.55 (1H, m), 3.62 (3H, s), 3.68 (1H, br dd, J ) 12.4, 1.9 Hz),
3.72 (1H, dd, J ) 10.1, 9.3 Hz), 3.94 (1H, br dd, J ) 12.5, 2.9
Hz), 4.00 (1H, dddd, J ) 9.8, 6.1, 6.1, 6.1 Hz), 4.70 (1H, dd, J )
10.1, 2.9 Hz), 4.81 (1H, dd, J ) 8.5, 2.9 Hz), 4.84 (1H, d, J ) 3.7
Methyl 2,3,4,6-Tetra-O-methyl-r-D-mannopyranosyl-(1f4)-2,3-
di-O-methyl-6-O-phthalimido-r-D-glucopyranoside (18). DEAD
(330 µL, 2.09 mmol) was added dropwise to a stirred solution of
the alcohol 17 (368 mg, 0.836 mmol), N-hydroxyphthalimide (272
mg, 1.67 mmol) and PPh3 (548 mg, 2.09 mmol) in dry THF (9.2
mL) and the resulting solution was stirred at 0 °C for 1 h. Then
the solvent was removed and the crude was quenched with water
and extracted with CHCl3. The combined extracts were dried over
Na2SO4 and concentrated under reduced pressure. The residue
obtained was purified by column chromatography (hexanes-EtOAc,
30:70) to give compound 18 (224 mg, 0.383 mmol, 46%) as a white
foam: [R]D +76.0 (c, 0.213); IR 1790, 1734 cm-1; 1H NMR (C6D6)
δH 3.06 (3H, s), 3.11 (3H, s), 3.17 (1H, dd, J ) 9.7, 3.3 Hz), 3.22
(3H, s), 3.29 (3H, s), 3.34 (3H, s), 3.44 (3H, s), 3.516 (3H, s),
3.522 (1H, dd, J ) 10.1, 6.1 Hz), 3.59 (1H, dd, J ) 10.6, 1.6 Hz),
3.68-3.73 (3H, m), 3.76 (1H, dd, J ) 9.7, 8.9 Hz), 3.99 (1H, dd,
J ) 10.1, 8.9 Hz), 4.01 (1H, m), 4.10 (1H, ddd, J ) 10.2, 5.3, 1.2
Hz), 4.60 (1H, d, J ) 3.6 Hz), 4.74 (1H, dd, J ) 11.4, 5.3 Hz),
4.88 (1H, dd, J ) 11.8, 1.6 Hz), 5.52 (1H, d, J ) 1.6 Hz), 6.78
(2H, m), 7.30 (2H, m); 13C NMR (100.6 MHz, C6D6) δC 55.2 (CH3),
57.1 (CH3), 57.6 (CH3), 58.5 (CH3), 58.9 (CH3), 60.3 (CH3), 60.8
(CH3), 70.4 (CH), 72.7 (CH2), 73.5 (CH), 77.0 (CH), 78.0 (CH2),
78.1 (CH), 78.5 (CH), 81.7 (CH), 82.3 (CH), 83.2 (CH), 97.5 (CH),
100.7 (CH), 122.9 (2 × CH), 129.5 (2 × C), 133.5 (2 × CH),
163.2 (2 × C); MS (FAB) m/z (rel int) 608 (M+ + Na, 17), 219
(48), 187 (100); HRMS m/z calcd for C27H39NNaO13 608.2319,
Hz), 5.22 (1H, d, J ) 8.5 Hz), 5.60 (1H, dd, J ) 2.9, 2.9 Hz); 13
C
NMR (100.6 MHz) δC 17.157 (CH3), 20.57 (2 × CH3), 20.63 (CH3),
55.2 (CH3), 59.0 (CH3), 61.0 (CH3), 61.3 (CH2), 68.5 (CH), 68.6
(CH), 69.7 (CH), 70.0 (CH), 71.062 (CH), 74.5 (CH), 82.3 (CH),
83.4 (CH), 97.6 (CH), 98.8 (CH), 169.0 (C), 169.3 (C), 169.8 (C);
MS m/z (%) 434 (M+ - AcOH, 1), 390 (1), 375 (1), 273 (18), 105
(100), 88 (80); HRMS m/z calcd for C19H30O11 434.1788, found
434.1795. Anal. Calcd for C21H34O13: C, 51.01; H, 6.93. Found:
C, 51.06; H, 6.94.
Method B with n-Bu3SnD. A solution of phthalimide 12 (44
mg, 0.069 mmol) in dry benzene (5.2 mL) containing n-Bu3SnD
(19 µL, 0.069 mmol) and AIBN (1 mg, 0.007 mmol) was heated
at reflux temperature for 2 h. After this time another portion of
n-Bu3SnD (19 µL, 0.069 mmol) and AIBN (1 mg, 0.007 mmol)
were added and heating at reflux was continued for an additional
1 h. After cooling to room temperature the reaction mixture was
concentrated under reduced pressure. The residue was dissolved
in CH3CN, washed with n-hexane and the combined more polar
extracts were concentrated under reduced pressure. Chromatotron
chromatography (hexanes-EtOAc, 60:40 f 40:60) gave methyl
5,6-anhydro-2,3-di-O-acetyl-4,6-dideoxy-ꢀ-L-[4-2H]ribo-hexos-5-
ulopyranosyl-(1f4)-2,3-di-O-methyl-R-D-glucopyranoside (16) (13
mg, 0.014 mmol, 43%, 1H/2H ratio, 1:6), methyl 2,3,4-tri-O-acetyl-
6-deoxy-ꢀ-L-(5-2H)allopyranosyl-(1f4)-2,3-di-O-methyl-R-D-glu-
7716 J. Org. Chem. Vol. 73, No. 19, 2008

Intramolecular 1,8-Hydrogen Atom Transfer
found 608.2330. Anal. Calcd for C27H39NO13: C, 55.38; H, 6.71;
N, 2.39. Found: C, 55.45; H, 6.44; N, 2.10.
3:7) both as colorless oils. Compound 21-(D): 1H NMR (C6D6) δH
1.75 (3H, s), 3.11 (3H, s), 3.136 (3H, s), 3.137 (1H, dd, J ) 9.2,
3.6 Hz), 3.16 (3H, s), 3.18 (3H, s), 3.28 (1H, d, J ) 3.6 Hz), 3.29
(3H, s), 3.36 (3H, s), 3.45 (1H, dd, J ) 8.1, 2.8 Hz), 3.55 (1H, d,
J ) 9.2 Hz), 3.67 (1H, dd, J ) 3.6, 3.4 Hz), 3.68 (1H, d, J ) 9.5
Hz), 3.75 (3H, s), 3.85-3.91 (2H, m), 4.00 (1H, ddd, J ) 8.9, 6.7,
2.2 Hz), 4.64 (1H, dd, J ) 12.3, 6.7 Hz), 4.65 (1H, d, J ) 3.6 Hz),
4.83 (1H, dd, J ) 11.8, 2.2 Hz), 5.43 (1H, d, J ) 8.1 Hz); 13C
NMR (C6D6) δC 20.6 (CH3), 54.8 (CH3), 58.1 (CH3), 58.4 (CH3),
58.8 (CH3), 59.3 (CH3), 59.5 (CH3), 61.1 (CH3), 64.6 (CH2), 68.9
(CH), 71.091 (CH2), 76.3 (CH), 77.47 (CH), 77.522 (CH), 80.0
(CH), 82.5 (CH), 84.0 (CH), 97.7 (CH), 101.6 (CH), 170.0 (C);
MS m/z (rel int) 452 (M+ - CH3O, <1), 307 (43), 247 (70), 88
(100); HRMS m/z calcd for C20H342HO11 452.2242, found 452.2242.
Reductive HAT of Methyl 2,3,4,6-Tetra-O-methyl-r-D-man-
nopyranosyl-(1f4)-2,3-di-O-methyl-6-O-phthalimido-r-D-glu-
copyranoside (18). Method A with n-Bu3SnH. A solution of
phthalimide 18 (100 mg, 0.170 mmol) in dry benzene (12 mL)
containing n-Bu3SnH (68 µL, 0.255 mmol) and AIBN (5.5 mg,
0.034 mmol) was heated at reflux temperature for 2.5 h. After this
time another portion of n-Bu3SnH (23 µL, 0.086 mmol) and AIBN
(5.5 mg, 0.034 mmol) were added and heating at reflux was
continued for an additional 1 h. After cooling to room temperature
the reaction mixture was concentrated under reduced pressure. The
residue was dissolved in CH3CN, washed with n-hexane and the
combined more polar extracts were concentrated under reduced
pressure. Acetylation of the crude residue in dry pyridine (3 mL)
containing Ac2O (1 mL) at room temperature for 4 h gave after
chromatotron chromatography (hexanes-EtOAc, 40:60) methyl
2,3,4,6-tetra-O-methyl-ꢀ-L-gulopyranosyl-(1f4)-6-O-acetyl-2,3-di-
O-methyl-R-D-glucopyranoside (21) (38 mg, 0.078 mmol, 46%) and
methyl 2,3,4,6-tetra-O-methyl-R-D-mannopyranosyl-(1f4)-6-O-
acetyl-2,3-di-O-methyl-R-D-glucopyranoside (41S) (14 mg, 0.029
mmol, 17%) both as colorless oils. Compound 21: [R]D +89.6 (c,
1
Compund 41S-[D]: H NMR (400 MHz, C6D6) δH 1.77 (3H, s),
3.06 (1H, dd, J ) 9.5, 3.4 Hz), 3.08 (3H, s), 3.09 (3H, s), 3.28
(3H, s), 3.34 (3H, s), 3.36 (3H, s), 3.48 (3H, s), 3.51 (3H, s),
3.69-3.82 (7H, m), 3.89 (1H, d, J ) 9.0 Hz), 3.90 (1H, dd, J )
9.8, 9.8 Hz), 4.01 (1H, ddd, J ) 9.8, 5.0, 1.9 Hz), 4.40 (1H, dd, J
) 12.2, 4.8 Hz), 4.58 (1H, d, J ) 3.4 Hz), 4.67 (1H, dd, J ) 11.9,
2.1 Hz), 5.55 (1H, d, J ) 1.8 Hz); 13C NMR (125.7 MHz, C6D6)
δC 20.5 (CH3), 54.8 (CH3), 57.3 (CH3), 57.6 (CH3), 58.6 (CH3),
59.1 (CH3), 60.4 (CH3), 60.8 (CH3), 63.9 (CH2), 68.8 (CH), 72.312
(CH2), 72.376 (CH2), 73.8 (CH), 76.894 (CH), 76.947 (CH), 77.3
(CH), 78.3 (CH), 81.9 (CH), 82.6 (CH), 83.8 (CH), 97.4 (CH),
100.2 (CH), 170.0 (C); MS m/z (rel int) 451 (M+ - CH3OH, <1),
450 (<1), 307 (19), 247 (26), 88 (100); HRMS m/z calcd for
C20H342HO11 451.2164, found 451.2179.
1
0.24); IR 1739 cm-1; H NMR (C6D6) δH 1.75 (3H, s), 3.11 (3H,
s), 3.136 (3H, s), 3.138 (1H, dd, J ) 8.9, 3.6 Hz), 3.16 (3H, s),
3.18 (3H, s), 3.28 (1H, dd, J ) 3.6, 1.4 Hz), 3.29 (3H, s), 3.36
(3H, s), 3.46 (1H, dd, J ) 8.1, 3.1 Hz), 3.55 (1H, dd, J ) 9.2, 5.9
Hz), 3.67 (1H, dd, J ) 3.6, 3.6 Hz), 3.68 (1H, dd, J ) 9.2, 7.6
Hz), 3.75 (3H, s), 3.85-3.91 (2H, m), 4.00 (1H, ddd, J ) 8.9, 6.7,
1.9 Hz), 4.14 (1H, ddd, J ) 7.6, 6.2, 1.4 Hz), 4.64 (1H, dd, J )
12.3, 6.7 Hz), 4.65 (1H, d, J ) 3.6 Hz), 4.83 (1H, dd, J ) 12.0,
2.2 Hz), 5.43 (1H, d, J ) 8.1 Hz); 13C NMR (C6D6) δC 20.6 (CH3),
54.8 (CH3), 58.1 (CH3), 58.4 (CH3), 58.8 (CH3), 59.3 (CH3), 59.5
(CH3), 61.1 (CH3), 64.6 (CH2), 68.9 (CH), 71.160 (CH2), 71.9 (CH),
76.3 (CH), 77.4 (CH), 77.574 (CH), 80.0 (CH), 82.5 (CH), 84.0
(CH), 97.7 (CH), 101.6 (CH), 170.0 (C); MS m/z (rel int) 450 (M+
- CH3OH, <1), 419 (<1), 307 (48), 247 (100); HRMS m/z calcd
for C20H34O11 450.2101, found 450.2108. Anal. Calcd for
C21H38O12: C, 52.27; H, 7.94. Found: C, 52.28; H, 7.91. Compound
Methyl 2,3,4,6-Tetra-O-acetyl-r-D-mannopyranosyl-(1f4)-2,3-
di-O-methyl-6-O-phthalimido-r-D-glucopyranoside (20). DEAD
(192 µL, 1.22 mmol) was added dropwise to a stirred solution of
the alcohol 19 (270 mg, 0.489 mmol), N-hydroxyphthalimide (199
mg, 1.22 mmol) and PPh3 (320 mg, 1.22 mmol) in dry THF (5.3
mL) and the resulting solution was stirred at 0 °C for 2 h. Then
the solvent was removed and the crude was quenched with water
and extracted with CHCl3. The combined extracts were dried over
Na2SO4 and concentrated under reduced pressure. The residue
obtained was purified by column chromatography (hexanes-EtOAc,
70:30 f 30:70) to give compound 20 (284 mg, 0.407 mmol, 83%)
1
41S: [R]D +62.3 (c, 0.96); IR 1742 cm-1; H NMR (400 MHz,
1
as a white foam: [R]D +72.9 (c, 0.122); IR 1791, 1734 cm-1; H
C6D6) δH 1.77 (3H, s), 3.06 (1H, dd, J ) 9.5, 3.4 Hz), 3.08 (3H,
s), 3.09 (3H, s), 3.28 (3H, s), 3.34 (3H, s), 3.36 (3H, s), 3.48 (3H,
s), 3.51 (3H, s), 3.69-3.82 (7H, m), 3.89 (1H, dd, J ) 9.8, 9.8
Hz), 4.01 (1H, ddd, J ) 9.8, 5.0, 1.9 Hz), 4.40 (1H, dd, J ) 12.2,
4.8 Hz), 4.58 (1H, d, J ) 3.4 Hz), 4.67 (1H, dd, J ) 11.9, 2.1 Hz),
5.55 (1H, d, J ) 1.8 Hz); 13C NMR (100.6 MHz, C6D6) δC 20.5
(CH3), 54.8 (CH3), 57.3 (CH3), 57.6 (CH3), 58.6 (CH3), 59.1 (CH3),
60.4 (CH3), 60.8 (CH3), 63.9 (CH2), 68.8 (CH), 72.4 (CH2), 73.8
(CH), 76.9 (CH), 77.3 (CH), 78.2 (CH), 81.9 (CH), 82.6 (CH),
83.8 (CH), 97.4 (CH), 100.2 (CH), 170.0 (C); MS m/z (rel int) 419
(M+ - C2H7O2, 1), 405 (1), 307 (100); HRMS m/z calcd for
C19H31O10 419.1917, found 419.1927. Anal. Calcd for C21H38O12:
C, 52.27; H, 7.94. Found: C, 52.25; H, 8.03.
NMR δH 1.98 (3H, s), 2.04 (3H, s), 2.06 (3H, s), 2.13 (3H, s), 3.25
(1H, dd, J ) 9.8, 3.5 Hz), 3.41 (3H, s), 3.48 (3H, s), 3.59 (1H, dd,
J ) 8.6, 8.6 Hz), 3.61 (3H, s), 3.88 (1H, ddd, J ) 10.0, 2.6, 2.6
Hz), 3.95 (1H, dd, J ) 10.0, 8.6 Hz), 4.07 (1H, dd, J ) 11.8, 2.3
Hz), 4.11 (1H, ddd, J ) 9.2, 5.5, 2.0 Hz), 4.23 (1H, dd, J ) 12.1,
5.5 Hz), 4.43-4.48 (2H, m), 4.71 (1H, d, J ) 3.4 Hz), 5.260 (1H,
d, J ) 2.0 Hz), 5.262 (1H, dd, J ) 9.8, 9.8 Hz), 5.31 (1H, dd, J )
9.8, 3.2 Hz), 5.36 (1H, dd, J ) 3.2, 2.0 Hz), 7.73 (2H, m), 7.81
(2H, m); 13C NMR (100.6 MHz) δC 20.58 (CH3), 20.63 (CH3),
20.7 (CH3), 20.8 (CH3), 55.6 (CH3), 58.8 (CH3), 61.1 (CH3), 62.8
(CH2), 66.1 (CH), 69.0 (CH), 69.36 (CH), 69.43 (CH), 69.6 (CH),
76.4 (CH2), 77.7 (CH), 81.8 (CH), 82.6 (CH), 97.5 (CH), 99.9 (CH),
123.4 (2 × CH), 128.9 (2 × C), 134.4 (2 × CH), 163.1 (2 × C),
169.7 (C), 169.8 (C), 169.9 (C), 170.7 (C); MS m/z (rel int) 577
(M+ - 2AcOH, <1), 492 (<1), 417 (1), 331 (70), 88 (100); HRMS
m/z calcd for C27H31NO13 577.1795, found 577.1814. Anal. Calcd
for C31H39NO17: C, 53.37; H, 5.63; N, 2.01. Found: C, 53.61; H,
5.62; N, 1.80.
Method B with n-Bu3SnD. A solution of phthalimide 18 (82
mg, 0.140 mmol) in dry benzene (10 mL) containing n-Bu3SnD
(56 µL, 0.210 mmol) and AIBN (4.6 mg, 0.028 mmol) was heated
at reflux temperature for 2.5 h. After this time another portion of
n-Bu3SnD (37 µL, 0.138 mmol) and AIBN (4.6 mg, 0.028 mmol)
were added and heating at reflux was continued for an additional
1 h. After cooling to room temperature the reaction mixture was
concentrated under reduced pressure. The residue was dissolved
in CH3CN, washed with n-hexane and the combined more polar
extracts were concentrated under reduced pressure. Acetylation of
the crude residue in dry pyridine (3 mL) containing Ac2O (1 mL)
at room temperature for 4 h after gave chromatotron chromatog-
raphy (hexanes-EtOAc, 40:60) methyl 2,3,4,6-tetra-O-methyl-ꢀ-
L-(5-2H)gulopyranosyl-(1f4)-2,3-di-O-methyl-R-D-glucopyrano-
side [21-(D)] (35 mg, 0.072 mmol, 52%) and methyl 2,3,4,6-tetra-
O-methyl-R-D-[5-2H]mannopyranosyl-(1f4)-2,3-di-O-methyl-R-D-
glucopyranoside (41S-[D]) (14 mg, 0.029 mmol, 21%, 1H/2H ratio,
Reductive HAT of Methyl 2,3,4,6-Tetra-O-acetyl-r-D-man-
nopyranosyl-(1f4)-2,3-di-O-methyl-6-O-phthalimido-r-D-glu-
copyranoside (20). Method A with n-Bu3SnH. A solution of
phthalimide 20 (80 mg, 0.114 mmol) in dry benzene (8 mL)
containing n-Bu3SnH (37 µL, 0.136 mmol) and AIBN (2 mg, 0.011
mmol) was heated at reflux temperature for 2 h. After this time
another portion of n-Bu3SnH (15 µL, 0.057 mmol) and AIBN (2
mg, 0.011 mmol) were added and heating at reflux was continued
for an additional 1 h. After cooling to room temperature the reaction
mixture was concentrated under reduced pressure. The residue was
dissolved in CH3CN, washed with n-hexane and the combined more
J. Org. Chem. Vol. 73, No. 19, 2008 7717

Mart´ın et al.
polar extracts were concentrated under reduced pressure. Column
chromatography of the crude residue (hexanes-EtOAc, 80:20 f
20:80) afforded methyl 2,3,4,6-tetra-O-acetyl-R-D-mannopyranosyl-
(1f4)-2,3-di-O-methyl-R-D-glucopyranoside (19) (26.7 mg, 0.048
mmol, 42%) and methyl 2,3,4,6-tetra-O-acetyl-ꢀ-L-gulopyranosyl-
(1f4)-2,3-di-O-methyl-R-D-glucopyranoside (22) (27 mg, 0.049
mmol, 43%), as colorless oils. Compound 22: [R]D +66.2 (c, 0.12);
IR 3544, 1750 cm-1; 1H NMR δH 2.01 (3H, s), 2.10 (3H, s), 2.13
(3H, s), 2.17 (3H, s), 2.70 (1H, dd, J ) 9.0, 5.5 Hz), 3.24 (1H, dd,
J ) 9.5, 3.5 Hz), 3.41 (3H, s), 3.52 (3H, s), 3.54 (1H, m), 3.55
(1H, dd, J ) 9.3, 9.3 Hz), 3.62 (3H, s), 3.67 (1H, ddd, J ) 12.5,
9.1, 2.0 Hz), 3.74 (1H, dd, J ) 9.5, 9.5 Hz), 3.97 (1H, dd, J )
11.0, 8.0 Hz), 4.03 (1H, ddd, J ) 12.5, 6.0, 2.5 Hz), 4.23-4.29
(2H, m), 4.86 (1H, d, J ) 3.5 Hz), 4.92 (1H, d, J ) 3.5 Hz), 4.95
(1H, dd, J ) 8.5, 3.5 Hz), 5.21 (1H, d, J ) 8.5 Hz), 5.38 (1H, dd,
J ) 3.5, 3.5 Hz); 13C NMR δC 20.6 (CH3), 20.7 (3 × CH3), 55.2
(CH3), 58.9 (CH3), 60.8 (CH2), 61.1 (CH3), 62.560 (CH2), 67.8
(CH), 68.122 (CH), 68.4 (CH), 70.0 (CH), 70.9 (CH), 74.9 (CH),
82.3 (CH), 83.1 (CH), 97.5 (CH), 99.1 (CH), 168.8 (C), 169.36
(C), 169.44 (C), 170.6 (C); MS m/z (rel int) 492 (M+ - AcOH,
<1), 331 (35), 169 (26), 88 (100); HRMS m/z calcd for C21H32O13
492.1843, found 492.1826. Anal. Calcd for C23H36O15: C, 50.00;
H, 6.57. Found: C, 50.06; H, 6.72.
Methyl 2,3,4-Tri-O-methyl-r-L-rhamnopyranosyl-(1f4)-2,3-di-
O-methyl-6-O-phthalimido-r-D-galactopyranoside (24). DEAD (234
µL, 1.462 mmol) was added dropwise to a stirred solution of the
alcohol 23 (300 mg, 0.732 mmol), N-hydroxyphthalimide (239 mg,
1.464 mmol) and PPh3 (383 mg, 1.464 mmol) in dry THF (8 mL)
and the resulting solution was stirred at 0 °C for 3 h. Then the
solvent was removed and the crude was quenched with water and
extracted with Et2O. The combined extracts were dried over Na2SO4
and concentrated under reduced pressure. The residue obtained was
purified by column chromatography (hexanes-AcOEt, 50:50 f
30:70) to give compound 24 (331 mg, 0.596 mmol, 82%) as a foam:
1
[R]D +17.5 (c, 0.12); IR 1793, 1739 cm-1; H NMR (400 MHz)
δH 1.21 (3H, d, J ) 6.1 Hz), 3.08 (1H, dd, J ) 9.4, 9.4 Hz), 3.42
(1H, dd, J ) 9.3, 3.2 Hz), 3.45 (3H, s), 3.47 (3H, s), 3.48 (3H, s),
3.496 (3H, s), 3.501 (6H, s), 3.54 (1H, m), 3.56 (1H, dd, J ) 9.3,
2.9 Hz), 3.61 (1H, dd, J ) 10.1, 2.6 Hz), 3.71 (1H, dd, J ) 3.4,
2.1 Hz), 4.15 (1H, ddd, J ) 5.6, 5.6, 0 Hz), 4.31 (1H, m), 4.33
(2H, d, J ) 5.6 Hz), 4.90 (1H, d, J ) 3.2 Hz), 5.15 (1H, d, J ) 1.9
Hz), 7.73-7.76 (2H, m), 7.82-7.84 (2H, m); 13C NMR (100.6
MHz) δC 17.6 (CH3), 55.7 (CH3), 57.6 (CH3), 58.48 (CH3), 58.53
(CH3), 58.67 (CH3), 60.7 (CH3), 68.2 (CH), 68.8 (CH), 74.0 (CH),
77.4 (CH), 77.7 (CH), 78.3 (CH2), 80.0 (CH), 80.6 (CH), 81.8 (CH),
98.0 (CH), 98.5 (CH), 123.6 (2 × CH), 128.9 (2 × C), 134.5 (2 ×
CH), 163.4 (2 × C); MS m/z (%) 554 (M+ - H, 4), 524 (6), 492
(100); HRMS m/z calcd for C26H36NO12 554.2238, found 554.2216.
Anal. Calcd for C26H37NO12: C, 56.21; H, 6.71; N, 2.52. Found:
C, 56.40; H, 6.98; N, 2.40.
Method B with n-Bu3SnD. A solution of phthalimide 20 (129
mg, 0.185 mmol) in dry benzene (13 mL) containing n-Bu3SnH
(55 µL, 0.277 mmol) and AIBN (3 mg, 0.018 mmol) was heated
at reflux temperature for 2 h. After this time another portion of
n-Bu3SnD (55 µL, 0.277 mmol) and AIBN (3 mg, 0.018 mmol)
was added and heating at reflux continued for an additional 1 h.
After cooling to room temperature the reaction mixture was
concentrated under reduced pressure. The residue was dissolved
in CH3CN, washed with n-hexane and the combined more polar
extracts were concentrated under reduced pressure. Column chro-
matography of the crude residue (hexanes-EtOAc, 80:20 f 20:
80) afforded methyl 2,3,4,6-tetra-O-acetyl-R-D-[5-2H]mannopyranosyl-
(1f4)-2,3-di-O-methyl-R-D-glucopyranoside (19-[D]) (30 mg, 0.054
Reductive HAT of Methyl 2,3,4-Tri-O-methyl-r-L-rhamnopy-
ranosyl-(1f4)-2,3-di-O-methyl-6-O-phthalimido-r-D-glucopyra-
noside (24). Method A with n-Bu3SnH. A solution of phthalimide
24 (40 mg, 0.072 mmol) in dry benzene (5.5 mL) containing
n-Bu3SnH (19 µL, 0.072 mmol) and AIBN (1.2 mg, 0.007 mmol)
was heated at reflux temperature for 1 h. After cooling to room
temperature the reaction mixture was concentrated under reduced
pressure. The residue was dissolved in CH3CN, washed with
n-hexane and the combined more polar extracts were concentrated
under reduced pressure. Column chromatography (hexanes-EtOAc,
50:50 f 30:70) gave methyl 6-deoxy-2,3,4-tri-O-methyl-ꢀ-D-
gulopyranosyl-(1f4)-2,3-di-O-methyl-R-D-galactopyranoside (27)
(18 mg, 0.044 mmol, 61%) and the alcohol 23 (4.5 mg, 0.011 mmol,
15%), both as colorless oils. Compound 27: [R]D +20.0 (c, 0.18);
IR 3482 cm-1; 1H NMR (400 MHz) δH 1.25 (3H, d, J ) 6.6 Hz),
3.08 (1H, dd, J ) 3.4, 1.6 Hz), 3.27 (1H, dd, J ) 8.0, 3.2 Hz),
3.39 (3H, s), 3.45 (3H, s), 3.47 (3H, s), 3.49 (3H, s), 3.50 (3H, s),
3.55 (1H, m), 3.57 (1H, dd, J ) 10.1, 2.9 Hz), 3.60 (3H, s), 3.62
(1H, dd, J ) 10.1, 3.2 Hz), 3.73 (1H, dd, J ) 3.2, 3.2 Hz),
3.75-3.82 (2H, m), 3.96 (1H, dddd, J ) 6.4, 6.4, 6.4, 1.6 Hz),
4.26 (1H, dd, J ) 2.7, 0 Hz), 4.81 (1H, d, J ) 3.2 Hz), 4.90 (1H,
d, J ) 8.0 Hz); 13C NMR (100.6 MHz) δC 15.668 (CH3), 55.3
(CH3), 58.6 (CH3), 59.1 (CH3), 59.3 (CH3), 59.4 (CH3), 59.9 (CH2),
60.0 (CH3), 68.9 (CH), 69.3 (CH), 71.2 (CH), 77.7 (CH), 78.26
(CH), 78.31 (CH), 79.212 (CH), 79.6 (CH), 98.3 (CH), 101.4 (CH);
MS (FAB) m/z (%) 433 (M+ + Na, 88), 411 (26), 133 (100); HRMS
m/z calcd for C18H34NaO10 433.2050, found 433.2051. Anal. Calcd
for C18H34O10: C, 52.67; H, 8.35. Found: C, 52.73; H, 8.06.
Method B with n-Bu3SnD. A solution of phthalimide 24 (43
mg, 0.078 mmol) in dry benzene (5.8 mL) containing n-Bu3SnD
(21 µL, 0.078 mmol) and AIBN (1.3 mg, 0.008 mmol) was heated
at reflux temperature for 1 h. After this time another portion of
n-Bu3SnD (21 µL, 0.078 mmol) and AIBN (1.3 mg, 0.008 mmol)
were added and heating at reflux was continued for an additional
1 h. After cooling to room temperature the reaction mixture was
concentrated under reduced pressure. The residue was dissolved
in CH3CN, washed with n-hexane and the combined more polar
extracts were concentrated under reduced pressure. Column chro-
matography (hexanes-EtOAc, 50:50 f 30:70) gave methyl 6-deoxy-
2,3,4-tri-O-acetyl-ꢀ-D-(5-2H)gulopyranosyl-(1f4)-2,3-di-O-methyl-
R-D-galactopyranoside [27-(D)] (16.6 mg, 0.040 mmol, 52%),
methyl 2,3,4-tri-O-methyl-R-L-[5-2H]rhamnopyranosyl-(1f4)-2,3-
1
mmol, 29%, H/2H ratio, 3:7) and methyl 2,3,4,6-tetra-O-acetyl-
ꢀ-L-(5-2H)gulopyranosyl-(1f4)-2,3-di-O-methyl-R-D-glucopyrano-
side [22-(D)] (40.2 mg, 0.072 mmol, 39%), as colorless oils.
1
Compound 19-[D]: H NMR δH 1.99 (3H, s), 2.04 (3H, s), 2.11
(3H, s), 2.14 (3H, s), 3.19 (1H, dd, J ) 9.3, 3.7 Hz), 3.42 (3H, s),
3.49 (3H, s), 3.58 (1H, dd, J ) 8.9, 8.9 Hz), 3.59 (3H, s), 3.62-3.65
(2H, m), 3.81 (2H, m), 4.05 (1H, ddd, J ) 8.9, 6.1, 2.0 Hz), 4.134
(1H, d, J ) 12.1 Hz), 4.137 (1H, dd, J ) 12.1, 2.8 Hz), 4.210 (1H,
d, J ) 12.2 Hz), 4.215 (1H, d, J ) 12.2, 4.5 Hz), 4.81 (1H, dd, J
) 3.6 Hz), 5.236 (1H, d, J ) 9.7 Hz), 5.238 (1H, dd, J ) 9.7, 9.7
Hz), 5.25 (1H, d, J ) 1.6 Hz), 5.30 (1H, dd, J ) 9.8, 3.2 Hz), 5.31
(1H, dd, J ) 3.2, 1.6 Hz). 13C NMR δC 20.6 (3 × CH3), 20.8 (CH3),
55.3 (CH3), 58.9 (CH3), 61.3 (CH3), 61.5 (CH2), 62.942 (CH2),
63.011 (CH2), 62.235 (CH), 66.287 (CH), 68.8 (CH), 69.5 (CH),
69.6 (CH), 70.0 (CH), 76.6 (CH), 82.4 (CH), 83.0 (CH), 97.5 (CH),
99.5 (CH), 169.7 (C), 169.8 (C), 169.9 (C), 170.7 (C); MS m/z (rel
int) 493 (M+ - AcOH, 2), 492 (<1), 332 (44), 331 (15), 88 (100);
HRMS m/z calcd for C21H312HO13 493.1906, found 493.1914.
1
Compound 22-(D): H NMR δH 2.00 (3H, s), 2.08 (3H, s), 2.12
(3H, s), 2.16 (3H, s), 2.69 (1H, dd, J ) 8.9, 6.1 Hz, OH), 3.22
(1H, dd, J ) 9.3, 3.6 Hz), 3.40 (3H, s), 3.506 (3H, s), 3.510 (1H,
m), 3.55 (1H, dd, J ) 9.4, 9.4 Hz), 3.61 (3H, s), 3.66 (1H, ddd, J
) 12,6, 8.9, 2.0 Hz), 3.73 (1H, dd, J ) 9.4, 9.4 Hz), 3.96 (1H, d,
J ) 11.8 Hz), 4.01 (1H, ddd, J ) 13.0, 6.1, 2.4 Hz), 4.26 (1H, d,
J ) 11.8 Hz), 4.85 (1H, d, J ) 3.6 Hz), 4.90 (1H, d, J ) 3.7 Hz),
4.94 (1H, dd, J ) 8.5, 3.2 Hz), 5.20 (1H, d, J ) 8.5 Hz), 5.37 (1H,
dd, J ) 3.2, 3.2 Hz); 13C NMR δC 20.5 (CH3), 20.6 (3 × CH3),
55.2 (CH3), 58.9 (CH3), 60.7 (CH2), 61.0 (CH3), 62.439 (CH2),
67.8 (CH), 68.021 (CH), 68.4 (CH), 69.9 (CH), 74.9 (CH), 82.2
(CH), 83.1 (CH), 97.5 (CH), 99.0 (CH), 168.8 (C), 169.3 (C), 169.4
(C), 170.5 (C); MS m/z (rel int) 493 (M+ - AcOH, 2), 332 (59),
170 (36), 88 (100); HRMS m/z calcd for C21H312HO13 493.1906,
found 493.1894.
7718 J. Org. Chem. Vol. 73, No. 19, 2008

Intramolecular 1,8-Hydrogen Atom Transfer
di-O-methyl-R-D-galactopyranoside (23-[D]) (4.8 mg, 0.012 mmol,
663.2166. Anal. Calcd for C29H37NO15: C, 54.46; H, 5.83; N, 2.19.
Found: C, 54.10; H, 5.78; N, 2.38.
1
15%, H/2H ratio 2:8) (contaminated with ca. 30% of compound
29), and methyl (5S)-5,6-anhydro-2,3-di-O-methyl-4,6-dideoxy-R-
D-erythro-hexos-5-ulopyranosyl-(1f4)-2,3-di-O-methyl-R-D-glu-
copyranoside (29) (3.6 mg, 0.010 mmol, 12%), all as colorless oils.
Compound 27-(D): 1H NMR δH 1.24 (3H, s), 3.07 (1H, d, J ) 3.5
Hz), 3.27 (1H, dd, J ) 8.0, 3.0 Hz), 3.38 (3H, s), 3.45 (3H, s),
3.47 (3H, s), 3.48 (3H, s), 3.49 (3H, s), 3.55 (1H, m), 3.57 (1H,
dd, J ) 10.0, 3.0 Hz), 3.60 (3H, s), 3.61 (1H, dd, J ) 10.0, 3.0
Hz), 3.72 (1H, dd, J ) 3.5, 3.5 Hz), 3.74-3.82 (2H, m), 4.25 (1H,
dd, J ) 2.5, 0 Hz), 4.80 (1H, d, J ) 3.5 Hz), 4.90 (1H, d, J ) 8.0
Hz); 13C NMR δC 15.541 (CH3), 55.3 (CH3), 58.6 (CH3), 59.1
(CH3), 59.3 (CH3), 59.4 (CH3), 59.9 (CH2), 60.0 (CH3), 69.2 (CH),
71.1 (CH), 77.6 (CH), 78.20 (CH), 78.26 (CH), 79.075 (CH), 79.6
(CH), 98.3 (CH), 101.3 (CH); MS (FAB) m/z (%) 434 (M+ + Na,
100), 133 (51); HRMS m/z calcd for C18H332HNaO10 434.2112,
found 434.2109. Compound 23-[D] (data taken from a mixture 23-
Reductive HAT of Methyl 2,3,4-Tri-O-acetyl-r-L-rhamnopy-
ranosyl-(1f4)-2,3-di-O-methyl-6-O-phthalimido-r-D-galactopy-
ranoside (26). Method A with n-Bu3SnH. A solution of phthal-
imide 26 (95 mg, 0.149 mmol) in dry benzene (11.2 mL) containing
n-Bu3SnH (40 µL, 0.149 mmol) and AIBN (2.4 mg, 0.015 mmol)
was heated at reflux temperature for 1.5 h. After cooling to room
temperature the reaction mixture was concentrated under reduced
pressure. The residue was dissolved in CH3CN, washed with
n-hexane and the combined more polar extracts were concentrated
under reduced pressure. The residue was purified by column
chromatography (hexanes-EtOAc, 50:50 f 30:70) to give methyl
2,3-di-O-acetyl-4,6-dideoxy-ꢀ-D-erythro-hex-4-enopyranosyl-(1f4)-
2,3-di-O-methyl-R-D-galactopyranoside (30) (3.5 mg, 0.008 mmol,
5%), the alcohol 25 (16.5 mg, 0.033 mmol, 22%), previously
described, and the methyl 2,3,4-tri-O-acetyl-6-deoxy-ꢀ-D-gulopy-
ranosyl-(1f4)-2,3-di-O-methyl-R-D-galactopyranoside (28) (38.2
mg, 0.077 mmol, 52%) as colorless oils. Compound 30: [R]D -33.8
(c, 0.29); IR 3468, 1747 cm-1; 1H NMR (400 MHz) δH 1.83 (3H,
s), 2.05 (3H, s), 2.10 (3H, s), 2.21 (1H, dd, J ) 9.8, 7.5 Hz), 3.41
(3H, s), 3.50 (3H, s), 3.51 (3H, s), 3.57-3.58 (2H, m), 3.60-3.75
(2H, m), 3.82 (1H, ddd, J ) 6.6, 6.6, 1.3 Hz), 4.24 (1H, dd, J )
1.1, 1.1 Hz), 4.66 (1H, br d, J ) 3.7 Hz), 4.85 (1H, d, J ) 1.6 Hz),
5.25 (1H, dd, J ) 5.0, 5.0 Hz), 5.30 (1H, d, J ) 5.3 Hz), 5.51 (1H,
ddd, J ) 5.3, 3.7, 1.6 Hz); 13C NMR (100.6 MHz) δC 19.5 (CH3),
20.8 (CH3), 20.9 (CH3), 55.4 (CH3), 58.7 (CH3), 59.1 (CH3), 61.4
(CH2), 64.1 (CH), 66.0 (CH), 69.6 (CH), 73.4 (CH), 78.0 (CH),
79.6 (CH), 95.1 (CH), 97.9 (CH), 98.4 (CH), 151.1 (C), 169.9 (C),
170.2 (C); MS m/z (%) 435 (M+ + H, <1), 402 (<1), 374 (1), 212
(11), 88 (100); HRMS calcd for C19H31O11 435.1866, found
435.1877. Anal. Calcd for C19H30O11: C, 52.53; H, 6.96. Found:
C, 52.23; H, 6.90. Compound 28: crystalline solid, mp 153.2-154.9
°C (from n-hexane-acetone); [R]D +60.0 (c, 0.53); IR 3506, 1748
1
[D]/29, 7:3): H NMR (400 MHz) δH 1.29 (3H, s), 3.13 (1H, d, J
) 9.3 Hz), 3.42 (3H, s), 3.46 (1H, dd, J ) 9.3, 2.7 Hz), 3.48 (3H,
s), 3.51 (6H, s), 3.52 (3H, s), 3.55 (3H, s), 3.58 (1H, dd, J ) 2.1,
2.1 Hz), 3.63-3.69 (2H, m), 3.75 (1H, dd, J ) 3.2, 1.8 Hz), 3.78
(1H, dd, J ) 11.1, 7.2 Hz), 3.86 (1H, ddd, J ) 6.9, 6.9, 0 Hz),
4.16 (1H, br s), 4.89 (1H, d, J ) 2.6 Hz), 5.11 (1H, d, J ) 1.9
Hz); 13C NMR δC 17.589 (CH3), 17.648 (CH3), 55.2 (CH3), 57.6
(CH3), 58.48 (CH3), 58.51 (CH3), 58.61 (CH3), 60.7 (CH3), 61.7
(CH2), 69.8 (CH), 73.8 (CH), 77.3 (CH), 77.8 (CH), 79.8 (CH),
80.5 (CH), 81.553 (CH), 81.628 (CH), 97.7 (CH), 99.1 (CH); MS
m/z (%) 411 (M+ + H, 6), 393 (17), 88 (100). Compound 29: [R]D
+103.3 (c, 0.12); IR 2930, 1104, 1053 cm-1; 1H NMR (400 MHz)
δH 1.36 (3H, s), 1.93 (1H, dd, J ) 12.5, 12.5 Hz), 2.09 (1H, dd, J
) 12.7, 4.8 Hz), 3.39 (3H, s), 3.40 (3H, s), 3.46-3.54 (2H, m),
3.47 (3H, s), 3.51 (3H, s), 3.52 (3H, s), 3.61 (1H, dd, J ) 10.0, 3.7
Hz), 3.74 (1H, m), 3.78 (1H, dd, J ) 13.5, 2.4 Hz), 3.95 (1H, ddd,
J ) 11.9, 4.8, 2.9 Hz), 4.08 (1H, dd, J ) 13.5, 1.3 Hz), 4.16 (1H,
dd, J ) 3.2, 0 Hz), 4.95 (1H, d, J ) 3.7 Hz), 5.01 (1H, d, J ) 1.8
Hz); 13C NMR (100.6 MHz) δC 25.3 (CH3), 35.6 (CH2), 55.3 (CH3),
56.0 (CH3), 58.1 (CH3), 58.7 (CH3), 59.1 (CH3), 63.2 (CH2), 67.4
(CH), 72.1 (CH), 73.5 (CH), 74.4 (CH), 77.3 (CH), 78.6 (CH),
98.0 (CH), 98.7 (CH), 100.4 (C); MS m/z (%) 378 (M+, 18), 347
(11), 88 (100); HRMS m/z calcd for C17H30O9 378.1890, found
378.1886. Anal. Calcd for C17H30O9: C, 53.96; H, 7.99. Found: C,
54.07; H, 7.97.
1
cm-1; H NMR δH 1.19 (3H, d, J ) 6.4 Hz), 2.03 (3H, s), 2.13
(3H, s), 2.17 (3H, s), 3.23 (1H, m), 3.39 (3H, s), 3.47 (1H, dd, J )
10.1, 3.5 Hz), 3.48 (3H, s), 3.49 (3H, s), 3.57 (1H, dd, J ) 10.1,
3.0 Hz), 3.63 (1H, m), 3.77-3.83 (2H, m), 4.15 (1H, dddd, J )
6.5, 6.5, 6.5, 1.3 Hz), 4.19 (1H, br d, J ) 3.1 Hz), 4.81 (1H, d, J
) 3.5 Hz), 4.83 (1H, dd, J ) 3.7, 1.4 Hz), 4.94 (1H, d, J ) 8.3
Hz), 5.04 (1H, dd, J ) 8.3, 3.5 Hz), 5.34 (1H, dd, J ) 3.6, 3.6
Hz); 13C NMR (100.6 MHz) δC 15.715 (CH3), 20.6 (CH3), 20.7
(CH3), 20.8 (CH3), 55.4 (CH3), 58.4 (CH3), 59.1 (CH3), 60.2 (CH2),
67.9 (CH), 68.4 (CH), 68.8 (CH), 69.0 (CH), 70.100 (CH), 73.3
(CH), 78.0 (CH), 79.2 (CH), 97.9 (CH), 99.8 (CH), 168.9 (C), 169.5
(C), 169.8 (C); MS (FAB) m/z (%) 518 (M+ + H + Na, 6), 517
(21), 391 (32), 273 (63), 73 (100); HRMS calcd for C21H35NaO13
518.1975, found 518.1984. Anal. Calcd for C21H34O13: C, 51.01;
H, 6.93. Found: C, 51.15; H, 6.89.
Methyl 2,3,4-Tri-O-acetyl-r-L-rhamnopyranosyl-(1f4)-2,3-di-
O-methyl-6-O-phthalimido-r-D-galactopyranoside (26). DEAD (278
µL, 1.77 mmol) was added dropwise to a stirred solution of the
alcohol 25 (350 mg, 0.708 mmol), N-hydroxyphthalimide (388 mg,
1.77 mmol) and PPh3 (464 mg, 1.77 mmol) in dry THF (7.7 mL)
under nitrogen at 0 °C and the resulting solution was stirred at this
temperature for 1.5 h. The reaction was quenched with water and
extracted with CHCl3. The combined extracts were dried over
Na2SO4 and concentrated under reduced pressure. The residue
obtained was purified by column chromatography (hexanes-EtOAc,
80:20) to give N-phthalimide 26 (380 mg, 0.595 mmol, 84%) as
Method B with n-Bu3SnD. A solution of phthalimide 26 (90
mg, 0.141 mmol) in dry benzene (10.6 mL) containing n-Bu3SnD
(38 µL, 0.141 mmol) and AIBN (2.3 mg, 0.014 mmol) was heated
at reflux temperature for 1 h. After this time another portion of
n-Bu3SnD (38 µL, 0.141 mmol) and AIBN (2.3 mg, 0.014 mmol)
were added and heating at reflux was continued for an additional
1 h. After cooling to room temperature the reaction mixture was
concentrated under reduced pressure. The residue was dissolved
in CH3CN, washed with n-hexane and the combined more polar
extracts were concentrated under reduced pressure. The residue was
purified by column chromatography (hexanes-EtOAc, 50:50 f
30:70) to give the olefin 30 (9 mg, 0.021 mmol, 15%), described
above, methyl 2,3,4-tri-O-acetyl-R-L-[5-2H]rhamnopyranosyl-(1f4)-
2,3-di-O-methyl-R-D-galactopyranoside (25-[D]) (12.6 mg, 0.025
mmol, 18%, 1H/2H ratio, 3:7), and methyl 2,3,4-tri-O-acetyl-6-
deoxy-ꢀ-D-(5-2H)gulopyranosyl-(1f4)-2,3-di-O-methyl-R-D-galac-
topyranoside [28-(D)] (31.2 mg, 0.063 mmol, 45%) as colorless
an amorphous solid: [R]D +17.5 (c, 0.245); IR 1791, 1735 cm-1
;
1H NMR δH 1.15 (3H, d, J ) 6.3 Hz), 1.97 (3H, s), 2.04 (3H, s),
2.12 (3H, s), 3.44 (3H, s), 3.48 (3H, s), 3.52 (3H, s), 3.59 (1H, dd,
J ) 10.1, 2.7 Hz), 3.66 (1H, dd, J ) 10.1, 3.5 Hz), 3.95 (1H, dddd,
J ) 9.9, 6.3, 6.3, 6.3 Hz), 4.13 (1H, ddd, J ) 6.1, 6.1, 0 Hz), 4.33
(1H, dd, J ) 11.1, 5.9 Hz), 4.36 (1H, dd, J ) 11.1, 6.2 Hz), 4.40
(1H, dd, J ) 1.1, 0 Hz), 4.87 (1H, d, J ) 3.5 Hz), 5.05 (1H, dd,
J ) 9.9, 9.9 Hz), 5.07 (1H, d, J ) 1.5 Hz), 5.29 (1H, dd, J ) 10.1,
3.3 Hz), 5.50 (1H, dd, J ) 3.0, 2.1 Hz), 7.76 (2H, m), 7.84 (2H,
m); 13C NMR (100.6 MHz) δC 17.3 (CH3), 20.7 (CH3), 20.8 (CH3),
20.9 (CH3), 55.8 (CH3), 58.6 (CH3), 59.3 (CH3), 67.3 (CH), 67.6
(CH), 69.1 (CH), 69.9 (CH), 70.8 (CH), 75.0 (CH), 77.4 (CH2),
77.6 (CH), 79.6 (CH), 98.4 (CH), 99.3 (CH), 123.6 (2 × CH), 128.8
(2 × C), 134.6 (2 × CH), 163.5 (2 × C), 169.8 (C), 169.9 (C),
170.0 (C); MS (FAB) m/z (%) 663 (M+ + H + Na, 3), 662 (9),
273 (28), 55 (100); HRMS calcd for C29H38NNaO15 663.2139, found
1
oils. Compound 25-[D]: H NMR δH 1.22 (3H, s), 1.23 (3H, d, J
) 6.6 Hz), 1.99 (3H, s), 2.05 (3H, s), 2.14 (3H, s), 3.42 (3H, s),
3.47 (3H, s), 3.54 (3H, s), 3.56 (1H, dd, J ) 10.1, 2.9 Hz), 3.64
J. Org. Chem. Vol. 73, No. 19, 2008 7719

Mart´ın et al.
(1H, dd, J ) 10.1, 3.5 Hz), 3.66 (1H, m), 3.80-3.86 (2H, m), 3.98
(1H, dddd, J ) 10.0, 6.3, 6.3, 6.3 Hz), 4.12 (1H, dd, J ) 2.7, 0
Hz), 4.88 (1H, d, J ) 3.5 Hz), 5.05 (1H, d, J ) 2.1 Hz), 5.071
(1H, d, J ) 10.0 Hz), 5.073 (1H, dd, J ) 9.8, 9.8 Hz), 5.31 (1H,
dd, J ) 10.0, 3.3 Hz), 5.47 (1H, dd, J ) 3.3, 2.1 Hz); 13C NMR
(100.6 MHz) δC 17.350 (CH3), 17.489 (CH3), 20.7 (CH3), 20.8
(CH3), 20.9 (CH3), 55.4 (CH3), 58.8 (CH3), 59.3 (CH3), 62.0 (CH2),
67.5 (CH), 69.0 (CH), 69.8 (CH), 69.9 (CH), 70.869 (CH), 70.932
(CH), 75.1 (CH), 78.0 (CH), 79.8 (CH), 98.1 (CH), 99.7 (CH),
67.9 (CH), 68.4 (CH), 69.0 (CH), 70.036 (CH), 73.3 (CH), 78.0
(CH), 79.2 (CH), 97.9 (CH), 99.8 (CH), 168.8 (C), 169.5 (C), 169.8
(C); MS (FAB) m/z (%) 519 (M+ + H + Na, 2), 518 (7), 355 (10),
274 (27), 73 (100); HRMS calcd for C21H342HNaO13 519.2038,
found 519.2014.
Acknowledgment. This work was supported by Research
programs CTQ2004-06381/BQU, CTQ2004-02367/BQU, and
CTQ2007-67492/BQU of the Ministerio de Educacio´n y Cien-
cia, Spain, cofinanced by the Fondo Europeo de Desarrollo
Regional (FEDER). I.P.-M. and L.M.Q. thank the I3P-CSIC
Program for fellowships.
169.8 (C), 170.0 (C), 170.0 (C); MS (FAB) m/z (%) 519 (M+
+
Na + H, 7), 518 (26), 517 (5), 274 (46), 273 (27), 73 (100); HRMS
calcd for C21H342HNaO13 519.2038, found 519.2042. Compound
1
28-(D): H NMR δH 1.18 (3H, s), 2.02 (3H, s), 2.12 (3H, s), 2.16
(3H, s), 3.24 (1H, m), 3.38 (3H, s), 3.46 (1H, dd, J ) 10.1, 3.5
Hz), 3.47 (3H, s), 3.48 (3H, s), 3.56 (1H, dd, J ) 10.1, 3.0 Hz),
3.63 (1H, m), 3.76-3.82 (2H, m), 4.19 (1H, dd, J ) 3.0, 0 Hz),
4.80 (1H, d, J ) 3.5 Hz), 4.81 (1H, d, J ) 3.7 Hz), 4.94 (1H, d,
J ) 8.3 Hz), 5.03 (1H, dd, J ) 8.3, 3.5 Hz), 5.33 (1H, dd, J ) 3.6,
3.6 Hz); 13C NMR (100.6 MHz) δC 15.576 (CH3), 20.6 (CH3), 20.7
(CH3), 20.7 (CH3), 55.4 (CH3), 58.4 (CH3), 59.0 (CH3), 60.2 (CH2),
Supporting Information Available: A complete description
of experimental details of precursors and copies of NMR spectra
(1H and 13C) for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO801499D
7720 J. Org. Chem. Vol. 73, No. 19, 2008